title: Impact assessment of mobility restriction, testing, and vaccination on the COVID-19 pandemic in India

abstract:
BackgroundBefore the availability of vaccines, countries largely relied on mobility restriction and testing to mitigate the COVID-19 pandemic. Our aim is to assess the combined impact of mobility restriction, testing, and vaccination on the COVID-19 pandemic in India.

MethodsWe conducted a multiple regression analysis to assess the impact of mobility, testing, and vaccination on COVID-19 incidence between April 28, 2021 to November 24, 2021 using data from Our World in Data and Google Mobility Report. The 7-day moving average was applied to offset the daily fluctuations in the mobility and testing. Each independent variable was lagged to construct a temporal relationship, and waning vaccination efficacy was taken into consideration. We performed additional analysis for three time periods between March 28, 2020 to November 24, 2021 (1st: March 28, 2020 [~] October 7, 2020, 2nd: October 8, 2020 [~] April 27, 2021, 3rd: April 28, 2021 [~] November 24, 2021) to examine potential heterogeneity over time.

ResultsMobility (0.041, 95% CI: 0.033 to 0.048), testing (-0.008, 95% CI: -0.015 to -0.001), and vaccination (quadratic term: 0.004, 95% CI: 0.003 to 0.005, linear term: -0.130, 95% CI: -0.161 to -0.099) were all associated with COVID-19 incidence. For vaccination rate, the decrease of number of cases demonstrated a U-shaped curve, while mobility showed a positive association and testing showed an inverse association with COVID-19 incidence. Mobility restriction was effective during all three periods - March 28, 2020 to November 24, 2021 (0.009, 0.048, and 0.026 respectively). Testing was effective during the second and third period - October 8, 2020 to November 24, 2021 (-0.036, and -0.006 respectively).

ConclusionMobility restriction and testing were effective even in the presence of vaccination. This shows the positive value of mobility restrictions, testing, and vaccination from the health system perspective on COVID-19 prevention and control, especially with continual emergence of variants in India and globally. At the same time, this health system gain must be balanced with the challenges in the delivery of non-COVID health services and broader socio-economic impact in deciding the prolonged continuance of mobility restriction.

category: public and global health


title: Altered Cerebral Blood Flow in Older Adults with Alzheimer's Disease: A Systematic Review

abstract: The prevalence of Alzheimers disease is projected to reach 13 million in the U.S. by 2050. Although major efforts have been made to avoid this outcome, so far there are no treatments that can stop or reverse the progressive cognitive decline that defines Alzheimers disease. The utilization of preventative treatment before significant cognitive decline has occurred may ultimately be the solution, necessitating a reliable biomarker of preclinical/prodromal disease stages to determine which older adults are most at risk. Quantitative cerebral blood flow is a promising potential early biomarker for Alzheimers disease, but the spatiotemporal patterns of altered cerebral blood flow in Alzheimers disease are not fully understood. The current systematic review compiles the findings of 29 original studies that compared quantitative cerebral blood flow in older adults with mild cognitive impairment or Alzheimers disease to that of cognitively normal older adults and/or assessed the relationship between cerebral blood flow and objective cognitive function. Individuals with Alzheimers disease had relatively decreased cerebral blood flow in all brain regions investigated, especially the temporoparietal and posterior cingulate, while individuals with mild cognitive impairment had less consistent results, with relatively increased cerebral blood flow reported in the temporal lobe and thalamus. Most papers reported a positive correlation between cerebral blood flow and cognitive function. This review highlights the need for more studies comparing cerebral blood flow between cognitively normal individuals and those with mild cognitive impairment, as well as the importance of including potential confounding factors in these analyses.

category: radiology and imaging


title: T1/T2 Ratio Imaging Improves Cortical Lesion Contrast in Multiple Sclerosis on 3T MRI

abstract:
BackgroundCortical demyelinated lesions are prevalent in multiple sclerosis (MS) and associated with disability; their presence on MRI has recently been incorporated into MS diagnostic criteria. Presently, advanced and ultra-high-field MRI -- not routinely available in clinical practice -- are the most sensitive methods for detection of cortical lesions, and approaches utilizing MRI sequences obtainable in routine clinical practice remain an unmet need.

ObjectiveTo assess the sensitivity of the ratio of T1-weighted and T2-weighted (T1/T2) signal intensity for focal cortical lesions in comparison to other established, sensitive, advanced and high-field imaging methods.

Methods3-tesla (3T) and 7-tesla (7T) MRI collected from 10 adults with MS participating in a natural history study at the National Institutes of Health were included in the study. T1/T2 images were calculated by dividing 3T T1w images by 3T T2w fluid-attenuated inversion recovery (FLAIR) images for each participant. Cortical lesions were identified using 7T T2*w and T1w images and corresponding voxels were assessed on registered 3T images. For each participant, ratios derived from the median signal intensity of nonlesional tissue in the cortical region of the lesion and the median lesional voxel intensity were computed. These values were compared across 3T imaging sequences, including the calculated T1/T2 image, as well as T1w, T2w, and Inversion Recovery Susceptibility Weighted Imaging with Enhanced T2 weighting (IR-SWIET) images.

Results614 cortical lesions were identified on 7T images. 3T T1/T2 images demonstrated a larger contrast between median nonlesional cortical signal intensity and median cortical lesion signal intensity (median ratio = 1.29, range 1.19 - 1.38) when compared to T1w (1.01, 0.97 - 1.10, p<0.002), T2w (1.17, 1.07 - 1.26, p<0.002), and IR-SWIET (1.21, 1.01 - 1.29, p<0.03).

ConclusionT1/T2 images are sensitive to cortical lesions. Approaches incorporating T1/T2 could improve the accessibility of cortical lesion detection in research settings and clinical practice.

category: neurology


title: Spatial Cluster Modeling of Rodent Infestations and Leptospirosis Risks in SE Asian Urban Areas

abstract: Urban areas in the Southeast Asia Region are characterized by rainfall, river networks, and rodent infestations. Combinations of these adverse conditions will lead to the increasing risk of leptospirosis as usually contained in rodents. Then this study aims to assess the spatial pattern of rodent infestations and estimate the potential leptospirosis risks using environmental variables including distance to the river and rainfall in a city in SE Asia. The spatial modeling of rodent infestations was developed based on GIS and interpolation analysis. Meanwhile, the cluster modeling of rodent infestations was developed using the K-means clustering method. The results revealed the rodent infestations represented by two rodent species were Rattus rattus and Rattus norvegicus. R. rattus has a higher abundance than R. norvegicus. In contrast, R. norvegicus has wider distribution areas than R. rattus. Regarding the distribution areas, both species overlapped in the Southern parts of the city. R. rattus and R. norvegicus showed a distinct cluster characterized by a high rodent population with affinity for the nearest river, and this indicates the urban inhabitants near the river have more leptospirosis risk. The model of leptospirosis risks estimated an urban area of 35.182 km2 or 17.56% having leptospirosis potential.

category: occupational and environmental health


title: A screening tool enhances home-based identification of adolescents (aged 10-14) living with HIV in Zambia and South Africa: HPTN 071 (PopART) Study

abstract:
IntroductionThe HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa (SA). We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10-14) who are frequently left out of HIV interventions.

MethodCommunity HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A "yes" response to one or more questions was classified as being "at risk" of being HIV-positive. The data were captured through an electronic data capturing device from August 2016 to December 2017. Proportions of adolescents who were deemed "at risk" were calculated and the association of screening "at risk" with age, sex and community was tested using a chi-squared test. The adjusted odds ratio (OR) comparing the odds of testing HIV-positive if "at risk" with the odds of testing positive if "not at risk" was estimated using logistic regression.

ResultsIn our 14 study sites, 33,283 adolescents aged 10-14 in Zambia and 8,610 in SA participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in SA as "at risk". In Zambia and SA, the "at risk" adolescents were 4.6 and nearly 16.7 times more likely to test HIV-positive compared to the "not at risk", respectively (both p<0.001). Using the screening tool, one-third of HIV-positive adolescents could be diagnosed using just a tenth of the number of HIV tests compared to universal testing.

ConclusionThe screening tool may be of some value where UTT is not possible and limited resources must be prioritised toward adolescents who are more likely to be living with HIV. Further, the tool is of greater value in settings where there are more adolescents living with HIV who are undiagnosed. However, given our goal is to identify and treat all ALHIV, as well as link all HIV uninfected young people to prevention services, this screening tool should not be a substitute for UTT in community settings.

Clinical Trial NumberNCT01900977

category: hiv aids


title: Incidence and Predictors of Antiretroviral Treatment Failure among Children in Public Health Facilities of Kolfe Keranyo Sub-City, Addis Ababa, Ethiopia: Institution-based retrospective cohort study

abstract:
BackgroundHuman immunodeficiency virus (HIV) infection is a public health concern globally. The numbers of people living with HIV worldwide in 2018 was estimated at 37.9 million; from those, 1.7 million are children. Globally, 62% of the 37.9 million people were receiving Antiretroviral treatment (ART); 53% had achieved viral suppression. This study aimed to assess the incidence and predictors of Antiretroviral treatment failure among children in Kolfe Keranyo sub-city, Addis Ababa, Ethiopia.

MethodsAn institution-based retrospective cohort study was conducted among 250 children who were enrolled to first-line Antiretroviral treatment from January 2013 to May 2020 in Kolfe Keranyo sub-city. Data was collected by using data extraction checklist and data were extracted by reviewing childrens medical chart and electronic database. Kaplan-Meier method was used to estimate the probability of treatment failure. During bivariable analysis variables with p-value < 0.25 were taken for multivariable Cox regression analysis to assess predictors of treatment failure. Statistically significant association was declared at p-value < 0.05 with 95% confidence interval.

