title: Assessing the impact of community-based interventions on hypertension and diabetes management in three Minnesota communities: findings from the prospective evaluation of US HealthRise programs

abstract:
BackgroundCommunity-based health interventions are increasingly viewed as models of care that can bridge healthcare gaps experienced by underserved communities in the United States (US). With this study, we sought to assess the impact of such interventions, as implemented through the US HealthRise program, on hypertension and diabetes among underserved communities in Hennepin, Ramsey, and Rice Counties, Minnesota.

Methods and findingsHealthRise patient data from June 2016 to October 2018 were assessed relative to comparison patients in a difference-in-difference analysis, quantifying program impact on reducing systolic blood pressure (SBP) and hemoglobin A1c, as well as meeting clinical targets (< 140 mmHg for hypertension, < 8% Al1c for diabetes), beyond routine care. For hypertension, HealthRise participation was associated with SBP reductions in Rice (6.9 mmHg [95% confidence interval: 0.9-12.9]) and higher clinical target achievement in Hennepin (27.3 percentage-points [9.8-44.9]) and Rice (17.1 percentage-points [0.9 to 33.3]). For diabetes, HealthRise was associated with A1c decreases in Ramsey (1.3 [0.4-2.2]). Qualitative data showed the value of home visits alongside clinic-based services; however, challenges remained, including community health worker retention and program sustainability.

ConclusionsHealthRise participation had positive effects on improving hypertension and diabetes outcomes at some sites. While community-based health programs can help bridge healthcare gaps, they alone cannot fully address structural inequalities experienced by many underserved communities.


title: Willingness and influential factors of parents to vaccinate their children against the COVID-19: a systematic review and meta-analysis

abstract:
BackgroundCoronavirus disease 2019 (COVID-19) vaccine uptake among children will be critical in limiting the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease. Parents are key decision-makers for whether their children will receive a COVID-19 vaccine.

ObjectiveTo estimate parents willingness to vaccinate their children against the COVID-19, and to investigate the predictors for their decision.

MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for this systematic review and meta-analysis. We searched Scopus, Web of Science, Medline, PubMed, ProQuest, and CINAHL from inception to August 11, 2021. The review protocol was registered with PROSPERO (CRD42021273125). We applied a random effect model to estimate pooled effects since the heterogeneity was very high. We used subgroup analysis and meta-regression analysis to explore sources of heterogeneity.

ResultsWe found 17 studies including 45,783 parents. The overall proportion of parents that intend to vaccinate their children against the COVID-19 was 56.8% (95% confidence interval: 51.8-61.8%). Parents willingness ranged from 29% to 72.7%. Studies quality, sample size, data collection time, and the continent that studies were conducted did not affect the results. The main predictors of parents intention to vaccinate their children against COVID-19 were male gender, older age of parents and children, higher socio-economic status, white race, positive attitudes toward vaccination, higher levels of knowledge, and higher levels of perceived threat from the COVID-19, worry, fear, and anxiety.

ConclusionsParents willingness to vaccinate their children against the COVID-19 is moderate and several factors affect this decision. Understanding parental COVID-19 vaccine hesitancy does help policy makers to change the stereotypes and establish broad community COVID-19 vaccination. Identification of the factors that affect parents willingness to vaccinate their children against COVID-19 will provide opportunities to enhance parents trust in the COVID-19 vaccines and optimize childrens uptake of a COVID-19 vaccine.

category: public and global health


title: Impact of Covid-19 Pandemic on Racial/Ethnic Differences in Mortality by Cause of Death

abstract:
ObjectivesTo quantify changes in all-cause and cause-specific mortality by race and ethnicity between 2019 and 2020.

MethodsUsing 2019 and 2020 provisional death counts from the National Center for Health Statistics and population estimates from the US Census Bureau, we estimate age-standardized death rates by race/ethnicity and attribute changes in mortality to various causes of death. We also examine how patterns of change across racial/ethnic groups vary by age and sex.

ResultsCovid-19 death rates in 2020 were highest in the Hispanic community whereas Black individuals had the largest increase in all-cause mortality between 2019 and 2020. Increases in mortality from heart disease, diabetes, and external causes of death accounted for the adverse trend in all-cause mortality within the Black population. Percentage increases in all-cause mortality were similar for men and women and for ages 25-64 and 65+ for Black and White populations, but increases were greatest for working-aged men among the Hispanic population.

ConclusionsExamining increases in non-Covid-19 causes of death is essential for fully capturing both the direct and indirect impact of the Covid-19 pandemic on racial/ethnic mortality disparities.


title: The Unequal Burden of the Covid-19 Pandemic: Racial/Ethnic Disparities in US Cause-Specific Mortality


title: Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence, 1999-2018

abstract:
BackgroundDisparities in multimorbidity prevalence indicate health inequalities. This study sought to determine if gaps in multimorbidity prevalence by race and ethnicity are decreasing over time.

Methods and findingsSerial cross-sectional analysis of the National Health Interview Survey from years 1999 to 2018. The study included individuals [≥]18 years old, categorized by self-reported race, ethnicity, age, and income. The main outcomes were temporal trends in multimorbidity prevalence based on the self-reported presence of [≥]2 of 9 chronic conditions. The study sample included 596,355 individuals (4.7% Asian, 11.8% Black, 13.8% Latino/Hispanic, and 69.7% White). In 1999, the estimated prevalence of multimorbidity was 5.9% among Asian, 17.4% among Black, 10.7% among Latino/Hispanic, and 13.5% among White individuals. Prevalence increased for all racial/ethnic groups during the study period (P<0.005 for each), with no significant change in the differences between them. In 2018, when compared with White people, multimorbidity was more prevalent among Black individuals (+2.5 percent points [95% CI: +0.5, +4.6]) and less prevalent among Asian and Latino individuals (-6.6 points [-8.8, -4.4] and -2.1 points [-4.0, -0.2], respectively). The estimated prevalence of reporting at least 1, 2, 3, or 4 conditions all increased with age across all groups, with Black individuals having the greatest prevalence in each age category. Among those aged [≥]30 years, Black people had multimorbidity rates equivalent to those of Latino/Hispanic and White people aged 5 years older, and Asian people aged 10 years older. Notably, the prevalence of multimorbidity diverged between Black people and White people among those aged 30 years, reached its maximum difference of 10.1 percentage points (95% CI: 8.2, 12.1) among those aged 60, and converged to reach similar rates among those aged [≥]80.

ConclusionsFrom 1999 to 2018, a period of increasing multimorbidity prevalence for all the groups studied, there has not been any significant progress in eliminating disparities between Black and White people. The disparity began among young adults. Public health interventions that prevent the onset of chronic conditions in early life may be needed to eliminate these disparities.


title: Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States: A Serial Cross-Sectional National Health Interview Survey Analysis from 1999 to 2018


title: Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999 to 2018


title: Democratic governance and excess mortality during the COVID-19 pandemic

abstract:
BackgroundExcess mortality has been used to assess the health impact of COVID-19 across countries. Democracies aim to build trust in government and enable checks and balances on decision-making, which may be useful in a pandemic. On the other hand, democratic governments have been criticised as slow to enforce restrictive policies and being overly influenced by public opinion. This study sought to understand whether strength of democratic governance is associated with the variation in excess mortality observed across countries during the pandemic.

MethodsThrough linking open-access datasets we constructed univariable and multivariable linear regression models investigating the association between country EIU Democracy Index (representing strength of democratic governance on a scale of 0 to 10) and excess mortality rates, from February 2020 to May 2021. We stratified our analysis into high-income and low and middle-income country groups and adjusted for several important confounders.

ResultsAcross 78 countries, the mean EIU democracy index was 6.74 (range 1.94 to 9.81) and the mean excess mortality rate was 128 per 100,000 (range -55 to 503 per 100,000). A one-point increase in EIU Democracy Index was associated with a decrease in excess mortality of 26.3 per 100,000 (p=0.002), after accounting for COVID-19 cases, age [≥] 65, gender, prevalence of cardiovascular disease, universal health coverage and the strength of early government restrictions. This association was particularly strong in high-income countries ({beta} -47.5, p<0.001) but non-significant in low and middle-income countries ({beta} -10.8, p=0.40).

ConclusionsSocio-political factors related to the way societies are governed have played an important role in mitigating the overall health impact of COVID-19. Given the omission of such considerations from outbreak risk assessment tools, and their particular significance in high-income countries rated most highly by such tools, this study strengthens the case to broaden the scope of traditional pandemic risk assessment.

