title: Comparative Effectiveness of BNT162b2 versus Ad26.COV2.S for the Prevention of COVID-19 among Dialysis Patients

abstract:
BackgroundmRNA-based SARS-CoV-2 vaccines have been shown to be highly effective among dialysis patients. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness of other vaccines, such those based on adeno-virus technologies.

MethodsThis retrospective study compared the clinical effectiveness of Ad26.COV2.S (Janssen/Johnson and Johnson) to BNT162b2 among dialysis patients. Patients initiating BNT162b2 (Pfizer/BioNTech) were matched 1:1 to Ad26.COV2.S recipients based on age, race, US state of residence, calendar week of first vaccine receipt, and history of COVID-19. The primary outcome was the comparative rate of COVID-19 considered over 3 follow-up intervals: weeks 1-3, 4-6, and [≥] 7 post-vaccination. In a subset of consented Ad26.COV2.S patients, blood samples were collected [≥]28 days after vaccination and anti-SARS-Cov-2 immunoglobulin G antibodies were measured.

ResultsThere were 2659 matched pairs of patients who received a first dose of each vaccine. During weeks 1-3, incidence rates were 1.13 vs 1.39 per 1000 patient-weeks (pt-wks) for BNT162b2 and Ad26.COV2.S recipients, respectively (incident rate difference [IRD]: 0.25; 95% CI: -0.90, 1.36). During weeks 4-6, incidence rates were 0.78 vs 0.39 per 1000 pt-wks for BNT162b2 and Ad26.COV2.S recipients, respectively (IRD: -0.39; 95% CI: -1.16, 0.38). After week 7, incidence rates were 1.29 vs 1.39 per 1000 pt-wks for BNT162b2 and Ad26.COV2.S recipients, respectively (IRD: 0.10; 95% CI: -0.35, 0.55). Results were similar when considering only patients without a history of COVID-19 and among matched pairs in which BNT162b2 recipients completed the 2-dose regimen. SARS-CoV-2 antibodies were detected in 59.4% (95% CI: 53.0%-65.5%) of Ad26.COV2.S patients.

ConclusionIn a large real-world cohort of dialysis patients, no difference was detected in the clinical effectiveness of BNT162b2 and Ad26.COV2.S, despite an inconsistent antibody response to the latter. These data support the use of either agent in ongoing vaccination efforts in this population.

category: nephrology


title: Prediction and predictor elucidation of the onset of metabolic syndrome among young workers using machine learning techniques: A nationwide study in Japan

abstract:
ObjectivesPredictive models for the onset of metabolic syndrome (MS) among people in their 30s are scarce. This study aimed to construct a highly accurate model to predict MS onset by age 40 years and to identify the important predictors of MS onset using health checkup data of Japanese company employees aged 30 and 35.

MethodsThe study included 6,048 Japanese employees aged 40 years who had undergone periodic health examinations over 10 years. We developed prediction models for MS onset using machine learning methods including the random forest and logistic regression, and evaluated the models using the receiver operating characteristics and precision-recall curves. For the random forest models, the variable importance of each explanatory variable was calculated to identify important predictors of MS onset.

ResultsThe random forest had higher predictive power than logistic regression in all models, although the differences were non-significant. Regarding important predictors, diastolic blood pressure was the most important predictor of MS onset for men aged 30 and 35 years, while body mass index was the most important predictor for women aged 30 and 35 years.

ConclusionsWe created a machine learning model to predict MS onset at age 40 with high accuracy from health examination data obtained at ages 30 or 35. Sex differences in important predictors of MS onset was shown by the variable importance indices of the random forest. Applying our model in routine healthcare management should provide early and appropriate health interventions to prevent MS onset in young people.

category: occupational and environmental health


title: Association of lipid-regulating drugs with dementia and related conditions: an observational study of data from the Clinical Practice Research Datalink

abstract:
2BackgroundThere is some evidence that circulating blood lipids play a role in the development of Alzheimers disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of dementia and related conditions in the Clinical Practice Research Datalink (CPRD), an United Kingdom-based electronic health record database.

MethodsA retrospective cohort study was performed using routinely collected CPRD data (January 1995 and March 2016). Multivariable Cox proportional hazard models, allowing for a time-varying treatment indicator, were used to estimate the association between seven lipid-regulating drug classes (vs. no drug) and five dementia outcomes (all-cause, vascular and other dementias, and probable and possible Alzheimers disease).

ResultsWe analyzed 1,684,564 participants with a total follow-up of 10,835,685 patient-years (median: 5.9 years (IQR:2.7-9.7)). We found little evidence that lipid-regulating agents were associated with incidence of Alzheimers disease (probable HR:0.98, 95%CI:0.94-1.01; possible HR:0.97, 95%CI:0.93-1.01), but there was evidence of an increased risk of all-cause (HR:1.17, 95%CI:1.14-1.19), vascular (HR:1.81, 95%CI:1.73-1.89) and other dementias (HR:1.19, 95%CI:1.15-1.24). Evidence from a number of control outcomes indicated the presence of substantial residual confounding by indication (ischaemic heart disease HR: 1.62, 95%CI: 1.59-1.64; backpain HR: 1.04, 95%CI: 1.03-1.05; and Type 2 diabetes HR: 1.50, 95%CI: 1.48-1.51).

ConclusionLipid-regulating agents were not associated with reduced Alzheimers disease risk. There was some evidence of an increased the risk of all-cause, vascular and other dementias, likely due to residual confounding by indication.

3 Key messagesO_LIA large cohort of patients from the Clinical Practice Research Datalink (CPRD) electronic health record database was assembled to examine the association of lipid-regulating agents, such as statins, with dementia outcomes.
C_LIO_LIThere was little evidence that lipid-regulating agents were associated with Alzheimers disease, but there was some evidence for a harmful association with all-cause, vascular and other dementias. In all cases, the estimated associations were driven by the any statin subgroup, which comprised most participants in our cohort.
C_LIO_LIEvidence from the control outcome analyses indicated strong residual confounding by indication, mostly likely related to vascular factors.
C_LI

category: epidemiology


title: Cohort Profile: National Institute for Health Research Health Informatics Collaborative: Hepatitis B Virus (NIHR HIC HBV) Research Dataset

abstract:
PurposeThe National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) was established to enable re-use of routinely collected clinical data across National Health Service (NHS) Trusts in the United Kingdom to support translational research. Viral hepatitis is one of the first five exemplar themes and hepatitis B virus (HBV) is the current focus of the theme. The NIHR HIC HBV dataset, derived from the central data repository of NIHR HIC viral hepatitis theme, aims to describe and characterise HBV infection in secondary care in the United Kingdom, and provides a resource for translational research.

ParticipantsThe dataset comprises >5000 individuals (99% adults aged [≥]18, 1% children aged <18) with chronic HBV (CHB) infection from five NHS Trusts across England, representing clinical data collected between August 1994 and August 2021.

Findings to dateData on demographics, laboratory tests, antiviral treatment, elastography scores, imaging/biopsy reports, death information, and potential risk factors for liver disease have been collected. Data are captured by electronic patient record (EPR) systems, and records are updated prospectively as new results are added. This cohort profile describes the dataset in its current form. Among the adults, 55% are male, and the median age at index date (defined as the first recorded positive hepatitis B virus surface antigen (HBsAg) or HBV DNA in EPR systems) was 40 years (interquartile range [IQR]: 32-50). For those individuals with ethnicity reported, 30% were Asian, 24% were Black, 30% were White, and the remaining 16% were mixed or other ethnic groups. Currently, the median follow-up duration of the adult patients in this dataset was 5.0 (IQR: 2.7-7.5) years, with 9.3 (95% CI: 8.2-10.5) deaths per 1,000 person-years. We have already conducted several analyses using subsets of this dataset including an evaluation of distribution and trajectories of HBsAg and HBV viral load in CHB, reviewing the use of antiviral treatment, quantifying the burden of liver disease in the untreated population, and studying the use of laboratory biomarkers to improve stratification and surveillance.

Future plansLongitudinal data collection is continuing, with the sample growing in size, more parameters being collected, average follow-up increasing, and more NHS Trusts participating. This dataset offers important opportunities for epidemiological studies and biomedical informatics research, as well as characterising an HBV population for clinical trials through external collaborations with industry.


title: The impact of vaccinating adolescents and children on COVID-19 disease outcomes

abstract:
IntroductionDespite the high COVID-19 vaccination coverage among adults, there is concern over a peak in SARS-CoV-2 infections in the coming months. To help ensure that healthcare systems are not overwhelmed in the event of a new wave of SARS-CoV-2 infections, many countries have extended vaccination to adolescents (those aged 12-17 years) and may consider further extending to children aged 5-11 years. However, there is considerable debate about whether or not to vaccinate healthy adolescents and children against SARS-CoV-2 because, while vaccination of children and adolescents may limit transmission from these groups to other, more vulnerable groups, adolescents and children themselves have limited risk of severe disease if infected and may experience adverse events from vaccination. To quantify the benefits of extending COVID-19 vaccination beyond adults we compare daily cases, hospital admissions, and intensive care (IC) admissions for vaccination in adults only, those 12 years and above, and those 5 years and above.

Methods and FindingsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model to simulate disease outcomes (e.g., cases, hospital admissions, IC admissions) under different vaccination scenarios. The model is partitioned into 10-year age bands (0-9, 10-19, ..., 70-79, 80+) and accounts for differences in susceptibility and infectiousness by age group, seasonality in transmission rate, modes of vaccine protection (e.g., infection, transmission), and vaccine characteristics (e.g., vaccine effectiveness). Model parameters are estimated by fitting the model piecewise to daily cases from the Dutch notification database Osiris from 01 January 2020 to 22 June 2021. Forward simulations are performed from 22 June 2021 to 31 March 2022. We performed sensitivity analyses in which vaccine-induced immunity waned.

