title: Asthma treatment outcome and factors associated with uncontrolled asthma among adult asthmatic patients in Addis Ababa, Ethiopia

abstract:
BackgroundAsthma is a major public health challenge in the world resulting in significant health and economic burden. The modifiable and non-modifiable risk factors could have considerable impact on Asthma control and medical care. Our goal was to evaluate the treatment outcome and identify risk factors for poor asthma control among asthmatic patients in Addis Ababa, Ethiopia.

MethodA multicentre cross-sectional study using interview and chart review was conducted among asthmatic patients attending ambulatory care of two large public hospitals in Addis Ababa, Ethiopia between March and June 2018. The Global Initiative for Asthma Guideline was used to determine treatment outcomes. The variables of interest were described using descriptive statistics such as frequencies, percentages, mean, and standard deviations. Multivariable logistic regression was used to determine factors associated with uncontrolled asthma. All statistical significance level was determined at p<0.05.

ResultA total of 230 asthmatic patients were interviewed. More than half (65.2%) of patients were females and their mean age was 54{+/-}15.1 years. Overall, 50.4% of the patients had uncontrolled asthma status. More than two number of trigger factors (AOR=1.88; 95%CI:1.09-2.01), cold weather (AOR=2.11;95%CI: 1.51-2.42), exacerbations of asthma in the last 12 months (AOR=2.01;95%CI:1.39-2.32), moderate persistent asthma (AOR=3.47;95%CI:1.75-5.13), severe persistent asthma (AOR=2.90;95%CI:2.56-3.98) and Salbutamol Puff alone regimen (AOR=2.30;95%CI:2.01-2.76) use were significantly associated with uncontrolled asthma.

ConclusionMore than half of asthmatic patients had uncontrolled asthma treatment outcome. This indicates the need to give due attention to asthma patients with uncontrolled status particularly to those with identified risk factors. Health care providers should work in creating patient awareness on appropriate use of their prescribed medications, avoidance of asthma triggering factors for decreasing the progression of the disease and better asthma control.


title: Genetic Associations with Polycystic Ovary Syndrome: The Role of The Mitochondrial Genome; A Systematic Review and Meta-analysis

abstract:
1.BackgroundPolycystic Ovary Syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, whilst the contribution of mitochondrial genetics in PCOS remains largely unknown.

AimThis study aims to systematically evaluate the literature regarding the associations between the mitochondrial genome and PCOS.

MethodsA literature search focused on PCOS and mitochondrial genetics was conducted on (1) MEDLINE (2) EMBASE and (3) The Cochrane Library (CENTRAL and Cochrane Reviews). Search results were screened for eligibility, and data involving genetic variants of mitochondrial DNA (mtDNA) was extracted. Quantitative data was presented in forest plots, and where this was not possible, data was analysed in a qualitative manner. Quality of studies was assessed using the Q-Genie tool.

ResultsOf the 13,812 identified studies, 15 studies were eligible for inclusion, with 8 studies suitable for meta-analysis. Women with PCOS showed higher frequencies of a 9-bp deletion, and aberrant SNPs in the ND5, A6, and 7 tRNA-encoding genes. They also showed lower frequencies of two SNPs in the D-Loop of the genome. Women with PCOS also exhibited significantly lowered mtDNA copy number.

ConclusionWomen with PCOS harbour genetic variants in coding and non-coding regions of the mitochondrial genome. This may disrupt the electron transport chain and lead to oxidative stress, causing apoptosis of cells and further genetic damage. However, further studies of higher quality are required to confirm these associations.

category: genetic and genomic medicine


title: Somatic mutations in both blood cells and vascular endothelium from patients with severe coronary artery diseases

abstract: Individuals with clonal hematopoiesis of indeterminate potential (CHIP) is associated with a 2-4 fold increase in cardiovascular diseases (CVDs). While most studies focus on mutant blood cells, we propose that a better insight into the CHIP-CVD connection can be obtained by examining the genetic mutations in both the vascular endothelium and peripheral blood samples from the same patient. In this study, we examined somatic mutations by whole exome sequencing in paired blood and vascular samples from 4 patients with severe coronary artery disease who underwent coronary artery bypass graft surgery. We found that blood and endothelium can acquire the same mutations during aging and CHIP-associated mutations are not uncommon in vascular endothelium in patients with severe CVDs. Since vascular endothelial cells have critical roles in the regulation of cardiovascular function, mutant vascular endothelium offers an opportunity for further investigations to improve our diagnosis and management of individuals with CHIP.

category: cardiovascular medicine


title: Hierarchical true prevalence, risk factors and clinical symptoms of tuberculosis among suspects in Bangladesh

abstract:
BackgroundThe study was aimed to estimate the true prevalence of human tuberculosis (TB); identify risk factors and clinical symptoms of TB; and detect rifampicin (RIF) sensitivity in Bangladesh.

MethodsThe cross-sectional study was conducted in three Bangladesh districts during 2018. Potential risk factors, clinical symptoms, and comorbidities were collected from 684 TB suspects. Sputum specimens were examined by LED microscopy. TB hierarchical true prevalence, risk factors and clinical symptoms were estimated and identified using a Bayesian analysis framework. Rifampicin sensitivity of M. tuberculosis (MTB) was detected by GeneXpert MTB/RIF assay.

ResultsThe median TB true prevalence was 14.2% (3.8; 34.5). Although overall clustering of prevalence was not found, several DOTS centers were identified with high prevalence (22.3% to 43.7%). Risk factors for TB identified (odds ratio) were age (> 25 to 45 years 2.67 (1.09; 6.99), > 45 to 60 years 3.43 (1.38; 9.19) and individuals in families/neighborhoods where a TB patient(s) has (ve) already been present (12.31 (6.79; 22.60)). Fatigue, night sweat, fever and hemoptysis were identified as important clinical symptoms. Seven of the GeneXpert MTB/RIF positive sputum specimens (65) were resistant to rifampicin.

ConclusionsAbout one in every seven TB suspects was affected with TB. Around 11% of the TB patients carry multi drug resistant MTB. Hierarchical true prevalence estimation allowed identifying DOTS centers with high TB burden. Insights from this study will enable more efficient use DOTS centers-based TB surveillance to end the TB epidemic in Bangladesh by 2035.

category: epidemiology


title: Effectiveness of Pfizer-BioNTech Vaccine Against COVID-19 Associated Hospitalizations among Lebanese Adults >=75 years- Lebanon, April-May 2021

abstract:
IntroductionIn Lebanon, the nationwide vaccination against COVID-19 was launched in February-2021 using Pfizer-BioNTech vaccine and prioritizing elderly, persons with comorbidities and healthcare workers. Our study aims to estimate the post-introduction vaccine effectiveness (VE) of Pfizer-BioNTech in preventing COVID-19 hospitalization among [≥]75 years in Lebanon.

MethodsA case-control study design was used. Cases were Lebanese, [≥]75 years and hospitalized with positive PCR result during April-May 2021. Cases were randomly selected from the COVID-19 database of the Epidemiological Surveillance Unit(ESU) at the Ministry of Public Health(MOPH). Each case was matched by age and locality to 2 controls. Controls were hospitalized, non-COVID-19 patients with negative PCR result, randomly selected from the MOPH hospital admission database. VE was calculated for fully and partially vaccinated, using multivariate conditional logistic regression analyses.

Results345 cases and 814 controls were recruited. Half were females, with a mean age of 83 years. 14 cases(5%) and 143 controls(22%) were fully vaccinated. Bivariate analysis showed significant association with: gender, month of confirmation/admission, general health, chronic medical conditions, main income source and living arrangement. After adjusting for month of admission and gender, multivariate analysis yielded a VE of 82% (95%CI = 69%-90%) against COVID-19 associated hospitalization for those fully vaccinated and 53% (95%CI = 23%-71%) for those partially vaccinated ([≥]14 days of first or within 14 days of second dose).

ConclusionsOur study showed that Pfizer-BioNTech vaccine is effective in reducing risk for COVID-19- associated hospitalization in Lebanese elderly([≥]75 years). Additional studies are warranted to explore vaccine effectiveness in reducing hospitalization in younger age groups, as well as in reducing covid-19 infections.


title: The influence of sex steroid treatment on insular connectivity in gender dysphoria

abstract:
The influence of sex hormones on brain function has been investigated in multiple neuroimaging studies. Sexually dimorphic characteristics were found for the insular cortex, though little is known about hormonal effects on sex-specific functional connectivity patterns and insular functions ranging from emotion regulation to interoception and higher-level cognition. Thus, better understanding of direct sex steroid effects on insular connectivity remains essential. Thereby, gender-dysphoric individuals receiving gender-affirming hormone therapy represent an interesting cohort to address this gap in available knowledge.

To analyze the potential effect of sex steroids on insular connectivity at rest, 14 transgender women, 19 transgender men, 24 cisgender women, and 15 cisgender men were recruited. All participants underwent two magnetic resonance imaging sessions involving resting-state acquisitions separated by a median time period of 4.5 months. Between scans, transgender subjects received gender-affirming hormone therapy.

A seed based functional connectivity analysis revealed a significant 2-way interaction effect of group-by-time between right insula, cingulum, left middle frontal gyrus and left angular gyrus. Post-hoc tests revealed an increase in connectivity for transgender women when compared to cisgender men. Furthermore, spectral dynamic causal modelling showed reduced effective connectivity from the posterior cingulum and left angular gyrus to the left middle frontal gyrus as well as from the right insula to the left middle frontal gyrus.

