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Differences between 5-Minute and 15-Minute Measurement Time Intervals of the CGM Sensor Glucose Device Using GH-Method: Math-Physical Medicine (No. 281)

DOI: 10.31038/IMROJ.2020532

Introduction

This paper describes the research results by comparing the glucose data from a Continuous Glucose Monitor (CGM) sensor device collecting glucose at 5-minute (5-min) and 15-minute (15-min) intervals during a period of 125 days, from 2/19/2020 to 6/23/2020, using the GH-Method: math-physical medicine approach. The purposes of this study are to compare the measurement differences and to uncover any possible useful information due to the different time intervals of the glucose collection.

Methods

Since 1/1/2012, the author measured his glucose values using the finger-piercing method: once for FPG and three times for PPG each day. On 5/5/2018, he applied a CGM sensor device (brand name: Libre) on his upper arm and checked his glucose measurements every 15 minutes, a total of ~80 times each day. After the first bite of his meal, he measured his Postprandial Plasma Glucose (PPG) level every 15 minutes for a total of 3-hours or 180 minutes. He maintained the same measurement pattern during all of his waking hours. However, during his sleeping hours (00:00-07:00), he measured his Fasting Plasma Glucose (FPG) in one-hour intervals.

With his academic background in mathematics, physics, computer science, and engineering including his working experience in the semiconductor high-tech industry, he was intrigued with the existence of “high frequency glucose component” which is defined as those lower glucose values (i.e. lower amplitude) but occurring frequently (i.e.. higher frequency). In addition, he was interested in identifying those energies associated with higher frequency glucose components such as the various diabetes complications that would contribute to the damage of human organs and to what degree of impact. For example, there are 13 data-points for the 15-minute PPG waveforms, while there are 37 data-points for the 5-minute PPG waveforms. These 24 additional data points would provide more information about the higher frequency PPG components.

Starting from 2/19/2020, he utilized a hardware device based on Bluetooth technology and embedded with customized application software to automatically transmit all of his CGM collected glucose data from the Libre sensor directly into his customized research program known as the eclaireMD system, but in a shorter time period for each data transfer. On the same day, he made a decision to transmit his glucose data at 5-minute time intervals continuously throughout the day; therefore, he is able to collect ~240 glucose data within 24 hours.

He chose the past 4-months from 2/19/2020 to 6/19/2020, as his investigation period for analyzing the glucose situation. The comparison study included the average glucose, high glucose, low glucose, waveforms (i.e. curves), correlation coefficients (similarity of curve patterns), and ADA-defined TAR/TIR/TBR analyses. This is his secondresearch report on the 5-minute glucose data. His first paper focused on the most rudimentary comparisons [1].

References 2 through 4 explained some example research using his developed GH-Method: math-physical medicine approach [2,3].

Results

The top diagram of Figure 1 shows that, for 125 days from 2/19/2020 – 6/23/2020, he has an average of 259 glucose measurements per day using 5-minute intervals and an average of 85 measurements per day using 15-minute intervals. Due to the signal stability of using Bluetooth technology, for the 5-min, it actually has 259 data instead of the 240 data per day.

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Figure 1. Daily glucose, 30-days & 90-days moving average glucose of both 15-minutes and 5-minutes.

The middle diagram of Figure 1 illustrates the 30-days moving average of the same dataset as the “daily” glucose curve. Therefore, after ignoring the curves during the first 30 days, we focus on the remaining three months and can detect the trend of glucose movement easier than “daily” glucose data chart. There are two facts that can be observed from this middle diagram. First, the gap between 5-min and 15-min is wider in the second month, while the gap becomes smaller during the third and fourth month. This means that the 5-min results are converging with the 15-min results.Secondly, both curves of 5-min and 15-min are much higher than the finger glucose (blue line). This indicates that the Libre sensor provides a higher glucose reading than the finger glucose. From the listed data below, the CGM sensor daily average glucoses are about 8% to 10% higher than the finger glucose.

5-min sensor: 118 mg/dL (108%)

15-min sensor: 120 mg/dL (110%)

Finger glucose: 109 mg/dL (100%).

The bottom diagram of Figure 1 is the 90-days moving average glucose. Unfortunately, his present dataset only covers 4 months due to late start of collecting his 5-min data; however, the data trend of the last month, from 5/19-6/23/2020, can still provide a meaningful trend indication. As time goes by, additional data will continue to be collected, his 5-min glucose’s 90-days moving trend will be seen more clearly.

Figure 2 shows the synthesized views of his daily glucose, PPG, and FPG.Here, “synthesized” is defined as the average data of 125 days.For example, the PPG curve is calculated based on his 125×3=375 meals. Listed below is a summary of his primary glucose data (mg/dL) in the format of “average glucose/extreme glucose”. Extreme means either maximum or minimum, where the maximum for both daily glucose and PPG due to his concerns of hyperglycemic situation, and the minimum for FPG due to his concerns of insulin shock. The percentage number in prentice is the correlation coefficients between the curves of 15-min and 5-min.

Daily (24 hours):15-min vs. 5-min

117/143vs. 119/144(99%)

PPG (3 hours):15-min vs. 5-min

126/135vs. 125/134(98%)

FPG (7 hours):15-min vs. 5-min

102/95 vs. 105/99 (89%).

Those primary glucose values between 15-min and 5-min are close to each other in the glucose categories. It is evident that the author’s diabetes conditions are under well control for these 4 months. However, by looking at Figure 2 and three correlation coefficients %, we can see that daily glucose and PPG have higher similarity of curve patterns (high correlation coefficients of 98% and 99%) between 15-min and 5-min, but FPG curves have a higher degree of mismatch in patterns (lower correlation coefficient of 89%). This signifies that his FPG values during sleeping hours have a bigger difference between 15-min and 5-min.

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Figure 2. Synthesized daily glucose, PPG, and FPG of both 15-minutes and 5-minutes.

Figure 3 are the results using candlestick model [4,5]. The top diagram is the 15-min candlestick chart and the bottom diagram is the 5-min candlestick chart. Candlestick chart, also known as the K-Line chart, includes five primary values of glucoses during a particular time period; “day” is used in this study. These five primary glucose data are:

Start: beginning of the day.

Close: end of the day.

Minimum: lowest glucose.

Maximum: highest glucose.

Average: average for the day.

Listed below are five primary glucose values of both 15-min and 5-min.

15-min: 108/116/86/170/120.

5-min: 111/116/84/173/118.

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Figure 3. Candlestick charts of both 15-minutes and 5-minutes.

By ignoring the first two glucoses, start and close, let us focus on the last three glucoses: minimum, maximum, and average. The 5-min method has a lower minimum and a higher maximum than the 15-min method. This is due to the 5-min method capturing more glucose data; therefore, it is easier to catch the lowest and highest glucoses during the day. The difference of 2mg/dL between 15-min’s average 120 mg/dL and 5-min’s average 118 mg/dL is only a negligible 1.7%.

Again, it is also obvious from these candlestick charts that the author’s diabetes conditions are under well control for these 4 months.

Conclusion

In summary, the glucose differences between 5-min and 15-min based on simple arithmetic and statistical calculations are not significant enough to draw any conclusion or make any suggestion on which are the “suitable” or better measurement time intervals. However, the author will continue his research to pursue this investigation of energy associated with higher-frequency glucose components in order to determine the glucose energy’s impact or damage on human organs (i.e. diabetes complications).

The author has read many medical papers about diabetes. The majority of them are related to the medication effects on glucose symptoms control, not so much on investigating and understanding “glucose” itself. This situation is similar to taming and training a horse without a good understanding of the temperament and behaviors of the animal. Medication is like giving the horse a tranquilizer to calm it down. Without a deep understanding of glucose behaviors, how can we truly control the root cause of diabetes disease by only managing the symptoms of hyperglycemia?

References

  1. Hsu, Gerald C. eclaireMD Foundation, USA (2020) Analyzing CGM sensor glucoses at 5-minute intervals using GH-Method: math-physical medicine (No. 278).
  2. Hsu, Gerald C. eclaireMD Foundation, USA(2020) Predicting Finger PPG by using Sensor PPG waveform and data via regression analysis with three different methods using GH-Method: math-physical medicine (No. 249).
  3. Hsu, Gerald C. eclaireMD Foundation, USA (2019) Applying segmentation pattern analysis to investigate postprandial plasma glucose characteristics and behaviors of the carbs/sugar intake amounts in different eating places using GH Method: math-physical medicine (No. 150).
  4. Hsu, Gerald C. eclaireMD Foundation, USA (2019) A case study of the impact on glucose, particularly postprandial plasma glucose based on the 14-day sensor device reliability using GH-Method: math-physical medicine (No. 124).
  5. Hsu, Gerald C. eclaireMD Foundation, USA. Comparison study of PPG characteristics from candlestick model using GH-Method: Math-Physical Medicine (No. 261).

Management of Cancer Patients Undergoing Radiation Therapy during the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: A Review of the Literature

DOI: 10.31038/CST.2020531

Abstract

Cancer patients are more vulnerable to acquiring COVID 19 infection and may also experience higher morbidity and mortality. In the context of COVID-19, cancer patients may be affected through delayed diagnosis and have significant impact on management in resource strained settings. Cancer treatment typically involves a possible combination of surgical resection, chemotherapy and radiation therapy (RT). RT delivery requires often daily attendance to a cancer center, is complex and poses potentially additional risks for infection as well as treatment related complications. Optimization of infection control measures and RT treatment schedules is paramount to minimize the impact of the pandemic on patients and optimize outcomes. This review aims to summarize the existing limited literature surrounding RT administration and optimization in the context of COVID-19.

Introduction

Since the recognition of the COVID-19 pandemic, evidence has become available that a cancer diagnosis is considered one of the comorbid conditions that increase the risk of COVID 19 infection [1- 3]. Meanwhile COVID-19 infection in cancer patients is associated with higher morbidity and mortality [4]. Data is still preliminary, but it is likely that both the increased risk of acquiring COVID-19 and more severe consequences thereof in cancer patients are multifactorial in nature likely involving complex relationships between the type of cancer site and extent or location of the disease as well as more nuanced patient and treatment related factors. While a number of publications have delved into the presentation and management of COVID-19, and its relationship to comorbid conditions including malignancy, and yet others into the implications of systemic management (chemotherapy, targeted agents), fewer publications specifically discuss the implications for patients who undergo radiation therapy (RT) and the operational considerations of radiation therapy (RT) departments. RT is administered mostly on a daily basis in cancer centers or facilities with complex logistics, unique organizational demands, high possibility of interaction between vulnerable patients and risk of exposure to multiple patients and staff. The lack of evidence surrounding best practices has left radiation oncology providers and patients with many questions still unanswered.

These questions include the level of vulnerability of cancer patients, who for example may undergo radiation but may not be undergoing systemic management and may therefore not necessarily be immune- compromised, as well as the implication for daily attendance to a RT facility and the associated infection risk and how to best mitigate it. Other questions involve the ability to and safety of delaying or altering RT treatment schedules to minimize risk of infection. Important additional considerations abound in particular settings such a RT emergencies and treatment of the COVID-19 positive patient as well as the administration of radioactive isotopes such as radioactive iodine in thyroid patients who then need to self-isolate at home or as inpatients for several days. Since the COVID-19 pandemic has raised unprecedented challenges and questions, with ongoing lack of robust data, periodic review of the available evidence is important to help guide providers and patients in order to enable evidence-based care hence prompting this scoping review.

Materials and Methods

To carry out the scoping review, publications that specifically addressed the impact and management of cancer patients undergoing radiation therapy in the context of the COVID 19 pandemic were identified in PubMed using the following mesh terms: ((“risk”[MeSH Terms] OR “risk”[All Fields]) OR “risk of”[All Fields]) AND (((((((“covid 19”[All Fields] OR “covid 2019”[All Fields]) OR “severe acute respiratory syndrome coronavirus 2”[Supplementary Concept]) OR “severe acute respiratory syndrome coronavirus 2”[All Fields]) OR “2019 ncov”[All Fields]) OR “sars cov 2”[All Fields]) OR “2019ncov”[All Fields]) OR ((“wuhan”[All Fields] AND (“coronavirus”[MeSH Terms] OR “coronavirus”[All Fields])) AND (2019/12/1:2019/12/31[Date – Publication] OR 2020/1/1:2020/12/31[Date – Publication]))) AND ((((“patient s”[All Fields] OR “patients”[MeSH Terms]) OR “patients”[All Fields]) OR “patient”[All Fields]) OR “patients s”[All Fields]) AND (((((((((“cancer s”[All Fields] OR “cancerated”[All Fields]) OR “canceration”[All Fields]) OR “cancerization”[All Fields]) OR “cancerized”[All Fields]) OR “cancerous”[All Fields]) OR “neoplasms”[MeSH Terms]) OR “neoplasms”[All Fields]) OR “cancer”[All Fields]) OR “cancers”[All Fields]) AND ((((((((((((“radiate”[All Fields] OR “radiated”[All Fields]) OR “radiates”[All Fields]) OR “radiating”[All Fields]) OR “radiation”[MeSH Terms]) OR “radiation”[All Fields]) OR “electromagnetic radiation”[MeSH Terms]) OR (“electromagnetic”[All Fields] AND “radiation”[All Fields])) OR “electromagnetic radiation”[All Fields]) OR “radiations”[All Fields]) OR “radiation s”[All Fields]) OR “radiator”[All Fields]) OR “radiators”[All Fields]). 87 abstracts were identified.

Results

As of July 10, 2020: 1706 papers were published on the topic of COVID 19 and oncology in 2020 to date of which 457 (27%) of these discussed cancer as a risk factor for the development of the COVID 19 infection. The MeSH term was generated to capture papers specific to the context of the cancer patient undergoing radiation therapy during the COVID 19 pandemic. 87 papers were identified using the above MeSH term. Of these 5 (6%) were literature reviews or broad guideline recommendation papers, 12 (14%) dealt related to oncology but were not RT specific (eg. systemic management of hematological malignancies), 63 (72%) were oncology and RT specific and 7 (8%) were not directly relevant to either oncology or radiation but were relevant to COVID 19 more broadly. All of the abstracts were published between March and July, with 75% of the abstracts between the end of April and beginning of July 2020.

Types of Publications Identified

Four types of publications were broadly identified: 1) Literature reviews and operational/planning guidelines which did not contain patient data but rather represent institutional or expert opinion (Table 1); 2) consensus guidelines generated by governing bodies and site- specific groups for specific cancer histologies (Table 2); 3) retrospective single or multiple institution papers (Table 3) and 4) more context focused papers eg. management of the elderly with cancer during COVID-19 and palliative management (Table 4).

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Literature reviews involving COVID-19 and oncology identified with ** were made available by Al-Shamsi et al., Shankar et al. and Anderson et al. (Table 1 ** denotes encompassing reviews), * smaller important reviews) [1-3]. These broader reviews (**) were not necessarily RT specific but contained some information regarding RT. Discussion of RT departmental planning, logistics and operational considerations were available in other reviews (Table 1). Site specific consensus guideline papers with recommendations (organ or histology specific) were also identified specifically for head and neck, lung, genitourinary and hematological malignancies and to a lesser extent in other sites (Table 2). Some papers dealt more generally with single center experiences which also provided some guidelines while others reported on testing for COVID 19 in cancer patients undergoing or about to undergo radiation therapy (Table 1). Finally, there were also papers that were more specifically targeting the elderly patient with cancer, palliative management and other smaller topics (Table 4).

Logistical and Operational Focused Publications

Logistics and Operational Considerations – Limit the Risk of Infection

From a practical day to day perspective the ability to effectively manage new logistical and operational challenges in order to mitigate risk of infection to patients and staff with need of frequent adaptation, poses one of the greatest challenges to RT in the context of COVID-19 [5-7]. In the absence of both data and homogenous higher-level guidelines, cancer therapy centers and individual radiation therapy departments have created their own guidelines and this is reflected in the publications uncovered in this review. Important insights originate in virus epicenters like Italy [8], New York in the US [9,10]. According to a survey by Opperman et al., who conducted an online survey among medical physicists in Germany, Austria and Switzerland from March 23rd to 26th 2020, 72.4% of the respondents stated that their processes were affected due to COVID-19, with longer processing times (54.2%), patient no-shows (42.5%) and staff reduction (36.7%). 75.8% expected further unavailability of their personnel in the upcoming weeks [11].

COVID-19 Testing in Cancer Patients Undergoing RT – Address Testing Practices

Another challenge is that of the selection, timing and actions taken with respect to patient and staff testing for COVID-19. As noted with respect to other aspects of the management of the pandemic, guidelines are lacking and complex standard of care practices had to be rapidly adapted to include patient (and staff) testing when appropriate [12]. This is particularly complex when patients may need to undergo brachytherapy or radioactive iodine and carry significant risk on infecting other staff if they themselves are infected and/or pose significant logistical challenges eg. Isolation as in or outpatient in the case of radioactive iodine administration. We now understand that testing negative for COVID carries a not in-insignificant possibility that the patient may have a false negative test and that the timing of the test is also impacting on its usefulness and accuracy. Testing itself is not readily available in many jurisdictions and may take some time to obtain results. Patients have to be pre-screened and directed to undergo testing, which may be difficult or impossible. However, data does support the notion that a positive result may render cancer patients more vulnerable to COVID-19 [4,13]. Bajaj et al. report on the salivary detection of SARS-CoV-2 (COVID-19) and implications for oral health-care providers summarizing guidelines for oral care specialists [14]. This literature review notes that salivary specimens have a higher than 90% concordance rate with nasopharyngeal specimens which while enabling PCR testing of salivary samples also reveals that saliva poses additional risk to health care providers. Since there is currently no data available to assess the risk of transmission of COVID-19 in dental practices, and since cancer patients in particular with head and neck primaries require dental interventions, this is an area where further data is required to optimize management and outcomes. Madriaga et al. reviewed the literature for COVID-19 testing in cancer patients and describe the approach to COVID-19 testing adopted in a large cancer center in Toronto [15].

Indications for/Modification of RT – Modify RT When Possible to Mitigate Risk

Parashar et al. from a tertiary cancer center in New York provides a general set of robust guidelines for curative RT in the context of the pandemic echoing other site-specific papers and setting some “ground rules” for this approach while summarizing alternative dose and fractionation options for each tumor site that may be employed in the context of COVID-19 to minimize risk to patients and staff [16]. They discuss the scenarios of RT as an alternative to surgery when immediate surgery is not possible, RT as a ‘bridge’ to surgery and radiation options as an alternative to chemotherapy given the risk of hospitalization with high-dose chemotherapy. It should be noted that while enrollment of patients on clinical trials is considered in this paper and would be preferable when fractionation schemes with lesser evidence are employed or patients are documented COVID-19 positive, in practical terms this is often curtailed as clinical trials are on hold in many centers due to the pandemic. Vordermark also provides a review of organ-specific cancer management [17]. In this publication the author searched for multidisciplinary and expert recommendations to guide potential shift in RT indications and found limited data as of April 2020 when it was published however provides a good summary of the available data at that point. Chen et al. and Franco et al. provide broader frameworks for prioritization of patients [6,18]. Franco et al. also provides guidelines for the management of patients with COVID-19 [18].

Brachytherapy

Williams et al. provide a thorough review of the impact of delaying or prolonging brachytherapy treatment courses in multiple disease sites including gynecological sites, prostate and breast [19]. While the timing and duration of brachytherapy is highly sensitive in sites like cervix and vaginal cancer, breast and in particular prostate may allow for some postponement of brachytherapy. Additional alternative fractionation schemes are also discussed for each cancer site. Aghili et al. review brachytherapy guidelines in the context of COVID-19 highlighting the need to consider the best regimens as opposed to discontinuation or postponement of brachytherapy [20].

Oncology Site Specific Publications and Consensus Guidelines

Head and Neck Cancers

Head and neck cancer patients are vulnerable to COVID-19 because in addition to the cancer diagnosis they may also share other risk factors (smoking, nutritional depletion, swallowing and/ or breathing dysfunction) [21,22]. In addition, many head and neck primaries are rapidly progressive causing significant clinical deterioration and often requiring hospital admission for nutritional support and refeeding syndrome. Delay in diagnosis is particularly detrimental [23] and in the case of nasopharyngeal cancer additional chemotherapy could be employed to counteract the delay in diagnosis [23]. Head and neck cancers also require significant PPE due to the diagnoses requiring examination under anesthesia or direct laryngoscopy with biopsy [24]. Thomson et al. provide the ASTRO-ESTRO consensus to risk adapted head and neck cancer RT [25]. Two pandemic scenarios: early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated and a panel of experts developed treatment recommendations for 5 HNC cases. They evaluated potential symptomatic benefit with the risk of active COVID-19 infection balancing potential for cure and risk of progression as well as patient fitness to recommended rational patient triage. With respect to interventions in the upper aerodigestive tract region (eg. rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves [26]. Additional guidelines are provided by Werner et al. and Mehanna et al. [24,27].

Breast Cancer

Breast cancer patients make up a large proportion of the patients on treatment and follow-up in most cancer treatment centers and therefore a robust approach to risk stratification is crucial to ensure adequate access to care and diminish the risk of adverse outcomes while minimizing risk of COVID-19 infection. Curigliano et al. creates a framework on how to approach these using scenarios often encountered in clinical practice [28]. The use of primary systemic therapy is also discussed as an alternative to upfront surgery in the context of COVID-19. RT is prioritized according to the risk categorization of the cancer and whether the patient is already on treatment. Palliative treatments and acute spinal cord compression are considered urgent, followed by high risk patients while postoperative RT for low risk patients and post treatment visits are of lower priority. Additional recommendations include the omission of boost RT and accelerated partial breast RT for low risk patients. It is recognized that patients receiving chemotherapy regimens with intermediate/ high risk of immunosuppression, such as anthracyclines, 3-weekly docetaxel or 3 weekly platinum are at intermediate or high risk of immunosuppression. Vuagnat et al. set up a prospective registry for 15600 patients actively treated for early or metastatic breast cancer in the last 4 months [29]. They found that the COVID-19 mortality rate depended more on the comorbidities prior to RT that the treatment itself. Other recommendations are also provided by Chan et al. and Braunstein et al. but patient outcome data is still lacking [30,31].

Lung Cancer

Lung cancer patients pose a uniquely challenging scenario in the context of COVID-19 in part because they are already vulnerable to lung infections and in the context of RT because they are at risk for radiation pneumonitis which can be challenging to distinguish clinically and radiographically [32] but is also treated with high dose steroids which may worsen COVID-19 related lung injury. Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic are provided in an ESTRO-ASTRO consensus statement by Guckenberger et al. Singh et al. and Dingemans et al. also make recommendations on standardizing the care of lung cancer patients during COVID-19 while recommending that general standard principles of practice be followed [33-35]. Wu et al. provide guidelines for thoracic radiation therapy specifically while Kumar et al. discusses alternative management options [36,37].

Genito-Urinary

Delaying treatment in genito-urinary cancers is potentially of significant detriment [38]. In penile cancer, surgery should proceed when possible due to the aggressive nature of the disease, with RT as an organ preserving approach [39]. Zaorsky et al. provide RT recommendations for prostate cancer [40]. However, since prostate cancer is a more indolent malignancy in early stages, treatment can be avoided or delayed for very low, low, and favorable intermediate- risk disease For unfavorable intermediate-risk, high-risk, clinical node positive, recurrence post-surgery, oligometastatic, and low- volume M1 disease neoadjuvant hormone therapy for 4-6 months was recommended [40]. Ultrahypofractionation may be preferred for localized, oligometastatic, and low volume M1, and moderate hypofractionation may be preferred for post-prostatectomy and clinical node positive disease. Postoperatively, salvage RT is preferred to adjuvant radiation [40]. Short fractionation RT for early prostate cancer is at the forefront of the field and is discussed in the context of COVID-19 by Barra et al. [41].

Central Nervous System Cancers

In the context of central nervous system cancers, the unique aspects include the often older age of the patients and co-existing neurological symptoms requiring ongoing steroid use to decrease increased intracranial pressure. In addition to these, the prognosis is often guarded, and advanced care planning will be more important than ever to address upon diagnosis and initiation of management. Guidelines are provided by Mohile et al. [42]. These include mitigating risk through social distancing and discussions of goals of care (considering that ventilator use may unfortunately be denied to some of these patients considering that high grade glioma such as glioblastoma will be considered a terminal diagnosis particularly in the elderly). Nonetheless maximal safe resection is recommended both to decrease intracranial pressure but also to improve longevity and diminish steroid use. In lower grade glioma prognosis may be far superior and thus some interventions may be deferred. Tabrizi et al. extracted patient level data from 1321 elderly glioblastoma patients to provide a quantitative framework for modelling COVID-19 risk using published randomised trials in the elderly with glioblastoma [43]. They support hypofractionated RT and increased utilization of temozolomide alone in patients with MGMT methylation when the risk of COVID-19 infection is high. With respect to WHO grade III and IV gliomas Bernhardt et al. combined the opinion of 6 international experts in a consensus-based practice recommendation including neuro-oncologists, neurosurgeons, radiation -oncologists and a medical physicist [44]. Overall agreement was had that treatment cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19.

Hematological  Cancers

Patients with hematological cancers are vulnerable to COVID-19 as they may suffer for cytopenias and may be immunosuppressed. Yahalom et al. offer guidelines to potentially omit RT in order to decrease the risk of exposure as a result of daily attendance to the cancer center [45]. They recommend possible omission of RT in: palliative settings where alternatives can be offered, for completely excised localized low-grade lymphomas and localized nodular lymphocyte- predominant Hodgkin lymphoma and for consolidation RT for diffuse large B-cell lymphoma/aggressive non-Hodgkin lymphoma (NHL) in patients who have completed a full chemotherapy course and achieved a complete remission [45]. Some lymphomas can safely delay RT (eg. asymptomatic localized low-grade lymphomas, localized nodular lymphocyte-predominant Hodgkin lymphoma, patients who develop COVID-19 infection prior to commencing RT), while others can benefit from shortened RT courses (eg. 20 Gy in 10 fractions or 30.6 Gy in 17 fractions). A consensus statement is available from Di Ciaccio et al. and Kirova et al. [46,47].