We found that upon relaxation of all non-pharmaceutical control measures a large wave occurred regardless of vaccination strategy. We found overall reductions of 5.7% (4.4%, 6.9%) of cases, 2.0% (0.7%, 3.2%) of hospital admissions, and 1.7% (0.6%, 2.8%) of IC admissions when those 12 years and above were vaccinated compared to vaccinating only adults. When those 5 years and above were vaccinated we observed reductions of 8.7% (7.5%, 9.9%) of cases, 3.2% (2.0%, 4.5%) of hospital admissions, and 2.4% (1.2%, 3.5%) of IC admissions compared to vaccination in adults only. Benefits of extending vaccination were larger within the age groups included in the vaccination program extension than in other age groups. The benefits of vaccinating adolescents and children were smaller if vaccine protection against infection, hospitalization, and transmission (once infected) wanes.

DiscussionOur results highlight the benefits of extending COVID-19 vaccination programs beyond adults to reduce infections and severe outcomes in adolescents and children and in the wider population. A reduction of infections in school-aged children/adolescents may have the added benefit of reducing the need for school closures during a new wave. Additional control measures may be required in future to prevent a large wave despite vaccination program extensions. While the results presented here are based on population characteristics and the COVID-19 vaccination program in The Netherlands, they may provide valuable insights for other countries who are considering COVID-19 vaccination program extensions.


title: Geographic Disparities and Predictors of COVID-19 Hospitalization Risk in the St. Louis Area, Missouri (USA).

abstract:
BackgroundCOVID-19 has overwhelmed the US healthcare system, with over 44 million cases and over 700,000 deaths as of October 6, 2021. There is evidence that some communities are disproportionately affected. This may result in geographic disparities in COVID-19 hospitalization risk that, if identified, could guide control efforts. Therefore, the objective of this study is to investigate Zip Code Tabulation Area (ZCTA)-level geographic disparities and identify predictors of COVID-19 hospitalization risk in the St. Louis area.

MethodsHospitalization data for COVID-19 and several chronic diseases were obtained from the Missouri Hospital Association. ZCTA-level data on socioeconomic and demographic factors were obtained from the US Census Bureau American Community Survey. Age-adjusted COVID-19 and several chronic disease hospitalization risks were calculated. Geographic disparities in distribution of COVID-19 age-adjusted hospitalization risk, socioeconomic and demographic factors as well as chronic disease risks were investigated using choropleth maps. Predictors of ZCTA-level COVID-19 hospitalization risks were investigated using global negative binomial and local geographically weighted negative binomial models.

ResultsThere were geographic disparities of COVID-19 hospitalization risks. COVID-19 hospitalization risks were significantly higher in ZCTAs with high diabetes hospitalization risks (p<0.0001), high risks of COVID-19 cases (p<0.0001), as well as high percentages of black population (p=0.0416) and populations with some college education (p=0.0005). The coefficients of the first three predictors varied across ZCTAs, implying that the associations between COVID-19 hospitalization risks and these predictors varied by geographic location. This implies that a "one-size-fits-all" approach may not be appropriate for management and control.

ConclusionsThere is evidence of geographic disparities in COVID-19 hospitalization risks that are driven by differences in socioeconomic, demographic and health-related factors. The impacts of these factors vary by geographical location with some factors being more important predictors in some locales than others. Use of both global and local models leads to a better understanding of the determinants of geographic disparities in health outcomes and utilization of health services. These findings are useful for informing health planning to identify geographic areas likely to have high numbers of individuals needing hospitalization as well as guiding vaccination efforts.


title: Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition

abstract:
Study ObjectivesTo assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective sleep, sleep-state misperception as well as self-reported and objective cognitive performance.

MethodsWe performed a randomized controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index (ISI), sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording, cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. At 6 months post-randomization, we collected similar data from the wait-list group after CBTi. We also assessed ISI one year after CBTi in both groups. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list group). In secondary analyses, we pooled data from both groups to observe changes after CBTi.

ResultsISI score was reduced and self-reported sleep quality improved after CBTi (treatment group at 3 months and pooled groups after CBTi). Sleep misperception in sleep onset latency and sleep duration decreased after CBTi. In contrast, objective sleep, objective and subjective cognitive functioning did not improve after CBTi.

ConclusionsWe showed that CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no significant effect of CBTi on measures of cognitive functioning.

STATEMENT OF SIGNIFICANCENighttime sleep difficulties and daytime cognitive impairment are the two main complaints of individuals suffering from insomnia. We investigated the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on these two aspects of chronic insomnia, using both self-reported and objective measures, as well as sleep-state misperception (i.e., the discrepancy between self-reported and objective sleep). We showed significant changes after CBTi in insomnia severity, subjective sleep quality and perception of sleep, while no consistent benefit emerged for objective measures of sleep and assessments of cognitive functioning. CBTi thus appears to primarily benefit subjective sleep quality as well as the alignment between subjective and objective estimates of sleep.

category: psychiatry and clinical psychology


title: COVID-19 Prevention Facilitators and Barriers among Specific Ethnic Minority Communities in Rural Ohio

abstract:
ObjectiveTo assess knowledge, beliefs, and behaviors concerning COVID-19 among Guatemalan, Marshallese, and Amish populations in rural Ohio; identify individual, interpersonal, community, and structural level challenges within each community; and provide population-specific recommendations to prevent and mitigate further SARS-CoV-2 transmission among these rural communities.

MethodsWe conducted 30 key informant interviews in four rural counties in Ohio, in May 2020. Three teams of two investigators conducted interviews with local health department staff, community members, meat packing plant management, and community leaders from three communities disproportionately affected by the COVID-19 pandemic [Guatemalan (N=12), Marshallese (N=7), Amish (N=11)]. We used the Social Ecological Model to identify and categorize themes.

ResultsEmerging and overall themes were identified and defined. Investigators identified COVID-19 knowledge gaps, myths, and misinformation, food insecurity, community cohesion, stigma, community culture and norms, lack of workplace safety policies, and access to testing as key themes to COVID-19 prevention.

ConclusionsUnderstanding specific barriers and identifying facilitators that most effectively provide resources, healthcare services, education, and social support tailored to specific communities would help deter SARS-CoV-2 transmission.

category: public and global health


title: Predictors of treatment outcomes with Auto-titrating CPAP therapy in adults with Obstructive Sleep Apnea

abstract:
ObjectivesTo determine factors that predict OSA therapy outcomes with auto-titrating positive airway pressure (APAP).

MethodsWe sequentially grouped patients from a retrospective cohort based on APAP efficacy (sufficiently vs. insufficiently treated; insufficiently treatment defined as residual AHI of [≥] 5); therapy adherence (compliant vs. non-compliant, non-compliance defined as < 70% usage for [≥] 4 hours/night); and therapy outcomes (optimal vs non-optimal (non-optimal outcomes defined as non-compliant and insufficiently treated). We subsequently compared each group.

ResultsThe insufficiently treated were older (68.4 {+/-} 12.5 vs. 60.4 {+/-} 13.1 years, p < 0.01) and had lower BMI (31.9 {+/-} 6.3 vs.37.9 {+/-} 9.1 kg/m2, p < 0.01). They had higher baseline central apnea indices (CAI), longer leaks, higher peak pressures and were less compliant.

The non-compliant were younger (61.1 {+/-} 12.6 vs. 65.5 {+/-} 13.2 years, p = 0.03) and comprised more females (56.1 vs. 43.9%, p = 0.04). The leak duration per usage hour was higher in the non-compliant (13.9 {+/-} 42.1 vs. 1.83 {+/-} 3.53 minutes/hour, p < 0.01). The non-optimally treated had lower BMI, longer leaks and shorter nightly usage.

Following multivariate analysis, the aforementioned variables except age were predictive of higher residual AHI, while age and gender predicted compliance.

ConclusionsVarious demographic and clinical factors were predictive of treatment efficacy and adherence. Overall, lower BMI, longer leaks and shorter nightly usage predicted poor therapy outcomes.

category: respiratory medicine


title: COVID-19 Vaccination Mandates and Vaccine Uptake

abstract: We evaluate the impact of government mandated proof of vaccination requirements for access to public venues and non-essential businesses on COVID-19 vaccine uptake. We find that the announcement of a mandate is associated with a rapid and significant surge in new vaccinations (more than 60% increase in weekly first doses) using the variation in the timing of these measures across Canadian provinces in a difference-in-differences approach. Time-series analysis for each province and for France, Italy and Germany corroborates this finding, and we estimate cumulative gains of up to 5 percentage points in provincial vaccination rates and 790,000 or more first doses for Canada as a whole as of October 31, 2021 (5 to 13 weeks after the provincial mandate announcements). We also find large vaccination gains in France (3 to 5 mln first doses), Italy (around 6 mln) and Germany (around 3.5 mln) 11 to 16 weeks after the proof of vaccination mandate announcements.

category: health economics


title: Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T cell response

abstract:
BackgroundMyeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination.

MethodsUsing a prospective study of myeloma patients in UK Rudy Study cohort, we assessed humoral and Interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration.

FindingsWe report data from 214 adults with myeloma (n=204) or smouldering myeloma (n=10) who provided blood samples at least 3 weeks after second vaccine dose. Positive Anti-Spike antibody levels (> 50 IU/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative Anti-Spike protein antibody response. 95/158 (60.1%) patients produced positive results for both anti-Spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/ anti-BCMA therapy and Pfizer-BioNTech (PB) vaccination.

