title: Initial Antidepressant Choice by Non-Psychiatrists: Learning from Large-scale Electronic Health Records

abstract:
IntroductionPharmacological treatment of depression mostly occurs in non-psychiatric settings, but factors that determine the initial choice of antidepressant treatment in these settings are not well-understood. This study models how non-psychiatrists choose among four antidepressant classes at first prescription (selective serotonin reuptake inhibitors [SSRI], bupropion, mirtazapine, or serotonin-norepinephrine reuptake inhibitors [SNRI]), by analyzing electronic health record (EHR) data.

MethodsEHR data were from the Mass General Brigham Healthcare System (Boston, Massachusetts, USA) for the period from 1990 to 2018. From a literature search and expert consultation, we selected 64 variables that may be associated with antidepressant choice. Patients who participated in the study were aged 18 to 65 at the time of first antidepressant prescription with a co-occurring International Classification of Diseases (ICD) code for a depressive disorder. Multinomial logistic regression with main effect terms for all 64 variables was used to model the choice of antidepressant. Using SSRI as the reference class, odds ratios, 95% confidence intervals (CI), and likelihood ratio-based p-values for each variable were reported. We used a false discovery rate (FDR) with the Benjamini-Hochberg procedure to correct for multiple comparisons.

FindingsA total of 47,107 patients were included after application of inclusion/exclusion criteria. We observed significant associations for 36 of 64 variables after multiple comparison corrections. Many of these associations suggested that antidepressants known pharmacological properties/actions guided choice. For example, there was a decreased likelihood of bupropion prescription among patients with epilepsy (adjusted OR 0.41, 95% CI: 0.33-0.51, p < 0.001), an increased likelihood of mirtazapine prescription among patients with insomnia (adjusted OR 1.58, 95% CI: 1.39-1.80, p < 0.001), and an increased likelihood of SNRI prescription among patients with pain (adjusted OR 1.22, 95% CI: 1.11-1.34, p = 0.001).

InterpretationNon-psychiatrists selection of antidepressant class appears to be guided by clinically relevant pharmacological properties, indications, and contraindications, suggesting that broadly speaking they choose antidepressants based on meaningful differences among medication classes.


title: Disability Training for Health Care Workers: A Global Narrative Systematic Review

abstract:
BackgroundHealth worker training on disability is a recognized component of achieving high standards of health for people with disabilities, given that health workers lack of knowledge, stigma, and negative attitudes towards people with disabilities act as barriers to high quality health care.

ObjectiveTo understand the published literature on training health workers about disability.

MethodsWe searched five databases for relevant peer-reviewed articles published between January 2012 and January 2021. Studies that focused on training health care workers to improve knowledge, confidence, self-efficacy, and competence to support people with physical, sensory, or intellectual impairments were included. Data about the details of the intervention (setting, participants, format, impact assessments, etc.) and its effects were extracted.

ResultsThere is an array of highly local tools to train health workers across stages of their training and careers (pre-service, in-service, and continuing professional development). Studies involving people with disabilities in the training, community placements, simulations, or interactive sessions were found to be most effective in improving knowledge, confidence, competency, and self-efficacy.

ConclusionsAs part of initiatives to build inclusive health systems and improve health outcomes for people with disabilities, health workers around the world need to receive appropriate and evidence-based training that combine multiple methods and involve people with disabilities.

category: medical education


title: Prospective cohort study of socioeconomic status and subsequent unemployment under COVID-19 in Japan

abstract:
ObjectivesTo examine the relationship between socioeconomic factors and unemployment among workers during COVID-19 pandemic in Japan.

DesignA prospective cohort study, follow-up from December 22-25, 2020 through February 18-19, 2021.

SettingThe panelists registered with an Internet survey company

ParticipantsA cluster random sample of 33,087 workers with stratification by sex, job type, and region among Japans working population

Main outcomes and measuresUnemployment between December 2020 and February 2021

ResultsAmong the 19,941 participants, 725 (3.6%) had experienced unemployment. Multivariate analysis showed that the significant high unemployment for women (compared to men); younger age (compared to older age); being married (spouse not working), bereaved or divorced, and unmarried (compared to married (spouse working)); annual household income less than 6 million yen, (compared to more than 10 million yen); junior high or high school, vocational school, junior college, or technical school (compared to graduate school); and temporary or contract employees, self-employed, agriculture, forestry, or fishing (compared to general employees).

ConclusionsCOVID-19 appears to have created difficulties for the vulnerable groups. This suggests the need for employment and economic support for such individuals.

Strengths and limitations of this studyUnder the pandemic of COVID-19, we found that unemployment was associated with socioeconomic factors such as age, sex, marriage, income, education and occupation.

Our findings suggest that in the event of a major epidemic, resulting in unemployment among vulnerable segments of the labour market, regardless of whether workers themselves are infected.