Other Cancer Subtypes

Guidelines have been published for pancreatic cancer [48], representing the UK consensus position. Endoscopy is recommended to continue for malignant biliary obstruction, however as it is an aerosol-generating procedure it is recommended that all elective and non-essential endoscopic procedures not be performed. Chemotherapy is suggested when surgery is not possible in the context of COVID-19 as are hypofractionated RT approaches (eg. 5-15 fraction regimens). Skin cancer management and triage was discussed by Baumann et al. and Tagliaferri et al. [49,50]. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, unless favorable T1 disease. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For squamous cell carcinoma, early disease can have treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is considered acceptable. For squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless symptomatic [49]. With respect to gynecological cancers Martinelli et al. carried out a survey showing that responders prioritized treatment of early stage high-risk uterine cancers (45%), newly diagnosed epithelial ovarian cancer (41%), and locally advanced cervical cancer (41%) [51]. 77% of respondents reported no changes in surgical treatment for early stage cervical cancer in COVID-19- negative patients, but treatment was postponed by 54% if the patient tested COVID-19-positive. Responders also considered neoadjuvant chemotherapy for advanced ovarian cancers and hypofractionation of RT for locally advanced cervical cancers. A similar survey was carried out by Nakayama et al. Rossi et al. report on their early experience in the management of sarcoma with priority given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. For these and other sites further publications are as yet lacking [52,53].

Single Center Experiences

Single center experiences provide an “on the ground” perspective of the transformative experience COVID-19 has had on radiation oncology practice and health care resources and can provide an avenue for practical guidelines. Several papers exemplify this in particular in areas that were/are epicenters for the disease. Tey et al. provides a workflow for the COVID-19 positive patient on RT [54]. Chen et al. reports from a multicenter New York area institution with experience- based guidelines for disease sites that require concurrent chemo- irradiation and thus were more likely to result in patient presentation to the emergency room or in hospital admission [6]. The priority framework in this publication implemented as of April 13, 2020 is extremely practical in that it addresses efficiency from a systemic standpoint to optimize care for all patients within a RT department. Three priority levels are described; the first for cases where delay may result in loss of life, progression of disease or permanent loss of neurologic or other function (oncologic emergencies, advanced head and neck, gastrointestinal, gynecologic and lung cancers); priority 2 for cases that may be delayed for up to 4 weeks (early stage head and neck, lung and lymphoma, benign central nervous system cases) and priority 3 for cases that may be delayed for 30 days or more (early prostate, breast or prostate already on androgen deprivation therapy). This publication also presents patient data and addresses approaches to toxicity management in the context of COVID-19. Press et al. also described a single institution experience from a proton center in Manhattan quantifying the impact of treatment delays and interruptions [9]. Chhabra et al. also provide recommendations for prioritization of proton patient in the New York Proton Center [55]. Additional radiation oncology center experiences are published by Tan et al. (Singapore), Montesi et al. (Italy), Wu et al. (Wuhan), Handoko et al. (Indonesia), Mishra et al. (New York) [8,56-59].

Specific Considerations

The Elderly: Desideri et al. provides a very good summary of the data surrounding COVID-19 and the elderly [60]. Freedman et al. report specifically on managing older adults with breast cancer noting appropriately that considerations for management are highly relevant “within the new normal” considering that 30% of breast cancer patients are 70 years old or older [61]. They provide options for the most commonly encountered scenarios within the framework of existing evidence. Interestingly they also recommend deferral of routine follow-up and routine breast imaging and anticipate that this postponement will prompt discussion of the limited utility of these measures beyond the pandemic, as will no doubt be the case for other low value interventions. Asokan et al. provide a review of the impact of COVID-19 on the cardio-oncology population [62]. This is a population that also includes elderly patients with pre- existing cardiac comorbidities and possibly additional cardiotoxic insults such as chemotherapy and/or radiation or systemic treatment such as androgen deprivation therapy. Data surrounding the risk of COVID-19 infection and outcomes in this population is currently lacking.

Palliative RT: Yerramilli et al. provide a review of palliative RT for oncologic emergencies with emphasis on balancing risk and benefit [63]. Palliative treatments make up a large proportion of the workload of the RT department and the patients who require palliative RT often require it within days if not hours. This patient population is particularly vulnerable to the impact of the pandemic in a resource strained environment. Yerramilli et al. provides a framework for the triaging a patient with an oncologic emergency which is not dissimilar from frameworks already employed in resources strained environments [63]. Patients who are symptomatic and/or have an oncologic emergency and a more prolonged life expectancy are recommended to receive short course palliative RT, delay of RT or best supportive in the case of limited life expectancy is otherwise recommended. Thureau et al. in their GEMO (the European Study Group of Bone Metastases) position paper, astutely note that the indications and treatment modalities for palliative bone metastases must be re-discussed in the context of COVID-19 [64-67]. Palliative treatments often require the most clinical judgement and can benefit the most from available evidence surrounding reduction in the number of treatments and the complexity thereof in a resource strained setting. Their recommendations to carry out simulation planning and treatment at the same time as the consult, carry out tele- consults when appropriate, and use existing criteria to assess bone instability to allow for optimization of decision making enabling the least invasive technique. They also provide guidelines for retreatment of bone metastasis, spinal cord compression and SBRT (Stereotactic Body Radiation Therapy) for which they consider the level of evidence too low to be considered in the current situation.

Conclusions

Although multiple attempts at guideline and consensus generation have been made with respect to RT administration in the context of the COVID-19 pandemic in several tumor sites, evidence for the effectiveness or adequacy of these is lacking and some cancer sites have as yet very little or no guidelines. This is equally so the case with respect to the utilization of altered fractionation schemes being potentially proposed to diminish patient visits to cancer centers which should likely be approached with some caution and emphasis on following standard of care practice whenever possible. Several frameworks have been published for the optimization of logistics and operational planning that may be employed in radiation therapy centers and departments. Over time it is likely that more data will become available with respect to patient management and outcome, however as of July 2020, very few small retrospective data sets are available with respect to the outcomes of COVID-19 positive cancer patients undergoing RT. It is as yet unclear to what extent adverse outcomes in cancer patients may be related to preexisting comorbidities, the cancer diagnosis and its implications or the treatment of the cancer itself. Additional areas where evidence is lacking include:

1) The impact on of COVID-19 on older patients with cancer

2) The impact of treatment delay in patients currently considered intermediate or low risk for tumor progression

3) The impact of altered fractionation schedules

4) The long and short-term psychological impact of COVID-19 and altered cancer management on patients and staff.

Declarations

Ethics approval and consent to participate: This study is a literature review and does not report on data collected from humans and is exempt from ethics approval.

Consent for publication: Not applicable.

Availability of data and material: The data supporting the conclusions of this article are included within the article as references.

Competing Interests: The author declares that they have no competing interests.

Authors’ contributions: AVK conceived the idea for the review, reviewed the literature, created the accompanying material, and wrote the manuscript.

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Aspirin Use for Enhanced Primary Cardiovascular Prevention during the Coronavirus-19 Pandemic

DOI: 10.31038/JCCP.2020324

 

The 2019 American Heart Association/American College of Cardiology guidelines for the primary prevention of atherosclerotic cardiovascular disease virtually preclude aspirin use for adults ages 40-70 unless at long-term high risk (>10% threshold by 10-year risk calculators) [1]. The cardiovascular complications of coronavirus-19 (COVID-19) infection may require us to reconsider this, however, to take short-term high risk into account. Likened to a cytokine tsunami,elevated levels of interleukin-6 and C-reactive protein predict cardiac and respiratory failure, indicatingthat inflammation mediates excess morbidity and mortality [2-4].While dipyridamole has been associated with clinical improvement which was not observed with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers [5,6], the effect of aspirin on clinical outcomeshas yet to be reported. Based on evidence that inhibition of inflammation prevents cardiovascular events andthat low-dose aspirinconclusively reducedfirst heart attacks in middle-aged men in the randomized controlled Physicians Health Study [7,8], this latter approach has been recommended to protect athletes from theincreased risk of event-related cardiac arrest and sudden death triggered by inflammation due to exertional rhabdomyolysis [9-11]. Aspirin’s anti-inflammatory and anti-thrombotic effects may mitigate pandemic-related increased short-term risk, perhaps bluntingthe surge in coronary heart disease deaths which have occurredunder such conditions [12]. C-reactive protein levels can reliably stratify risk for low-dose aspirin as have coronary artery calcium scores for statin therapy [13,14] (Table 1).

JCCP-3-2-313-g001

Prophylactic low-dose aspirin usefor susceptible individuals presents a window of opportunity toreduce the cardiovascularcomplications of COVID-19 infection ahead of the second wave anticipated by the United States Center for Disease Control [15]. Based on inflammation as the root cause of atherothrombosis, a predominance of current clinical evidencesupports this interventionwithout a randomized controlled clinical trial asnecessary for novel interventions such as the high-dose interleukin-1 receptor antagonist tocilizumab [16]. Revised guidelines for primary prevention to accommodate short-term high risk may facilitate this goal as accomplished by subspecialty societies for treating acute myocardial infarction [17]. Preventing fatal strokes in young persons might be anunintended collateral benefit [18].

Keywords

Aspirin, Coronary heart disease, COVID-19 pandemic, Primarycardiovascular prevention

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Towards COVID-19 Prophylaxis: An AIDS Preclinical Research Perspective

DOI: 10.31038/CST.2020525

Abstract

The success of an antiviral drug depends on its potency to neutralize the virus in vitro and its ability after administration in vivo to reach the anatomic compartments that fuel viral dissemination in the body. For instance, remdesivir, a potent SARS-CoV-2 antiviral drug based on studies in vitro, if administered orally would be poorly effective because low drug levels would reach the lungs due to its high first pass destruction in the liver. This is the reason remdesivir can only be administered intravenously, a requirement that clearly limits its use as a prophylactic agent for COVID-19, although novel formulations for its easier administration are under development. Whether an antiviral prophylaxis could further control or even stop the COVID-19 epidemic in synergy with other non-pharmacological based mitigation strategies is today unknown. Since the mid-1960s, pharmacologists have investigated the use of lipid-based nanoparticles for efficient delivery of antivirals to tissues, for example by transforming the route of administration from intravenous to oral, subcutaneous or aerosol administrations. These novel encapsulation strategies have also the potential to maintain high levels of the antiviral drugs in tissues, with reduced dose frequency compared to the non-encapsulated drug. Several lipid-based nanoparticles are today approved by the US Food and Drug Administration or being tested in clinical studies with favorable toxicity profiles.

Nonhuman primate models of coronavirus infection offer unique platforms to accelerate the search for SARS-CoV-2 antiviral prophylaxis.Paradigms, to corroborate this claim, are borrowed from nonhuman primate research studies, some of which had a profound impact on global public health in the specific setting of the AIDS pandemic. Sharing information from nonhuman primate research programs, invoking principles of scientific transparency and bioethics similar to those universally agreed for human studies, would also likely significantly help our collective fight (as the human species) against this public health emergency.

What Makes an Antiviral Potent Against SARS-CoV-2?

Remdesivir, a nucleoside analogue specific for the RNA-dependent RNA polymerase of several coronaviruses, is a potent SARS-CoV-2 antiviral drug based on studies in vitro. Its half maximal effective concentration (EC50) leans consistently towards the lowest estimates when screened, using the same assay, with other antivirals tested against several coronaviruses [1-4] hence, a relatively lower concentration of the drug is needed to cut similar levels of viral replication in vitro, compared to other antiviral drugs less successfully repurposed, so far, as medical countermeasures against COVID-19. These include the HIV-1 protease inhibitor lopinavir/ritonavir (Kaletra) and the immunosuppressive and anti-parasitic drug hydroxychloroquine [5,6].

The success of an antiviral drug in fighting a virus depends, however, not only on how potent the drug is in inhibiting the virus in vitro but also on how well the drug penetrates the anatomic compartments in which the virus mostly replicates in vivo; the lungs for COVID-19. If administered orally, for instance, remdesivir would be ineffective because low drug levels would reach the lungs due to its high first pass destruction in the liver, resulting in poor oral bioavailability. This is the reason remdesivir can only be administered intravenously to exert its viral inhibitory function, a requirement that clearly limits its use as a prophylactic agent or as a test-and-treat pharmacologic-based mitigation strategy for COVID-19.

Delivering Potent Antivirals Straight to the Lungs, without Calling a Nurse

What can be done to transform the route of administration of an antiviral or to enhance its concentration into the lungs? Since the mid-1960s, pharmacologists have investigated the use of lipid-based nanoparticles for efficient delivery of antivirals and other drugs, for example by transforming the route of administration from intravenous to oral, subcutaneous or aerosol administrations [7,8], with potentially useful ramifications in the pharmacoeconomics of developing countries [9]. These novel encapsulation strategies are capable of maintaining high levels of the antiviral drugs in tissues, with reduced dose frequency. For instance, Kaletra in its oral formulation requires daily administration due to its rapid clearance, but data produced from nonhuman primates have demonstrated that the equivalent mass of one pill of Kaletra formulated as a lipid-nanoparticle for subcutaneous administration achieves approximately 10-fold higher concentrations in lymph nodes for about one week [10]. Similarly, the lipid-nanoparticle encapsulation of tenofovir, a nucleotide analogue used to treat HIV and hepatitis B infection that has some structural and functional similarities with remdesivir, has also been shown to enhance tissue concentrations and prolong retention of its active phosphorylated moieties in nonhuman primate studies [11]. The opportunity offered by nanoparticle technologies, not only to simplify the administration of a candidate antiviral drug, but also to enhance its concentrations in tissues, is relevant in the search for SARS-CoV-2 antiviral prophylaxes, especially given the limited data we have today for the penetration in the lungs or in the upper airways of most anti-SARS-CoV-2 repurposed antivirals [12], including lopinavir/ritonavir [13] and nelfinavir (another HIV-1 protease-inhibitor with a favorable EC50 against coronaviruses [14]). It is well known that lipophilic drugs preferentially penetrate the lungs and, in fact, this formed the rationale for encapsulating certain hydrophilic drugs in liposomes to promote delivery to the pulmonary compartment [15,16]. One example is amphotericin, an antifungal drug encapsulated in nanocochleates (soy-bean organic-based lipid particles) which can be formulated as an oral drink. Pharmacodynamic animal studies have advanced to phase-II clinical trials, in which patients are being administered the oral nanocochleate antifungal formulation, which appears to offer an overall effective oral formulation associated with low toxicity after prolonged (more than one year) continuous treatment [17]. Several lipid-based nanoparticles are today approved by the US Food and Drug Administration or being tested in clinical studies with favorable toxicity profiles [18]. Indeed these nanocarriers, by affecting the biodistribution in the body of the encapsulated antiviral compound, can substantially modify toxicological properties of the formulated drug. Of note, subcutaneous and aerosol formulations of remdesivir are now under development [19].

Consistent with the ranking by in vitro potency (the EC50), clinical trials in which these drugs have been administered to COVID-19 patients have thus far shown clear evidence of therapeutic potential only for remdesivir(intravenous formulation) [5,6]. Pharmacodynamic correlates of poor clinical responses could guide efforts in the search for an optimal prophylaxis. For instance, the antiviral drug Kaletra (available in pills) has been administered to COVID-19 patients with the same dose used to treat HIV-1 infected patients; however, its potency in vitro against SARS-CoV-2 is known to be significantly weaker than against HIV-1 [20].

Lessons Learned from the History of HIV-Prophylaxis Research

A successful antiviral prevention strategy is Truvada-PrEP for HIV, a combination of two nucleo(t)side analogues, that is lighter than the combination therapies (Highly Active Anti-Retroviral Therapy, HAART) used to treat HIV-1 infected patients, with important toxicological implications. Of note, dosing and administration strategies to conceive Truvada-PrEP (tenofovir+emtricitabine) were generated primarily from two monkey studies that produced, through invasive experimental designs not implementable in humans, precious data on the minimal drug levels needed in tissues to achieve protection from viral challenges [21,22]. These molecules attack the polymerase of HIV (or of lentiviruses that possess replication capacity in monkeys similar to HIV in humans, e.g. the simian-human immunodeficiency virus, SIV/SHIV) with a mechanism similar to the one adopted by remdesivir to attack the polymerase of several coronaviruses (including SARS-CoV-2), i.e. as chain terminators by mimicking the structure of a natural nucleoside [23].

Those studies demonstrated that the administration of two pills of Truvada (two hours prior to viral exposure) followed by two consecutive pills at 24 and 48 hours post-exposure provided sufficient drug levels in the rectal mucosa tissue to cut most viral transmissions. That prophylactic regimen (later called “On-Demand”) achieved in monkeys a protection similar to that achieved through daily drug administrations. This data prompted randomized clinical trials of “On-Demand-PrEP” prophylaxis, which confirmed an efficacy similar to the one estimated with the heavier “Daily-PrEP” regimen [24] and which later received endorsement in revised HIV treatment and prevention recommendations issued by the International Antiviral Society–USA [25]. Hence the former are two examples of nonhuman primate studies that have had a profound impact on public health worldwide.

Similarly, two decades earlier, the simian-human immunodeficiency virus (SIV/SHIV)-monkey model had been used to generate the HIV Post-Exposure Prophylaxis (PEP) guidelines we are using today for both occupational and non-occupational exposure to HIV, by demonstrating the effectiveness of a cocktail of HIV drugs (a combination of antiretrovirals similar to the one administered to HIV-1 infected patients, for four consecutive weeks), in preventing viral transmission if administered within 72 hours (but the sooner the better) from viral exposure [26,27]. The length of this window of opportunity for HIV PEP was identified, again, through nonhuman primate studies, in which lentiviruses replicate with dissemination capacity and antiviral drugs distribute in tissues with kinetics, much more similar to humans than any other animal model in our hands. In general, although animal models (including nonhuman primates) are known to be poor predictors (for obvious reasons) of the efficacy of specific HIV vaccines in humans [28], the monkey models proved to be valuable resources, during the past decades, in predicting the efficacy of antiviral HIV strategies not only as prophylaxis but also in the therapeutic arena.

The lessons learned from HIV and Truvada-PrEP studies include the following: 1) an antiviral may show a weak therapeutic effect, especially if administered late in the course of the viral induced disease, yet can effectively cut most viral transmissions if administered prophylactically. This observation holds true also for COVID-19. For instance, a recent study in a coronavirus rodent model showed that another nucleoside analogue with in vitro inhibitory activity similar to remdesivir can efficiently reduce viral replication in the lungs yet may fail to prevent disease progression if administered too late [29]; and 2) the higher the drug concentration in the anatomic compartments that fuel viral dissemination in the body, the higher the efficacy of the pharmacologic prevention strategy aimed at promptly eradicating the virus from the body [30]. The latter observation built the rationale for encapsulating HIV drugs in lipid-nanoparticles in research programs developed in the past decades [31], with the dual objective of simplifying (by reducing dosing frequency) and optimizing (by enhancing drug tissue levels) the delivery of antiretroviral drugs for both HIV-1 prevention and treatment, through proof-of-concept studies in nonhuman primate models of AIDS; an important experimental step for its effective translation into human studies.

The same experimental designs can be efficiently conceived to develop medical countermeasures to COVID-19 through the SARS-CoV-2 rhesus macaque model [32], which induces a respiratory disease milder than in COVID-19 patients, but that replicates at similar levels in the lungs [33,34]. In general, although non-invasive in vivo imaging technologies have also been used to study the biodistribution of antiviral drugs (including in the upper and lower respiratory tracts of humans [35,36]), our understanding of how an antiviral prophylaxis strategy succeeds or fails in protecting people from SARS-CoV-2 infection would inherently advance (as it did for HIV prophylaxis), by designing viral challenge experiments and producing measurements directly in tissues using these animal models. Sharing information from nonhuman primate research programs on what antiviral strategies are being tested on these animal models for COVID-19 throughout the world, invoking principles of scientific transparency and bioethics similar to those universally agreed for human studies (e.g. by registering studies in public databases) [37], would also likely significantly help our collective fight (as the human species) against this public health emergency [38].

These studies could also, in principle, be efficiently designed using other nonhuman-primate coronavirus animal models [39], especially if the antiviral target is the polymerase gene, given its high level of sequence conservation through evolution [29]. To date, remdesivir is the only antiviral drug tested in nonhuman primate models of SARS-CoV-2 with published observations [39,40]. Macaques infected with either the MERS-CoV [39] or the SARS-CoV-2 [40] rapidly cleared the virus following intravenous administration of remdesivir compared to untreated controls, consistent with the successful therapeutic effect of remdesivir observed in COVID-19 patients [6]. Data from both monkey studies also predict that remdesivir could prevent SARS-CoV-2 infection in humans, if used prophylactically. Prophylactic remdesivir (intravenous) treatment had been also successfully tested in nonhuman primates models of Ebola virus [41] and Nipah virus infection [42], two RNA viruses with an RNA-dependent RNA polymerase also highly sensitive to its inhibitory activity [43]. Indeed, both the cynomolgus [44] and the rhesus macaque models [45] of SARS-CoV-2 infection are being interrogated in these weeks to test the prophylactic efficacy of hydroxychloroquine.

These studies have been run in laboratories with the highest levels of biological safety (biosafety level-3 [39,40,44,45] and biosafety level-4 [41,42]) due to the high risk these pathogens pose to research personnel, which are very expensive to build and maintain, hence not readily available in most countries [46]. The modification of an antiviral, e.g. through lipid nanoparticle technology, as anticipated above, requires preliminary testing in vitro as well as in animal models. Specifically, there is need to demonstrate that the lipid structure does not impair the inhibitory activity of the encapsulated antiviral (e.g. does not increase its EC50 against the challenge virus). In healthy uninfected animals, biodistribution studies are subsequently needed to demonstrate that the encapsulated antiviral is capable of reaching the tissues in which the virus is expected to mostly replicate in vivo, and, in the case of a nucleoside analogue (like remdesivir), that its active phosphorylated moieties are produced at sufficient concentrations in those tissues. These preliminary pharmacokinetic studies will inform on the optimal dose of the encapsulated antiviral under scrutiny and on how frequently it will need to be administered in the pharmacodynamic studies. The latter studies can demonstrate the feasibility of the modified antiviral drug to exert its inhibitory activity in an infected host, hence an important step for the translation of the nanoparticle approach to human studies.

While alternative animal models could possibly serve the pharmacodynamic study objectives, the nonhuman primate model is likely the best model to accelerate this area of research. To my knowledge, coronaviruses less pathogenic to humans [47] but still sensitive to the inhibitory activity of remdesivir [48] (and possibly to other antiviral drugs [29]) have not been tested in nonhuman primates, although serologic studies suggest that these viruses may be able to replicate well in these hosts [49]. Indeed, a 229E coronavirus experimental infection study in normal volunteers failed to demonstrate efficacy of a nucleoside analogue for prophylaxis, as previously shown in rodent models, possibly due to the differential tissue pharmacokinetics of the specific drug under scrutiny in the two evolutionarily distant hosts [50].

In other words, “non-perfect” nonhuman primate models (i.e. those in which the SARS-CoV-2 or an older cousin does not cause disease yet replicates in tissues at levels similar to humans) can still generate useful data to screen prophylactic antiviral strategies, including, for instance, lipid nanoparticle formulations of “non-perfect” antiviral drugs (i.e. a putative antiviral drug failing to demonstrate a robust therapeutic effect in patients with advanced COVID-19 or if suboptimal drug levels in the lungs are confirmed from preclinical or post-mortem studies). Had we not discovered the rhesus-macaque model of HIV infection (in which the simian immunodeficiency virus [SIV] causes a disease similar to AIDS), we likely still would have generated pharmacodynamic data using the natural hosts of SIV infection (in which SIV does not cause disease, but still replicates in the body at levels similar to HIV in humans or SIV in the non-natural nonhuman-primate hosts [51]) equally useful for their inference to HIV-(post- and pre-exposure) prophylaxis (PEP and PrEP, respectively) in humans.

Had We the Equivalent of Truvada-Prep for SARS-CoV-2, How Would We Use it to Mitigate COVID-19?

Pharmacologic-based mitigation strategies to curb epidemics have been postulated [52], but their efficacy in synergy with social distancing and face mask wearing mitigation strategies (with or without digital contact-tracing technology [53]) for an epidemic with a doubling-time and dynamic features similar to COVID-19 [54,55] is today unknown. Consensus is growing among modelers, however, that mitigation strategies interventions (which primarily act on reducing the same variable of the viral transmission dynamic models adopted in their studies, i.e. the infectivity rate) work best in keeping the number of new cases at bay (or could even stop the epidemic [53]), if administered when the pool of infected people is small, i.e. during the early steps of a viral outbreak or when the R-naught (average number of people that one infected person will pass the virus to) has been sufficiently reduced, for instance following a period of effective lock-down [53,55]. The larger the initial pool of infected people, the more aggressive the interventions aimed to promptly control an epidemic may need to be (including voluntary centralized quarantine) [56].

Efforts in this area of mathematical modeling research are critically needed to serve this and any future viral outbreak. For bioethical reasons, similarly to what happened for PEP studies in the 1990s, once the effectiveness of the first available COVID-19 prophylaxes is demonstrated, it will be difficult to estimate the relative contribution of each mitigation strategy to the curve of new cases in a given region. Epidemiological models of COVID-19 for instance predict that a 50% reduction in within-population contact rates can already have a dramatic effect in slowing the course of the epidemic [54]. Massive data sharing among countries, which will likely adopt different combinations of those strategies at different times, will be of utmost importance to produce that knowledge.

The role of an antiviral prophylaxis goes beyond its ability to substantially impact the curve of cases. The high likelihood of SARS-CoV-2 transmission among individuals living in households with infected people [57] offers an important context in which a safe antiviral drug is highly desired to protect, first of all, those at high risk of severe disease, such as the elderly with chronic health conditions, as well as those at high risk of contracting the virus through occupational exposure. This would enhance the quality of life not only for uninfected adults living in the same household but also for the COVID-19 patients who could go through the quarantine period with less fear of infecting those who gravitate around their lives; a peace of mind that carries priceless benefits to patient welfare, somewhat similar (within the limitations of the proposed parallelism) to those experienced by HIV serodiscordant couples with the advent of Truvada-PrEP.

Acknowledgements

The author thanks Katelyn W. Le, from Frederick National Laboratory for Cancer Research/Leidos Biomedical Research, for providing medical writing editorial support during the preparation of this paper.