InterpretationSignificant majority of myeloma patients elicit Anti-Spike protein antibody responses to COVID-19 vaccine with 60% of myeloma patients showing both humoral and T cell response. Predictors of a poor immune response included male gender, myeloma therapy regimen and administration of Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.

FundingFunding for this study has been received from Blood Cancer Vaccine Consortium and Janssen UK. RUDY platform has been funded by NIHR.

category: hematology


title: How different pre-existing mental disorders and their co-occurrence affects clinical outcomes of COVID-19? A study based on real-world data in the Southern United States

abstract:
ImportanceA growing body of research focuses on the impact of pre-existing mental disorders on clinical outcomes of COVID-19 illness. Although a psychiatric history might be an independent risk factor for COVID-19 infection and mortality, no studies have systematically investigated how different clusters of pre-existing mental disorders may affect COVID-19 clinical outcomes or showed how the coexistence of mental disorder clusters is related to COVID-19 clinical outcomes.

ObjectiveTo explore how different pre-existing mental disorders and their co-occurrence affects COVID-19-related clinical outcomes based on real-world data.

Design, Setting, and ParticipantsUsing a retrospective cohort study design, a total of 476,775 adult patients with lab-confirmed and probable COVID-19 between March 06, 2020 and April 14, 2021 in South Carolina, United States were included in the current study. The electronic health record data of COVID-19 patients were linked to all payer-based claims data through the SC Revenue and Fiscal Affairs Office.

Main Outcomes and MeasuresKey COVID-19 clinical outcomes included severity, hospitalization, and death. COVID-19 severity was defined as asymptomatic, mild, and moderate/severe. Pre-existing mental disorder diagnoses from Jan 2, 2019 to Jan 14, 2021 were extracted from the patients healthcare utilization data via ICD-10 codes. Mental disorders were categorized into internalizing disorders, externalizing disorders, and thought disorders.

ResultsOf the 476,775 COVID-19 patients, 55,300 had pre-existing mental disorders. There is an elevated risk of COVID-19-related hospitalization and death among participants with pre-existing mental disorders adjusting for key socio-demographic covariates (i.e., age, gender, race, ethnicity, residence, smoking). Co-occurrence of any two clusters was positively associated with COVID-19-related hospitalization and death. The odds ratio of being hospitalized was 2.50 (95%CI 2.284, 2.728) for patients with internalizing and externalizing disorders, 3.34 (95%CI 2.637, 4.228) for internalizing and thought disorders, 3.29 (95%CI 2.288, 4.733) for externalizing and thought disorders, and 3.35 (95%CI 2.604, 4.310) for three clusters of mental disorders.

Conclusions and RelevancePre-existing internalizing disorders, externalizing disorders, and thought disorders are positively related to COVID-19 hospitalization and death. Co-occurrence of any two clusters of mental disorders have elevated risk of COVID-19-related hospitalization and death compared to those with a single cluster.

category: infectious diseases


title: Social mixing patterns in the UK following the relaxation of COVID-19 pandemic restrictions: a cross-sectional online survey

abstract:
BackgroundSince 23 March 2020, social distancing measures have been implemented in the UK to reduce SARS-CoV-2 transmission. We conducted a cross-sectional survey to quantify and characterize non-household contact and to identify the effect of shielding and isolating on contact patterns.

MethodsThrough an online questionnaire, the CoCoNet study measured daily interactions and mobility of 5143 participants between 28 July and 14 August 2020. Negative binomial regression modelling identified participant characteristics associated with contact rates.

ResultsThe mean rate of non-household contacts per person was 2.9 d-1. Participants attending a workplace (adjusted incidence rate ratio (aIRR) 3.33, 95%CI 3.02 to 3.66), self-employed (aIRR 1.63, 95%CI 1.43 to 1.87) or working in healthcare (aIRR 5.10, 95%CI 4.29 to 6.10) reported significantly higher non-household contact rates than those working from home. Participants self-isolating as a precaution or following Test and Trace instructions had a lower non-household contact rate than those not self-isolating (aIRR 0.58, 95%CI 0.43 to 0.79). We found limited evidence that those shielding had reduced non-household contacts compared to non-shielders.

ConclusionThe daily rate of non-household interactions remains lower than pre-pandemic levels, suggesting continued adherence to social distancing guidelines. Individuals attending a workplace in-person or employed as healthcare professionals were less likely to maintain social distance and had a higher non-household contact rate, possibly increasing their infection risk. Shielding and self-isolating individuals required greater support to enable them to follow the government guidelines and reduce non-household contact and therefore their risk of infection.

Summary boxO_ST_ABSWhat is already known on this subject?C_ST_ABSO_LIThe introduction of social distancing guidelines in March 2020 reduced social contact rates in the UK.
C_LIO_LIEvidence of low levels of adherence to self-isolation.
C_LI

What does this study add?O_LIThis study provides quantitative insight into the social mixing patterns in the UK at the beginning of the second wave of SARS-CoV2 infection.
C_LIO_LIHealthcare professionals and individuals attending their workplace in-person were less able to follow social distancing guidelines and made more contact with people outside their household than those working from home.
C_LIO_LIShielding individuals did not make fewer non-household contacts than those not shielding.
C_LI


title: Modeling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil

abstract:
Among the various non-pharmaceutical interventions implemented in response to the COVID-19 pandemic during 2020, school closures have been in place in several countries to reduce infection transmission. Nonetheless, the significant short and long-term impacts of prolonged suspension of in-person classes is a major concern. There is still considerable debate around the best timing for school closure and reopening, its impact on the dynamics of disease transmission, and its effectiveness when considered in association with other mitigation measures. Despite the erratic implementation of mitigation measures in Brazil, school closures were among the first measures taken early in the pandemic in most of the 27 states in the country. Further, Brazil delayed the reopening of schools and stands among the countries in which schools remained closed for the most prolonged period in 2020. To assess the impact of school reopening and the effect of contact tracing strategies in rates of COVID-19 cases and deaths, we model the epidemiological dynamics of disease transmission in 3 large urban centers in Brazil under different epidemiological contexts. We implement an extended SEIR model stratified by age and considering contact networks in different settings - school, home, work, and elsewhere, in which the infection transmission rate is affected by various intervention measures. After fitting epidemiological and demographic data, we simulate scenarios with increasing school transmission due to school reopening.

Our model shows that reopening schools results in a non-linear increase of reported COVID-19 cases and deaths, which is highly dependent on infection and disease incidence at the time of reopening. While low rates of within-school transmission resulted in small effects on disease incidence (cases/100,000 pop), intermediate or high rates can severely impact disease trends resulting in escalating rates of new cases even if other interventions remain unchanged. When contact tracing and quarantining are restricted to school and home settings, a large number of daily tests is required to produce significant effects of reducing the total number of hospitalizations and deaths. Our results suggest that policymakers should carefully consider the epidemiological context and timing regarding the implementation of school closure and return of in-person school activities. Also, although contact tracing strategies are essential to prevent new infections and outbreaks within school environments, our data suggest that they are alone not sufficient to avoid significant impacts on community transmission in the context of school reopening in settings with high and sustained transmission rates.


title: Long-term health-related quality of life in non-hospitalised COVID-19 cases with confirmed SARS-CoV-2 infection in England: Longitudinal analysis and cross-sectional comparison with controls

abstract:
BackgroundThis study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D).

MethodsProspective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls.

ResultsOf 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of {pound}18.1 on non-prescription drugs (median: {pound}10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England.

ConclusionsOne in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

summaryLosses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.


title: Psychological Distress Before and During the COVID-19 Pandemic: Sociodemographic Inequalities in 11 UK Longitudinal Studies

abstract:
ImportanceHow population mental health has evolved across the COVID-19 pandemic under varied lockdown measures is poorly understood, with impacts on health inequalities unclear.

ObjectiveWe investigated changes in mental health and sociodemographic inequalities from before and across the first year of the COVID-19 pandemic in 11 longitudinal studies.

Design, Setting and ParticipantsData from 11 UK longitudinal population-based studies with pre-pandemic measures of psychological distress were jointly analysed and estimates pooled. Multi-level regression was used to examine changes in psychological distress from pre-pandemic to during the first year of the COVID-19 pandemic.

ExposuresTrends in the prevalence of poor mental health were assessed pre-pandemic (TP0) and at three pandemic time periods: initial lockdown (TP1, Mar-June 20); easing of restrictions (TP2, July-Oct 20); and a subsequent lockdown (TP3, Nov 20-Mar 21). We stratified analyses by sex, ethnicity, education, age, and UK country.

Main Outcomes and MeasuresPsychological distress was assessed using the General Health Questionnaire 12 (GHQ-12), Kessler-6, 9-item Malaise Inventory, Short Mood and Feelings Questionnaire (SMFQ), Patient Health Questionnaire-8 and 9 (PHQ-8/9), Hospital Anxiety and Depression Scale (HADS) and Centre for Epidemiological Studies - Depression (CES-D), across different studies.