It was unclear why the participants had experienced unemployment

This study was conducted as an Internet survey, so the generalizability of our results is limited.

category: occupational and environmental health


title: The socioeconomic factors that led to unemployment under COVID-19 pandemic among Japanese workers: a prospective cohort study


title: Multi-trait genome-wide association study identifies novel endometrial cancer risk loci that are associated with obesity or female testosterone levels

abstract:
We have performed genetic correlation and Mendelian randomization analyses using publicly available genome-wide association study (GWAS) data to identify endometrial cancer risk factors. These and previously established risk factors of endometrial cancer were then included in a multi-trait Bayesian GWAS analysis to detect endometrial cancer susceptibility variants, identifying three novel loci (7q22.1, 8q24.3 and 16q12.2); two of which were replicated in an independent endometrial cancer GWAS dataset. These loci are hypothesized to affect endometrial cancer risk through altered sex-hormone levels or through effects on obesity. Consistent with this hypothesis, several genes with established roles in these pathways (CYP11B1, CYP3A7, IRX3 and IRX5) were prioritized as candidate endometrial cancer risk genes by interrogation of quantitative trait loci data and chromatin capture assays in endometrial cell lines. The findings of this study identify additional opportunities for hormone treatment and further support weight loss to reduce the risk of developing endometrial cancer.

Statement of SignificanceThis study prioritizes four genes related to testosterone and obesity as candidate endometrial cancer risk genes, as well as identifies additional opportunities for hormone treatment and further supports weight loss to reduce endometrial cancer risk.

category: oncology


title: Trends and Intensity of Human Rhinovirus Invasions in Kilifi, Coastal Kenya Over a Twelve-Year Period, 2007-2018

abstract:
BackgroundHuman rhinovirus (HRV) is an ubiquitous pathogen and the principal etiologic agent of common cold. Despite the high frequency of HRV infections, data describing its long-term epidemiological patterns in a single population remain limited.

MethodsWe analysed 1,070 VP4/VP2 genomic region sequences obtained from samples collected between 2007-2018 from hospitalised paediatric patients (< 60 months) with acute respiratory disease in Kilifi County Hospital on the Kenya Coast.

ResultsOf 7,231 children enrolled, HRV was detected in 1,497 (20.7%) andVP4/VP2 sequences were recovered from 1,070 samples (71.5%). A total of 144 different HRV types were identified (67 HRV-A, 18 HRV-B and 59 HRV-C) and at any time-point, several types co-circulated with alternating predominance. Within types multiple genetically divergent variants were observed. Ongoing HRV infections appeared to be a combination of (i) persistent types (observed up to seven consecutive months), (ii) reintroduced genetically distinct variants and (iii) new invasions (average of 8 new types, annually).

ConclusionSustained HRV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than prolonged circulation of locally established strains.

category: infectious diseases


title: A single intramuscular injection of monoclonal antibody MAD0004J08 induces in healthy adults SARS-CoV-2 neutralising antibody titres exceeding those induced by infection and vaccination

abstract:
BackgroundThe emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is an extremely potent Fc-engineered monoclonal antibody (mAb) able to neutralise in vitro all current SARS-CoV-2 variants of concern (VoCs). This ongoing study, evaluates safety, pharmacokinetics and SARS-CoV-2 sera neutralization effect of MAD0004J08 when administered as single dose intramuscularly in healthy adults.

MethodWe conducted a dose escalation study with sequential enrolment of three cohorts, each with an increasing dose level of MAD0004J08 (48mg, 100mg and 400mg). Within each cohort, 10 young healthy adults were randomized with 4:1 ratio to a single intramuscular (i.m.) injection of MAD0004J08 or placebo. The primary endpoint is the proportion of subjects with severe and/or serious treatment emergent adverse events (TEAEs) within 7 days post-treatment. Secondary endpoints reported in this paper are the proportion of subjects with solicited TEAEs up 7 days post dosing, MAD0004J08 serum concentrations and neutralising activity versus the original SARS-COV-2 Wuhan virus at different timepoints post-dosing. As post-hoc analyses, we compared the sera neutralising titres of subjects who received MAD0004J08 with those of people that had received the COVID-19 BNT162b2 mRNA vaccine in the previous sixty days (n=10) and COVID-19 convalescent patients (n=20), and assessed serum neutralisation activity against the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS-CoV-2 variants of concern.

FindingsA total of 30 subjects, 10 per cohort, were enrolled and randomized. Data up to 30 days were available and analysed in this report. No severe TEAEs were reported in any of the cohorts in the 7 days post-treatment. MAD0004J08 was detected in the sera of treated subjects within few hours post-administration and reached almost maximal levels on day 8. The geometric mean neutralising titres (GMT) assessed against the original Wuhan virus peaked on day 8 and ranged 226 - 905, 905 - 2,560, and 1,280 - 5,120 for cohort 1, 2 and 3 respectively. The sera neutralising GMT in MAD0004J08 treated subjects in all the three cohorts were found to be 1{middle dot}5-54{middle dot}5-fold higher compared to sera from convalescent patients and 1{middle dot}83- 76{middle dot}4-fold higher compared to sera from COVID-19 vaccinees. Finally, GMT in MAD0004J08 treated subjects showed high neutralising titres versus the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) SARS-CoV-2 VoCs.

