title: Acute temporal effect of ambient air pollution on common congenital cardiovascular defects and cleft palate: a case-crossover study

abstract: This symmetric bidirectional case-crossover study examined the association between short-term ambient air pollution exposure during weeks 3-8 of pregnancy and certain common congenital anomalies in Ulaanbaatar, Mongolia, between 2014 and 2018. Using predictions from a Random Forest regression model, authors assigned daily ambient air pollution exposure of particulate matter <2.5 um aerodynamic diameter, sulphur dioxide, nitrogen dioxide, and carbon monoxide for each subject based on their administrative area of residence. We used conditional logistic regression with adjustment for corresponding apparent temperature to estimate relative odds of select congenital anomalies per IQR increase in mean concentrations and quartiles of air pollutants. The adjusted relative odds of cardiovascular defects (ICD-10 subchapter: Q20-Q28) was 2.64 (95% confidence interval: 1.02-6.87) per interquartile range increase in mean concentrations of particulate matter <2.5 um aerodynamic diameter for gestational week 7. This association was further strengthened for cardiac septal defects (ICD-10 code: Q21, odds ratio: 7.28, 95% confidence interval: 1.6-33.09) and isolated ventricular septal defects (ICD-10 code: Q21.0, odds ratio: 9.87, 95% confidence interval: 1.6-60.93). We also observed an increasing dose-response trend when comparing the lowest quartile of air pollution exposure with higher quartiles on weeks 6 and 7 for Q20-Q28 and Q21 and week 4 for Q21.0. Other notable associations include increased relative odds of cleft lip and cleft palate subchapter (Q35-Q37) and PM2.5 (OR: 2.25, 95% CI: 0.62-8.1), SO2 (OR: 2.6, 95% CI: 0.61-11.12), and CO (OR: 2.83, 95% CI: 0.92-8.72) in week 4. Our findings contribute to the limited body of evidence regarding the acute effect of ambient air pollution exposure on common adverse birth outcomes.


title: The Relationship between Continuity of Care with a Primary Care Provider and Duration of Work Disability in Workers with Low Back Pain: A Retrospective Cohort Study

abstract:
ObjectiveTo determine the continuity of care (CoC) provided by general practitioners among workers with low back pain; identify personal, workplace and social factors associated with CoC in this population; and investigate if CoC is associated with working time loss.

Data sourcesAn administrative database containing accepted workers compensation claim and service level data, for workers with back pain from five Australian jurisdictions, injured between July 2010 and June 2015.

Study DesignA retrospective cohort study. Outcomes were CoC with a general practitioner, measured with the Usual Provider Continuity index, and working time loss, measured as the number of weeks for which workers compensation income support benefits were paid.

Extraction methodsEligible workers had at least four general practitioner services, and greater than two weeks working time loss. Usual Provider Continuity index score was categorised as complete, high, moderate, or low CoC. Ordinal logistic regression models examined factors associated with Usual Provider Continuity category. Quantile regression models examined association between duration of working time loss and Usual Provider Continuity category, in four groups with different volumes of general practitioner services.

Principal FindingsComplete CoC was observed in 33.8% of workers, high CoC among 37.7%, moderate CoC in 22.1%, and low CoC in 6.4%. Higher Usual Provider Continuity was associated with fewer general practitioner services, older age, living in urban areas, an occupation as a Community and Personal Service Worker or Clerical and Administrative Worker, and the state of Victoria. In workers with more than two months of time loss, those with complete CoC consistently had shorter durations of time loss.

ConclusionsHigher CoC with a general practitioner is associated with less working time loss and this relationship is strongest in the sub-acute phase of low back pain.

Callout Box

What is known on this topicO_LIContinuity of care is a key component of best practice primary care
C_LIO_LILow back pain is a condition that often requires ongoing management and care from a general practitioner
C_LIO_LIThe relationship between continuity of care and work disability duration, recovery and return to work in workers with low back pain is not known
C_LI

What this study addsO_LIWorkers with low back pain who see the same general practitioner for all services (i.e., have a greater continuity of care) generally have shorter durations of working time loss
C_LIO_LIHigher continuity of care was observed in workers who had fewer PCP services, were aged over 45, lived in urban areas, and worked as a Community and Personal Service Worker or Clerical and Administrative Worker
C_LIO_LIWorkers compensation systems should consider policies and guidelines that increase continuity of care in injured workers
C_LI

category: primary care research


title: mtDNA copy number, mtDNA total somatic deletions, Complex I activity, synapse number and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

abstract: Mitochondrial dysfunction is a neurobiological phenomenon implicated in the pathophysiology of schizophrenia and bipolar disorder that can synergistically affect synaptic neurotransmission. We hypothesized that schizophrenia and bipolar disorder share molecular alterations at the mitochondrial and synaptic level: mtDNA copy number (CN), mtDNA common deletion (CD), mtDNA total deletion, complex I activity, synapse number, and synaptic mitochondria number. These mitochondrial parameters were studied in dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), primary visual cortex (V1), and nucleus accumbens (NAc) of 44 controls (CON), 27 schizophrenia (SZ), and 26 bipolar disorder (BD) subjects. The results showed- (i) the mtDNA CN is significantly higher in DLPFC of both SZ and BD, decreased in the STG of BD, and unaltered in V1 and NAc of both SZ and BD; (ii) the mtDNA CD is significantly higher in DLPFC of BD while unaltered in STG, V1 and NAc of both SZ and BD; (iii) The total deletion burden is significantly higher in DLPFC in both SZ and BD while unaltered in STG, V1, and NAc of SZ and BD; (iv) Complex I activity is significantly lower in DLPFC of both SZ and BD with no alteration in STG, V1 and NAc. (v) The number of synapses is decreased in DLPFC of both SZ and BD, while the synaptic mitochondria number was significantly lower in female SZ and female BD compared to female controls. Overall, these findings will pave the way to better understand the pathophysiology of schizophrenia and bipolar disorder for therapeutic interventions.

category: psychiatry and clinical psychology


title: DIAGNOSTIC ACCURACY OF NON-INVASIVE DETECTION OF SARS-COV-2 INFECTION BY CANINE OLFACTION

abstract:
BACKGROUNDThroughout the COVID-19 pandemic, testing individuals remains a key action. One approach to rapid testing is to consider the olfactory capacities of trained detection dogs.

METHODSProspective cohort study in two community COVID-19 screening centers. Two nasopharyngeal swabs (NPS), one saliva and one sweat samples were simultaneously collected. The dog handlers (and the dogs...) were blinded with regards to the Covid status. The diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction was assessed as compared to nasopharyngeal RT-PCR as the reference standard, saliva RT-PCR and nasopharyngeal antigen testing.

RESULTS335 ambulatory adults (143 symptomatic and 192 asymptomatic) were included. Overall, 109/335 participants tested positive on nasopharyngeal RT-PCR either in symptomatic (78/143) or in asymptomatic participants (31/192). The overall sensitivity of canine detection was 97% (95% CI, 92 to 99) and even reached 100% (95% CI, 89 to 100) in asymptomatic individuals compared to NPS RT-PCR. The specificity was 91% (95% CI, 72 to 91), reaching 94% (95% CI, 90 to 97) for asymptomatic individuals. The sensitivity of canine detection was higher than that of nasopharyngeal antigen testing (97% CI: 91 to 99 versus 84% CI: 74 to 90, p=0.006), but the specificity was lower (90% CI: 84 to 95 versus 97% CI: 93 to 99, p=0.016).

CONCLUSIONSNon-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.

category: public and global health


title: Automatic Extraction of Social Determinants of Health from Medical Notes of Chronic Lower Back Pain Patients

abstract:
BackgroundAdverse social determinants of health (SDoH), or social risk factors, such as food insecurity and housing instability, are known to contribute to poor health outcomes and inequities. Our ability to study these linkages is limited because SDoH information is more frequently documented in free-text clinical notes than structured data fields. To overcome this challenge, there is a growing push to develop techniques for automated extraction of SDoH. In this study, we explored natural language processing (NLP) and inference (NLI) methods to extract SDoH information from clinical notes of patients with chronic low back pain (cLBP), to enhance future analyses of the associations between SDoH and low back pain outcomes and disparities.

MethodsClinical notes (n=1,576) for patients with cLBP (n=386) were annotated for seven SDoH domains: housing, food, transportation, finances, insurance coverage, marital and partnership status, and other social support, resulting in 626 notes with at least one annotated entity for 364 patients. We additionally labelled pain scores, depression, and anxiety. We used a two-tier taxonomy with these 10 first-level ontological classes and 68 second-level ontological classes. We developed and validated extraction systems based on both rule-based and machine learning approaches. As a rule-based approach, we iteratively configured a clinical Text Analysis and Knowledge Extraction System (cTAKES) system. We trained two machine learning models (based on convolutional neural network (CNN) and RoBERTa transformer), and a hybrid system combining pattern matching and bag-of-words models. Additionally, we evaluated a RoBERTa based entailment model as an alternative technique of SDoH detection in clinical texts. We used a model previously trained on general domain data without additional training on our dataset.

ResultsFour annotators achieved high agreement (average kappa=95%, F1=91.20%). Annotation frequency varied significantly dependent on note type. By tuning cTAKES, we achieved a performance of F1=47.11% for first-level classes. For most classes, the machine learning RoBERTa-based NER model performed better (first-level F1=84.35%) than other models within the internal test dataset. The hybrid system on average performed slightly worse than the RoBERTa NER model (first-level F1=80.27%), matching or outperforming the former in terms of recall. Using an out-of-the-box entailment model, we detected many but not all challenging wordings missed by other models, reaching an average F1 of 76.04%, while matching and outperforming the tested NER models in several classes. Still, the entailment model may be sensitive to hypothesis wording and may require further fine tuning.