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Diabetes Mellitus at the Intersection of the COVID-19 Pandemic and the Opioid Crisis

DOI: 10.31038/EDMJ.2020432

Introduction

Boslet et al. used a secondary data analysis of the universe of drug overdoses in 1999-2016 obtained from the National Center for Health Statistics Detailed Multiple Cause of Death records to demonstrate that the number of deaths attributed to opioid-related overdoses could be 28 percent higher than first reported due to incomplete death records [1]. This discrepancy was more pronounced in several states, to include Alabama, Mississippi, Pennsylvania, Louisiana, and Indiana, where the estimated number of deaths more than doubles obscuring the scope of the opioid crisis and potentially affecting programs and funding intended to confront the epidemic [1]. Logistic regression and random forest models were performed to determine contributing causes substantially that improved predictive accuracy, while including county characteristics. Using a superior prediction model, they found that 71.8% of unclassified drug overdoses in 1999- 2016 involved opioids, and thus translating into 99 160 additional opioid-related deaths, or approximately 28% more than previously reported [1]. It is hoped a physician relies on census data as essential tools for understanding the importance of place-level characteristics on opioid mortality. Opioid mortality rates overall are higher in counties characterized by more economic disadvantage, more blue- collar and service employment, and higher opioid-prescribing rates [2]. Medical literature have reported that high rates of prescription opioid overdoses and overdoses involving both prescription and synthetic opioids cluster in more economically disadvantaged counties with larger concentrations of service industry workers [2]. Further, Monnat et al. suggest national policies to combat the opioid and larger drug crises, emphasis should be on developing locally  and regionally tailored interventions, with attention to place-based structural economic and social characteristics [2].

An appreciation as of April 2020, the United States now has 22 million unemployed, wiping out a decade of job gains. Woolhandler and Himmelstein assert with jobs and health insurance coverage disappearing as the COVID-19 pandemic rages, states that have declined to expand Medicaid should urgently reconsider [3]. Moreover, state tax revenues are plunging due to shelter in place orders and initiatives in place to have only essential workers to attend their place of business. The foreboding realization is that only the federal government can address this financial impending crisis [3]. Secondly these authors state health care coverage losses are likely to be steepest in states that have turned down the Patient Protection and Affordable Care Act’s Medicaid expansion [3]. Additionally, in expansion states, the share of persons who have lost or left a job who lacked coverage was 22.1% versus 8.3% for employed persons-a difference of 13.8 percentage points [3]. These authors acknowledge  that  although  the COVID-19 crisis demands urgent action, it also exposes the carelessness of tying health insurance to employment and the need for more thoroughgoing reform [3]. It is hoped that the issue of families who face the dual disaster of job loss and health insurance loss and who may suffer from opioid use disorder will be among the foremost issues on the legislative branch of the United States’ agenda. Haffajee et al., report opioid overdose deaths in the United  States continue to increase, reflecting a growing need to treat those with opioid use disorder [4]. Acknowledging that fading economic opportunity has been hypothesized to be an important factor associated with the United States opioid overdose crisis. Automotive assembly plant closures are culturally significant events that substantially erode local economic opportunities [5]. Moreover, Venkataramani et al. explores and investigates a community’s economy has on opioid overdose mortality. Their primary outcome was the county-level age-adjusted opioid overdose mortality rate [5]. Their secondary outcomes included the overall drug overdose mortality rate and prescription vs. illicit drug overdose mortality rates [5]. They discovered that from 1999 to 2016, automotive assembly plant closures were associated with increases in opioid overdose mortality [5]. These findings highlight the potential importance of eroding economic opportunity as a factor in the United States opioid overdose crisis [5]. Finally, Langbeer et al. concluded univariate, opioid-related morality was positively correlated with tobacco use, being non-Hispanic Caucasian individual, living in a rural area, obesity, being 65-years of age or older, and a higher rate of unemployment [6].

Gautam et al. reported that diabetes mellitus has well known costly complications but wanted to show through a retrospective model that costs of care for chronic pain treated with opioid analgesic medications would also be substantial [7]. They found that higher costs of care for opioid-treated patients appeared for all types of services and likely reflects multiple factors including morbidity from the underlying cause of pain, care and complications related to opioid use, and poorer control of diabetes as found in other investigations [7]. Schiemsky et al. reported a case of hypoglycemia caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol [8]. They further explain the sudden hypokalemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose [8]. Makunts et al. analyzed over twelve million reports from United States Food and Drug Administration Adverse Event Reporting System to provide evidence of increased propensity for hypoglycemia in patients taking tramadol when compared to patients taking other opioids, serotonin-norepinephrine reuptake inhibitors, and drugs affecting (NMDAR) activity [9]. They identified that both tramadol and methadone behave similarly to tramadol and has an association with hypoglycemia [9]. These findings accentuates the need for monitoring of a patient’s blood glucose given the overlap of the opioid crisis and COVID-19 pandemic.

As people across the United States and the rest of the world contends with coronavirus disease 2019 (COVID-19), the medical community to include podiatric physicians should realize the possibility that COVID-19 infection could hit some populations with  Substance Use Disorders (SUDs) particularly hard [10]. The coronavirus that causes COVID-19 attacks the lungs and could be an especially serious threat to those patients who smoke tobacco, marijuana or who vape. People with Opioid Use Disorder (OUD)  and  methamphetamine use disorder may also be vulnerable due to those drugs’ effects on respiratory and pulmonary health [10]. Additionally,  patients with   a substance use disorder are more likely to experience homelessness or incarceration than those in the general population, and these circumstances pose unique challenges regarding transmission of the virus that causes COVID-19. All these possibilities should be a focus of active surveillance as we work to understand this emerging health threat [10].

According to Volkow those persons who are isolated and stressed as much of the population is during the COVID-19 pandemic frequently turn to substances to alleviate their negative feelings [11]. Those in substance recovery will face stresses and heightened urges to use substances and will be at greatly increased risk for relapse [11]. Further, vulnerable populations those who smoke or vape, use opioids, or have a Substance Use Disorder (SUD) may have direct challenges to respiratory health, those with SUD may be especially susceptible to infection by the virus that causes COVID-19 and associated complications [11]. Impediments to delivering care to  this population, persons with SUD who develop COVID-19 may find it harder to get healthcare [11]. Those in recovery will also be uniquely challenged by social distancing measures [11]. Lastly, a risk for severe COVID-19 and death escalates with older age but is also concentrated among those who are immunocompromised or have underlying health conditions, including diabetes, cancer, and heart and respiratory diseases [11].

Mukherjee and El-Bassel report that people with opioid and other substance use disorders are disproportionately incarcerated, and recently released prisoners are ten times more likely to become homeless [12]. During the COVID-19 pandemic coupled without adequate planning, de-carceration efforts in may move people with Opioid Use Disorder from one at risk environment to another at risk environment [12]. Upon release, the risks associated with COVID-19, as well as HIV, viral hepatitis, Tuberculosis, overdose and homelessness that often accompany incarceration must be considered [12].

It is an accepted fact that not only does COVID-19 make addiction services harder to access but people who use drugs may   be at higher risk of infection given the dangerous overlap between addiction, incarceration, and the rapid spread of infections within confined spaces. Community campaigns to get nonviolent drug offenders released during this pandemic may not be sufficient to avoid incarcerated persons from becoming infected with COVID-19. A prisoner re-entry into regular society is difficult and dangerous from a health perspective, even during normal times. As the economy collapses, shelters and food banks have been overwhelmed, with already limited resources stretched thin on all levels in many communities.

Opioids and Increase of Infections

Schwetz et al. rely on clinical evidence to assert in their commentary that the rise in Opioid Use Disorder (OUD), bolstered by injection opioid use, conveys numerous downstream consequences and is fueling a surge in infectious diseases, such as Human Immunodeficiency Virus (HIV) infection with or  without  AIDS, the viral hepatitides, infective endocarditis, pneumonia, and  skin and soft-tissue infections [13,14]. Further, Schwetz et al. note the increasing infection rates and demographic trends of bacterial and fungal infections appear to mirror trends observed with the opioid epidemic [13,15]. They cite the example of the rate of methicillin- resistant Staphylococcus aureus infections among people who inject drugs more than doubled between the years of 2011 and 2016 [16]. Additionally, they assert the growing evidence has shown that certain opioids to include both morphine and fentanyl that have putative effects on both the innate and adaptive immune systems, dependent on drug dosage and duration of delivery [13]. Finally, these authors concluded using published data that the growing trend of infectious diseases emerging across the United States in areas with high rates of opioid use has created a significant combined impact on morbidity and mortality [13].

Wiese et al, conducted a retrospective cohort study to investigate long-acting opioid use and the risk of serious infections [17]. They used multivariable Poisson regression models to calculate adjusted incidence rate ratios and 95% confidence intervals to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores [17]. Moreover, they compared users of individual long-acting opioids to long-acting morphine users that considered the prototypical immunosuppressive opioid [17]. They determined the risk of serious infections among long-acting opioid users varies by opioid type [17]. They suggest that providers should carefully consider the risk of serious infections when making pain management decisions [17]. Karagiannis et al. acknowledge that chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system [18]. Further they ask the question how do opioids impact the immune system and recognize it is still barely characterized systematically [18]. In order to understand the immune modulatory effect of opioids in an unbiased way, here they perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls  to show that chronic opioid usage evokes widespread suppression   of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide [18]. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment was discovered [18]. Their findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program [18]. Lastly, their results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids [18]. These results are of upmost importance in understanding the use of opioids in patients with diabetes mellitus during the current COVID-19 pandemic.

Diabetes Mellitus and COVID-19 Pandemic

In the United States, 34.2 million or 10.5% of the total population have diabetes mellitus [19]. Among those aged 65 years or older, a population at higher risk for death from COVID-19, 26.8% has diabetes mellitus [19]. Muniyappa and Gubbi summarize that individuals with diabetes mellitus, hypertension, and severe obesity (BMI 40 kg/m2) are more likely to be infected and are at a higher risk for complications and death from COVID-19 [20]. Given, consideration to the high prevalence of cardiovascular disease (CVD), obesity, and hypertension in patients with diabetes mellitus, according to Muniyappa and Gubbi it is unknown whether .diabetes mellitus independently contributes to the increased risk of being infective with COVID-19 [20]. However, plasma glucose levels and diabetes mellitus are independent predictors for mortality and morbidity in patients with SARS [21]. Potential mechanisms that may increase the susceptibility for COVID-19 in patients with diabetes mellitus include: 1) higher affinity cellular binding and efficient virus entry, 2) decreased viral clearance, 3) diminished T cell function, 4) increased susceptibility to hyperinflammation and cytokine storm syndrome, and 5) presence of cardiovascular disease [20]. Additionally, diabetes mellitus inhibits neutrophil chemotaxis, phagocytosis, and intracellular killing of microbes. Impairments in adaptive immunity characterized by an initial delay in the activation of Th1 cell-mediated immunity and a late hyperinflammatory response is often observed in patients with diabetes [22].

Another point explained by Hussain et al. is that the clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death [23]. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and  mortality [23]. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19 [23].

Finally, Bode et al. proposed the concept that diabetes and/or uncontrolled hyperglycemia occur frequently among hospitalized patients with COVID-19 and are associated with worse outcomes [24]. To investigate this concept they performed a retrospective observational study of laboratory-confirmed COVID-19 adults evaluated glycemic and clinical outcomes in patients with and without  diabetes  and/or  acutely  uncontrolled  hyperglycemia  who were hospitalized [24]. Among hospitalized patients with COVID-19, diabetes and/or uncontrolled hyperglycemia occurred frequently [24]. These COVID-19 patients with diabetes and/or uncontrolled hyperglycemia had a longer length of stay and markedly higher mortality than patients without diabetes or uncontrolled hyperglycemia [24]. These investigators observed  that  patients  with uncontrolled hyperglycemia had a particularly high mortality rate [24]. The physician can appreciate the potential effects of drug treatment options being used in the management of COVID-19 on glucose and lipid profiles summarized in Table 1 [25].

Table 1: Summary of the potential effects of Medications options being used in the management of COVID-19 on glucose and lipid profiles.

Medications

Mechanism of action on COVID-19

Effect on glucose profile

Effect on lipid profile

Corticosteroids

Anti-inflammatory, blocks cytokine storm

Hyperglycemia

Dyslipidemia

Lopinavir/Ritonavir

Protease inhibitors, blocks viral cellular entry

Hyperglycemia Lipodystrophy

Dyslipidemia

Darunavir/Cobicistat

Protease inhibitors, blocks viral cellular entry

Hyperglycemia Lipodystrophy

Dyslipidemia

Remdesivir

Adenosine analogue, inhibits viral replication

Increased blood glucose

Increased blood lipids

Interferons (b1)

Cytokine, stimulate innate antiviral immunity

Can lead to autoimmune b-cell damage thereby, precipitating or worsening diabetes mellitus

Dyslipidemia

Chloroquine/Hydroxychloroquine

Increases host cell endosomal pH, prevents viral entry and immunomodulator

Improves glucose profile and HbA1c in people with Type 2 Diabetes Mellitus

Improves lipid profile in people with Type 2 Diabetes Mellitus

Azithromycin

Macrolide antibiotic

Risk of dysglycemia in people with diabetes mellitus

No robust data Being an enzyme inhibitor, may prolong half-life of statins

Camostat mesilate

Protease inhibitors, blocks viral maturation and entry into cells

Found to lower blood glucose levels in insulin-treated patients with diabetes mellitus

Not known

Tocilizumab

Monoclonal antibody against IL-6, blocks cytokine storm

Improves glucose profile and reduces HbA1c in people with rheumatoid arthritis and diabetes mellitus

Alters lipid profile in people with rheumatoid arthritis

Convalescent plasma

Provides anti-SARS-CoV-2 antibodies

Not known

Not known

Strategies for Managing Chronic Pain

The COVID-19 public health crisis has strained health care systems, creating an enigma for patients, pain medicine practitioners, hospital leaders, and regulatory officials [26]. Pain management providers rely on infection control precautions form a backbone of interventional- based and some alternative medicine to include: acupuncture, hands- on therapies such as massage and manual therapy practices [26]. These precautions are even more important during a pandemic where the potential exists for viral shedding from asymptomatic patients and disease transmission [26]. The clinicians need to acknowledge that many patients who would be seen in for chronic pain issues during the COVID-19 pandemic are in higher risk groups and full consideration should be given to minimizing patients congregating in a waiting room. Specialists should familiarize themselves to the new Health Human Services and Centers for Medicare and Medicaid Services relaxations on telemedicine provide a method for new patient and established patient visits [26]. In patients on opioids who may have run out of medications because of logistical obstacles or overuse, assessment of withdrawal signs can be challenging during remote visits. These symptoms such as diarrhea, rhinorrhea, abdominal pain and chills can be garnered from patient interviews, but may be difficult to corroborate [26]. On the other hand, some physical signs indicative of opioid withdrawal, particularly if prominent, can be observed remotely such as agitation, diaphoresis, piloerection, and possibly even pupillary size [26]. Monitoring patients for an elevated heart or pulse rate, which is a classic sign of opioid withdrawal, can sometimes be done by reliable patients or their caregivers [26]. The salient point that typical symptoms of COVID-19 overlap the typical symptoms of opioid withdrawal has to be realized by the podiatric physician so that a correct diagnosis can be determined and a negative outcome can be avoided. A list of the typical symptoms of COVID-19 infection along with the presenting typical symptoms of opioid withdrawal are presented in Table 2 so a comparison can be appreciated [27,28].

Table 2: Comparison List of the Typical Symptoms of Covid-19 Infection and Opioid Withdrawal Symptoms.

Covid-19 Infection Symptoms [25]

Opioid Withdrawal Symptoms [26] Symptomsappear72hoursafterlastdose

Fever

87.90%

Fever

Dry Cough

67.70%

Chills

Fatigue

38.10%

Body Aches

Sputum Production

Diarrhea

Shortness of Breath

Insomnia

Myalgia-Arthralgia

14.80%

Muscle Pain

Sore Throat

13.90%

Nausea

Headache

13.60%

Dilated Pupils

Chills

11.40%

Nausea-Vomiting

5%

Nasal Congestion

4.80%

Diarrhea

3.70%

Source: National Institute of Drug Abuse.
Source: Report of the WHO China.
Joint Mission on Coromavirus Disease 2019.

Conclusion

First, the negative economic impact of the COVID-19 pandemic and how it exacerbates the opioid crisis in America was presented.

Then certain factors of patients with substance abuse disorders and how they are disadvantaged by excessive and prolonged isolation and social distancing is presented. The effects of opioid use and addiction as well as the pathology Diabetes Mellitus on pulmonary and immune function that effect a patient’s response COVID-19 was presented. Lastly, strategies for managing chronic pain and access to medical care were presented. It is hoped the physician can appreciate the over shadowed area at the intersection of the COVID-19 Pandemic and the Opioid Crisis.

References

  1. Boslett AJ, Denham A, Hill EL (2020) Using contributing causes of death improves prediction of opioid involvement in unclassified drug overdoses in US death records. Addiction 115: 1308-1317.
  2. Monnat SM, Peters DJ, Berg MT, Hochstetler A (2019) Using Census Data to Understand County-Level Differences in Overall Drug Mortality and Opioid-Related Mortality by Opioid Type. Am J Public Health 109: 1084-1091. [crossref]
  3. Woolhandler S, Himmelstein DU (2020) Intersecting US. Epidemics: COVID-19 and Lack of Health Insurance [published online ahead of print, 2020 Apr 7]. Ann Intern Med 173: 63-64. [crossref]
  4. Haffajee RL, Lin LA, Bohnert ASB, Goldstick JE (2019) Characteristics of US Counties with High Opioid Overdose Mortality and Low Capacity to Deliver Medications for Opioid Use Disorder. JAMA Netw Open 2: e196373. [crossref]
  5. Venkataramani AS, Bair EF, O’Brien RL, Tsai AC (2019) Association between Automotive Assembly Plant Closures and Opioid Overdose Mortality in the United States: A Difference-in-Differences Analysis. JAMA Intern Med 180: 254-262. [crossref]
  6. Langabeer  JR,  Chambers  KA,  Cardenas-Turanzas  M,  Champagne-Langabeer   T (2020) County-level factors underlying opioid mortality in the United States [published online ahead of print, 2020 Mar 18]. Subst Abus 1-7.
  7. Gautam S, Franzini L, Mikhail OI, Chan W, Turner BJ (2016) Novel Measure of Opioid Dose and Costs of Care for Diabetes Mellitus: Opioid Dose and Health Care Costs. J Pain 17: 319-327. [crossref]
  8. Schiemsky T, Vundelinckx G, Croes K, Penders J, Desmet K, et al. (2020) An unconscious man with profound drug-induced hypoglycaemia. Biochem Med (Zagreb) 30: 010802. [crossref]
  9. Makunts TUA, Atayee RS, Abagyan R (2019) Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids. Sci Rep 9: 12490. [crossref]
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  12. Mukherjee TI, El-Bassel N (2020) The perfect storm: COVID-19, mass incarceration and the opioid epidemic [published online ahead of print, 2020 Jun 11]. Int J Drug Policy 102819.
  13. Schwetz TA, Calder T, Rosenthal E, Kattakuzhy S, Fauci AS (2019) Opioids, and Infectious Diseases: A Converging Public Health Crisis. J Infect Dis 220: 346-349. [crossref]
  14. Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, et al. (2018) Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study. Ann Intern Med 168: 396-404. [crossref]
  15. Ronan MV, Herzig SJ (2016) Hospitalizations related to opioid abuse/dependence and associated serious infections increased sharply, 2002-12. Health Aff (Millwood) 35: 832-837. [crossref]
  16. Jackson KA, Bohm MK, Brooks JT, Asher A, Nadle J, et al. (2018) Invasive methicillin- resistant Staphylococcus aureus infections among persons who inject drugs– six sites, 2005-2016. MMWR Morb Mortal Wkly Rep 67: 625-628. [crossref]
  17. Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, et al. (2019) Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study. Clin Infect Dis 68: 1862-1869. [crossref]
  18. Karagiannis TT, Cleary JP, Gok B, et al. (2020) Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program. Nat Commun 11: 2611.
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Prevalence of Colorectal Polyps in Patients with Chronic Hepatitis C Virus Infection in a Multi-Ethnic Hospital Population

DOI: 10.31038/AGHE.2020211

Abstract

Chronic hepatitis C virus infection has been associated with pre-cancerous colorectal lesions; however, there are limited data regarding the prevalence of Colorectal Polyps (CRP) in patients with Chronic Viral Hepatitis C (C-HCV). Accordingly, we conducted a retrospective study to explore this potential association by the review of an endoscopy database that included 1928 charts of adult patients who had undergone colonoscopies, and that revealed a higher prevalence of CRP in individuals with C-HCV, 67.1%, than in those without, 51.3%, (p= 0.001). Hyperplastic polyps comprised 56.8%, and tubular adenomata 36.5% of the polyps reported.In addition, there was a preponderance of C-HCV in subjects of Hispanic ethnicity, men, and individuals who had a history of smoking and alcohol use. The most common hepatitis C virus genotype was 1a, 62%.The prevalence of CRP in patients with C-HCV was higher than in those without; however, there was no significant association between C-HCV and adenomatous polyps, which suggests that C-HCV does not predispose to colorectal cancer.

Background

Chronic hepatitis C (C-HCV) is an important public health concern; thus, the impact of this viral infection on other comorbidities is of interest. Colorectal Polyps (CRP) are common gastrointestinal lesions but there are limited data regarding their prevalence in patients with C-HCV.

As C-HCV has been associated with malignancy [1-6], we hypothesized that CRPs would be more common in patients with C-HCV than in those without. Accordingly, the aim of this study was to explore that prevalence of CRPs, which can develop into colorectal cancer, in patients with C-HCV who had had a screening colonoscopy at H+H, Metropolitan, a community hospital that serves the multiethnic population of East Harlem.

Methods

Data from records of 1,928 patients who had a complete colonoscopy report in the database from the Division of Gastroenterology and Hepatobiliary Diseases from January 1st, 2011 to December 31st, 2015 were retrospectively reviewed. The study group was comprised of adults with C-HCV, defined as detected HCV RNA in serum, who had undergone a complete screening or diagnostic colonoscopy after a good bowel preparation confirmed during the procedure.The control group was composed of patients who underwent a screening colonoscopy and who did not have antibodies for the hepatitis C virus.

In addition, we examined some of the characteristics of the population such as ethnicity, gender, and toxic habits to explore potential associations with C-HCV. Correlations between categorical variables were analyzed by the use of Chi-square test, and t-test for continuous variables between groups. Bivariate analysis was applied to identify any links between the exposure variable and the outcome variable. A p value of < 0.05 was considered significant. Statistical analysis was performed with SPSS 24 software. This study was approved by the Biomedical Research Alliance of New York (BRANY).

Results

Among 1928 individuals with complete colonoscopies, we identified 960 patients who had been tested for hepatitis C virus infection, of whom 159 had C-HCV. Gender was the only factor that was significantly different in the C-HCV group versus the control, with the majority, 65%, being men (p<0.001) (Figure1). Fifty-three percent of the patients with C-HCV self-identified as Hispanics. In addition, 34% and 38% of the patients in the HCV infected group reported an active/former smoker status or admitted being at least a social alcohol consumer, respectively.

AGHE-2-1-203-g001

Figure 1. Complete colonoscopies among 1928 individuals.

There was a higher prevalence of CRP in individuals with C-CHV, 67.1%, in comparison with those without, 51.3% (p= 0.001). Hyperplastic polyps comprised 56.8% of the polyps and tubular adenomata, 36%. Hyperplastic was the histopathologic predominant type in patients with C-HCV, 75%, and in the control group, 69%; however, this difference was statistically significant (p<0.005). Most patients with C-HCV, 62%, had genotype 1a (Figure 2). Mostpatients with C-HCV, 62%, had genotype 1a.

AGHE-2-1-203-g002

Figure 2. Distribution of colorectal polyps by histopathology.

Discussion

In this study, the prevalence of CRP in patients with C-HCV was higher than in those without.The predominant histology of the CRP was hyperplastic. There was a preponderance of C-HCV in men, in smokers, in those who used alcohol, and in subjects of Hispanic ethnicity, consistent with the ethnicity of the majority of patients attended at Metropolitan Hospital.

Colorectal cancer has been associated with C-HCV [7]; however, we excluded from this study patients with history or active colorectal cancer.CRP were more prevalent in the C-HCV group of patients with a predominance of hyperplastic histology [8-44]. Hyperplastic Polyps (HP) are included in the serrated polyp classification [45-50], which encompasses Sessile Serrated Lesions (SSL) and Traditional Serrated Adenomas (TSA).SSL and TSA have been associated with malignancy; however, none of the polyps found in this study had a serrated histology.

The HCV virus itself may stimulate cell proliferation, inflammation and apoptosis increasing the risk of polyp formation [26-29]. The hepatitis C virus has been found in colonic cells such as lymphocytes, macrophages, monocytes [6,8-15]. As polyps possibly result from a defective/enhanced repair process after a mucosal injury [26], and mutations seem to be the molecular events leading to polyp’s formation, we may speculate that the presence of viral RNA in the colonic mucosal cells may also cause some disruption in this process [51-78].

53% and 38% of the patients with C-HCV reported active or former smoker status or admitted being at least a social alcohol consumer.Cigarette smoking has been associated with an increased in progression of liver disease in patients with C-HCV [20]. In this study, data were recorded as current smokers and former smokers while the Nonsmokers (NS) were those who stated have never smoked. This group was comprised of 34% of the patients with C-HCV versus 14% in the control group, a difference that was statistically significant (p<0.001). This finding is consistent with a prior report [18,19].

The association between alcohol use disorder and C-HCV has been described [23,24]. Alcohol use was reported more frequently by the patients with C-HCV, 38% versus 20% in the control group (p< 0.001).

In summary,there was a preponderance of C-HCV, most commonly genotype 1a, among subjects of Hispanic ethnicity, men, and individuals who had a history of smoking and alcohol use.Hepatitis C virus infection is not associated with adenomatous colonic polyps, and thus, it does not predispose by itself to colorectal cancer.

