2020-05-29/30/31 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM Highlights: NM case count. Navajo Nation case update. Largest COVID-19 surge in Taos. ABQ BioPark to reopen. NM public schools reopening plan. NM unemployment claims. Rise in domestic and sexual abuse. US Highlights: Protests inspire fear of surge. Trump withdraws from WHO. Last aid bill. No new NY patients. ICE detainees sick. International Highlights: South Korea schools close. Undercounting in Russia. South African overburdened health care system. Economics, Workforce, Supply Chain, PPE: Reusable protection system. Protective household products. Longterm economic challenges. Epidemiology Highlights: Estimate virus reproduction numbers. Hypertension & cardiovascular disease impact on mortality. Gastrointestinal manifestations. Healthcare Policy Recommendations: Immunity passports are bad idea. Evaluation of hand WHO-recommended products. Opioid use-related challenges of COVID-19 management. Practice Guidelines: NICE guidelines on COVID-19 and acute kidney injury. Example of rapid conversion of an outpatient psychiatric hospital to a virtual telepsychiatry clinic. JAMA recommendations on conducting and reporting COVID-19 clinical research. Testing: Comparison of 4 antigen tests. Validation of antibody assays. Drugs, Vaccines, Therapies, Clinical Trials: Encouraging results of Ruxolitinib phase II RCT. Benefits of adjunctive herbal medicine. Potential inhibitors of viral protease screened. Anticoagulation alone is unlikely to protect from COVID-19 related morbidity and mortality. Open access database Covid19db for COVID-19 drugs. 49 new trials registered. Other Science: COVID-19 collateral damage. Telomere length and COVID-19 outcomes. Wastewater RNA early warning. Neurologic manifestation review. MRI reveals predominant anosmia cases. Self-quarantine weight gain. Immunosuppression vs. cytokine storm. Combatting misinformation

2020-06-03/04 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM Highlights: Navajo Nation to end weekend curfew. NM case count. Navajo Nation case updates. Food distribution by PepsiCo. APS to get funding. US Highlights: 5 vaccine candidates. Arizona’s increased cases. Some states postpone primaries. Pork plant infections. Economics, Workforce, Supply Chain, PPE: Impact on global supply chains. Residency selection process disrupted. Facemask filtration efficiency. Resources for underserved countries. Epidemiology Highlights: Morbidity and mortality in Africa. Healthcare Policy Recommendations: Need for social distancing. Psychological support guide. Return to work guidelines. Practice Guidelines: Anesthesia recommendations for ECT. Extracorporeal membrane oxygenation outcomes. Testing: Roche Elecsys IL-6 test is authorized by FDA to identify severe inflammatory response. Drugs, Vaccines, Therapies, Clinical Trials: HCQ RCT does not show disease prevention. Lancet HCQ study retraction. Adjunctive convalescent plasma did not show clinical improvement. Mixed remdesivir results. Virtual drug screening. Heparin improved survival. Moderna phase 3. Skin science for vaccine development. ECMO therapy. 48 new clinical trials. Other Science: Androgens and poor male outcomes. Trust in science enhances prevention compliance. High VTE prevalence in critically ill

2020-06-22/23 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM Highlights: Balloon Fiesta postponed. Robot to sanitize ABQ International Sunport. NMSU plan for fall 2020. NM public schools reopening plan. Fewer hospitalizations for COVID-19. NM case update. US Highlights: Visa restrictions. International Highlights: Second wave in South Korea. Epidemiology: Lockdown can suppress COVID-19. Case fatality rate associated with incidence. Predictors of ICU care and ventilators. Anxiety and depression from COVID-19. Asymptomatic patients as source of infection. Heterogeneous populations affect herd immunity. Healthcare Policy Recommendations: New FDA guidance on clinical trials conduct. Practice Guidelines: The guidelines are provided on COVID-19 diagnostics (Infectious Diseases Society of America), respiratory support for COVID-19 patients and optimizing mental care delivery during COVID-19 pandemic. Drugs, Vaccines, Therapies, Clinical Trials: Antithrombotic therapy systematic review. Drug repurposing. 58 new trials. Other Science: Safety of antihypertensives (ACEs and ARBs). Low testosterone linked to escalation of care. Neurological findings and hypercoagulability

Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio

Defining abnormal fetal growth and perinatal risk—population or customized standards?