Key MessagesO_ST_ABSWhat is already known?C_ST_ABSO_LIPrevious studies have found that as countries become more democratic they experience a decline in rates of infant and child mortality, infections such as tuberculosis, and non-communicable diseases.
C_LIO_LIIn Europe, more democratic countries were initially more reluctant to adopt restrictive COVID-19 measures that could conflict with democratic principles, including lockdowns.
C_LI

What are the new findings?O_LIWe found that a one-point increase in EIU Democracy Index was associated with a decrease in excess mortality of 26.3 per 100,000 (p=0.002), after accounting for several confounders including demographics, numbers of cases and the strength of early government responses.
C_LIO_LIThis association was particularly significant in high-income countries ({beta} - 47.5, p<0.001), suggesting that way societies are governed has played an important role in mitigating the impact of COVID-19.
C_LI

What do the new findings imply?O_LIGiven the omission of social, political and cultural considerations from outbreak risk assessment tools, and criticisms of such tools that have failed to accurately reflect the observed impact of the pandemic across high-income countries, this study builds on the case to broaden of the scope of traditional pandemic risk assessment.
C_LIO_LIFuture research into the mechanisms underlying our findings will help to understand and address the complex and deep-rooted vulnerabilities countries face in a protracted and large-scale public health emergency.
C_LI


title: A computational optimization approach for the automatic generation of Gamma Knife radiosurgery treatment plans

abstract: Gamma Knife (GK) radiosurgery is a non-invasive treatment modality which allows single fraction delivery of focused radiation to one or more brain targets. Treatment planning mostly involves manual placement and shaping of shots to conform the prescribed dose to a surgical target. This process can be time consuming and labour intensive. An automated method is needed to determine the optimum combination of treatment parameters to decrease planning time and chance for operator-related error. Recent advancements in hardware platforms which employ parallel computational methods with stochastic optimization schemes are well suited to solving such combinatorial optimization problems efficiently. We present a method of generating optimized GK radiosurgery treatment plans using these techniques, which we name ROCKET (Radiosurgical Optimization Configuration Kit for Enhanced Treatments). Our approach consists of two phases in which shot isocenter positions are generated based on target geometry, followed by optimization of sector collimator parameters. Using this method, complex treatment plans can be generated, on average, in less than one minute, a substantial decrease relative to manual planning. Our results also demonstrate improved selectivity and treatment safety through decreased exposure to nearby organs-at-risk (OARs), compared to manual reference plans with matched coverage. Stochastic optimization is therefore shown to be a robust and efficient clinical tool for the automatic generation of GK radiosurgery treatment plans.

category: radiology and imaging


title: Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous?-A retrospective cohort study

abstract:
BackgroundHypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterized by the presence of hypoxia without dyspnea.. Silent hypoxia has been shown to affect the outcomes in previous studies.

Research QuestionAre the outcomes in patients presenting with silent hypoxia different from those presenting with dyspneic hypoxia?

Study design and MethodsThis was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory, and treatment parameters in patients with silent hypoxia and dyspneic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality.

ResultsAmong 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2<94% at the time of presentation. 174 (21.45%) did not have dyspnea since the onset of COVID-19 symptoms. 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspneic hypoxic patients (P=0.202). The odds ratio of death was 1.1 (95% CI 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment, and in-hospital complications, which did not reach statistical significance (P=0.851).

InterpretationSilent hypoxia may be the only presenting feature of COVID-19. Since the case fatality rate is comparable between silent and dyspneic hypoxia, it should be recognized early and treated as aggressively. Since home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry at the home setting to identify these patients.

category: respiratory medicine


title: Comprehensive genetic and functional analysis of FcγRs in rituximab therapy for autoimmunity reveals a key role for FcγRIIIa on NK cells

abstract:
B cell depletion using rituximab is widely used to treat autoimmune diseases, but patient response varies. The efficacy of rituximab is limited by the efficiency of depletion. Strategies to improve response include altering rituximab dosing, switching anti-CD20-mAb, alternative B cell targets, or non-B cell targeted therapies. Implementing an appropriate strategy requires understanding of the mechanism(s) of resistance to depletion and, if this varies between individuals, a means to test for it. Rituximab kills B cells via a variety of Fc{gamma} receptor (Fc{gamma}R)-dependent mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), as well as non-Fc{gamma}R mechanisms. We conducted a longitudinal cohort study in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) using two national registries. Qualitative and quantitative FCGR functional variants were measured using multiplexed ligation-dependent probe amplification, supplemented by novel FCGR2C assays.

We provide consistent evidence that FCGR3A, specifically increased number of copies of the FCGR3A-158V allele, was the major Fc{gamma}R gene associated with rituximab response, including clinical response in RA and SLE and depth of B cell depletion in the combined cohort. In SLE, we provide preliminary data suggesting increased FCGR2C ORF copies were also associated with improved clinical response. Furthermore, we demonstrated the impact of disease status and concomitant therapies on both natural killer cell Fc{gamma}RIIIa expression and rituximab-induced ADCC; demonstrating increased Fc{gamma}RIIIa expression and FCGR3A genotype were independently associated with clinical response and B cell depletion. Our findings highlight the importance of enhancing Fc{gamma}R-effector functions, may help stratify patients, and support ongoing development of next-generation CD20 depleting therapeutics.

One Sentence SummaryThe high affinity Fc{gamma}RIIIa allotype on NK cells explains depth of B cell depletion and clinical response in rituximab therapy for autoimmune disease

category: rheumatology


title: What medical students think about measurement of their wellbeing and the implications for pastoral support: cross sectional survey and qualitative interviews

abstract:
ObjectivesTo find out how, why and when medical students think wellbeing should be measured.

DesignA mixed methods study comprising a cross-sectional online survey (November 2020-March 2021) and semi-structured on-line interviews. Views on the frequency of availability for measurement, the format, type and purpose of measurement, and with whom wellbeing should be discussed were measured. When an outcome was scored 7-9 on a 9-point Likert scale of agreement by [≥]75% of participants it was considered critical, in line with COMET and GRADE processes for rating recommendations. Inductive thematic analysis was undertaken on the interview transcripts by two independent researchers.

SettingAll Medicine programmes at University of Southampton.

ParticipantsMedical students from all years took part in the survey (n=118) and interviews (n=16).

ResultsParticipant demographics were similar to national medical student demographics. Most participants (94%) felt able to give 5 minutes to measure their wellbeing at least once a month. No single format of measurement was rated critical. Research, governance and individual feedback all reached the 75% threshold for the purpose being considered critically important. Only subjective assessments undertaken by the individual in real-time were rated as critically important (78.1%) measurement tools. Students selected that they would discuss their wellbeing with other medical students (n=87) nearly as often as they selected a member of the Faculty (n=104). Top determinants of wellbeing picked by medical students were energy, ability to do activities of daily living, and negative feelings. Five interview themes further explained these findings.

ConclusionsFive recommendations about self-care teaching, quality-assured pastoral and peer support, proactive wellbeing check-ins and demographic data are discussed in light of these findings. Methods to achieve them are suggested, which are medical student-centred, and which make use of existing resources.

Strengths and limitations of this studyO_LIThis study provides new information on how, why and when medical students think their wellbeing should be measured.
C_LIO_LIA mixed methods approach allowed the reasons behind the survey answers to be captured in ensuing interviews.
C_LIO_LIUsing the [≥]75% a prior cut off for critical importance from COMET and GRADE allowed evidence-based recommendations for wellbeing measurement for medical students.
C_LIO_LIIt was not possible to recruit the number of students needed to make national inferences, although participant demographics were similar to national medical student demographics.
C_LIO_LIA national cross-sectional survey would provide further evidence for medical schools in devising wellbeing provisions.
C_LI

category: medical education


title: Effectiveness of a novel non-intrusive continuous-use air decontamination technology to reduce microbial contamination in clinical settings: A multi-centric study

abstract:
BackgroundDespite rigorous disinfection, fumigation and air treatment, infectious microbial load has been found to circulate and survive for significant durations in health care settings. This raises significant concerns for hospital acquired infections. We have developed a novel, hybrid, trap- and-kill airborne-microbicidal technology called "ZeBox" which is efficient in clearing 99.999% of airborne microbial load under controlled lab conditions. In this study we evaluate the clinical performance of the ZeBox in reducing airborne and surface microbial load in two independent hospital settings.

MethodsThe studies were conducted in single bed and multi bed ICU of two hospitals. Airborne and surface microbial loads were collected at pre-determined sampling sites pre- and post-deployment of the ZeBox enabled device. The Normality of data distribution was determined using the Shapiro-Wilk test. Statistical significance was determined using Students T test and Mann-Whitneys U test. Pathogenic and opportunistic organisms were characterized using 16S rDNA sequencing. Furthermore, the antibiotic sensitivity of the isolated organisms was tested against current treatments of choice across major antibiotic classes.

ResultsPost-deployment, we found statistically significant reductions in both airborne and surface microbial load within the operating range of the ZeBox enabled technology. Across the both hospital ICUs, there was 90% reduction of airborne microbial load on average, and 75% reduction of surface microbial load on average, providing a low bioburden zone of roughly 10-15 feet diameter around the unit. These reduced microbial levels were maintained during the entire duration of device operation over several weeks. Many of the clinical isolates recovered from one of the hospitals were drug resistant, which highlighted the potential ability of ZeBox to eliminate drug-resistant microbes and thereby reduce the frequency of hospital acquired infections.

ConclusionsZeBox enabled technology can significantly reduce a broad spectrum of microbial burden in air and on surfaces in clinical settings. It can thereby serve an unmet need in reducing the incidence of hospital acquired infections.

category: occupational and environmental health


title: Predicted long-term impact of COVID-19 pandemic-related care delays on cancer incidence and mortality in Canada

abstract:
ObjectivesThe COVID-19 pandemic has affected cancer care worldwide. This study aimed to estimate the long-term impacts of the pandemic on cancer incidence and mortality in Canada using a mathematical model.

MethodsWe developed a stochastic microsimulation model to estimate the cancer care disruptions and its long-term impact on cancer incidence and mortality in Canada. The model reproduces cancer incidence, survival, and epidemiology in Canada, by using cancer incidence, stage at diagnosis and survival data from the Canadian Cancer Registries. We modeled reported declines in cancer diagnoses and treatments recorded in provincial administrative datasets from March 2020-June 2021. We assumed that diagnostic and treatment delays lead to an increased rate of death. Based on the literature, we assumed each 4-week delay in diagnosis and treatment would lead to a 6% to 50% higher rate of cancer death. Results are the median predictions of 10 stochastic simulations.

FindingsThe model predicts that cancer care disruptions during the COVID-19 pandemic could lead to 21,247 (2{middle dot}0%) more cancer deaths in Canada in 2020-2030, assuming treatment capacity is recovered to 2019 pre-pandemic levels in 2021. This represents 355,172 life years lost expected due to pandemic-related diagnostic and treatment delays. The highest absolute expected excess cancer mortality was predicted in breast, lung, and colorectal cancers, and in the provinces of Ontario, Quebec, and British Columbia. Diagnostic and treatment capacity in 2021 onwards highly influenced the number of predicted cancer deaths over the next decade.