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Albedo Changes Drive 4.9 to 9.4°C Global Warming by 2400

Abstract

This study ties increasing climate feedbacks to projected warming consistent with temperatures when Earth last had this much CO2 in the air. The relationship between CO2 and temperature in a Vostok ice core is used to extrapolate temperature effects of today’s CO2 levels. The results suggest long-run equilibrium global surface temperatures (GSTs) 5.1°C warmer than immediately “pre-industrial” (1880). The relationship derived holds well for warmer conditions 4 and 14 million years ago (Mya). Adding CH4 data from Vostok yields 8.5°C warming due to today’s CO2 and CH4 levels. Long-run climate sensitivity to doubled CO2, given Earth’s current ice state, is estimated to be 8.2°C: 1.8° directly from CO2 and 6.4° from albedo effects. Based on the Vostok equation using CO2 only, holding ∆GST to 2°C requires 318 ppm CO2. This means Earth’s remaining carbon budget for +2°C is estimated to be negative 313 billion tonnes. Meeting this target will require very large-scale CO2 removal. Lagged warming of 4.0°C (or 7.4°C when CH4 is included), starting from today’s 1.1°C ∆GST, comes mostly from albedo changes. Their effects are estimated here for ice, snow, sulfates, and cloud cover. This study estimates magnitudes for sulfates and for future snow changes. Magnitudes for ice, cloud cover, and past snow changes are drawn from the literature. Albedo changes, plus their water vapor multiplier, caused an estimated 39% of observed GST warming over 1975-2016. Estimated warming effects on GST by water vapor; ocean heat; and net natural carbon emissions (from permafrost, etc.), all drawn from the literature, are included in projections alongside ice, snow, sulfates, and clouds. Six scenarios embody these effects. Projected ∆GSTs on land by 2400 range from 2.4 to 9.4°C. Phasing out fossil fuels by 2050 yields 7.1°C. Ending fossil fuel use immediately yields 4.9°C, similar to the 5.1°C inferred from paleoclimate studies for current CO2 levels. Phase-out by 2050 coupled with removing 71% of CO2 emitted to date yields 2.4°C. At the other extreme, postponing peak fossil fuel use to 2035 yields +9.4°C GST, with more warming after 2400.

Introduction

The December 2015 Paris climate pact set a target of limiting global surface temperature (GST) warming to 2°C above “pre-industrial” (1750 or 1880) levels. However, study of past climates indicates that this will not be feasible, unless greenhouse gas (GHG) levels, led by carbon dioxide (CO2) and methane (CH4), are reduced dramatically. Already, global air temperature at the land surface (GLST) has warmed 1.6°C since the 1880 start of NASA’s record [1]. (Temperatures in this study are 5-year moving averages from NASA, Goddard Institute for Space Studies, in °C. Baseline is 1880 unless otherwise noted.) The GST has warmed by 2.5°C per century since 2000. Meanwhile, global sea surface temperature (=(GST – 0.29 * GLST)/0.71) has warmed by 0.9°C since 1880 [2].

The paleoclimate record can inform expectations of future warming from current GHG levels. This study examines conditions during ice ages and during the most recent (warmer) epochs when GHG levels were roughly this high, some lower and some higher. It strives to connect future warming derived from paleoclimate records with physical processes, mostly from albedo changes, that produce the indicated GST and GLST values.

The Temperature Record section examines Earth’s temperature record, over eons. Paleoclimate data from a Vostok ice core covering 430,000 years (430 ky) is examined. The relations among changes in GST relative to 1880, hereafter “∆°C”, and CO2 and CH4 levels in this era colder than now are estimated. These relations are quite consistent with the ∆°C to CO2 relation in eras warmer than now, 4 and 14 Mya. Overall climate sensitivity is estimated based on them. Earth’s remaining carbon budget to keep warming below 2°C is calculated next, based on the equations relating ∆°C to CO2 and CH4 levels in the Vostok ice core. That budget is far less than zero. It requires returning to CO2 levels of 60 years ago.

The Feedback Pathways section discusses the major factors that lead from our present GST to the “equilibrium” GST implied by the paleoclimate data, including a case with no further human carbon emissions. This path is governed by lag effects deriving mainly from albedo changes and their feedbacks. Following an overview, eight major factors are examined and modeled to estimate warming quantities and time scales due to each. These are (1) loss of sulfates (SO4) from ending coal use; (2) snow cover loss; (3) loss of northern and southern sea ice; (4) loss of land ice in Antarctica, Greenland and elsewhere; (5) cloud cover changes; (6) water vapor increases due to warming; (7) net emissions from permafrost and other natural carbon reservoirs; and (8) warming of the deep ocean.

Particular attention is paid to the role that anthropogenic and other sulfates have played in modulating the GST increase in the thermometer record. Loss of SO4 and northern sea ice in the daylight season will likely be complete not long after 2050. Losses of snow cover, southern sea ice, land ice grounded below sea level, and permafrost carbon, plus warming the deep oceans, should happen later and/or more slowly. Loss of other polar land ice should happen still more slowly. But changes in cloud cover and atmospheric water vapor can provide immediate feedbacks to warming from any source.

In the Results section, these eight factors, plus anthropogenic CO2 emissions, are modeled in six emission scenarios. The spreadsheet model has decadal resolution with no spatial resolution. It projects CO2 levels, GSTs, and sea level rise (SLR) out to 2400. In all scenarios, GLST passes 2°C before 2040. It has already passed 1.5°. The Discussion section lays out the implications of Earth’s GST paths to 2400, implicit both in the paleoclimate data and in the development of specific feedbacks identified for quantity and time-path estimation. These, combined with a carbon emissions budget to hold GST to 2°C, highlights how crucial CO2 removal (CDR) is. CDR is required to go beyond what emissions reduction alone can achieve. Fifteen CDR methods are enumerated. A short overview of solar radiation management follows. It may be required to supplement ending fossil fuel use and large-scale CDR.

The Temperature Record

In a first approach, temperature records from the past are examined for clues to the future. Like causes (notably CO2 levels) should produce like effects, even when comparing eras hundreds of thousands or millions of years apart. As shown in Figure 1, Earth’s surface can grow far warmer than now, even 13°C warmer, as occurred some 50 Mya. Over the last 2 million years, with more ice, temperature swings are wider, since albedo changes – from more ice to less ice and back – are larger. For GSTs 8°C or warmer than now, ice is rare. Temperature spikes around 55 and 41 Mya show that the current one is not quite unique.

fig 1

Figure 1: Temperatures and Ice Levels over 65 Million Years [3].

Some 93% of global warming goes to heat Earth’s oceans [4]. They show a strong warming trend. Ocean heat absorption has accelerated, from near zero in 1960: 4 zettaJoules (ZJ) per year from 1967 to 1990, 7 from 1991 to 2005, and 10 from 2010 to 2016 [5]. 10 ZJ corresponds to 100 years of US energy use. The oceans now gain 2/3 as much heat per year as cumulative human energy use or enough to supply US energy use for 100 years [6] or the world’s for 17 years. By 2011, Earth was absorbing 0.25% more energy than it emits, a 300 (±75) million MW heat gain [7]. Hansen deduced in 2011 that Earth’s surface must warm enough to emit another 0.6 Wm-2 heat to balance absorption; the required warming is 0.2°C. The imbalance has probably increased since 2011 and is likely to increase further with more GHG emissions. Over the last 100 years (since 1919), GSTs have risen 1.27°C, including 1.45°C for the land surface (GLST) alone [1]. The GST warming rate from 2000 to 2020 was 0.24°C per decade, but 0.35 over the most recent decade [1,2]. At this rate, warming will exceed 2°C in 2058 for GST and in 2043 for GLST only.

Paleoclimate Analysis

Atmospheric CO2 levels have risen 47% since 1750, including 40% since 1880 when NASA’s temperature records begin [8]. CH4 levels have risen 114% since 1880. CO2 levels of 415 parts per million (ppm) in 2020 are the highest since 14.1 to 14.5 Mya, when they ranged from 430 to 465 ppm [9]. The deep ocean then (over 400 ky) ranged around 5.6°C±1.0°C warmer [10] and seas were 25-40 meters higher [9]. CO2 levels were almost as high (357 to 405 ppm) 4.0 to 4.2 Mya [11,12]. SSTs then were around 4°C±0.9°C warmer and seas were 20-35 meters higher [11,12].

The higher sea levels in these two earlier eras tell us that ice then was gone from almost all of the Greenland (GIS) and West Antarctic (WAIS) ice sheets. They hold an estimated 10 meters (7 and 3.2 modeled) of SLR between them [13,14]. Other glaciers (chiefly in Arctic islands, the Himalayas, Canada, Alaska, and Siberia) hold perhaps 25 cm of SLR [15]. Ocean thermal expansion (OTE), currently about (~) 1 mm/year [5], is another factor in SLR. This corresponds to the world ocean (to the bottom) currently warming by ~0.002°Kyr-1. The higher sea levels 4 and 14 Mya indicate 10-30 meters of SLR that could only have come from the East Antarctic ice sheet (EAIS). This is 17-50% of the current EAIS volume. Two-thirds of the WAIS is grounded below sea level, as is 1/3 in the EAIS [16]. Those very areas (which are larger in the EAIS than the WAIS) include the part of East Antarctica most likely to be subject to ice loss over the next few centuries [17]. Sediments from millions of years ago show that the EAIS then had retreated hundreds of kilometers inland [18].

CO2 levels now are somewhat higher than they were 4 Mya, based on the current 415 ppm. This raises the possibility that current CO2 levels will warm Earth’s surface 4.5 to 5.0°C, best estimate 4.9°, over 1880 levels. (This is 3.4 to 3.9°C warmer than the current 1.1°C.) Consider Vostok ice core data that covers 430 ky [19]. Removing the time variable and scatter-plotting ∆°C against CO2 levels as blue dots (the same can be done for CH4), gives Figure 2. Its observations span the last 430 ky, at 10 ky resolution starting 10 kya.

fig 2

Figure 2: Temperature to Greenhouse Gas Relationship in the Past.

Superimposed on Figure 2 are trend lines from two linear regression equations, using logarithms, for temperatures at Vostok (left-hand scale): one for CO2 (in ppm) alone and one for both CO2 and CH4 (ppb). The purple trend line in Figure 2, from Equation (1) for Vostok, uses only CO2. 95% confidence intervals in this study are shown in parentheses with ±.

(1) ∆°C = -107.1 (±17.7) + 19.1054 (±3.26) ln(CO2).

The t-ratios are -11.21 and 11.83 for the intercept and CO2 concentration, while R2 is 0.773 and adjusted R2 is 0.768. The F statistic is 139.9. All are highly significant. This corresponds to a climate sensitivity of 13.2°C at Vostok [19.1054 * ln (2)] for doubled CO2, within the range of 180 to 465 ppm CO2. As shown below, most of this is due to albedo changes and other amplifying feedbacks. Therefore, climate sensitivity will decline as ice and snow become scarce and Earth’s albedo stabilizes. The green trend line in Figure 2, from Equation (2) for Vostok, adds a CH4 variable.

(2) ∆°C = -110.7 (±14.8) +11.23 (±4.55) ln(CO2) + 7.504 (±3.48) ln(CH4).

The t-ratios are -15.05, 4.98, and 4.36 for the intercept, CO2, and CH4. R2 is 0.846 and adjusted R2 is 0.839. The F statistic of 110.2 is highly significant. To translate temperature changes at the Vostok surface (left-hand axis) over 430 ky to changes in GST (right-hand axis), the ratio of polar change to global over the past 2 million years is used, from Snyder [20]. Snyder examined temperature data from many sedimentary sites around the world over 2 My. Her results yield a ratio for polar to global warming: 0.618. This relates the left- and right-hand scales in Figure 2. The GST equations, global instead of Vostok local, corresponding to Equations (1) and (2) for Vostok, but using the right-hand scale for global temperature, are:

(3) ∆°C = -66.19 + 11.807 ln(CO2) and

(4) ∆°C = -68.42 + 6.94 ln(CO2) + 4.637 ln(CH4).

Both equations yield good fits for 14.1 to 14.5 Mya and 4.0 to 4.2 Mya. Equation 3 yields a GST climate sensitivity estimate of 8.2° (±1.4) for doubled CO2. Table 1 below shows the corresponding GSTs for various CO2 and CH4 levels. CO2 levels range from 180 ppm, the lowest recorded during the past four ice ages, to twice the immediately “pre-industrial” level of 280 ppm. Columns D, I and N add 0.13°C to their preceding columns, the difference the 1880 GST and the 1951-80 mean GST used for the ice cores. Rows are included for CO2 levels corresponding to 1.5 and 2°C warmer than 1880, using the two equations, and for the 2020 CO2 level of 415 ppm. The CH4 levels (in ppb) in column F are taken from observations or extrapolated. The CH4 levels in column K are approximations of the CH4 levels about 1880, before human activity raised CH4 levels much – from some mixture of fossil fuel extraction and leaks, landfills, flooded rice paddies, and large herds of cattle.

Other GHGs (e.g., N2O and some not present in the Vostok ice cores, such as CFCs) are omitted in this discussion and in modeling future changes. Implicitly, this simplifying assumption is that the weighted rate of change of other GHGs averages the same as CO2.

Implications

Applying Equation (3) using only CO2, now at 415 ppm, yields a future GST 4.99°C warmer than the 1951-80 baseline. This translates to 5.12°C warmer than 1880, or 3.99°C warmer than 2018-2020 (2). This is consistent not only with the Vostok ice core records, but also with warmer Pliocene and Miocene records using ocean sediments from 4 and 14 Mya. However, when today’s CH4 levels, ~ 1870 ppb, are used in Equation (4), indicated equilibrium GST is 8.5°C warmer than 1880. Earth’s GST is currently far from equilibrium.

Consider the levels of CO2 and CH4 required to meet Paris goals. To hold GST warming to 2°C requires reducing atmospheric CO2 levels to 318 ppm, using Equation (3), as shown in Table 1. This requires CO2 removal (CDR), at first cut, of (415-318)/(415-280) = 72% of human CO2 emissions to date, plus any future ones. Equation (3) also indicates that holding warming to 1.5°C requires reducing CO2 levels to 305 ppm, equivalent to 81% CDR. Using Equation (4) with pre-industrial CH4 levels of 700 ppb, consistent with 1750, yields 2°C GST warming for CO2 at 314 ppm and 1.5°C for 292 ppm CO2. Human carbon emissions from fossil fuels from 1900 through 2020 were about 1600 gigatonnes (GT) of CO2, or about 435 GT of carbon [21]. Thus, using Equation (3) yields an estimated remaining carbon budget, to hold GST warming to 2°C, of negative 313 (±54) GT of carbon, or ~72% of fossil fuel CO2 emissions to date. This is only the minimum CDR required. First, removal of other GHGs may be required. Second, any further human emissions make the remaining carbon budget even more negative and require even more CDR. Natural carbon emissions, led by permafrost ones, will increase. Albedo feedbacks will continue, warming Earth farther. Both will require still more CDR. So, the true remaining carbon budget may actually be in the negative 400-500 GT range, and most certainly not hundreds of GT greater than zero.

Table 1: Projected Equilibrium Warming across Earth’s Surface from Vostok Ice Core Analysis (1951-80 Baseline).

table 1

The difference between current GSTs and equilibrium GSTs of 5.1 and 8.5°C stem from lag effects. The lag effects come mostly from albedo changes and their feedbacks. Most albedo changes and feedbacks happen over days to decades to centuries. Ones due to land ice and vegetation changes can continue over longer timescales. However, cloud cover and water vapor changes happen over minutes to hours. The specifics (except vegetation, not examined or modelled) are detailed in the Feedback Pathways section below.

However, the bottom two lines of Table 1 probably overestimate the temperature effects of 500 and 560 ppm of CO2, as discussed further below. This is because albedo feedbacks from ice and snow, which in large measure underlie the derivations from the ice core, decline with higher temperatures outside the CO2 range (180-465 ppm) used to derive and validate Equations (1) through (4).

Feedback Pathways to Warming Indicated by Paleoclimate Analysis

To hold warming to 2°C or even 1.5°, large-scale CDR is required, in addition to rapid reductions of CO2 and CH4 emissions to almost zero. As we consider the speed of our required response, this study examines: (1) the physical factors that account for this much warming and (2) the possible speed of the warming. As the following sections show, continued emissions speed up amplifying feedback processes, making “equilibrium” GSTs still higher. So, rapid emission reductions are the necessary foundation. But even an immediate end to human carbon emissions will be far from enough to hold warming to 2°C.

The first approach to projecting our climate future, in the Temperature Record section above, drew lessons from the past. The second approach, in the Feedback Pathways section here and below, examines the physical factors that account for the warming. Albedo effects, where Earth reflects less sunlight, will grow more important over the coming decades, in part because human emissions will decline. The albedo effects include sulfate loss from ending coal burning, plus reduced extent of snow, sea ice, land-based ice, and cloud cover. Another key factor is added water vapor, a powerful GHG, as the air heats up from albedo changes. Another factor is lagged surface warming, since the deeper ocean heats up more slowly than the surface. It will slowly release heat to the atmosphere, as El Niños do.

A second group of physical factors, more prominent late this century and beyond, are natural carbon emissions due to more warming. Unlike albedo changes, they alter CO2 levels in the atmosphere. The most prominent is from permafrost. Other major sources are increased microbial respiration in soils currently not frozen; carbon evolved from warmer seas; release of seabed CH4 hydrates; and any net decreased biomass in forests, oceans, and elsewhere.

This study estimates rough magnitudes and speeds of 13 factors: 9 albedo changes (including two for sea ice and four for land ice); changes in atmospheric water vapor and other ocean-warming effects; human carbon emissions; and natural emissions – from permafrost, plus a multiplier for the other natural carbon emissions. Characteristic time scales for these changes to play out range from decades for sulfates, northern and southern sea ice, human carbon emissions, and non-polar land ice; to centuries for snow, permafrost, ocean heat content, and land ice grounded below sea level; to millennia for other land ice. Cloud cover and water vapor respond in hours to days, but never disappear. The model also includes normal rock weathering, which removes about 1 GT of CO2 per year [22], or about 3% of human emissions.

Anthropogenic sulfur loss and northern sea ice loss will be complete by 2100 and likely more than half so by 2050, depending on future coal use. Snow cover and cloud cover feedbacks, which respond quickly to temperature change, will continue. Emissions from permafrost are modeled as ramping up in an S-curve through 2300, with small amounts thereafter. Those from seabed CH4 hydrates and other natural sources are assumed to ramp up proportionately with permafrost: jointly, by half as much. Ice loss from the GIS and WAIS grounded below sea level is expected to span many decades in the hottest scenarios, to a few centuries in the coolest ones. Partial ice loss from the EAIS, led by the 1/3 that is grounded below sea level, will happen a bit more slowly. Other polar ice loss should happen still more slowly. Warming the deep oceans, to reestablish equilibrium at the top of the atmosphere, should continue for at least a millennium, the time for a circuit of the world thermohaline ocean circulation.

This analysis and model do not include changes in (a) black carbon; (b) mean vegetation color, as albedo effects of grass replacing forests at lower latitudes may outweigh forests replacing tundra and ice at higher latitudes; (c) oceanic and atmospheric circulation; (d) anthropogenic land use; (e) Earth’s orbit and tilt; or (f) solar output.

Sulfate Effects

SO4 in the air intercepts incoming sunlight before it arrives at Earth’s surface, both directly and indirectly via formation of cloud condensation nuclei. It then re-radiates some of that energy upward, for a net cooling effect at Earth’s surface. Mostly, sulfur impurities in coal are oxidized to SO2 in burning. SO2 is converted to SO4 by chemical reactions in the troposphere. Residence times are measured in days. Including cooling from atmospheric SO4 concentrations explains a great deal of the variation between the steady rise in CO2 concentrations and the variability of GLST rise since 1880. Human SO2 emissions rose from 8 Megatonnes (MT) in 1880 to 36 MT in 1920, 49 in 1940, and 91 in 1960. They peaked at 134 MT in 1973 and 1979, before falling to 103-110 during 2009-16 [23]. Corresponding estimated atmospheric SO4 concentrations rose from 41 parts per billion (ppb) in 1880 (and a modestly lower amount before then), to 90 in 1920, 85 in 1940, and 119 in 1960, before reaching peaks of 172-178 during 1973-80 [24] and falling to 130-136 over 2009-16. Some atmospheric SO4 is from natural sources, notably dimethyl sulfides from some ocean plankton, some 30 ppb. Volcanoes are also an important source of atmospheric sulfates, but only episodically (mean 8 ppb) and chiefly in the stratosphere (from large eruptions), with a typical residence time there of many months.

Figure 3 shows the results of a linear regression analysis, in blue, of ∆°C from the thermometer record and concentrations of CO2, CH4, and SO4. SO4 concentrations between the dates referenced above are interpolated from human emissions, added to SO4 levels when human emissions were very small (1880). All variables shown are 5-year moving averages and SO4 is lagged by 1 year. CO2, CH4, and SO4 are measured in ppm, ppb and ppb, respectively. The near absence of an upward trend in GST from 1940 to 1975 happened at a time when human SO2 emissions rose 170% from 1940 to 1973 [23]. This large SO4 cooling effect offset the increased GHG warming effect, as shown in Figure 3. The analysis shown in Equation (5) excludes the years influenced by the substantial volcanic eruptions shown. It also excludes the 2 years before and 2-4 years after the years of volcanic eruptions that reached the stratosphere, since 5-year moving temperature averages are used. In particular, it excludes data from the years surrounding eruptions labeled in Figure 3, plus smaller but substantial eruptions in 1886, 1901-02, 1913, 1932-33, 1957, 1979-80, 1991 and 2011. This leaves 70 observations in all.

fig 3

Figure 3: Land Surface Temperatures, Influenced by Sulfate Cooling.

Equation (5)’s predicted GLSTs are shown in blue, next to actual GLSTs in red.

(5) ∆°C = -20.48 (±1.57) + 09 (±0.65) ln(CO2) + 1.25 (±0.33) ln(CH4) – 0.00393 (±0.00091) SO4

R2 is 0.9835 and adjusted R2 0.9828. The F-statistic is 1,312, highly significant. T-ratios for CO2, CH4, and SO4 respectively are 7.10, 7.68, and -8.68. This indicates that CO2, CH4, and SO4 are all important determinants of GLSTs. The coefficient for SO4 indicates that reducing SO4 by 1 ppb will increase GLST by 0.00393°C. Deleting the remaining human 95 ppb of SO4 added since 1880, as coal for power is phased out, would raise GLST by 0.37°C.

Snow

Some 99% of Earth’s snow cover, outside of Greenland and Antarctica, is in the northern hemisphere (NH). This study estimates the current albedo effect of snow cover in three steps: area, albedo effect to date, and future rate of snow shrinkage with rising temperatures. NH snow cover averages some 25 million km2 annually [25,26]. 82% of month-km2 coverage is during November through April. 25 million km2 is 2.5 times the 10 million km2 mean annual NH sea ice cover [27]. Estimated NH snow cover declined about 9%, about 2.2 million km2, from 1967 to 2018 [26]. Chen et al. [28] estimated that NH snow cover decreased by 890,000 km2 per decade for May to August over 1982 to 2013, but increased by 650,000 km2 per decade for November to February. Annual mean snow cover fell 9% over this period, as snow cover began earlier but also ended earlier: 1.91 days per decade [28]. These changes resulted in weakened snow radiative forcing of 0.12 (±0.003) W m-2 [28]. Chen estimated the NH snow timing feedback as 0.21 (±0.005) W m-2 K-1 in melting season, from 1982 to 2013 [28].

Future Snow Shrinkage

However, as GST warms further, annual mean snow cover will decline substantially with GST 5°C warmer and almost vanish with 10°. This study considers analog cities for snow cover in warmer places and analyzes data for them. It follows with three latitude and precipitation adjustments. The effects of changes in the timing of when snow is on the ground (Chen) are much smaller than from how many days snow is on the ground (see analog cities analysis, below). So, Chen’s analysis is of modest use for longer time horizons.

NH snow-covered area is not as concentrated near the pole as sea ice. Thus, sun angle leads to a larger effect by snow on Earth’s reflectivity. The mean latitude of northern snow cover, weighted over the year, is about 57°N [29], while the corresponding mean latitude of NH sea ice is 77 to 78°N. The sine of the mean sun angle (33°) on snow, 0.5454, is 2.52 times that for NH sea ice (12.5° and 0.2164). The area coverage (2.5) times the sun angle effect (2.52) suggests a cooling effect of NH snow cover (outside Greenland) about 6.3 times that for NH sea ice. [At high sun angles, water under ice is darker (~95% absorbed or 5% reflected when the sun is overhead, 0°) than rock, grass, shrubs, and trees under snow. This suggests a greater albedo contrast for losing sea ice than for losing snow. However, at the low sun angles that characterize snow latitudes, water reflects more sunlight (40% at 77° and 20% at 57°), leaving much less albedo contrast – with white snow or ice – than rocks and vegetation. So, no darkness adjustment is modeled in this study]. Using Hudson’s 2011 estimate [30] for Arctic sea ice (see below) of 0.6 W m-2 in future radiative forcing, compared to 0.1 to date for the NH sea ice’s current cooling effect, indicates that the current cooling effect of northern snow cover is about 6.3 times 0.6 W m-2 = 3.8 W m-2. This is 31 times the effect of snow cover timing changes, from Chen’s analysis.

To model evolution of future snow cover as the NH warms, analog locations are used for changes in snow cover’s cooling effect as Earth’s surface warms. This cross-sectional approach uses longitudinal transects: days of snow cover at different latitudes along roughly the same longitude. For the NH, in general (especially as adjusted for altitude and distance from the ocean), temperatures increase as one proceeds southward, while annual days of snow cover decrease. Three transects in the northern US and southern Canada are especially useful, because the increases in annual precipitation with warmer January temperatures somewhat approximate the 7% more water vapor in the air per 1°C of warming (see “In the Air” section for water vapor). The transects shown in Table 2 are (1) Winnipeg, Fargo, Sioux Falls, Omaha, Kansas City; (2) Toronto, Buffalo, Pittsburgh, Charleston WV, Knoxville; and (3) Lansing, Detroit, Cincinnati, Nashville. Pooled data from these 3 transects, shown at the bottom of Table 2, indicate 61% as many days as now with snow cover ≥ 1 inch [31] with 3°C local warming, 42% with 5°C, and 24% with 7°C. However, these degrees of local warming correspond to less GST warming, since Earth’s land surface has warmed faster than the sea surface and observed warming is generally greater as one proceeds from the equator toward the poles; [1,2,32] the gradient is 1.5 times the global mean for 44-64°N and 2.0 times for 64-90°N [32]. These latitude adjustments for local to global warming pair 61% as many snow cover days with 2°C GLST warming, 42% with 3°C, and 24% with 4°C. This translates to approximately a 19% decrease in days of snow cover per 1°C warming.