These findings suggest a considerable influence of long-term estrogen administration and androgen suppression on brain networks implicated in interoception, own-body perception and higher-level cognition. Nevertheless, further studies are needed to shed light on the underlying mechanisms.

category: psychiatry and clinical psychology


title: Assessing responsiveness to direct verbal suggestions in depersonalization-derealization disorder

abstract: The dissociative disorders and germane conditions are reliably characterized by elevated responsiveness to direct verbal suggestions. However, it remains unclear whether atypical responsiveness to suggestion is similarly present in depersonalization-derealization disorder (DDD). 55 DDD patients and 36 healthy controls completed a standardised behavioural measure of direct verbal suggestibility that includes a correction for compliant responding (BSS-C), and psychometric measures of depersonalization-derealization (CDS), mindfulness (FFMQ), imagery vividness (VVIQ), and anxiety (GAD-7). Patients displayed nonsignificantly lower suggestibility than controls, (g = 0.26) but significantly lower mindfulness (g = 1.38), and imagery vividness (g = 0.63), and significantly greater anxiety (g = 1.39). Although suggestibility did not correlate with severity of depersonalization-derealization symptoms in controls, r=-.03 [95% CI: -.36, .30], there was a weak tendency for a positive association in patients, r=.25, [95% CI: -.03, .48]. Exploratory analyses revealed that patients with more severe anomalous bodily experiences were also more responsive to suggestion, an effect not seen in controls. This study demonstrates that DDD is not characterized by elevated responsiveness to direct verbal suggestions. These results have implications for the aetiology and treatment of this condition, as well as its classification as a dissociative disorder in psychiatric nosology.


title: 3D Capsule Networks for Brain MRI Segmentation

abstract:
INTRODUCTIONSegmenting the brain anatomy around a tumor on brain images is important for radiotherapy and surgical planning. Current auto-segmentation methods often fail to segment the brain anatomy when it is distorted by tumors.

OBJECTIVETo develop and validate 3D capsule networks (CapsNets) that can segment brain structures with spatial features that were not represented in the training data.

MethodsWe developed, trained, and tested 3D CapsNets using 3430 brain MRIs acquired in a multi-institutional study. We compared our CapsNets with U-Nets using a battery of performance measures, including accuracy in segmenting various brain structures, segmenting brain structures with spatial features not represented in the training data, performance when the models are trained using limited data, memory requirements, and computation times.

RESULTS3D CapsNets can segment third ventricle, thalamus, and hippocampus with Dice scores of 94%, 94%, and 91%, respectively. 3D CapsNets outperform 3D U-Nets in segmenting brain structures that were not represented in the training data, with Dice scores more than 30% higher. 3D CapsNets are also remarkably smaller models compared to 3D U-Nets, with 93% fewer trainable parameters. This led to faster convergence of 3D CapsNets during training, making them faster to train compared to U-Nets. The two models were equally fast during testing.

CONCLUSION3D CapsNets can segment brain structures with high accuracy, outperform U-Nets in segmenting brain structures with features that were not represented during training, and are remarkably more efficient compared to U-Nets, achieving similar results while their size is an order of magnitude smaller.

category: radiology and imaging


title: Safety and Efficacy of Navigational Bronchoscopy with Archimedes Virtual Bronchoscopic Platform in Patients with Advanced Pulmonary Disease

abstract:
BackgroundPatients with advanced lung disease who present with suspicious pulmonary nodules (SPNs) undergoing transthoracic needle aspiration pose a diagnostic challenge given risk for complications. Virtual bronchoscopic navigation (VBN) is an alternative means to biopsy patients.

Study DesignThe study was a retrospective chart review of all patients who underwent VBN with the Archimedes platform. Demographic information, radiographic evidence of parenchymal lung disease and pulmonary function testing were gathered. Peri-procedure complications and clinical data on biopsy results were gathered to assist in determining both adequate tissue sample (defined if adequate specimen was obtained as per pathology/cytology report) and diagnostic yield (defined as if after further testing/CT imaging from 1 year post-procedure the diagnosis did not change). Univariate analysis was performed to determine the impact of clinical factors on diagnostic yield.

ResultsNinety-six patients with 110 nodules underwent VBN. Eight-eight patients (92%) had radiographic emphysema with 56% having moderate to severe. Fourteen patients (17%) had radiographic ILD. Adequate tissue sample at time of VBN was 93%. Overall diagnostic yield in 80 patients (excluding 16 patients who were initially benign/non-diagnostic that were lost to follow-up) was 72%. Overall complication rate was 7% with 1-pneumothorax (1%), 3-significant bleeding and 3-hospitalized for respiratory failure.

ConclusionIn our cohort of patients the diagnostic yield and complication rate were comparable to other studies where there were fewer patients with advanced lung disease. This data suggests that VBN-guided bronchoscopic biopsy of SPNs is a viable diagnostic option with an acceptable safety profile.

category: respiratory medicine


title: RBDAct: Home screening of REM sleep behaviour disorder based on wrist actigraphy in Parkinson's patients

abstract:
BackgroundREM sleep behaviour disorder (RBD) is a disabling, often overlooked sleep disorder affecting up to 70% of patients with Parkinsons disease. Identifying and treating RBD is critical to prevent severe sleep-related injuries, both to patients and bedpartners. Current diagnosis relies on nocturnal video-polysomnography, which is an expensive and cumbersome exam requiring specific clinical expertise.

ObjectivesTo design, optimise, and validate a novel home-screening tool, termed RBDAct, that automatically identifies RBD in Parkinsons patients based on wrist actigraphy only.

MethodsTwenty-six Parkinsons patients underwent two-week home wrist actigraphy worn on their more affected arm, followed by two non-consecutive in-lab evaluations. Patients were classified as RBD versus non-RBD based on dream enactment history and video-polysomnography. We characterised patients movement patterns during sleep using raw tri-axial accelerometer signals from wrist actigraphy. Machine learning classification algorithms were then trained to discriminate between patients with or without RBD using actigraphic features that described patients movements. Classification performance was quantified with respect to clinical diagnosis, separately for in-lab and at-home recordings.

ResultsClassification performance from in-lab actigraphic data reached an accuracy of 92.9{+/-}8.16% (sensitivity 94.9{+/-}7.4%, specificity 92.7{+/-}13.8%). When tested on home recordings, accuracy rose to 100% over the two-week window. Features showed robustness across tests and conditions.

ConclusionsRBDAct provides reliable predictions of RBD in Parkinsons patients based on home wrist actigraphy only. These results open new perspectives for faster, cheaper and more regular screening of sleep disorders, both for routine clinical practice and for clinical trials.

category: neurology


title: Post-COVID-19 Memory Impairment: Prevalence and Associated Factors

abstract:
IntroductionMemory complaints resulting from COVID-19 may have a significant impact on the survivors quality of life. Unfortunately, there is insufficient information available on memory loss and its relationship to COVID-19. Therefore, the purpose of this research was to determine the prevalence of memory complaints in post-COVID-19 patients and to find potential contributing factors.

MethodA cross-sectional survey was conducted on 401 individuals who had previously been diagnosed with COVID-19 at four COVID testing centers situated across Bangladesh. The MAC-Q questionnaire was used to evaluate memory. A binary logistic regression model was fit to study the variables related to memory complaints, with a p-value of <0.05 deemed statistically significant.

ResultMemory complaints was prevalent in 19.2% of the post-COVID patients. Individual predictor analysis revealed that among the treatment modalities, steroids and antibiotics were associated with impaired memory. Multiple logistic regression showed that individuals who recovered from COVID-19 within six to twelve months were more likely to have memory deficits. Even though age, sex, oxygen demand, and hospitalization were not linked with memory complaints, rural residents exhibited more significant memory complaints than urban residents.

ConclusionNearly one-fifth of the COVID-19 patients suffer from various degrees of memory complaints within one year. However, no association was found between COVID-19 severity to memory complaints.


title: Post-COVID-19 Memory Complaints: Prevalence and Associated Factors


title: A Machine-Learning Based Objective Measure for ALS Disease Severity

abstract: Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). An objective measure for tracking disease severity and progression would be a powerful tool for evaluating real-world drug effectiveness, efficacy in clinical trials, as well as identifying participants for cohort studies. Here we develop a machine learning (ML) based objective measure for ALS disease severity, based on voice samples and accelerometer measurements from a longitudinal dataset collected by the ALS Therapy Development Institute (ALS-TDI) over four years. 584 people living with ALS consented and carried out prescribed speaking and limb-based tasks. 542 participants contributed 5814 voice recordings, and 350 contributed 13009 accelerometer samples, while simultaneously measuring ALSFRS-R scores. Using the data from 475 participants, we trained machine learning (ML) models to predict bulbar-related FRS scores from speech, and limb-related scores from accelerometer samples. On the test set (n=109 participants) the voice models achieved a multiclass AUC of 0.86 (95% CI, 0.85-0.88) on speech FRS prediction, whereas the accelerometer models achieved a median multiclass AUC of 0.73 on 6 limb-related functions. Further, the correlation (and inverse correlations) across different bulbar and limb functions observed in the self-reported ALSFRS-R scores are preserved in the ML-derived scores. Next, we used these models and self-reported ALSFRS-R scores to evaluate the real-world effects of edaravone, a drug recently approved for use in ALS. In the cohort of 54 test participants who received edaravone as part of their usual care, the ML-derived objective scores were consistent with the self-reported ALSFRS-R scores, and both showed highly variable outcomes from edaravone treatment from person to person. At the individual level, the continuous ML-derived score is able to capture a gradual change that is absent in the integer ALSFRS-R scores. This demonstrates the value of these tools for assessing both disease severity and potentially drug effects.