ResultThe overall treatment failure rate within the follow-up period was 17.2%. This study also found that the overall incidence density rate was 3.45% (95% CI: 2.57-4.67) per 1000 person-month observation. Infant prophylaxis for PMTCT (AHR: 3.59, 95% CI: 1.65-7,82), drug substitution (AHR: 0.18, 95% CI: 0.09-0.37), AZT/3TC/NVP based regimen (AHR: 2.27, 95% CI: 1.14-4.25), and more than 3 episodes of poor ART adherence (AHR: 2.27, 95% CI: 1.17-4.38) were found to be predictors of treatment failure among children.

ConclusionHigh proportion of treatment failure was found among children on first-line ART in Kolfe Keranyo sub-city, Addis Ababa. Infant prophylaxis for PMTCT, drug substitution, initial regimen, and poor ART adherence were found to be predictors of first-line ART treatment failure. Close follow-up of children on medication adherence and effective trainings to health care professionals need to be considered.


title: Optimized infection control practices augment the robust protective effect of vaccination for ESRD patients during a hemodialysis facility SARS-CoV-2 outbreak

abstract:
BackgroundWhile dialysis patients are at greater risk of serious SARS-CoV-2 complications, stringent infection prevention measures can help mitigate the risk of infection and transmission within dialysis facilities. We describe an outbreak of 14 cases diagnosed in a 13-day period in the second quarter of 2021 in a hospital-based ESRD facility, and our coordinated use of epidemiology, viral genome sequencing, and infection control practices to quickly end the cycle of transmission.

MethodsSymptomatic patients and staff members were diagnosed via RT-PCR tests. Facility-wide screening was conducted using rapid SARS-CoV-2 antigen tests. SARS-CoV-2 genome sequences were obtained from residual diagnostic PCR specimens.

ResultsOf the 106 patients who received dialysis in the facility, 10 were diagnosed with SARS-CoV-2 infection, as was one patient support person. Of three positive staff members, two were unvaccinated and had provided care for six and four of the affected patients, respectively. Sequencing demonstrated that all the cases in the cluster shared an identical B.1.1.7./Alpha substrain. Attack rates were greatest among unvaccinated patients and staff. Vaccine effectiveness was 88% among patients.

ConclusionsPrompt recognition of an infection cluster and rapid intervention efforts successfully ended the outbreak. Alongside consistent adherence to core infection prevention measures, vaccination was highly effective in reducing disease incidence and morbidity in this vulnerable population.

category: infectious diseases


title: Risk factors and preventive interventions for post Covid-19 condition: systematic reviews

abstract:
BackgroundThe Covid-19 outbreak has presented many challenges to governments and healthcare systems, including observations of symptoms that persist beyond acute infection labelled as post Covid-19 condition.

ObjectivesTo systematically identify and synthesize evidence around pre-existing and clinical risk factors for post Covid-19 condition (occurring [≥]12 weeks after positive test/symptom onset) (KQ1), and interventions during the acute and post-acute phases of the illness that could potentially prevent post Covid-19 condition (KQ2).

MethodsWe searched Medline and Embase (Jan 2021-Aug 12 2021 [KQ1], and Jan 2020-Jul 28, 2021 [KQ2]), Clinicaltrials.gov, organizational websites, and reference lists of included studies and relevant systematic reviews. Two investigators independently reviewed abstracts and full-text articles against a priori inclusion criteria, and disagreements were resolved through discussion or by consulting a third reviewer. One investigator abstracted data and assessed risk of bias using design-specific criteria, and a second investigator checked data abstraction and assessments for completeness and accuracy. Meta-analysis was performed when there was sufficient clinical and methodological similarity in an exposure-outcome comparison, based on prespecified variables. We assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE). A relative effect/association of 0.75-1.49 was considered as "little-to-no", whereas 0.50-0.74/1.5-1.99 was "small-to-moderate" and <0.50/ [≥]2.00 was "large" for fewer/benefit or more/harm, respectively

ResultsFrom 4,672 (KQ1) and 3,781 (KQ2) citations we included 17 and 18 studies, though 4 studies were included for both KQs. We found small-to-moderate associations between female sex and higher non-recovery, fatigue, and dyspnea (moderate certainty). Severe or critical acute-phase Covid-19 severity (versus not) has probably (moderate certainty) a large association with increased cognitive impairment, a small-to-moderate association with more non-recovery, and a little-to-no association with dyspnea. There may be (low certainty) large associations between hospitalization during the acute illness and increased non-recovery, increased dyspnea, and reduced return to work. There may be small-to-moderate associations between several other risk factors and post Covid-19 condition outcomes, including age [≥]60 versus <60 (functional incapacity), non-White people (lower return to work), children age >6 versus <2 years (non-recovery), having [≥]1 versus no comorbidities (non-recovery), chronic pulmonary disease (fatigue), rheumatologic disorder (depression/anxiety), and chronic obstructive pulmonary disease or hypertension (cognitive impairment). Several other risk factors had low certainty for little-to-no association with one or more outcomes (e.g. diabetes, cardiovascular disease) or very low certainty. Interventions to prevent post Covid-19 condition included medications (standard and traditional/ayurvedic), stem cell therapy, rehabilitation or similar therapies, and screening/referrals at either acute phase (symptom onset to 4 weeks) or early post-acute phase (4-8 week), with short (12-16 weeks) or longer (>16 weeks) follow-up for outcomes. We are very uncertain about the effects of preventive interventions, mainly due to risk of bias, inconsistency/lack of consistency (single studies), and in some cases imprecision.

ConclusionsGuidelines in relation to surveillance, screening services, and other services such as access to sickness and disability benefits, might need to focus on females and those with previously severe Covid-19 illness. Interventions targeting fatigue, dyspnea, and cognitive impairment (especially in those who had severe Covid-19) may be good to prioritize for development and evaluation to provide evidence on their effects. Inputs from patients and primary care providers should be taken into account when developing new care pathways and some tailoring to individual needs will likely be paramount. Continuous assessment of the rapidly emerging evidence is important to better shape our understanding as the body of evidence grows. Sufficiently powered prospective trials of preventive interventions are warranted.

PROSPERO registrationCRD42021270354


title: The scope and needs related to training, research, and mentorship among early-career addiction medicine professionals: an online global survey followed by expert group discussions

abstract:
Addiction medicine is a developing field, with many young professionals opting for a career in this area. However, globally, early-career professionals often face challenges in this field, such as lack of competency-based training due to a shortage of trainers, low availability of institutions with appropriate infrastructure, and limited resources for adequate training, particularly in developing countries. On the other hand, in developed countries, early career professionals may struggle with mentorship, limited job opportunities, and challenges with establishing a suitable research area.

The International Society of Addiction Medicine (ISAM) New Professionals Exploration, Training & Education (NExT) committee, a global platform for early-career addiction medicine professionals (ECAMPs), conducted an online survey using a modified Delphi-based approach among ECAMPs across 56 countries to assess and understand the need and scope for standardized training, research opportunities, and mentorship. The survey was conducted in 2 phases. A total of 110 respondents participated in Phase I (online key informant survey), and 28 respondents participated in Phase II (online expert group discussions on the three themes identified in Phase I). Most participants agreed with the lack of standardized training, structured mentorship programmes, research funding, and research opportunities in addiction medicine for ECAMPs. There is a need for standardized training programmes, improving research opportunities, and effective mentorship programmes to promote the next generation of addiction medicine professionals and further development to the entire field. The efforts of ISAM-NExT are well-received and give a template of how this gap can be addressed.

category: addiction medicine


title: A comparison of the genes and genesets identified by EWAS and GWAS of fourteen complex traits

abstract: Identifying the genes, properties of these genes and pathways to understand the underlying biology of complex traits responsible for differential health states in the population is a common goal of epigenome-wide and genome-wide association studies (EWAS and GWAS). GWAS identify genetic variants that effect the trait of interest or variants that are in linkage disequilibrium with the true causal variants. EWAS identify variation in DNA methylation, a complex molecular phenotype, associated with the trait of interest. Therefore, while GWAS in principle will only detect variants within or near causal genes, EWAS can also detect genes that confound the association between a trait and a DNA methylation site, or are reverse causal. Here we systematically compare association EWAS and GWAS results of 14 complex traits (N > 4500). A small fraction of detected genomic regions were shared by both EWAS and GWAS (0-9%). We evaluated if the genes or gene ontology terms flagged by GWAS and EWAS overlapped, and after a multiple testing correction, found substantial overlap for diastolic blood pressure (gene overlap P = 5.2x10-6, term overlap P = 0.001). We superimposed our empirical findings against simulated models of varying genetic and epigenetic architectures and observed that in a majority of cases EWAS and GWAS are likely capturing distinct genesets, implying that genes identified by EWAS are not generally causally upstream of the trait. Overall our results indicate that EWAS and GWAS are capturing different aspects of the biology of complex traits.