InterpretationA single dose administration of MAD0004J08 via i.m. route is safe and well tolerated and results in a rapid systemic distribution of the MAD0004J08 and sera neutralising titres higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralise major SARS-CoV-2 variants of concern. Based on these results, a Phase 2-3 trial is ongoing to further assess the safety, dosage, and efficacy of MAD0004J08 in asymptomatic or mild-moderate symptomatic COVID-19 patients.

FundingEU Malaria Fund, Ministero dello Sviluppo Economico, Ministero della Salute, Regione Toscana, Toscana Life Sciences Sviluppo and European Research Council.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PUBMED, MEDLINE and MedRxiv for clinical trials, meta-analyses and randomized controlled trials evaluating the antibody neutralization titres vs. different SARS-CoV-2 variants of concern obtained from subjects who received monoclonal antibodies for the treatment of COVID-19 using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("monoclonal antibody" OR "neutralising antibody") AND ("variants" OR "variants of concern"). No relevant studies were identified.

Added value of this studyThis is the first human study assessing safety, PK and neutralising potential of MAD0004J08, a monoclonal antibody against SARS-CoV-2 wild type Wuhan virus and variants of concern, administered intramuscularly at low dosages (48, 100 and 400 mg). MAD0004J08 showed to be safe and well tolerated in the tested dose range. Anti-spike antibodies were detected in the sera of tested SARS-CoV-2 negative healthy adults few hours post-injection. In addition, the sera obtained from MAD0004J08treated subjects, showed to have high neutralisation titres against the Wuhan virus, the B.1.1.7 (alpha), B.1.351 (beta) and B.1.1.248 (gamma) variants of concern.

Implications of all the available evidenceA potent monoclonal antibody such as MAD0004J08, capable of neutralising multiple variants of concern of SARS-CoV-2 rapidly and long lastingly when given as a single intramuscular injection. The antibody, presently tested in a phase 2-3 efficacy trial, can be a major advancement in the prophylaxis and clinical management of COVID-19, because of its broad spectrum, ease of use in non-hospital settings and economic sustainability.


title: Azithromycin in patients with Covid-19; a systematic review and metanalysis

abstract:
BackgroundAzithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the available evidence to date on the beneficial and adverse effect of AZM in patients with Covid-19.

MethodsThe PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data.

ResultsThe initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated, or not, with AZM, OR: 0.95 (0.79-1.13). There was also no significant difference for those treated, and not, with AZM in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects.

ConclusionsThese results presented in this review do not support the use of AZM in the management of Covid-19. They also show that any harm caused to the patient who received it is unlikely. Future research on treatment for patients with Covid-19 may need to focus on other drugs.


title: A Sustainable Development Goal framework to guide multisectoral action on NAFLD through a societal approach

abstract: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines. In the absence of a multisectoral framework, we developed a NAFLD-Sustainable Development Goals (SDG) framework to converge thinking about the design and delivery of NAFLD public health responses. A multidisciplinary group identified SDG targets and indicators for inclusion in the NAFLD-SDG framework through a two-stage process. Firstly, a core team of three researchers independently reviewed the 169 SDG targets and 231 unique indicators proposed by the Inter-Agency and Expert Group on SDG to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include in the NAFLD-SDG framework. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final NAFLD-SDG framework. The final framework comprises 16 targets-representing 9% of all SDG targets and 62% (16/26) of the shortlisted targets-and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all SDG indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy and the built environment. Addressing the challenge of NAFLD will require re-envisioning the liver health landscape, with a greater focus on joined-up systems thinking and action. The NAFLD-SDG framework can help guide this process, including by outlining the key stakeholders with whom the liver health community needs to engage.

category: public and global health


title: Cytocapsular Tube-Based Precise Cancer Diagnosis in Colon Cancers

abstract: Colorectal (colon) cancer ranks second in terms of cancer lethality worldwide. It is estimated that approximately 1.93 million new colorectal (colon) cancer cases and approximate one million colorectal cancer deaths occur worldwide in 2020 alone. Cancer metastasis is a major source of cancer lethality. Mechanisms underlying colorectal cancer metastases are long-term obscure. Recently, a new organelle associated with aggressive cancer cells, dubbed cytocapsular tube, was recognized to conduct cancer cell metastases in tissues in vivo. Here, we investigated the roles of cytocapsular tubes in colon cancer metastasis in 9 subtypes of colon cancers with original clinical colon cancer tissues, paracancer tissues of colon cancer, and metastatic colon cancers in multiple other tissues and organs. We found that colon cancer metastasized via cytocapsular tubes and their networks in clinical tissues in vivo. Furthermore, we applied the cytocapsular tube analyses in precise cancer diagnosis in clinical colon cancers and obtained better outcomes in clinical colon cancer management.


title: An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19

abstract:
BackgroundBoth continuous positive airway pressure (CPAP) and high-flow nasal oxygenation (HFNO) have been recommended for acute respiratory failure in COVID-19. However, uncertainty exists regarding effectiveness and safety.