InterpretationCancer care disruptions during the Covid-19 pandemic could lead to significant life loss; however, most of these could be mitigated by increasing diagnostic and treatment capacity in the post-pandemic era to address the service backlog.

FundingCanadian Institutes of Health Research

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe performed a review of modeling studies predicting the impact of pandemic-induced disruptions to cancer care on cancer survival outcomes. We searched MEDLINE on 2 July 2021 for records published from 1 January 2020 with no language restrictions. Our search consisted of index keywords [Cancer AND COVID-19 AND [(delay AND diagnosis) OR (delay AND screening) OR (delay AND treatment)] AND outcomes AND modelling study]. We identified 14 studies that model the long-term effect of disruptions to cancer screening programs, diagnostic intervals, and to treatment intervals for common cancers. Most studies (9/14) assessed the impact of cancer screening disruptions but did not assume any treatment disruptions. Disruptions to cancer screening services in high income health systems were estimated to lead to small increases in cancer incidence and mortality, even with immediate resumption of screening to services after disruption periods. Fewer studies examined the impact of diagnostic referral and treatment disruptions; these are similarly predicted to lead to increases in cancer incidence and mortality, with varying impacts depending on cancer site. Due to difficulties in obtaining real-time healthcare data, previous studies have relied on assumptions regarding the duration of health care disruptions (1-, 3-, 6-, 12-, to 24-months) rather than on empirical data. All studies restricted their analysis to the impact on a single or a few cancer sites.

Added value of this studyOur stochastic microsimulation model is the first to assess the population-level impact of diagnostic and treatment disruptions on overall cancer mortality across all sites. Using Canadian cancer statistics and expert validation of treatment modalities, we constructed a model that reproduced pre-pandemic cancer mortality data. An important added value of this analysis compared to previous studies was that we were able to integrate empirical data on cancer-related procedures during the pandemic era to model disruptions to cancer care.

Implications of all the available evidenceWe estimate there could be a 2{middle dot}0% increase over expected cancer mortality between 2020-2030 in Canada due to pandemic-related disruptions to diagnostic and treatment intervals. Our results identified that a 10-20% increase in cancer care service capacity over pre-pandemic levels could prevent a considerable amount of the predicted excess cancer-related deaths by reducing diagnostic and treatment backlogs. By stratifying our reported outcomes by sex, age, province, and cancer site, we provide a long-term perspective that can inform post-pandemic public health policy or aid in prioritization of patients in the event of a resurgence of COVID-19. While our model is specific to Canada, it could be applied to countries that have experienced comparable COVID-19-related healthcare disruptions.

category: oncology


title: Estimating the global demand curve for a leishmaniasis vaccine: a generalisable approach based on global burden of disease estimates

abstract:
BackgroundA pressing need exists to develop vaccines for neglected diseases, including leishmaniasis. However, the development of new vaccines is dependent on their value to two key players - vaccine developers and manufacturers who need to have confidence in the global demand in order to commit to research and production; and governments (or other international funders) who need to signal demand based on the potential public health benefits of the vaccine in their local context, as well as its affordability. A detailed global epidemiological analysis is rarely available before a vaccine enters a market due to lack of resources as well as insufficient global data necessary for such an analysis. Our study seeks to bridge this information gap by providing a generalisable approach to estimating the commercial and public health value of a vaccine in development relying primarily on publicly available Global Burden of Disease (GBD) data. This simplified approach is easily replicable and can be used to guide discussions and investments into vaccines and other health technologies where evidence constraints exist. The approach is demonstrated through the estimation of the demand curve for a future leishmaniasis vaccine.

Methodology/Principal findingsWe project the ability to pay over the period 2030-2040 for a vaccine preventing cutaneous and visceral leishmaniasis (CL / VL), using an illustrative set of countries which account for most of the global disease burden. First, based on previous work on vaccine demand projections in these countries and CL / VL GBD-reported incidence rates, we project the potential long-term impact of the vaccine on disability-adjusted life years (DALYs) averted as a result of reduced incidence. Then, we apply an economic framework to our estimates to determine vaccine affordability based on the abilities to pay of governments and global funders, leading to estimates of the demand and market size. Based on our estimates, the maximum ability-to-pay of a leishmaniasis vaccine (per course, including delivery costs), given the current estimates of incidence and population at risk, is higher than $5 for nearly half of the 24 countries considered, with a median value-based maximum price of $4.4-$5.3, and total demand of over 560 million courses.

Conclusion/SignificanceOur results demonstrate that both the quantity of vaccines estimated to be required by the countries considered as well as their ability-to-pay could make a vaccine for leishmaniasis commercially attractive to potential manufacturers. The methodology used can be equally applied to other technology developments targeting health in developing countries.

Author summaryAs of 2019, between 498,000 and 862,000 new cases of all forms of leishmaniasis were estimated to occur each year resulting in up to 18,700 deaths and up to 1.6 million DALYs lost. Given low treatment coverage, poor compliance and the emergence of drug resistance, challenges in sustaining vector control strategies and the ability of parasites to persist in animal reservoirs independent of human infection, an effective vaccine could significantly reduce the health and economic burden of these diseases. However, commitment to the development of a new vaccine requires a market signal from governments and global funders who in turn require better estimates of the potential public health value of the vaccine. This study uses the development of a leishmaniasis vaccine as a case study to illustrate a generalizable approach to estimating the commercial and public health value of a technology relying primarily on publicly available GBD data. More specifically, by projecting the potential public health impact of the rollout of a leishmaniasis vaccine and translating this into monetary values based on the concept of health opportunity cost, we estimate the demand curve for such a vaccine for an 11-year period between 2030 and 2040. At an estimated global demand of over 560 million courses and a median value-based maximum price of $4.4-$5.3, our results demonstrate that both the quantity of vaccines estimated to be required by the countries considered as well as their ability-to-pay make the vaccine commercially attractive to potential manufacturers.

category: health economics


title: When do we need massive computations to perform detailed COVID-19 simulations?

abstract: The COVID-19 pandemic has infected over 200 million people worldwide and killed more than 4 million as of August 2021. Many intervention strategies have been utilized by governments around the world, including masks, social distancing, and vaccinations. However, officials making decisions regarding interventions may have a limited time to act. Computer simulations can aid them by predicting future disease outcomes, but they also have limitations due to requirements on processing power or time. This paper examines whether a machine learning model can be trained on a small subset of simulation runs to inexpensively predict future disease trajectories very close to the original simulation results. Using four previously published agent-based models for COVID-19, this paper analyzes the predictions of decision tree regression machine learning models and compares them to the results of the original simulations. The results indicate that accurate machine learning meta-models can be generated from simulation models with no strong interventions (e.g., vaccines, lockdowns) using small amounts of simulation data. However, meta-models for simulation models that include strong interventions required much more training data to achieve a similar accuracy. This indicates that machine learning meta-models could be used in some scenarios to assist in faster decision making.

category: health informatics


title: Community-Based Culturally Tailored Education Programs for Black Adults with Cardiovascular Disease, Diabetes, Hypertension, and Stroke: A Systematic Review Protocol

abstract:
BackgroundChronic conditions and stroke disproportionately affect Black adults in communities all around the world due patterns of systemic racism, disparities in care, and lack of resources. To address unequal care received by Black communities, a shift to community-based programs that deliver culturally-tailored programs to meet the needs of the communities they serve, including Black adults who tend to have reduced access to postacute services, may give an alternative to a healthcare model which reinforces health inequities. However, community-based culturally-tailored programs (CBCT) are relatively understudied but show promise to improve the delivery of services to marginalized communities. The objectives of this review are to: (i) determine key program characteristics and outcomes of CBCT programs that are designed to improve health outcomes in Black adults with cardiovascular disease, hypertension, diabetes, or stroke and (ii) identify which of the five categories of culturally appropriate programs from Kreuter and colleagues have been used to implement CBCT programs.

MethodsThis is a protocol for a systematic review that will search MEDLINE, EMBASE, and CINAHL databases to identify community-based culturally-tailored programs for Black adults with cardiovascular disease, hypertension, diabetes, or stroke.

DiscussionHealth inequities have disproportionately impacted Black communities and will continue to persist if adjustments are not prioritized within healthcare to provide services, care, and programs meant to address the specific barriers to better health experienced. Many interventions meant to improve the health outcomes of marginalized groups are created with little input from target communities, leading to interventions that may not address the specific barriers contributing to poor health outcomes and are designed and implemented from an outsiders perspective. The inclusion of community members allows for a deeper understanding of the issues facing the community and provides an opportunity to incorporate cultural values to potentially increase the efficacy, tailoring the intervention to distinct communities. An alternative to current healthcare interventions must be explored to reduce the health gap experienced by Black adults.

Trial registrationPROSPERO CRD42021245772

category: health systems and quality improvement


title: A Learning Health System Approach to the COVID-19 Pandemic: System-Wide Changes in Clinical Practice and 30-Day Mortality Among Hospitalized Patients

abstract:
IntroductionRapid, continuous implementation of credible scientific findings and regulatory approvals is often slow in large, diverse health systems. The COVID-19 pandemic created a new threat to this common "slow to learn and adapt" model in healthcare. We describe how UPMC committed to a rapid learning health system (LHS) model to respond to the COVID-19 pandemic.