ResultsIn total, 49,993 adult participants (61.2% female; 8.7% Non-White) were analysed. Across the 11 studies, mental health deteriorated from pre-pandemic scores across all three pandemic time periods, but with considerable heterogeneity across the study-specific effect sizes estimated (pooled estimate TP1 Standardised Mean Difference (SMD): 0.15 (95% CI: 0.06, 0.25); TP2 SMD: 0.18 (0.09, 0.27); TP3 SMD: 0.21 (0.10, 0.32)). Changes in psychological distress across the pandemic were higher in females (TP3 SMD: 0.23 (0.11, 0.35)) than males (TP3 SMD: 0.16 (0.06, 0.26)), and lower in below-degree level educated persons at TP3 (SMD: 0.18 (0.06, 0.30)) compared to those who held degrees (SMD: 0.26 (0.14, 0.38)). Increased psychological distress was most prominent amongst adults aged 25-34 and 35-44 years compared to other age groups. We did not find evidence of changes in distress differing by ethnicity or UK country.

Conclusions and RelevanceThe substantial deterioration in mental health seen in the UK during the first lockdown did not reverse when lockdown lifted, and a sustained worsening was observed across the pandemic. Mental health declines have been unequal across the population, with females, those with higher degrees, and those aged 25-44 years more affected.


title: Psychological Distress Before and During the COVID-19 Pandemic Among Adults in the United Kingdom: Coordinated Analyses of 11 Longitudinal Studies


title: The effect of social restrictions, loss of social support, and loss of maternal autonomy on postpartum depression in 1 to 12-months postpartum women during the COVID-19 pandemic

abstract:
BackgroundThis study focuses on postpartum women, who are one of the most vulnerable populations during the COVID-19 pandemic, aiming to reveal mental health consequences of social restrictions, loss of social support, or loss of autonomy.

MethodsA cross-sectional study for postpartum women was conducted in October 2020 (N = 600). The Edinburgh Postpartum Depression Scale (EPDS) was used to measure postpartum depression. The prevalence ratios were estimated by log-binomial regression models, adjusting for age, education, household income, residence area, parity, the timing of delivery, and a prior history of depression.

ResultsThe prevalence of postpartum depression was 28.7% (EPDS [≥] 9), 18.6% ([≥] 11), and 13.1% ([≥] 13). Social restrictions including cancellation of home visits by health care professionals, or cancellation of infant checkups or vaccinations, loss of support during pregnancy or after delivery including loss of opportunities to consult with health care professionals or friends, or cancellation of parents or other family members visits to support, and loss of autonomy about delivery or breastfeeding, were associated with postnatal depression.

ConclusionAbout 30% of women who delivered and raised a baby during the COVID-19 pandemic had postpartum depression, which is much higher than a pre-pandemic meta-analysis. COVID-19 related social restrictions or loss of social support from healthcare professionals, family, and friends were significantly associated with postpartum depression. Also, loss of maternal autonomy in delivery and breastfeeding is associated with postpartum depression. The results indicate that both formal and informal support should not be limited to prevent postpartum depression during the pandemic.


title: Household contact tracing with intensified tuberculosis and HIV screening in South Africa: a cluster randomised trial

abstract:
BackgroundHousehold contact tracing for tuberculosis (TB) may facilitate TB diagnosis and identify individuals who may benefit from TB preventive therapy (TPT). In this cluster-randomised trial, we investigated whether household contact tracing and intensive TB/HIV screening would improve TB-free survival.

MethodsHousehold contacts of index TB patients in two Provinces of South Africa were randomised to home tracing and intensive HIV/TB screening (sputum Xpert and culture; HIV testing with treatment linkage; and TPT, if eligible), or standard of care (SOC, clinic referral letters). The primary outcome was incident TB or death at 15-months. Secondary outcomes included tuberculin skin test (TST) positivity in children [≤]14 years and undiagnosed HIV. (ISRCTN16006202).

ResultsFrom December 2016-March 2019, 1,032 index patients (4,459 contacts) and 1,030 (4,129 contacts) were randomised to the intervention and SOC arms. 3.2% (69/2166) of intervention arm contacts had prevalent microbiologically-confirmed TB. At 15-months, the cumulative incidence of TB or death did not differ between the intensive screening (93/3230, 2.9%) and SOC (80/2600, 3.1%) arms (hazard ratio: 0.90, 95% confidence interval (CI): 0.66-1.24). TST positivity was higher in the intensive screening arm (38/845, 4.5%) compared to the SOC arm (15/800, 1.9%, odds ratio: 2.25, 95% CI: 1.07-4.72). Undiagnosed HIV was similar between arms (41/3185, 1.3% vs. 32/2543, 1.3%; odds ratio: 1.02, 95% CI: 0.64-1.64).

ConclusionsHousehold contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits in high TB/HIV-prevalence settings.

Author SummaryIn South Africa, household contacts of TB cases received referral letters or home-tracing with intensified TB/HIV screening. At 15-months, the cumulative incidence of TB or death did not differ between the intensive screening (93/3230, 2.9%) and SOC (80/2600, 3.1%) arms.


title: Perceived Stress Among Faculty and First Year Students at a College of Pharmacy

abstract:
PurposeFemale faculty and students could be affected by stressors disproportionately compared to male counterparts, especially those with children or family obligations. A study was undertaken to determine: 1) stress levels of pharmacy faculty and first-year pharmacy students; 2) whether gender affected faculty and/or student stress levels disproportionally; and 3) how child and family care responsibilities influenced stress levels.

MethodsAll first-year (P1) students enrolled in a College of Pharmacy were surveyed along with faculty. Stress levels were assessed using the Perceived Stress Scale (PSS10). Additional demographic information, including items related to children and family obligations, was collected.

ResultsFaculty reported average perceived stress levels (M=15.50) while first-year students reported high perceived stress levels (M=21.14). Perceived stress levels of female faculty (M=16.43) were higher than those of male faculty (M=12.00). Perceived stress levels of female students (M=22.60) were higher than those of male students (M=16.78). Perceived stress levels of female faculty with younger children (M=18.85) were higher than those of male faculty with younger children (M=9.67). Perceived stress levels of female students with [≥]10 hours of family obligations per week (M=22.71) were higher than male pharmacy students with [≥]10 hours (M=12.80).

ConclusionLower levels of perceived stress for faculty compared to students may be due to the development of coping strategies coinciding with maturity. Results suggest more time spent on family obligations is negatively associated with stress levels for females, but not males. Colleges of pharmacy should invest resources to help reduce stress levels in faculty and student populations, particularly for the female gender.

category: medical education


title: Safety and Effectiveness of COVID-19 SPUTNIK V Vaccine in Dialysis Patients

abstract:
Given the vulnerability of people with chronic kidney disease to COVID-19, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines confer the same high level of protection in patients with kidney disease. The aims of this study were to evaluate the safety measured by the events supposedly attributed to vaccines and the effectiveness evaluated by the presence of antibodies in dialysis patients immunized with the COVID-19 Sputnik V vaccine.

Methodsmulticenter, observational and analytical study of a prospective cohort of hemodialysis patients in the Autonomous City of Buenos Aires with a vaccination plan. Patients older than 18 years on dialysis who received both components of the COVID-19 vaccine were included.

Results491 patients included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9% 95% CI 33.6%-42.34%). The effectiveness analysis measures of antibodies against SARS-Cov-2 were performed in 102 patients, 98% had positive IgG against SARS-Cov-2 antibodies 21 days after the second component .In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to those patients who did not have COVID-19, and the rise between the last measures was lower than patients without COVID-19.

ConclusionDialysis patients constitute a vulnerable population for SARS-Cov-2 infection, beyond the recommendations that were implemented by dialysis units, full vaccination is a priority and necessary. The Sputnik V vaccine has been shown to be safe and effective in this patient population.


title: Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial

abstract:
IntroductionEvent free survival rates at 15 years for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia (ALL) are 30-50%, with 5-year survival for adult patients only 20%. A large proportion of patients with newly diagnosed and relapsed ALL harbour somatic mutations that activate the RAS-signalling cascade. Steroids are a backbone of all induction blocks of ALL therapy, with preclinical data suggesting the combination of dexamethasone with the MEK1/2 inhibitor, selumetinib (ARRY-142886), results in a potent synergistic anti-cancer effect.

Methods and analysisThe SeluDex trial is an international, parallel-group, dose-finding with expansion, phase I/II trial to assess the selumetinib/dexamethasone combination in adult and paediatric patients with relapsed/refractory, RAS pathway mutant ALL. The Cancer Research UK Clinical Trials Unit at University of Birmingham is the UK Coordinating Centre, with national hubs in Copenhagen, Denmark; Monza, Italy; Munster, Germany; Paris, France; and Utrecht, Netherlands. Paediatric centres are all part of the Innovative Therapies for Children with Cancer consortium. Patients with morphologically proven relapsed/refractory or progressive B-cell precursor or T-ALL, with demonstrated RAS pathway activating mutations are eligible. Adult patients are [≥]18 years old, ECOG [≤]2 and paediatric <18 years old, Lansky play scale [≥]60% or Karnofsky score [≥]60%. The primary objective in phase I is to determine the recommended phase II dose of selumetinib as defined by occurrence/non-occurrence of dose limiting toxicities using the continual reassessment method, and phase II will evaluate preliminary anti-leukaemic activity of the selumetinib/dexamethasone combination, as defined by morphological response 28 days post treatment using a Bayesian approach. Target recruitment is between 26 and 42 patients (minimum of 13 and maximum of 21 in each group), depending on how many phase I patients are included also in phase II.

Ethics and disseminationMedical ethical committees of all the participating countries will approve the study protocol. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration numberThe trial was registered on EudraCT 2016-003904-29 on 21st September 2016, ISRCTN 92323261, ClinicalTrials.Gov NCT03705507, and ITCC-063 study.