category: epidemiology


title: Estimating time-dependent infectious contact: a multi-strain epidemiological model of SARS-CoV-2 on the island of Ireland

abstract: Mathematical modelling plays a key role in understanding and predicting the epidemiological dynamics of infectious diseases. We construct a flexible discrete-time model that incorporates multiple viral strains with different transmissibilities to estimate the changing infectious contact that generates new infections. Using a Bayesian approach, we fit the model to longitudinal data on hospitalisation with COVID-19 from the Republic of Ireland and Northern Ireland during the first year of the pandemic. We describe the estimated change in infectious contact in the context of government-mandated non-pharmaceutical interventions in the two jurisdictions on the island of Ireland. We take advantage of the fitted model to conduct counterfactual analyses exploring the impact of lockdown timing and introducing a novel, more transmissible variant. We found substantial differences in infectious contact between the two jurisdictions during periods of varied restriction easing and December holidays. Our counterfactual analyses reveal that implementing lockdowns earlier would have decreased subsequent hospitalisation substantially in most, but not all cases, and that an introduction of a more transmissible variant - without necessarily being more severe - can cause a large impact on the health care burden.


title: Tracking population mental health before and across stages of the COVID-19 pandemic in young adults

abstract: The SARS-CoV-2 (COVID-19) pandemic has been associated with worsening mental health. Longitudinal studies have monitored changes in mental health from pre-pandemic levels, identifying critical points for mental health as COVID-19 restrictions evolve. Here we highlight changes in depression and anxiety in the UK from pre-pandemic across four pandemic occasions: April and June 2020, January, and July 2021 - corresponding to changes in COVID-19 restrictions. Data were from >5,000 27-29-year-olds from the Avon Longitudinal Study of Parents and Children (ALSPAC). We found that anxiety almost doubled throughout the pandemic compared to pre-pandemic levels and remained high until July 2021 when COVID-19 restrictions were fully lifted. Depression was lower than pre-pandemic levels in April 2020 but increased as the pandemic evolved until July 2021. Women, those with existing mental/physical health conditions and those with economic hardship were most at risk of sustained poorer mental health across the pandemic. Our results highlight the importance of longitudinal studies for tracking mental health during the COVID-19 pandemic and across virus suppression policy changes.

category: psychiatry and clinical psychology


title: The effect of galvanic vestibular stimulation on postural balance in Parkinsons Disease: A systematic review and meta-analysis

abstract:
People with Parkinsons disease (PD) experience postural imbalance, leading to considerably increased risk of falls. Galvanic Vestibular Stimulation (GVS) is postulated to modulate postural balance in humans and improve it in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD.

Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges g) as a measure of effect size in all studies.

We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n= 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [- 0.17, 1.41], I2 = 96.21%). Eggers test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%).

Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.


title: Metabolic associations with stroke, dementia, and imaging markers of cerebral small vessel disease: a comprehensive metabolomics study

abstract:
BackgroundCerebral small vessel disease is a major cause of ischemic stroke and vascular dementia, which are among the leading causes of death and disability worldwide. Metabolomics can help identify novel risk factors to better understand pathogenesis, predict disease progression and severity, and identify therapeutic targets.

MethodsWe analyzed metabolomics profiles from 118,021 UK Biobank participants with baseline metabolomics measurements (baseline surveys, 2006-2010; latest follow-up, March 2022). We examined cross-sectional associations of 325 metabolites with clinical diagnoses of stroke and dementia and MRI markers of small vessel disease. We also evaluated relationships between metabolites and future risk of stroke and dementia and performed Mendelian randomization to ascertain causal relationships.

ResultsAmong 118,021 participants (54% women; mean recruitment age, 56.5 years), 2,477 stroke and 1,785 dementia events were recorded (median follow-up, 13.1 years). In cross-sectional analyses, lower levels of apolipoproteins, free cholesterol, cholesteryl esters, fatty acids, lipoprotein particle concentrations, phospholipids, and triglycerides were associated with increased white matter microstructural damage on diffusion tensor MRI. Lower levels of amino acids and fatty acids and higher levels of ketone bodies were associated with increased risk of dementia. In longitudinal analyses, lipoprotein subclasses of very large HDL were associated with increased risk of stroke, and acetate, 3-hydroxybutyrate, and relative lipoprotein lipid concentrations were associated with increased risk of dementia. Mendelian randomization analyses identified strong evidence supporting causal relationships for many associations.

Conclusionsbiomarker profiling platform and experimentation In this large-scale metabolomics study, we found multiple metabolites associated with stroke, dementia, and MRI markers of small vessel disease. Further studies may help develop personalized prediction models for patients at increased risk of stroke and dementia and provide insights into mechanistic pathways and future treatment approaches.

Key PointsO_ST_ABSQuestionC_ST_ABSAre metabolites associated with stroke, dementia, and MRI markers of cerebral small vessel disease?

FindingsIn an analysis of individual-participant data from 118,021 participants, we identified 289 metabolites that were significantly associated with stroke, dementia, and MRI markers of small vessel disease.

MeaningMetabolic markers were associated with risk of stroke, dementia, and MRI markers of small vessel disease, which could be used to develop personalized prediction models and novel treatment approaches for patients at increased risk of vascular-related conditions.


title: Enhanced Recovery After Surgery reduced length of stay after colorectal surgery in a small rural hospital in Ontario

abstract:
BackgroundEnhanced Recovery After Surgery (ERAS) programs include preoperative, intraoperative and postoperative clinical pathways to improve quality of patient care while reducing length of stay and readmission. This study assessed the feasibility and outcomes of an ERAS protocol for colorectal surgery implemented over two-years in a small, resource-challenged rural hospital.

Study designA prospective cohort study used retrospectively matched controls to assess the effect of ERAS on LOS in patients undergoing colorectal surgery in a small rural hospital in northern Ontario, Canada. ERAS patients were matched to two patients in the control group based on diagnosis, age and gender. Patients had open or laparoscopic colorectal surgeries, with those in the intervention group treated per ERAS protocol and given instructions on pre- and post-operative self-care.

ResultsMost ERAS patients reported adherence to ERAS protocols prior to surgery. Approximately one quarter of patients chose not to complete the postoperative survey. Of those who completed the survey, adherence to protocol was strongest for chewing gum in the days after surgery. Most patients were sitting in a chair for their afternoon meal by the first day and most were walking down the hallway by the second day. The control and ERAS patient groups did not differ significantly (p[≥]0.07) in age ([Formula]years, sd=13.1), gender (52% male), nor in the Canadian Classification of Health Interventions 5-character code. The control group significantly higher (p<0.001) malignant neoplasm of colon (C18, 69% vs 35%), and significantly lower malignant neoplasm of rectum (C20, 0% vs 5%), relative to the ERAS group. The control group had an average ln-transformed LOS that was significantly longer (exponentiated as 1.7 days) than ERAS patients (t-test, p<0.001).

ConclusionThis study found that ERAS could be implemented in a small rural hospital and provided evidence for a reduced LOS of approximately two days.

category: gastroenterology


title: International comparison of the impact of the pandemic and vaccination measures adopted on children and adolescent population

abstract:
BackgroundThe objectives of this study were to compare the cumulative incidence, hospitalizations and mortality, by country and age group, in child and young people (CYP) from the beginning of the pandemic to January 2022, and to describe the differences and similarities and justification in the measures adopted in relation to CYP vaccination against SARS-CoV-2.

MethodsA descriptive quantitative summary of the available data on the impact of the COVID-19 on children and adolescents (<18y) from 7 countries (Chile, Colombia, Paraguay, Nigeria, Ghana, Spain) or regions (Kocaeli, Turkey), based on official published data was performed. Outcome measures were: available data on incidence, admission to hospital and to intensive care units (ICU), and deaths, by country or region; vaccination plans, including age, type of vaccine and official justification about the proposal.

ResultsAll countries analyzed data showed variable incidence rate, and relatively low ICU hospitalizations and deaths. Vaccines used and age at starting were also variable, i.e. starting at 3-5y in some Latin American countries, while in other countries proposal starts at 15y old. Almost all justifications were based on the idea to promote collective protection, and that vaccination is important as it -directly and indirectly-protect the rest of the population.

ConclusionsThe results reinforce the idea of the urgent need to prioritize globally and equitably distribution of vaccines in the population at greatest risk, and to apply the precautionary principle in CYP before deciding to massively vaccinate it.

What is knownThe child population has less severe infections and seems to transmit the infection less than the adult population.

Published data from the Randomized Clinical Trials (RCT) of vaccines in minors presented short follow-up than in the adult population and basically studied the incidence of infection as the main endpoint

What this study addsMortality in the child population due to COVID-19 since the start of the pandemic has been low in all the countries analyzed

The vaccines used as well as the vaccination guidelines shows high variability in these countries

The results of the study reinforce the need to establish global and equitable mechanisms for the distribution of vaccines and prioritize the population at greatest risk, such as older people.

In the child population, it is necessary to apply the precautionary principle before establishing massive vaccination plans

category: pediatrics


title: A Qualitative Study Regarding Messages of the COVID-19 Vaccine from Vaccinated Healthcare Providers and Healthy Adults

abstract:
1.BackgroundTo promote the vaccination against COVID-19, person-to-person communication from vaccinated people will play an important role. The objectives of this study are to identify what messages were shared by vaccinated people, and the relationship between these messages and their background.

MethodsThis study was an exploratory and prospective basis with individual interviews. The participants were healthcare providers and healthy adults who were recruited at a vaccination site in Chuo-City, Tokyo. The online interviews were conducted using a semi-structured interview. Based on the Health Belief Model (HBM), the participants were asked about their perspectives on vaccines and what they talked about after their vaccination. The interviews were categorized into each item of the HBM and analyzed using NVivo software.