ConclusionThis study developed a corpus of annotated clinical notes covering a broad spectrum of SDoH classes. This corpus provides a basis for training machine learning models and serves as a benchmark for predictive models for named entity recognition for SDoH and knowledge extraction from clinical texts.


title: 13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial

abstract: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical investigation of approved drugs is a promising alternative to find a timely effective treatment. In this randomized trial, we investigated the activity of both oral and aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care treatment in patients with COVID-19 versus standard of care treatment alone. This was a randomized controlled trial conducted at Kafrelsheikh Universitys Quarantine Hospitals, Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment as a control group. The two groups were age and gender matched. There was no statistically significant difference between them in any of the baseline characteristics or laboratory parameters. The results showed that there was a high significant difference between the two groups regarding intensive care unit (ICU) admission, mortality and improvement (P<0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis retinoic acid group, whereas about 14.35% were died in the group II. All patients who received 13 cis retinoic acid noticed a high improvement (P<0.001), and the mean value for clinical improvement was 16.3{+/-}4.5 days. There was no significant difference regarding the laboratory parameters before and after 14 days of treatment in the group of patients received the standard of care treatment (P=0.66). Univariate logistic regression analysis showed overall mortality was significantly related to the patients age, serum ferritin, C-reactive protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients with COVID-19 infection, when added to the standard of care treatment.

category: respiratory medicine


title: Recovery of kicking kinematics and performance following intermittent high-intensity running bouts in young soccer players: can a local cooling intervention help?

abstract:
Repeated high-intensity running (RHIR) exercise is known to affect central and peripheral functioning. Declines in RHIR performance are exacerbated by environmental heat stress. Accordingly, the use of post-exercise cooling strategies (COOL) is recommended as it may assist recovery. The present study aimed to investigate, in a hot environment (> 30{o}C), the effects of local COOL following RHIR on indices of soccer kicking movement and performance in youth soccer. Fifteen academy under-17 players (16.27 {+/-} 0.86 years-old; all post-PHV), acting as their own controls, participated. In #Experiment 1, players completed an all-out RHIR protocol (10 x 30 m bouts interspersed with 30 s intervals). In #Experiment 2, the same players performed the same running protocol under two conditions, 1) 5 minutes of COOL where ice packs were applied to the quadriceps and hamstrings regions and, 2) a control condition involving only passive resting. In both experiments, perceptual measures [ratings of perceived exertion (RPE), pain and recovery], thigh temperature and kick-derived video kinematics (hip, knee, ankle and foot) and performance (ball speed and placement) were collected at baseline and post exercise and intervention. In the first experiment, RHIR led to moderate-to-large increases (p < 0.03) in RPE (d = 4.08), ankle eversion/inversion angle (d = 0.78) and mean radial error (d = 1.50) and small-to-large decreases (p < 0.04) in recovery (d = -1.83) and average/peak ball speeds (d = -0.42--0.36). In the second experiment RPE (p < 0.01; Kendalls W = 0.30) and mean radial error (p = 0.057; {eta}2 = 0.234) increased only post-control. Significant small declines in ball speed were also observed only post-control (p < 0.05; d = 0.35). Post-intervention CMfoot velocity was moderately faster in COOL as compared to control (p = 0.04; d = 0.60). RHIR acutely impaired kicking movement, ball speed and placement in youth soccer players. However, a short period of local cryotherapy may be beneficial in counteracting declines in indices of kicking performance in hot environment.

Trial registration number#RBR-8prx2m - ReBEC Brazilian Clinical Trials Registry

category: sports medicine


title: Increased variance in second electrode accuracy during deep brain stimulation and its relationship to pneumocephalus, brain shift, and clinical outcomes: a retrospective cohort study.

abstract:
IntroductionAccurate placement of deep brain stimulation electrodes within the intended target is believed to be a key variable related to outcomes. However, methods to verify electrode location are not universally established.

Research QuestionThe aim of this study was to determine the feasibility of post-op lead localisation in clinical practice and its utility to audit our own DBS accuracy.

Material and MethodsA retrospective cohort study was performed of a consecutive series of patients with Parkinsons disease who underwent deep brain stimulation of either the globus pallidus internus (GPi) or subthalamic nucleus (STN) between 2016 and 2019. Image processing was performed using the Lead-DBS toolbox. Institutional ethical approval was granted as a review of service.

ResultsIn total 38 participants met the inclusion criteria. Electrode localisation was completed in 79%. Clinical outcomes included improvement in UPDRS III of 46% and PDQ39 of 32%. Overall electrode accuracy was 0.22 +/- 0.4mm for all electrodes to the main nucleus with 9 (12%) outliers but only 3 (4%) electrodes out with 2mm from the intended target. Accuracy was worse for the second electrode implanted and in the GPi but was not affected by pneumocephalus or brain shift. Neither clinical outcomes nor the volume of activated tissue was affected by electrode accuracy.

Discussion and ConclusionsA neuroimaging approach to electrode localisation allows qualitative appraisal of targeting accuracy and is feasible with routine clinical data. Such methods are complimentary to traditional co-ordinate approaches and lend themselves to developing large, collaborative, and quantitative projects.

HIGHLIGHTSO_LIOverall electrode accuracy was 0.22 +/- 0.4mm with only 3 (4%) electrodes out with 2mm from the intended target
C_LIO_LIAccuracy was significantly worse in the GPi versus the STN and on the second side implanted
C_LIO_LIInaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift
C_LI

category: neurology


title: A multi-phenotype analysis reveals 19 novel susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma.

abstract: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of skin cancer. There is genetic overlap between skin cancers, pigmentation traits, and autoimmune diseases. We use linkage disequilibrium score regression to identify 20 traits (melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers) with a high genetic correlation (rg > 10%, P < 0.05) with BCC (20,791 cases and 286,893 controls in the UK Biobank) and SCC (7,402 cases and 286,892 controls in the UK Biobank), and use a multi-trait genetic analysis to identify 78 and 69 independent genome-wide significant (P < 5 x 10-8) susceptibility loci for BCC and SCC respectively; 19 BCC and 15 SCC loci are both novel and replicated (P < 0.05) in a large independent cohort; 23andMe, Inc (BCC: 251,963 cases and 2,271,667 controls, and SCC: 134,700 cases and 2,394,699 controls. Novel loci are implicated in BCC/SCC development and progression (e.g. CDKL1), pigmentation (e.g. DSTYK), cardiometabolic pathways (e.g. FADS2), and immune-regulatory pathways including; innate immunity against coronaviruses (e.g. IFIH1), and HIV-1 viral load modulation and disease progression (e.g. CCR5). We also report a powerful and optimised BCC polygenic risk score that enables effective risk stratification for keratinocyte cancer in a large prospective Canadian Longitudinal Study of Aging (794 cases and 18139 controls); e.g. percentage of participants reclassified; MTAGPRS = 36.57%, 95% CI = 35.89-37.26% versus UKBPRS= 33.23%, 95% CI=32.56-33.91%).

category: oncology


title: Assessment of an AI-based triage and notification system in detecting clinical signs of retinal diseases

abstract:
PurposeThis study evaluates the performance of an artificial intelligence based triage and notification system that analyzes fundus photographs for nine signs: cotton wool spots, dot & blot hemorrhages, drusens, flame shaped hemorrhages, glaucomatous disc, hard exudates, retinal neovascularization, preretinal hemorrhage and vascular tortuosity. These signs may be present in multiple retinal diseases.

MethodsIn a blinded and adjudicated study, a set of 3484 photographs of unique eyes from 3305 patients, from 15 fundus cameras, were graded by retina specialists, and the results compared with an AI-based system.

ResultsThe AI performed at a mean sensitivity of 90.19% and a mean specificity of 88.38% across all signs. The best performance was in detecting glaucomatous disc with a sensitivity of 94.65% and a specificity of 95.36%. The worst performance for sensitivity was for detecting vascular tortuosity at 85.06% and that for specificity was for detecting drusens 85.21%.

ConclusionThe AI-based system performs at acceptable sensitivity and specificity levels in comparison to retina specialists in a large sample pooled across 15 fundus cameras for 9 different clinical signs.

category: ophthalmology


title: Therapeutic effects of Rosa Canina, Urtica Dioica and Tanacetum Vulgare Herbal Combination in Treatment of Tinnitus Symptoms; A Double-blind Randomized Clinical Trial

abstract:
BackgroundTinnitus is defined as the perception of sound in the ear or head in the absence of an external stimulus for which we have no definite treatment. Neurotec(R) is a medication of herbal origin with IFDA approval. Previous studies showed the neuroprotective effect of Neurotec(R). In this study we evaluated the effectiveness of Neurotec in improving tinnitus symptoms.

MethodsThis double-blind randomized clinical trial was performed on patients with tinnitus. Patients received Neurotec 100 mg capsules (BID) or placebo for three months. Pure tone audiometry (PTA) was measured at 0.5, 1, 2, 4 and 6 KHz frequencies. Using a Tinnitus Handicap Inventory (THI) questionnaire, tinnitus loudness, daily annoyance, daily life or sleep disturbance, daily perception and mood alteration were evaluated.

ResultsFinally, 103 (69 male and 34 female) patients with a mean age of 51.33{+/-}13.91 years were analyzed. There was no significant difference between the intervention (n=53) and the control group (n=50) regarding baseline symptoms before and one month after the intervention (P>0.05). While, they were significantly different three months after the intervention (P<0.05). The mean pure tone air and bone conduction were not significantly different between the control and the intervention group before and three months after the intervention at 0.5,1,2 and 4 kHz (P>0.05). The mean pure tone air conduction was not significantly different between the two groups before and three months after the intervention at 6 kHz (P>0.05).

ConclusionA three-month treatment with Neurotec Capsules beside patient education can effectively control symptoms of patients with tinnitus.

category: otolaryngology


title: Attempt to replicate voxel-based morphometry analysis in fibromyalgia: Detection of below threshold differences framed by contributions of variable clinical presentation to low reproducibility.

abstract:
BackgroundFibromyalgia is a prevalent chronic pain condition characterized by widespread pain and sensory hypersensitivity. While much remains unknown about fibromyalgias neurobiological underpinnings, central nervous system alterations appear to be heavily implicated in its pathophysiology. Previous research examining brain structural abnormalities associated with fibromyalgia has yielded inconsistent findings. Thus, we followed previous methods to examine brain gray matter differences in fibromyalgia. We hypothesized that, relative to healthy controls, participants with fibromyalgia would exhibit lower gray matter volume in regions consistently implicated in fibromyalgia: the anterior cingulate cortex and medial prefrontal cortex.