MethodsAn observational cohort study was conducted among 11,429 hospitalized patients from 22 hospitals (PA, NY) with a primary diagnosis of COVID-19 infection (March 19, 2020 - June 6, 2021). Sociodemographic and clinical data were captured from UPMC electronic medical record (EMR) systems. Patients were grouped into four time-defined patient "waves" based on nadir of daily hospital admissions, with wave 3 (September 20, 2020 - March 10, 2021) split at its zenith due to high volume with steep acceleration and deceleration. Outcomes included changes in clinical practice (e.g., use of corticosteroids, antivirals, and other therapies) in relation to timing of internal system analyses, scientific publications, and regulatory approvals, along with 30-day rate of mortality over time.

ResultsMean (SD) daily number of hospital admissions was 26 (28) with a maximum 7-day moving average of 107 patients. System-wide implementation of the use of dexamethasone, remdesivir, and tocilizumab occurred within days of release of corresponding seminal publications and regulatory actions. After adjustment for differences in patient clinical profiles over time, each month of hospital admission was associated with an estimated 5% lower odds of 30-day mortality (adjusted OR = 0.95, 95% confidence interval: 0.92 - 0.97, p < .001).

ConclusionsIn our large LHS, near real-time changes in clinical management of COVID-19 patients happened promptly as scientific publications and regulatory approvals occurred throughout the pandemic. Alongside these changes, patients with COVID-19 experienced lower adjusted 30-day mortality following hospital admission over time.


title: How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from Zambia

abstract:
IntroductionAttrition from HIV treatment is high during patients first 6 months after antiretroviral therapy (ART) initiation and patients with less than 6 months on ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to reduce attrition. Despite eligibility criteria requiring greater than 6 months on ART, some patients enroll earlier. Using routinely-collected medical record data in Zambia, we compared loss to follow-up (LTFU) among patients enrolling in DSD models early (<6 months on ART) to LTFU among those who enrolled according to guidelines ([≥]6 months on ART) in order to assess whether the ART experience eligibility criterion is necessary.

MethodsWe extracted data from electronic medical records for adults ([≥]15 years) who initiated ART between 01/01/2019 and 31/12/2019 and evaluated LTFU, defined as >90 days late for last scheduled medication pickup, at 18 months for "early enrollers" (DSD enrolment after <6 months on ART) and "established enrollers" (DSD enrolment after [≥]6 months on ART). We used a log-binomial model to compare LTFU risk between groups, adjusting for age, sex, urban/rural status, ART refill interval and DSD model.

ResultsFor 6,340 early enrollers and 25,857 established enrollers there were no important differences between the groups in sex (61% female), age (median 37 years), or setting (65% urban). ART refill intervals were longer for established vs early enrollers (72% vs 55% were given 4-6-month refills). LTFU at 18 months was 3% (192/6,340) for early enrollers and 5% (24,646/25,857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio [95% confidence interval] 0.59 [0.50-0.68]).

ConclusionsPatients enrolled in DSD models in Zambia with < 6 months on ART were more likely to be retained in care than patients referred after they were established on ART. A limitation of the analysis is that early enrollers may have been selected for DSD participation due to providers and patients expectations about future retention. Offering DSD model entry to at least some ART patients <6 months after ART initiation may help address high attrition during the early treatment period.

category: hiv aids


title: Erytra Blood Group Analyser and Kode Technology testing of SARS-CoV-2 antibodies among convalescent patients and vaccinated individuals

abstract: Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires tests to monitor antibody formation and prevalence. We detected SARS-CoV-2 antibodies using red cells coated by Kode technology with short peptides derived from the SARS-CoV-2 spike protein. Such modified red cells, called C19-kodecytes, can be used as reagent cells in any manual or automated column agglutination assay. We investigated the presence of SARS-CoV-2 antibodies in 130 samples from COVID-19 convalescent plasma donors using standard manual technique, two FDA authorized ELISA assays and a virus neutralisation assay. The sensitivity of the C19-kodecyte assay was 88%, comparable to the anti-SP and anti-NCP ELISAs (86% and 83%) and the virus neutralisation assay (88%). The specificity of the C19-kodecyte assay was 90% (anti-SP 100% and anti-NCP 97%). Likewise, 231 samples from 73 vaccinated individuals were tested with an automated analyser and we monitored the appearance and persistence of SARS-CoV-2 antibodies. The C19-kodecyte assay is a robust tool for SARS-CoV-2 antibody detection. Automated blood group analyser use enables large-scale SARS-CoV-2 antibody testing for vaccination monitoring in population surveys.

category: infectious diseases


title: Effect of losartan on hospitalized patients with COVID-19-induced lung injury: A randomized clinical trial

abstract:
BackgroundSARS-CoV-2 viral entry may disrupt angiotensin II (Ang II) homeostasis in part via ACE2 downregulation, potentially contributing to COVID-19 induced lung injury. Preclinical models of viral pneumonias that utilize ACE2 demonstrate Ang II type 1 receptor (AT1R) blockade mitigates lung injury, though observational COVID-19 data addressing the effect of AT1R blockade remain mixed.

MethodsMulticenter, blinded, placebo-controlled randomized trial of losartan (50 mg PO twice daily for 10 days) versus placebo. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already taking a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible. The primary outcome was the imputed partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity, oxygen, ventilator, and vasopressor-free days, and mortality. Losartan pharmacokinetics (PK) and RAAS components [Ang II, angiotensin-(1-7) (Ang-(1-7)), ACE, ACE2] were measured in a subgroup of participants.

FindingsFrom April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]. Losartan did not improve any secondary clinical outcome, but worsened vasopressor-free days. PK data were consistent with appropriate steady-state concentrations, but we observed no significant effect of losartan on RAAS components.

InterpretationInitiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury does not improve PaO2 / FiO2 ratio at 7 days. These data may have implications for ongoing clinical trials.

Trial RegistrationLosartan for Patients With COVID-19 Requiring Hospitalization (NCT04312009), https://clinicaltrials.gov/ct2/show/NCT04312009


title: Effectiveness of the WHO-authorized Covid-19 Vaccines: a Rapid Review of Global Reports till June 30, 2021

abstract:
ObjectiveLarge clinical trials have proved the efficacy of Covid-19 vaccine, and the number of literature about the effectiveness is rapidly growing in the first half of year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings.

MethodsThis review is conducted based on the updated guideline of PRISMA 2020. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). The studies that assessed the VE of the 6 WHO-authorized vaccines (BNT162b2, ChAdOx1, Ad26.COV2.S, mRNA-1273, BBIBP-CorV, and CoronaVac) were eligible to be included. Quality assessment was performed based on ROBINS-I by 2 independent reviewers.

FindingsA total of 39 studies were included, covering over 15 million of participants from 11 nations. Among the general population after 2 doses of vaccination, the VE against symptomatic SARS-CoV-2 infection was estimated at 89%-97%, 92% (95% CI, 78%-97%) and 94% (95% CI, 86%-97%) for BNT162b2, ChAdOx1 and mRNA-1273, respectively. As for the protective effects against B.1.617.2 related symptomatic infection, the VE was 88% (95% CI, 85.3%-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3%-71.8%) by ChAdOx1 after fully vaccination.

ConclusionThis review revealed a consistently high effectiveness of vaccines among the general population in real-world settings. Further studies are needed to provide the information on different races/ethnicity, the effects against SARS-CoV-2 variants, and the duration of protection with longer study time.


title: Balanced crystalloids compared to normal saline for fluid therapy in critically ill adult patients: Systematic review and meta-analysis protocol

abstract:
IntroductionThe choice of intravenous fluid for fluid therapy in critically ill adult patients remains a matter of debate. Currently, crystalloids are used more often than colloids, with ongoing controversy over the relative efficacy and safety of buffered salt solutions (BSS) versus normal saline (0.9% sodium chloride). In 2021 two large pragmatic trials enrolling critically ill patients will add substantial new data to address this controversy. We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) that will include the data from these two trials to provide clinicians with the most up to date evidence and robust evidence to guide their choice of crystalloid fluids.

Methods and analysisWe will include RCTs that compare the effect of buffered salt solutions to normal saline for fluid resuscitation and/or fluid therapy in critically ill adults, on all-cause mortality and other patient centred outcomes. We will perform a search that includes the electronic databases MEDLINE and EMBASE, and clinical trial registries. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data, with discrepancies resolved by a third reviewer. We will report study characteristics and assess risk of bias using the Cochrane Risk-of-Bias tool. We will perform Hartung-Knapp-Sidik-Jonkman random-effects aggregate data meta-analysis whenever it is feasible to do so. We will evaluate overall certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Ethics and disseminationThis systematic review and meta-analysis does not require ethical approval as it does not involve primary data collection. We will publish our results in a peer-reviewed scientific journal and present them at national and international scientific conferences.

PROSPERO registration numberCRD42021243399

Strengths and limitations of this review [box]This systematic review will provide up-to-date evidence to answer the focused clinical question: In adult patients who are critically ill, does administering balanced crystalloid solutions for fluid therapy reduce mortality and other patient-centered outcomes, compared with administering 0.9% sodium chloride?

We will conduct a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines, searching three electronic databases, clinical trial registries and published conference abstracts, with two independent reviewers evaluating studies and extracting data.

A meta-analysis will assess the primary outcome of all-cause mortality at 90 days and secondary outcomes of ventilator and vasopressor free days, renal replacement therapy use, incidence of acute kidney injury, and patient quality of life outcomes.