Table 2: Snow Cover Days for Transects with ~7% More Precipitation per °C. Annual Mean # of Days with ≥ 1 inch of Snow on Ground.

table 2

This study makes three adjustments to the 19%. First, the three transects feature precipitation increasing only 4.43% (1.58°C) per 1°C warming. This is 63% of the 7% increase in global precipitation per 1°C warming. So, warming may bring more snowfall than the analogs indicate directly. Therefore the 19% decrease in days of snow cover per 1°C warming of GLST is multiplied by 63%, for a preliminary 12% decrease in global snow cover for each 1°C GLST warming. Second, transects (4) Edmonton to Albuquerque and (5) Quebec to Wilmington NC, not shown, lack clear precipitation increases with warming. But they yield similar 62%, 42%, and 26% as many days of snow cover for 2, 3, and 4°C increases in GST. Since the global mean latitude of NH snow cover is about 57°, the southern Canada figure should be more globally representative than the 19% figure derived from the more southern US analysis. Use of Canadian cities only (Edmonton, Calgary, Winnipeg, Sault Ste. Marie, Toronto, and Quebec, with mean latitude 48.6°N) yields 73%, 58%, and 41% of current snow cover with roughly 2, 3, and 4°C warming. This translates to a 15% decrease in days of snow cover in southern Canada per 1°C warming of GLST. 63% of this, for the precipitation adjustment, yields 9.5% fewer days of snow cover per 1°C warming of GLST. Third, the southern Canada (48.6°N) figure of 9.5% warrants a further adjustment to represent an average Canadian and snow latitude (57°N). Multiplying by sin(48.6°)/sin(57°) yields 8.5%. The story is likely similar in Siberia, Russia, north China, and Scandinavia. So, final modeled snow cover decreases by 8.5% (not 19, 12 or 9.5%) of current amounts for each 1°C rise in GLST. In this way, modeled snow cover vanishes completely at 11.8°C warmer than 1880, similar to the Paleocene-Eocene Thermal Maximum (PETM) GSTs 55 Mya [3].

Ice

Six ice albedo changes are calculated separately: for NH and Antarctic (SH) sea ice, and for land ice in the GIS, WAIS, EAIS, and elsewhere (e.g., Himalayas). Ice loss in the latter four leads to SLR. This study considers each in turn.

Sea Ice

Arctic sea ice area has shown a shrinking trend since satellite coverage began in 1979. Annual minimum ice area fell 53% over the most recent 37 years [33]. However, annual minimum ice volume shrank faster, as the ice also thinned. Estimated annual minimum ice volume fell 73% over the same 37 years, including 51% in the most recent 10 years [34]. Trends in Arctic sea ice volume [34] are shown in Figure 4, with their corresponding R2, for four months. One set of trend lines (small dots) is based on data since 1980, while a second, steeper set (large dots) uses data since 2000. (Only four months are shown, since July ice volume is like November’s and June ice volume is like January’s). The graph suggests sea ice will vanish from the Arctic from June through December by 2050. Moreover, NH sea ice may vanish totally by 2085 in April, the minimum ice volume month. That is, current volume trends yield an ice-free Arctic Ocean about 2085.

fig 4

Figure 4: Arctic Sea Ice Volume by Month and Year, Past and Future.

Hudson estimated that loss of Arctic sea ice would increase radiative forcing in the Arctic by an amount equivalent to 0.7 W m-2, spread over the entire planet, of which 0.1 W m-2 had already occurred [30]. That leaves 0.6 W m-2 of radiative forcing still to come, as of 2011. This translates to 0.31°C warming yet to come (as of 2011) from NH sea ice loss. Trends in Antarctic sea ice are unclear. After three record high winter sea ice years in 2013-15, record low Antarctic sea ice was recorded in 2017-19 and 2020 is below average [27]. If GSTs rise enough, eventually Antarctic land ice and sea ice areas should shrink. Roughly 2/3 of Antarctic sea ice is associated with West Antarctica [35]. Therefore, 2/3 of modeled SH sea ice loss corresponds to WAIS ice volume loss and 1/3 to EAIS. However, to estimate sea ice area, change in estimated ice volume is raised to the 1.5 power (using the ratio of 3 dimensions of volume to 2 of area). This recognizes that sea ice area will diminish more quickly than the adjacent land ice volume of the far thicker WAIS (including the Antarctic Peninsula) and the EAIS.

Land Ice

Paleoclimate studies have estimated that global sea levels were 20 to 35 meters higher than today from 4.0 to 4.2 Mya [13,14]. This indicates that a large fraction of Earth’s polar ice had vanished then. Earth’s GST then was estimated to be 3.3 to 5.0°C above the 1951-80 mean, for CO2 levels of 357-405 ppm. Another study estimated that global sea levels were 25-40 meters higher than today’s from 14.1 to 14.5 Mya [11]. This suggests 5 meters more of SLR from vanished polar ice. The deep ocean then was estimated to be 5.6±1.0°C warmer than in 1951-80, in response to still higher CO2 levels of 430-465 ppm CO2 [11,12]. Analysis of sediment cores by Cook [20] shows that East Antarctic ice retreated hundreds of kilometers inland in that time period. Together, these data indicate large polar ice volume losses and SLR in response to temperatures expected before 2400. This tells us about total amounts, but not about rates of ice loss.

This study estimates the albedo effect of Antarctic ice loss as follows. The area covered by Antarctic land ice is 1.4 times the annual mean area covered by NH sea ice: 1.15 for the EAIS and 0.25 for the WAIS. The mean latitudes are not very different. Thus, the effect of total Antarctic land ice area loss on Earth’s albedo should be about 1.4 times that 0.7 Wm-2 calculated by Hudson for NH sea ice, or about 1.0 Wm-2. The model partitions this into 0.82 Wm-2 for the EAIS and 0.18 Wm-2 for the WAIS. Modeled ice mass loss proceeds more quickly (in % and GT) for the WAIS than for the EAIS. Shepherd et al. [36] calculated that Antarctica’s net ice volume loss rate almost doubled, from the period centered on 1996 to that on 2007. That came from the WAIS, with a compound ice mass loss of 12% per year from 1996 to 2007, as ice volume was estimated to grow slightly in the EAIS [36,37] over this period. From 1997 to 2012, Antarctic land ice loss tripled [36]. Since then, Antarctic land ice loss has continued to increase by a compound rate of 12% per year [37]. This study models Antarctic land ice losses over time using S-curves. The curve for the WAIS starts rising at 12% per year, consistent with the rate observed over the past 15 years, starting from 0.4 mm per year in 2010, and peaks in the 2100s. Except in CDR scenarios, remaining WAIS ice is negligible by 2400. Modeled EAIS ice loss increases from a base of 0.002 mm per year in 2010. It is under 0.1% in all scenarios until after 2100, peaks from 2145 to 2365 depending on scenario, and remains under 10% by 2400 in the three slowest-warming scenarios.

The GIS area is 17.4% of the annual average NH sea ice coverage [27,38], but Greenland experiences (on average) a higher sun angle than the Arctic Ocean. This suggests that total GIS ice loss could have an albedo effect of 0.174 * cos (72°)/cos (77.5°) = 0.248 times that of total NH sea ice loss. This is the initial albedo ratio in the model. The modeled GIS ice mass loss rate decreases from 12% per year too, based on Shepherd’s GIS findings for 1996 to 2017 [37]. Robinson’s [39] analysis indicated that the GIS cannot be sustained at temperatures warmer than 1.6°C above baseline. That threshold has already been exceeded locally for Greenland. So it is reasonable to expect near total ice loss in the GIS if temperatures stay high enough for long enough. Modeled GIS ice loss peaks in the 2100s. It exceeds 80% by 2400 in scenarios lacking CDR and is near total by then if fossil fuel use continues past 2050.

The albedo effects of land ice loss, as for Antarctic sea ice, are modeled as proportional to the 1.5 power of ice loss volume. This assumes that the relative area suffering ice loss will be more around the thin edges than where the ice is thickest, far from the edges. That is, modeled ice-coved area declines faster than ice volume for the GIS, WAIS, and EAIS. Ice loss from other glaciers, chiefly in Arctic islands, Canada, Alaska, Russia, and the Himalayas, is also modeled by S-curves. Modeled “other glaciers” ice volume loss in the 6 scenarios ranges from almost half to almost total, depending on the scenario. Corresponding SLR rise by 2400 ranges from 12 to 25 cm, 89% or more of it by 2100.

In the Air: Clouds and Water Vapor

As calculated by Equation (5), using 70 years without significant volcanic eruptions, GLST will rise about 0.37°C as human sulfur emissions are phased out. Clouds cover roughly half of Earth’s surface and reflect about 20% [40] of incoming solar radiation (341 W m–2 mean for Earth’s surface). This yields mean reflection of about 68 W m–2, or 20 times the combined warming effect of GHGs [41]. Thus, small changes in cloud cover can have large effects. Detecting cloud cover trends is difficult, so the error bar around estimates for forcing from cloud cover changes is large: 0.6±0.8 Wm–2K–1 [42]. This includes zero as a possibility. Nevertheless, the estimated cloud feedback is “likely positive”. Zelinka [42] estimates the total cloud effect at 0.46 (±0.26) W m–2K –1. This comprises 0.33 for less cloud cover area, 0.20 from more high-altitude ones and fewer low-altitude ones, -0.09 for increased opacity (thicker or darker clouds with warming), and 0.02 for other factors. His overall cloud feedback estimate is used for modeling the 6 scenarios shown in the Results section. This cloud effect applies both to albedo changes from less ice and snow and to relative changes in GHG (CO2) concentrations. It is already implicit in estimates for SO4 effects. 1°C warmer air contains 7% more water vapor, on average [43]. That increases radiative forcing by 1.5 W m–2 [43]. This feedback is 89% as much as from CO2 emitted from 1750 to 2011 [41]. Water vapor acts as a warming multiplier, whether from human GHG emissions, natural emissions, or albedo changes. The model treats water vapor and cloud feedbacks as multipliers. This is also done in Table 3 below.

Table 3: Observed GST Warming from Albedo Changes, 1975-2016.

table 3

Albedo Feedback Warming, 1975-2016, Informs Climate Sensitivities

Amplifying feedbacks, from albedo changes and natural carbon emissions, are more prominent in future warming than direct GHG effects. Albedo feedbacks to date, summarized in Table 3, produced an estimated 39% of GST warming from 1975 to 2016. This came chiefly from SO4 reductions, plus some from snow cover changes and Arctic sea ice loss, with their multipliers from added water vapor and cloud cover changes. On the top line of Table 3 below, the SO4 decrease, from 177.3 ppb in 1975 to 130.1 in 2016, is multiplied by 0.00393°C/ppb SO4 from Equation (5). On the second line, in the second column, Arctic sea ice loss is from Hudson [30], updated from 0.10 to 0.11 W m–2 to cover NH sea ice loss from 2010 to 2016. The snow cover timing change effect of 0.12 W m–2 over 1982-2013 is from Chen [28]. But the snow cover data is adjusted to 1975-2016, for another 0.08 W m-2 in snow timing forcing, using Chen’s formula for W m-2 per °C warming [28] and extra 0.36°C warming over 1975-82 plus 2013-16. The amount of the land ice area loss effect is based on SLR to date from the GIS, WAIS, and non-polar glaciers. It corresponds to about 10,000 km2, less than 0.1% of the land ice area.

For the third column of Table 3, cloud feedback is taken from Zelinka [42] as 0.46 W m–2K–1. Water-vapor feedback is taken from Wadhams [43], as 1.5 W m–2K–1. The combined cloud and water-vapor feedback of 1.96 W m–2K–1 modeled here amounts to 68.8% of the 2.85 total forcing from GHGs as of 2011 [41]. Multiplying column 2 by 68.8% yields the numbers in column 3. Conversion to ∆°C in column 4 divides the 0.774°C warming from 1880 to 2011 [2] by the total forcing of 2.85 W m-2 from 1880 to 2011 [41]. This yields a conversion factor of 0.2716°C W-1m2, applied to the sum of columns 2 and 3, to calculate column 4. Error bars are shown in column 5. In summary, estimated GST warming over 1975-2016 from albedo changes, both direct (from sulfate, ice, and snow changes) and indirect (from cloud and water-vapor changes due to direct ones), totals 0.330°C. Total GST warming then was 0.839°C [2]. (This is more than the 0.774°C (2) warming from 1880 to 2011, because the increase from 2011 to 2016 was greater than the increase from 1880 to 1975.) So, the ∆GST estimated for albedo changes over 1975-2016, direct and indirect, comes to 0.330/0.839 = 39.3% of the observed warming.

1975-2016 Warming Not from Albedo Effects

The remaining 0.509°C warming over 1975-2016 corresponds to an atmospheric CO2 increase from 331 to 404 ppm [44], or 22%. This 0.509°C warming is attributed in the model to CO2, consistent with Equations (3) and (1), using the simplification that the sum total effect of other GHGs changes as the same rate as for CO2. It includes feedbacks from H2O vapor and cloud cover changes, estimated, per above, as 0.686/(1+1.686) of 0.509°C, which is 0.207°C or 24.7% of the total 0.839°C warming over 1975-2016. This leaves 0.302°C warming for the estimated direct effect of CO2 and other factors, including other GHGs and factors not modeled, such as black carbon and vegetation changes, over this period.

Partitioning Climate Sensitivity

With the 22% increase in CO2 over 1975-2016, we can estimate the change due to a doubling of CO2 by noting that 1.22 [= 404/331] raised to the power 3.5 yields 2.0. This suggests that a doubling of CO2 levels – apart from surface albedo changes and their feedbacks – leads to about 3.5 times 0.509°C = 1.78°C of warming due to CO2 (and other GHGs and other factors, with their H2O and cloud feedbacks), starting from a range of 331-404 ppm CO2. In the model, for projected temperature changes for a particular year, 0.509°C is multiplied by the natural logarithm of (the CO2 concentration/331 ppm in 1975) and divided by the natural logarithm of (404 ppm/331 ppm), that is divided by 0.1993. This yields estimated warming due to CO2 (plus, implicitly, other non-H2O GHGs) in any particular year, again apart from surface albedo changes and their feedbacks, including the factors noted that are not modelled in this study.

Using Equation (3), warming associated with doubled CO2 over the past 14.5 million years is 11.807 x ln(2.00), or 8.184°C per CO2 doubling. The difference between 8.18°C and 1.78°C, from CO2 and non-H2O GHGs, is 6.40°C. This 6.40°C climate sensitivity includes the effect of albedo changes and the consequent H2O vapor concentration. Loss of tropospheric SO4 and Arctic sea ice are the first of these to occur, with immediate water vapor and cloud feedbacks. Loss of snow and Antarctic sea ice follow over centuries to decades. Loss of much land ice, especially where grounded above sea level, happens more slowly.

Stated another way, there are two climate sensitivities: one for the direct effect of GHGs and one for amplifying feedbacks, led by albedo changes. The first is estimated as 1.8°C. The second is estimated as 6.4°C in epochs, like ours, when snow and ice are abundant. In periods with little or no ice and snow, this latter sensitivity shrinks to near zero, except for clouds. As a result, climate is much more stable to perturbations (notably cyclic changes in Earth’s tilt and orbit) when there is little snow or ice. However, climate is subject to wide temperature swings when there is lots of snow and ice (notably the past 2 million years, as seen in Figure 1).

In the Oceans

Ocean Heat Gain: In 2011, Hansen [7] estimated that Earth is absorbing 0.65 Wm-2 more than it emits. As noted above, ocean heat gain averaged 4 ZJ per year over 1967 to 1990, 7 over 1991-2005, and 10 over 2006-16. Ocean heat gain accelerated while GSTs increased. Therefore, ocean heat gain and Earth’s energy imbalance seem likely to continue rising as GSTs increase. This study models the situation that way. Oceans would need to warm up enough to regain thermal equilibrium with the air above. While oceans are gaining heat (now ~ 2 times cumulative human energy use every 3 years), they are out of equilibrium. The ocean thermohaline circuit takes about 1,000 years. So, if human GHG emissions ended today, this study assumes that it could take Earth’s oceans 1,000 years to thermally re-equilibrate heat with the atmosphere. The model spreads the bulk of that over 400 years, in an exponential decay shape. The rate peaks during 2130 to 2170, depending on the scenario. The modeled effect is about 5% of total GST warming. Ocean thermal expansion (OTE), currently about 0.8 mm/year [5], is another factor in SLR. Changes to its future values are modeled as proportional to future temperature change.

Land Ice Mass Loss, Its Albedo Effect, and Sea Level Rise: Modeled SLR derives mostly from modeled ice sheet losses. Their S-curves were introduced above. The amount and rate parameters are informed by past SLR. Sea levels have varied by almost 200 meters over the past 65 My. They were almost 125 meters lower than now during recent Ice Ages [3]. SLR reached some 70 meters higher in ice-free warm periods more than 10 Mya, especially more than 35 Mya [3]. From Figure 1, Earth was largely ice-free when deep ocean temperature (DOT) was 7°C or more, for SLR of about 73 meters from current levels, when DOT is < 2°C. This yields a SLR estimate of 15 meters/°C of DOT in warm eras. Over the most recent 110-120 ky, 110 meters of SLR is associated with 4 to 6°C GST warming (Figure 2), or 19-28 meters/°C GST in a cold era. The 15:28 warm/cold era ratio for SLR rate shows that the amount of remaining ice is a key SLR variable. However, this study projects only 1.5 to 4 meters rate of SLR by 2400 per °C of GST warming, but still rising. The WAIS and GIS together hold 10-12 meters of SLR [15,16]. So, 25-40 meter SLR during 14.1-14.5 Mya suggests that the EAIS lost about 1/3 to 1/2 of its current ice volume (20 to 30 meters of SLR, out of almost 60 today in the EAIS [45]) when CO2 levels were last at 430-465 ppm and DOTs were 5.6±1.0°C [11,12]. This is consistent with this study’s two scenarios with human CO2 emissions after 2050 and even 2100: 13 and 21 meters of SLR from the EAIS by 2400, with Δ GLSTs of 8.2 and 9.4°C. DeConto [19] suggested that sections of the EAIS grounded below sea level would lose all ice if we continue emissions at the current rate, for 13.6 or even 15 meters of SLR by 2500. This model’s two scenarios with intermediate GLST rise yield SLR closest to his projections. SLR is even higher in the two warmest scenarios. Modeled SLR rates are informed by the most recent 19,000 years of data ([46,47], chart by Robert A. Rohde). They include a SLR rate of 3 meters/century during Meltwater Pulse 1A for 8 centuries around 14 ky ago. They also include 1.5 meters/century over the 70 centuries from 15 kya to 8 kya. The DOT rose 3.3°C over 10,000 years, for an average rate of 0.033°C per century. However, the current SST warming rate is 2.0°C per century [1,2], about 60 times as great. Although only 33-40% as much ice (73 meters SLR/(73+125)) is left to melt, this suggests that rates of SLR will be substantially higher, at current rates of warming, than the 1.5 to 3 meters per century coming out of the most recent ice age. In four scenarios without CDR, mean rates of modeled SLR from 2100 to 2400 range from 4 to 11 meters per century.

Summary of Factors in Warming to 2400

Table 4 summarizes the expected future warming effects from feedbacks (to 2400), based on the analyses above.

Table 4: Projected GST Warming from Feedbacks, to 2400.

table 4

The 3.5°C warming indicated, added to 1.1°C warming since 1880, or 4.6°C, is 0.5°C less than the 5.1°C warming based on Equation (4) from the paleoclimate analysis. This gap suggests four overlapping possibilities. First, underestimations (perhaps sea ice and clouds) may exceed overestimations (perhaps snow) for the processes shown in Table 4. Underestimation of cloud feedbacks, and their consequent warming, is quite possible. Using Zelinka’s 0.46 Wm–2K–1 in this study, instead of the IPCC central estimate of 0.6, is one possibility. Moreover, recent research suggests that cloud feedbacks may be appreciably stronger than 0.6 Wm–2K–1 [48]. Second, change in the eight factors not modelled (black carbon, vegetation and land use, ocean and air circulation, Earth’s orbit and tilt, and solar output) may provide feedbacks that, on balance, are more warming than cooling. Third, temperatures used here for 4 and 14 Mya may be overestimated or should not be used unadjusted. Notably, the joining of North and South America about 3 Mya rearranged ocean circulation and may have resulted in cooling that led to ice periodically covering much of North America [49]. Globally, Figure 1 above suggests this cooling effect may be 1.0-1.6°C. In contrast, solar output increases as our sun ages, by 7% per billion years [50], so that solar forcing is now 1.4 W m–2 more than 14 Mya and 0.4 more than 4 Mya. A brighter sun now indicates that, for the same GHG levels and albedo levels, GST would be 0.7°C warmer than it would have been 14 Mya and 0.2°C warmer than 4 Mya. Fourth, nothing (net) may be amiss. Underestimated warming (perhaps permafrost, clouds, sea ice, black carbon) may balance overestimated warming (perhaps snow, land ice, vegetation). The gap would then be due to a lower albedo climate sensitivity than 6.4°C, as discussed above using data for 1975-2016, because all sea ice and much snow vanish by 2400.

Natural Carbon Emissions

Permafrost: One estimate of the amount of carbon stored in permafrost is 1,894 GT of carbon [51]. This is about 4 x carbon that humans have emitted by burning fossil fuels. It is also 2 x as much as in Earth’s atmosphere. More permafrost may lie under Antarctic ice and the GIS. DeConto [52] proposed that the PETM’s large carbon and temperature (5-6°C) excursions 55 Mya are explained by “orbitally triggered decomposition of soil organic carbon in circum-Arctic and Antarctic terrestrial permafrost. This massive carbon reservoir had the potential to repeatedly release thousands of [GT] of carbon to the atmosphere-ocean system”. Permafrost area in the Northern Hemisphere shrank 7% from 1900 to 2000 [53]. It may shrink 75-88% more by 2100 [54]. Carbon emissions from permafrost are expected to accelerate, as the ground in which they are embedded warms up. In general, near-surface air temperatures have been warming twice as fast in the Arctic as across the globe as a whole [32]. More research is needed to estimate rates of permafrost warming at depth and consequent carbon emissions. Already in 2010, Arctic permafrost emitted about as carbon as all US vehicles [55]. Part of the carbon emerges as CH4, where surface water prevents carbon under it being oxidized. That CH4 changes to CO2 in the air over several years. This study accounts for the effects of CO2 derived from permafrost. MacDougall et al. estimated that thawing permafrost can add up to ~100 ppm of CO2 to the air by 2100 and up to 300 more by 2300, depending on the four RCP emissions scenarios [56]. This is 200 GT of carbon by 2100 plus 600 GT more by 2300. The direct driver of such emissions is local temperatures near the air-soil interface, not human carbon emissions. Since warming is driven not just by emissions, but also by albedo changes and their multipliers, permafrost carbon losses from thawing may proceed faster than MacDougall estimated. Moreover, MacDougall estimated only 1,000 GT of carbon in permafrost [56], less than more recent estimates. On the other hand, a larger fraction of carbon may stay in permafrost soil in than MacDougall assumed, leaving deep soil rich in carbon, similar to that left by “recent” glaciers in Iowa.

Other Natural Carbon Emissions

Seabed CH4 hydrates may hold a similar amount of carbon to permafrost or somewhat less, but the total amount is very difficult to measure. By 2011, subsea CH4 hydrates were releasing 20-30% as much carbon as permafrost was [57]. This all suggests that eventual carbon emissions from permafrost and CH4 hydrates may be half to four times what MacDougall estimated. Also, the earlier portion of those emissions may happen faster than MacDougall estimated. In all, this study’s modeled permafrost carbon emissions range from 35 to 70 ppm CO2 by 2100 and from 54 to 441 ppm CO2 by 2400, depending on the scenario. As stated earlier, this model simply assumes that other natural carbon reservoirs will add half as much carbon to the air as permafrost does, on the same time path. These sources include outgassing from soils now unfrozen year-round, the warming upper ocean, seabed CH4 hydrates, and any net decrease in worldwide biomass.

Results

The Six Scenarios

  1. “2035 Peak”. Fossil-fuel emissions are reduced 94% by 2100, from a peak about 2035, and phased out entirely by 2160. Phase-out accelerates to 2070, when CO2 emissions are 25% of 2017 levels, then decelerates. Permafrost carbon emissions overtake human ones about 2080. Natural CO2 removal (CDR) mostly further acidifies the oceans. But it includes 1 GT per year of CO2 by rock weathering.
  2. “2015 Peak”. Fossil-fuel emissions are reduced 95% by 2100, from a peak about 2015, and phased out entirely by 2140. Phase-out accelerates to 2060, when CO2 emissions are 40% of 2017 levels, then decelerates. Compared to a 2035 peak, natural carbon emissions are 25% lower and natural CDR is similar.
  3. “x Fossil Fuels by 2050”, or “x FF 2050”. Peak is about 2015, but emissions are cut in half by 2040 and end by 2050. Natural CDR is the same as for the 2015 Peak, but is lower to 2050, since human CO2 emissions are less. This path has a higher GST from 2025 to 2084, while warming sooner from less SO4 outweighs less warming from GHGs.
  4. “Cold Turkey”. Emissions end at once after 2015. Natural CDR is only by rock weathering, since no new human CO2 emissions push carbon into the ocean. After 2060, cooling from ending CO2 emissions earlier outweighs warming from ending SO2
  5. “x FF 2050, CDR”. Emissions are the same as for “x FF 2050”, as is natural CDR. But human CDR ramps up in an S-curve, from less than 1% of emissions in 2015 to 25% of 2015 emissions over the 2055 to 2085 period. Then they ramp down in a reverse S-curve, to current levels in 2155 and 0 by 2200.
  6. “x FF 2050, 2xCDR” is like “x FF 2050, CDR”, but CDR ramps up to 52% of 2015 emissions over 2070 to 2100. From 2090, it ramps down to current levels in 2155 and 0 by 2190. CDR = 71% of CO2 emissions to 2017 or 229% of soil carbon lost since farming began [58], almost enough to cut CO2 in the air to 313 ppm, for 2°C warming.

Projections to 2400

The results for the six scenarios shown in Figure 5 spread ocean warming over 1,000 years, more than half of it by 2400. They use the factors discussed above for sea level, water vapor, and albedo effects of reduced SO4, snow, ice, and clouds. Permafrost emissions are based on MacDougall’s work, adjusted upward for a larger amount of permafrost, but also downward and to a greater degree, assuming much of the permafrost carbon stays as carbon-rich soil as in Iowa. As first stated in the introduction to Feedback Pathways, the model sets other natural carbon emissions to half of permafrost emissions. At 2100, net human CO2 emissions range from -15 GT/year to +2 GT/year, depending on the scenario. By 2100, CO2 concentrations range from 350 to 570 ppm, GLST warming from 2.9 to 4.5°C, and SLR from 1.6 to 2.5 meters. CO2 levels after 2100 are determined mostly by natural carbon emissions, driven ultimately by GST changes, shown in the lower left panel of Figure 5. They come from permafrost, CH4 hydrates, unfrozen soils, warming upper ocean, and biomass loss.

fig 5

Figure 5: Scenarios for CO2 Emissions and Levels, Temperatures and Sea Level.