MethodsThis study used magnetic resonance imaging to evaluate regional and whole brain differences in gray matter among females with and without fibromyalgia. Group differences were analyzed with two-sample t-tests, controlling for total intracranial volume.

ResultsNo significant differences in regional or whole brain gray matter volumes were detected between fibromyalgia and healthy controls.

ConclusionsResults add to an existing body of disparate findings regarding brain gray matter volume differences in fibromyalgia, and suggest structural differences previously detected in fibromyalgia should be examined for reproducibility. Absent significant differences may also suggest that functional, but not structural, brain adaptations are primarily associated with fibromyalgia.

category: pain medicine


title: Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors

abstract: Venous thromboembolism (VTE) is a complex disease with environmental and genetic determinants. We present new cross-ancestry meta-analyzed genome-wide association study (GWAS) results from 30 studies, with replication of novel loci and their characterization through in silico genomic interrogations. In our initial genetic discovery effort that included 55,330 participants with VTE (47,822 European, 6,320 African, and 1,188 Hispanic ancestry), we identified 48 novel associations of which 34 replicated after correction for multiple testing. In our combined discovery-replication analysis (81,669 VTE participants) and ancestry-stratified meta-analyses (European, African and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein QTL Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 novel GWAS loci provided insights to biological pathways contributing to VTE, indicating that some loci may contribute to VTE through well-characterized coagulation pathways while others provide new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. In summary, these findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of antithrombosis treatments with reduced risk of bleeds.

category: genetic and genomic medicine


title: Navigating life with HIV as an older adult on the Kenyan coast: perceived health challenges seen through the biopsychosocial model

abstract:
BackgroundKenya, like many sub-Saharan African countries (SSA), is experiencing a rise in the number of HIV infected adults aged [≥]50 years (recognized as older adults living with HIV [OALWH]). This trend has created a subgroup of vulnerable older adults demanding a prompt response in research, policy, and practice to address their complex and transitioning needs. Unfortunately, little is known about the health and wellbeing of these adults in Kenya. As such, we explore the experiences of OALWH and key stakeholders at the coast of Kenya to understand the health challenges facing the OALWH.

Material and methodsWe utilized the biopsychosocial model to explore views from 34 OALWH and 22 stakeholders (11 health care providers and 11 primary caregivers) on the physical, mental, and psychosocial health challenges of ageing with HIV in Kilifi County, Kenya, between October and December 2019. Data were drawn from semi-structured in-depth interviews, which were audio-recorded and transcribed. A framework approach was used to synthesize the data.

ResultsSymptoms of common mental disorders (e.g. stress, worry, thinking too much), comorbidities (especially ulcers/hyperacidity, hypertension, visual and memory difficulties), somatic symptoms (especially pain/body aches, fatigue, and sleep problems), financial difficulties, stigma, and discrimination were viewed as common across the participants. Suicidal ideation and substance use problems (especially  mnazi - the local palm wine and  ugoro - snuff) were also raised. There was an overlap of perceived risk factors across the three health domains, such as family conflicts, poverty, lack of social support, stigma, and the presence of comorbid health complaints.

ConclusionOur findings provide a preliminary understanding of challenges, using the biopsychosocial model, facing OALWH in a low-literacy Kenyan setting. We found that OALWH at the Kenyan coast are at risk of multiple physical, mental, and psychosocial challenges, likely affecting their HIV treatment and overall health. Before programmes can have any lasting impact on these adults, improved access to basic needs, including food, financial support, and caregiving, and a reduction of stigma and discrimination must be addressed. Future research should quantify the burden of these challenges and examine the resources available to these adults before piloting and testing feasible interventions.

category: hiv aids


title: Defining factors that influence vaccine-induced, cross-variant neutralizing antibodies for SARS-CoV-2 in Asians

abstract: The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced neutralizing antibody responses for key variants in an Asian volunteer cohort. We demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination and show a marked reduction in the serological binding and neutralizing response targeting Omicron compared to other viral variants. We also highlight the increase in cross-protective neutralizing antibody responses against Omicron induced by a third dose (booster) of vaccine. These data illustrate how key virological factors such as immune escape mutation combined with host factors such as age and sex of the vaccinated individuals influence the strength and duration of cross-protective serological immunity for COVID-19.

category: allergy and immunology


title: Impact on alcohol selection and purchasing of increasing the proportion of non-alcoholic versus alcoholic drinks: randomised controlled trial

abstract:
ObjectiveIncreasing the availability of non-alcoholic options is a promising population-level intervention to reduce alcohol consumption, currently unassessed in naturalistic settings. This study in an online retail setting aimed to estimate the impact of increasing the proportion of non-alcoholic (relative to alcoholic) drinks, on selection and actual purchasing of alcohol.

DesignParallel-group randomised controlled trial.

SettingParticipants selected drinks in a simulated online supermarket, before purchasing them in an actual online supermarket.

ParticipantsAdults in England and Wales who regularly consumed and purchased beer and wine online (n=737).

InterventionParticipants were randomised to one of three groups: Higher Proportion of non-alcoholic drinks available (75%); Same Proportion (50%); Lower Proportion (25%).

Main outcome measureThe primary outcome was the number of alcohol units selected (with intention to purchase); secondary outcomes included purchasing.

Results607 participants completed the study and were included in the primary analysis. The Higher Proportion group selected 10.0 fewer alcohol units than the Lower Proportion group (-32%; 95%CI -42%,-22%) and 7.1 fewer units compared to the Same Proportion group (-25%; 95%CI -36%,-13%), based on model results in those selecting any drinks containing alcohol (559/607). There was no evidence of a difference between the Same Proportion and Lower Proportion groups (2.9 fewer units, -9%; 95%CI -22%,5%). For all other outcomes, alcohol selection and purchasing were consistently lowest in the Higher Proportion group.

ConclusionThis study provides evidence that substantially increasing the proportion of non-alcoholic drinks - from 25% to 50% or 75% - meaningfully reduces alcohol selection and purchasing. Further studies are warranted to assess whether these effects are realised in a range of real-world settings.


title: Factors affecting zero-waste behaviors: Focusing on the health effects of microplastics

abstract: Microplastics harm human health. Therefore, the present study assessed the knowledge and attitude of university students towards reducing microplastic use and examined their zero-waste behaviors. Our results lay the foundation for program development aimed at promoting zero-waste activities. The study was conducted from August 20, 2021, to September 10, 2021, including students at a university in G metropolitan city. Questions were developed to verify how the use of disposables and the knowledge, attitude, and behaviors related to zero-waste were affected after the COVID-19 pandemic. A survey was conducted with 197 students, and the data of 196 students were analyzed. Family type ({beta}=0.146, p=0.042) and usage of disposables ({beta}=0.158, p=0.049) were the factors affecting zero-waste behavior in Model 1. In Model 2, which included the subcategory of zero-waste knowledge, the health effects of microplastics ({beta}=0.197, p=0.008) and environmental preservation ({beta}=0.236, p=0.001) were significant factors. In Model 3, which included the subcategory of zero-waste attitude, the health effects of microplastics ({beta}=0.149, p=0.016), use of eco-friendly products ({beta}=0.342, p<0.001), and environmental preservation ({beta}=0.317, p<.001) were significant factors. Therefore, additional studies and education on the health effects of microplastics are warranted, and suitable alternatives for disposables must be developed.

category: nursing


title: Proteogenomic analysis identifies the persistence of targetable lesions and proteomes through disease evolution in pediatric acute lymphoblastic leukemia

abstract:
Childhood acute lymphoblastic leukemia (ALL) genome landscapes indicate that relapses often arise from subclonal outgrowths. However, the impact of clonal evolution on the actionable proteome and response to targeted therapy is not known. Here, we present a comprehensive retrospective analysis of paired ALL diagnosis and relapsed specimen. Targeted next generation sequencing and proteome analysis indicated persistence of genome variants and stable proteomes through disease progression. Although variant-targeted therapies showed poor selectivity against viably-frozen tumor samples, paired samples showed high correlation of drug response. Proteome analysis prioritized PARP1 as a new pan-ALL target candidate; diagnostic and relapsed ALL samples demonstrated robust sensitivity to treatment with two PARP1/2 inhibitors. Together, these findings support initiating prospective precision oncology approaches at ALL diagnosis and emphasize the need to incorporate proteome analysis to prospectively determine tumor sensitivities, which are likely to be retained at disease relapse.

STATEMENT OF SIGNIFICANCEWe discover that disease progression and evolution in pediatric acute lymphoblastic leukemia is defined by the persistence of targetable genomic variants and stable proteomes, which reveal pan-ALL target candidates. Thus, personalized treatment options in childhood ALL may be improved with the incorporation of prospective proteogenomic approaches initiated at disease diagnosis.


title: Familial Clustering and Genetic Analysis of Severe Thumb Carpometacarpal Joint Osteoarthritis in a Large Statewide Cohort

abstract:
ObjectivesThe objectives of this study are to 1) identify individuals that required surgery for thumb carpometacarpal osteoarthritis (CMCJ OA), 2) determine if CMCJ OA clusters in multigenerational families, 3) define the magnitude of familial risk of CMCJ OA, 4) identify risk factors associated with CMCJ OA and 5) identify rare genetic variants that segregate with familial CMCJ OA.

MethodsWe searched the Utah Population Database to identify a cohort of CMCJ OA patients that required a surgical procedure (CMC fusion or arthroplasty). Affected individuals were mapped to pedigrees to identify high-risk multigenerational families with excess clustering of CMCJ OA. Cox regression models were used to calculate familial risk of CMCJ OA in related individuals. Risk factors were evaluated using logistic regression models. Whole exome sequencing was used to identify a rare coding variant associated with familial CMCJ OA.