The limitations of this review include the clinical heterogeneity of the included trials, diversity of the targeted population receiving fluid therapy, variability in the composition of balanced crystalloid solutions, and timing of initiation of study crystalloids. We will address all limitations with the Grading of Recommendations, Assessment, Development and Evaluations framework.

category: intensive care and critical care medicine


title: Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells.

abstract:
The IKAROS family transcription factors regulate lymphocyte development. Loss-of-function variants in IKZF1 cause primary immunodeficiency, but IKAROS family members IKZF2 and IKZF3 have not yet been associated with immunodeficiency yet. Here, we describe a pedigree with a heterozygous truncating variant in IKZF2, encoding the translational activator and repressor HELIOS which is highly expressed in regulatory T cells and effector T cells, particularly of the CD8+ T cell lineage. Protein-protein interaction analysis revealed that the variant abolished HELIOS dimerizations as well as binding to members of the Mi-2/NuRD chromatin remodeling complex. Patients carrying the IKZF2 variant presented with a combined immunodeficiency phenotype characterized by recurrent upper respiratory infections, thrush and mucosal ulcers, as well as chronic lymphadenopathy. With extensive immunophenotyping, functional assays, and transcriptional analysis we show that reduced HELIOS expression was associated with chronic T cell activation and increased production of pro-inflammatory cytokines both in effector and regulatory T cells. Lymph node histology from patients indicated dysregulated germinal center reactions. Moreover, affected individuals displayed profoundly reduced circulating MAIT cell numbers. In summary, we show that this novel loss-of-function variant in HELIOS leads to an immunodeficiency with signs of immune overactivation.

One sentence summaryTruncating variant of HELIOS causes immunodeficiency with signs of immune overactivation.

category: allergy and immunology


title: Causal and Associational Linking Language From Observational Research and Health Evaluation Literature in Practice: A systematic language evaluation

abstract:
We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality.

We searched and screened for 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, three reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations.

Reviewers rated the causal implication of exposure/outcome linking language as None (no causal implication) in 13.8%, Weak 34.2%, Moderate 33.2%, and Strong 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication.

This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

category: epidemiology


title: Causal and Associational Language in Observational Health Research: A systematic evaluation


title: Mental health and substance use associated with hospitalization among people with laboratory confirmed diagnosis of COVID-19 in British Columbia: a population-based cohort study

abstract:
BackgroundThis study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia.

MethodsThis study was performed using the BC COVID-19 Cohort, which integrates data on all COVID-19 cases, hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia as of January 15th, 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance.

FindingsFrom 56,874 COVID-19 cases included in the analyses, 2,298 were hospitalized. Models showed significant association of the following factors with increased hospitalization risk: male sex (adjusted risk ratio (aRR)=1.27; 95%CI=1.17-1.37), older age (p-trend <0.0001 across age groups with a graded increase in hospitalization risk with increasing age [aRR 30-39 years=3.06; 95%CI=2.32-4.03, to aRR 80+years=43.68; 95%CI=33.41-57.10 compared to 20-29 years-old]), asthma (aRR=1.15; 95%CI=1.04-1.26), cancer (aRR=1.19; 95%CI=1.09-1.29), chronic kidney disease (aRR=1.32; 95%CI=1.19-1.47), diabetes (treated without insulin aRR=1.13; 95%CI=1.03-1.25, requiring insulin aRR=5.05; 95%CI=4.43-5.76), hypertension (aRR=1.19; 95%CI=1.08-1.31), injection drug use (aRR=2.51; 95%CI=2.14-2.95), intellectual and developmental disabilities (aRR=1.67; 95%CI=1.05-2.66), problematic alcohol use (aRR=1.63; 95%CI=1.43-1.85), immunosuppression (aRR=1.29; 95%CI=1.09-1.53), and schizophrenia and psychotic disorders (aRR=1.49; 95%CI=1.23-1.82). Among women of reproductive age, in addition to age and comorbidities, pregnancy (aRR=2.69; 95%CI=1.42-5.07) was associated with increased risk of hospital admission.

InterpretationOlder age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

FundingBC Centre for Disease Control, Canadian Institutes of Health Research.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSFactors such as older age, social inequities and chronic health conditions have been associated to severe COVID-19 illness. Most of the evidence comes from studies that dont include all COVID-19 diagnoses in a jurisdiction), focusing on in-hospital mortality. In addition, mental illness and substance use were not evaluated in these studies. This study assessed factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia.

Added value of this studyIn this population-based cohort study that included 56,874 laboratory-confirmed COVID-19 cases, older age, male sex, injection drug use, problematic alcohol use, intellectual and developmental disability, schizophrenia and psychotic disorders, chronic comorbidities and pregnancy were associated with the risk of hospitalization. Insulin-dependent diabetes was associated with higher risk of hospitalization, especially in the subpopulation younger than 40 years. To the best of our knowledge this is the first study reporting this finding, (insulin use and increased risk of COVID-19-related death has been described previously).

Implications of all the available evidencePrioritization of vaccination in population groups with the above mentioned risk factors could reduce COVID-19 serious outcomes. The findings indicate the presence of the syndemic of substance use, mental illness and COVID-19, which deserve special public health considerations.


title: Imputing cognitive impairment in SPARK, a large autism cohort

abstract:
BackgroundDiverse large cohorts are necessary for dissecting subtypes of autism, and intellectual disability is one of the most robust endophenotypes for analysis. However, current cognitive assessment methods are not feasible at scale.

MethodsWe developed five commonly used machine learning models to predict cognitive impairment (FSIQ<80 and FSIQ<70) and FSIQ scores among 521 children with autism using parent-reported online surveys in SPARK, and evaluated them in an independent set (n=1346) with a missing data rate up to 70%. We assessed accuracy, sensitivity and specificity by comparing predicted cognitive level against clinical IQ data.

ResultsThe elastic-net model has good performance (AUC=0.876, sensitivity=0.772, specificity=0.803) using 129 predictive features to impute cognitive impairment (FSIQ<80). Top ranked predictive features included parent-reported language and cognitive levels, age at autism diagnosis, and history of services. Prediction of FSIQ<70 and FSIQ scores also showed good prediction performance.

ConclusionsWe show cognitive levels can be imputed with high accuracy for children with autism, using commonly collected parent-reported data and standardized surveys. The current model offers a method for large scale autism studies seeking estimates of cognitive ability when standardized psychometric testing is not feasible.

Lay summaryChildren with autism who have more severe learning challenges or cognitive impairment have different needs that are important to consider in research studies. When children in our study were missing standardized cognitive testing scores, we were able to use machine learning with other information to correctly "guess" when they have cognitive impairment about 80% of the time. We can use this information in research in the future to develop more appropriate treatments for children with autism and cognitive impairment.

category: psychiatry and clinical psychology


title: History of suicide attempts and COVID-19 infection in Veterans with schizophrenia or schizoaffective disorder: effect modification by age and obesity

abstract:
ImportanceAs patients with schizophrenia or schizoaffective disorder have a high risk of suicide, and a history of suicide attempt is a strong predictor of suicide, determining whether history of suicide attempt is associated with COVID-19 in patients with schizophrenia or schizoaffective disorder has implications for suicide prevention in this patient population.

ObjectiveTo determine whether a history of suicide attempt is associated with COVID-19 in Veterans with schizophrenia or schizoaffective disorder.

DesignCross-sectional analyses of nation-wide electronic health records (EHR).

SettingUnited States Veterans Health Administration.

ParticipantsVeterans with a diagnosis of schizophrenia or schizoaffective disorder that received treatment at any United States Veterans Affairs Medical Center from January 1, 2020 to January 31, 2021.

ExposureHistory of suicide attempt.

Main OutcomeAdjusted and unadjusted odds ratios (ORs) for COVID-19 positivity in suicide attempters relative to non-attempters. Adjusted analyses included age, sex, race, marital status, BMI, and a medical comorbidity score.

ResultsA total of 101,032 Veterans [mean age 56.67 {+/-} 13.13 years; males 91,715 (90.8%)] were included in the analyses. There were 2,703 (2.7%) suicide attempters and 719 (0.7%) patients were positive for COVID-19. There was effect modification by age and BMI in the association of history of suicide attempt with COVID-19 positivity such that the association was only significant in obese (BMI [≥] 30) patients and patients younger than 59 years respectively. In the entire sample, the unadjusted OR for COVID-19 positivity in attempters was 1.42 (95% CI 0.97 to 2.10) and the adjusted odds ratio was 1.90 (95% CI 1.28 to 2.80). In patients younger than 59 years, and in the obese patients respectively, history of suicide attempt was associated with COVID-positive status in unadjusted analyses [OR 3.53 (95% CI 2.10 to 5.94); OR 2.22 (95% CI 1.29 to 3.81)] and adjusted analyses [OR 3.42 (95% CI 2.02 to 5.79); OR 2.85 (95% CI 1.65 to 4.94)].

Conclusions and RelevanceYoung or obese suicide attempters with a diagnosis of schizophrenia or schizoaffective disorders have higher rates of COVID-19 diagnosis; due to possible long-term neuropsychiatric sequelae of infection with SARS-CoV-2, such patients should be monitored closely.


title: Socioeconomic and comorbid factors affecting mortality and length of stay in COVID-19

abstract:
BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic exposed and exacerbated health disparities between socioeconomic groups. Our purpose was to determine which disparities are most prevalent and their impact on length of stay (LoS) and in hospital mortality in patients diagnosed with Covid-19.

MethodsDe-Identified data for patients who tested positive for COVID-19 was abstracted from the HCA enterprise database. Data was binned into summary tables. A negative binomial regression with LoS as the dependent variable and a logistic regression of in-hospital mortality data, using age, insurance status, sex, comorbidities as the dependent variables, were performed.