Comparing temperatures to CO2 levels allows estimates of long-run climate sensitivity to doubled CO2. Sensitivity is estimated as ln(2)/ln(ppm/280) * ∆T. By scenario, this yields > 4.61° (probably ~5.13° many decades after 2400) for 2035 Peak, > 4.68° (probably ~5.15°) for 2015 Peak, > 5.22° (probably 5.26°) for “x FF by 2050”, and 8.07° for Cold Turkey. Sensitivities of 5.13, 5.15 and 5.26° are much less than the 8.18° derived from the Vostok ice core. This embodies the statement above, in the Partitioning Climate Sensitivity section, that in periods with little or no ice and snow [here, ∆T of 7°C or more – the 2035 and 2015 Peaks and x FF by 2050 scenarios], this albedo-related sensitivity shrinks to 3.3-3.4°. Meanwhile, the Cold Turkey scenario (with a good bit more snow and a little more ice) matches well the relationship from the ice core (and validated to 465 ppm CO2, in the range for Cold Turkey: 4 and 14 Mya). Another perspective is the climate sensitivity starting from a base not of 280 ppm CO2, but from a higher level: 415 ppm, the current level and the 2400 level in the Cold Turkey case. Doubling CO2 from 415 to 830 ppm, according to the calculations underlying Figure 5, yields a temperature in 2400 between the x FF by 2050 and the 2015 Peak cases, about 7.6°C and rising, to perhaps 8.0°C after 1-2 centuries. This yields a climate sensitivity of 8.0 – 4.9 = 3.1°C in the 415-830 ppm range. The GHG portion of that remains near 1.8° (see Partitioning Climate Sensitivity above). But the albedo feedbacks portion shrinks further, from 6.4°, past 3.3° to 1.3°, as thin ice and most snow are gone, as noted above, plus all SO4 from fossil fuels, leaving mostly thick ice and feedbacks from clouds and water vapor.

Table 5 summarizes estimated temperatures effects of 16 factors in the 6 scenarios to 2400. Peaking emissions now instead of in 2035 can keep eventual warming 1.1°C lower. Phasing out fossil fuels by 2050 gains another 1.2°C relatively cooler. Ending fossil fuel use immediately gains another 2.2°C. Also removing 2/3 of CO2 emissions to date gains another 2.4°C relatively cooler. Eventual warming in the higher emissions scenarios is a good bit lower than what would be inferred by using the 8.2°C climate sensitivity based on an epoch rich in ice and snow. This is because the albedo portion of that climate sensitivity (currently 6.4°) is greatly reduced as ice and snow disappear. More human carbon emissions (the first three scenarios especially) warm GSTs further, especially from less snow and cloud cover, more water vapor, and more natural carbon emissions. These in turn accelerate ice loss. All further amplify warming.

Table 5: Factors in Projected Global Surface Warming, 2010-2400 (°C).

table 5

Carbon release from permafrost and other reservoirs is lower in scenarios where GSTs do not rise as much. GSTs grow to the end of the study period, 2400, except for the CDR cases. Over 99% of warming after 2100 is due to amplifying feedbacks from human emissions during 1750-2100. These feedbacks amount to 1.5 to 5°C after 2100, in the scenarios without CDR. Projected mean warming rates with continued human emissions are similar to current rates of 2.5°C per century over 2000-2020 [2]. Over the 21st century, they range from 62 to 127% of the rate over the most recent 20 years. The mean across the 6 scenarios is 100%, higher in the 3 warmest scenarios. Warming slows in later centuries. The key to peak warming rates is disappearing northern sea ice and human SO4, mostly by 2050. Peak warming rates per decade in all 6 scenarios occur this century. They are fastest not for the 2035 Peak scenario (0.38°C), but for Cold Turkey (.80°C when our SO2 emissions stop suddenly) and xFF2050 (0.48°C, as SO2 emissions phase out by 2050). Due to SO4 changes, peak warming in the x FF 2050 scenario, from 2030 to 2060, is 80% faster than over the past 20 years, while for the 2035 Peak, it is only 40% faster. Projected SLR from ocean thermal expansion (OTE) by 2400 ranges from 3.9 meters in the 2035 Peak scenario to 1.5 meters in the xFF’50 2xCDR case. The maximum rate of projected SLR by 2400 is 15 meters from 2300 to 2400, in the 2035 Peak scenario. That is 5 times the peak 8-century rate 14 kya. However, the mean SLR rate over 2010-2400 is less than the historical 3 meters per century (from 14 kya) in the CDR scenarios and barely faster for Cold Turkey. The rate of SLR peaks from 2130 to 2360 for the 4 scenarios without CDR. In the two CDR scenarios, projected SLR comes mostly from the GIS, OTE, and the WAIS. But the EAIS is the biggest contributor in the three fastest warming scenarios.

Perspectives

The results show that the GST is far from equilibrium; barely more than 20% of 5.12°C warming to equilibrium. However, the feedback processes that warm Earth’s climate to equilibrium will be mostly complete by 2400. Some snow melting will continue. So will melting more East Antarctic and (in some scenarios) Greenland ice, natural carbon emissions, cloud cover and water vapor feedbacks, plus warming the deep ocean. But all of these are tapering off by 2400 in all scenarios. Two benchmarks are useful to consider: 2°C and 5°C above 1880 levels. The 2015 Paris climate pact’s target is for GST warming not to exceed 2°C. However, projected GST warming exceeds 2°C by 2047 in all six scenarios. Focus on GLSTs recognizes that people live on land. Projected GLST warming exceeds 2°C by 2033 in all six scenarios. 5° is the greatest warming specifically considered in Britain’s Stern Review in 2006 [59]. For just 4°, Stern suggested a 15-35% drop in crop yields in Africa, while parts of Australia cease agriculture altogether [59]. Rind et al. projected that the major U.S. crop yields would fall 30% with 4.2°C warming and 50% with 4.5°C warming [60]. According to Stern, 5° warming would disrupt marine ecosystems, while more than 5° would lead to major disruption and large-scale population movements that could be catastrophic [59]. Projected GLST warming passes 5°C in 2117, 2131, and 2153 for the three warmest scenarios. But it never does in the other three. With 5° GLST warming, Kansas, until recently the “breadbasket of the world”, would become as hot in summer as Las Vegas is now. Most of the U.S. warms faster than Earth’s land surface in general [32]. Parts of the U.S. Southeast, including most of Georgia, become that hot, but much more humid. Effects would be similar elsewhere.

Discussion

Climate models need to account for all these factors and their interactions. They should also reproduce conditions for previous eras when Earth had this much CO2 in the air, using current levels of CO2 and other GHGs. This study may underestimate warming due to permafrost and other natural emissions. It may also overestimate how fast seas will rise in a much warmer world. Ice grounded below sea level (by area, ~2/3 of the WAIS, 2/5 of the EAIS, and 1/6 of the GIS) can melt quickly (decades to centuries). But other ice can take many centuries or millennia to melt. Continued research is needed, including separate treatment of ice grounded below sea level or not. This study’s simplifying assumptions, that lump other GHGs with CO2 and other natural carbon emissions proportionately with permafrost, could be improved with modeling for the individual factors lumped here. More research is needed to better quantify the 12 factors modeled (Table 5) and the four modeled only as a multiplier (line 10 in Table 5). For example, producing a better estimate for snow cover, similar to Hudson’s for Arctic sea ice, would be useful. So would other projections, besides MacDougall’s, of permafrost emissions to 2400. More work on other natural emissions and the albedo effects of clouds with warming would be useful.

This analysis demonstrates that reducing CO2 emissions rapidly to zero will be woefully insufficient to keep GST less than 2°C above 1750 or 1880 levels. Policies and decisions which assume that merely ending emissions will be enough will be too little, too late: catastrophic. Lag effects, mostly from albedo changes, will dominate future warming for centuries. Absent CDR, civilization degrades, as food supplies fall steeply and human population shrinks dramatically. More emissions, absent CDR, will lead to the collapse of civilization and shrink population still more, even to a small remnant.

Earth’s remaining carbon budget to hold warming to 2°C requires removing more than 70% of our CO2 emissions to date, any future emissions, and all our CH4 emissions. Removing tens of GT of CO2 per year will be required to return GST warming to 2°C or less. CDR must be scaled up rapidly, while CO2 emissions are rapidly reduced to almost zero, to achieve negative net emissions before 2050. CDR should continue strong thereafter.

The leading economists in the USA and the world say that the most efficient policy to cut CO2 emissions is to enact a worldwide price on them [61]. It should start at a modest fraction of damages, but rise briskly for years thereafter, to the rising marginal damage rate. Carbon fee and dividend would gain political support and protect low-income people. Restoring GST to 0° to 0.5°C above 1880 levels calls for creativity and dedication to CDR. Restoring the healthy climate on which civilization was built is a worthwhile goal. We, our parents and our grandparents enjoyed it. A CO2 removal price should be enacted, equal to the CO2 emission price. CDR might be paid for at first by a carbon tax, then later by a climate defense budget, as CO2 emissions wind down.

Over 1-4 decades of research and scaling up, CDR technology prices may drop far. Sale of products using waste CO2, such as concrete, may make the transition easier. CDR techniques are at various stages of development and prices. Climate Advisers provides one 2018 summary for eight CDR approaches, including for each: potential GT CO2 removed per year, mean US$/ton CO2, readiness, and co-benefits [62]. The commonest biological CDR method now is organic farming, in particular no-till and cover cropping. Others include several methods of fertilizing or farming the ocean; planting trees; biochar; fast-rotation grazing; and bioenergy with CO2 capture. Non-biological ones include direct air capture with CO2 storage underground in carbonate-poor rocks such as basalts. Another increases surface area of such rocks, by grinding them to gravel, or dust to spread from airplanes. They react with weak carbonic acid in rain. Another adds small carbonate-poor gravel to agricultural soil.

CH4 removal should be a priority, to quickly drive CH4 levels down to 1880 levels. With a half-life of roughly 7 years in Earth’s atmosphere, CH4 levels might be cut back that much in 30 years. It could happen by ending leaks from fossil fuel extraction and distribution, untapped landfills, cattle not fed Asparagopsis taxiformis, and flooding rice paddies. Solar radiation management (SRM) might play an important supporting role. Due to loss of Arctic sea ice and human SO4, even removing all human GHGs (scenario not shown) will likely not bring GLST back below 2°C by 2400. SRM could offset these two soonest major albedo changes in coming decades. The best known SRM techniques are (1) putting SO4 or calcites in the stratosphere and (2) refreezing the Arctic Ocean. Marine cloud brightening could play a role. SRM cannot substitute for ending our CO2 emissions or for vast CDR, both of them soon. We may need all three approaches working together.

In summary, the paleoclimate record shows that today’s CO2 level entails GST roughly 5.1°C warmer than 1880. Most of the increase from today’s GST will be due to amplification by albedo changes and other factors. Warming gets much worse with continued emissions. Amplifying feedbacks will add more GHGs to the air, even if we end our GHG emissions now. Further GHGs will warm Earth’s surface, oceans and air even more, in some cases much more. The impacts will be many, from steeply reduced crop yields (and widespread crop failures) and many places too hot to survive sometimes, to widespread civil wars, billions of refugees, and many meters of SLR. Decarbonization of civilization by 2050 is required, but far from enough. Massive CO2 removal is required as soon as possible, perhaps supplemented by decades of SRM, all enabled by a rising price on CO2.

List of Acronyms

List of Acro

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Factors Influencing the Adoption of Cocoa Agroforestry Systems in Mitigating Climate Change in Ghana: The Case of Sefwi Wiawso in Western Region

Introduction

Climate change is having great impact on agricultural productivity worldwide. Agriculture is strongly influenced by weather and climate [1,2]. Climate change and variability adversely affect environmental resources such as soil and water upon which agricultural production depends, which poses a serious threat to sustainable agricultural production [2]. In Ghana climate variability and change is expected to have an adversely effect on the agriculture sector. According to the NIC, (2009) by 2030 temperature are projected to rise by 0.5 °C. This situation would result in fewer rainy days and more extreme weather conditions like prolonged droughts. The impacts of a changing climate will have direct and indirect effects on global and domestic food systems [3,4]. Rioux [5] reported that climate change has affected yields in food crop production in many Africa countries. If the issues of climate change and variability are not addressed incomes and food security of rural households in Ghana would be undermined because there would be increased incidence of diseases and pest as well as prolonged variable rainfall patterns.

Cocoa production employs over 15 million people worldwide with over 10.5 million workers in West Africa [6]. Cocoa, in addition to cereals and other root and tuber  crops  contribute  largely  to  food security in Ghana. In Ghana cocoa production is an essential component of  rural  livelihoods  and  its  cultivation  is  considered a ‘way of life’ in many production communities [7]. The cocoa sub sector cocoa employs about 800,000 farm families spread across the cocoa growing regions of Ghana and generating about $2 billion in foreign exchange annually [8,9]. The expansion of cocoa production is replacing substantial areas of primary forest. It’s of no surprise that the total area under cocoa cultivation increased by 50,000 hectares between 2012 and 2013 and there is no indication that the rate is slowing down. According to Anim Kwapong et al. [10] the government of Ghana recognizes that climate change is already negatively affecting Ghana’s cocoa sector in myriad ways and that, it is likely to continue hampering Ghana’s environmental and socio-economic prospects in the coming decades. Cocoa agroforestry system has been identified as is an important strategy that can ameliorate climate change [11].

This system can play a dual role of mitigation and adaptation, which makes it one of the best responses to climate change. It is noted that agroforestry has multi-functional purposes which makes it one of  the most promising strategies for climate change adaptation [11,12]. The use of trees and shrubs in agricultural systems help to tackle the triple challenge of securing food security, mitigation and reducing the vulnerability and increasing the adaptability of agricultural systems to climate change [13,14]. With this view, serious attention must be given to cocoa agroforestry which is capable of reducing temperatures and enhancing the growing of cocoa thus sustaining livelihood of many households in this climate changing pattern. According to previous studies [11,13,15] agroforestry as an adaptation strategy could sustain agricultural production and enhance farmers’ ability to improve livelihoods and will minimize the impacts of climate change which include drought, variable rainfall and extreme temperatures. Agroforestry as a forest-based system plays a significant role in conserving existing carbons, thereby limiting carbon emissions and also absorbing carbons that are released into the atmosphere [16]. Nair [17] also indicated that agroforestry has received international attention as an effective strategy for carbon sequestration and greenhouse mitigation. Cocoa agroforestry can increase farmers’ resilience and position them strategically to adapt to the impacts of a changing climate. This system of cocoa production can be very useful because it generates quite substantial benefits on arable lands in diverse ways; trees in agricultural fields improve soil fertility through control of erosion, improve nitrogen content of the soil and increase organic matter of the soil [18,19]. Agroforestry can also transform degraded lands into productive agricultural lands and improves productive capacities of soils [18]. Although agroforestry is not new in Ghana, it is quite optimistic that effective adoption to climate change will contribute towards the achievement of sustainable development and to a large extent, the attainment of the Sustainable Development Goals (SDGs). Despite the immeasurable benefits of cocoa agroforestry system, adoption is not widespread and for that matter success stories are found in isolated cocoa farming areas among few adapters of cocoa agroforestry system initiatives. Aidoo and Fromm [20] report that although cocoa farmers are aware about sustainability issues, they hardly adopt sustainable production practices. It is quite not always the case that policies are implemented as they were intended and so the need to assess farmers’ perspectives on cocoa agroforestry adoption and implementation especially when climate change has become a serious constraint to cocoa production in Ghana. Traditional coping mechanisms to the impact of climate change in the Western Region of Ghana include mixed cropping, non-farm activities and traditional agroforestry practices by some individual cocoa farmers. However, non-shade cocoa production systems, bush burning, slash and burn farming methods expose the cocoa communities to further impacts of climate change. This calls for swift attention from all, especially cocoa farmers in the study communities to tackle the problem. Despite the economic, environmental and sustainable cocoa production potential via agroforestry systems, farmers have not adopted cocoa agroforestry practices entirely especially in Sefwi Wiawso District. Understanding cocoa farmers decision making processes in ensuring sustainable food supply and cocoa yield in cocoa agroforestry system is critical. Research frontiers in cocoa agroforestry systems need to be identified and better understand barriers to adoption and the development of strategies to support cocoa agroforestry that enhance food security in climate changing conditions. The objectives of this study are therefore to empirically assess the factors that affect farmers’ decision to adopt cocoa agroforestry systems and determine cocoa farmers’ perception on cocoa agroforestry as an adaptation strategy to climate change.

Methodology

The study was conducted at Sefwi Wiawso in the Western and region of Ghana. The district lies within latitudes 6º 00“and 6º 30 North and Longitudes 2º 15‟ and 2º 45 West. The District covers an area of about 2,634 square kilometers. The detailed hydrometeorological characteristics of the study area are provided in Table 1.

Table 1: Hydrometeorological characteristics of the study area.

Characteristics

Levels

Mean temperature

Maximum: 33°C Minimum: 26°C

Climate

Tropical rainforest

Average humidity

Dry season: 50-75%
Rainy season: 85-90%

Average rainfall

1500-1800 mm

Topography

Undulating

Soil condition

Loamy

Average elevation

206 m

A stratified random sampling technique was employed in the selection of the 300 cocoa farmers interviewed for the study. In the first stage, Western Region was purposively selected due to the fact that apart from being one of the highest cocoa producing regions    in Ghana, it is one of the regions which has experienced significant impact as a result of climate change. In the second stage, Sefwi Wiawso was randomly selected. In the third stage, five communities were randomly selected. In the final stage 60 cocoa farmers were randomly selected from each village. Primary data were employed in the study. The primary data consisted of qualitative data and household survey interviews. Specifically, the primary data were collected through focus group discussions (FGD), stakeholder interviews, and field observations. The household survey interviews employed both open- ended and close ended survey instruments.

To examine the factors that influence a household’s decision to participate in agroforestry a logistic regression model was employed.

The model was specified as:

ESCC-2-1-202-e001

Where: i = 1, 2, 3………., k are the observations, α= constant. β = the regression parameter to be estimated. βX= linear combination of independent variables.  Zi= the log odds of choice for the  ithobservation. Pi= the probability of observing
a specific outcome of the dependent variable (adoption). Xn = nth explanatory observation. u = the error term.

Results and Discussion

The gender composition of the cocoa farmers among revealed that 81.5 percent of the respondent are males with 19.5 percent been females. This indicates that cocoa production is a male dominated occupation in the study area. In Ghana cocoa production is considered a male job but this is not the situation at the study sites because both women and men play a critical role in the production cycle. Within the last 30 years, cocoa farmers observed some impacts of climate change in the study communities, information gather from the cocoa farmers showed that there has been varying pattern in rainfall and sunshine. With regards to drought, overwhelming 98 percent of cocoa farmers reported the occurrence of drought in the study area and linked it to climate change. The pattern of rainfall distribution has changed as reported from the study. The study reported high level of windstorm, high incidence of flooding and frequent occurrences of pests and disease on their cocoa farms in recent time. These are attributed to climate change. Frequent felling of trees, non-shade cocoa production systems, wood harvesting for charcoal and firewood and bush burning among others were mention as some course of changing climate in the farming communities. About two thirds of the farmers reported unplanned trees harvesting as a major cause for variable rainfall thus climate change. This suggest that majority of farmers are aware of some of the causes of climate change in the study area. About 58 percent of cocoa farmers are using doing the non-shade cocoa production system. This result confirms a report [21], indicating that high proportion of Ghana’s cocoa is grown in full sun at the expense of primary or secondary forest conversion. A study [22] reported that shaded tree densities, and average number of tree species per hectare vary according to cultural tradition and ethnic group, age of farms, proximity to markets, and intensity of farming, this situation is similar to that of the study area after personal interaction with the cocoa farmers. This current trend of no shade is not only common in Ghana but other cocoa growing countries like Cote d’Ivoire, Malaysia, Indonesia and Ecuador. A study [23] in Ecuador reported that half of the new cocoa plantations are now full-sun and are from high-yielding variety. A study [24] also revealed that in Sulawesi cocoa farmers are switching from long-fallow shifting cultivation of food crops to intensive full-sun cocoa. This current trend of cocoa production put the food security of these cocoa farmers in doubt with the impact of climate change.

Cocoa farmers acknowledge the benefits of adopting cocoa agroforestry system in cocoa production. Farmers indicated that cocoa agroforestry has the potential of maintaining soil moisture, improving soil fertility as well as suppressing weeds within the cocoa farm. A study by Bentley [23] on cocoa farmers in Ecuador also indicated similar characteristics. Cocoa farmers acknowledged that no shade cocoa system is agriculturally unsustainable and is becoming common in the study area. The study reported that cocoa agroforestry mimics the natural sub canopy cover of traditional cocoa tree in the forest thus good practice to mitigate climate change. The shade trees selected by the cocoa farmers need to provide products and additional income when sold. Terminalia superb, Milicia excels, Terminalia ivorensis, Cedrella odorata,Ceiba pentandra and Ceiba pentandraas are the most dominant shade tree on cocoa farms  and are retained because of their economic importance. Eighty-five percent have little knowledge about the tree rights in the community although there are existing policies and legislations in Ghana. The average knowledge of useful species in this cocoa farming communities are fading out. For example, some of the younger farmers interviewed retain shade trees on an interest in the knowledge of their parents and grandparents.

Cocoa farmers have various levels of perception on certain characteristics of cocoa agroforestry. About 54 percent of cocoa farmers strongly perceive that cocoa agroforestry improves yield of cocoa. These trees ensure a microclimate condition which enhance the yield of the cocoa and thus mitigate climate change. Other perception held by cocoa farmers for cocoa agroforestry are enhancing soil moisture, improve farm humidity and environment, protecting young cocoa trees from pest and diseases and direct sun rays (Table 2).

Table 2: Perception of cocoa farmers on cocoa agroforest in mitigating climate change.

Cocoa agroforestry ensure sustainable yield

Strongly agree

162 (54)

Agree

66 (22)

Undecided

54 (18)

Disagree

18 (6)

Cocoa agroforestry improves soil fertility

Strongly agree

195 (65)

Agree

75 (25)

Undecided
Disagree

30 (10)

Cocoa agroforestry improve farm humidity

Strongly agree

204 (68)

Agree

60 (20)

Undecided

18 (6)

Disagree

8 (24)

Cocoa agroforestry enhance rainfall

Strongly agree

225 (75)

Agree

45 (15)

Undecided

21 (7.0)

Disagree

9 (3.0)

Cocoa agroforestry serves as a wind break on farms

Strongly agree

240 (80)

Agree

45 (15)

Undecided
Disagree

15 (5)

Factors Affecting Adoption of Climate-Smart Agriculture Innovations in Isolation and in Combination

Farmers’ adaption decisions were found to be influenced by several varying factors. The factors include farming experience, agricultural land size, belonging to farmer association, access to extension services, awareness of climate change, and experience in farming.

Results from the regression are reported here to tell the factors determining of adoption of individual farmer. The base category used in the analysis was non-adoption. Table 3 report coefficients and marginal effects from MNL regression respectively. Marginal effects (Table 3) are reported and discussed here. In this instance,  the marginal effects measure the expected change in probability of   a certain choice (of a cocoa agroforestry system) being made with respect to a unit change in an explanatory variable, all in comparison to the no adoption category.

Table 3: Factors influencing farmers adaption decision.

Variable Name

Estimate

SE

Wald

p (Sig.)

Odds ratio

Agriculture land size

0.239

.139

2.944

.086*

.787

Experience in farming

0.823

.388

4.499

.034**

2.278

Member of farmer Assciation

1.037

.453

5.240

.022**

2.821

Gender

0.474

.502

.892

.345

1.607

Awareness of climate change

0.063

.054

1.378

.0240**

1.065

Age of respondent

-011

.016

.447

.504

0.989

Access to extension service

2.976

0.756

15.510

.000***

0.51

Constant

2.901

1.092

7.060

.008***

18.19

Model chi-square 53.87 p<0.000

-2 log likelihood 171.058a

Nagelkerke (R Square) .730

***Significant at 1%, **Significant at 5%, *Significant at 10%.

Results are compared to the base category of no-adoption. The results indicated that adoption of cocoa agroforestry is negatively associated with age of farmer and positively associated with agriculture land size, experience in farming, member of farmer association, gender, awareness of climate change and access to extension service. Results imply that probability of adopting cocoa agroforestry decreases with ageing of cocoa farmer possibly due to risk aversion of innovative practices like cocoa agroforestry by older cocoa farmers. The positive association of cocoa agroforestry adoption with agriculture land size imply that larger plot sizes could be more flexible to experiment with cocoa agroforestry. Also, the positive association of extension could be due to availability of information for cocoa farmers with access to it. The factors of cocoa agroforestry adoption is in agreement with studies [25,26]. Extension services are very critical for availing necessary information on cocoa agroforestry. Overall, results show the importance of cocoa agroforestry system at the farmer level in building resilience to climate variability and change as well as other productivity related challenges in cocoa farming in Ghana. Adoption of cocoa agroforestry system reduces the impacts of climate change on cocoa productivity and hence farmer incomes. The enhanced impact of adopting cocoa agroforestry systems possibly arise as a result of the micro climatic conditions that is favorable for cocoa production. Findings of the study conform to other related literature that indicates that, adoption  of new agricultural technologies needs to positively impact on productivity, income and other welfare related variables of the adaptors.

Conclusion and Recommendation

Cocoa researchers and development partners are becoming more concern with welfare of cocoa farm in Ghana by promoting cocoa agroforestry systems which is essential in a bid to improve climate resilience. Cocoa agroforestry has the potential to improve soil fertility, regulate soil temperature, control soil moisture among other benefits. The study outcomes have shown that climatic changes have occurred over the years and these have had effect on the annual cocoa yield. The study revealed that some cocoa farmers are presently ignorant about their tree ownership on their farms. It therefore recommended that agricultural extension officers should educate these farmers on tree rights. Cocoa farmers in the study areas have noticed changes   in climate conditions through their own experiences and careful observations over the year of farmers. Also, respondents reported that cocoa agroforestry systems can offer numerous environmental, social and financial benefits, and can lead to an alternative way to mitigate climate change and variability. Land size, member of farmer association, experience in farming, awareness of climate change and access to extension service are the main factors that influence cocoa farmers’ decision to adopt cocoa agroforestry system. There is the need for effective provision of extension services through farmer field school programs. Programs of this nature have the potential to change farmers’ attitudes towards adopting a technology. Access to information and credit needs to be enhanced so as to get the needed logistics for managing cocoa agroforestry systems. This would facilitate farmers’ access to information about technical issues of the systems and how it can be managed in mitigating climate change. Finally, government should support cocoa famers through subsidies and long-term loans. There is also the need for more concerted and strong collaborative effort among Ghana COCOBOD, the Ministry of Food and Agriculture and Forestry Commission so as to reach greater a policy impacts on cocoa agroforestry system.