title: Quantitative proteomics and phosphoproteomics of urinary extracellular vesicles define diagnostic and prognostic biosignatures for Parkinson's Disease

abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been recognized as genetic risk factors for both familial and sporadic forms of Parkinsons disease (PD). However, compared to cancer, overall lower genetic mutations contribute to the cause of PD, propelling the search for protein biomarkers for early detection of the disease. Utilizing 141 urine samples from four groups, healthy individuals (control), healthy individuals with G2019S mutation in the LRRK2 gene (non-manifesting carrier/NMC), PD individuals without G2019S mutation (idiopathic PD/iPD), and PD individuals with G2019S mutation (LRRK2 PD), we applied a proteomics strategy to determine potential diagnostic and prognostic biomarkers for PD from urinary extracellular vesicles (EVs). After efficient isolation of urinary EVs through chemical affinity followed by mass spectrometric analyses of EV peptides and enriched phosphopeptides, we identified and quantified 4,480 unique proteins and 2,682 unique phosphoproteins. We detected multiple proteins and phosphoproteins elevated in PD EVs that are known to be involved in important PD pathways such as neuronal cell death, neuroinflammation, autophagy, and formation of amyloid fibrils. We established two panels of proteins and phosphoproteins as novel candidates for disease and risk biomarkers, and substantiated using ROC, machine learning, and in-depth network analysis. Several disease biomarkers were further validated in patients with PD using parallel reaction monitoring (PRM) and immunoassay for targeted quantitation. These findings demonstrate a general strategy of utilizing biofluid EV proteome/phosphoproteome as an outstanding and non-invasive source for a wide range of disease exploration.


title: Developing a multivariate predictive model of hospital outpatient attendance for patients of all ages

abstract:
ObjectivesPatient non-attendance at outpatient appointments (DNA) is a major concern for healthcare providers. Non-attendances increase waiting lists, reduce access to care and may be detrimental not for the patient who did not attend. However, non-targeted interventions to reduce the DNA rate may not be effective and thus we aim to produce a model which can accurately predict which appointments will be attended.

MethodsIn this work, a random forest classification algorithm was trained to predict whether an appointment will be missed using 7 million past outpatient appointments. The model was applied to patients of all ages and appointments with all specialties at a major London teaching hospital including a validation set covering the COVID-19 pandemic.

ResultsThe model achieves an AUROC score of 0.76 and accuracy of 73% on test data. We find that the waiting period between booking an the appointment, the patients past DNA behaviour, and the levels of deprivation in their local area are important factors in predicting future DNAs.

DiscussionOur model is strongly predictive of whether a hospital outpatient appointment will be attended. Its performance on both patients who did not appear in the training data and appointments from a different time period which covers the Covid-19 pandemic indicate it generalized well across both face to face and virtual appointments and could be used to target resources and intervention towards those patients who are likely to miss an appointment. Moreover, it highlights the impact of deprivation on patient access to healthcare

ConclusionOur model successfully predicts patient attendance at outpatient appointments.

FundingThis study was partially funded by STFC DiRAC innovation fellowships which funded the work of Jonathan Holdship and Harpreet Dhanoa. An Award/Grant number is not applicable to this funding.

Strentghs and limitations of this studyO_LIWe produce the first model which can accurately predict the attendance of all outpatient appoints for all ages and specialities at a large, multisite teaching hospital.
C_LIO_LIWe show a strong correlation between patient non-attendance and deprivation demonstrating that random forest algorithms can provide insight as well as useful predictions
C_LIO_LIWe find that the broad target population results in a slightly less accurate model than those from the literature that are built for specific outpatient clinics
C_LI

category: health informatics


title: Clonal hematopoiesis and risk of chronic liver disease

abstract: Chronic liver disease is a major public health burden worldwide. Despite various liver injury mechanisms, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis. We examined the association between clonal hematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 58,358 individuals from four prospective cohorts with whole exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent chronic liver disease (OR 2.70 CI 1.42, 5.16, p=0.002) and incident chronic liver disease (HR 2.01 CI 1.46, 2.79, p=0.001) from both alcoholic and nonalcoholic causes. Individuals with CHIP showed 75% greater odds of MRI detectable liver inflammation and fibrosis (5.9% versus 3.5%, p=0.007) compared to those without CHIP. To assess causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (OR 2.37 CI 1.57, 3.6, p<0.001). In a dietary model of nonalcoholic steatohepatitis (NASH), mice transplanted with Tet2-deficient hematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated via NLRP3 inflammasome and increased downstream inflammatory cytokine expression, including IL6. In summary, clonal hematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression via an aberrant inflammatory response.

category: hematology


title: Association of Sleep Behaviors with Risk of Esophageal Cancer

abstract:
IMPORTANCEEsophageal cancer is among the most lethal type of cancers worldwide. However, risk factors contributing to more than tenfold increase in esophageal cancer in the last 50 years remain underexplored.

OBJECTIVEThis study aimed to examine the associations between sleep behaviors and esophageal cancer overall, by histology, and according to genetic predispositions.

DESIGNA prospective cohort study.

SETTINGA population-based study.

PARTICIPANTSA total of 410,428 participants aged 37-73 years at enrollment between 2006 and 2010 in the UK Biobank were followed up until March 31st, 2016 for England and Wales and October 31st, 2015 for Scotland.

MAIN OUTCOME AND MEASUREThe risk of incident esophageal cancer.

RESULTSDuring 2,799,342 person-years of follow-up, 410 incident esophageal cancer cases (294 adenocarcinomas) were diagnosed. Evening chronotype, sleep <6 or >9 h/day, daytime napping, and daytime sleepiness were significantly associated with increased risk of esophageal cancer in age-adjusted models and had a Plikelihood ratio test [≤]0.20 after multivariable adjustment. Compared with the group without these high-risk behaviors, participants with one high-risk behavior had a 41% (HR=1.41, 95%CI: 1.13, 1.77) increased risk of esophageal cancer, and those with two or more behaviors showed a 79% higher risk (HR=1.79, 95%CI: 1.32, 2.42) (Ptrend<0.001). These associations were largely driven by esophageal adenocarcinoma (Ptrend<0.001) but not squamous cell carcinoma (Ptrend=0.340). The elevated risks for esophageal adenocarcinoma were similar within strata of PRS quintiles (Pinteraction=0.791).

CONCLUSION AND RELEVANCEUnhealthy sleep behaviors were associated with an increased risk of esophageal cancer, primarily adenocarcinoma, independent of genetic risk. Sleep behaviors may serve as modifiable factors for the prevention of esophageal cancer, particularly esophageal adenocarcinomas.

Key PointsO_ST_ABSQuestionC_ST_ABSAre sleep behaviors associated with the risk of esophageal cancer?

FindingsIn this prospective cohort study that included 410,428 participants in the UK Biobank, evening chronotype, sleep <6 or >9 h/day, daytime napping, and sleepiness were associated with increased risk of esophageal cancer. A greater number of these unhealthy sleep behaviors was associated with a higher risk of esophageal cancer. The elevated risks were primarily observed for esophageal adenocarcinoma and were independent of genetic risk.

MeaningSleep behaviors may serve as modifiable factors for the esophageal cancer prevention, particularly esophageal adenocarcinoma, independent of genetic risk.


title: COVID-19 vaccines effectiveness against symptomatic SARS-CoV-2 Delta variant infection: a population-based case-control study in St. Petersburg, Russia

abstract:
BackgroundStudies of mRNA and vector-based vaccines used in different countries report acceptable levels of effectiveness against SARS-CoV-2 infection caused by the Delta variants of SARS-CoV-2. No studies estimated vaccine effectiveness (VE) of Gam-COVID-Vac and other vaccines used in Russia against symptomatic infection with Delta variant. In this population-based case-control study, we aimed to estimate the effectiveness of the Russian COVID-19 vaccines against symptomatic SARS-CoV-2 during the recent outbreak caused by the Delta VOC in October 2021 in St. Petersburg, Russia.

MethodsIn a population-based case-control study with density sampling of controls, we acquired information on cases and controls from two independent studies conducted in St. Petersburg. Cases were symptomatic patients with confirmed SARS-CoV-2 (using polymerase chain reaction (PCR) test) referred to low-dose computed tomography (LDCT) triage in two outpatient centres between October 6 and 14, 2021 during the Delta variant outbreak. We recruited the controls during the representative survey of the seroprevalence study conducted during the same period in St. Petersburg using random digit dialling. In the primary analysis, we used logistic regression models to estimate the adjusted (age, gender, and history of confirmed COVID-19) VE against symptomatic SARS-CoV-2 resulted in a referral to triage centre for three vaccines used in Russia: Gam-COVID-Vac, EpiVacCorona, and CoviVac.

FindingsWe included 1,254 cases and 2,747 controls recruited between the 6th and 14th of October in the final analysis. VE was 56% (95% CI: 48 to 63) for Gam-COVID-Vac (Sputnik V), 49% (95% CI: 29 to 63) for 1-dose Gam-COVID-Vac (Sputnik V) or Sputnik Light, -58% (95% CI: -225 to 23) for EpiVacCorona and 40% (95% CI: 3 to 63) for CoviVac. Without adjustment for the history of confirmed COVID-19 VE for all vaccines was lower, except for one-dose Gam-COVID-Vac (Sputnik Light). The adjusted VE was slightly lower in women -- 51% (95% CI: 39 to 60) than men -- 65% (95% CI: 5 to 73). It was also higher in younger age. However, in the analysis restricted to participants without a history of confirmed COVID-19, the differences in VE by age group were smaller.