ResultsFrom March 1, 2020 to August 23, 2020, of 111,849 covid testing patient records, excluding those with missing data (n=7), without confirmed COVID-19 (n=27,225), and those from a carceral environment (n=1,861), left 84,624 eligible patients. Compared to the US population, the covid cohort had more black patients (23.17% vs 13.4%). Compared to the white cohort, the black cohort had higher private insurance rates (28.52% vs. 23.68%), shorter LoS (IRR=0.97 CI=0.95-0.99, P<0.01) and lower adjusted mortality (OR 0.81, 95% CI 0.75-0.97). Increasing age was associated with increased mortality and LoS. Patients with Medicare or Medicaid had longer LoS (IRR=1.07, 95% CI=1.04-1.09) and higher adjusted mortality rates (OR=1.11, 95% CI=1-1.23) than those with private insurance

ConclusionConclusions We found that when blacks have higher rates of private insurance, they have shorter hospitalizations and lower mortality than whites, when diagnosed with Covid-19. Some other psychiatric and medical conditions also significantly impacted outcomes in patients with Covid-19.

Key PointsO_ST_ABSQuestionC_ST_ABSWhich social determinants of health and comorbidities are most prevalent and their impact on length of stay and in-hospital mortality in patients diagnosed with Covid-19?

FindingsIn this retrospective cohort of 84,624 with the black cohort having higher private insurance rates (28.52% vs. 23.68%), there was shorter LoS (IRR=0.97 CI=0.95-0.99, P<0.01) and lower adjusted mortality (OR 0.81, 95% CI 0.75-0.97). Age and several other medical and psychiatric comorbidities were also found to correlate with length of stay and mortality.

MeaningThe genetics of race is not important in predicting mortality and length of stay in COVID-19 patients, but age, comorbidities, and insurance status appear to have a significant difference in mortality and length of stay.


title: Implementation of a Web-Based Symptom Checker to Manage the Quarantine of the USS Theodore Roosevelt Crew Following a Shipboard Outbreak of SARS-CoV-2

abstract:
IntroductionIn late March 2020, the USS Theodore Roosevelt (TR), a nuclear-powered aircraft carrier, pulled into port in the US territory of Guam to assess the severity of a developing outbreak of COVID-19 aboard the ship. A small staff contingent of 60 personnel from US Naval Hospital (USNH) Guam was tasked with the medical care of 4,079 sailors who were placed in single room quarantine amongst 11 hotels across the island of Guam. With the assistance of the Defense Digital Service, the USNH Guam staff implemented a web-based symptom checker, which allowed for monitoring of developing COVID symptoms, and selective testing of symptomatic individuals.

Materials and MethodsSailors from the TR were placed in quarantine or isolation cohorts upon debarking the ship. Sailors not positive for COVID-19 were quarantined amongst 11 hotels on Guam. Sailors positive for COVID-19 were isolated aboard Naval Base Guam (NBG). A retrospective cohort analysis and subgroup analyses were performed on symptom data obtained from sailors in quarantine. The sailors recorded their symptoms and temperature in a web-based symptom checker that assigned a symptom severity score (SSS). Sailors with a SSS >50 were evaluated by a medical provider and re-tested. Data were collected from 4 April 2020 to 1 May 2020. Sailors required two negative tests to exit quarantine and re-embark the ship. The time course, and most common cluster of symptoms associated with a positive COVID-19 PCR test were determined retrospectively after data collection.

ResultsThe web-based symptom checker was successful in establishing daily positive contact and symptom monitoring of susceptible individuals in quarantine. 4,079 sailors in quarantine maintained positive contact with medical staff via the symptom checker, with at least 81% of the sailors recording their symptoms on a daily basis. Individuals with high symptom scores were quickly identified and underwent further evaluation and repeat COVID-19 testing. A cohort of 331 sailors tested positive for COVID-19 while in quarantine and recorded symptoms in the symptom checker before and after a positive COVID-19 test. In this cohort, the most frequent symptoms reported prior to a positive test were headache, anosmia, followed by cough. The symptom of anosmia was reported more frequently in sailors positive for COVID-19, compared to a cohort of matched controls. A small medical staff was able to monitor developing symptoms in a large quarantined population, while efficiently allocating resources, preserving personal protective equipment (PPE), and maintaining isolation and social distancing protocols.

Conclusions and RelevanceThe application provided a tool for broad health surveillance over a large population while maintaining strict quarantine and social distancing protocols. Highly symptomatic sailors were quickly identified, triaged, and transferred to a higher level of care if indicated. The symptom checker and predictive model generated from the data can be utilized by military and civilian public health officials to triage large populations and make rapid decisions on isolation measures, resource allocation, selective testing.


title: Novel Electrode Architecture for Subgaleal Electroencephalography: A Feasibility Study

abstract: AO_SCPLOWBSTRACTC_SCPLOWElectroencephalography (EEG) has been widely used to understand the nervous system and as a clinical diagnostic tool. In the case of neurological conditions with intermittent episodes, such as epilepsy, long-term EEG monitoring outside the clinics and in the community setting is vital. Subgaleal EEG (sgEEG) has emerged as an essential tool for long-term monitoring over several years. Current sgEEG solutions share a need for at least a 10 cm long lead wire, resulting in a bulky and invasive device. This work introduces a novel electrode architecture for subgaleal EEG recording, which forgoes the need for lead wires. A back-to-back electrode configuration with an electrode spacing of less than 1 mm is proposed. Compared to the current side-by-side approaches with an electrode spacing of several cm, our proposed approach results in at least one order of magnitude reduction in volume. The efficacy of the proposed electrode architecture is investigated through finite element modeling, phantom measurements, and cadaver studies. Our results suggest that compared to the conventional side-by-side electrode configuration, the source signal can be recorded reliably. Lead wires have posed a significant challenge from a device reliability and measurement quality perspective. Moreover, lead wires and the associated feedthrough connectors are bulky. Our proposed lead-free EEG recording solution may lead to a less invasive surgical placement through volume reduction and improve EEG recording quality.

category: neurology


title: Automation improves repeatability of retinal oximetry measurements

abstract:
PurposeRetinal oximetry is a technique based on spectrophotometry where images are analyzed with software capable of calculating vessel oxygen saturation and vessel diameter. In this study, the effect of automation of measurements of retinal vessel oxygen saturation and vessel diameter is explored.

MethodsUntil now, operators have had to choose each vessel segment to be measured explicitly. A new, automatic version of the software automatically selects the vessels once the operator defines a measurement area.

Five operators analyzed image pairs from the right eye of 23 healthy subjects with semiautomated retinal oximetry analysis software, Oxymap Analyzer (v2.5.1), and an automated version (v3.0). Inter- and intra-operator variability was investigated using the intraclass correlation coefficient (ICC) between oxygen saturation measurements of vessel segments in the same area of the retina.

ResultsFor manual saturation measurements, the inter-rater ICC was 0.80 for arterioles and venules. For automated saturation measurements, the inter-rater ICC was 0.97 for arterioles and 0.96 for venules. For manual diameter measurements, the inter-rater ICC was 0.71 for arterioles and venules. For automated diameter measurements the inter-rater ICC was 0.97 for arterioles and 0.95 for venules. The inter-rater ICCs were different (p < 0.01) between the semiautomated and automated version in all instances.

ConclusionAutomated measurements of retinal oximetry values are more repeatable compared to measurements where vessels are selected manually.

category: ophthalmology


title: Cost saving in primary versus tertiary level of reproductive health services in Sana'a, Yemen

abstract:
IntroductionIn Yemen, women tend to bypass the nearby primary health level facilities (PHLF) for using vaginal delivery (VD), antenatal care (ANC) and intrauterine device (IUD) services. This study aimed to estimate the cost saving for utilization of VD, ANC and IUD services at PHLF instead of tertiary health level facilities (THLF) in Sanaa.

MethodsA comparative cross sectional study design was conducted in 2013. It was used to estimate the costs from the patients perspective. A structured questionnaire was used to collect data. Descriptive analyses were performed. P value <0.05 was considered as the cut point for significance. The SPSS version 17 was used.

ResultsA total of 180 women were found. The median of DMC of VD, ANC and IUD services were US$43.9, US$14.8 and US$9.1 at THLF compared with US$19.5, US$0.9 and US$11.2 at PHLF, respectively. The DMC difference of VD, ANC and IUD services between THLF and PHLF was US$24.4, US$13.9 and US$-2.1, respectively. Regarding the DNMC, the median of VD, ANC and IUD services were US$43.1, US$19.1 and US$17.3 at THLF compared with US$14.0, US$0.0 and US$0.0 at PHLF, respectively. The DNMC difference of VD, ANC and IUD service between THLF and PHLF was US$29.1, US$19.1 and US$17.3, respectively. Moreover, the median of INDC for VD, ANC and IUD services were US$23.9, US$9.5 and US$10.4 at THLF compared with US$7.9, US$1.6 and US$1.1 at PHLF, respectively. The INDC difference of VD, ANC and IUD service between THLF and PHLF was US$16.0, US$7.9 and US$9.3.

ConclusionThe study found the utilization of VD, ANC and IUD services at PHLF instead of THLF is a considerable cost saving for families. Therefore, shifting the utilization of services from THLF to PHLF reduces the financial burden affecting individuals, families and their productivity. Implementation of the health referral system is recommended.

Key questionsO_ST_ABSWhat is already known?C_ST_ABS[tpltrtarr] Women tend remarkably to bypass the nearby primary reproductive health services that are rising the expenses and increasing the burden borne by individuals, families and their productivity.
[tpltrtarr]Few studies have estimated the cost saving for utilization of primary instead tertiary level of reproductive health services in the world, while no such study was conducted in Yemen.

What are the new findings?[tpltrtarr] A significant difference in the expenses on reproductive health services between the primary and tertiary health level facilities.
[tpltrtarr]A significant cost is saved for women and families as a result of utilization of primary instead tertiary level of reproductive health services.