MethodsIn the Recovery-Respiratory Support multi-center, three-arm, open-label, adaptive, randomized controlled trial, adult hospitalized patients with acute respiratory failure due to COVID-19, deemed suitable for treatment escalation, were randomly assigned to receive CPAP, HFNO, or conventional oxygen therapy. Comparisons were made between each intervention and conventional oxygen therapy. The primary outcome was a composite of tracheal intubation or mortality within 30-days.

ResultsOver 13-months, 1272 participants were randomized and included in the analysis (380 (29.9%) CPAP; 417 (32.8%) HFNO; 475 (37.3%) conventional oxygen therapy). The need for tracheal intubation or mortality within 30-days was lower in the CPAP group (CPAP 137 of 377 participants (36.3%) vs conventional oxygen therapy 158 of 356 participants (44.4%); unadjusted odds ratio 0.72; 95% CI 0.53 to 0.96, P=0.03). There was no difference between HFNO and conventional oxygen therapy (HFNO 184 of 414 participants (44.4%) vs conventional oxygen therapy 166 of 368 participants (45.1%); unadjusted odds ratio 0.97; 95% CI 0.73 to 1.29, P=0.85).

ConclusionsCPAP, compared with conventional oxygen therapy, reduced the composite outcome of intubation or death within 30 days of randomisation in hospitalized adults with acute respiratory failure due to COVID-19. There was no effect observed, compared with conventional oxygen therapy, with the use of HFNO.

(Funded by the UK National Institute for Health Research; ISRCTN 16912075).

category: intensive care and critical care medicine


title: Increased brain atrophy over 3 years in stroke survivors is linked to early post-stroke cognitive impairment

abstract:
BackgroundStroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants.

MethodsCognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years; secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error.

ResultsNinety-three stroke (26 women, 66.7{+/-}12 years) and 39 control participants (15 women, 68.7{+/-}7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M)=20.3cm3{+/-}SD14.8cm3; controls M=14.2cm3{+/-}SD13.2cm3; (adjusted mean difference 7.88 95%CI [2.84,12.91] p-value=0.002). TBV decline was greater in those stroke participants who were cognitively impaired (M=30.7cm3; SD=14.2cm3) at 3 months (M=19.6cm3; SD=13.8cm3); (adjusted mean difference 10.42; 95%CI [3.04,17.80], p-value=0.006). No statistically significant differences in HV change were observed.

ConclusionsIschaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired people early after their stroke. Early cognitive impairment may predict greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke cognitive impairment.

category: neurology


title: Complementing Tissue Testing with Plasma mutation Profiling Improves Therapeutic Decision Making for Lung Cancer Patients

abstract:
BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and associated with limitations of tissue heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.

MethodsPatients with suspected lung cancer (n=71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 hrs of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples, where available (tissue EGFR testing). Concordance of clinically actionable mutations between methods and sample types were assessed.

ResultsFor confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF and MET. Overall sensitivity of EGFR sensitizing mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n=37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a near doubling (1.9-fold increase) of clinically relevant findings. The average turnaround time (TAT) of plasma NGS was shorter than standard tissue testing (10 days vs. 29.9 days, p-value <0.05).

ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with shorter time to results. This study outlines the clinical utility of a complementary plasma mutation profiling in the routine management of lung cancer patients.


title: Novel Driver Strength Index highlights important cancer genes in TCGA PanCanAtlas patients

abstract: Elucidating crucial driver genes is paramount for understanding the cancer origins and mechanisms of progression, as well as selecting targets for molecular therapy. Cancer genes are usually ranked by the frequency of mutation, which, however, does not necessarily reflect their driver strength. Here we hypothesize that driver strength is higher for genes that are preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer. We propose a formula to calculate the corresponding Driver Strength Index (DSI), as well as the Normalized Driver Strength Index (NDSI), the latter completely independent of the overall gene mutation frequency. We validate these indices using the largest database of human cancer mutations - TCGA PanCanAtlas, multiple established algorithms for cancer driver prediction (2020plus, CHASMplus, CompositeDriver, dNdScv, HotMAPS, OncodriveCLUSTL, OncodriveFML) and four custom computational pipelines that integrate driver contributions from SNA, CNA and aneuploidy at the patient-level resolution. We demonstrate that DSI and especially NDSI provide substantially different rankings of genes as compared to frequency approach. For example, NDSI prioritized members of specific protein families, including G proteins GNAQ, GNA11 and GNAS, isocitrate dehydrogenases IDH1 and IDH2, and fibroblast growth factor receptors FGFR2 and FGFR3. KEGG analysis shows that top NDSI-ranked genes comprise EGFR/FGFR2/GNAQ/GNA11 - NRAS/HRAS/KRAS - BRAF pathway, AKT1 - MTOR pathway, and TCEB1 - VHL - HIF1A pathway. NDSI does not seem to correlate with the number of protein-protein interactions. We share our software to enable calculation of DSI and NDSI for outputs of any third-party driver prediction algorithms or their combinations.


title: Negative impact of COVID-19 associated health system shutdown on patients diagnosed with colorectal cancer: a retrospective study from a large tertiary center in Ontario, Canada.

abstract:
BackgroundIn March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown.