InterpretationIn contrast to other Russian vaccines, Gam-COVID-Vac is effective against symptomatic SARS-CoV-2 infection caused by Delta VOC. Effectiveness is likely higher than the estimated 56% due to bias arising from high prevalence of the past COVID-19 in St. Petersburg.

FundingPopulation-based survey in St. Petersburg was funded by Polymetal International, plc.


title: COVID-19 vaccines effectiveness against symptomatic SARS-CoV-2 during Delta variant surge: a population-based case-control study in St. Petersburg, Russia


title: Modelling preventive measures and their effect on generation times in emerging epidemics

abstract: AO_SCPLOWBSTRACTC_SCPLOWWe present a stochastic epidemic model to study the effect of various preventive measures, such as uniform reduction of contacts and transmission, vaccination, isolation, screening and contact tracing, on a disease outbreak in a homogeneously mixing community. The model is based on an infectivity process, which we define through stochastic contact and infectiousness processes, so that each individual has an independent infectivity profile. In particular, we monitor variations of the reproduction number and of the distribution of generation times. We show that some interventions, i.e. uniform reduction and vaccination, affect the former while leaving the latter unchanged, whereas other interventions, i.e. isolation, screening and contact tracing, affect both quantities. We provide a theoretical analysis of the variation of these quantities, and we show that, in practice, the variation of the generation time distribution can be significant and that it can cause biases in the estimation of basic reproduction numbers. The framework, because of its general nature, captures the properties of many infectious diseases, but particular emphasis is on COVID-19, for which numerical results are provided.


title: Values and preferences of the general population in Indonesia in relation to COVID-19 self-testing: A cross-sectional survey

abstract:
ObjectivesInnovative diagnostics are essential to assist members of the general population become active agents of case detection. In Indonesia, a country with an over-burdened healthcare system, individuals could use self-tests for SARS-CoV-2 to determine their COVID-19 status. To assess the acceptability of SARS-CoV-2 self-testing among the general population in Indonesia, a cross-sectional, population-based survey was conducted in mid-2021 in Jakarta and the provinces of Banten and North Sulawesi.

MethodsThis was a survey that approached respondents in >600 randomly selected street-points in the three study geographies. A 35-item questionnaire was used to collect data on key variables, such as willingness to use and to pay for a SARS-CoV-2 self-test and likely actions following a positive result. Bivariate and multivariate regression analyses were performed.

ResultsOf 630 respondents, (318 were female), 14% knew about COVID-19 self-testing, while 62.7% agreed with the concept of people being able to self-test at home, unassisted, for COVID-19. If self-tests were available in Indonesia, >60% of respondents would use them if they felt it necessary and would undertake regular self-testing e.g., weekly if recommended. Upon receiving a positive self-test result, most respondents would communicate it (86.03%), request post-test counseling (80.79%), self-isolate (97.46%), and/or warn their close contacts (n=570, 90.48%).

ConclusionsSARS-CoV-2 self-testing would be acceptable to a majority of the Indonesian public, to learn whether they have COVID-19. Self-testing could contribute to an over-burdened healthcare system by helping COVID-19-infected people become agents of change in epidemiological surveillance of SARS-CoV-2 in their communities.

category: public and global health


title: Effectiveness of BBV152 vaccine against SARS-CoV-2 infections, hospitalizations, and deaths among healthcare workers in the setting of high delta variant transmission in New Delhi, India

abstract:
BackgroundDelta variant transmission resulted in surge of SARS CoV-2 cases in New Delhi, India during the early half of year 2021. Health Care Workers (HCWs) received vaccines on priority for prevention of infection. Real life effectiveness of BBV152 vaccine against severe disease including hospitalization and death was not known.

ObjectiveTo estimate effectiveness of BBV152 vaccine among HCWs against SARS CoV-2 infection, hospitalization or death

DesignObservational study

Settinga multi -speciality tertiary care public funded hospital in New Delhi, India.

Participants12,237 HCWs

InterventionsBBV152 vaccine (Covaxin, Bharat Biotech limited, Hyderabad, India); whole virion inactivated vaccine; two doses four weeks apart

Measurementsvaccine effectiveness after receipt of two doses of BBV152 protecting against any SARS CoV-2 infection, symptomatic infections or hospitalizations or deaths, and hospitalizations or deaths.

ResultsThe mean age of HCWs was 36({+/-}11) years, 66% were men and 16% had comorbidity. After adjusting for potential covariates viz age, sex, health worker type category, body mass index, and comorbidity, the vaccine effectiveness (95% Confidence Interval) in fully vaccinated HCWs and [≥]14 days elapsed after the receipt of second dose was 44% (37 to 51, p<0.001) against symptomatic infection, hospitalization or death due to SARS CoV-2, and 61% (37 to 76, p<0.001) against hospitalization or death, respectively.

ConclusionsBBV152 vaccine with complete two doses offer a modest response to SARS CoV-2 infection in real life situations against a backdrop of high delta variant community transmission. Efforts in maximizing receipt of full vaccines should be invested for HCWs, who are at higher occupational risk for infection.


title: Super-Resolution of Magnetic Resonance Images Acquired Under Clinical Protocols using Deep Attention-based Method

abstract: AO_SCPLOWBSTRACTC_SCPLOWVast quantities of Magnetic Resonance Images (MRI) are routinely acquired in clinical practice but, to speed up acquisition, these scans are typically of a quality that is sufficient for clinical diagnosis but sub-optimal for large-scale precision medicine, computational diagnostics, and large-scale neuroimaging research. Here, we present a critic-guided framework to upsample low-resolution (often 2D) MRI scans. In addition, we incorporated feature-importance and self-attention methods into our model to improve the interpretability of this work. We evaluate our framework on paired low- and high-resolution brain MRI structural full scans (i.e. T1-, T2-weighted and FLAIR sequences are simultaneously input) obtained in clinical and research settings from scanners manufactured by Siemens, Phillips and GE. We showed that the upsampled MRIs are qualitatively faithful to the ground-truth high-quality scans (PSNR = 35.39; MAE = 3.78E -3; NMSE = 4.32E -10; SSIM = 0.9852; mean normal-appearing grey/white matter ratio intensity differences ranging from 0.0363 to 0.0784 for FLAIR, from 0.0010 to 0.0138 for T1-weighted and from 0.0156 to 0.074 for T2-weighted sequences). The automatic raw segmentations of tissues and lesions using the super-resolved images have fewer false positives and higher accuracy than those obtained from interpolated images in protocols represented with more than three sets in the training sample, making our approach a strong candidate for practical application in clinical research.


title: Segmentation stability of human head and neck medical images for radiotherapy applications under de-identification conditions: benchmarking for data sharing and artificial intelligence use-cases

abstract:
Background and PurposeIncreased demand for head and neck cancer (HNC) radiotherapy data for algorithmic development has prompted an escalation of head and neck image dataset sharing. Medical images must comply with data protection requirements so that data re-use is enabled without disclosing direct or indirect identifiers of study participants. Defacing, i.e., the removal of facial features, is often considered an acceptable compromise between data protection and re-usability. While existing defacing tools have been developed by the neuroimaging community, their acceptability for preserving data that is crucial to radiotherapy applications have not been previously explored. Therefore, we systematically investigated the impact of currently available defacing algorithms on HNC organs at risk (OARs) used for radiotherapy planning.

Materials and MethodsWe utilized a publicly available dataset of T2-weighted magnetic resonance imaging (MRI) scans for 55 HNC patients with eight previously segmented OARs (right/left submandibular glands, right/left parotid glands, right/left level II neck lymph nodes, right/left level III neck lymph nodes). Four publicly available defacing algorithms were investigated: mri_deface, defacer, fsl_deface, and pydeface. We implemented a 5-fold cross-validation 3D U-net based OAR auto-segmentation model to perform two main experiments: 1.) comparing original and defaced data for training when evaluated on original data; 2.) using original data for training and comparing model evaluation on original and defaced data. These models were primarily investigated using the Dice similarity coefficient (DSC). The mean surface distance (MSD), and mean Hausdorff distance at 95% (MHD95) were also explored.

ResultsOf the studied algorithms, mri_deface and defacer were unable to produce any usable images for evaluation, while fsl_deface and pydeface were unable to remove the face for 18 and 24% of subjects, respectively. All the remaining subjects had voxels removed from all OARs. Composite OAR DSC using defaced data for model training and evaluation yielded statistically worse mean DSC performance (p [≤] 0.05) for both fsl_deface (training = 0.770, evaluation = 0.709) and pydeface (training = 0.631, evaluation = 0.453) compared to the original data (0.780). Significance testing demonstrated that the DSC and MHD95 were significantly better (p [≤] 0.05) for the model trained with the original data for both submandibular glands and for the right parotid gland compared to the model trained with fsl_deface data. Similarly, the MSD was significantly better (p [≤] 0.05) for the model trained with the original data for the left submandibular gland and both parotid glands. When trained with pydeface data, the model had significantly worse performance (p [≤] 1e-5) compared to the model trained with the original data for all structures and metrics.