ResultsDuring August to October 2021, five healthcare providers and seven healthy adults were enrolled in the study. One healthy adult could not be contacted resulting in a total of 11 participants interviewed. Both the healthcare providers and the healthy adults mainly talked about side effects after their vaccination, and to ease the other persons concerns based on their experience. Meanwhile, there were differences in the recommendations for vaccination between the two groups. The healthcare providers were strongly aware of the severity of COVID-19 infection and recommended vaccination to others as a useful measure to suppress becoming severely ill. On the other hand, the healthy adults recommended the vaccine with varying degree depending on their expectations and concerns about the vaccine and external factors such as living with a family member.

ConclusionBoth the healthcare providers and healthy adults shared similar messages to ease the vaccination concerns of others. However, their vaccine recommendation level was varied, which may be influenced not only by expectations and concerns toward the vaccine, but also by external factors such as family members living together.


title: Does contrast-enhancement improve visualisation of lenticulostriate arteries in cerebral small vessel disease using time-of-flight magnetic resonance angiography at 7 Tesla?

abstract:
Background And Purpose7 Tesla-field-strength (7T) Magnetic Resonance Imaging (MRI) allows the small perforating arteries in the brain to be visualised, and this modality may allow visualisation of the arterial pathology in cerebral small vessel disease (cSVD). Most studies have used standard Time-of-Flight (ToF) Magnetic Resonance Angiography (MRA). Whether the use of contrast enhancement improves perforating artery visualisation at 7T remains unclear.

Materials And MethodsIn a prospective study, we compared standard ToF MRA with contrast-enhanced (CE) ToF MRA at 7T for the visualisation of the lenticulostriate arteries (LSAs). Ten patients with symptomatic lacunar stroke were recruited (mean age, SD, 64{+/-}9.9 years). Visualisation was assessed using a visual rating scale administered by two independent expert readers and length of the LSAs visible.

ResultsVisualisation of the LSAs was improved with CE ToF MRA. The mean Visibility and Sharpness Score was higher for CE ToF MRA over standard ToF MRA (2.55{+/-}0.64 vs 1.75{+/-}0.68; P=0.0008). The mean length of LSA visualised was significantly longer with CE ToF MRA compared to standard ToF MRA (24.4{+/-}4.5 vs 21.9{+/-}4.0 mm; P=0.01).

ConclusionCE ToF MRA offers improved visualisation of the LSAs over standard ToF MRA. The addition of contrast may improve the ability to visualise cerebral small vessel disease arterial pathology.


title: Multilevel Correlates of Abdominal Obesity in Adolescents and Youth Living with HIV in peri-urban Cape Town, South Africa.

abstract:
BackgroundChronic non-communicable disease comorbidities are a major problem faced by people living with HIV (PLHIV). Obesity is an important factor contributing to such comorbidities and PLHIV face an elevated risk of obesity. However, there is data paucity on the intersection of obesity and HIV in adolescents and youth living with HIV (AYLHIV) in sub-Saharan Africa. We therefore aimed to investigate the prevalence of abdominal obesity and associated multilevel factors in AYLHIV in peri-urban Cape Town, South Africa.

MethodsWe conducted a cross-sectional study enrolling AYLHIV aged 15 - 24 years attending primary healthcare facilities in peri-urban Cape Town in 2019. All measures, except for physical examination measures, were obtained via self-report using a self-administered electronic form. Our outcome of interest was abdominal obesity (waist-to-height ratio [≥] 0.5). We collected individual-level data and data on community, built and food environment factors. Data was summarized using descriptive statistics, stratified by sex. Multilevel logistic regression was conducted to investigate factors associated with abdominal obesity, adjusted for sex and age.

FindingsA total of 87 participants were interviewed, 76% were female and the median age was 20.7 (IQR 18.9-23.0) years. More than two fifths had abdominal obesity (41%; 95% CI: 31.0-51.7%), compared to published rates for young people in the general population (13.7-22.1%). In multilevel models, skipping breakfast (aOR= 5.42; 95% CI: 1.32 - 22.25) was associated with higher odds of abdominal obesity, while daily wholegrain consumption (aOR= 0.20; 95% CI: 0.05 - 0.71) and weekly physical activity (aOR = 0.24; 95% CI: 0.06 - 0.92) were associated with lower odds of abdominal obesity. Higher anticipated stigma was associated with reduced odds of obesity (aOR= 0.58; 95% CI: 0.33 - 1.00). Land-use mix diversity (aOR= 0.52; 95% CI: 0.27 - 0.97), access to recreational places (aOR= 0.37; 95% CI: 0.18 - 0.74), higher perceived pedestrian and traffic safety (aOR= 0.20; 95% CI: 0.05 - 0.80) and having a non-fast-food restaurant within walking distance (aOR= 0.30; 95% CI: 0.10 - 0.93) were associated with reduced odds of abdominal obesity. The main limitations of the study were low statistical power and possible reporting bias from self-report measures.

ConclusionsOur findings demonstrate a high prevalence of abdominal obesity and highlight multilevel correlates of obesity in AYLHIV in South Africa. An intersectoral approach to obesity prevention, intervening at multiple levels is necessary to intervene at this critical life stage.


title: The Impact on Staff of Providing Non-Invasive Advanced Respiratory Support During the Covid-19 Pandemic A Qualitative Study in an Acute Hospital

abstract:
ObjectivesTo explore the experiences of healthcare workers of providing Non-Invasive Advanced Respiratory Support (NARS) to critically unwell patients with covid-19.

DesignA qualitative study drawing on a social constructionist perspective using thematic analysis of semi-structured interviews.

SettingA single acute UK NHS Trust across two hospital sites.

ParticipantsMultidisciplinary team members in acute, respiratory and palliative medicine.

Results21 nurses, doctors (juniors and consultants) and physiotherapists described the provision of NARS to critically unwell covid-19 patients as extremely challenging. The main themes were of feeling ill prepared and unsupported, a need to balance complex moral actions, a sense of duty to patients and their families. The impact on staff was profound and findings are discussed via a lens of moral injury. Injurious events included staff feeling they had acted in a way that caused harm, failed to prevent harm or had been let down by seniors or the Trust. Participants identified factors that mitigated adverse impact.

ConclusionsAlthough many of the issues described by participants are likely immutable components of healthcare in a pandemic there were several important protective factors that emerged from the data. Experience, debriefing and breaks from covid-19 wards were valuable to participants and successfully achieving a peaceful death for the patient was often viewed as compensation for a difficult journey. These protective factors may provide modelling for future education and support services to help prevent moral injury - or aide in its recovery.

Registrationregistered on the Open Science Framework 10.17605/OSF.IO/XB8YH

Strengths and LimitationsO_LISingle Centre Study
C_LIO_LIThe lead author had pre-existing relationships with study participants
C_LIO_LIThe lead author, under strict supervision, practiced a reflexivity based approach to data collection and analysis with objectivity benchmarking from the second author.
C_LI

category: palliative medicine


title: Patterns of presentations of children to emergency departments across Europe and the impact of the COVID-19 pandemic: retrospective observational multinational study.

abstract:
BackgroundTo investigate the impact of the COVID-19 pandemic and infection prevention measures on children visiting emergency departments across Europe.

MethodsRoutine health data were extracted retrospectively from electronic patient records of children aged <16 years, presenting to 38 emergency departments (ED) in 16 European countries for the period January 2018 - May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRR) were used to compare age groups, diagnoses and outcomes.

FindingsReductions in pediatric ED attendances, hospital admissions and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (incidence rate ratio (IRR) 2{middle dot}62, 95% CI 2{middle dot}19 to 3{middle dot}13) and in children aged >12 months (12-<24 months IRR 0{middle dot}89, 95% CI 0{middle dot}86 to 0{middle dot}92; 2-<5years IRR 0{middle dot}84, 95% CI 0{middle dot}82 to 0{middle dot}87; 5-<12 years IRR 0{middle dot}74, 95% CI 0{middle dot}72 to 0{middle dot}76; 12-<16 years IRR 0{middle dot}74, 95% CI 0{middle dot}71 to 0{middle dot}77; vs. age <12 months as reference group). The impact on pediatric intensive care admissions (IRR 1{middle dot}30, 95% CI 1{middle dot}16 to 1{middle dot}45) was not as great as the impact on general admissions. Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1{middle dot}10, 95% CI 1{middle dot}08 to 1{middle dot}12; emergent and very urgent triage IRR 1{middle dot}53, 95% CI 1{middle dot}49 to 1{middle dot}57; vs. non-urgent triage category). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases.

InterpretationReductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell.

FundingRGN was supported by National Institute of Health Research, award number ACL-2018-021-007.

