How prevalent is COVID-19 vaccine hesitancy in low-income and middle-income countries and what are the key drivers of hesitancy? Results from 53 countries.

OBJECTIVES: This study aims to estimate the levels of COVID-19 vaccine hesitancy in 53 low-income and middle-income countries, differences across population groups in hesitancy, and self-reported reasons for being hesitant to take the COVID-19 vaccine. METHODS: This paper presents new evidence on levels and trends of vaccine hesitancy in low-income and middle-income countries based on harmonised high-frequency phone surveys from more than 120 000 respondents in 53 low-income and middle-income countries collected between October 2020 and August 2021. These countries represent a combined 53% of the population of low-income and middle-income countries excluding India and China. RESULTS: On average across countries, one in five adults reported being hesitant to take the COVID-19 vaccine, with the most cited reasons for hesitancy being concerns about the safety of the vaccine, followed by concerns about its efficacy. Between late 2020 and the first half of 2021, there tended to be little change in hesitancy rates in 11 of the 14 countries with available data, while hesitancy increased in Iraq, Malawi and Uzbekistan. COVID-19 vaccine hesitancy was higher among female, younger adults and less educated respondents, after controlling for selected observable characteristics. CONCLUSIONS: Country estimates of vaccine hesitancy from the high-frequency phone surveys are correlated with but lower than those from earlier studies, which often relied on less representative survey samples. The results suggest that vaccine hesitancy in low-income and middle-income countries, while less prevalent than previously thought, will be an important and enduring obstacle to recovery from the pandemic.

Omics and Extreme Phenotyping Reveal Longitudinal Association Between Left Atrial Size and Pulmonary Vascular Resistance in Group 2 Pulmonary Hypertension.

BACKGROUND: Left heart disease is the most common cause of pulmonary hypertension (PH) and is frequently accompanied by increases in pulmonary vascular resistance. However, the distinction between phenotypes of PH due to left heart disease with a normal or elevated pulmonary vascular resistance-isolated postcapillary PH (IpcPH) and combined pre- and postcapillary PH (CpcPH), respectively-has been incompletely defined using unbiased methods. METHODS AND RESULTS: Patients with extremes of IpcPH versus CpcPH were identified from a single-center record of those who underwent right heart catheterization. Individuals with left ventricular ejection fraction <40% or with potential causes of PH beyond left heart disease were excluded. Medication usage in IpcPH and CpcPH was compared across Anatomical Therapeutic Chemical classes and identified vitamin K antagonists as the only medication with pharmacome-wide significance, being more commonly used in CpcPH and for an indication of atrial fibrillation in ≈90% of instances. Accordingly, atrial fibrillation prevalence was significantly higher in CpcPH in a phenome-wide analysis. Review of echocardiographic data most proximal to right heart catheterization revealed that left atrial diameter indexed to body surface area-known to be associated with atrial fibrillation-was increased in CpcPH regardless of the presence of atrial fibrillation. An independent cohort with serial right heart catheterizations and PH-left heart disease showed a significant positive correlation between change in left atrial diameter indexed to body surface area and change in pulmonary vascular resistance. CONCLUSIONS: Guided by pharmacomic and phenomic screens in a rigorously phenotyped cohort, we identify a longitudinal association between left atrial diameter indexed to body surface area and pulmonary vascular resistance with implications for the future development of diagnostic, prognostic, and therapeutic tools.

How did the COVID-19 crisis affect different types of workers in the developing world?

This paper examines how the COVID-19 pandemic affected the employment of different groups of workers across 40 mostly low and middle-income countries. Employment outcomes during the crisis are tracked through high-frequency phone surveys conducted by the World Bank and national statistics offices. Our results show that larger shares of female, young, less educated, and urban workers stopped working at the beginning of the pandemic. Gender gaps in work stoppage stemmed mainly from gender differences within sectors rather than differential employment patterns of men and women across sectors. Differences in work stoppage between urban and rural workers were markedly smaller than those across gender, age, and education groups. Preliminary results from 10 countries suggest that following the initial shock at the start of the pandemic, employment rates partially recovered between April and August 2020, with greater gains for those groups that had borne the brunt of the early jobs losses. Although the high-frequency phone surveys over-represent household heads and therefore overestimate employment rates, a validation exercise for five countries suggests that they provide a reasonably accurate measure of disparities in employment levels by gender, education, and urban/rural location following the onset of the crisis, although they perform less well in capturing disparities between age groups. These results shed new light on the distributional labor market consequences of the COVID-19 crisis in developing countries, and suggest that real-time phone surveys, despite their lack of representativeness, are a valuable source of information to measure differential employment impacts across groups during an unfolding crisis.

Back Table Preparation of the Right Lobe Live Donor Liver Allograft: A Crucial Part of the Adult Live Donor Liver Transplant Procedure.