Strengths and limitations of this studyO_LINovel combination of the MEK1/2 inhibitor, selumetinib, with dexamethasone
C_LIO_LISeamless phase I/II Bayesian trial design with a Continual Reassessment Method for dose escalation in phase I
C_LIO_LIParallel cohort trial design of adult and paediatric patients within one protocol
C_LIO_LIAvailability of CAR T-cell therapy since this trial started recruitment has competed for the same patient population
C_LIO_LIOffers a bridging treatment option for patients awaiting CAR T-cell therapy outside clinical studies or at relapse after CAR-T treatment
C_LI

category: oncology


title: Acute Pain Pathways: protocol for a prospective cohort study

abstract:
IntroductionOpioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses.

Methods and analysisThis multi-center prospective observational study will recruit 1,550 opioid-naive participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments, and dental clinics. Participants will be followed for 6 months with the aid of a patient-centered health data aggregating platform that consolidates data from study questionnaires, electronic health record data on health care services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centered outcomes including resolution of pain, satisfaction with care, and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids.

Ethics and disseminationThis study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community, and the public.

Trial registration numberNCT04509115

Strengths and limitations of this studyO_LIThis study addresses a key knowledge gap by recruiting a large and diverse group of patients with acute pain, following them for 6 months, and prospectively assessing their pain experience and acute pain treatment
C_LIO_LIPatients will be recruited from multiple treatment settings that are important in the treatment of acute pain, including emergency departments, primary care, dental settings, and surgical settings.
C_LIO_LIA patient-centered health data aggregating platform reduces the patient burden of participating in the trial by allowing participants to complete questionnaires when it is convenient and by automatically collecting data on physical activity, healthcare service use, and prescription fills
C_LIO_LIAll participants will have been offered an opioid prescription, reducing the ability to compare outcomes across opioid and non-opioid pain medications
C_LIO_LIDespite a large sample size, there may be limited numbers of specific acute pain diagnoses with a sufficient sample to analyze and compare by condition/diagnosis
C_LI

category: pain medicine


title: An atlas of associations between polygenic risk scores from across the human phenome and circulating metabolic biomarkers

abstract: Polygenic risk scores (PRS) are becoming an increasingly popular approach to predict complex disease risk, although they also hold the potential to develop insight into the molecular profiles of patients with an elevated genetic predisposition to disease. In this study, we have constructed an atlas of associations between 129 different PRS and 249 circulating metabolites in up to 83,004 participants from the UK Biobank study. As an exemplar to demonstrate the value of this atlas we conducted a hypothesis-free evaluation of all associations with glycoprotein acetyls (GlycA), an inflammatory biomarker. Using bi-directional Mendelian randomization, we find that the associations highlighted likely reflect the effect of risk factors, such as body mass index (Beta=0.16 per standard deviation change in GlycA, 95% CI=0.11 to 0.21, P=9.9x10-10) or liability towards smoking cigarettes (Beta=0.28, 95% CI=0.20 to 0.35, P=2.4x10-14), on systemic inflammation as opposed to the converse direction of effect. Furthermore, we repeated all analyses in our atlas within age strata to investigate potential sources of collider bias, such as medication usage. This was exemplified by comparing associations between lipoprotein lipid profiles and the coronary artery disease PRS in the youngest and oldest age strata, which had differing proportions of individuals undergoing statin therapy. All results can be visualised at http://mrcieu.mrsoftware.org/metabolites_PRS_atlas.

category: genetic and genomic medicine


title: Genetically predicted levels of the human plasma proteome and risk of stroke: a Mendelian Randomization study

abstract:
Proteins are the effector molecules of biology and are the target of most drugs. To identify proteins and related pathways that may play a causal role in stroke pathogenesis, we used Mendelian randomisation (MR). We tested potential causal effects of 308 plasma proteins (measured in 4,994 blood donors from the INTERVAL study) on stroke outcomes (derived from the MEGASTROKE GWAS) in a two-sample MR framework and assessed whether these associations could be mediated by cardiovascular risk factors. We extended the analysis to identify whether pharmacological targeting of these proteins might have potential adverse side-effects or beneficial effects for other conditions through Phenome-wide MR (Phe-MR) in UK Biobank.

MR showed an association between stroke and genetically predicted plasma levels of TFPI, IL6RA, MMP12, CD40, TMPRSS5 and CD6 (P[≤]1.62x10-4). We identified six risk factors (atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes) that were associated with stroke (P[≤]0.0071) using MR. The association of TFPI, IL6RA and TMPRSS5 with stroke could be mediated by these risk factors, such as body mass index, white matter hyperintensity and atrial fibrillation. Thirty-six additional proteins were potentially causal for one or more of these risk factors. The Phe-MR suggested that targeting TFPI could have potential beneficial effects on other disorders of arteries and hyperlipidaemia in addition to stroke. Our results highlight novel causal pathways and potential therapeutic targets for stroke.


title: Unveiling sex-based differences in Parkinson Disease: a comprehensive meta-analysis of transcriptomic studies

abstract: In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinsons disease (PD) incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in PD as epidemiological and clinical features differ between males and females. To study sex bias in PD, we conducted a systematic review, tissue-specific meta-analyses of transcriptomic data from the frontal cortex (FC), striatum tissue (ST), and substantia nigra (SN), and a global meta-analysis of all 3 brain regions. We selected 7 PD studies that included sex information, analyzing 267 samples. The tissue-specific meta-analyses linked PD to the enhanced expression of MED31 in the female FC and the dysregulation of 237 genes in the SN. The global meta-analysis detected 15 genes with sex-differential patterns in PD, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein-protein interaction networks, and transcription factors that differed by sex. While male PD patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female PD patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. Overall, we believe that our findings will provide new insight into the perspective of sex in PD, thereby underscoring the importance of including sex information in future PD studies.


title: Unveiling Sex-based Differences in Parkinson's Disease: A Comprehensive Meta-analysis of Transcriptomic Studies


title: The Contribution of Pharmacogenetic Drug Interactions to 90-Day Hospital Readmissions: Preliminary Results from a Real-World Healthcare System

abstract: Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines exist for many medications commonly prescribed prior to hospital discharge, yet there is limited data regarding the contribution of gene-x-drug interactions to hospital readmissions. The present study evaluated the relationship between prescription of CPIC medications prescribed within 30 days of hospital admission and 90-day hospital readmission from 2010-2020 in a study population (N=10,104) who underwent sequencing with a 14-gene pharmacogenetic panel. The presence of at least one pharmacogenetic indicator for a medication prescribed within 30 days of hospital admission was considered a gene-x-drug interaction. Multivariable logistic regression analyzed the association between one or more gene-x-drug interactions with 90-day readmission. There were 2,211/2,354 (93.9%) admitted patients who were prescribed at least one CPIC medication. Univariate analyses indicated that the presence of at least one identified gene-x-drug interaction increased risk of 90-day readmission by more than 40% (OR=1.42, 95% confidence interval (CI) 1.09-1.84)(p=0.01). A multivariable model adjusting for age, race, sex, employment status, body mass index, and medical conditions, slightly attenuated the effect (OR=1.33, 95% CI 1.02-1.75)(p=0.04). Our results suggest that the presence of one or more CPIC gene-x-drug interactions increases the risk of 90-day hospital readmission, even after adjustment for demographic and clinical risk factors.


title: Trends in the conduct and reporting of clinical prediction model development and validation: a systematic review

abstract:
ObjectivesThis systematic review aims to provide further insights into the conduct and reporting of clinical prediction model development and validation over time. We focus on assessing the reporting of information necessary to enable external validation by other investigators.

Materials and MethodsWe searched Embase, Medline, Web-of-Science, Cochrane Library and Google Scholar to identify studies that developed one or more multivariable prognostic prediction models using electronic health record (EHR) data published in the period 2009-2019.

ResultsWe identified 422 studies that developed a total of 579 clinical prediction models using EHR data. We observed a steep increase over the years in the number of developed models. The percentage of models externally validated in the same paper remained at around 10%. Throughout 2009-2019, for both the target population and the outcome definitions, code lists were provided for less than 20% of the models. For about half of the models that were developed using regression analysis, the final model was not completely presented.

DiscussionOverall, we observed limited improvement over time in the conduct and reporting of clinical prediction model development and validation. In particular, the prediction problem definition was often not clearly reported, and the final model was often not completely presented.

ConclusionImprovement in the reporting of information necessary to enable external validation by other investigators is still urgently needed to increase clinical adoption of developed models.

category: health informatics


title: Provider preferences for delivery of HIV care coordination services: results from a discrete choice experiment

abstract:
IntroductionThe PROMISE study was launched in 2018 to assess and document the implementation of changes to an existing HIV Care Coordination Program (CCP) designed to address persistent disparities in care and treatment engagement among persons with HIV in New York City. We evaluated provider endorsement of features of the CCP to identify opportunities for improvement.

MethodsWe used a discrete choice experiment (DCE) to measure provider endorsement of four CCP attributes, including: a) how CCP helps with medication adherence, b) how CCP helps with primary care appointments, c) how CCP helps with issues other than primary care, and d) where CCP visits take place (visit location). Each attribute had three to four levels. Our primary outcomes were relative importance and part-worth utilities, measures of preference for the levels of the four CCP program attributes.

ResultsVisit location (28.6%) had the highest relative importance, followed by how staff help with ART adherence (24.3%), how staff help with issues other than primary care (24.2%), and how staff help with primary care appointments (22.9%). Within each of the above attributes, respectively, the levels with the highest part-worth utilities were home visits 60 minutes from the program or agency (19.9 utiles, 95% CI 10.7-29.0), directly observed therapy (26.1 utiles, 95% CI 19.1-33.1), help with non-HIV specialty medical care (26.5 utiles, 95% CI 21.5-31.6), and reminding clients about and accompanying them to primary care appointments (20.8 utiles, 95% CI 15.6-26.0).