ConclusionWe demonstrate the choice of defacing algorithm has a significant impact on HNC OAR auto-segmentation model development and deployment. Our work incentivizes the further development of HNC radiotherapy-specific defacing methods.


title: Muscle and Adipose Tissue Segmentations at the C3 Vertebral Level for Sarcopenia-Related Clinical Decision-Making in Patients with Head and Neck Cancer

abstract: The accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets of head and neck CT imaging currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, we detail the annotation of a large set of head and neck CT images for use in automated sarcopenia-related clinical decision making and body composition analysis. A set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was manually segmented at the C3 vertebral level using sliceOmatic in .tag format. Subsequently, using publicly disseminated Python scripts, we generated corresponding segmentations files in Neuroimaging Informatics Technology Initiative format. In addition to segmentation data, additional clinical demographic data germane to body composition analysis have been retrospectively collected for these patients from the University of Texas MD Anderson Cancer Center databases. These data are a valuable resource for studying sarcopenia and body composition analysis in patients with HNC.


title: Should healthcare workers with SARS-CoV-2 household exposures work? A Cohort Study.

abstract:
ImportanceDue to high community transmission of the Omicron variant, healthcare workers (HCWs) have been increasingly reporting household exposures to confirmed COVID-19 cases. Quebec (Canada) provincial guidelines required to quarantine these HCWs. Facing the risk of staffing shortages, our hospital decided to allow them to work.

ObjectiveTo evaluate the risk for HCWs, who were household contacts, to become positive for COVID-19 by RT-PCR and evaluate the risk of nosocomial COVID-19 transmission.

DesignCohort of HCWs with a history of household exposure to a confirmed case of COVID-19.

SettingCHU Sainte-Justine, a tertiary care mother and child center in Montreal (QC) Canada

ParticipantsConsecutive HCWs who contacted OHS between December 20, 2021 and January 17, 2022 for a history of household exposure to COVID-19.

ExposureConfirmed case of COVID-19 in the household

Main outcome and measuresThe main outcome was a positive RT-PCR for SARS-CoV-2. Outbreaks and nosocomial cases were identified through daily analysis of COVID-19 cases, by sector and part of the usual Infection Prevention and Control surveillance process.

ResultsOverall, 237 of 475 (50%) HCWs who declared a known household contact with a confirmed COVID-19 case remained negative. Of those who became positive, 196 (82.4%) were positive upon initial testing and were quarantined. Only 42 (15%) of 279 HCWs who were allowed to work became positive, a median of 4 days after the initial test. The absence of symptoms at initial evaluation (OR 3.8, 95% CI 2.5-5.7) and having received a third vaccine dose more than 7 days before (OR 1.88, 95% CI 1.3 - 2.8) were associated with an increased odds of remaining negative. There was no outbreak among HCWs and no nosocomial transmission to patients from a HCW that was allowed to work, while a known household contact.

Conclusion and relevanceMeasures taken to protect the health care environment from COVID-19 must be cautiously balanced with the risk of staffing shortage. Allowing vaccinated asymptomatic HCWs who are known household contacts of confirmed COVID-19 cases to work is likely a safe alternative, when staff shortage is anticipated.

category: occupational and environmental health


title: A multilevel approach to individual and organizational predictors of stress and fatigue among healthcare workers of a university hospital: A longitudinal study

abstract:
ObjectiveHealthcare workers are at high risk of experiencing stress and fatigue due to the demands of their work within hospitals. Improving their physical and mental health and in turn, the quality and safety of care, requires considering factors at both individual and organizational levels. Using a multi-center prospective cohort, this study aims to identify the individual and organizational predictors of stress and fatigue of healthcare workers in several wards from university hospitals.

MethodsOur cohort consist of 695 healthcare workers from 32 hospital wards drawn at random within four volunteer hospital centers in Paris-area. Three-level longitudinal analyses, accounting for repeated measures (level 1) across participants (level 2) nested within wards (level 3) and adjusted for relevant fixed and time varying confounders were performed.

ResultsAt baseline, the sample was composed by 384 registered nurses, 300 auxiliary nurses and 11 midwives. According to the 3-level longitudinal models, some predictors were found in common for both stress and fatigue (low support from the hierarchy, low safety culture, overcommitment at work, presenteeism while sick...). However, specific predictors for high level of stress (negative life events, low support from the colleagues and high frequency of break cancellation) and fatigue (commuting duration, frequent use of interim staff in the ward...) were also found.

ConclusionOur results may help identify at-risk healthcare workers and wards, where interventions to reduce stress and fatigue should be focused. These interventions could include manager training to favor better staff support and overall safety culture of healthcare workers.

1. What is already known about this subject?O_LIHealthcare workers have high levels of perceived stress and fatigue, particularly in medical fields highly exposed to infectious risks.
C_LIO_LIHigh occupational stress and fatigue can negatively affect healthcare workers behaviors in terms of absenteeism, and ultimately intention to leave as well as quality of care.
C_LIO_LIIndividual and organizational differences contribute to different perceptions and consequences of occupational stress and fatigue in healthcare workers.
C_LI

2. What are the new findings?O_LIThe ward-level environment significantly influences the stress and fatigue of healthcare workers, in addition to individual factors and time variations.
C_LIO_LIHierarchy providing low support and with low safety culture, work overinvestment, presenteeism while sick, and working in smaller wards were identified as predictors of both high stress and fatigue of healthcare workers.
C_LIO_LINegative life events (whether personal or professional), low support from the colleagues and high frequency of break cancellation are specific predictors of high level of stress. While commuting duration, frequent use of interim staff and working in a medical ward were associated with high level of fatigue.
C_LI

3. How might this impact on policy or clinical practice in the foreseeable future?O_LIIn this study, we can identify some areas for improvement to better prevent stress and fatigue for healthcare workers. High stress and fatigue can be reduced through mutual and specific organizational intervention strategies.
C_LI


title: Interactions between nuclear and mitochondrial SNPs and Parkinson's disease risk

abstract: Interactions between the products of the nuclear and mitochondrial genomes are critical for the function of most eukaryotic cells. Recently the introduction of mitochondrial replacement therapy has raised the question of incompatibilities between mitochondrial and nuclear variants, and their potential influence on the genetic makeup of human populations. Such interactions could also contribute to the variability of the penetrance of pathogenic DNA variants. This led us to investigate the frequencies of combinations of nuclear and mitochondrial SNP alleles (mitonuclear combinations) in healthy individuals (n=5375) and in a cohort of patients with Parkinsons disease (PD, n=2210). In the unaffected population, we were not able to find associations between nuclear and mitochondrial variants with a false discovery rate below 0.05 after accounting for multiple testing (i.e., the number of combinations examined). However, in the PD cohort, five combinations surpassed this threshold. Next, combining both cohorts, we investigated whether these associations were modulated by disease status. All five combinations were significant (p<10-3 for all tests).These combinations also showed significant evidence for an effect of the interaction between the mitochondrial and nuclear variants on disease risk. Their nuclear components mapped to TBCA, NIBAN3 and GLT25D1 and an uncharacterised intergenic region. In summary, starting from a single cohort design we identified combinations of nuclear and mitochondrial variants affecting PD disease risk.


title: SARS-CoV-2 viremia precedes an IL6 response in severe COVID-19 patients: results of a longitudinal prospective cohort

abstract:
BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.

MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.

ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with >1.3 log10 copies/ml) and also in those with at least one IL6>30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.

ConclusionsIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

category: infectious diseases


title: Systemic adverse effects induced by the BNT162b2 vaccine are associated with higher antibody titers from 3 to 6 months after vaccination

abstract:
ObjectiveWe aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan.

MethodsWe enrolled 378 healthcare workers (255 women, 123 men) whose Ab titers 3 and 6 months after the second dose were analyzed in our previous study and whose characteristics and adverse effects were collected previously using a structured self-report questionnaire.

ResultsMedian age was 44 years. While injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first. Multivariate analysis showed that fever was significantly correlated with female sex for the second dose (odds ratio [OR], 2.139; 95% confidence interval [95%CI], 1.185-3.859), older age for the first dose (OR, 0.962; 95%CI, 0.931-0.994) and second dose (OR, 0.957; 95%CI, 0.936-0.979), and dyslipidemia for the first dose (OR, 8.750; 95%CI, 1.814-42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with fever than in those without fever after first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were respectively 21.7% and 19.3% higher in the group with anti-inflammatory agent use than in the group without anti-inflammatory agent use.

ConclusionParticipants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects.


title: A NOVEL METHOD FOR HANDLING PRE-EXISTING CONDITIONS IN PREDICTION MODELS FOR COVID-19 DEATH

abstract:
ObjectiveTo derive a predicted probability of death (PDeathDx) based upon complete sets of ICD-10 codes assigned to patients prior to their diagnosis of COVID-19. PDeathDx is intended for use as a summary metric for pre-existing conditions in multivariate models for COVID-19 death.