ResultsWe identified 550 pedigrees with excess clustering of severe CMCJ OA. The relative risk of developing CMCJ OA requiring surgical treatment was significantly elevated in first- and third-degree relatives of affected individuals, and significant associations with advanced age, female sex, obesity, and tobacco use were observed. A dominantly segregating, rare variant in CHSY3 was associated with familial CMCJ OA.

ConclusionsFamilial clustering of severe CMCJ OA was observed in a statewide population. Identification of a candidate gene indicates a genetic contribution to the etiology of the disease. Our data indicate the genetic and environmental factors contribute to the disease process, further highlighting the multifactorial nature of the disease.

Key messagesO_LIWe study a unique cohort of individuals requiring surgical management of CMCJ OA.
C_LIO_LISevere CMCJ OA clusters in large, multigenerational families indicating a genetic contribution to the disease.
C_LIO_LI.We discovered a dominant coding variant in CHSY3 in a family with severe CMCJ OA.
C_LI

category: orthopedics


title: Determinants of Neonatal Sepsis Admitted In Neonatal Intensive Care Unit At Public Hospitals Of Kaffa Zone, South West Ethiopia

abstract:
BackgroundNeonatal sepsis is a systemic inflammatory response syndrome in the presence of infection during the first 28 days of life. Globally every year about 4 million children die in the first 4 weeks of life, of which 99% of the deaths occur in low and middle income countries and the most common causes of neonatal death in Ethiopia. Identification of the determinants for neonatal sepsis and treatment of newborns with sepsis is not adequate in low income countries like Ethiopia especially in southern part of the country.

ObjectiveTo identify determinants of neonatal sepsis admitted in neonatal intensive care unit at public hospitals of Kaffa zone, south west Ethiopia 2021.

MethodsInstitutional based unmatched case control study was conducted on a total sample of 248 (62 cases and 186 controls) in public Hospitals of kaffa zone from March to April 2021.The collected data were entered, coded and cleaned by Epidata version 3.1 and it was exported to SPSS version 25. Bi-variable and multivariable logistic regression was conducted. Variables with (p< 0.25) in bi-variable logistic regression analysis, were entered to multivariable logistic regression and then determinants which is statistical significant will be declared at P<0.05.

ResultA total of 248 (62 cases and 186 controls) were included in the study. variables like prolonged rupture of membrane [≥]18 hours [AOR =5.13, 95%CI=1.38-19.05], meconium stained amniotic fluid[AOR =6.03, 95%CI=2.16-16.90], intra-partum fever [AOR =8.26, 95%CI=3.12-21.97], urinary tract infections [AOR=14,55, 95%CI=4.91-43.10], breast feeding after a hour [AOR =3.9, 95%CI=1.27-12.02], resuscitation [AOR =13.25, 95%CI=3.44-51.01], no chlorohexidine application [AOR =4.27, 95%CI=1.65-11.08] were significantly associated with neonatal sepsis.

Conclusion and RecommendationAmong the variables prolonged rupture of membranes, meconium stained amniotic fluid, intra-partum fever, UTI/STI, and not breast feeding with in a hour were maternal variables and resuscitation at birth and not application of chlorohexidine ointment on the umbilicus were neonatal variables that were found to be neonatal-related risk factors of neonatal sepsis. Infection prevention strategies and clinical management need to be strengthening and/or implementing by providing especial attention for the specified determinants.

category: health systems and quality improvement


title: Preferences for the management of sexually transmitted infections in the South African health system: A discrete choice experiment

abstract:
IntroductionYoung people have a disproportionate burden of sexually transmitted infections. Despite strengthening HIV prevention with the introduction of PrEP, STI services have remained relatively unchanged, and the standard of care remains syndromic management. We used a discrete choice experiment to investigate young peoples preferences for the diagnosis and treatment of STIs in South Africa.

Methods and FindingsBetween 1 March 2021 and 20 April 2021, a cross-sectional online questionnaire hosted on REDCap was administered through access links sent to WhatsApp support groups for HIV PrEP users and attendees of two primary healthcare clinics and two mobile facilities in the Eastern Cape and Gauteng provinces aged between 18-49 years. Participants either self-completed the questionnaire or received support from a research assistant. We used a CLOGIT model for the initial analysis and latent class model (LCM) to establish class memberships with results displayed as odds ratios and probabilities.

We enrolled 496 individuals, the majority were female (69%) and <30 years (74%). About 29% reported previous STI treatment and 20% reported current STI symptoms.

The LCM showed two distinct groups within the respondent sample with different preferences for STI care. The first group comprising 68% of participants showed a strong preference for self-sampling compared to sampling by a healthcare professional (HCP) [OR 2.32; 95%-CI (1.79-3.00)] and viewed no sampling as similar to HCP sampling [OR 1.08; 95%-CI (0.92-1.26)]. There was a lower preference to receive results within 4 hours versus 2 hours [OR 0.63; 95%-CI (0.51-0.77)] and the later was viewed as equal to the receipt of results in 1-7 days by SMS or online [OR 1.03; 95%-CI (0.88-1.21). A clinic follow-up appointment for treatment was less preferable than same-day treatment [OR 0.78; 95%-CI (0.63-0.95)] while treatment from a local pharmacy was viewed with equal preference as same-day treatment [OR 1.16; 95%-CI (1.04-1.29)]. Contact slip from index patient [OR 0.86; 95%-CI (0.76-0.96)] and HCP-initiated partner notification [OR 0.63; 95%-CI (0.55-0.73)] were both less preferable than expedited partner treatment (EPT). The second group included 32% of participants with a much lower preference for self-sampling compared to sampling by HCP [OR 0.55; 95%-CI (0.35-0.86)]. No sampling was not significantly different to HCP-sampling [OR 0.85; 95%-CI (0.64-1.13)]. There was a strong preference for a 4-hour wait than a 2-hour wait for results [OR 1.45; 95%-CI (1.05-2.00)]. There was no treatment option that was significantly different from the others, however there was a strong preference for HCP-initiated partner notification than EPT [OR 1.53; 95%-CI (1.10-2.12)]. Participants were more likely to be members of group 1 than group 2 if they were aged 25-49 years compared to 18-24 years (p=0.001) and receive care from a rural compared to urban facility (p=0.011). Employed individuals were more likely to be in group 2 than group 1 (p=0.038).

ConclusionsOur results suggest that health service users preferred to undergo STI testing prior to treatment but there were subgroups who differed on how this should be done. This highlights the need for STI care to be flexible to accommodate different patient choices.

category: sexual and reproductive health


title: Prion protein gene mutation detection using long-read Nanopore sequencing

abstract: Prion diseases are fatal neurodegenerative conditions that affect humans and animals. Rapid and accurate sequencing of the prion gene PRNP is paramount to human prion disease diagnosis and for animal surveillance programmes. Current methods for PRNP genotyping involve sequencing of small fragments within the protein-coding region. The contribution of variants in the non-coding regions of PRNP including large structural changes is poorly understood. Here we use long-range PCR and Nanopore sequencing to sequence the full length of PRNP, including its regulatory region, in 25 samples from blood and brain of individuals with various prion diseases. Nanopore sequencing detected the same variants as identified by Sanger sequencing, including repeat expansions/contractions. Nanopore identifies additional single-nucleotide variants in the non-coding regions of PRNP, but no novel structural variants were discovered. Finally, we explore somatic mosaicism of PRNPs octapeptide repeat region, which is a hypothetical cause of sporadic prion disease. While we find changes consistent with somatic mutations, we demonstrate that they may have been generated by the PCR. Our study illustrates the accuracy of Nanopore sequencing for rapid and field prion disease diagnosis and highlights the need for single-molecule sequencing methods for the detection of somatic mutations.


title: Understanding frailty: probabilistic causality between components and their relationship with death through a Bayesian network and evidence propagation

abstract: Identifying relationships between components of an index helps to have a better understanding of the condition they define. The Frailty Index (FI) measures the global health of individuals and can be used to predict outcomes as mortality. Previously, we modelled the relationship between the FI components (deficits) and death through an undirected graphical model, analyzing their relevance from a social network analysis framework. Here, we model the FI components and death through an averaged Bayesian network obtained through a structural learning process and resampling, to understand how the FI components and death are causally related. We identified that the components are not similarly related between them and that deficits are related according to its type. Two deficits were the most relevant in terms of their connections and other two were directly associated with death. We also obtained the strength of the relationships to identify the most plausible, identifying clusters of deficits heavily related. Finally, we propagated evidence (assigned values to all deficits) and studied how FI components predict mortality, obtaining a correct assignation of almost 74%, whereas a sensitivity of 56%. As a classifier of death, the more number of deficits included for the evidence, the best performance; but the FI seems not to be very good to correctly classify death people.

category: geriatric medicine


title: Selection of optimum formulation of RBD-based protein sub-unit covid19 vaccine (Corbevax) based on safety and immunogenicity in an open-label, randomized Phase-1 and 2 clinical studies

abstract:
BackgroundWe present the data from an open-label study involved in the selection of optimum formulation of RBD-based protein sub-unit COVID-19 vaccine.

MethodsThe randomized Phase-1/2 trial followed by a Phase-2 trial was carried out to assess safety and immunogenicity of different formulation of COVID-19 vaccine (Corbevax) and select an optimum formulation for a phase 3 study. Healthy adults without a history of Covid-19 vaccination or SARS-CoV-2 infection, were enrolled.

FindingsLow incidence of adverse events were reported post-vaccination of different Corbevax formulations and majority were mild in nature and no Grade-3 or serious adverse events were observed. All formulations in Phase-1/2 study showed similar profile of humoral and cellular immune-response with higher response associated with increasing CpG1018 adjuvant content at same RBD protein content. Hence, high concentration of CpG1018 was tested in phase-2 study, which showed significant improvement in immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, nAb-titers and cellular immune-responses while maintaining the safety profile. Interestingly, binding and neutralizing antibody titers were persisted consistently till 6 months post second vaccine dose.