MethodsCRC resections collected within the Champlain catchment area of eastern Ontario in the six months prior to COVID-19 (August 1, 2019-January 31, 2020) were compared to CRC resections collected in the six months post-COVID-19 slowdown (August 1, 2020-January 31, 2021). Clinical (e.g. gender, patient age, tumour site, clinical presentation) and pathological (tumour size, tumour stage, nodal stage, lymphovascular invasion) features were evaluated using chi square tests, T-tests and Mann-Whitney tests where appropriate.

Results343 CRC specimens were identified (175 pre-COVID-19, 168 post-COVID-19 slowdown). CRC patients treated surgically post-COVID-19 slowdown had larger tumours (44 mm vs. 35 mm; p = 0.0048) and were more likely to have presented emergently (24% vs .10%; p < 0.001). While there was a trend towards higher tumour stage, nodal stage, and clinical stage, these differences did not reach statistical significance. Other demographic and pathologic variables including patient gender, age, and tumour site were similar between the two cohorts.

InterpretationThe COVID-19 slowdown resulted in a shift in the severity of disease experienced by CRC patients in Ontario. Pandemic planning in the future should consider the long-term consequences to cancer diagnosis and management.


title: The genomic and transcriptional landscape of primary central nervous system lymphoma

abstract: Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the genomic and transcriptional landscape of PCNSL, we here performed whole-genome and transcriptome sequencing and integrative analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL and matched controls. The results were compared to an independent validation cohort of 31 FFPE CNSL specimens (PCNSL, n = 19; SCNSL, n = 9; EBV+ CNSL, n = 3) as well as 39 FL and 36 systemic DLBCL cases outside the CNS. Somatic genomic alterations in PCNSL mainly affect the JAK-STAT, NFkB, and B-cell receptor signaling pathways, with hallmark recurrent mutations including MYD88 L265P (67%) and CD79B (63%), CDKN2A deletions (83%) and also non-coding RNA genes such as MALAT1 (70%), NEAT (60%), and MIR142 (80%). Kataegis events, which affected 15 of 50 identified driver genes and 21 of the top 50 mutated ncRNAs, played a decisive role in shaping the mutational repertoire of PCNSL. Compared to systemic DLBCL, PCNSLs exhibited significantly more focal deletions in 6p21 targeting the HLA-D locus that encodes for MHC class II molecules as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis (SBS1, ID1 and ID2) were significantly enriched in PCNSL (SBS1: p = 0.0027, ID1/ID2: p < 1x10-4). Furthermore, TERT gene expression was significantly higher in PCNSL compared to ABC-DLBCL (p = 0.027). Although PCNSL share many genetic alterations with systemic ABC-DLBCL in the same signaling pathways, transcriptome analysis clearly distinguished both into distinct molecular subtypes. EBV+ CNSL cases may be distinguished by lack of recurrent mutational hotspots apart from IG and HLA-DRB loci.


title: Integrated miRNA/cytokine/chemokine profiling reveals immunopathological step changes associated with COVID-19 severity

abstract: Circulating microRNAs (miRNAs) are exceptional mechanism-based correlates of disease, yet their potential remains largely untapped in COVID-19. Here, we determined circulating miRNA and cytokine and chemokine (CC) profiles in 171 blood plasma samples from 58 hospitalised COVID-19 patients. Thirty-two miRNAs were differentially expressed in severe cases when compared to moderate and mild cases. These miRNAs and their predicted targets reflected key COVID-19 features including cell death and hypoxia. Compared to mild cases, moderate and severe cases were characterised by a global decrease in circulating miRNA levels. Partial least squares regression using miRNA and CC measurements allowed for discrimination of severe cases with greater accuracy (87%) than using miRNA or CC levels alone. Correlation analysis revealed severity group-specific associations between CC and miRNA levels. Importantly, the miRNAs that correlated with IL6 and CXCL10, two cardinal COVID-19-associated cytokines, were distinct between severity groups, providing a novel qualitative way to stratify patients with similar levels of proinflammatory cytokines but different disease severity. Integration of miRNA and CC levels with clinical parameters revealed severity-specific signatures associated with clinical hallmarks of COVID-19. Our study highlights the existence of severity-specific circulating CC/miRNA networks, providing insight into COVID-19 pathogenesis and a novel approach for monitoring COVID-19 progression.


title: Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19

abstract:
BackgroundThe longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19.

MethodsFifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months.

FindingsAt 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET.

By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4{middle dot}3 mls/m2, P=0{middle dot}005) decreased and RV ejection fraction (+3{middle dot}2%, P=0{middle dot}0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures.

InterpretationIn patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.

FundingNIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.


title: Epidemiological analysis of 869,220 varicose vein surgeries over 12 years in Brazil: trends, costs and mortality rate.

abstract:
2.Structured AbstractO_ST_ABSObjectivesC_ST_ABSto assess the total numbers of surgical procedures performed between 2008 and 2019 for the treatment of varicose veins in the Public Health System, which exclusively insures more than 160 million Brazilians, the distribution of surgeries over time, as well as its costs and mortality rates.