References

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The Urgent Need to Optimize Gestational Weight in Overweight/Obese Women to Lower Maternal- Fetal Morbidities: A Retrospective Analysis on 59,000 Singleton Term Pregnancies

DOI: 10.31038/AWHC.2020342

Abstract

Objective: We retrospectively did a simulation applying the optimal gestational weight gain (optGWG) equation (that we have proposed in 2018) on our population, and observed if its effect on maternal/fetal morbidities in singleton term pregnancies (≥37 weeks).

Design: Retrospective observational study.

Setting: Single large tertiary maternity unit in Reunion Island, Indian Ocean, overseas French department.

Population or sample: All consecutive singleton births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity. Standardized epidemiological perinatal database.

Methods: Mathematical simulation on a 19-year historical cohort (2001-2019).

Main outcome measures: Five Maternal/fetal morbidities.

Results: Beginning with overweight women, and enlarging the effect with the rise of different obesities (class I to III) and considering maternal pre- pregnancy BMI (ppBMI), individualized counselling women on their GWG (optimal gestational weight gain, optGWG) lowers significantly maternal/ fetal morbidities: in a logistic regression model among overweight/obese women, with the outcome optGWG, several morbidities have a negative coefficient as independent factors: cesarean-section, birthweight ≥ 4000 g, term preeclampsia, lowering the effect of rising maternal ppBMI per increment of 5 kg/m2 (coefficient -0.13), all p < 0.001.

We propose as a prediction to be verified in future prospective studies that a follow-up and counselling since the first prenatal visit should also lower gestational diabetes mellitus rates.

Conclusion: We may have significant health (and cost) benefits by lowering c-section rates, term preeclampsia, macrosomic babies and LGA babies  in overweight/obese women and low-birthweights babies in lean women. We  may have much to win from reducing weight gain during pregnancy in overweight/obese women. It is urgent to verify and establish in all continents the specific linear-curve of optGWG for each geographic/ethnic area.

Keywords

Pregnancy, Epidemiology, Pre-pregnancy body mass index, Gestational weight gain, Caesarean section, Obesity, Preeclampsia

Introduction

Based on a simple axiom: “what is the optimal gestational weight (optGWG) in women to achieve in term pregnancies the natural rate of 10% of SGA (small for gestational age) as well as 10% of LGA (Large for gestational age) in newborns”, we have found in our population that it is a mathematical linear equation: opGWG (kg) = -1.2 ppBMI (Kg/m2) + 42 ± 2 kg [1,2].

As a matter of fact, when we plot on a graph maternal pre- pregnancy BMI (ppBMI), and the babies’ percentiles, 10% SGA- LGA 10% is materialized by a crossing point. The fact that  this 10% corresponds to a given maternal BMI category suggests that there is a biological maternal-foetal connection. We proposed to call this crossing point the Maternal-Fetal Corpulence Symbiosis (MFCS) [1].

Also, since it is a mathematical linear equation it allows that    all single women may be considered as a single plot and that we may calculate for each woman at the beginning of pregnancy the individualized optGWG for that pregnancy. Analysing our 19-year cohort, we applied our linear equation on this study population, looking if our proposed optGWG would have changed important outcomes in our population (mathematical simulation).

The purpose of this study is, first, to collect what have been several important maternal/fetal morbidities in our term pregnancies during this 19-year clinical experience: rates of cesarean section, term preeclampsia, gestational diabetes mellitus in women, rates of SGA, LGA, macrosomia (≥ 4kg), low birthweights (< 2500g) and transfers in the neonatal department of newborns. Second, to make  a simulation of what would have happened in women with optGWG (optimal weight gain ± 2kg) and those with moderately insufficient or excessive GWG (± 3-9kg as compared with optGWG) or severely insufficient or excessive GWG (± 10kg as compared with optGWG).

Material and Methods

From January 1st, 2001, to December 31st, 2019, the hospital records of all women who gave birth at the maternity of the University South Reunion Island were abstracted in a standardized fashion. The study sample was drawn from the hospital perinatal database which prospectively records data of all mother-infant pairs since 2001. Information is collected at the time of delivery and at the infant hospital discharge and regularly audited by appropriately trained staff. This epidemiological perinatal data base contains information on obstetrical risk factors, description of delivery, and maternal and neonatal outcomes. For the purpose of this study, records have been validated and have been used anonymously. All pregnant women in Reunion Island as part of the French National Health Care System have their prenatal visits, biological and ultasonographic examinations, and anthropological characteristics recorded in a maternity booklet.

Preeclampsia, gestational hypertension and eclampsia were diagnosed according to the definition issued by the International Society for the Study of Hypertension in Pregnancy (ISSHP) relatively to the guidelines in force at the year of pregnancy. In the present study, because optimal weight gain has been described only for term pregnancies [1], we have selected only women who delivered live births at term (37-42 weeks).

Design and Study Population

The maternity department of Saint Pierre hospital is a tertiary care centre that performs about 4,300 deliveries per year, thus representing about 85% of deliveries of the Southern area of Reunion Island, and it is the only level-3 maternity (the other maternity is a private clinic). Reunion Island is a French overseas region in the Southern Indian Ocean. The entire pregnant population has access to maternity care free of charge as provided by the French healthcare system, which combines freedom of medical practice with nationwide social security. Prenatal system is based on scheduled appointments (9 prenatal visits and on average 4 ultrasounds) starting from 6 to 8 (see below) weeks of gestation.

Definition of Exposure and Outcomes

Booking BMI (ppBMI), was obtained at the first antenatal visit (average 6-8 weeks). Women are systematically weighted at their arrival in labour & delivery. In rare cases of imminent delivery (< 10%) the documented weight during the last antenatal visit prior to birth was used for calculations.

Primary Outcome

We arbitrarily created 5 categories of GWG using the published formula:

(optGWG = -1.2x +42 ppBMI -kg/m2– ± 2 kg) [1] defined in our population of Reunion island.

– Optimal GWG range: optimal GWG result PLUS or MINUS 2 kg (the formula).

– Insufficient GWG:

• Moderately insufficient: adequate GWG minus 3 to minus 9 kg.

• Severely insufficient: adequate GWG minus 10 kg and below:

– Excessive GWG:

• Moderately excessive: adequate GWG PLUS 3 to plus 9 kg.

• Severely excessive: adequate GWG PLUS 10 kg and over.

– Screening of GDM is systematically made in all pregnant women in the first trimester: until 2016 it was the O’Sullivan test (50g glucose, blood glucose level after 1 hour). The threshold for hyperglycemia being 1.4 g/l. Since 2016, this test has been replaced in all women by a fasting glycemia    in the first trimester, the threshold for positivity being 0.92 g/l. As the incidence of gestational diabetes mellitus is very high in Reunion GTT is made (between 24-28 weeks) to ALL pregnant women (even if they have a normal 1st trimester blood glucose). Those who have no GTT are only those who have a 1st trimester blood glucose over 1.26g/l, these last being considered as Type 2 diabetes.

Statistical Analysis

– Data is presented as numbers and proportions (%) for categorical variables and as mean and Standard Deviation (SD) for continuous ones. Comparisons between groups were performed by using χ;2-test; Odds Ratio (OR) with 95% Confidence Interval (CI) was also calculated. Paired t-test was used for parametric and the Mann-Whitney U test for non-parametric continuous variables. P-values <0.05 were considered statistically significant. Epidemiological data have been recorded and analysed with the software EPI-INFO 7.1.5 (2008, CDC Atlanta, OMS), EPIDATA 3.0 and EPIDATA Analysis V2.2.2.183. Denmark.

Ethnic Origin

Reunionese women comprise a melting pot of African and African intermixed populations for ap. 82% of the inhabitants (the 18% other being Europeans from mainland France): Dravidian Indian (South- India, Madras and Pondichery) and very few Chinese origin. Therefore “Reunion origin” comprises roughly African intermixed origin for approximately 75% and Dravidian Indians (South India, Tamils) for 25%. The French Constitution (and therefore laws) forbids ethnicity, religion or political opinions of the citizens on viral or scientific records. Therefore, we could not include ethnicity in any logistical model.

– To validate the independent association of maternal age and other confounding factors on term optimal gestational weight gain (optGWG) we realized a multiple regression logistic model. Variables associated with optGWG in bivariate analysis, with a p-value below 0.1 or known to be associated with the outcome in the literature were included in the model. A stepwise backward strategy was then applied to obtain the final model. The goodness of fit was assessed using the Hosmer-Lemeshow test. A p-value below 0.05 was considered significant. All analyses were performed using MedCalc software (version 12.3.0; MedCalc Software’s, Ostend, Belgium).

– Optimal gestational weight gain (YES/NO) being the outcome measure, we considered the following covariates as possible confounders in this analysis: pre-pregnancy maternal BMI by increment of 5kg/m2, gestational diabetes, caesarean section rates, term preeclampsia, birthweights over 4 kg, and newborn’s transfers in the neonatal departments. We included these variables and calculated the χ² for trend (Mantel extension), the odds ratios for each exposure level compared with the first exposure level.

Results

During the 19-year period, there were 68,047 term (37-42 weeks) singleton live births in University maternity of South-Reunion Island. We could determine gestational weight gain in 65,738 women (96.6% of women) and determine optimal GWG in 59,171 (87%) of women (requirement to have also the information on mothers’ heights to calculate the BMI).

Table 1 shows population characteristics depicts crude results in our population. Pregnancies were well followed (9 prenatal visits, 4.4 ultrasonographies in average), our population is young (27 years in average), with a high rate of women declaring living single (36%), and a high rate of obesity (≥ 30 kg/m2, 17.6%).

Table 1: Population characteristics. Term pregnancies ≥ 37 weeks gestation with known GWG end of pregnancy N=65,738 (96.6% of the entire cohort). Live births only (and total births for intrauterine fetal deaths).

Characteristics

All term pregnancies (≥37 weeks) N=65,738 (%)

Women with optimal weight gain N=12,594

Other women “reference” N=55,453

OR [95% CI] Optimal GWG vs. reference

p-value

Maternal age (SD)

27.7 ± 6.5

27.7 ± 6.5

28.0 ± 6.5

Difference 0.3 year

0.001

Parity ± sd

1.28 ± 1.5

1.24 ± 1.5

1.28 ± 1.5

0.03

Primiparity

25,297 (37.2)

4655 (37.0)

20,642 (37.2)

0.58

Women living single

24,528 (36.2)

4309 (34.3)

20,219 (36.6)

Education > 10 years

38,466 (58.1)

7310 (59.7)

31,156 (58.3)

1.06
[1.02-1.1]

0.005

Origin Reunion Island

55,700 (82.2)

10,403 (82.8)

45,297 (81.9)

NS

BMI (mean ± sd,kg/m2)

24.7 ± 5.9
N=65,738

24.4 ± 4.3
N=12,592

24.8 ± 6.3
N=53,146

Difference
0.4 kg/m²

< 0.0001

Obesity ≥ 30 kg/m²

11,547 (17.6)

1418 (11.3)

10,129 (19.1)

0.54
[0.51-0.57]

< 0.0001

BMI categories

1 ≤19 (underweight)

13,713 (20.8)

1589 (12.6)

12,124 (22.6)

0.51 [0.48-0.55]

< 0.0001

1 20-24 (normal)

26,294 (40.0)

6032 (47.9)

20,262 (38.1)

1.6 [1.53-1.66]

< 0.0001

1 25-29 overweight

14,184 (21.6)

3553 (28.2)

10,631 (20.0)

1.7 [1.58-1.73]

< 0.0001

1 30-34 (obesity I)

7017 (10.7)

1175 (9.3)

5842 (11.0)

0.87 [0.82-0.93]

< 0.0001

1 35-39 (obesity II)

3021 (4.6)

205 (1.6)

2816 (5.3)

0.31 [0.27-0.35]

< 0.0001

1 >40 (obesity III)

1509 (2.2)

38 (0.3)

1471 (2.8)

0.11 [0.08-0.15]

< 0.0001

Smoking

8205 (12.1)

1880 (11.8)

6725 (12.1)

0.96

0.25

Nb of prenatal visits

9.0 ± 2.73

9.1 ± 2.62

8.9 ± 2.74

0.001

Number of ultrasonographies

4.4 ± 1.7

4.4 ± 1.5

4.4 ± 1.7

0.99

0.93

Weight gain (kg)

12.1 ± 6.2
N=65,738

12.6 ± 5.1
N=12,592

11.9 ± 6.5
N=47,798

Difference 0.7 kg

< 0.0001

Gestational diabetes

7061 (10.8)

1371 (11.0)

6103 (11.1)

0.99

0.64

Chronic hypertension

902 (1.3)

141 (1.1)

761 (1.4)

0.81 [0.68-0.97]

0.02

Term preeclampsia

760 (1.1)

100 (0.8)

660 (1.2)

0.66 [0.54-0.82

0.001

Hospitalization

7949 (11.7)

1422 (11.3)

6527 (11.8)

0.95

0.12

C-section

9971 (14.7)

1478 (13.9)

8223 (14.8)

0.93 [0.88-0.98]

0.007

Induced delivery

14,979 (22.0)

2738 (21.7)

12241 (22.1)

0.098

0.42

Birth weight (g)

3184 ± 440

3226 ± 421

3175 ± 447

Difference 51 g

< 0.0001

Low BW <2500 g

3592 (5.3)

473 (3.8)

3119 (5.8)

0.65 [0.6-0.7]

< 0.0001

Small for gestational age

7139 (10.5)

1053 (8.4)

6086 (11.0)

0.74 [0.7-0.8]

< 0.0001

Large for gestational age

6434 (9.5)

1248 (9.9)

5186 (9.4)

1.07 [1.0-1.14]

0.05

Birthweight ≥ 4000 g

2636 (3.9)

473 (3.8)

3119 (5.6)

0.65 [0.59-0.72]

< 0.0001

Neonatal transfers

2918 (4.3)

467 (3.7)

2451 (4.4)

0.83 [0.75-0.92]

0.001

Intrauterine fetal deaths

115/68,179 (0.2)

19/12611 (0.2)

96/55,668 (0.2)

0.87

0.58

When we look at crude results of BMI categories, it is of note (second column, women with optGWG) that only women with normal BMI (20-24.9 kg/m2) reached an acceptable score of optGWG in 48% of cases. For overweight women (25-29.9 kg/m2), 28% of cases only. For underweight women < 19 kg/m2, only 12%. For obese and severe obese women, it is worse: 9% to 1%.

Comparing maternal/foetal morbidities, in these crude  results the compared Odds-ratios between “optGWG” vs. “reference” (those who did not achieve optGWG ± 2kg): C-section rate OR 0.93 [0.88- 0.98], p = 0.007, term preeclampsia OR 0.66 [0.54-0.82], p = 0.001, low birthweights < 2500g, OR 0.65 [0.6-0.7], p = 0.0001, birthweights ≥ 4000 g, OR 0.65 [0.59-0.72], p = 0.0001, neonatal transfers OR 0.83 [0.75-0.92], p = 0.001.

Tables 2-5, with known GWG and ppBMI (information on height), N = 59,171 (87% of the entire cohort) detail the GWG for non-obese women (<25kg/m2), overweight (25-29.9), obese class I (30-34.9 kg/m2) and severe obese (35 kg/m2 and over). We categorized in optGWG, moderately insufficient or excessive optGWG ± 3-9kg, severely insufficient or excessive optGWG ±10kg.

For all the tables (first column on the left) we observed in our population during this 19-year period a majority of women considered by our proposed equation as inadequate GWG:

For Table 2, non obese: 63% in categories of INSUFFICIENT GWG (18,121+4518/36,167).

Table 2: Simulation from the perspective of optimal or non-optimal GWG. Rates (%) of several maternal/foetal morbidities. Non obese women < 25 kg/m2. N=36,167.

Differences with adequate Weight gain Non-obese women

C-section rate (%)

Term preeclampsia (%)

Gestational diabetes

SGA (%)

LGA (%)

BW ≥ 4 kg (%)

Neonatal Transfers (%)

-10 kg and lower N=4518

384 (8.5)

20 (0.4)

295 (6.5)

1028 (22.8)

89 (2.0)

24 (0.5)

181 (4.0)

-3-9 kg, N=18,121

1921 (10.6)

103 (0.6)

1167 (6.4)

2161 (11.9)

1034 (5.7)

316 (1.7)

573 (3.2)

Adequate GWG ± 2 kg, N=7621

985 (12.9)

67 (0.9)

438 (5.8)

629 (8.3)

714 (9.4)

270 (3.5)

270 (3.5)

+3-9 kg. N=5187

786 (15.2)

72 (1.4)

243 (4.7)

302 (5.8)

649 (12.5)

331 (6.4)

204 (3.9)

10 kg+ N=703

125 (17.8)

24 (3.4)

46 (6.6)

41 (5.8)

133 (18.9)

81 (11.5)

31 (4.4)

Observed rates. N=36,167

4201 (11.6)

286 (0.8)

2189 (6.1)

4161 (11.5)

2619 (7.2)

1022 (2.8)

1259 (3.5)

Odds Ratios: “Adequate” vs. observed

1,12 [1.04-1.2] P=0.001

1.11 P=0.21

0.94 P=0.15

0.69 [0.63-0.75] P=0.001

1.32 [1.2-1.4] P=0,001

1.26 [1.1-1.4] P=0.001

1.01 P=0.39

For Table 3, overweight: 47% in categories of EXCESSIVE GWG (4736+1268/12,701).

Table 3: Simulation from the perspective of optimal or non-optimal GWG. Rates (%) of several maternal/foetal morbidities. Overweight women 25-29.9 kg/m2. N=12,701.

Differences with adequate Weight gain Overweight 25-29.9 kg/m2

C-section rate (%)

Term preeclampsia (%)

Gestational diabetes

SGA (%)

LGA (%)

BW ≥ 4 kg (%)

Neonatal Transfers (%)

-10 kg and lower N=267

22 (8.2)

0 (0.0)

52 (19.6)

51 (19.1)

89 (2.0)

11 (4.1)

9 (3.4)

-3-9 kg, N=2877

382 (13.3)

25 (0.9)

519 (18.2)

365 (12.7)

1034 (5.7)

186 (6.5)

91 (3.2)

Adequate GWG ± 2 kg, N=3553

522 (14.7)

22 (0.6)

577 (16.4)

294 (8.3)

714 (9.4)

377 (10.6)

145 (4.1)

+3-9 kg. N=4736

847 (17.9)

66 (1.4)

562 (12.0)

327 (6.9)

649 (12.5)

642 (13.6)

186 (3.9)

10 kg+ N=1268

288 (22.7)

33 (2.6)

120 (9.6)

78 (6.2)

133 (18.9)

245 (19.3)

61 (4.8)

Observed rates. N=12,701

2061 (16.2)

146 (1.2)

1830 (14.6)

1115 (8.8)

2619 (7.2)

1461 (11.5)

492 (3.9)

Odds Ratios: “Adequate” vs. observed

0.88 [0.79-0.98] P=0.01

0.53 [0.33-0.83] P=0.003

1.15 [1.04-1.3] P=0.003

0.93 P=0.17

0.96 P=0.24

0.91 P=0.07

0.91 P=0.28

For Table 4, Obese class I: 71% in categories of EXCESSIVE GWG (2898+1525/6232).

Table 4: Mmulation from the perspective of optimal or non-optimal GWG. Rates (%) of several maternal/foetal morbidities. Obesity class I: 30-34.9 kg/m2. N=6232.

Differences with adequate Weight gain Obese I 30-34.9 kg/m2

C-section rate (%)

Term preeclampsia (%)

Gestational diabetes

SGA (%)

LGA (%)

BW ≥ 4 kg (%)

Neonatal. Transfers (%)

-10 kg and lower N=73

11 (15.1)

0 (0.0)

18 (25.0)

11 (15.1)

2 (2.7)

1 (1.4)

5 (6.8)

-3-9 kg, N=561

85 (15.2)

4 (0.7)

152 (27.3)

70 (12.5)

39 (7.0)

14 (2.5)

21 (3.7)

Adequate GWG ± 2 kg, N=1175

198 (16.9)

9 (0.8)

279 (24.1)

111 (9.4)

136 (11.6)

53 (4.5)

48 (4.1)

+3-9 kg. N=2898

623 (21.5)

47 (1.6)

582 (20.5)

228 (7.9)

413 (14.3)

151 (5.2)

107 (3.7)

10 kg+ N=1525

364 (23.9)

43 (2.8)

223 (15.0)

109 (7.1)

293 (19.2)

150 (9.8)

72 (4.7)

Observed rates. N=6232

1281 (20.6)

103 (1.7)

1254 (20.5)

529 (8.5)

883 (14.2)

369 (5.9)

253 (4.1)

Odds Ratios: “Adequate” vs. observed

0.78 [0.66-0.92] P=0.002

0.45 [0.22-0.87] P=0.01

1.23 [1.06-1.4] P=0.002

1.12 P=0.14

0.79 [0.65-0.96] P=0.009

0.75 [0.55-1.0] P=0.03

1.0 P=0,48

For Table 5, Severe obese: 91% in categories of EXCESSIVE GWG (1300+2406/4071).

Table 5: Simulation from the perspective of optimal or non-optimal GWG. Rates (%) of several maternal/foetal morbidities. Severe Obesity ≥ 35 kg/m2. N=4071.

Differences with adequate Weight gain Obese I 30-34.9 kg/m2

C-section rate (%)

Term preeclampsia (%)

Gestational diabetes

SGA (%)

LGA (%)

BW ≥ 4 kg (%)

Neonatal. Transfers (%)

-10 kg and lower N=16

1 (6.3)

0 (0.0)

5 (33.3)

3 (18.8)

1 (6.3)

1 (6.3)

0 (0.0)

-3-9 kg, N=106

13 (12.3)

2 (1.9)

37 (35.2)

14 (13.2)

9 (8.5)

3 (2.8)

6 (5.7)

Adequate GWG ± 2 kg, N=243

43 (17.7)

2 (0.8)

77 (32.5)

19 (7.8)

21 (8.6)

5 (2.1)

4 (1.6)

+3-9 kg. N=1300

276 (21.2)

24 (1.8)

357 (28.0)

113 (8.7)

164 (12.6)

61 (4.7)

66 (5.1)

10 kg+ N=2406

655 (27.2)

76 (3.2)

608 (26.3)

144 (6.0)

492 (20.4)

229 (9.5)

139 (5.8)

Observed rates. N=4071

988 (24.3)

104 (2.6)

1084 (27.5)

293 (7.2)

687 (16.9)

299 (7.3)

215 (5.3)

Odds Ratios: “Adequate” vs. observed

0.67 [0.47-0.93] P=0.009

0.31 [0.05-1.07] P=0.07

1.27 [0.97-1.7] P=0.06

1.09 P=0.40

0.46 [0.29-0.73] P=0.001

0.46 [0.1-0.6] P=0.001

0.30 [0.1-0.74] P=0.006

In all the Tables 2 to 5 the calculated crude odds-ratios are comparisons between optGWG and the observed rate in the total population (and not with some categories of inadequate GWG). These OR may be easily calculated as much higher if compared with for example the 71% of excessive weight gain seen in obese class I (30-34.9 kg/m2) and optGWG.

Table 2 (non obese women), N = 36,167 women (61% of our population): For this “normal” population, comparisons with optimal GWG did not give important differences with actually happened during the 19 year clinical practice. It is of note that the optGWG women had 10% more C-sections (OR 1.12, p = 0.001), LGA babies (9.4% vs. 7.2) and birthweights over 4 kg (3.5% vs. 2.8%)

Table 3 (overweight women), N = 12,701 women: OptGWG women have significantly less caesarean section rate (OR 0.88, p = 0.01), less term preeclampsia (OR 0.53, p = 0.003, and a tendency to have less newborns with birthweights over 4 kg (OR 0.91, p = 0.07).

Table 4 obesity class I and Table 5 severe obese (≥ 35 kg/m2):  All crude comparisons for the chosen morbid items are statistically significant: OptGWG women had less caesarean section rate (respectively OR 0.78 and 0.67, p = 0.002), less term preeclampsia (OR 0.45, p = 0.01 and 0.31 p = 0.07), less LGA (OR 0.79 and 0.46, p = 0.001), less birthweights over 4 kg (OR 0.75, p = 0.03 and 0.46, p = 0.001) and less neonatal transfers in neonatology for severe obese (≥ 35 kg/m2): OR 0.30, p = 0.006.

It is of special note that in overweight and all obese women (Tables 3-5) incidence of GDM is higher in optGWG women than in the observed rate.

Table 6 As the effect of achieving optimal weight gain is largely concentrated in overweight and all kind of obesities, we performed our logistic model only in overweight and obese class I,II and III women (therefore the 25,731 pregnancies with pre-pregnancy BMI ≥ 25 kg/ m2). Multiple logistic regression model to validate the independent association of optimal GWG with different maternal-foetal morbidities. Controlling for all the other variables, several morbidities have a negative coefficient as independent factors: cesarean-section (coefficient -0.20, decrease of 20%), birthweight ≥ 4000 g (coefficient
– 0.38), term preeclampsia (coefficient -0.79), maternal overweight pre-pregnancy BMI (coefficient -0.13, decrease of 13% of the BMI effect per increment of 5 kg/m2 using optimal weight gain). However, adequate GWG have a positive coefficient with GDM: 0.19, increase of the risk by 19%.

Table 6: Outcome: optimal gestational weight gain in overweight/obese women (pre-pregnancy BMI ≥ 25 kg/m2, N=25,731 pregnancies). Multiple logistic regression model to validate the independent association of optimal GWG with different maternal-foetal morbidities. Controlling for all the other variables, several morbidities have a negative coefficient as independent factors: cesarean-section (coefficient -0.20, decrease of 20%), birthweight ≥ 4000 g (coefficient -0.38), term preeclampsia (coefficient -0.79), maternal overweight pre-pregnancy BMI (coefficient -0.13, decrease of 13% of the BMI effect per increment of 5 kg/m2 using optimal weight gain). However, adequate GWG have a positive coefficient with GDM: 0.19, increase of the risk by some 20%.