ConclusionsOngoing CCP refinements should account for how best to support and evaluate the intensive CCP components endorsed by providers in this study.

category: hiv aids


title: SARS-CoV-2 Receptor Binding Domain IgG Response to AstraZeneca (AZD1222) COVID-19 Vaccination, Jamaica

abstract: The Caribbean region is lacking an assessment of the antibody response and side effects experienced after AstraZeneca COVID-19 vaccination (AZD1222). We examined SARS-CoV-2 spike receptor binding domain (RBD) IgG levels and reported side effects in a Jamaican population after AZD1222 vaccination. Median RBD IgG levels for persons without evidence of previous SARS-CoV-2 infection were 43.1 bIU/mL after 3-7 weeks post first dose, rising to 100.1 bIU/mL 3-7 weeks post second dose, and falling 46.9 bIU/mL 16-22 weeks post second dose. The median RBD IgG level 2-8 weeks after symptom onset for unvaccinated SARS-CoV-2 infected persons of all disease severities was 411.6 bIU/mL. Common AZD1222 side effects after first dose were injection site pain, headache and chills. Most persons reported no side effects after second dose. AZD1222 is widely used across the English-speaking Caribbean and the study provides evidence for its continued safe and effective use in vaccination programs.


title: The Impact of SARS-CoV-2 Lineages (Variants) on the COVID-19 Epidemic in South Africa

abstract: Emerging SARS-CoV-2 variants have been attributed to the occurrence of secondary and tertiary COVID-19 epidemic waves and also threatening vaccine efforts due to their immune invasiveness. Since the importation of SARS-CoV-2 in South Africa, with the first reported COVID-19 case on the 5th of March 2020, South Africa has observed 3 consecutive COVID-19 epidemic waves. The evolution of SARS-CoV-2 has played a significant role in the resurgence of COVID-19 epidemic waves in South Africa and across the globe. South Africa has a unique observation of the evolution of SARS-CoV-2, with distinct SARS-CoV-2 lineages dominating certain epidemic periods. This unique observation allows for an investigation of the detected SARS-CoV-2 lineages impact on COVID-19 transmissibility and severity through analysis of epidemiological data. In this study, inferential statistical analysis was conducted on South African COVID-19 epidemiological data to investigate the impact of SARS-CoV-2 lineages in the South African COVID-19 epidemiology. The general methodology in this study involved the collation of South African COVID-19 epidemiological data, the regression and normalisation of the epidemiological data, and inferential statistical analysis. This study shows that the evolution of SARS-CoV-2 resulted in an increase in COVID-19 transmissibility and severity in South Africa. The Delta SARS-CoV-2 VOC resulted in increased COVID-19 transmissibility in the South African population by 53.9 to 54.8 % more than the Beta SARS-CoV-2 VOC and the predominantly B.1.1.54, B.1.1.56 C.1 SA SARS-CoV-2 lineage cluster. The Beta SARS-CoV-2 VOC resulted in more severe COVID-19 in South Africa than the Delta SARS-CoV-2 VOC. While, both the Beta and Delta SARS-CoV-2 VOC resulted in more severe COVID-19 than the initial SARS-CoV-2 lineages detected in South Africas first epidemic wave period. The Delta, Beta SARS-CoV-2 VOCs and the predominantly B.1.1.54, B.1.1.56 C.1 SA SARS-CoV-2 lineage cluster were observed to cause similar COVID-19 hospital case fatality and discharge rates in South African hospitals.


title: A comprehensive framework to estimate the frequency, duration and risk factors for diagnostic delays using simulation-based methods

abstract: The incidence of diagnostic delays is unknown for many diseases and particular healthcare settings. Many existing methods to identify diagnostic delays are resource intensive or inapplicable to various diseases or settings. In this paper we propose a comprehensive framework to estimate the frequency of missed diagnostic opportunities for a given disease using real-world longitudinal data sources. We start by providing a conceptual model of the disease-diagnostic, data-generating process. We then propose a simulation-based method to estimate measures of the frequency of missed diagnostic opportunities and duration of delays. This approach is specifically designed to identify missed diagnostic opportunities based on signs and symptoms that occur prior to an initial diagnosis, while accounting for expected patterns of healthcare that may appear as coincidental symptoms. Three different simulation algorithms are described for implementing this approach. We summarize estimation procedures that may be used to parameterize the simulation. Finally, we apply our approach to the diseases of tuberculosis, acute myocardial infarction, and stroke and evaluate the estimated frequency and duration of diagnostic delays for these diseases. Our approach can be customized to fit a range of disease and we summarize how the choice of simulation algorithm may impact the resulting estimates.


title: Effects of Confounding Bias in COVID-19 and Influenza Vaccine Effectiveness Test-Negative Designs Due to Correlated Influenza and COVID-19 Vaccination Behaviors

abstract:
BackgroundThe test-negative design is commonly used to estimate influenza and COVID-19 vaccine effectiveness (VE). In these studies, correlated COVID-19 and influenza vaccine behaviors may introduce a confounding bias where controls are included with the other vaccine-preventable acute respiratory illness (ARI). We quantified the impact of this bias on VE estimates in studies where this bias is not addressed.

MethodsWe simulated study populations under varying vaccination probabilities, COVID-19 VE, influenza VE, and proportions of controls included with the other vaccine-preventable ARI. Mean bias was calculated as the difference between true and estimated VE. Absolute mean bias in VE estimates was classified as low (<10%), moderate (10% to <20%), and high ([≥]20%).

ResultsWhere vaccination probabilities are positively correlated, COVID-19 and influenza VE test-negative studies with influenza and SARS-CoV-2 ARI controls, respectively, underestimate VE. For COVID-19 VE studies, mean bias was low for all scenarios where influenza represented [≤]50% of controls. For influenza VE studies, mean bias was low for all scenarios where SARS-CoV-2 represented [≤]10% of controls. Although bias was driven by the conditional probability of vaccination, low VE of the vaccine of interest and high VE of the confounding vaccine increase its magnitude.

ConclusionsWhere a low percentage of controls are included with the other vaccine-preventable ARI, bias in COVID-19 and influenza VE estimates is low. However, influenza VE estimates are likely more susceptible to bias. Researchers should consider potential bias and its implications in their respective study settings to make informed methodological decisions in test-negative VE studies.


title: Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis

abstract:
Background and AimsNon-alcoholic steatohepatitis (NASH) is the most common cause of liver disease contributing to significant disease burden worldwide. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs.

Approach & ResultsMedline, EMBASE and CENTRAL were searched for articles evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid, and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis.

From the 48 trials included, treatments modulating energy (Risk ratio (RR): 1.84, Credible intervals (Crl): 1.29 - 2.65) were the most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.68, Crl: 0.55 - 5.28), bile acids (RR: 1.34, Crl: 0.78 - 2.26) and inflammation (RR: 0.94, Crl: 0.59 - 1.46). Energy and bile acids modulation were effective in 2-point NAS reduction without worsening of fibrosis (RR: 1.60, Crl 1.13 - 2.30 and RR: 1.79, Crl 1.14 - 2.86) and 1-point fibrosis (RR: 1.27, Crl:1.05 - 1.52 and RR: 1.54, Crl: 1.20 - 1.97).

ConclusionsThis network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.

category: gastroenterology


title: Stool Antigen Test is Effective and Sensitive for Detecting Helicobacter Pylori Infection in Bangladeshi Peptic Ulcer Patients

abstract:
AimsHelicobacter pylori (H. pylori) is the primary causative agent of peptic ulcer in multiple developing countries, including Bangladesh. This study was designed to investigate the diagnostic value of a rapid immunochromatography-based H. Pylori stool antigen (HpSAg) test to screen H. pylori infection in Bangladeshi population.

Methodology and resultsA total of 140 suspected peptic ulcer patients who underwent upper gastrointestinal endoscopy at Chittagong Medical College and Hospital, Chattogram, Bangladesh, were included in the study. Histopathology, Rapid Urease Test (RUT), and Microscopic examination of the stained smears were conducted to define H. pylori positive cases. Later, stool antigen detection test was done in H. pylori positive status group, H. pylori negative status group, indeterminate status group, and healthy controls. Out of 140 peptic ulcer suspected patients, 75 (53.6%) patients were confirmed to have peptic ulcer or erosions. Although the proportion of antral erosion was 57.4% in patients who were below 40 years, the proportion decreased to 23.4% in patients over 40 years. Patients over 40 years were mostly suffering from Prepyloric erosion (42.9%). All peptic ulcer patients were also positive on histopathological analysis. However, micorscopic grading of curved bacilli and RUT found 93.3% (70/75) and 89.3% (67/75) patients positive, respectively. High sensitivity (95%), specificity (80%), and diagnostic accuracy (91%) scores for HpSAg assay was obtained in our study.

Conclusions, significance and impact of studiesThe HpSAg test, for a comparatively less sophisticated assay, can be efficient in detecting the presence of H. pylori pre-and post-therapy and provide more valid test results than other invasive test methods.


title: Aligning staffing schedules with testing and isolation strategies reduces the risk of COVID-19 outbreaks in carceral and other congregate settings: A simulation study

abstract:
COVID-19 outbreaks in congregate settings remain a serious threat to the health of disproportionately affected populations such as people experiencing incarceration or homelessness, the elderly, and essential workers. An individual-based model accounting for individual infectiousness over time, staff work schedules, and testing and isolation schedules was developed to simulate community transmission of SARS-CoV-2 to staff in a congregate facility and subsequent transmission within the facility that could cause an outbreak. Systematic testing strategies in which staff are tested on the first day of their workweek were found to prevent up to 16% more transmission events than testing strategies unrelated to staff schedules. Testing staff at the beginning of their workweek, implementing timely isolation following testing, limiting test turnaround time, and increasing test frequency in high transmission scenarios can supplement additional mitigation measures to aid outbreak prevention in congregate settings.