Trial registryISRCTN91495258


title: Deterioration of patients with mental disorders in Denmark coinciding with the invasion of Ukraine

abstract: The Russian invasion of Ukraine on February 24, 2022 has led to a humanitarian crisis of immense proportions. In turn, this will, inevitably, also lead to a mental health crisis among those affected by the war - either directly or by proxy. The mental health impact of the war in Ukraine is also likely to affect people beyond the borders of the countries directly involved. Here, we investigated whether Danish patients with mental disorders seem to be affected by the war in Ukraine. Specifically, we searched the Electronic Patient Record system of the Psychiatric Services of the Central Denmark Region in the period from January 1, 2022 to March 8, 2022 for clinical notes containing the word *ukrain* (*irrespective of letters and symbols prior to- or following ukrain). We then manually assessed (read) 100 randomly drawn notes containing *ukrain* to determine whether they described worsening of the mental health/symptoms of the patients that was likely attributable to the war in Ukraine. We identified a total of 16,341 adult patients (57% women, mean age 40 years, SD=18) who were registered with at least one clinical note in the Electronic Patient Record system of the Psychiatric Services of the Central Denmark Region in the period from January 1, 2022 to March 8, 2022. During this period, 567,647 clinical notes were entered into the electronic patient record system. Among these, 502 notes from 369 unique patients contained *ukrain* with a sharp rise in incidence following the Russian invasion of Ukraine on February 24, 2022. Among the 100 randomly drawn clinical notes containing *ukrain* (stemming from 94 unique patients), 62 notes from 58 unique patients described worsening of the mental health/symptoms of the patients that seemed attributable to the war in Ukraine. Although causal inference is challenging in this regard, the results of this study suggest that even individuals remotely distanced from the war in Ukraine may be psychologically affected by it - serving as an early warning sign of the potential width of the negative mental health impact from the war, which will, inevitably, hit the Ukrainian population the hardest.


title: Machine Learning Enabled Non-invasive Diagnosis of Nonalcoholic Fatty Liver Disease and Assessment of Abdominal Fat from MRI Data

abstract: Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to chronic liver disease worldwide with high disease burden and suffers from limitations in diagnosis. Inspired by recent advances in machine learning digital diagnostics, we explored the efficacy of training a neural network to classify high risk NAFLD vs. non-NAFLD patients in the UK Biobank dataset based on proton density fat fraction (PDFF). We compared the performance of several ResNet-derived architectures in the context of whole abdomen MRI, segmented liver and abdomen excluding liver (sans-liver). Non-local ResNet trained on whole abdomen MRI images yielded the highest precision (0.88 for NAFLD) and F1 (0.89 for NAFLD). Furthermore, our work on a second, larger cohort explored multi-task learning and the relationship among PDFF, visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT). Interestingly, multi-task learning experiments found a decline in performance for PDFF when combined with VAT and ASAT. We address this deterioration using Multi-gate Mixture-of-Experts (MMoE) approaches. Our work opens the possibility for using a non-invasive deep learning-based diagnostic for NAFLD, and directly enables clinical and genomic research using a larger cohort of potential NAFLD patients in the UK Biobank study.


title: Plasma cell-free DNA as a prognostic biomarker in small cell lung cancer patients

abstract:
BackgroundLack of biomarkers for treatment selection and monitoring in small-cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC.

MethodsWe quantified cfDNA in 46 SCLC patients at different times during therapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch(R) system. Both biomarkers were associated with patients outcomes and a prognostic model was developed.

ResultsHigh cfDNA levels before therapy were associated with shorter progression-free survival and overall survival. Furthermore, changes in cfDNA levels between baseline and 3 weeks and cfDNA levels at progression disease were also associated with patients outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included ECOG Performance Status, gender and baseline cfDNA levels was associated with a higher risk of progression and death.

ConclusionsWe confirmed the prognostic utility of cfDNA in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

category: oncology


title: RNAseq analysis reveals prominent and distinct expressed variants that are related to disease severity in SARS-CoV-2 infected patients with mild-to-severe disease

abstract:
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant public health challenge globally. SARS-CoV-2 is a novel virus, and the understanding of what constitutes expressed RNAseq variants in healthy, convalescent, severe, moderate and to those admitted at the Intensive Care Unit (ICU) is yet to be presented. We set to characterize the different expressed RNAseq variants in healthy, severe, moderate, ICU, and convalescent individuals.

Materials and methodsThe bulk RNA sequencing data with identifier PRJNA639275 was download from Sequence Reads Archive (SRA). The individuals were divided into: (i) healthy, n=34, severe, n=16, ICU, n=8, moderate, n=8, and convalescent, n=2. Fastqc version 0.11.9 and Cutadapt version 3.7 was used to asses the reads quality and to perform adapter trimming respectively. STAR was using to align reads to the reference genome and GATK best practice was followed to call variants using rnavar pipeline, part of the nf-core pipelines.

ResultsOur analysis demonstrated that convalescent, moderate, severe and those admitted to the ICU are characterized by different sets of unique RNAseq variants. The data shows that the individuals who recover from SARS-CoV-2 infection have the same set of expressed variants as in the healthy controls. We showed that the healthy and SARS-CoV-2 infected individuals display different sets of expressed varinats which is characteristic of the patient phenotype.

ConclusionThe individuals with severe, moderate, those admitted at the ICU, and convalescent individuals display a unique set of variants. The findings in this study will inform the test kit development and SARS-CoV-2 patients classification to enhance management and control of SARS-CoV-2 infection in our population.

category: health informatics


title: Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

abstract:
Vaccines are the most important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 - including variants of concern such as Delta or Omicron - was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. T-cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long-term humoral and cellular immune protection.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDue to some rare severe side effects after the administration of the adenoviral vaccine, ChAdOx1 nCoV-19, many countries recommended a heterologous vaccination scheme including mRNA vaccines like BNT162b2 for the second dose. We performed a PubMed search (with no restrictions on time span) using the search terms "SARS-CoV-2" and "heterologous vaccination" and obtained 247 results. Only a fraction of manuscripts included direct comparisons of patient cohorts that received either a heterologous or a homologous vaccination regimen. Of those, the vast majority investigated only short-term immunogenicity after vaccination. Thus, little is known about the long-term maintenance of immunity by heterologous compared to homologous vaccination.

Added value of this studyWe add a very comprehensive and comparative study investigating heterologous and homologous vaccination regimens early and late after vaccination. Key features include the number of patients (n = 473), the number of vaccination cohorts (n= 3), the fact that samples were derived from three independent study centers and comparative analyses were performed at two independent study centers, as well as in-depth investigation of humoral and T cellular immunity.

Implications of all the available evidenceThe recent data creates a line of evidence that heterologous vaccination, compared to homologous vaccination regimens, results in at least non-inferior maintenance of humoral and cellular immunity. The enhanced understanding of immunity induced by individual vaccination regimens is crucial for further recommendations regarding the necessity, timing and choice of additional vaccinations and public health policies.


title: Analysis of humoral immunity against emerging SARS-CoV-2 variants: a population-based prevalence study in Yokohama, Japan

abstract:
BackgroundLittle is known about the population prevalence of antibodies against emerging immune escape variants of SARS-CoV-2.

MethodsA population-based prevalence study was conducted in Yokohama City, the most populous municipality of Japan. Quantitative measurements of immunoglobulin G against SARS-CoV-2 spike protein (SP-IgG) and qualitative measurements of neutralization antibodies against the Omicron BA.1 and BA.2 variants were performed.

ResultsOf 6,000 randomly selected residents aged 20-74, 1,277 participated in the study during a period from January 30 to February 28, 2022. Of them, 3% had prior diagnosis of COVID-19, 96% received at least two-doses of SARS-CoV-2 vaccines, and 94% were positive for SP-IgG. The positive rates of neutralizing antibodies were 28% to Omicron BA.1 and BA.2 variants in a random sample of 10% of participants (n=123) and 100% to BA.1 and BA.2 among participants who received the third vaccination at least 7 days before (n=66).

ConclusionsIn this population-based prevalence study in Japan, most had SP-IgG antibodies but the overall neutralizing antibody positive rate was 28% against the Omicron BA.1 and BA.2 variants. The population-level insufficient humoral immunity against the Omicron variants may explain the outbreak of COVID-19 during this period in Japan.


title: Monitoring of the SARS-CoV-2 Omicron BA.1/BA.2 variant transition in the Swedish population reveals higher viral quantity in BA.2 cases

abstract: Throughout the SARS-CoV-2 pandemic, multiple waves of variants of concern have swept across populations, leading to a chain of new and yet more contagious lineages dominating COVID-19 cases. Here, we tracked the remarkably rapid shift from Omicron BA.1 to BA.2 sub-variant dominance in the Swedish population during January-March 2022. By analysis of 174,933 clinical nasopharyngeal swab samples using a custom variant-typing RT-PCR assay, we uncover nearly two-fold higher levels of viral RNA in cases with Omicron BA.2. Importantly, increased viral load in the upper pharynx upon BA.2 infection may provide part of the explanation why Omicron BA.2 is more transmissible and currently outcompetes the BA.1 variant across populations.


title: Damaging missense variants in IGF1R implicate a role for IGF-1 resistance in the aetiology of type 2 diabetes

abstract: Type 2 diabetes (T2D) is a chronic metabolic disorder with a significant genetic component. While large-scale population studies have identified hundreds of common genetic variants associated with T2D susceptibility, the role of rare (minor allele frequency < 0.1%) protein coding variation is less clear. To this end, we performed a gene burden analysis of 18,691 genes in 418,436 (n=32,374 T2D cases) individuals sequenced by the UK Biobank (UKBB) study to assess the impact of rare genetic variants on T2D risk. Our analysis identified T2D associations at exome-wide significance (P < 6.9x10-7) with rare, damaging variants within previously identified genes including GCK, GIGYF1, HNF1A, and TNRC6B. In addition, individuals with rare, damaging missense variants in the genes ZEB2 (N=31 carriers; OR=5.5 [95% CI=2.5-12.0]; p=6.4x10-7), MLXIPL (N=245; OR=2.3 [1.6-3.2]; p=3.2x10-7), and IGF1R (N=394; OR=2.4 [1.8-3.2]; p=1.3x10-10) have higher risk of T2D. Carriers of damaging missense variants within IGF1R were also shorter (-2.2cm [-1.8-2.7]; p=1.2x10-19) and had higher circulating protein levels of insulin-like growth factor-1 (IGF-1; 2.3 nmol/L [1.7-2.9] p=2.8x10-14), indicating relative IGF-1 resistance. A likely causal role of IGF-1 resistance on T2D was further supported by Mendelian randomisation analyses using common variants. Our results increase our understanding of the genetic architecture of T2D and highlight a potential therapeutic benefit of targeting the Growth Hormone/IGF-1 axis.

category: endocrinology


title: Epidemiologic Assessment of Pediatric Inflammatory Bowel Disease Presentation in NYC During COVID-19

abstract:
SARS-nCoV2 may have increased capacity to generate autoimmune disease; multiple reports suggest increased risk of Type 1 Diabetes, and case reports suggest other autoimmune linkages. Inflammatory Bowel Disease (IBD) pathogenesis appears to be a mix of genetic susceptibility, microbial populations, and immune triggers such as infections. Given the perceived role of infection in pathogenesis, decreased incidence of all infections during the pandemic secondary to non-pharmaceutical interventions should decrease IBD incidence rates. The aim of this study was to evaluate the association between the Covid-19 pandemic and IBD presentation in NYC using data from new diagnoses at a consortium of institutions.