Multiple Logistic Regression Outcome: optimal gestational weight gain

Coefficient

Odds Ratio

95% CI

P

Cesarean section

-0.20

0.81

[0.74-0.89]

<0.0001

Birthweight ≥ 4000 g

-0.38

0.67

[0.57-0.79]

<0.0001

Pre pregnancy maternal BMI (increment of 5 kg/m2)

-0.13

0.87

[0.86-0.88]

<0.0001

Gestational diabetes mellitus

0.19

1.21

[1.11-1.31]

<0.0001

Term preeclampsia

-0.79

0.45

[0.31-0.65]

<0.0001

Transfer in neonatal department

-0.09

0.90

[0.77-1.06]

0.25

Figure 1 shows simulation based on maternal pre-pregnancy BMI by increments of 5 kg/m2 (upper case) maternal morbidities C-sections and term preeclampsia rates and (lower case) neonatal morbidities birthweight over 4 kg and transfers in neonatal department. These figures consider all the spectrum of maternal pre-pregnancy BMI from lean women to obesity class III. In dark lines, the 19 year- experience observed rates, in dash lines the calculated rates if women had achieved the optGWG (window of 4 kg specific to each woman). Visually, we can estimate the strong effect of optGWG beginning with overweight BMI and emphasized with rising BMI.

AWHC-3-3-320-g001

Figure 1.Simulation based on maternal pre-pregnancy BMI by increments of 5 kg/m2. Maternal and neonatal morbidities. Dark lines: observed rates, in dash lines the calculated rates if women had achieved the optGWG (window of 4 kg specific to each woman).

Figure 2 shows simulation of optimal or non-optimal GWG for all categories of ppBMI (lean to obese). We can visualize the effect of insufficient or excessive GWG on the outcomes LGA, macrosomic babies, SGA and C-sections rates.

AWHC-3-3-320-g002

Figure 2. Simulation from the perspective of optimal or non-optimal GWG. Women having achieved their personal optGWG vs. moderately or severe insufficient or excessive GWG.

Not shown in the Tables and Figures: the rate of low birthweight newborns (< 2500g). In non obese women (< 25kg/m2), it is of 3.7% in optGWG vs. 5.8% in observed rates OR 0.64 [0.57-0.73], p < 0.001 women. Respectively in overweight 3.9% vs. 4.3% (NS), class I obese 4.1% vs. 3.7% (NS), in severely obese women (≥ 35 kg/m2) 3.7% vs. 3.7%.

Discussion

Our calculations on simulated maternal/fetal morbidities in our term pregnancies, (rates of cesarean section, term preeclampsia, GDM, SGA, LGA, macrosomia (≥ 4kg), low birthweights (< 2500g) and transfers in the neonatal department of newborns) demonstrate that achieving “Maternal Fetal Corpulence Symbiosis, MFCS” [1] in all women would have the potential to significantly lower important maternal/fetal morbidities, except, surprisingly and for now, the rate of GDM.

We have put an online calculator consultable on smart phone at REPERE.RE (REseau PErinatal REunion), in three languages (French, Spanish and English) [2], and any reader is invited to validate these findings in their own populations.

It is of note that achieving MFCS, our rates of SGA-LGA in all the tables and figures reproduced in this paper, we notice that the equilibrium points (optGWG) show the closest combination to the 10% SGA/LGA crossing point. First, concerning the huge debates on gestational weight gain and maternal obesity (class I-III), we will not in this paper recall all these controversies (and the numerous critics, for example, those made by our Asian colleagues [3], China, Korea, Japan, India on the current  IOM  2009  recommendations [4]) as they have been recently extensively discussed by ourselves elsewhere [1,5,6].

Second, the “gestational diabetes mellitus paradox” it is noteworthy in all the tables to find an inverse relationship between optimal GWG and the risk of gestational diabetes. Lowering the GWG seems to heighten the risk of GDM, and excessive weight gain to lower it! GDM seems to be the only significant maternal risk that is not ameliorated by achieving an optGWG. In Table 6, the logistic regression model, controlling for other risks, the coefficient for GDM is 0.19 (an increase of 19% of the risk with optimal GWG). This phenomenon has also been described by preceding authors [7-9], and in fact, it might be  an “optical” or a “perspective” bias due to our retrospective data. Li et al. [7] proposed an explanation which may be the good one: because the diagnosis of GDM occurs primarily at 26-28 weeks of gestation, treatment with diet and/or insulin plus increased physical activity may affect subsequent weight gain resulting in decreased weight gain in late pregnancy. This is emphasized in a recent paper in the United Kingdom (UPBEAT study): obese women with a positive OGTT at 27 weeks, and afterward a strong follow-up until delivery present lower weight gain than obesity considered as non-diabetic [10].

Indeed, it is because our study is retrospective, and that we mix the concept of optimal weight gain which could be theoretically known since the beginning of pregnancy with the diagnosis of GDM which is made much later: 24-28 weeks. If we did a prospective follow-up of obese pregnancies since the beginning of counselling to the woman, a moderate GWG (or even a loss of weight in severe obesities), incidence of GDM being quasi-parallel and proportional with the increase of BMI [10,11], we predict that women would reach the 24th week of gestation with lower rates of GDM diagnoses in a prospective management of such pregnancies.

Third: applicability of our linear equation for pragmatic management of future pregnancies elsewhere. The fact that the Maternal Fetal Corpulence Symbiosis (MFCS) has been achieved   as a mathematical linear equation, it implies that it is also similar elsewhere. But, we do not feel fair to state that our formula, designed in our Reunionese population, would be adapted everywhere [1,2]. MFCS is based on the 10% crossing point of SGA-LGA. Therefore, these SGA/LGA definitions are different in different ethnicities (e.g. Eastern Asians, India, Africa etc…).

Let us consider the problem of SGA: for us, in Reunion island, being SGA at term is to be approximately less than 2500g. But, in India, the physiological SGA birthweight at term is 2200g [12,13]. This may be also in line with a recent WHO study arguing that definition of low-birthweight should be different (< 2200g in Africa, < 2100g in Asia, < 2200g in Latin America) between different populations, and no more the universal below 2500g [14].

Considering the mothers, and countries like India or Japan which have a high rate of lean women [12-15]. In our formula, lean women of 18.5 kg/m2 should have an optGWG of 20 kg (instead of 12.5-18 kg, IOM 2009 recommendations), but we do not feel that counselling a great proportion of Indian or Japenese women to gain 20 kg in their pregnancies before knowing their newborns’ SGA-LGA rates is legitimate.

Considering now the problem of LGA: for example, macrosomic newborns with birthweights ≥ 4000 g, in Reunion represent 3.9% of term babies, but it is 0.5% in India, 6.9% in China, 2.0% in Niger, 2.2% in Thailand, 9.3% in Paraguay 1.3% in Philippines, Nepal, Sri-Lanka etc…[16].

Therefore and logically, an Indian, Japenese, Chinese or Swedish linear equation should then be slightly different than ours ( y = -1.2 x
+ 42). This has been recently stated by Guan et al.: “There are specific Chinese birthweight curves for neonates. Therefore, with knowledge of the 10th percentile (SGA) and the 90th percentile (LGA) of newborns, we could test the proposed ‘maternal-fetal-corpulence symbiosis’, which was recently proposed ….” [3]. It is time and urgent to verify and establish in all continents the specific MFCS linear equation, to make it accessible everywhere on smartphones for health workers and women themselves [2,17]. Knowing the specific SGA-LGA definitions of newborns in a setting or a country, allows to easily find the MFCS curve everywhere.

Forth, the problem of macrosomia (≥ 4kg). These newborns are well-known to present a 10 fold higher risk of the fearsome shoulder dystocia [16]. The limit of 4kg is considered to be the point where significant morbidities at delivery may occur [18], moreover, in the case of associated GDM [19]. Our simulation suggests that optGWG could lower very significantly the rate of macrosomia at birth: OR 0.75, p = 0.03 in class 1 obesity, OR 0.46, P = 0.001 in severely obese women (Tables 4 and 5) and, for all overweight women adjusted OR 0.67, p <0.0001, Table 6. There is a strong current ongoing consensus on obesity, GWG, and consequences for maternal-fetal health. Urgent further work is required to identify ways to assist women in achieving an optimal GWG, with further RCT to confirm that such interventions would translate in a marked reduction in maternal/fetal morbidities, especially for macrosomia.

We do not comment here on the significant decrease of term preeclampsia, with high potential consequences also in health-costs policies. It has just been recently published in a specific study [6].

We have also tested intrauterine fetal deaths (IUFD, bottom of Table 1) as a meta-analysis showed that maternal obesity increases the risk for fetal deaths (OR 1.21 [1.09-1.35]), [20]. For the entire cohort, we did not find any difference between optGWG women and controls (Table 1) [21]. Finally, our results seem in contradiction of the large number of clinical trials, meta-analyses and individual participant data meta-analyses that have robustly shown that at best, dietary   and lifestyle interventional studies have reduced GWG by 0.7kg or 3.7kg (minus the IOM recommendations for obese women 5-9 kg) and had no effect on other pregnancy and birth outcomes including GDM, PE, PIH, LGA and macrosomic infants [22-25]. We have shown previously in our population that the IOM recommendations are correct for normal weight and overweight women [1], but not for obese, moreover if splitting them in Class I to III. Beginning at class II, women should even lose weight to achieve the SGA/LGA crossing point (“maternal fetal corpulence symbiosis”, MFCS) [1]. All these studies [22-25] considered obesity as a whole (≥ 30 kg/m2), while it seems more and more evident for many scholars that obesities class I, class II, and class III are somehow very different worlds concerning maternal/fetal morbidities.

The strength of our study is the capturing of all perinatal outcomes in a population of the area (ap. 360,000 inhabitants, and  5,000  births per year. With 4,300 births per year, the university maternity represents 85% of all births in the south of the island, all receiving level 3, European standard of care. The data in this large cohort are homogeneous as they were collected in a single center (no intercenter variability) and not based on national birth registers but directly from medical records (avoiding inadequate codes). The obvious weakness is the retrospective nature of this study, especially with the above discussion on GDM, demonstrating an association and not necessarily causation but we sincerely hope that our observations will trigger proper prospective trials because the potential health care benefits are immense.

Conclusion

We can help to actively counterbalance the morbid effects of high BMIs by individualized counselling for women on their GWG and have significant health (and cost) benefits with lowering c-section, term preeclampsia, low birthweights, and macrosomia rates. We renew our prediction that it should be also beneficial for gestational diabetes mellitus, but it can be verified only with a prospective study beginning since the first prenatal visit. We may have much to win from reducing weight gain during pregnancy in overweight/obese women. It is urgent to verify and establish in all continents the specific linear-curve of optGWG of each geographical/ethnic area, to make it accessible everywhere on smartphones for health workers and women themselves [2].

Disclosure of interest: All the authors attest that no conflict of interest exists regarding this work.

Contribution to authorship: All authors participated equally to this work and writings of the manuscript.

Ethics approval: This study was conducted in accordance with French legislation. As per new French law applicable to trials involving human subjects (Jardé Act), a specific approval of an ethics committee (comité de protection des personnes- CPP) is not required for this non-interventional study based on retrospective, anonymized data of authorized collections and written patient consent is not needed. Nevertheless, the study was registered on UMIN Clinical Trials Registry (identification number is UMIN000037012).

Funding: No special funding besides the normal existence of the South-Reunion perinatal database since 2001.

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Factors Influencing the Adoption of Cocoa Agroforestry Systems in Mitigating Climate Change in Ghana: The Case of Sefwi Wiawso in Western Region

Introduction

Climate change is having great impact on agricultural productivity worldwide. Agriculture is strongly influenced by weather and climate [1,2]. Climate change and variability adversely affect environmental resources such as soil and water upon which agricultural production depends, which poses a serious threat to sustainable agricultural production [2]. In Ghana climate variability and change is expected to have an adversely effect on the agriculture sector. According to the NIC, (2009) by 2030 temperature are projected to rise by 0.5 °C. This situation would result in fewer rainy days and more extreme weather conditions like prolonged droughts. The impacts of a changing climate will have direct and indirect effects on global and domestic food systems [3,4]. Rioux [5] reported that climate change has affected yields in food crop production in many Africa countries. If the issues of climate change and variability are not addressed incomes and food security of rural households in Ghana would be undermined because there would be increased incidence of diseases and pest as well as prolonged variable rainfall patterns.

Cocoa production employs over 15 million people worldwide with over 10.5 million workers in West Africa [6]. Cocoa, in addition to cereals and other root and tuber  crops  contribute  largely  to  food security in Ghana. In Ghana cocoa production is an essential component of  rural  livelihoods  and  its  cultivation  is  considered a ‘way of life’ in many production communities [7]. The cocoa sub sector cocoa employs about 800,000 farm families spread across the cocoa growing regions of Ghana and generating about $2 billion in foreign exchange annually [8,9]. The expansion of cocoa production is replacing substantial areas of primary forest. It’s of no surprise that the total area under cocoa cultivation increased by 50,000 hectares between 2012 and 2013 and there is no indication that the rate is slowing down. According to Anim Kwapong et al. [10] the government of Ghana recognizes that climate change is already negatively affecting Ghana’s cocoa sector in myriad ways and that, it is likely to continue hampering Ghana’s environmental and socio-economic prospects in the coming decades. Cocoa agroforestry system has been identified as is an important strategy that can ameliorate climate change [11].

This system can play a dual role of mitigation and adaptation, which makes it one of the best responses to climate change. It is noted that agroforestry has multi-functional purposes which makes it one of  the most promising strategies for climate change adaptation [11,12]. The use of trees and shrubs in agricultural systems help to tackle the triple challenge of securing food security, mitigation and reducing the vulnerability and increasing the adaptability of agricultural systems to climate change [13,14]. With this view, serious attention must be given to cocoa agroforestry which is capable of reducing temperatures and enhancing the growing of cocoa thus sustaining livelihood of many households in this climate changing pattern. According to previous studies [11,13,15] agroforestry as an adaptation strategy could sustain agricultural production and enhance farmers’ ability to improve livelihoods and will minimize the impacts of climate change which include drought, variable rainfall and extreme temperatures. Agroforestry as a forest-based system plays a significant role in conserving existing carbons, thereby limiting carbon emissions and also absorbing carbons that are released into the atmosphere [16]. Nair [17] also indicated that agroforestry has received international attention as an effective strategy for carbon sequestration and greenhouse mitigation. Cocoa agroforestry can increase farmers’ resilience and position them strategically to adapt to the impacts of a changing climate. This system of cocoa production can be very useful because it generates quite substantial benefits on arable lands in diverse ways; trees in agricultural fields improve soil fertility through control of erosion, improve nitrogen content of the soil and increase organic matter of the soil [18,19]. Agroforestry can also transform degraded lands into productive agricultural lands and improves productive capacities of soils [18]. Although agroforestry is not new in Ghana, it is quite optimistic that effective adoption to climate change will contribute towards the achievement of sustainable development and to a large extent, the attainment of the Sustainable Development Goals (SDGs). Despite the immeasurable benefits of cocoa agroforestry system, adoption is not widespread and for that matter success stories are found in isolated cocoa farming areas among few adapters of cocoa agroforestry system initiatives. Aidoo and Fromm [20] report that although cocoa farmers are aware about sustainability issues, they hardly adopt sustainable production practices. It is quite not always the case that policies are implemented as they were intended and so the need to assess farmers’ perspectives on cocoa agroforestry adoption and implementation especially when climate change has become a serious constraint to cocoa production in Ghana. Traditional coping mechanisms to the impact of climate change in the Western Region of Ghana include mixed cropping, non-farm activities and traditional agroforestry practices by some individual cocoa farmers. However, non-shade cocoa production systems, bush burning, slash and burn farming methods expose the cocoa communities to further impacts of climate change. This calls for swift attention from all, especially cocoa farmers in the study communities to tackle the problem. Despite the economic, environmental and sustainable cocoa production potential via agroforestry systems, farmers have not adopted cocoa agroforestry practices entirely especially in Sefwi Wiawso District. Understanding cocoa farmers decision making processes in ensuring sustainable food supply and cocoa yield in cocoa agroforestry system is critical. Research frontiers in cocoa agroforestry systems need to be identified and better understand barriers to adoption and the development of strategies to support cocoa agroforestry that enhance food security in climate changing conditions. The objectives of this study are therefore to empirically assess the factors that affect farmers’ decision to adopt cocoa agroforestry systems and determine cocoa farmers’ perception on cocoa agroforestry as an adaptation strategy to climate change.

Methodology

The study was conducted at Sefwi Wiawso in the Western and region of Ghana. The district lies within latitudes 6º 00“and 6º 30 North and Longitudes 2º 15‟ and 2º 45 West. The District covers an area of about 2,634 square kilometers. The detailed hydrometeorological characteristics of the study area are provided in Table 1.

Table 1: Hydrometeorological characteristics of the study area.

Characteristics

Levels

Mean temperature

Maximum: 33°C Minimum: 26°C

Climate

Tropical rainforest

Average humidity

Dry season: 50-75%
Rainy season: 85-90%

Average rainfall

1500-1800 mm

Topography

Undulating

Soil condition

Loamy

Average elevation

206 m

A stratified random sampling technique was employed in the selection of the 300 cocoa farmers interviewed for the study. In the first stage, Western Region was purposively selected due to the fact that apart from being one of the highest cocoa producing regions    in Ghana, it is one of the regions which has experienced significant impact as a result of climate change. In the second stage, Sefwi Wiawso was randomly selected. In the third stage, five communities were randomly selected. In the final stage 60 cocoa farmers were randomly selected from each village. Primary data were employed in the study. The primary data consisted of qualitative data and household survey interviews. Specifically, the primary data were collected through focus group discussions (FGD), stakeholder interviews, and field observations. The household survey interviews employed both open- ended and close ended survey instruments.

To examine the factors that influence a household’s decision to participate in agroforestry a logistic regression model was employed.

The model was specified as:

ESCC-2-1-202-e001

Where: i = 1, 2, 3………., k are the observations, α= constant. β = the regression parameter to be estimated. βX= linear combination of independent variables.  Zi= the log odds of choice for the  ithobservation. Pi= the probability of observing
a specific outcome of the dependent variable (adoption). Xn = nth explanatory observation. u = the error term.

Results and Discussion

The gender composition of the cocoa farmers among revealed that 81.5 percent of the respondent are males with 19.5 percent been females. This indicates that cocoa production is a male dominated occupation in the study area. In Ghana cocoa production is considered a male job but this is not the situation at the study sites because both women and men play a critical role in the production cycle. Within the last 30 years, cocoa farmers observed some impacts of climate change in the study communities, information gather from the cocoa farmers showed that there has been varying pattern in rainfall and sunshine. With regards to drought, overwhelming 98 percent of cocoa farmers reported the occurrence of drought in the study area and linked it to climate change. The pattern of rainfall distribution has changed as reported from the study. The study reported high level of windstorm, high incidence of flooding and frequent occurrences of pests and disease on their cocoa farms in recent time. These are attributed to climate change. Frequent felling of trees, non-shade cocoa production systems, wood harvesting for charcoal and firewood and bush burning among others were mention as some course of changing climate in the farming communities. About two thirds of the farmers reported unplanned trees harvesting as a major cause for variable rainfall thus climate change. This suggest that majority of farmers are aware of some of the causes of climate change in the study area. About 58 percent of cocoa farmers are using doing the non-shade cocoa production system. This result confirms a report [21], indicating that high proportion of Ghana’s cocoa is grown in full sun at the expense of primary or secondary forest conversion. A study [22] reported that shaded tree densities, and average number of tree species per hectare vary according to cultural tradition and ethnic group, age of farms, proximity to markets, and intensity of farming, this situation is similar to that of the study area after personal interaction with the cocoa farmers. This current trend of no shade is not only common in Ghana but other cocoa growing countries like Cote d’Ivoire, Malaysia, Indonesia and Ecuador. A study [23] in Ecuador reported that half of the new cocoa plantations are now full-sun and are from high-yielding variety. A study [24] also revealed that in Sulawesi cocoa farmers are switching from long-fallow shifting cultivation of food crops to intensive full-sun cocoa. This current trend of cocoa production put the food security of these cocoa farmers in doubt with the impact of climate change.

Cocoa farmers acknowledge the benefits of adopting cocoa agroforestry system in cocoa production. Farmers indicated that cocoa agroforestry has the potential of maintaining soil moisture, improving soil fertility as well as suppressing weeds within the cocoa farm. A study by Bentley [23] on cocoa farmers in Ecuador also indicated similar characteristics. Cocoa farmers acknowledged that no shade cocoa system is agriculturally unsustainable and is becoming common in the study area. The study reported that cocoa agroforestry mimics the natural sub canopy cover of traditional cocoa tree in the forest thus good practice to mitigate climate change. The shade trees selected by the cocoa farmers need to provide products and additional income when sold. Terminalia superb, Milicia excels, Terminalia ivorensis, Cedrella odorata,Ceiba pentandra and Ceiba pentandraas are the most dominant shade tree on cocoa farms  and are retained because of their economic importance. Eighty-five percent have little knowledge about the tree rights in the community although there are existing policies and legislations in Ghana. The average knowledge of useful species in this cocoa farming communities are fading out. For example, some of the younger farmers interviewed retain shade trees on an interest in the knowledge of their parents and grandparents.

Cocoa farmers have various levels of perception on certain characteristics of cocoa agroforestry. About 54 percent of cocoa farmers strongly perceive that cocoa agroforestry improves yield of cocoa. These trees ensure a microclimate condition which enhance the yield of the cocoa and thus mitigate climate change. Other perception held by cocoa farmers for cocoa agroforestry are enhancing soil moisture, improve farm humidity and environment, protecting young cocoa trees from pest and diseases and direct sun rays (Table 2).

Table 2: Perception of cocoa farmers on cocoa agroforest in mitigating climate change.

Cocoa agroforestry ensure sustainable yield

Strongly agree

162 (54)

Agree

66 (22)

Undecided

54 (18)

Disagree

18 (6)

Cocoa agroforestry improves soil fertility

Strongly agree

195 (65)

Agree

75 (25)

Undecided
Disagree

30 (10)

Cocoa agroforestry improve farm humidity

Strongly agree

204 (68)

Agree

60 (20)

Undecided

18 (6)

Disagree

8 (24)

Cocoa agroforestry enhance rainfall

Strongly agree

225 (75)

Agree

45 (15)

Undecided

21 (7.0)

Disagree

9 (3.0)

Cocoa agroforestry serves as a wind break on farms

Strongly agree

240 (80)

Agree

45 (15)

Undecided
Disagree

15 (5)

Factors Affecting Adoption of Climate-Smart Agriculture Innovations in Isolation and in Combination

Farmers’ adaption decisions were found to be influenced by several varying factors. The factors include farming experience, agricultural land size, belonging to farmer association, access to extension services, awareness of climate change, and experience in farming.

Results from the regression are reported here to tell the factors determining of adoption of individual farmer. The base category used in the analysis was non-adoption. Table 3 report coefficients and marginal effects from MNL regression respectively. Marginal effects (Table 3) are reported and discussed here. In this instance,  the marginal effects measure the expected change in probability of   a certain choice (of a cocoa agroforestry system) being made with respect to a unit change in an explanatory variable, all in comparison to the no adoption category.

Table 3: Factors influencing farmers adaption decision.

Variable Name

Estimate

SE

Wald

p (Sig.)

Odds ratio

Agriculture land size

0.239

.139

2.944

.086*

.787

Experience in farming

0.823

.388

4.499

.034**

2.278

Member of farmer Assciation

1.037

.453

5.240

.022**

2.821

Gender

0.474

.502

.892

.345

1.607

Awareness of climate change

0.063

.054

1.378

.0240**

1.065

Age of respondent

-011

.016

.447

.504

0.989

Access to extension service

2.976

0.756

15.510

.000***

0.51

Constant

2.901

1.092

7.060

.008***

18.19

Model chi-square 53.87 p<0.000

-2 log likelihood 171.058a

Nagelkerke (R Square) .730

***Significant at 1%, **Significant at 5%, *Significant at 10%.

Results are compared to the base category of no-adoption. The results indicated that adoption of cocoa agroforestry is negatively associated with age of farmer and positively associated with agriculture land size, experience in farming, member of farmer association, gender, awareness of climate change and access to extension service. Results imply that probability of adopting cocoa agroforestry decreases with ageing of cocoa farmer possibly due to risk aversion of innovative practices like cocoa agroforestry by older cocoa farmers. The positive association of cocoa agroforestry adoption with agriculture land size imply that larger plot sizes could be more flexible to experiment with cocoa agroforestry. Also, the positive association of extension could be due to availability of information for cocoa farmers with access to it. The factors of cocoa agroforestry adoption is in agreement with studies [25,26]. Extension services are very critical for availing necessary information on cocoa agroforestry. Overall, results show the importance of cocoa agroforestry system at the farmer level in building resilience to climate variability and change as well as other productivity related challenges in cocoa farming in Ghana. Adoption of cocoa agroforestry system reduces the impacts of climate change on cocoa productivity and hence farmer incomes. The enhanced impact of adopting cocoa agroforestry systems possibly arise as a result of the micro climatic conditions that is favorable for cocoa production. Findings of the study conform to other related literature that indicates that, adoption  of new agricultural technologies needs to positively impact on productivity, income and other welfare related variables of the adaptors.

Conclusion and Recommendation

Cocoa researchers and development partners are becoming more concern with welfare of cocoa farm in Ghana by promoting cocoa agroforestry systems which is essential in a bid to improve climate resilience. Cocoa agroforestry has the potential to improve soil fertility, regulate soil temperature, control soil moisture among other benefits. The study outcomes have shown that climatic changes have occurred over the years and these have had effect on the annual cocoa yield. The study revealed that some cocoa farmers are presently ignorant about their tree ownership on their farms. It therefore recommended that agricultural extension officers should educate these farmers on tree rights. Cocoa farmers in the study areas have noticed changes   in climate conditions through their own experiences and careful observations over the year of farmers. Also, respondents reported that cocoa agroforestry systems can offer numerous environmental, social and financial benefits, and can lead to an alternative way to mitigate climate change and variability. Land size, member of farmer association, experience in farming, awareness of climate change and access to extension service are the main factors that influence cocoa farmers’ decision to adopt cocoa agroforestry system. There is the need for effective provision of extension services through farmer field school programs. Programs of this nature have the potential to change farmers’ attitudes towards adopting a technology. Access to information and credit needs to be enhanced so as to get the needed logistics for managing cocoa agroforestry systems. This would facilitate farmers’ access to information about technical issues of the systems and how it can be managed in mitigating climate change. Finally, government should support cocoa famers through subsidies and long-term loans. There is also the need for more concerted and strong collaborative effort among Ghana COCOBOD, the Ministry of Food and Agriculture and Forestry Commission so as to reach greater a policy impacts on cocoa agroforestry system.

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