INTRODUCTION: We aimed to describe our procedure for vascular reconstruction and back table bench preparation for the right lobe live donor allograft. Live donor liver transplantation (LDLT) remains an important option for the expansion of the donor pool. The procedure has been widely used, and its success is dependent on a technically perfect operation with appropriate inflow and outflow of the allograft. Adequate preparation of the right lobe (RL) allograft prior to implantation remains a vital part of the procedure. METHODS: Our technique of back table vascular reconstruction of the RL allograft has been performed using a hepatic vein patch venoplasty, inferior hepatic vein inclusion, portal vein reconstruction, and segment V and VIII reconstruction for all of our LDLTs. RESULTS: Between March 2009 and January 2020, 321 consecutive adult LDLTs were performed and underwent back table reconstruction with the techniques described. During that time period, no patients had hepatic insufficiency. There was a single thrombosis of a superior mesenteric vein (SMV) to PV jump conduit. CONCLUSIONS: Our technique of back table reconstruction of the LDLT right lobe graft remains a crucial part of the operative procedure. Our experience with RL grafts without middle hepatic vein (MHV) and our systematic approach for inflow and outflow reconstruction has yielded excellent results with no technical outflow issues and minimal inflow complications.

Guideline-Directed Medical Therapy and the Risk of Death in Primary Prevention Defibrillator Recipients.

BACKGROUND: Contemporary guideline-directed medical therapy (GDMT) confers a significant mortality benefit for patients with heart failure with reduced ejection fraction (HFrEF), as compared to GDMT prevalent at the time of landmark primary prevention implantable cardioverter-defibrillator (ICD) trials. The impact of modern era GDMT on survival in this population is unknown. OBJECTIVES: This study sought to investigate the impact of number of GDMT medications prescribed for HFrEF on all-cause mortality in recipients of primary prevention ICD. METHODS: A cohort of 4,972 recipients with primary prevention ICD (n = 3,210) or cardiac resynchronization therapy-defibrillator (CRT-D) (n = 1,762) was studied. The association of number of GDMT medications prescribed at the time of device implantation and all-cause mortality at 2 years post implantation was examined. RESULTS: In our primary prevention cohort, 5%, 20%, 52%, and 23% of patients were prescribed 0, 1, 2, or 3-4 GDMT medications, respectively. After risk adjustment for age, sex, ejection fraction, body mass index, the Elixhauser comorbidity score, the type of cardiomyopathy, and the year of device implantation, each additional GDMT conferred a reduction in the risk of death of 36% in recipients of ICD (HR: 0.64; P < 0.001) and 30% in recipients of CRT-D (HR: 0.70; P < 0.001). CONCLUSIONS: A higher number of prescribed GDMT medications is associated with an incremental 1-year survival in recipients of primary prevention ICD with or without CRT. Initiation of maximum number of tolerated GDMT medications should therefore be the goal for all patients with HFrEF. In the setting of robust GDMT, the risk versus benefit of a primary prevention ICD warrants re-examination in future studies.

Foregone healthcare during the COVID-19 pandemic: early survey estimates from 39 low- and middle-income countries.

In addition to the direct health effects of the Coronavirus disease (COVID-19) pandemic, the pandemic has increased the risks of foregone non-COVID-19 healthcare. Likely, these risks are greatest in low- and middle-income countries (LMICs), where health systems are less resilient and economies more fragile. However, there are no published studies on the prevalence of foregone healthcare in LMICs during the pandemic. We used pooled data from phone surveys conducted between April and August 2020, covering 73 638 households in 39 LMICs. We estimated the prevalence of foregone care and the relative importance of various reported reasons for foregoing care, disaggregated by country income group and region. In the sample, 18.8% (95% CI 17.8-19.8%) of households reported not being able to access healthcare when needed. Financial barriers were the most-commonly self-reported reason for foregoing care, cited by 31.4% (28.6-34.3%) of households. More households in wealthier countries reported foregoing care for reasons related to COVID-19 [27.2% (22.5-31.8%) in upper-middle-income countries compared to 8.0% (4.7-11.3%) in low-income countries]; more households in poorer countries reported foregoing care due to financial reasons [65.6% (59.9-71.2%)] compared to 17.4% (13.1-21.6%) in upper-middle-income countries. A substantial proportion of households in LMICs had to forgo healthcare in the early months of the pandemic. While in richer countries this was largely due to fear of contracting COVID-19 or lockdowns, in poorer countries foregone care was due to financial constraints.

Estimating small-area population density in Sri Lanka using surveys and Geo-spatial data.

Country-level census data are typically collected once every 10 years. However, conflicts, migration, urbanization, and natural disasters can rapidly shift local population patterns. This study demonstrates the feasibility of a "bottom-up"-method to estimate local population density in the between-census years by combining household surveys with contemporaneous geo-spatial data, including village-area and satellite imagery-based indicators. We apply this technique to the case of Sri Lanka using Poisson regression models based on variables selected using the Least Absolute Shrinkage and Selection Operator (LASSO). The model is estimated in villages sampled in the 2012/13 Household Income and Expenditure Survey, and is employed to obtain out-of-sample density estimates in the non-surveyed villages. These estimates approximate the census density accurately and are more precise than other bottom-up studies using similar geo-spatial data. While most open-source population products redistribute census population "top-down" from higher to lower spatial units using areal interpolation and dasymetric mapping techniques, these products become less accurate as the census itself ages. Our method circumvents the problem of the aging census by relying instead on more up-to-date household surveys. The collective evidence suggests that our method is cost effective in tracking local population density with greater frequency in the between-census years.

Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes.

Importance: Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention. Objective: To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin. Design, Setting, and Participants: This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018. Exposures: Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure. Main Outcomes and Measures: All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort. Results: Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding. Conclusions and Relevance: This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.

First Nation paths to well-being: lessons from the Poverty Action Research Project.

This paper describes a poverty reduction approach to addressing an important determinant of health and well-being among Canada's First Nations. The Poverty Action Research Project (PARP) has its origins in the Make Poverty History Committee established by the Assembly of First Nations (AFN) in 2008. Academic members of the Committee in cooperation with the AFN subsequently applied for an action research grant to the Canadian Institutes of Health Research (CIHR). The project selected five volunteer First Nations from different parts of Canada, hiring a coordinator in each, undertaking background research, developing a profile and working with First Nation representatives in the development of a strategy to address upstream determinants of health and well-being. Subsequently, project team members within each region assisted where needed with plan implementation, supporting some initiatives with small grants. This paper provides insights from the project in several key areas, including First Nation rejection of the concept of poverty as usually defined, the importance of taking action to strengthen collectivities as well as individuals, the feasibility of assisting First Nations who are at different points in their development journey, the strengths of the leadership within the First Nations, and finding the appropriate balance between the elected and business leadership. These insights emerged from dialogue and reflection among project team members and community participants over the life of the project. We also describe what we have learned about how to engage effectively and with mutual respect with First Nations in this kind of project. The paper concludes with a review of our experiences with the policies and practices of the national research granting councils and the universities, which have not fully adjusted to the requirements of action research involving First Nations.

Synthesis and evaluation of esterified Hsp70 agonists in cellular models of protein aggregation and folding.

Over-expression of the Hsp70 molecular chaperone prevents protein aggregation and ameliorates neurodegenerative disease phenotypes in model systems. We identified an Hsp70 activator, MAL1-271, that reduces α-synuclein aggregation in a Parkinson's Disease model. We now report that MAL1-271 directly increases the ATPase activity of a eukaryotic Hsp70. Next, twelve MAL1-271 derivatives were synthesized and examined in a refined α-synuclein aggregation model as well as in an assay that monitors maturation of a disease-causing Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutant, which is also linked to Hsp70 function. Compared to the control, MAL1-271 significantly increased the number of cells lacking α-synuclein inclusions and increased the steady-state levels of the CFTR mutant. We also found that a nitrile-containing MAL1-271 analog exhibited similar effects in both assays. None of the derivatives exhibited cellular toxicity at concentrations up to 100 µm, nor were cellular stress response pathways induced. These data serve as a gateway for the continued development of a new class of Hsp70 agonists with efficacy in these and potentially other disease models.

Does health aid matter?

This paper examines the relationship between health aid and infant mortality, using data from 118 countries between 1973 and 2004. Health aid has a beneficial and statistically significant effect on infant mortality: doubling per capita health aid is associated with a 2 percent reduction in the infant mortality rate. For the average country, this implies that increasing per capita health aid by US$1.60 per year is associated with 1.5 fewer infant deaths per thousand births. The estimated effect is small, relative to the 2015 target envisioned by the Millennium Development Goals. It implies that achieving the MDG target through additional health aid alone would require a roughly 15-fold increase in current levels of aid.

Service score segmentation of diverse populations to improve patient and physician satisfaction- a multicase quality improvement study.

The changing demographics in the country require new strategies for providing culturally competent care. The Northern California Region Member Patient Survey provides detailed information for the clinician when the data is segmented into subsets by age, gender, and race/ethnicity. Any gaps identified allow for the clinician to focus on key areas for improvement in an efficient manner respecting the time constraints of a busy practice.

The impact of state physical education requirements on youth physical activity and overweight.

To combat childhood overweight in the US, which has risen dramatically in the past three decades, many medical and public health organizations have called for students to spend more time in physical education (PE) classes. This paper is the first to examine the impact of state PE requirements on student PE exercise time. It also exploits variation in state laws as quasi-natural experiments in order to estimate the causal impact of PE on overall student physical activity and weight. We study nationwide data from the Youth Risk Behavior Surveillance System for 1999, 2001, and 2003 merged with data on state minimum PE requirements from the 2001 Shape of the Nation Report. We find that high school students with a binding PE requirement report an average of 31 additional minutes per week spent physically active in PE class. Our results also indicate that additional PE time raises the number of days per week that girls report having exercised vigorously or having engaged in strength-building activity. We find no evidence that PE lowers BMI or the probability that a student is overweight. We conclude that raising PE credit requirements may make girls more physically active overall but there is not yet the scientific base to declare raising PE requirements an anti-obesity initiative for either boys or girls.