Article summary lineAligning routine testing with work schedules among staff in carceral facilities and other congregate settings can enhance the early detection and isolation of COVID-19 cases, limiting the potential for staff to inadvertently trigger outbreaks in high-risk settings.


title: Practices, norms, and aspirations regarding the construction, validation, and reuse of code sets in the analysis of real-world data

abstract:
ObjectiveCode sets play a central role in analytic work with clinical data warehouses, as components of phenotype, cohort, or analytic variable algorithms representing specific clinical phenomena. Code set quality has received critical attention and repositories for sharing and reusing code sets have been seen as a way to improve quality and reduce redundant effort. Nonetheless, concerns regarding code set quality persist. In order to better understand ongoing challenges in code set quality and reuse, and address them with software and infrastructure recommendations, we determined it was necessary to learn how code sets are constructed and validated in real-world settings.

MethodsSurvey and field study using semi-structured interviews of a purposive sample of code set practitioners. Open coding and thematic analysis on interview transcripts, interview notes, and answers to open-ended survey questions.

ResultsThirty-six respondents completed the survey, of whom 15 participated in follow-up interviews. We found great variability in the methods, degree of formality, tools, expertise, and data used in code set construction and validation. We found universal agreement that crafting high-quality code sets is difficult, but very different ideas about how this can be achieved and validated. A primary divide exists between those who rely on empirical techniques using patient-level data and those who only rely on expertise and semantic data. We formulated a method- and process-based model able to account for observed variability in formality, thoroughness, resources, and techniques.

ConclusionOur model provides a structure for organizing a set of recommendations to facilitate reuse based on metadata capture during the code set development process. It classifies validation methods by the data they depend on -- semantic, empirical, and derived -- as they are applied over a sequence of phases: (1) code collection; (2) code evaluation; (3) code set evaluation; (4) code set acceptance; and, optionally, (5) reporting of methods used and validation results. This schematization of real-world practices informs our analysis of and response to persistent challenges in code set development. Potential re-users of existing code sets can find little evidence to support trust in their quality and fitness for use, particularly when reusing a code set in a new study or database context. Rather than allowing code set sharing and reuse to remain separate activities, occurring before and after the main action of code set development, sharing and reuse must permeate every step of the process in order to produce reliable evidence of quality and fitness for use.


title: A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting

abstract: These studies aimed to further understand the antiviral effects of safe, visible light and demonstrate a therapeutic effect of an investigational treatment device for outpatients with mild to moderate COVID-19. RD-X19 is a handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses that are well-tolerated in an in vitro human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of IL-1 and IL-1{beta} cytokines with corresponding inhibition of SARS-CoV-2 replication. A randomized, double-blind, sham-controlled early feasibility study using the investigational device enrolled 31 subjects with a positive SARS-CoV-2 antigen test and possessing at least two moderate COVID-19 signs and symptoms. Subjects were randomized 2:1 (RD-X19 to sham), treated twice daily for four days, and evaluated over one week. Prespecified outcome measures included assessments of SARS-CoV-2 viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. The time-weighted average change in log viral load throughout the study demonstrated a favorable reduction for RD-X19 compared to sham and at the end of study the mean change in log10 viral load was -3.29 for RD-X19 and -1.81 for sham at Day 8, demonstrating a treatment benefit of -1.48 [95% confidence internal (CI), -2.88 to -0.071]. Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-hour reduction of median time to sustained resolution of COVID-19 signs and symptoms.


title: The Genetic Determinants of Aortic Distension

abstract: As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous blood delivery to peripheral arteries. Distension during systole and recoil during diastole conserves ventricular energy and is enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and prematurely in vascular disease. To discover genetic determinants of aortic distensibility we trained a deep learning model to quantify aortic size throughout the cardiac cycle and calculate aortic distensibility and aortic strain in 42,342 participants in the UK Biobank with available cardiac magnetic resonance imaging. In up to 40,028 participants with genetic data, common variant analysis identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were specific to strain or distensibility and were not identified in a thoracic aortic diameter GWAS within the same samples. Loci associated with both aortic diameter and aortic strain or distensibility demonstrated a consistent, inverse directionality. Transcriptome-wide analyses, rare-variant burden tests, and analyses of gene expression in single nucleus RNA sequencing of human aorta were performed to prioritize genes at individual loci. Loci highlighted multiple genes involved in elastogenesis, matrix degradation, and extracellular polysaccharide generation. Characterization of the genetic determinants of aortic function may provide novel targets for medical intervention in aortic disease.

category: cardiovascular medicine


title: From Feasibility to Utility: A Meta-Analysis of Amygdala-Neurofeedback

abstract:
Amygdala dysregulation is core to multiple psychiatric disorders. Real-time fMRI enables Amygdala self-modulation through NeuroFeedback (NF).

Despite a surge in Amygdala-NF studies, a systematic quantification of self-modulation is lacking. Amygdala-NF dissemination is further restricted by absence of unifying framework dictating design choices and insufficient understanding of neural changes underlying successful self-modulation.

The current meta-analysis of Amygdala-NF literature found that real-time feedback facilitates learned self-modulation more than placebo. Intriguingly, while we found that variability in design choices could be explained by the targeted domain, this was rarely highlighted by authors. Lastly, reanalysis of six fMRI data-sets (n=151), revealed that successful Amygdala down-modulation is coupled with deactivation of posterior insula and Default-Mode-Network major nodes, pointing to regulation related processes.

While findings point to Amygdala self-modulation as a learned skill that could modify brain functionality, further placebo-controlled trials are necessary to prove clinical efficacy. We further suggest that studies should explicitly target neuro-behavioral domain, design studies accordingly and include  target engagement measures. We exemplify this idea through a  process-based NF approach for PTSD.


title: Disease waves of SARS-CoV-2 in Iran closely mirror global pandemic trends

abstract:
SARS-CoV-2 genome surveillance projects provide a good measure of transmission and monitor the circulating SARS-CoV-2 variants at regional and global scales. Iran is one of the most affected countries still involved with the virus circulating in at least five significant disease waves, as of September 2021. Complete genome sequencing of 50 viral isolates in an early phase of outbreak in Iran, shed light on the origins and circulating lineages at that time. As part of a genomic surveillance program, we provided an additional 319 complete genomes from October 2020 onwards. The current study is the report of complete SARS-CoV-2 genome sequences of Iran in the March 2020-May 2021 time interval. We aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year.

Overall, 35 different lineages and 8 clades were detected. Temporal dynamics of the prominent SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and introduces the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades, dominating second, third and fourth disease waves, respectively. We observed a mixture of circulating 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7) clades in winter 2021, paralleled in a diminishing manner for 20A/20B and a growing rise for 20I, eventually prompting the 4th outbreak peak. Furthermore, our study provides evidence on the entry of the Delta variant in April 2021, leading to the 5th disease wave in summer 2021.

Three lineages are highlighted as hallmarks of SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (specific B.1.1 lineage carrying a combination of [D138Y-S477N-D614G] spike mutations) in October 2020-February 2021, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak.

Continuous monthly monitoring of SARS-CoV-2 genome mutations led to the detection of 1577 distinct nucleotide mutations, in which the top recurrent mutations were D614G, P323L, R203K/G204R, 3037C>T, and 241C>T; the renowned combination of mutations in G and GH clades. The most frequent spike mutation is D614G followed by 13 other frequent mutations based on the prominent circulating lineages; B.1.1.7 (H69_V70del, Y144del, N501Y, A570D, P681H, T716I, S982A, D1118H, I100T, and L699I), B.1.1.413 (D138Y, S477N) and B.1.36 (I210del).

In brief, mutation surveillance in this study provided a real-time comprehensive picture of the SARS-CoV-2 mutation profile in Iran, which is beneficial for evaluating the magnitude of the epidemic and assessment of vaccine and therapeutic efficiency in this population.


title: Salicylic acid and risk of colorectal cancer: a two sample Mendelian randomization study

abstract:
BackgroundSalicylic acid (SA) is a metabolite that can be obtained from the diet via fruit and vegetable ingestion, of which increased consumption has observationally been shown to decrease risk of colorectal cancer (CRC). Whilst primary prevention trials of SA and CRC risk are lacking, there is strong evidence from clinical trials and prospective cohort studies that aspirin (acetylsalicylic acid) is an effective primary and secondary chemopreventative agent. Since aspirin is rapidly deacetylated to form SA, it follows that SA may have a central role for aspirin chemoprevention. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, and whether aspirin intake as a proxy for increased SA levels was required to identify an effect.

Methods and FindingsA two sample MR analysis was carried out using genome-wide association study summary statistics of SA from INTERVAL and EPIC-Norfolk (N= 14,149) and CRC from Colon Cancer Family Registry (CCFR), Colorectal Cancer Transdisciplinary Study (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). The Darmkrebs: Chancen der Verhutung durch Screening (DACHS) study (4,410 cases and 3,441 controls) was used for replication and stratification of aspirin-users and non-users. Single nucleotide polymorphisms (SNPs) for SA were selected via three methods: (1) Functional SNPs that influence aspirin and SA metabolising enzymes activity; (2) Pathway SNPs, those that are present in the coding regions of genes involved in aspirin and SA metabolism; and (3) genome-wide significant SNPs associated with levels of circulating SA.