What do the new findings imply?[tpltrtarr] The primary health level facilities reduce the financial burden affecting individuals, families and their productivity.
[tpltrtarr]This study provides evidence for decision-makers to implement the health referral system and protect the families from incurring the high expenditure.


title: Clinical Evaluation of the Novel Rapid Nucleic Acid Amplification Point-of-Care Test (Smart Gene SARS-CoV-2) in the analysis of Nasopharyngeal and Anterior Nasal samples.

abstract:
IntroductionSmart Gene is a point-of-care (POC)-type automated molecular testing platform that can be performed with 1 minute of hands-on-time. Smart Gene SARS-CoV-2 is a newly developed Smart Gene molecular assay for the detection of SARS-CoV-2. The analytical and clinical performance of Smart Gene SARS-CoV-2 has not been evaluated.

MethodsNasopharyngeal and anterior nasal samples were prospectively collected from subjects referred to the local PCR center from March 25 to July 5, 2021. Two swabs were simultaneously obtained for the Smart Gene SARS-CoV-2 assay and the reference real-time RT-PCR assay, and the results of Smart Gene SARS-CoV-2 were compared to the reference real-time RT-PCR assay.

ResultsAmong a total of 1150 samples, 68 of 791 nasopharyngeal samples and 51 of 359 anterior nasal samples were positive for SARS-CoV-2 in the reference real-time RT-PCR assay. In the testing of nasopharyngeal samples, Smart Gene SARS-CoV-2 showed the total, positive and negative concordance of 99.2% (95% confidence interval [CI]: 98.4-99.7%), 94.1% (95% CI: 85.6-98.4%) and 99.7% (95% CI: 99.0-100%), respectively. For anterior nasal samples, Smart Gene SARS-CoV-2 showed the total, positive and negative concordance of 98.9% (95% CI: 97.2-99.7%), 98.0% (95% CI: 89.6-100%) and 99.0% (95% CI: 97.2-99.8%), respectively. In total, 5 samples were positive in the reference real-time RT-PCR and negative in Smart Gene SARS-CoV-2, whereas 5 samples were negative in the reference real-time RT-PCR and positive in Smart Gene SARS-CoV-2.

ConclusionSmart Gene SARS-CoV-2 showed sufficient analytical performance for the detection of SARS-CoV-2 in nasopharyngeal and anterior nasal samples.


title: Profile of Mucormycosis Cases from a Network of Hospitals in North India Amidst COVID-19 Pandemic

abstract:
Incidence of mucormycosis suddenly surged in India after the second wave of COVID-19. This is a crippling disease and needs to be studied in detail to understand the disease, its course, and the outcomes.

Between 1st March and 15th July 2021, our network of hospitals in North India received a total of 155 cases of COVID-associated mucormycosis cases as all of them reported affliction by COVID-19 earlier or concurrent. Their records were retrieved from the Electronic Health Records system of the hospitals and their demographics, clinical features, treatments, and outcomes were studied. More than 80% (125 cases) had proven disease and the remaining 30 were categorized as  possible mucormycosis as per the EORTC criteria.

More than two-thirds (69.0%) of the cases were males and the mean age was 53 years for either sex. Nearly two-thirds (64.5%) had symptoms of nose and jaws and 42.6% had eye involvement. Some had multiple symptoms. As many as 78.7% had diabetes and 91.6% gave history of use of steroids during COVID-19 treatment. The primary surgery was functional endoscopic sinus surgery (FESS) (83.9%). Overall mortality was 16.8%, which is one-and-a-half times the mortality in hospitalized COVID-19 patients in the corresponding population. Occurrence of mucormycosis was associated with diabetes and use of steroids, but mortality was not associated with either of them. Cases undergoing surgery and on antifungal had steeply lower mortality (11.9% vs. 50.0%, P < 0.001) than those who were exclusively on antifungal drugs. Treatment by different drugs did not make much of a difference in mortality.


title: Effectiveness of vaccination against symptomatic and asymptomatic SARS-CoV-2  infection: a systematic review and meta-analysis

abstract:
OBJECTIVETo assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus vectored vaccines.

METHODSA frequentist random effects meta-analysis was carried out after data extraction. Risk of bias of the included studies was assessed using New-Castle-Ottawa Scale. The overall risk of SARS-CoV-2 infection confirmed by real time Polymerase Chain Reaction (PCR) was estimated in partially and fully vaccinated individuals. The effect size was expressed as Relative Risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection after vaccination. Potential sources of heterogeneity were investigated through between-study heterogeneity analysis and subgroup meta-analysis.

RESULTSThe systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR=73% (95%CI=59%-83%) for any positive SARS-CoV-2 PCR (RR=0.27) and a RRR=79% (95%CI=30%-93%) for symptomatic SARS-CoV-2 PCR (RR=0.21). Fully vaccinated individuals showed a RRR=94% (95%CI=88%-98%) for any SARS-CoV-2 positive PCR (RR=0.06) compared to unvaccinated. According to the subgroup meta-analysis, full BNT162b2 vaccination protocol achieved a RRR=84%-94% against any SARS-CoV-2 positive PCR and a RRR=68%-84% against symptomatic positive PCR. The RR for any SARS-CoV-2 positive PCR remained higher within elderly groups aged [≥]69 years (RR=0.12-0.15) compared to younger individuals (RR=0.05-0.12). The RR against B.1.351 infection approached 0.40 for any positive PCR and 0.36 for symptomatic SARS-COV-2 while the RR of any B.1.1.7 infection was 0.14.

CONCLUSIONThe current licensed vaccines may be transmission blocking, especially after full vaccination protocol. Given the substantial heterogeneity, results should be interpreted with caution. Subgroups meta-analyses suggested that the risk of any SARS-CoV-2 infection may be higher for non-B.1.1.7 variants and individuals aged [≥]69 years. Further data and longer follow-up are required to investigate additional sources of heterogeneity and the effectiveness of SARS-CoV-2 vaccination within population subgroups.

STRENGTHSO_LIReal-world data suggest that the current licensed vaccines may be transmission blocking, in particular after full vaccination protocol.
C_LIO_LIThe risk of any SARS-CoV-2 infection either symptomatic or asymptomatic, may be higher for non-B.1.1.7 variants and individuals aged [≥]69 years.
C_LI

LIMITATIONSO_LIGiven the substantial heterogeneity encountered in this meta-analysis, results should be interpreted with caution
C_LIO_LIFur ther evidence on the impact of SARS-CoV-2 variants are vital in order to monitor mutations associated with vaccine escape
C_LI


title: Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalized patients with COVID-19: A network meta-analysis

abstract:
ObjectiveTo estimate pairwise associations between administration of tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and non-invasive or mechanical ventilation, based on all available direct and indirect evidence.

MethodsEligible trials randomized hospitalized patients with COVID-19 that compared either interleukin-6 receptor antagonist with usual care or placebo in a recent prospective meta-analysis (27 trials, 10930 patients) or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomization.

Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomization were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.

ResultsOne trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0.82 [0.71-0.95, P=0.008]] and sarilumab [0.80 [0.61-1.04, P=0.09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1.03 [95%CI 0.81-1.32, P=0.80]. The P value for the global test for inconsistency was 0.28.

ConclusionAdministration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.


title: Nurse-physician Communication around Identifying Palliative Care Needs in Nursing Home Residents

abstract:
ObjectiveTo assess experiences of medical practitioners who are on the staff of nursing homes with communication with nursing staff about identifying emerging and changing (palliative) care needs of residents of nursing homes in the Netherlands.

DesignQualitative interview study.

Setting and ParticipantsFifteen physicians and two nurse practitioners employed by eight care organizations in the western urbanized region of the Netherlands.

MethodsWe conducted individual semi-structured interviews in 2018 informed by a topic list that was based on a qualitative dataset about facilitators to palliative care in dementia reported by elderly care physicians. The interviews were recorded, transcribed verbatim and analysed with Atlas.ti. We used both deductive and inductive coding adding refined codes related to communication.

ResultsAll interviewees expressed appreciation for nursing staff on whom they relied to communicate palliative care needs, yet they reported a variety of communication challenges around important changes in residents condition which were covered by two themes. (1) Teamwork was facilitated or impeded by team size and structure, quality of relationships and clarity in hierarchical relationships. (2) Continuity of information was affected by (in)effective routes of consultation and (lack of) detail in communicating observations.

Conclusions and ImplicationsAlso in the case of on-staff physicians, functioning of the multidisciplinary team and accurate sharing of observed changes in nursing home residents condition are crucial for physicians to be able to address palliative care needs. The physicians expressions of how they would favor nursing staff to communicate can inspire interprofessional training, such as reporting objective observations and phrasing a clear request for help while avoiding overly demanding appeals.

category: palliative medicine


title: Cognitive functioning in anxiety and depression: Results from the ALSPAC cohort

abstract:
BackgroundUnderstanding the nature of cognitive deficits in anxiety and depression may identify intervention targets and help prevent functional decline. This study used observational and genetic methods to investigate the association of anxiety and depression with emotion recognition, response inhibition, and working memory, in young adulthood.

MethodsThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a large prospective birth cohort study. Participants completed regular postal questionnaires and in-clinic assessments, starting from September 6, 1990. Data collection is ongoing. Linear regression was used to assess 1) cross-sectional associations between anxiety, depression, and cognition at age 24 (n = 2,187) and 2) prospective associations between anxiety and depression at age 18 and cognition at age 24 (n = 1,855). Mendelian randomization analyses were conducted to assess causal pathways between anxiety, depression, and cognition.

ResultsPrimary analyses were conducted on 3,087 participants following multiple imputation. There was evidence for anxiety being associated with a decreased recognition of happiness (b = -0.27, 95% CI -0.54 to 0.01, p = .045), and depression being associated with an increased recognition of sadness (b = 0.35, 95% CI 0.07 to 0.64, p = .016). Anxiety was negatively associated with working memory (b = -0.14, 95% CI -0.24 to 0.04, p = .005), but no association was found for depression (b = 0.06, 95% CI -0.05 to 0.16, p = .284). There was no evidence for any association with response inhibition. Results from Mendelian randomization analyses were inconclusive, likely due to low statistical power.