Study designretrospective cross-sectional population-based study

Materials and Methodspublic and open data referring to all surgeries to treat chronic venous disease between 2008 and 2019 were extracted from the database of the Brazilian Public Health System.

ResultsIn total, 869,220 surgeries were performed to treat chronic venous disease in public hospitals and outpatient clinics in Brazil, with an average rate of 4.5 surgeries per 10,000 inhabitants per year. From 2015 on, we observed a slight downward trend in the total number of procedures. The total amount reimbursed by the government was US$ 232,775,518.11. A total of 49 deaths were registered following varicose vein surgery, corresponding to a mortality rate of 0.0056%.

Conclusionsa total of 869,220 surgeries performed to treat chronic venous disease over twelve years, with an overall rate of 4.52 procedures per 10,000 inhabitants per year. The mortality rate was very low, 0.0056%.

category: cardiovascular medicine


title: Building knowledge of university campus population dynamics to enhance near-to-source sewage surveillance for SARS-CoV-2 detection

abstract: Wastewater surveillance has been widely implemented for monitoring of SARS-CoV-2 during the global COVID-19 pandemic, and near-to-source monitoring is of particular interest for outbreak management in discrete populations. However, variation in population size poses a challenge to the triggering of public health interventions using wastewater SARS-CoV-2 concentrations. This is especially important for near-to-source sites that are subject to significant daily variability in upstream populations. Focusing on a university campus in England, this study investigates methods to account for variation in upstream populations at a site with highly transient footfall and provides a better understanding of the impact of variable populations on the SARS-CoV-2 trends provided by wastewater-based epidemiology. The potential for complementary data to help direct response activities within the near-to-source population is also explored, and potential concerns arising due to the presence of heavily diluted samples during wet weather are addressed. Using wastewater biomarkers, it is demonstrated that population normalisation can reveal significant differences between days where SARS-CoV-2 concentrations are very similar. Confidence in the trends identified is strongest when samples are collected during dry weather periods; however, wet weather samples can still provide valuable information. It is also shown that building-level occupancy estimates based on complementary data aid identification of potential sources of SARS-CoV-2 and can enable targeted actions to be taken to identify and manage potential sources of pathogen transmission in localised communities.

category: epidemiology


title: Temporal considerations in the 2021 COVID-19 lockdown of Ho Chi Minh City

abstract:
The success of Vietnam in controlling the spread of COVID-19 hinges on a timely implementation of its coherent strategy of containment and rapid tracing and testing efforts. The Vietnamese living in Mekong Delta are currently being besieged by the SARS-Cov-2 Delta variant as they undergo several and extended levels of lockdown. In this work we examine the temporal aspects of the lockdown in Ho Chi Minh City and predict the progress of the outbreak in terms of the total number of confirmed cases.

A compartmental model with containment is fit to data to estimate the rate of transmission in Ho Chi Minh City. The severity of the lockdown is estimated from publicly-available data on mobility and coupled to the rate of infection. Various scenarios on when to begin a lockdown and its duration are assessed. This report, dated 27 July 2021, supports a lockdown of at least 3 weeks and predicts that there could be half as many cases had the inevitable lockdown started a week earlier.


title: Population normalisation in wastewater-based epidemiology for improved understanding of SARS-CoV-2 prevalence: A multi-site study

abstract: This paper aims to determine whether population normalisation significantly alters the SARS-CoV-2 trends revealed by wastewater-based epidemiology, and whether it is beneficial and/or necessary to provide an understanding of prevalence from wastewater SARS-CoV-2 concentrations. It uses wastewater SARS-CoV-2 data collected from 394 sampling sites, and implements normalisation based on concentrations of a) ammoniacal nitrogen, and b) orthophosphate. Wastewater SARS-CoV-2 metrics are evaluated at a site and aggregated level against three indicators prevalence, based on positivity rates from the Office for National Statistics Coronavirus Infection Survey and test results reported by NHS Test and Trace. Normalisation is shown to have little impact on the overall trends in the wastewater SARS-CoV-2 data on average. However, significant variability between the impact of population normalisation at different sites, which is not evident from previous WBE studies focussed on a single site, is also revealed. Critically, it is demonstrated that while the impact of normalisation on SARS-CoV-2 trends is small on average, it is not reasonable to conclude that it is always insignificant. When averaged across many sites, normalisation strengthens the correlation between wastewater SARS-CoV-2 data and indicators of prevalence; however, confidence in the improvement is low. Lastly, it is noted that most data were collected during periods of national lockdown and/or local restrictions, and thus the impacts and benefits of population normalisation are expected to be higher when normal travel habits resume.


title: Quantifying the ongoing epidemic of disability after covid-19 in the UK population aged under 35 years; secondary analysis of the ONS Infection Survey

abstract:
Web-based survey and anecdotal evidence suggest that many people infected with covid-19 go on to develop long covid (symptoms persisting for more than 12 weeks) despite mild initial disease. There is particular concern that this epidemic is unfolding in the younger population where vaccination rates are low. The Covid Infection Survey (CIS) has recently published estimates of the proportion of people with long covid whose daily activities are affected a little or a lot.