InterpretationsCorbevax was well tolerated with no observed safety concerns. Neutralizing antibody titers were suggestive of high vaccine effectiveness compared with human convalescent plasma or protective thresholds observed during vaccine efficacy trials of other COVID-19 vaccines. The study was prospectively registered with clinical trial registry of India-CTRI/2021/06/034014 and CTRI/2020/11/029032.

FundingBill & Melinda Gates Foundation, BIRAC-division of Department of Biotechnology, Govt of India, and the Coalition for Epidemic Preparedness Innovations funded the study.

category: infectious diseases


title: Multi-steroid profiling by uPLC-MS/MS with post-column infusion of ammonium fluoride

abstract:
BackgroundMulti-steroid profiling is a powerful analytical tool that simultaneously quantifies steroids from different biosynthetic pathways. Here we present an ultra-high performance liquid chromatography-tandem mass spectrometry (uPLC-MS/MS) assay for the profiling of 25 steroids using post-column infusion of ammonium fluoride.

MethodsFollowing liquid-liquid extraction, steroids were chromatographically separated over 5 minutes using a Phenomenex Luna Omega C18 column and a water (0.1 % formic acid) methanol gradient. Quantification was performed on a Waters Acquity uPLC and Xevo(R) TQ-XS mass spectrometer. Ammonium fluoride (6 mmol/L, post-column infusion) and formic acid (0.1 % (vol/vol), mobile phase additive) were compared as additives to aid ionisation.

ResultsPost-column infusion (PCI) of ammonium fluoride (NH4F) enhanced ionisation in a steroid structure-dependent fashion compared to formic acid (122-140% for 3{beta}OH-{Delta}5 steroids and 477-1274% for 3-keto-{Delta}4 steroids). Therefore, we fully analytically validated PCI with NH4F. Lower limits of quantification ranged from 0.28 to 3.42 nmol/L; 23 of 25 analytes were quantifiable with acceptable accuracy (bias range -14% to 11.9%). Average recovery ranged from 91.6% to 113.6% and average matrix effects from -29.9% to 19.9%. Imprecision ranged from 2.3% to 23.9% for all analytes and was <15% for 18/25 analytes. The serum multi-steroid profile of 10 healthy men and 10 healthy women was measured.

ConclusionsuPLC-MS/MS with post-column infusion of ammonium fluoride enables comprehensive multi-steroid profiling through enhanced ionisation particularly benefiting the detection of 3-keto-{Delta}4 steroids.

HighlightsO_LIThis multi-steroid profiling assay quantifies 25 steroids in 5.5 minutes
C_LIO_LIPost-column infusion of NH4F enhances the ionisation of 3-keto-{Delta}4 steroids
C_LIO_LIThe assay simultaneously quantifies steroids from several biosynthetic pathways
C_LIO_LIWe present analytical data validated for serum steroid profiling
C_LI

category: endocrinology


title: Severity of maternal SARS-CoV-2 infection and perinatal outcomes during the Omicron variant dominant period: UK Obstetric Surveillance System national cohort study.

abstract:
ObjectivesTo describe the severity of maternal infection when the Omicron SARS-CoV-2 variant was dominant (15/12/21-14/01/22) and compare outcomes among groups with different vaccination status.

DesignProspective cohort study

SettingUK consultant-led maternity units

ParticipantsPregnant women hospitalised with a positive SARS-CoV-2 PCR test up to 7 days prior to admission and/or during admission up to 2 days after giving birth.

Main outcome measuresSymptomatic or asymptomatic infection. Vaccination status. Severity of maternal infection (moderate or severe infection according to modified WHO criteria). Mode of birth and perinatal outcomes.

ResultsOut of 1561 women admitted to hospital with SARS-CoV-2 infection, 449 (28.8%) were symptomatic. Among symptomatic women admitted, 86 (19.2%) had moderate to severe infection; 51 (11.4%) had pneumonia on imaging, 62 (14.3%) received respiratory support, and 19 (4.2%) were admitted to the intensive care unit (ICU). Three women died (0.7%). Vaccination status was known for 383 symptomatic women (85.3%) women; 249 (65.0%) were unvaccinated, 45 (11.7%) had received one vaccine dose, 76 (19.8%) had received two doses and 13 (3.4%) had received three doses. 59/249 (23.7%) unvaccinated women had moderate to severe infection, compared to 10/45 (22.2%) who had one dose, 9/76 (11.8%) who had two doses and 0/13 (0%) who had three doses. Among the 19 symptomatic women admitted to ICU, 14 (73.7%) were unvaccinated, 3 (15.8%) had received one dose, 1 (5.3%) had received two doses, 0 (0%) had received 3 doses and 1 (5.3%) had unknown vaccination status.

ConclusionThe risk of severe respiratory disease amongst unvaccinated pregnant women admitted with symptomatic SARS-CoV-2 infection during the Omicron dominance period was comparable to that observed during the period the wildtype variant was dominant. Most women with severe disease were unvaccinated. Vaccine coverage among pregnant women admitted with SARS-CoV-2 was low compared to the overall pregnancy population and very low compared to the general population. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential.

O_TEXTBOXSUMMARY BOX

What is already known on this topic

O_LIIn non-pregnant adults, growing evidence indicates a lower risk of severe respiratory disease with the Omicron SARS-CoV-2 Variant of Concern (VOC).
C_LIO_LIPregnant women admitted during the periods in which the Alpha and Delta VOC were dominant were at increased risk of moderate to severe SARS-CoV-2 infection compared to the period when the original wildtype infection was dominant.
C_LIO_LIMost women admitted to hospital with symptomatic SARS-CoV-2 infection have been unvaccinated.
C_LI

What this study adds

O_LIOne in four women who had received no vaccine or a single dose had moderate to severe infection, compared with one in eight women who had received two doses and no women who had received three doses
C_LIO_LIThe proportional rate of moderate to severe infection in unvaccinated pregnant women during the Omicron dominance period is similar to the rate observed during the wildtype dominance period
C_LIO_LIOne in eight symptomatic admitted pregnant women needed respiratory support during the period when Omicron was dominant
C_LI

C_TEXTBOX

category: epidemiology


title: Low cost and real-time surveillance of enteric infection and diarrhoeal disease using rapid diagnostic tests: A pilot study

abstract:
BackgroundReal-time disease surveillance is an important component of infection control in at-risk populations. However, data on cases or from lab testing is often not available in many low-resource settings. Rapid diagnostic tests (RDT), including immunochromatographic assays, may provide a low cost, expedited source of infection data.

MethodsWe conducted a pilot survey-based prevalence mapping study of enteric infection in Camp 24 of the camps for the forcibly displaced Rohingya population from Myanmar in Coxs Bazar, Bangladesh. We randomly sampled the population and collected and tested stool from under-fives for eight pathogens using RDTs in January-March 2021 and September-October 2021. A Bayesian geospatial statistical model allowing for imperfect sensitivity and specificity of the tests was adapted.

ResultsWe collected and tested 396 and 181 stools in the two data collection rounds. Corrected prevalence estimates ranged from 0.5% (Norovirus) to 27.4% (Giardia). Prevalence of E.coli O157, Campylobacter, and Cryptosporidium were predicted to be higher in the high density area of the camp with relatively high probability (70-95%), while Adenovirus, Norovirus, and Rotavirus were lower in the areas with high water chlorination. Clustering of cases of Giardia and Shigella was also observed, although associated with relatively high uncertainty.

ConclusionsWith an appropriate correction for diagnostic performance RDTs can be used to generate reliable prevalence estimates, maps, and well-calibrated uncertainty estimates at a significantly lower cost than lab-based studies, providing a useful approach for disease surveillance in these settings.


title: Changes in outpatient care patterns and subsequent outcomes during the COVID-19 pandemic: A retrospective cohort analysis from a single payer healthcare system

abstract:
BackgroundThere have been rapid shifts in outpatient care models during the COVID-19 pandemic but the impact of these changes on patient outcomes are uncertain. We designed this study to examine ambulatory outpatient visit patterns and outcomes between March 1, 2019 to February 29, 2020 (pre-pandemic) and from March 1, 2020 to February 28, 2021 (pandemic).

MethodsWe conducted a population-based retrospective cohort study of all 3.8 million adults in the Canadian province of Alberta, which has a single payer healthcare system, using linked administrative data. We examined all outpatient physician encounters (virtual or in-person) and outcomes (emergency department visits, hospitalizations, or deaths) in the next 30- and 90-days.

ResultsAlthough in-person outpatient visits declined by 38.9% in the year after March 1, 2020 (10,142,184 vs. 16,592,599), the increase in virtual visits (7,152,147; 41.4% of total) meant that total outpatient encounters increased by 4.1% in the first year of the pandemic. Outpatient care and prescribing patterns remained stable for adults with ambulatory-care sensitive conditions (ACSC): 97.2% saw a primary care physician (median 6 visits), 59.0% had at least one specialist visit, and 98.5% were prescribed medications (median 9) in the year prior to the pandemic compared to 96.6% (median 3 in-person and 2 virtual visits), 62.6%, and 98.6% (median 8 medications) during the first year of the pandemic. In the first year of the pandemic, virtual outpatient visits were associated with less subsequent healthcare encounters than in-person ambulatory visits, particularly for patients with ACSC (9.2% vs. 10.4%, aOR 0.89 [95% confidence interval 0.87-0.92] at 30 days and 26.9% vs. 29.3%, aOR 0.93 [0.92-0.95] at 90 days).

ConclusionsThe shifts in outpatient care patterns caused by the COVID-19 pandemic did not disrupt prescribing or follow-up for patients with ACSC and did not worsen post-visit outcomes.

FundingNone

RegistrationNone

KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSThere have been rapid shifts in outpatient care models during the COVID-19 pandemic but outcomes are uncertain.

What this study addsTotal outpatient encounters increased by 4% in the first year of the pandemic due to a rapid increase in virtual visits (which made up 41% of all outpatient encounters). Prescribing patterns and frequency of follow-up were similar in the first year after onset of the pandemic in adults with ambulatory-care sensitive conditions. Compared to in-person visits, virtual outpatient visits were associated with less subsequent healthcare encounters, particularly for patients with ambulatory-care sensitive conditions (11% less at 30 days and 7% less at 90 days).