Using EMR systems all diagnoses at 4 collaborating institutions were retrieved from 2015-2021. We fit time series model (ARIMA) to the quarterly number of cases of each disease for January 2016-March 2020 and forecast the subsequent 21 months. We not only did not observe a decline in pediatric IBD secondary to absent viral illness but noted a statistically significant increase in Crohns Disease approximately 6 months after the initial 2020 COVID wave in NYC, and trends suggesting increases overall in IBD diagnoses above the existing trend towards increased disease presentation that pre-dated the pandemic. This data suggests that there may be a linkage between SARS-nCoV2 infection rates and subsequent pediatric IBD presentation, warranting further evaluation in the aftermath of the Omicron wave.


title: Service-user experiences of an integrated psychological intervention for depression or anxiety and tobacco smoking in IAPT: A qualitative investigation into mechanisms of change in quitting smoking

abstract:
BackgroundHigh smoking prevalence leads to increased morbidity and mortality in individuals with depression/anxiety. Integrated interventions targeting both smoking and mood have been found to be more effective than those targeting smoking alone, but the mechanisms of change of these integrated interventions have not been investigated.

AimsThis qualitative study aimed to investigate participants subjective experiences of the mechanisms underlying change in smoking behaviour following an integrated CBT-based intervention for smoking cessation and depression/anxiety.

MethodsThis study was embedded within an ongoing randomised controlled acceptability and feasibility trial (http://www.isrctn.com/ISRCTN99531779). Semi-structured interviews were conducted with 15 IAPT service users and data were analysed using thematic analysis.

ResultsFive themes were identified: (1) acquiring an increased awareness of smoking patterns, (2) developing individualised strategies, (3) practitioner style as "supportive but not lecture-y" (4) importance of regular sessions, and (5) having the opportunity to access intervention at "the right time".

ConclusionsThese findings further our understanding of the mechanisms of change towards smoking cessation in this integrated intervention and highlight the need to emphasise and embed these components in manualised interventions to optimise therapeutic benefits and reduce smoking prevalence in people with depression/anxiety.

Relevance statementThis study qualitatively investigated mechanisms underlying change in smoking behaviour following an integrated intervention for depression/anxiety and smoking cessation. Research shows interventions integrating smoking cessation and mood management are more effective than smoking cessation interventions alone; however further investigation is needed to understand mechanisms of change for integrated interventions. The current results identified key factors that were important for participants in the integrated intervention to reduce smoking. An improved understanding of mechanisms underlying change in smoking behaviour helps to identify therapist characteristics and treatment components that improve therapeutic outcomes which future research could investigate using a randomised controlled trial design.


title: Infection Prevention and Control practices; an exploratory qualitative study of experiences of health care providers and support staff at the University Teaching Hospital, Lusaka, Zambia

abstract:
BackgroundInfection Prevention and Control is a public health concern to abate Hospital Acquired Infections. Hospital Acquired Infections are known to complicate clinical care, increase length of stay in hospitals and particularly have disturbing effects on patients recovery as well as devastating effects on health care facilities, especially in low resource settings. However, with effective infection prevention practices, the Microorganisms can be eradicated through proper hand hygiene practices of the health workers and proper waste management and disposal/adequate environmental sanitation.

We explored the experiences of health care providers and support staffing infection prevention practices in selected clinical areas at the University Teaching Hospital, in Lusaka.

Material and MethodsThis was a qualitative study that used an exploratory research design. The exploratory design allowed the participants to give in-depth narratives from their work environments as well as enabled the researcher to observe their Infection Prevention Practices. The observations provided an opportunity to make varied conclusions on compliance to infection prevention practices. The researcher collected data using an interview guide from the thirty (30) study respondents. Observations were conducted in their work environments to strengthen the conclusions made. Audio recordings were transcribed verbatim and then imported into Nvivo Version 11 for data management and analysis. Thematic analysis guided the conclusions made in the study.

ResultsThree main themes emerged from the data analyzed: These were existing guidelines on selected Infection Prevention and Control guidelines; Knowledge and use of the Infection Prevention and Control guidelines, and compliance to Infection Prevention and Control guidelines by health care providers and support staff. The participants demonstrated good understanding of the benefits of observing standard IPC guidelines in the workplace, barriers to compliance were reported in almost all the sites. Staff turnover, limitations in infrastructural, and heavy clinical workloads led to lapses in compliance with Infection Prevention Practices.

ConclusionThe study recommends the setting up of an effective and efficient Infection Prevention and Control Committee at the University Teaching Hospital. The committee should oversee the proper functioning of all safety and occupational Health activities and compliance to all infection prevention and control guidelines in the clinical areas and hospital environment by ensuring effective hand hygiene practices using elbow-operated taps and proper medical waste disposal starting with the use of foot-operated bins and compliance to all existing infection prevention guidelines in all clinical areas within the hospital..


title: Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

abstract:
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired.

We retrospectively analyzed serological response of up to five doses of SARS-CoV-2 vaccine in KTR from December 27, 2020, until December 31, 2021. Particularly, the influence of different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed.

In total, 4.277 vaccinations against SARS-CoV-2 in 1.478 patients were analyzed. Serological response was 19.5% after 1.203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%.

In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased serological response rate to 75% in comparison to no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations.

Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.

category: nephrology


title: Nature prescriptions: a scoping review with a nested meta-analysis

abstract:
Background"Nature prescriptions" are gaining popularity as a form of social prescribing and in response to calls for sustainable healthcare. Our review and meta-analysis appraised evidence of effectiveness of nature prescriptions on various health outcomes. In doing so, we sought to determine the factors that are critical for the success of nature prescriptions, based on Social Cognitive Theory.

MethodsThis is a scoping review with a nested meta-analysis for a subset of outcomes. Five databases were searched up to July 25, 2021. Randomised and non-randomised controlled studies featuring a nature prescription (i.e. an instruction or organised programme, by a health or social provider, to promote spending time in nature) are included. All health outcomes are eligible, but only key pre-specified outcomes are qualified for meta-analysis. Two reviewers independently conducted all steps of study selection; one reviewer conducted data collection and risk of bias assessment. Summary data was extracted from published reports for analysis. Random-effect models for meta-analysis were conducted using Review Manager 5.4.1.

FindingsWe identified 86 unique studies (116 reports), of which 26 studies contributed data to meta-analysis. Compared to control, nature prescription programmes resulted in a greater reduction in systolic blood pressure (MD = -4{middle dot}9mmHg [-9{middle dot}6 to -0{middle dot}1], I2=65%) and diastolic blood pressure (MD = -3{middle dot}6mmHg [-7{middle dot}4 to 0{middle dot}1], I2=67%). They also had a moderate-to-large effect on depression scores (SMD=0{middle dot}5 [0{middle dot}2 to 0{middle dot}8], I2=79%) and anxiety score (SMD=0{middle dot}6 [0{middle dot}1 to 1{middle dot}2], I2=90%). Lastly, they resulted in a greater increase in daily step counts (MD = 900 steps [790-1010], I2=0%), but did not improve weekly time of moderate physical activities (MD = 25{middle dot}9 minutes [-10{middle dot}3 to 62{middle dot}1], I2=53%). Most studies have moderate to high risk of bias, principally due to non-blinding nature of the interventions, small sample size and lack of analysis plan to rule out risks of bias.

InterpretationNature prescription programmes may provide cardiometabolic and mental health benefits and increase physical activity. Effective nature prescription programmes can select from a range of natural settings, activities and might be implemented via social and community channels, besides health providers. The Social Cognition Theory is useful in designing future nature prescription programmes.

FundingThis work was supported by the Hort Frontiers Green Cities Fund, part of the Hort Frontiers strategic partnership initiative developed by Hort Innovation, with co-investment from the University of Wollongong (UOW) Faculty of Social Sciences, the UOW Global Challenges initiative and contributions from the Australian Government (project number #GC15005). T.A-B. was supported by a National Health and Medical Research Council Boosting Dementia Research Leader Fellowship (#1140317). X.F. was supported by a National Health and Medical Research Council Career Development Fellowship (#1148792).