This paper focuses on the population aged under 35 years and uses the term  disabling long covid to describe those with symptoms lasting more than 12 weeks and daily activities limited a lot. By applying the CIS estimates to confirmed infections, with age breakdown from mid-2020 population estimates, this paper reports a first estimate of the cases of disabling long covid seeded from confirmed covid-19 infections to July 31st 2021.

Results suggest there will approximately 39,000 cases of disabling long covid in those aged under 35 seeded by Covid-19 infections confirmed to July 31st. There is a need for rapid action to prevent Covid-19 infection in the younger population and support those struggling with Long Covid-related disability.


title: High-risk alcohol consumption may increase the risk of SARS-CoV-2 seroconversion: a prospective seroepidemiologic cohort study among American college students

abstract:
AimsTo estimate the associations between high-risk alcohol consumption and (1) SARS-CoV-2 seroconversion, (2) self-reported new SARS-CoV-2 infection, and (3) symptomatic COVID-19.

DesignProspective cohort

SettingIndiana University Bloomington (IUB), a public university of 34,660 students in southern Indiana.

ParticipantsAt the beginning of the fall 2020 semester, we randomly sampled N=1,267 IU undergraduate students, aged 18 years or older and residing in Monroe County, IN.

MeasurementsPrimary exposure was high-risk alcohol consumption measured with the AUDIT questionnaire. We used an AUDIT score of 8 or more as the cut-off score when detecting high-risk alcohol consumption. Primary outcome was SARS-CoV-2 seroconversion, assessed with two SARS-CoV-2 antibody tests, at baseline and endline. Secondary outcomes were a) self-reported new SARS-CoV-2 infection at the study endline, and b) self-reported symptomatic COVID-19 at baseline.

FindingsPrevalence of high-risk alcohol consumption was 34%. We found that students with high-risk alcohol consumption status had 2.34 [95% CI: (1.29, 4.24)] times the risk of SARS-CoV-2 seroconversion and 1.89 [95% CI: (1.08, 3.32)] times the risk of self-reporting a positive SARS-CoV-2 infection, compared to students with no such risk. Moreover, students with high-risk alcohol consumption were 18% more likely to develop symptomatic COVID-19, though this association was not statistically significant. Similar results were found after adjusting for sex at birth, race, and year in school. Findings from sensitivity analyses corroborated these results and suggested potential for a dose-response relationship.

ConclusionsIn this sample of American college students, high-risk alcohol consumption was associated with higher risk for SARS-CoV-2 seroconversion/infection. These findings could have implications for colleges reopening planning in fall 2021.


title: Estimated pediatric SARS-CoV-2 seroprevalence in Arkansas over the first year of the COVID-19 pandemic

abstract:
BackgroundSARS-CoV-2 seroprevalence studies have largely focused on adults but little is known about spread in children. We determined SARS-CoV-2 seroprevalence in children and adolescents from Arkansas over the first year of the COVID-19 pandemic.

MethodsWe tested remnant serum samples from children from 1-18 years who visited Arkansas hospitals or clinics for non-COVID19-related reasons from April, 2020 through April, 2021 for SARS-CoV-2 antibodies. We used univariable and multivariable regression models to determine association between seropositivity and participant characteristics.

ResultsAmong 2400 participants, seroprevalence rose from 7.9% in April/May 2020 (95% CI, 4.9-10.9%) to 25.8% in April 2021 (95% CI, 22.2-29.3%). Hispanic and black children had a significantly higher association with antibody positivity than white children in multiple sampling periods.

ConclusionsBy spring 2021, most children in Arkansas had not been infected with SARS-CoV-2. With the emergence of SARS-CoV-2 variants, recognition of long-term effects of COVID-19, and the lack of an authorized pediatric SARS-CoV-2 vaccine, these results highlight the importance of including children in SARS-CoV-2 public health, clinical care, and research strategies. These findings are important for state and local officials as they consider measures to limit SARS-CoV-2 spread in schools and daycares for the 2021-2022 school year.


title: Pediatric SARS-CoV-2 seroprevalence in Arkansas over the first year of the COVID-19 pandemic


title: Survival of health workers infected by SARS-CoV-2 in the context of vaccination against COVID-19 in Peru

abstract:
ObjectivesTo evaluate the survival of health workers infected by SARS-CoV-2 in the context of the vaccination process against COVID-19 in Peru.

MethodsA survival analysis was performed using data from national health databases. Data from people between 18 and 59 years old infected with SARS-CoV-2 as evidenced by molecular or antigenic tests were included. Kaplan Meier graphs were produced to compare the survival of health workers and the rest of the population during 2021 and health workers during the first and second wave of mortality in Peru in 2020 and 2021, respectively.

ResultsData from 998,295 people were included. The average age was 41.2 years (SD 15.8) and 485,167 (48.6%) were women. A higher level of survival of health workers after vaccination was found compared to the general population and to the population of health workers before vaccination. It was evidenced that, at the beginning of the second wave, the risk of dying for health workers was twice that of the first wave (HR = 2). After vaccination (in the sixth month of the second wave), the risk of dying decreased to 87.5% less than in the first wave (HR = 0.125).