No association was found between the functional SNPs and SA levels, therefore they were not taken forward in an MR analysis. We identified 2 pathway SNPs (explaining 0.03% of the variance in SA levels and with an F statistic of 1.74) and 1 genome-wide independent SNP (explaining 0.05% of the variance and with an F statistic of 7.44) to proxy for SA levels. Using the pathway SNPs, an inverse variance weighted approach found no association between an SD increase in SA and CRC risk (GECCO OR:1.03, 95% CI: 0.84-1.27 and DACHS OR:1.10, 95% CI:0.58-2.07) and no association was found upon stratification between aspirin users and non-users in the DACHS study (OR:0.93, 95% CI:0.23-3.73 and OR:1.24, 95% CI:0.57-2.69, respectively). Wald ratio results using the genome-wide SNP also showed no association between an SD increase in SA and CRC risk (GECCO OR: 1.08, 95% CI:0.86-1.34 and DACHS OR: 1.01, 95% CI:0.44-2.31) and no effect was observed upon stratification by aspirin use (users OR:0.66, 95% CI: 0.11-4.12 and non-users OR: 1.12, 95% CI: 0.42-2.97).

ConclusionsWe found no evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use. However, based on the calculated variance explained by the SNPs and the F statistic, we acknowledge the possibility of weak instrument bias and the need to find better instruments for SA levels.


title: Safety and Efficacy of Daclatasvir with Sofosbuvir and Ribavirin in Hepatitis C Virus Infection: A Real World Experience from South Punjab, Pakistan

abstract:
Background & ObjectivesSofosbuvir (SOF) and daclatasvir (DCV) in combination with ribavirin (RBV) drastically changed the treatment scenario of chronic hepatitis C (CHC) patients, achieving remarkable efficacy and safety profile. Real world experience of SOF/DCV/RBV combination in this part of Asia was scant. This study aimed to evaluate the efficacy and safety of SOF/DCV/RBV combination to treat CHC patients at a tertiary care hospital in South Punjab.

MethodsPatients of CHC of any genotype were enrolled prospectively. They were treated with 12 weeks course of SOF/DCV/RBV combination. Effectiveness was evaluated by end of treatment response (ETR) and sustained virological response (SVR) at 12 and 24 weeks post-treatment. Adverse events were recorded for safety analysis.

ResultsWe analyzed data of 102 patients of CHC (40 males and 62 females). The mean age was 40.04 + 10.22 years. Mean weight was 67.24 + 11.78 kg, while mean body mass index (BMI) was 26.32 + 4.58 kg/m2. Eighty patients belonged to low socio-economic status, while 22 belonged to middle socio-economic status. Sixty-four had a rural background, while 38 were from urban background. Seventy-four patients had no co-morbid condition; 16 (15.7%) had diabetes and 12 (11.8%) patients had co-morbid hypertension. Ninety percent of the patients did not have cirrhosis; 6% had compensated liver disease, while 4 % had decompensated liver disease. All the patients achieved undetectable HCV RNA at the end of treatment and 12 weeks after completion of treatment, while SVR at 24 weeks was achieved in 98% of patients. Only 2 patients discontinued treatment as a result of side effects. The most common side effects reported include fatigue, headache and fever.

ConclusionCHC is a grave problem in developing countries like Pakistan. The SOF/DCV/RBV combination is very effective in eradicating CHC and has a very good side effect profile as well.


title: Seroconversion rate and socioeconomic and ethnic risk factors for SARS-CoV-2 infection in children in a population-based cohort

abstract:
IntroductionSocioeconomic and ethnic background have been discussed as possible risk factors for SARS-CoV-2 infections in children. Improved knowledge could lead way to tailored prevention strategies and help to improve infection control.

MethodsObservational population-based cohort study in children (6mo. - 18 ys.) scheduled for legally required preventive examination and their parents in a metropolitan region in Germany. Primary endpoint was the SARS-CoV-2 seroconversion rate during study period. Risk factors assessed included age, pre-existing medical conditions, socioeconomic factors, and ethnicity.

Results2124 children and their parents were included. Seroconversion rates among children in all age groups increased by 3-4-fold from 06/2020 to 02/2021. Only 41% of seropositive children were symptomatic. In 51% of infected children at least one parent was also SARS-CoV-2 positive.

Low level of parental education (OR 3.13 (0.72-13.69)) significantly increased the risk of infection. Of the total cohort, 38.5% had a migration background. Specifically, 9% were of Turkish and 5% of Middle Eastern origin. These children had the highest risk for SARS-CoV-2 infections (OR 6.24 (1.38-28.12) and 6.44 (1.14-36.45) after adjustment for other risk factors.

DiscussionSeroprevalence of SARS-CoV-2 infections in children increased by 3-4-fold within the study period. Frequently, more than one family member was infected. Children from families with lower socioeconomic status were at higher risk. The highest risk for SARS-CoV-2 infection was identified in families with Turkish or Middle Eastern background. Culture sensitive approaches are essential to improve infection control and serve as a blueprint for vaccination strategies in this population.

Trial RegistrationBMBF funding registration 01KI20173 (Corkid)

category: pediatrics


title: Domestic violence, mental health, and repeat self-harm in Sri Lanka

abstract:
BackgroundEvidence on the risk factors for repeat self-harm from low- and middle-income countries is scarce and requires urgent attention.

AimsWe sought to examine psychosocial correlates of repeat self-harm in Kandy, Sri Lanka.

MethodsLogistic regression models (adjusting for age and sex) were used to examine associations between study factors and repeat self-harm among adult patients (N=292) admitted for self-poisoning.

ResultsDepression (OR 2.8 95% CI 1.7-4.7), prior psychiatric diagnosis (OR 4.8 95% CI 2.2-10.2), past-year exposure to suicidal behaviour (OR 1.9 95% 1.1-3.3), physical/sexual abuse (OR 3.0 95% CI 1.3-6.9), and psychological abuse (OR 2.3 95% CI 1.3-4.2) were strongly associated with repeat self-harm.

ConclusionsIdentification and management of domestic violence and psychiatric morbidity should be part of routine clinical assessments of patients presenting with self-harm.


title: Main COVID-19 information sources in a culturally and linguistically diverse community in Sydney, Australia: A cross-sectional survey

abstract:
BackgroundLittle is known about COVID-19 information-seeking experiences for culturally and linguistically diverse groups in Australia.

MethodsParticipants were recruited using a cross-sectional survey from March 21 to July 9, 2021, translated into 11 languages, and with supporting bilingual staff. Linear regression models identified factors associated with difficulty finding easy-to-understand COVID-19 information.

ResultsAcross 708 participants (88% born overseas, 31% poor English proficiency), difficulty finding easy-to-understand COVID-19 information was rated 4.13 for English materials (95%CI: 3.85 to 4.41) and 4.36 for translated materials (95%CI: 4.07 to 4.66) (1 easy to 10 hard). Participants who were older (p<0.001), had inadequate health literacy (Mean Difference (MD)=-1.43, 95%CI -2.03 to - 0.82, p<0.001), or poor English proficiency (MD=-1.9, 95%CI-2.51 to -1.29, p<0.001) found it harder to find easy-to-understand English-language COVID-19 information. Those who had greater difficulty finding easy-to-understand translated COVID-19 information were younger (p=0.004), had poor English proficiency (MD=-1.61, 95%CI -2.29 to -0.9, p<0.001), university education (MD=0.77, 95%CI 0.00 to 1.53, p=0.05), and had spent longer living in Australia (p=0.001). They were more likely to rely on friends and family for COVID-19 information (p=0.02). There was significant variation in information-seeking experiences across language groups (ps<0.001).

ConclusionsEasy-to-understand and accessible COVID-19 information is needed to meet the needs of people in culturally and linguistically diverse communities. This approach should involve working alongside these communities to tailor messages and leverage existing communication channels.


title: MRI based Kidney Radiomics analysis during chronic lithium treatment: validation of a texture index associated with decreased kidney function.

abstract:
BackgroundChronic lithium therapy is associated with an increased risk of chronic kidney disease (CKD). Lithium nephrotoxicity is slowly progressive and difficult to detect at early stages. The aim of this study was to identify specific image texture changes of kidneys as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomic analysis of T2 weighted imaging magnetic resonance imaging.

MethodsOne hundred and nine patients treated with lithium carbonate were evaluated including mGFR and Kidney MRI, with T2 weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after a manual kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect a decreased mGFR <60 ml/min/1.73m2. The texture index was internally validated using a training and a validation cohort.

ResultsTexture analysis index was able to detect a decrease in mGFR, with an Area Under the Curve (AUC) of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 [42-66] versus 46 [34-54] years, p=0.001), with longer treatment duration (10 [3-22] versus 6 [2-10] years, p=0.02), and a lower mGFR (66 [46-84] versus 83 [71-94] ml/min/1.73m2, p<0.001). Texture analysis index was independently and negatively associated with age ({beta}= -0.004 {+/-}0.001, p<0.001), serum vasopressin (-0.005 {+/-} 0.002, p=0.02), lithium treatment duration (-0.01 {+/-} 0.003, p=0.001), with a significant interaction between lithium treatment duration and mGFR (p=0.02).

ConclusionA renal texture index was developed and validated among patients treated with lithium carbonate associated with a decreased mGFR. This index might be relevant in the diagnosis and prognosis of lithium-induced renal toxicity.

category: radiology and imaging