How this study might affect research, practice or policyOur data provides reassurance that the shifts in outpatient care patterns caused by the COVID-19 pandemic did not negatively impact follow-up, prescribing, or outcomes for patients with ACSC. Further research is needed to define which patients and which conditions are most suitable for virtual outpatient visits and, as with all outpatient care, the optimal frequency of such visits.

category: primary care research


title: Appropriateness of the current parasitological control target for hookworm morbidity: a statistical analysis of individual-level data

abstract:
BackgroundSoil-transmitted helminths affect almost 2 billion people globally. Hookworm species contribute to most of the related morbidity. Hookworms mainly cause anaemia, due to blood loss at the site of the attachment of the adult worms to the human intestinal mucosa. The World Health Organization (WHO) aims to eliminate hookworm morbidity by 2030 through achieving a prevalence of moderate and heavy intensity (M&HI) infections below 2%. In this paper, we aim to assess the suitability of this threshold to reflect hookworm-attributable morbidity.

Methodology/Principal FindingsWe developed a hierarchical statistical model to simulate individual haemoglobin concentrations in association with hookworm burdens, accounting for low haemoglobin values attributable to other causes. The model was fitted to individual-level data within a Bayesian framework. Then, we generated different endemicity settings corresponding to infection prevalence ranging from 10% to 90% (0% to 55% M&HI prevalence), using 1, 2 or 4 Kato-Katz slides. For each scenario, we estimated the prevalence of anaemia due to hookworm. Our results showed that on average, haemoglobin falls below the WHO threshold for anaemia when intensities are above 2000 eggs per gram of faeces. For the different simulated scenarios, the estimated prevalence of anaemia attributable to hookworm ranges from 0% to 30% (95%-PI: 24% - 36%) being mainly associated to the prevalence of M&HI infections. Simulations show that a 2% prevalence of M&HI infections in adults corresponds to a prevalence of hookworm-attributable anaemia lower than 1%.

Conclusions/SignificanceOur results support the use of the current WHO thresholds of 2% prevalence of M&HI as a proxy for hookworm morbidity. A single Kato-Katz slide may be sufficient to assess the achievement of the morbidity target. Further studies are needed to elucidate haemoglobin dynamics pre- and post-control, ideally using longitudinal data in adults and children.

Author summarySoil-transmitted helminths affect almost 2 billion people globally. About 65% of the related morbidity is attributable to hookworm infection, especially anaemia, which is caused by adult worms attaching to the intestinal mucosa of the human host to feed on blood. The World Health Organization (WHO) defines the target for the elimination of morbidity as reaching moderate-to-heavy intensity infections prevalence < 2%. In this paper, we aim to assess the suitability of the current WHO threshold to reflect hookworm-attributable anaemia. To this end, we developed a statistical model to simulate individual haemoglobin concentrations in association with hookworm burdens in adults, accounting for low haemoglobin values attributable to other causes, such as malnutrition and malaria. We used model outcomes to estimate the prevalence of hookworm-attributable anaemia in different endemicity scenarios. Our predictions suggested that anaemia is mainly associated to moderate-to-heavy intensity infection and that the 2% threshold corresponds to a prevalence of hookworm-attributable anaemia <1%. These results support the use of the current WHO threshold as a proxy for hookworm morbidity. Our predictions represent a first step towards better quantifying the prevalence of anaemia due to hookworm infection.

category: public and global health


title: Spectral imaging enables contrast agent-free real-time ischemia monitoring in laparoscopic surgery

abstract: Laparoscopic surgery has evolved as a key technique for cancer diagnosis and therapy. While characterization of the tissue perfusion is crucial in various procedures, such as partial nephrectomy, doing so by means of visual inspection remains highly challenging. Spectral imaging takes advantage of the fact that different tissue components have unique optical properties to recover relevant information on tissue function such as ischemia. However, clinical success stories for advancing laparoscopic surgery with spectral imaging are lacking to date. To address this bottleneck, we developed the first laparoscopic real-time multispectral imaging (MSI) system featuring a compact and lightweight multispectral camera and the possibility to complement the conventional RGB (Red, Green, and Blue) surgical view of the patient with functional information at a video rate of 25 Hz. To account for the high inter-patient variability of human tissue, we phrase the problem of ischemia detection as an out-of-distribution (OoD) detection problem that does not rely on data from any other patient. Using an ensemble of invertible neural networks (INNs) as a core component, our algorithm computes the likelihood of ischemia based on a short (several seconds) video sequence acquired at the beginning of each surgery. A first-in-human trial performed on 10 patients undergoing partial nephrectomy demonstrates the feasibility of our approach for fully-automatic live ischemia monitoring during laparoscopic surgery. Compared to the clinical state-of-the-art approach based on indocyanine green (ICG) fluorescence, the proposed MSI-based method does not require the injection of a contrast agent and is repeatable if the wrong segment has been clamped. Spectral imaging combined with advanced deep learning-based analysis tools could thus evolve as an important tool for fast, efficient, reliable and safe functional imaging in minimally invasive surgery.

category: radiology and imaging


title: Conceptualization, operationalization, and utilization of race and ethnicity in major medical journals 1995-2018: a systematic review

abstract:
BackgroundSystemic racial and ethnic inequities continue to be perpetuated through scientific methodology and communication norms despite efforts by medical institutions. We characterized methodological practices regarding race and ethnicity in U.S. research published in leading medical journals.

MethodsWe systematically reviewed randomly selected articles from prominent medical journals: Annals of Internal Medicine, BMJ, JAMA, The Lancet, and NEJM within five periods: 1995-99, 2000-04, 2005-09, 2010-14, 2015-18. Original human-subjects research conducted in the U.S. was eligible for inclusion. We extracted information on definitions (conceptualization), measurement/coding (operationalization), use in analysis (utilization), and justifications. We reviewed 1050, including 242 (23%) in analyses.

FindingsThe proportion of U.S. medical research studies including race and/or ethnicity data increased between 1995 and 2018. However, no studies defined race or ethnicity. Studies rarely delineated between race and ethnicity, frequently opting for a combined "ethno-racial" construct. In addition, most studies did not state how race and/or ethnicity was measured. Common coding schemes included: "Black, other, White," "Hispanic, Non-Hispanic," and "Black, Hispanic, other, White." Race and/or ethnicity was most often used as a control variable, descriptive covariate, or matching criteria. Under 30% of studies included a justification for their methodological choices regarding race and/or ethnicity.

InterpretationDespite regular efforts by medical journals to implement new policies around race and ethnicity in medical research, pertinent information around methodology was systematically absent from the majority of reviewed literature. This stymies critical disciplinary reflection and progress towards equitable practice.

FundingFunding was provided through training grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32 HD091058] and the Department of Sociology, UNC Chapel Hill. Carolina Population Center provided general support [P2C HD050924, P30 AG066615]. NRS received additional support from the National Cancer Institute [T32 CA057711].

category: medical education


title: Strongyloides stercoralis infection induces gut dysbiosis in chronic kidney disease patients

abstract:
BackgroundStrongyloides stercoralis infection typically causes severe symptoms in immunocompromised patients. However, the progression of infection-driven chronic kidney disease (CKD) is not understood fully. Recent studies have shown that gut dysbiosis plays an important role in the progression of CKD. Hence, this study aims to investigate the effect of S. stercoralis infection on the gut microbiome in CKD patients.

Methodology/Principal FindingsAmong 838 volunteers from Khon Kaen Province, northeastern Thailand, 40 subjects with CKD were enrolled and divided into two groups (S. stercoralis-infected and -uninfected) matched for age, sex and biochemical parameters. Next-generation technology was used to amplify and sequence the V3-V4 region of the 16S rRNA gene to provide a profile of the gut microbiota. Results revealed that members of the S. stercoralis-infected group had lower gut microbial diversity than was seen in the uninfected group. Interestingly, there was significantly greater representation of some pathogenic bacteria in the S. stercoralis-infected CKD group, including Escherichia-Shigella (P = 0.013), Rothia (P = 0.013) and Aggregatibacter (P = 0.03). There was also a trend towards increased Actinomyces, Streptococcus and Haemophilus (P > 0.05) in this group. On the other hand, the S. stercoralis-infected CKD group had significantly lower representation of SCFA-producing bacteria such as Anaerostipes (P = 0.01), Coprococcus_1 (0.043) and a non-significant decrease of Akkermansia, Eubacterium rectale and Eubacterium hallii (P > 0.05) relative to the uninfected group. Interesting, the genera Escherichia-Shigella and Anaerostipes exhibited opposing trends, which were significantly related to sex, age, infection status and CKD stages. The genus Escherichia-Shigella was significantly more abundant in CKD patients over the age of 65 years and infected with S. stercoralis. A correlation analysis showed inverse moderate correlation between the abundance of the genus of Escherichia-Shigella and the level of estimated glomerular filtration rate (eGFR).

Conclusions/SignificanceConclusion, the results suggest that S. stercoralis infection induced gut dysbiosis in the CKD patients, which might be involved in CKD progression.

Author summaryHuman strongyloidiasis is caused by a soil-transmitted helminth, Strongyloides stercoralis, which typically causes severe symptoms in immunocompromised. However the relationship between S. stercoralis and chronic kidney disease patients (CKD) progression was not known. This is the first study to investigate the gut microbiota of CKD patients with and without S. stercoralis using high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. Infection with S. stercoralis was associated with reduced gut microbiota diversity than in the uninfected group. In addition, infection with this nematode led to reduced abundance of SCFA-producing bacteria and enrichment of pathogenic bacteria. In particular, there were significant differences in abundance of the beneficial genus Anaerostipes (a decrease) and the pathogenic taxon Escherichia-Shigella (an increase) in CKD patients infected with S. stercoralis relative to controls. In the infected group, the representation of genus Escherichia-Shigella was significant higher in patients over the age of 65 years. There was a significant inverse moderate correlation of Escherichia-Shigella with the estimated glomerular filtration rate (eGFR).

category: nephrology


title: Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

abstract: Amyloid-beta 42 (A{beta}42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimers disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8,074; replication n = 5,042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for amyloid beta 42 (A{beta}42) and BIN1 for phosphorylated Tau (pTau). GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories (amyloid, astrocyte, processing & migration, and migration & motility) suggesting multiple A{beta}42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

category: neurology


title: The Sequence Effect Worsens over Time in Parkinson's disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation

abstract:
BackgroundThe sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open and closed-loop deep brain stimulation in people with PD.