O_TEXTBOXPanel: Research in context

Evidence before this studyExtensive evidence indicates contact with nature is associated with social, mental and physical health. However, little evidence exists on the effectiveness of nature prescriptions, which involve a health provider (e.g. general practitioner) recommending a patient to spend a fixed amount of time a week in a natural setting (e.g. a park). Other studies have attempted to evaluate the benefits of food prescription or green prescription programmes, which do not necessarily involve nature exposure. Only one systematic review on nature prescriptions has been conducted to date, which is a qualitative review without meta-analysis. The review concluded that the evidence (studies up to June 2019) was too sparse to discern any clear evidence of health impacts. There was insufficient information to assess the risk of bias or quality of evidence in the review. Moreover, the review included only nature prescriptions dispensed in outpatient settings, which left out prescription programmes implemented by other institutions, such as welfare centres, social services, universities or workplaces.

Added value of this studyOur review is the first to provide comprehensive appraisal including meta-analysis of the effectiveness of nature prescription programs on multiple health outcomes. The scoping review identified a range of promising nature-based interventions that were dispensed outside the clinic setting and did not self-label as a nature prescription, but would be effective as one. The nested meta-analyses on key outcomes demonstrated positive benefits on blood pressure, symptoms of depression and anxiety, and physical activity levels.

Implications of all the available evidenceOur findings suggest that an effective nature prescription programme can select from a range of natural settings, activities and can be implemented via social and community channels, in addition to health providers. In addition, we also demonstrated that the Social Cognition Theory framework is useful in designing future nature prescription programmes.

C_TEXTBOX


title: Study Protocol for a Phase III Randomised Controlled Trial of Sailuotong (SLT) for Vascular Dementia and Alzheimers Disease with Cerebrovascular Disease

abstract:
BackgroundVascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng, Ginkgo biloba and Crocus sativus extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention.

MethodsA rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimers disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimers Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinicians Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies.

DiscussionPrimary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD.

Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN 12616000057482. Registered on 20 January 2016. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369471&isReview=true

category: geriatric medicine


title: Machine Learning techniques for the diagnosis of Schizophrenia based on Event Related Potentials

abstract:
AntecedentThe diagnosis of schizophrenia could be enhanced with objective neurophysiological biomarkers, such as the event related potential features in conjunction with machine learning procedures. A previous work extracted features from event related responses to three oddball paradigms (auditory and visual P300, and mismatch negativity) for the discrimination of schizophrenic patients. They used several classifiers: Naive Bayes, Support Vector Machine, Decision Tree, Adaboost and Random Forest. The best accuracy was obtained with Random Forest (84.7%).

ObjectiveThe aim of this study was to examine the efficacy of Multiple Kernel Learning classifiers and Boruta feature selection method exploring different features for single-subject classification between schizophrenia patients and healthy controls.

MethodsA cohort of 54 schizophrenic subjects and 54 healthy control subjects were studied. Three sets of features related to the event related potentials signal were calculated: Peak related features, Peak to Peak related features and Signal related features. The Boruta feature selection algorithm was used to evaluate its impact on classification accuracy. A Multiple Kernel Learning algorithm was applied to address schizophrenia detection.

ResultsWe obtained a classification accuracy of 83% using Multiple Kernel Learning classifier with the whole dataset. This result in accuracy triangulates previous work and shows that the differences between schizophrenic patients and controls are robust even when different classifiers are used. Appling the Boruta feature selection algorithm a classification accuracy of 86% was yielded. The variables that contributed most to the classification were mainly related to the latency and amplitude of the auditory P300.

ConclusionThis study showed that Multiple Kernel Learning can be useful in distinguishing between schizophrenic patients and controls. Moreover, the combination with the Boruta algorithm provides an improvement in classification accuracy and computational cost.


title: Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation, France, December 2021 - February 2022

abstract: In Dec 2021-Feb 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and we developed an unbiased bioinformatics method which can detect all co-infections irrespective of the SARS-CoV-2 lineages involved. Applied on 21,387 samples collected between weeks 49-2021 and 08-2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.


title: Local CCL18 and CCL21 expand lung fibrovascular niches and recruit lymphocytes, leading to tertiary lymphoid structure formation in prolonged COVID-19

abstract: Post-acute lung sequelae of COVID-19 are challenging many survivors across the world, yet the mechanisms behind are poorly understood. Our results delineate an inflammatory cascade of events occurring along disease progression within fibrovascular niches. It is initiated by endothelial dysfunction, followed by heme scavenging of CD163+ macrophages and production of CCL18. This chemokine synergizes with local CCL21 upregulation to influence the stromal composition favoring endothelial to mesenchymal transition. The local immune response is further modulated via recruitment of CCR7+ T cells into the expanding fibrovascular niche and imprinting an exhausted, T follicular helper-like phenotype in these cells. Eventually, this culminates in the formation of tertiary lymphoid structures, further perpetuating chronic inflammation. Thus, our work presents misdirected immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and leads to profound tissue repurposing and chronic inflammation.

category: allergy and immunology


title: Validation of AI-based software for objectification of conjunctival provocation test results in routine examinations and clinical studies

abstract:
Abstracts1. BackgroundProvocation tests are widely used in allergology to objectively reveal patients sensitivity to specific allergens. The objective quantification of an allergic reaction is a crucial characteristic of the tests. Due to the absence of objective quantitative measurements the conjunctival provocation test (CPT) is a less frequently used method despite its sensitivity and simplicity. We developed a new method AllergoEye based on AI for quantitative evaluation of conjunctival allergic reactions and validated it in a clinical study.

2. MethodsAllergoEye was implemented as a two component system. The first component is based on an Android smartphone camera for imaging the patients eye and the second one is PC based for image analysis and quantification. For AllergoEye validation an open-label, prospective, monocentric study was carried out on 41 patients. Standardized CPT was performed with sequential titration of grass allergen in 4 dilutions with the reaction evaluated by subjective/qualitative symptom scores and by quantitative AllergoEye scores.

3. ResultsAllergoEye demonstrated high sensitivity (98%) and specificity (90%) as compared with human-estimated allergic reaction. Tuning cut-off threshold allowed to increase the specificity of AllergoEye to 97%, where correlation between detected sensitivity to allergen and sIgE CAP-class becomes obvious. Strikingly, such correlation was not found with sensitivity to allergen detected by subjective and qualitative symptom scores.

4. ConclusionClinical validation demonstrated that AllergoEye is a sensitive and efficient instrument for objective measurement of allergic reactions in CPT for clinical studies as well as for routine therapy control.


title: Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

abstract:
ObjectiveTo determine how the severity of successively dominant SARS-CoV-2 variants has changed over the course of the COVID-19 pandemic.

DesignProspective cohort analysis.

SettingCommunity- and hospital- sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board (1.2 million people).

ParticipantsAll sequenced non-nosocomial adult COVID-19 cases in NHS GG&C identified to be infected with the relevant SARS-CoV-2 lineage during the following analysis periods. B.1.177/Alpha analysis: 1st November 2020 - 30th January 2021 (n = 1640). Alpha/Delta analysis: 1st April - 30th June 2021 (n = 5552). AY.4.2 Delta/non-AY.4.2 Delta analysis: 1st July - 31st October 2021 (n = 9613). Non-AY.4.2 Delta/Omicron analysis: 1st - 31st December 2021 (n = 3858).

Main outcome measuresAdmission to hospital, admission to ICU, or death within 28 days of first positive COVID-19 test

ResultsIn the B.1.177/Alpha analysis, 300 of 807 (37.2%) B.1.177 cases were recorded as hospitalised or having a more severe outcome, compared to 232 of 833 (27.9%) Alpha cases. After adjusting for the following covariates: age, sex, time of positive test, comorbidities and partial postcode, the cumulative odds ratio was 1.51 (95% central credible interval 1.08-2.11) for Alpha versus B.1.177. In the Alpha/Delta analysis, 113 of 2104 (5.4%) Alpha cases were recorded as hospitalised or having a more severe outcome, compared to 230 of 3448 (6.7%) Delta cases. After adjusting for the above covariates plus number of vaccine doses and reinfection, the cumulative odds ratio was 2.09 (95% central credible interval 1.42-3.08) for Delta versus Alpha. In the non-AY.4.2 Delta/AY.4.2 Delta analysis, 845 of 8644 (9.8%) non-AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 101 of 969 (10.4%) AY.4.2 Delta cases. After adjusting for the previously stated covariates, the cumulative odds ratio was 0.99 (95% central credible interval 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta. In the non-AY.4.2 Delta/Omicron analysis, 30 of 1164 (2.6%) non-AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 26 of 2694 (1.0%) Omicron cases. After adjusting for the previously listed covariates, the median cumulative odds ratio was 0.49 (95% central credible interval 0.22-1.06) for Omicron versus non-AY.4.2 Delta.

ConclusionsThe direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity in virulence between variants, coupled with independent evolutionary emergence, demonstrates that severity associated with future SARS-CoV-2 variants is inherently unpredictable.


title: Blood-derived DNA methylation clusters associate with adverse social exposures and endophenotypes of stress-related psychiatric illness in a trauma-exposed cohort of women

abstract:
Adverse social exposures (ASEs) such as low income, low educational attainment, and childhood/adult trauma exposure are associated with variability in brain region measurements of grey matter volume (GMV), surface area (SA), and cortical thickness (CT). These CNS morphometries are associated with stress-related psychiatric illnesses and represent endophenotypes of stress-related psychiatric illness development. Epigenetic mechanisms, such as 5-methyl-cytosine (5mC), may contribute to the biological embedding of the environment but are understudied and not well understood. How 5mC relates to CNS endophenotypes of psychiatric illness is also unclear.