ConclusionsThere was little evidence that anxiety and depression are associated with significant impairments in executive functioning. However, both anxiety and depression were associated with altered emotion recognition. This may inform the development of interventions that target psychosocial functioning.


title: Behavioral and neural dissociation of social anxiety and loneliness

abstract:
BackgroundLoneliness is a public health concern with detrimental effects on physical and mental well-being. Given phenotypical overlaps between loneliness and social anxiety, cognitive behavioral interventions targeting social anxiety might be adopted to reduce loneliness. However, it is still elusive whether social anxiety and loneliness share the same underlying neurocognitive mechanisms. The current study aimed at investigating to what extent known behavioral and neural correlates of social avoidance in social anxiety are evident in loneliness.

MethodsWe used a pre-stratified approach involving 42 participants with high and 40 control participants with low loneliness scores. During functional magnetic resonance imaging, the participants completed a social gambling task to measure the subjective value of engaging in a social situation and responses to positive and negative social feedback.

ResultsUni- and multivariate analyses of behavioral and neural data replicated known task effects across groups. However, although lonely participants were characterized by increased social anxiety, loneliness was associated with a response pattern clearly distinct from social anxiety. Specifically, Bayesian analyses revealed moderate evidence for equal subjective values of engaging in social situations and comparable amygdala responses to social decision-making and striatal responses to positive social feedback in both groups. Conversely, lonely participants showed significantly altered behavioral responsiveness to negative feedback and reduced striatal activity, whereas striatal-hippocampal connectivity was increased compared to controls.

ConclusionOur findings suggest that loneliness is associated with altered emotional reactivity to social situations rather than behavioral tendencies to withdraw from social interactions. Thus, established interventions for social anxiety should be adjusted when targeting loneliness.


title: Behavioural barriers to COVID-19 testing in Australia: Two national surveys to identify barriers and estimate prevalence by health literacy level

abstract:
BackgroundCOVID-19 testing and contact tracing has been crucial in Australias prevention strategy. However, testing for COVID-19 is far from optimal, and behavioural barriers are unknown. Study 1 aimed to identify the range of barriers to testing. Study 2 aimed to estimate prevalence in a nationally relevant sample to target interventions.

MethodsStudy 1: National longitudinal COVID-19 survey from April-November 2020. Testing barriers were included in the June survey (n=1369). Open responses were coded using the COM-B framework (capability-opportunity-motivation). Study 2: Barriers from Study 1 were presented to a new nationally representative sample in November to estimate prevalence (n=2869). Barrier prevalence was analysed by health literacy level using Chi square tests.

ResultsStudy 1: 49% strongly agreed to get tested for symptoms, and 69% would self-isolate. Concern about pain was the top barrier from a provided list (11%), but 32 additional barriers were identified from open responses and coded to the COM-B framework. Study 2: The most prevalent barriers were motivation issues (e.g. dont believe symptoms are COVID-19: 28%, few local cases: 18%). Capability issues were also common (e.g. not sure symptoms are bad enough: 19%, not sure whether symptoms need testing: 15%). Many barriers were more prevalent amongst people with low compared to high health literacy, including motivation (preference to self isolate: 21% vs 12%, pain: 15% vs 9%) and capability (not sure symptom needs testing: 12% vs 8%, not sure how to test:11% vs 4%).

ConclusionEven in a health system with free and widespread access to COVID-19 testing, motivation and capability barriers were prevalent issues, particularly for people with lower health literacy. This study highlights the important of diagnosing behaviour barriers to target public health interventions for COVID-19 and future pandemics.

category: public and global health


title: The Effect of Residents Working-Hour Restrictions on Patient Safety, Resident Well-Being, and Resident Education: Protocol for a Systematic Review and Meta-Analysis

abstract:
IntroductionResidents duty hour restrictions have been a source of debate throughout the years, given that extended shifts have historically been associated with a negative effect on patient safety. Implementing restricted duty hours may help reduce sleep deprivation and workload, consequently improving residents sense of well-being. On the other hand, these reforms implicate a greater number of handoffs where communication errors may arise, and continuity of care being lost as a result. In a similar way, shorter shifts may implicate less time of direct patient contact and, consequently, decreased educational opportunities for residents. Various studies have attempted to explore the effect of resident work hour reforms on patient safety outcomes. However, these have been mainly based solely on observational studies that have not been subjected to the same rigor as experimental ones, primarily because no randomized controlled trials (RCT) were available in this matter. Nonetheless, more substantial evidence has become available in these last few years as three RCTs have been published exploring the impact of resident duty hour restrictions on patient safety as well as on residents wellbeing and education. An updated systematic review and meta-analysis are crucial to interpret this data that has now become available.

ObjectivesTo evaluate the effect of resident physicians working-hour restrictions on patient safety parameters, residents perceived well-being and resident education.

Methods and analysisThis research protocol was developed according to PRISMA-P and the Cochrane guidelines for systematic reviews and metanalysis. Electronic literature search strategies were developed using MeSH and free terms to be carried out in PubMed, MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov and Global Index Medicus with no restriction in language. Primary outcome measures include several patient safety parameters, whereas secondary outcome measures involve resident well-being and education. Two research team members will screen identified titles, abstract and full text, evaluate risk of bias and extract data in an independent manner. A qualitative narrative synthesis will be employed to summarize the key findings, population, and methodology of studies using text and tables for both primary and secondary outcomes. We will test for heterogeneity of the included studies by employing the I2 statistical test; if significant (I2 [≥] 75%), only qualitative synthesis will be presented. On the contrary, if studies are homogeneous, a meta-analysis will be considered using Review Manager 5.1 software. For continuous data, we will calculate the mean difference or standardized mean difference. For dichotomous data, the risk ratio (RR) will be calculated. Results will be displayed on a Forest Plot. To assess bias, a Funnel plot and Egger test will be employed.

ConclusionsThis systematic review will provide evidence regarding the effect of resident physicians working-hour restrictions on patient safety parameters, residents perceived well-being and resident education. All of these are variables that must be considered when determining policies regarding the medical training environment. It is essential to review the existing high-grade evidence regarding the impact of residents extended working hours so that authorities can optimize future graduate medical education regulations.


title: Dietary differences by job type and industry among workers in Japan during the COVID-19 pandemic: A cross-sectional study

abstract:
BackgroundThe COVID-19 pandemic requires people to change their lifestyles. This study aimed to examine the differences in dietary behaviors during the pandemic across job types and industries.

MethodsA cross-sectional study was conducted using data from the Novel-coronavirus and Work Project. Job type and industry were classified into 3 and 22 groups, respectively. Dietary behaviors were assessed using self-reported questionnaires regarding eating breakfast, frequency of meals, and eating fast foods. Changes in eating breakfast during the pandemic were also evaluated. Logistic regression analysis nested in the workplace prefecture was carried out and adjusted for gender, age, body mass index, presence of family members, educational background, and household income.

ResultsWorkers involved in jobs that require communicating with people were more likely to skip breakfast (OR 1.17, 95%CI 1.10-1.24) and had a lower frequency of meals (OR 1.25, 95%CI 1.17-1.34) than workers engaged in desk work. Manual workers were more likely to eat fast food or meals (OR 1.10, 95%CI 1.03-1.17) than workers engaged in desk work. Workers engaged in newspaper, magazine, television, radio, advertising, and other mass media industries were more likely to skip breakfast (OR 2.43, 95%CI 1.82-3.24) and have a lower frequency of meals (OR 3.90, 95%CI 2.87-5.28) than workers in public offices and organizations.

ConclusionThe tendencies of dietary behaviors across job types/industries during the pandemic were shown, partially consistent with a trend reported before the pandemic. Further studies should clarify the causes of differences in dietary behaviors among workers.


title: Brain Activation in Chronic Nonspecific Low Back Pain : A Systematic review and ALE Meta-analysis

abstract:
Pain, a protective mechanism turns into a pathologic response when it becomes chronic. Recent evidences are pointing towards neuroplastic brain changes as the primary factor for the persisting pain in chronic nonspecific low back pain (cLBP). To summarise the previous fMRI studies, a coordinate-based ALE meta-analysis of resting functional brain imaging studies is carried out to identify the clusters activated in the brain in cLBP.

Literature survey:  PubMed,  Scopus and  Sleuth were searched for studies with resting functional whole-brain imaging in cLBP. Till October 2020; 258, 238, and 7 studies were found respectively after search. The activity pattern was documented in  without stimulation and  with stimulation groups. The risk of bias was assessed by Joanna Briggs Institute critical appraisal checklist for analytical cross-section studies. Total seven (224 cLBP patients, 110 activation foci) and six studies (106 cLBP patients, 66 activation foci) were selected among 277 studies for metanalysis in the  without stimulation and  with stimulation group respectively. In the  without stimulation group 8 statistically significant clusters were found. The clusters are distributed in the prefrontal cortex, primary somatosensory cortex, and primary motor cortex, anterior cingulate cortex, insular cortex, putamen, claustrum, amygdala, and associated white matters in both hemispheres. On the other group, 3 statistically significant clusters were found in the frontal cortex, Parietal cortex, and Insula. In the  with stimulation group, significant lateralization was observed and most of the clusters were in the right hemisphere. The white matter involvement was more in the  with stimulation group (78.62% Vs 38.21%). The statistically significant clusters found in this study indicate a probable imbalance in GABAergic modulation of brain circuit and dysfunction in descending pain modulation system. This disparity in pain neuro-matrix is the source of spontaneous and persisting pain in cLBP.

category: pain medicine