In January's Guest Editorial, Sarah Stock and Jenny Myers discuss approaches to fetal and neonatal growth assessment

2020-05-11 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM case counts. Navajo Nation documentary. Medicaid reimbursement increase. Excess NYC mortality. German R0\u3e1. Chile COVID-19 certificates. High female incidence in Quebec. Swab 3D printing. Evidence lacking school reopening. Cloth mask review. WHO 2nd wave warning. Higher mortality in minorities. Environmental transmission controls. Behavior change. Correctional environment guidelines. Wuhan hospital transformation. Maximizing GI training. Threat and conformity. Recommendations on managing COVID-19 (first Italian SARS patients), and obesity and metabolic syndrome. Guidelines for neurologists. Ethics of off-label drugs use. Abbott antibody test approval. CRISPR test FDA approval. Viral sample inactivation. HCQ+azithromycin no benefit. Public-Private partnership for clinical trials. Drug repurposing. Cancer patient considerations. 35 new COVID-19 trials. Hyperinflammatory shock in children. Symptom app

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

Objective Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks’ with ultrasound parameters at 20±1 weeks’ gestation. Methods Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. Results 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks’ clinical variables, 15±1 weeks’ clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks’ were: 0.63 (0.59–0.67), 0.64 (0.60–0.68) and 0.69 (0.66–0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57–0.66), 0.61 (0.56–0.66) and 0.68 (0.64–0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70–0.82), 0.80 (0.75–0.86) and 0.84 (0.78–0.89) with minimal change in the Training datasets. Conclusion Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry

Equilibrium responses of global net primary production and carbon storage to doubled atmospheric carbon dioxide: sensitivity to changes in vegetation nitrogen concentration

We ran the terrestrial ecosystem model (TEM) for the globe at 0.5° resolution for atmospheric CO2 concentrations of 340 and 680 parts per million by volume (ppmv) to evaluate global and regional responses of net primary production (NPP) and carbon storage to elevated CO2 for their sensitivity to changes in vegetation nitrogen concentration. At 340 ppmv, TEM estimated global NPP of 49.0 1015 g (Pg) C yr−1 and global total carbon storage of 1701.8 Pg C; the estimate of total carbon storage does not include the carbon content of inert soil organic matter. For the reference simulation in which doubled atmospheric CO2 was accompanied with no change in vegetation nitrogen concentration, global NPP increased 4.1 Pg C yr−1 (8.3%), and global total carbon storage increased 114.2 Pg C. To examine sensitivity in the global responses of NPP and carbon storage to decreases in the nitrogen concentration of vegetation, we compared doubled CO2 responses of the reference TEM to simulations in which the vegetation nitrogen concentration was reduced without influencing decomposition dynamics (“lower N” simulations) and to simulations in which reductions in vegetation nitrogen concentration influence decomposition dynamics (“lower N+D” simulations). We conducted three lower N simulations and three lower N+D simulations in which we reduced the nitrogen concentration of vegetation by 7.5, 15.0, and 22.5%. In the lower N simulations, the response of global NPP to doubled atmospheric CO2 increased approximately 2 Pg C yr−1 for each incremental 7.5% reduction in vegetation nitrogen concentration, and vegetation carbon increased approximately an additional 40 Pg C, and soil carbon increased an additional 30 Pg C, for a total carbon storage increase of approximately 70 Pg C. In the lower N+D simulations, the responses of NPP and vegetation carbon storage were relatively insensitive to differences in the reduction of nitrogen concentration, but soil carbon storage showed a large change. The insensitivity of NPP in the N+D simulations occurred because potential enhancements in NPP associated with reduced vegetation nitrogen concentration were approximately offset by lower nitrogen availability associated with the decomposition dynamics of reduced litter nitrogen concentration. For each 7.5% reduction in vegetation nitrogen concentration, soil carbon increased approximately an additional 60 Pg C, while vegetation carbon storage increased by only approximately 5 Pg C. As the reduction in vegetation nitrogen concentration gets greater in the lower N+D simulations, more of the additional carbon storage tends to become concentrated in the north temperate-boreal region in comparison to the tropics. Other studies with TEM show that elevated CO2 more than offsets the effects of climate change to cause increased carbon storage. The results of this study indicate that carbon storage would be enhanced by the influence of changes in plant nitrogen concentration on carbon assimilation and decomposition rates. Thus changes in vegetation nitrogen concentration may have important implications for the ability of the terrestrial biosphere to mitigate increases in the atmospheric concentration of CO2 and climate changes associated with the increases