MethodsCases were identified through the COVID-19 Shared Data Resource (CSDR) of the Department of Veterans Affairs. The diagnosis required at least one positive nucleic acid amplification test (NAAT). The primary outcome was death within 60 days of the first positive test. We retrieved all diagnoses entered into the electronic medical record for visits, on problem lists, and at the time of hospital discharge if they were at least 14 days prior to the NAAT. ICD-9 codes were converted to ICD-10 equivalents using a crosswalk provided by the Centers for Medicare/Medicaid Services. ICD-10 codes were converted to their category diagnoses defined as all columns to the left of the decimal point. Each patient was considered to have or not have each category diagnosis prior to the NAAT. A computer program calculated the number of cases for each category diagnosis, the relative risk (RR) of death, and its confidence interval (CI) using a Bonferroni adjustment for multiple comparisons. RRs were re-centered by subtracting 1 so that high-risk conditions had a positive value while protective conditions had a negative one. Diagnoses found to be significant were entered into a logistic model for death in a stepwise fashion. Each patient was assigned (RR-1) to each category diagnosis if they had the condition or 0 otherwise. The resulting model was used to derive PDeathDx for each patient and the area under its receiver operating characteristic (ROC) curve calculated. Single variable logistic models were also derived for age at diagnosis, the Charlson 2-year (Charl2Yr) and lifetime (CharlEver) scores, and the Elixhauser 2-year (Elix2Yrs) and lifetime (ElixEver) scores. Stata was used to compare the ROCs for PDeathDx and each of the other metrics.

ResultsOn September 30, 2021 there were 347,220 COVID-19 patients in the CSDR. 18,120 patients (5.33%) died within 60 days of their diagnosis. After consolidating ICD-9 and ICD-10 codes, 29,162,710 separate diagnoses were given to the subjects representing 41,341 ICD-10 codes. This set was reduced to 1,890 category diagnoses assigned to the group for the first time on 19,184,437 occasions. Of the 1,890 category diagnoses, 425 involved >= 100 subjects and had a lower boundary for the CI >= 1.50 (a high-risk condition) or upper boundary <= 0.80 (a protective condition). Stepwise logistic regression showed that 153 were statistically significant, independent predictors of death. PDeathDx was slightly less powerful than age as a discriminator (ROC = 0.811 +/- 0.002 vs 0.812 +/- 0.001, respectively; P < 0.001) but was superior to the Charl2Yr (ROC = 0.727 +/- 0.002; P < 0.001), CharlEver (ROC = 0.753 +/- 0.002; P <= 0.001), Elix2Yr (ROC = 0.694 +/- 0.002; P < 0.001); and ElixEver (ROC = 0.731 +/- 0.002; P < 0.001). Univariate analysis and multivariate modeling showed that many of the most high-risk conditions are under-represented or not included in the Charlson Index. These include hypertension, dementia, degenerative neurologic disease, or diagnoses associated with severe physical disability.

ConclusionsOur method for handling pre-existing conditions in multivariate analysis has many advantages over conventional comorbidity indices. The approach can be applied to any condition or outcome, can use any categorical predictors including medications, creates its own condition weights, handles rare as well as protective conditions, and returns actionable information to providers. The latter include the specific ICD-10 groups, their contribution to the risk, and their rank order of importance. Finally, PDeathDx is equivalent to age as a discriminator of outcomes and outperforms 4 other comorbidity scores. If validated by others, this approach provides an alternative and more robust approach to handling comorbidities in multivariate models.


title: Detection of SARS-CoV-2 in Different Human Biofluids Using the Loop-Mediated Isothermal Amplification Assay: A Prospective Diagnostic Study in Fortaleza, Brazil

abstract:
We adopted the reverse transcriptase - loop mediated isothermal amplification (RT-LAMP) to detect SARS-Cov-2 in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 saliva, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the golden standard technique RT-qPCR. Accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis was 96% (95% CI 87-99) and 85% (95% CI 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swab processed via extraction kit. Accurate and rapid diagnosis could aid COVID-19 pandemic management by identifying, isolating, and treating patients rapidly.

HighlightsO_LINew nucleic acid amplification test for the diagnosis of SARS-CoV-2 using the RT-LAMP
C_LIO_LIN5 primer set showed mutations in strains of interest, such as the gamma strain (P.1) of SARS-CoV-2
C_LIO_LIWhen evaluated in combination N5 and Orf9 primer sets maintained high sensitivity and specificity
C_LI


title: Early Alveolar Epithelial Cell Necrosis is a Potential Driver of ARDS with COVID-19

abstract:
RationaleAcute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after passing the peak of viral load. However, the underlying mechanisms remain unclear.

ObjectivesHere, we assess whether alveolar epithelial cell necrosis and subsequent releases of damage associated molecular patterns (DAMPs) at an early disease stage aggravate ARDS with COVID-19

MethodsIn patients with COVID-19 with and without ARDS and healthy adults, serum levels of the following were quantified: an epithelial total cell death marker, cytokeratin18-M65; an epithelial apoptosis marker, CK18-M30; HMGB-1; and alveolar epithelial and endothelial injury markers, sRAGE, angiopoietin-2, and surfactant protein-D. Molecular mechanisms of alveolar epithelial cell death and effects of HMGB-1 neutralization on alveolar tissue injury were assessed using a mouse model of COVID-19-induced ARDS.

Measurements and main resultsThe levels of CK18-M65, CK18-M30, and alveolar tissue injury markers were elevated in early stages of ARDS. The median M30/M65 ratio, an epithelial apoptosis indicator, was 31.50% in patients with ARDS, a value significantly lower than that of non-ARDS patients or healthy subjects. Serum levels of HMGB-1, one of DAMPs released from necrotic cells, were also significantly elevated in ARDS versus non-ARDS patients. In a COVID-19-induced ARDS mouse model, alveolar epithelial cell necrosis involved two forms of programmed necrosis, necroptosis and pyroptosis. Finally, neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model.

ConclusionsNecrosis, including necroptosis and pyroptosis, seems to be the primary form of alveolar epithelial cell death, and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.

The impact of this researchAlveolar tissue injury in acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after passing the peak of viral load. Our analysis of serum samples from COVID-19 patients and an animal model revealed that alveolar epithelial necrosis, including necroptosis and pyroptosis, occurs at the early disease stage of COVID-19-induced ARDS. Moreover, our data indicated that damage-associated molecular patterns released from necrotic alveolar epithelial cells are promising therapeutic targets to prevent the COVID-19 aggravation.

category: intensive care and critical care medicine


title: Are allergic diseases a risk factor for systemic side effects after COVID-19 vaccines?

abstract:
Background/ aimMass vaccination seems to be the most effective way to turn back to the pre-pandemic period and end the pandemic. Unfortunately, COVID-19 vaccines have some side effects. In phase studies of currently-approved COVID-19 vaccines, patients with a known allergy or a history of anaphylaxis were excluded from the studies. This situation creates doubts about the course of atopy and the presence of allergic disease related to the side effects of COVID-19 vaccines in patients with allergic diseases. Therefore, our aim with this study was to evaluate local side effects (LSE) and systemic side effects (SSE) after COVID-19 vaccines in patients with allergic diseases and to determine possible risk factors.

Materials and MethodsSix hundred forty-eight adult patients who received any COVID-19 vaccine between April 1, 2021 and September 30, 2021 and agreed to participate in the study were included in this case-control retrospective study.

ResultsSix hundred forty-eight adult patients [Female: 446 (68.8%), Male: 202 (32.2%)] participated in the study. After the 1st dose of COVID-19 vaccine, 24.1% of patients reported SSE. After the 2nd dose of COVID-19 vaccine, 67 patients (12.3%) developed SSE. Female gender (OR: 1.757, 95%Cl: 1.143-2.702, p: 0.010), history of previous COVID-19 infection (OR: 1.762, 95%Cl: 1.068-2.906, p: 0.026), and COVID-19 vaccine type administered (OR: 4.443, 95% CI: 2.640-7.476, p<0.001) were found to be independent risk factors for SSE after COVID-19 vaccines. Premedication (OR: 0.454, 95% Cl: 0.281-0.733, p<0.001), was found to be a protective factor for SSE developing after COVID-19 vaccines.

ConclusionCoronoVac and Pfizer-BioNTech COVID-19 vaccines are shown to be well tolerated. Patients with allergic disease do not have an increased risk for SSE that may develop after COVID-19 vaccines. Moreover, doubts or fears about possible side effects in the allergic patient group should not be an obstacle to COVID-19 vaccination.

category: allergy and immunology


title: Genome-wide association analysis identifies ancestry-specific genetic variation associated with medication response in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)

abstract:
BackgroundCharacterization of genetic variation that influences response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes (T2D). SUGAR-MGH examined the acute response to two anti-diabetes medications in order to understand the functional relevance of known T2D- and glycaemic trait-associated genetic loci.

Methods1,000 participants at risk for T2D from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between variants and primary endpoints of drug response. We evaluated the influence of 804 unique T2D and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalization analyses to identify shared genetic signals.

FindingsFive genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency=0{middle dot}026) at rs149403252 and lower fasting glucose following metformin, adjusted for baseline glucose (p=1{middle dot}9x10-9), with a 0{middle dot}94 mmol/L larger decrease in fasting glucose after metformin. We identified associations between T2D-associated variants and glycaemic response, including the T2D-protective C allele of rs703972 near ZMIZ1 and increased levels of active GLP-1 (p=1{middle dot}6x10-5), supporting the role of alterations in incretin levels in T2D pathophysiology.

InterpretationWe present a well phenotyped, densely genotyped, multi-ancestry resource to study gene-drug interactions, uncover novel variation associated with response to common anti-diabetes medications, and provide insight into mechanisms of action of T2D-related variation.