ObjectiveTo investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) and closed-loop deep brain stimulation (DBS).

MethodsTwenty-one people with PD with bilateral STN DBS performed thirty seconds of instrumented repetitive wrist flexion extension and the MDS-UPDRS III off therapy, prior to activation of DBS and every six months for up to three years. A sub-cohort of ten people performed the task during randomized presentations of different intensities of STN DBS.

ResultsThe sequence effect was highly correlated with the overall MDS-UPDRS III score and the bradykinesia sub-score and worsened over three years. Increasing intensities of STN open-loop DBS improved the sequence effect and one subject demonstrated improvement on both open-loop and even further improvement on closed-loop DBS.

ConclusionsSequence effect in limb bradykinesia worsened over time off therapy due to disease progression but improved on open and closed-loop DBS. These results demonstrate that DBS is a useful treatment of the debilitating effects of the sequence effect in limb bradykinesia and that closed-loop DBS may offer added improvement.


title: The influence of genetic predisposition and physical activity on risk of Gestational Diabetes Mellitus in the nuMoM2b cohort

abstract:
ImportancePolygenic risk scores (PRS) for Type II Diabetes Mellitus (T2DM) can improve risk prediction for Gestational Diabetes Mellitus (GDM), yet the strength of the relationship between genetic and lifestyle risk factors has not been quantified.

ObjectiveTo assess the effects of PRS and physical activity on existing GDM risk models and identify patient subgroups who may receive the most benefits from receiving a PRS or activity intervention.

Design, Settings, and ParticipantsThe Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study was established to study individuals without previous pregnancy lasting 20 weeks or more (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A sub-cohort of 3,533 participants with European ancestry were used for risk assessment and performance evaluation.

ExposuresSelf-reported total physical activity in early pregnancy was quantified as metabolic equivalent of tasks (METs) in hours/week. Polygenic risk scores were calculated for T2DM using contributions of 85 single nucleotide variants, weighted by their association in the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium data.

Main Outcomes and MeasuresPrediction of the development of GDM from clinical, genetic, and environmental variables collected in early pregnancy. The risk model is assessed using measures of model discrimination and calibration. Odds ratio and positive likelihood ratio were used for evaluating the effect of PRS and physical activity on GDM risk.

ResultsIn high-risk population subgroups (body mass index [≥] 25 or age [≥] 35), individuals with PRS in the top 25th percentile or METs below 450 have significantly increased odds of GDM diagnosis. Participants with both high PRS and low METs have three times higher odds of GDM diagnosis than the population. Conversely, participants with high PRS and METs [≥] 450 do not exhibit increased odds of GDM diagnosis, and those with low METs and low PRS have reduced odds of GDM. The relationship between PRS and METs was found to be nonadditive.

Conclusions and RelevanceIn high-risk patient subgroups the addition of PRS resulted in increased risk of GDM diagnosis, suggesting the benefits of targeted PRS ascertainment to encourage early intervention. Increased physical activity is associated with decreased risk of GDM, particularly among individuals genetically predisposed to T2DM.

Key PointsO_ST_ABSQuestionC_ST_ABSDo genetic predisposition to diabetes and physical activity in early pregnancy cooperatively impact risk of Gestational Diabetes Mellitus (GDM) among nulliparas?

FindingsRisk of GDM diagnosis increases significantly for nulliparas with high polygenic risk score (PRS) and with low physical activity. The odds ratio of developing GDM with high PRS was estimated to be 2.2, 1.6 with low physical activity, and 3.5 in combination.

MeaningPhysical activity in early pregnancy is associated with reduced risk of GDM and reversal of excess risk in genetically predisposed individuals. The interaction between PRS and physical activity may identify subjects for targeted interventions.

category: obstetrics and gynecology


title: Patient-specific forecasting of post-radiotherapy prostate-specific antigen kinetics enables early prediction of biochemical relapse

abstract: The detection of prostate cancer recurrence after external beam radiotherapy relies on the measurement of a sustained rise of serum prostate-specific antigen (PSA). However, this biochemical relapse may take years to occur, thereby delaying the delivery of a secondary treatment to patients with recurring tumors. To address this issue, here we propose to use patient-specific forecasts of PSA dynamics to early predict biochemical relapse. Our forecasts are based on mechanistic models of prostate cancer response to external beam radio-therapy, which are fit to patient-specific PSA data collected during standard post-treatment monitoring. Our results show a remarkable performance of our models in recapitulating the observed changes in PSA and yielding short-term predictions over approximately one year (cohort median RMSE of 0.10 to 0.47 ng/mL and 0.13 to 1.41 ng/mL, respectively). Additionally, we identify three model-based biomarkers that enable an accurate identification of biochemical relapse (AUC > 0.80) significantly earlier than standard practice (p < 0.01).

category: oncology


title: Sequential epiretinal stimulation improves discrimination in simple shape discrimination tasks only

abstract:
ObjectiveElectrical stimulation of the retina can elicit flashes of light called phosphenes, which can be used to restore rudimentary vision for people with blindness. Functional sight requires stimulation of multiple electrodes to create patterned vision, but phosphenes tend to merge together in an uninterpretable way. Sequentially stimulating electrodes in human visual cortex has recently demonstrated that shapes could be "drawn" with better perceptual resolution relative to simultaneous stimulation. The goal of this study was to evaluate if sequential stimulation would also form clearer shapes when the retina is the neural target.

ApproachTwo human participants with retinitis pigmentosa who had Argus(R) II retinal prostheses participated in this study. We evaluated different temporal parameters for sequential stimulation in phosphene shape mapping and forced-choice discrimination tasks. For the discrimination tasks, performance was compared between stimulating electrodes simultaneously versus sequentially.

Main resultsPhosphenes elicited by different electrodes were reported as vastly different shapes. Sequential electrode stimulation outperformed simultaneous stimulation in simple discrimination tasks, in which shapes were created by stimulating 3-4 electrodes, but not in more complex discrimination tasks involving 5+ electrodes. For sequential stimulation, the optimal pulse train duration was 200 ms when stimulating at 20 Hz and the optimal gap interval was tied between 0 and 50 ms. Efficacy of sequential stimulation also depended strongly on selecting electrodes that elicited phosphenes with similar shapes and sizes.

SignificanceAn epiretinal prosthesis can produce coherent simple shapes with a sequential stimulation paradigm, which can be used as rudimentary visual feedback. However, success in creating more complex shapes, such as letters of the alphabet, is still limited. Sequential stimulation may be most beneficial for epiretinal prostheses in simple tasks, such as basic navigation, rather than complex tasks such as object identification.

category: ophthalmology


title: Virtual Assessment of Patients with Dry Eye Disease During the COVID-19 Pandemic: One clinicians experience

abstract:
ObjectivesTo report on 1) the impact of DED on social, mental, and financial well-being, and 2) the use of virtual consultations to assess DED during the COVID-19 pandemic.

Design & MethodsAn exploratory retrospective review of 35 charts. Telephone consultations for patients with DED conducted during the first lock-down period in Ontario in 2020 were reviewed.

ResultsThe most commonly reported DED symptoms were ocular dryness, visual disturbances, and burning sensation. The most common dry eye management practices were artificial tears, warm compresses, and omega-3 supplements. 20.0% of charts documented worsening of DED symptoms since the onset of the pandemic and 17.1% reported the lockdown had negatively affected their ability to perform DED management practices. 42.8% of patients reported an inability to enjoy their daily activities due to DED symptoms. 52.0% reported feeling either depressed, anxious, or both with 26.9% of patients accepting a referral to a social worker for counselling support. More than a quarter of the charts recorded financial challenges associated with the cost of therapy, and more than a fifth of patients reported that financial challenges were a direct barrier to accessing therapy.

ConclusionsPatients living with DED reported that their symptoms negatively affected their daily activities including mental health and financial challenges, that in turn impacted treatment practices. These challenges may have been exacerbated during the COVID-19 pandemic. Telephone consultations may be an effective modality to assess DED symptom severity, the impact of symptoms on daily functioning, and the need for counselling and support.

AUTHOR SUMMARYDry Eye Disease occurs when your tears do not provide enough lubrication for your eyes, which can be caused by either decreased tear production, or by poor quality tears. This study reviewed 35 patient charts to examine 1) the impact of Dry Eye Disease on patients well-being, and 2) the use of telephone appointments to assess Dry Eye Disease during the COVID-19 pandemic. Patients reported an inability to enjoy their daily activities due to symptoms of dry eye including burning sensation and blurred vision. Over half of patients reported mental health challenges. Over a quarter of patients reported that financial challenges prevented them from treating their Dry Eye Disease, such as affording eye drops, dietary supplements, and appointments to see their optometrist. These findings highlight that healthcare providers should considering quality of life, mental health, and financial challenges when treating patients with Dry Eye Disease. Through the experience of an ophthalmologist who specializes in Dry Eye Disease, telephone appointments may be an effective way to assess Dry Eye Disease symptoms, the impact of symptoms on daily functioning, and the need for counselling and support.


title: Penetrance of HFE haemochromatosis variants to clinical disease: polygenic risk score associations in UK Biobank

abstract:
BackgroundThe iron overload condition Hereditary Heamochromatosis (HH) can cause liver cirrhosis and cancer, diabetes and arthritis. In Europeans, most HH disease occurs in male HFE p.C282Y homozygotes, yet only a minority of homozygotes in the general population develop these conditions. We aimed to determine whether common genetic variants influencing iron levels or risks for liver, diabetes or arthritis diagnoses in the general population also modify clinical penetrance in HFE p.C282Y and p.H63D carriers.