In 97 female, African American, trauma-exposed participants from the Grady Trauma Project, we examined the associations of childhood trauma burden (CTQ), adult trauma burden, low income and low education with blood-derived 5mC clusters and variability in brain region measurements in the amygdala, hippocampus and frontal cortex subregions. To elucidate whether peripheral 5mC indexes CNS endophenotypes of psychiatric illness, we tested whether 73 brain/blood correlated 5mC clusters, defined by networks of correlated 5mC probes measured on Illuminas HumanMethylation Epic Beadchip, mediated the relationship between ASEs and brain measurements.

CTQ was negatively associated with rostral middle frontal gyrus (RMFG) SA ({beta} = - 0.231, p = 0.041). Low income and low education were also associated with SA or CT in a number of brain regions. Seven 5mC clusters were associated with CTQ (pmin = 0.002), two with low education (pmin = 0.010), and three with low income (pmin = 0.007). Two clusters fully mediated the relation between CTQ and RMFG SA, accounting for 47% and 35% of variability respectively. These clusters were enriched for probes falling in DNA regulatory regions, as well as signal transduction and immune signaling gene ontology functions. Methylome-network analyses showed enrichment of macrophage migration (p = 9x10-8), T cell receptor complex (p = 6x10-6), and chemokine-mediated signaling (p = 7x10-4) pathway enrichment in association with CTQ.

Our results support prior work highlighting brain region variability associated with ASEs, while informing a peripheral inflammation-based epigenetic mechanism of biological embedding of such exposures. These findings could also serve to potentiate increased investigation of understudied populations at elevated risk for stress-related psychiatric illness development.


title: Closed-loop stimulation of lateral cervical spinal cord in upper-limb amputees to enable sensory discrimination

abstract: Modern myoelectric prosthetic hands have multiple independently controllable degrees of freedom, but require constant visual attention to use effectively. As we know from motor control of our native limbs, somatosensory feedback is essential to control our movements and provides information not available through vision alone. Similarly, stimulation of the nervous system can potentially provide artificial somatosensory feedback to reduce the reliance on visual cues to efficiently operate prosthetic devices. We have shown previously that epidural stimulation of the lateral cervical spinal cord can evoke tactile sensations perceived as emanating from the missing arm and hand in people with upper-limb amputation. In this study, two subjects with upper-limb amputation used this somatotopically-matched tactile feedback to discriminate object size and compliance while controlling a prosthetic hand. With less than 30 minutes of training each day, both subjects were able to use artificial somatosensory feedback to perform a subset of the discrimination tasks at a success level well above chance. Subject 1 was consistently more adept at determining object size (74% accuracy; chance: 33%) while Subject 2 achieved a higher accuracy level in determining object compliance (60% accuracy; chance 33%). In each subject, discrimination of the other object property was only slightly above or at chance level suggesting that the task design and stimulation encoding scheme are important determinants of which object property could be reliably identified. Our observations suggest that artificial somatosensory feedback provided via spinal cord stimulation can be readily used to infer information about the real-world with minimal training, but that task design is critical and that performance improvements may not generalize across tasks.

category: rehabilitation medicine and physical therapy


title: Price and Tax Elasticity of Alcohol Consumption: Evidence from Seven Indian States

abstract: In this paper, we develop a novel methodology for constructing price indices of India Made Foreign Liquor (IMFL), which account for incompatible state-level taxation structure and policies across seven states in India. We use this price index to compute price and tax elasticity of IMFL in the seven states. We find that a 1% increase in price leads to only a 0.057% decline in consumption while a 1% increase in tax reduces alcohol consumption by 0.14%. We extend our estimates to show that a 10% increase in taxes will lead to an 8.4% increase in tax revenue. Our results are the most updated estimates of alcohol consumption elasticities, which overcomes several challenges such as varying manufacturing costs across states and varying tax across types of products within states, which other papers do not.

category: health economics


title: Impact of supplementary air filtration on airborne particulate matter in a UK hospital ward

abstract:
BackgroundDuring the COVID-19 pandemic, aerosol spread of SARS-CoV-2 has been a major problem in healthcare facilities, resulting in increased use of supplementary HEPA filtration to mitigate transmission. We report here a natural experiment that occurred when an air filtration unit (AFU) on an inpatient ward for older people was accidentally switched off.

AimTo assess aerosol transport within the ward and determine whether the AFU reduced particulate matter (PM) levels in the air.

MethodsTime-series PM, CO2, temperature and humidity data (at 1 minute intervals) was collected from multiple sensors around the ward over two days in August 2021. During this period, the AFU was accidentally switched off for approximately 7 hours, allowing the impact of the intervention on particulates (PM1-PM10) to be assessed using a Mann-Whitney test. Pearson correlation analysis of the PM and CO2 signals was also undertaken to evaluate the movement of airborne particulates around the ward.

FindingsThe AFU greatly reduced PM counts of all sizes throughout the ward space (p<0.001 for all sensors), with PM signals positively correlated with indoor CO2 levels (r = 0.343 - 0.817; all p<0.001). Aerosol particle counts tended to rise and fall simultaneously throughout the ward space when the AFU was off, with PM signals from multiple locations highly correlated (e.g. r = 0.343 - 0.868 (all p<0.001) for PM1).

ConclusionAerosols freely migrated between the various sub-compartments of the ward, suggesting that social distancing measures alone cannot prevent nosocomial transmission of SARS-CoV-2. The AFU greatly reduced PM levels throughout the ward space.

Practical implicationsO_LIAerosols can freely migrate throughout whole wards, suggesting that social distancing measures alone are not enough to prevent SARS-CoV-2 transmission.
C_LIO_LIAppropriately sized supplementary room air filtration, if utilised correctly, can greatly reduce aerosol levels throughout ward spaces.
C_LIO_LIAir filtration devices are often placed in rooms without any consideration given to their performance. It is therefore important to commission air filtration devices using PM and CO2 sensors before they are utilised in order to demonstrate that they are effective throughout entire ward spaces.
C_LI


title: Impact of the Russian invasion of Ukraine onthe COVID-19 pandemic dynamics

abstract: Full-scale invasion of Ukraine by Russian troops, which began on February 24, 2022, caused an unprecedented number of refugees, which in the ongoing COVID-19 pandemic could increase the number of patients. The recent pandemic dynamics in Ukraine, Poland, Germany and in the whole world was compared with the previous epidemic waves simulated with the use of the generalized SIR-model and corresponding parameter identification procedure. Since before the war the estimation of the number of infectious persons per capita in Ukraine 3.6 times exceeded the global figure, the increase of the number the new cases and the pandemic duration is expected. From the beginning of March 2022 the increase of the averaged number of new cases in Germany and worldwide is visible.


title: Mass Homicide by Firearm in Canada: Effects of Legislation

abstract:
Canada implemented a series of laws regulating firearms including background checks and licensing, references, psychological questionnaires, prohibition of paramilitary style rifles, and magazine capacity restrictions in order to decrease the incidences and deaths from mass shootings. The associated effects of these laws were examined over the years 1974 to 2020.

A model was constructed using difference-in-differences analysis of firearms and non-firearms mass homicide incidences and death rates. Mass homicides were defined as a homicide due to one event involving three or more deaths.

Incidence rates of mass homicide by firearm were found to be 0.11 (95%CI 0.08, 0.14) per million compared to a non-firearm mass homicide rate of 0.12 (95% CI 0.10, 0.15) per million. Mass homicide death rates by firearm were found to be 0.39 (95% CI 0.29, 0.49) per million compared to a non-firearm mass homicide rate of 0.47 (95% CI 0.34, 0.61) per million. Overall, there is a gradual declining trend in the incidence of mass homicide by firearm (IRR 0.97 (95% CI 0.96, 0.98)) and by non-firearm (IRR 0.97 (95% CI 0.97, 0.98)). The decline in mass homicide death rate by firearm and non-firearm is IRR 0.96 (95% CI 0.95, 0.97), and IRR 0.97 (95% CI 0.96, 0.98) respectively.

No associated decrease in mass homicide incidence rates or death rates with firearms legislation was found after the implementation of background checks and prohibition of full auto firearms in 1980, by the implementation of references and psychological questionnaires in 1994, by the restriction of magazine capacity in 1994, the prohibition of paramilitary rifles in 1994, or licensing in 2001.

category: health policy


title: Symptom Management When Non-Invasive Advanced Respiratory Support is Used During End-of-Life Care: A Systematic Review

abstract:
Objectivesto narrate the canon of knowledge around symptom control at end of life for patients using, or having recently used, non-invasive advanced respiratory support (NARS) at end of life for respiratory failure.

MethodsA systematic review forming a narrative synthesis from a wide range of sample papers from Medline, Embase, CINAHL, Emcare, Cochrane and OpenGrey databases. A secondary search of grey literature was also performed with hand searching reference lists and author citations. The review was undertaken using the ENTREQ checklist for quality.

ResultsIn total 15 studies were included in the synthesis and four themes were generated: NARS as a buoy (NARS can represent hope and relief from the symptoms of respiratory failure), NARS as an anchor (NARS brings significant treatment burden), Impact on Staff (uncertainty over the balance of benefit and burden as well as complex patient care drives distress amongst staff providing care) and the Process of Withdrawal (withdrawal of therapy felt to be futile exists as discrete event in patient care but is otherwise poorly defined).

ConclusionNARS represents a complex interplay of hope, symptom control, unnaturally prolonged death and treatment burden. The literature captures the breadth of these issues but further, detailed, research is required in almost every aspect of practice around end-of-life care and NARS - especially how to manage symptoms at the end of life.