FundingUS National Institutes of Health.

category: endocrinology


title: Estimated Fraction of Incidental COVID Hospitalizations in a Cohort of 250 High-Volume Hospitals Located in 164 Counties

abstract: Scattered reports have suggested that as many as one-half of all hospital inpatients identified as COVID-positive are incidental cases who were admitted primarily for reasons other than their viral infections. To date, however, there are no systemic studies of a representative panel of hospitals based on pre-established criteria for determining whether an individual patient was in fact admitted as a result of the disease. To fill this gap, we developed a formula to estimate the fraction of incidental COVID hospitalizations that relies upon measurable, population-based parameters. We applied this approach to a longitudinal panel of 164 counties throughout the United States, covering a 4-week interval ending in the first week of January 2022. Within this panel, we estimated that COVID incidence has been rising exponentially at a rate of 9.34% per day (95% CI, 8.93-9.87). Assuming that only one-quarter of all recent Omicron infections have been reported by public authorities, we further estimated the aggregate prevalence of active SARS-CoV-2 infection during the first week of January to be 4.89%. During the same week, among 250 high-COVID-volume hospitals within our 164-county panel, an estimated 1 in 4 inpatients was COVID-positive. Among such COVID-positive hospitalized patients, 15.2% were estimated to be incidental infections. Across individual counties, the median fraction of incidental COVID hospitalizations was 13.7%, with an interquartile range of 9.5 to 18.4%. Incidental COVID infections appear to be a nontrivial fraction of all COVID-positive hospitalized patients. In the aggregate, however, the burden of patients admitted for complications of their viral infections appears to be far greater.


title: Evidence on the role of journal editors in the COVID19 infodemic: metascientific study analyzing COVID19 publication rates and patterns

abstract:
ObjectiveInfodemic, a neologism characterizing an excess of fast-tracked low quality publications, has been employed to depict the scientific research response to the COVID19 crisis. The concept relies on the presumed exponential growth of research output. This study aimed to test the COVID19 infodemic claim by assessing publication rates and patterns of COVID19-related research and a control, a year prior.

DesignA Reproduction Number of Publications (Rp) was conceived. It was conceptualized as a division of a week incidence of publications by the average of publications of the previous week. The publication growth rates of preprint and MEDLINE-indexed peer-reviewed literature on COVID19 were compared using the correspondent Influenza output, a year prior, as control. Rp for COVID19 and Influenza papers and preprints were generated and compared and then analyzed in light of the respective growth patterns of their papers and preprints.

Main outcomesOutput growth rates and Reproduction Number of Publications (Rp).

ResultsCOVID19 peer-reviewed papers showed a fourteen fold increase compared to Influenza papers. COVID19 papers and preprints displayed an exponential growth curve until the 20th week. COVID19 papers displayed Rp=3.17{+/-}0.72, while the control group presented Rp=0.97{+/-}0.12. Their preprints exhibited Rp=2.18{+/-}0.54 and Rp=0.97{+/-}0.27 respectively, with no evidence of exponential growth in the control group, as its Rp remained approximately one.

ConclusionsCOVID19 publications displayed an epidemic pattern. As the growth patterns of COVID19 peer-reviewed articles and preprints were similar, and the majority of the COVID19 output came from indexed journals, not only authors but also editors appear to had played a significant part on the infodemic.

Review protocolhttps://osf.io/q3zkw/?view_only=ff540dc4630b4c6e9a2639d732047324

Ethical aspectsNo ethical clarence was required as all analyzed data were publicly available.

O_TEXTBOXSUMMARY BOX

1. What is already known about this subject?

Much has been commented on 2020s excess of publications on COVID19. Independent studies found evidence of increased volume and speed of publication, decreased methodological quality, and qualitative variations in peer review of COVID19 papers, when compared to the scholarly output from before the pandemic. This phenomenon has been branded an infodemic, a neologism implying an epidemic of low-quality information on COVID19 when high quality scientific reports to inform health policies would have been needed the most.

2. What are the new findings?

No study pushed the infodemic metaphor forward to analyze not only volume of publication but also publication rates comparing them to a control group as to clearly pinpoint an exponential phase of contagion in the infodemic (as it would take place in a real epidemic) through a mathematical analysis of the growth patterns and rates of those publications. In this paper, we were able to demonstrate that there has been an infodemic indeed and that the editor population was as susceptible to the infodemic bug as the author population because the exponential phase was shaped not only by authors but mainly by editors from PubMed-indexed journals.

3.How might it impact clinical practice in the foreseeable future?

These results and conclusions are consequential to subsequent studies on rigor and depth of post publication peer review and on editorial practices within the life and health sciences research community.

C_TEXTBOX


title: Point-of-Care MRI with Artificial Intelligence to Measure Midline Shift in Acute Stroke Follow-Up

abstract:
Background and PurposeIn stroke, timely treatment is vital for preserving neurologic function. However, decision-making in neurocritical care is hindered by limited accessibility of neuroimaging and radiological interpretation. We evaluated an artificial intelligence (AI) system for use in conjunction with bedside portable point-of-care (POC)-MRI to automatically measure midline shift (MLS), a quantitative biomarker of stroke severity.

Materials and MethodsPOC-MRI (0.064 T) was acquired in a patient cohort (n=94) in the Neurosciences Intensive Care Unit (NICU) of an academic medical center in the follow-up window during treatment for ischemic stroke (IS) and hemorrhagic stroke (HS). A deep-learning architecture was applied to produce AI estimates of midline shift (MLS-AI). Neuroradiologist annotations for MLS were compared to MLS-AI using non-inferiority testing. Regression analysis was used to evaluate associations between MLS-AI and stroke severity (NIHSS) and functional disability (mRS) at imaging time and discharge, and the predictive value of MLS-AI versus clinical outcome was evaluated.

ResultsMLS-AI was non-inferior to neuroradiologist estimates of MLS (p<1e-5). MLS-AI measurements were associated with stroke severity (NIHSS) near the time of imaging in all patients (p<0.005) and within the IS subgroup (p=0.005). In multivariate analysis, larger MLS-AI at the time of imaging was associated with significantly worse outcome at the time of discharge in all patients and in the IS subgroup (p<0.05). POC-MRI with MLS-AI >1.5 mm was positively predictive of poor discharge outcome in all patients (PPV=70%) and specifically in patients with IS (PPV=77%).

ConclusionThe integration of portable POC-MRI and AI provides automatic MLS measurements that were not inferior to time-consuming, manual measurements from expert neuroradiologists, potentially reducing neuroradiological burden for follow-up imaging in acute stroke.


title: The Epidemiology of Hundreds of Individuals Infected with Omicron BA.1 in Middle-Eastern Jordan

abstract: In less than two months of its detection in Jordan, lineage B.1.1.529 recognized as Omicron, is constituting 55% of all confirmed coronavirus disease of 2019 (COVID-19) infections causing a rise in the daily cases in the country. Herein, we report on 500 cases, among the first identified Omicron infections in Jordan. We also report on the genomic diversity of 25 Omicron viruses identified in nasopharyngeal swabs from Jordan. Our results indicated that 96% of study participants were vaccinated who had asymptomatic, mild or moderate disease. One unvaccinated individual developed severe disease. The median age of Omicron cases was 30 years, and most frequent disease symptoms were: fever, coughing, sore throat, runny nose, general fatigue and muscle/joint pain. Viral genomic analysis results revealed that the BA.1 is the dominant Omicron sublineage in Jordan, with 45 to 58 total mutations. We identified a few amino acid modifications that could impact the accuracy of some polymerase chain reaction (PCR) tests. In summary, infections caused by BA.1 seem milder than earlier infections. However, it is unknown whether this change is due to alterations in the immunity landscape of the infected population or is the result of viral genetic mutations that reduced viral virulence. Hence, comparing similar studies from different countries is likely to give us a get a better understanding of this variant, its behavior and the impact on disease characteristics.


title: DEVELOPMENT OF DISASTER EDUCATION IN THE INITIAL HANDLING OF MULTI-AGENT-BASED EMERGENCIES IN THE PRE-HOSPITAL AREA.

abstract:
BackgroundDisaster risk reduction involves several sectors, legal, social, structural, economic, technological, educational, environmental health, with improved preparedness will be able to reduce the impact of disasters. Capacity that continues to be added with knowledge about rapid disaster response to disasters can make resilience dealing with disasters and preventing the emergence of disaster risks.

PurposeConduct a literature review on articles that examine the importance of disaster education in the initial handling of emergencies in the hospital area

DesignLiterature review

MethodUsing databases with electronic search on ProQuest, SAGE, and Science Direct published in 2017-2021

Results100 articles were used in the review. These articles discuss the importance of disaster education in the initial handling of emergencies in the hospital area. The 15 articles reviewed are original research.

ConclusionLocal communities are well placed to play a central role in hazard identification, development of preparedness plans, detection and response to emergencies, and implementation of recovery efforts. Community leaders and local health workers (e.g. family doctors, nurses, midwives, pharmacists, community health workers) can build public trust, disseminate information, and identify people at risk


title: Identification of age-associated transcriptomic changes linked to immunotherapy response in primary melanoma

abstract: Melanoma is a lethal form of skin cancers that develops due to constitutive activation of MAPK signaling pathway driven by BRAF and NRAS mutations. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment, however drug resistance is rapidly acquired. Several studies reported the increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identified significant upregulation of extracellular matrix and cellular adhesion genes in young cohorts while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 were significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration, were differentially expressed. Differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism has been observed as well. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes during melanoma and novel therapeutic targets for future studies.

category: oncology


title: Effects of 12 weeks of Multi-nutrient supplementation on the Immune and Musculoskeletal systems of Older Adults in Aged-Care (The Pomerium Study): Protocol for a Randomised Controlled Trial

abstract:
IntroductionImmunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function.