Methods1,294 male and 1,596 female UK Biobank European-ancestry HFE p.C282Y homozygous participants with electronic medical records up to 14 years after baseline assessment were studied. Polygenic risk scores (PRS) quantified genetic effects on blood iron biomarkers and relevant diseases (identified in the general population). Analyses were repeated in 10,699 p.C282Y/p.H63D compound heterozygotes.

ResultsIn male p.C282Y homozygotes, higher iron PRS increased risk of liver fibrosis or cirrhosis diagnoses (top 20% of iron PRS had Odds Ratio 4.90: 95% Confidence Intervals 1.63 to 14.73, p=0.005 versus bottom 20%), liver cancer, and osteoarthritis, but not diabetes. The liver cirrhosis PRS also associated with increased liver cancer diagnoses, and greater type-2 diabetes PRS increased risk of type-2 diabetes. In female p.C282Y homozygotes, osteoarthritis PRS was associated with increased osteoarthritis diagnoses, and type-2 diabetes PRS with type-2 diabetes. However, the iron PRS was not robustly associated with diagnoses in p.C282Y homozygote females, or in other p.C282Y/p.H63D genotypes.

ConclusionsHFE p.C282Y homozygote penetrance to clinical disease in a large community cohort was partly explained by common genetic variants that influence iron and risks of related diagnoses in the general population. Including PRS in HH screening and diagnosis may help in estimating prognosis and treatment planning.

Lay SummaryTwo or three sentences summarizing the main message of the article expressed in plain English to describe your findings to a non-medical audience.

O_LIHereditary Haemochromatosis, an iron overload condition, is the most common genetic disease in Northern Europeans; 1 in 150 people carry two copies of the highest risk mutation (called HFE p.C282Y).
C_LIO_LIOnly a minority of those with high risk HH variants actually develop iron overload diseases, such as liver cancer, cirrhosis, diabetes and arthritis. We tested whether known genetic variants with smaller effects on iron levels in the whole population modify risk of iron overload related disease in those with the HH high risk variants. We did similar tests for variants linked to each of the diseases caused by iron overload.
C_LIO_LIIncreased genetic risk for higher iron significantly raised the likelihood of liver fibrosis, cirrhosis and cancer in mutation carriers. In the future this information could help identify at-risk haemochromatosis patients early.
C_LI

category: genetic and genomic medicine


title: Adequacy of Self-Collected Anterior Nares Swabs for SARS-CoV-2 Testing by Grade School Children

abstract:
BackgroundThe goal of this study was to characterize the ability of school-aged children to self-collect adequate anterior nares (AN) swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.

MethodsFrom July to August 2021, 287 children, age 4-14 years-old, were prospectively enrolled in the Atlanta area. Symptomatic (n=197) and asymptomatic (n=90) children watched a short instructional video before providing a self-collected AN specimen. Health care workers (HCWs) then collected a second specimen, and useability was assessed by the child and HCW. Swabs were tested side-by-side for SARS-CoV-2. RNase P RNA detection was investigated as a measure of specimen adequacy.

ResultsAmong symptomatic children, 87/196 (44.4%) tested positive for SARS-CoV-2 by both self- and HCW-swab. Two children each were positive by self- or HCW-swab; one child had an invalid HCW-swab. Compared to HCW-swabs, self-collected swabs had 97.8% and 98.1% positive and negative percent agreements, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups. Participants [≤]8 years-old were less likely than those >8 to be rated as correctly completing self-collection, but SARS-CoV-2 detection did not differ. Based on RNase P RNA detection, 270/287 children (94.1%) provided adequate self-swabs versus 277/287 (96.5%) HCW-swabs (p=0.24) with no difference when stratified by age.

ConclusionsChildren, aged 4-14 years-old, can provide adequate AN specimens for SARS-CoV-2 detection when presented with age-appropriate instructional material, consisting of a video and a handout, at a single timepoint. These data support the use of self-collected AN swabs among school-age children for SARS-CoV-2 testing.


title: Diagnostic accuracy of age-adjusted D-dimer for pulmonary embolism among Emergency Department patients with suspected SARS-COV-2: A Canadian COVID-19 Emergency Department Rapid Response Network study

abstract:
ImportanceRuling out pulmonary embolism (PE) among patients presenting to the Emergency Department (ED) with suspected or confirmed SARS-COV-2 is challenging due to symptom overlap, known increased pro-thrombotic risk, and unclear D-dimer test interpretation.

ObjectiveOur primary objective was to assess the diagnostic accuracy of standard and age-adjusted D-dimer test thresholds for predicting 30-day pulmonary embolism (PE) diagnosis in patients with suspected SARS-COV-2 infection.

Design, Setting, and ParticipantsThis was a retrospective observational study using data from 50 sites enrolling patients into the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry between March 1, 2020 to July 2, 2021. Adults ([≥]18 years) with SARS-COV-2 testing performed at index ED visit were included if they had any of the following presenting complaints: chest pain, shortness of breath, hypoxia, syncope/presyncope, or hemoptysis. We excluded patients with duplicate records or no valid provincial healthcare number.

Main Outcomes and MeasuresOur primary end point was 30-day PE diagnosis based on a positive computed tomography pulmonary angiogram (CTPA) or hospital discharge diagnosis code of PE. The outcome measure was the diagnostic accuracy of an age adjusted D-dimer strategy as compared to absolute D-dimer thresholds (500 - 5000 ng/mL).

Results52,038 patients met inclusion criteria. Age-adjusted D-dimer had a sensitivity (SN) of 96% (95% CI 93-98%) and a specificity (SP) of 48% (95% CI 48-49%) which was comparable to the most sensitive absolute threshold of 500 ng/mL (SN 98%, 95% CI 96-99%; SP 41%, 95% CI 40-42%). Other absolute D-dimer thresholds did not perform well enough for clinical reliability (SN <90%). Both age-adjusted and absolute D-dimer performed better in SARS-COV-2 negative patients as compared to SARS-COV-2 positive patients for predicting 30-day PE diagnosis (c-statistic 0.88 vs 0.80).

Conclusions and RelevanceIn this large Canadian cohort of ED patients with suspected SARS-COV-2 infection, an age-adjusted D-dimer strategy had similar sensitivity and superior specificity to the most sensitive D-dimer threshold of 500 ng/mL for predicting 30-day PE diagnosis irrespective of SARS-COV-2 infection status. Adopting an age-adjusted D-dimer strategy in patients with suspected SARS-COV-2 may help avoid unnecessary CTPA testing without compromising safety.

Trial RegistrationClinicaltrials.gov, NCT04702945

KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the diagnostic accuracy of age-adjusted and absolute D-dimer thresholds for investigating PE in ED patients with suspected SARS-COV-2?

FindingsAn age-adjusted D-dimer strategy had comparable sensitivity and higher specificity for 30-day PE diagnosis compared to the most sensitive absolute threshold of 500 ng/mL irrespective of patients SARS-COV-2 status.

MeaningConsider using an age-adjusted D-dimer threshold for PE risk stratification in ED patients with suspected SARS-COV-2.

category: emergency medicine


title: Is virtual care the new normal? Evidence supporting Covid-19's durable transformation on healthcare delivery

abstract:
ObjectiveDespite the surge of telemedicine use during the early stages of the coronavirus-19 (COVID-19) pandemic, research has not evaluated the extent to which the growth of telemedicine has been sustained during recurring pandemic waves. This study provides data on the long-term durability of video-based telemedicine visits and their impact on urgent and non-urgent healthcare delivery from one large health system in New York City.

Materials and MethodsElectronic health record (EHR) data of patients between January 1st, 2020 and November 30th, 2021 were used to conduct the analyses and longitudinal comparisons of telemedicine or in-person visit volumes. Patients diagnosis data were used to differentiate COVID-19 suspected visits from non-COVID-19 ones while comparing the visit types.

ResultsWhile COVID-19 prompted an increase in telemedicine visits and a simultaneous decline in in-person clinic visits, telemedicine use has stabilized since then for both COVID-19 and non-COVID suspected visits. For COVID-19 suspected visits, utilization of virtual urgent care facilities is higher than the trend. The data further suggests that virtual healthcare delivery supplements, rather than replaces, in-person care.

DiscussionThe COVID-19 pandemic has transformed the use of telemedicine as a means of healthcare delivery, and the data presented here suggests that this is an enduring transformation.

ConclusionTelemedicine use increased with the surge of infection cases during the pandemic, but evidence suggests that it will persist after the pandemic, especially for younger patients, for both urgent and non-urgent care. These findings have implications for the healthcare delivery system, insurers and policymakers.


title: Impact of long-term COVID on workers: a systematic review protocol

abstract:
IntroductionPart of the patients infected by COVID-19 have at least one lasting sequel of the disease and may be framed in the concept of long Covid. These sequelae can compromise the quality of life, increase dependence on other people for personal care, impair the performance of activities of daily living, thus compromising work activities and harming the health of the worker. This protocol aims to critically synthesize the scientific evidence on the effects of Covid-19 among workers and its impact on their health status and professional life.

MethodSearches will be performed in MEDLINE via PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, LILACS and Epistemonikos. Included studies will be those that report the prevalence of long-term signs and symptoms in workers and/or the impact on their health status and work performance, which may be associated with Covid-19 infection. Data extraction will be conducted by 3 reviewers independently. For data synthesis, a results report will be carried out, based on the main outcome of this study.

DiscussionThis review will provide evidence to support health surveillance to help decision makers (i.e. healthcare providers, stakeholders and governments) regarding long-term Covid.


title: A systematic review and meta-analysis of Long COVID symptoms

abstract:
BackgroundOngoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as ":Long COVID": (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres.

MethodsA systematic protocol was developed, peer reviewed and published in PROSPERO. The systematic review included publications from the 1st of December 2019-30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analysed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified.

ResultsOf the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported.

ConclusionsThe quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.

FundingNone