Methods and analysisThe Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D3, and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults ([≥]75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial.

DiscussionIf the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care.

Funding, Ethics, Registration and DisseminationThe study is funded by the Australian Medical Research Future Fund. It is approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115), and registered at ANZCTR (12621000420842). Results will be published in peer-reviewed journals and made available to aged-care stakeholders, including providers, residents, and government bodies.

Article Summary Strengths and LimitationsO_LIThis is the first study performing a comprehensive immune, respiratory and functional assessment in aged care residents after receiving a multi-nutrient solution that is commercially available.
C_LIO_LIOur design and tested intervention assure that the results of the study will be rapidly translated into practice.
C_LIO_LIThe main limitation is that any biological effect observed cannot be attributed to one component of the multi-nutrient supplement.
C_LIO_LIAnother limitation is that the potential effect of group differences in energy intake on outcomes can only be monitored by assessing regular dietary intake and weight changes during the study period.
C_LI

category: geriatric medicine


title: Evaluation of gonadal function in transfusion-dependent β-thalassemia patients of Bangladesh

abstract:
BackgroundHypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients, and early recognition and treatment is the core element to restore impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients. The pattern of gonadal function in transfusion-dependent thalassemia patients must be picturized before planning a generalized management plan; therefore, this study was conducted.

MethodsThis cross-sectional study was conducted at the Department of Transfusion Medicine of Bangabandhu Sheikh Mujib Medical University. According to inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, laboratory assessment of LH, FSH, testosterone and estradiol in serum were also done. Data were analyzed using STATA (v.16).

ResultsThe mean age of the patients with transfusion-dependent thalassemia was 18.81{+/-}4.65 (SD), with 53.3% of the patients being male. The most common symptoms of gonadal dysfunction among males were loss of body hair (6%) followed by fatigue (4%), and among females were slow or absent breast growth, hot flashes and amenorrhea (6.82% each).

ConclusionThe overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic, and 5.3% being hypergonadotropic. Therefore, gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.


title: Death review caused by Covid 19 in Bangladesh

abstract:
IntroductionCOVID-19 pandemic had taken away lots of human life prematurely worldwide and death laid its icy hands also on Bangladesh. So, objectives of this study were to explore the monthly distributions, age, sex, co-morbidities, localities and duration of hospital stay among the COVID death cases.

MethodsIn this observational study six months hospital death files were collected and explored for monthly distributions, age, sex, co-morbidities, localities and hospital stay. RT-PCR positive confirmed 113 COVID deaths were enrolled and suspected COVID deaths were excluded. Ethical clearance from the hospital authority was taken before hand. Data was compiled and analyzed by SPSS-20.

ResultsThere was a low frequency of death in May-2021 and October-2021(7.1% and 2.7% respectively) but more during June -2021 to September 2021 (12.4%, 16.8%, 42.5% and 18.6% respectively). Female deaths were little more than male deaths(53.1% vs 46.9%). Age more than 51 years were the most vulnerable where 26(23%) deaths were at age group 51-60 years, 39(34.5%) deaths were at 61-70 years and 22(19.4%) deaths were more than 71 years. Mean age of death was found 60.66 years and mean duration of hospital stay was found 9.45 days. Maximum duration of hospital stay was 45 days for one patient. Co-morbidities of death cases revealed 52(46.00%) patients had DM and HTN both, 17(15.0%) patients had HTN, 16(14.1%) had DM, 3(2.6%) had BA and COPD, 4(3.5%) had CKD, 2(1.7%) had cancer, 3(2.6%) had CVD, 19(16.8%) had IHD and 16(14.1%) patients had no co-morbidities. Locality of the death cases revealed 44(38.9%) came from rural areas and 69(61.1%) came from urban areas.

ConclusionHigher age group and multiple co-morbidities specially DM, HTN and IHD were related with COVID deaths mostly found in our study.


title: T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components

abstract: SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2-infected respiratory cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the alpha, beta, gamma, and delta variant lineages.


title: A qualitative process analysis of DCT as an alternative to self-isolation following close contact with a confirmed case of COVID-19

abstract:
BackgroundIn July 2021, a randomised controlled trial was conducted to compare the effect on SARS-CoV-2 transmission of seven days of daily contact testing (DCT) using lateral flow devise (LFT) and 2 PCR tests as an alternative to 10 days of standard self-isolation with 1 PCR, following close contact with a confirmed case of COVID-19. DCT appeared equivalent to self-isolation in terms of transmission in the trial, however it was not clear how tests were viewed and used in practice. In this qualitative study, we used a nested process to aid interpretation of the trial and provide insight into factors influencing use of tests, understanding of test results, and how tests were used to inform behavioural decisions.

MethodsInterviews were conducted with 60 participants (42 randomised to DCT and 18 randomised to self-isolation) who had been in close contact with a confirmed positive case of COVID-19 and had consented to take part in the trial.

ResultsSub-themes emerging from the data were organised into three overarching themes: (1) assessing the risks and benefits of DCT; (2) use of testing during the study period and (3) future use of testing. Attitudes toward DCT as an alternative to self-isolation, and behaviour during the testing period appeared to be informed by an assessment of the associated risks and benefits. Participants reported how important it was for them to avoid isolation, how necessary self-isolation was considered to be, and the ability of LFTs to detect infection. Behaviour during the testing period was modified to reduce risks and harms as much as possible. Testing was considered a potential compromise, reducing both risk of transmission and the negative impact of self-isolation and was highly regarded as a way to  return to new normal.

ConclusionParticipants in this study viewed DCT as a sensible, feasible and welcome means of avoiding unnecessary self-isolation. Although negative LFTs provided reassurance, most people still restricted their activity as recommended. DCT was also highly valued by those in vulnerable households as a means of providing reassurance of the absence of infection, and as an important means of detecting infection and prompting self-isolation when necessary.


title: Border closure and travel restrictions to control the spread of COVID-19: an update to a Cochrane review

abstract:
BackgroundCOVID-19 has proven to be more difficult to manage for many reasons including its high infectivity rate. One of the potential ways to limit its spread is by limiting free travel across borders, including via air travel. The objective of this systematic review is to identify, critically-appraise and summarize evidence on border closures and travel restrictions.

MethodsThis review is based on the Cochrane review: "International travel-related control measures to contain the COVID-19 pandemic" and followed the same methodology. In brief, we searched for clinical and modelling studies in general health and COVID-19-specific bibliographic databases. The primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome.

ResultsWe included 43, mostly modelling, studies that met our inclusion criteria. Fourteen new studies were identified in the updated search, as well as updated companions (e.g., peer-reviewed publications that were previously only available as pre-prints). Most studies were of moderate to high quality. The added studies did not change the main conclusions of the Cochrane review nor the quality of the evidence (very low to low certainty). However, it did add to the evidence base for most outcomes.

ConclusionsWeak evidence supports the use of border closures to limit the spread of COVID-19 via air travel. Real-world studies are required to support these conclusions.


title: A qualitative study exploring the impact of the COVID-19 pandemic on People Who Inject Drugs (PWID) and drug service provision in the UK: PWID and service provider perspectives

abstract:
BackgroundPeople Who Inject Drugs (PWID) are subject to distinct socio-structural inequalities that can expose them to high risks of COVID-19 transmission and related health and social complications. In response to COVID-19 mitigation strategies, these vulnerabilities are being experienced in the context of adapted drug treatment service provision, including reduced in-person support and increased regulatory flexibility in opioid substitution therapy (OST) guidelines. This study aimed to explore the longer-term impact of the pandemic on the health and wellbeing of PWID, including provider and client experiences of treatment changes.

MethodsInterviews were conducted with 19 PWID and 17 drug treatment providers between May - September 2021, recruited from third-sector drug services in the UK. Data were analysed using reflexive thematic analysis.

ResultsMost participants expressed ongoing fears of COVID-19 transmission, although socio-structural inequalities limited the contexts in which physical distancing could be practised. In addition, virus mitigation strategies altered the risk environment for PWID, resulting in ongoing physical (e.g. drug use patterns and characteristics), economic (e.g. sex work engagement and income generation) and social (e.g. stigmatization and marginalization) harms. Finally, whilst clients reported favourable experiences from service adaptations prompted by COVID-19, there was continued scepticism and caution among providers toward sustaining any treatment changes beyond the pandemic period.

ConclusionsWhilst our findings emphasize the importance of accessible support measures attending to the immediate priorities of PWID during this period, there is a need for additional supports to ensure socio-structural vulnerabilities that disproportionality affect PWID are not exacerbated by the pandemic. In addition, treatment adaptations initiated in response to the pandemic require further attention to ensure they are acceptable to both clients and providers.

category: addiction medicine


title: Over- and under-estimation of vaccine effectiveness

abstract: SARS-CoV-2 vaccines provide not just high protection against infection to the vaccinated individual but also provide indirect protection to its surroundings by blocking further transmission. Divergent results have been reported on the effectiveness of the SARS-CoV-2 vaccines. Here, we argue that this divergence is due to the fact that the analyses did not take into account the indirect protection. Using a novel heterogenous infection model and real-world data, we demonstrate that heterogeneous vaccination rates among families and communities, and the study design that is used, may significantly skew the vaccine effectiveness estimations. We show that estimations of a vaccine with 85% effectiveness will vary between marked underestimation of [~]70% and overestimation of [~]95% depending on the number of interactions between vaccinated and unvaccinated individuals.