ConclusionsA positive change has been evidenced in the level of survival of health workers infected by SARS-CoV-2 during the context of vaccination against COVID-19 in Peru.


title: Impact of the World Inflammatory Bowel Disease Day and Crohn's & Colitis Awareness Week on Population Interest between 2016 and 2020: Google Trends Analysis

abstract:
BackgroundMore than 6 million people are affected by inflammatory bowel disease (IBD) globally. World IBD Day (WID; May 19) and Crohns and Colitis Awareness Week (CCAW; December 1-7) occur yearly as national health observances to raise public awareness of IBD, but their effects are unclear.

MethodsThis study evaluates the impact of WID and CCAW on the public awareness of IBD in the United States (US) and worldwide from 2016 to 2020 using the relative search volume (RSV) of "IBD," "Ulcerative colitis," and "Crohns disease" in Google Trends (GT). To identify significant timepoints of trend changes (joinpoints), we performed Joinpoint regression analysis.

ResultsNo joinpoints were noted around the time of WID or CCAW during the study period in the search results of the US. Worldwide, joinpoints were noted around WID in 2020 with the search for "IBD" and around CAAW in 2017 and 2019 to search for "ulcerative colitis." However, the extents of trend changes were modest without statistically significant increases.

ConclusionsWID and CCAD may not have worked as expected to raise public awareness of IBD. Additional measures are necessary to help raise awareness of IBD related to the health observances.

SummaryWorld IBD Day and Crohns and Colitis Awareness Week are key health observances related to IBD. These observances, however, might not have been effective in raising public awareness of IBD in the US and worldwide, according to Google Trends analysis.


title: A qualitative exploration of the perspectives of international medical students residing in university hostels amid COVID-19 pandemic lockdown

abstract:
BackgroundCOVID-19 pandemic has portentously frightened the existence of life all over the world. The lockdown approach was adopted as a containment strategy as the disease itself has manifested severe social, economic, and psychiatric implications.

ObjectivesTo explore the perception and preparedness of international medical students residing in university hostels amid the COVID-19 pandemic lockdown.

DesignA semi-structured interview guide was developed in this qualitative study design. All the interviews were audio-taped, transcribed verbatim, and then analyzed for thematic contents by standard content analysis framework.

SettingInterviews were conducted in university hostels in Punjab, Pakistan.

ParticipantsA total of 11 international medical students were interviewed face-to-face through the purposive sampling technique to obtain in-depth individual viewpoints.

ResultsThe thematic content analysis yielded five major themes: Familiarity with COVID-19, Perceptions and attitudes towards COVID-19, Preparedness for safety against COVID-19, Barriers to lifestyle, and Psychological perspectives. A better general perception and preparedness among international medical students regarding COVID-19 was found. Good knowledge regarding the overview of COVID-19; adequate preventive approaches such as social distancing, use of masks, gloves, and sanitizers; and compliance with the lockdown measures were reported by the respondents. The pertinent issue raised by the respondents is the disturbance in normal routine due to distortion in social life and isolation that may cause psychological stress.

ConclusionsThe findings from this study lighten the peoples perspectives that help the government to prepare public health strategies based on population-focused approaches. The present study demonstrates the respondents opinion on COVID-19 management by personal hygiene, social distancing, and complying with the lockdown measures. Furthermore, it demands that timely and evidence-based teaching-learning techniques should be adopted for students engagement which ensures mental health and self-motivation as well. Therefore, they can utilize their time productively which could have a long-term effect on their careers and healthcare services.


title: Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States-January-April, 2021

abstract: As of March 2021, three COVID-19 vaccines have been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic vaccine breakthrough infections based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 51,000 symptomatic vaccine breakthrough infections (95% CI: [~]48,000-55,000 cases) occurred in the United States during January-April 2021 among >77 million fully vaccinated people, reflecting <0.5% of COVID-19 cases that occurred during that time. With ongoing SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate before population immunity is sufficient to interrupt transmission. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.


title: Playing the Harmonica with Chronic Obstructive Pulmonary Disease. A qualitative study

abstract:
IntroductionPulmonary Rehabilitation (PR) is the gold standard, group-based intervention for individuals with Chronic Obstructive Pulmonary Disease (COPD). However, accessibility and adherence to PR is sub-optimal. Arts in Health interventions also improve health outcomes for people living with long term conditions. Playing the harmonica with COPD could be clinically beneficial. However, little is known about the patient experiences of playing the harmonica.

MethodsA qualitative, interpretivist, phenomenological study was undertaken, exploring COPD patient experiences of harmonica playing with a group of others living with chronic respiratory disease. Semi-structured interviews were completed, transcribed, and reflexive inductive thematic analysis performed.

ResultsEight people with COPD were interviewed. Thematic analysis generated five themes. Themes included "Hard in the beginning", "Holding the condition", "Breathing control", "Gives you a high" and "Needing the Zoom class". Playing the harmonica with COPD is difficult at first, particularly drawing a breath through the harmonica. With practice, experience in a fun activity, and quality teaching, individuals were able to become more attuned and embodied with their breathing. As breathing became easier the songs, rather than breathing, became the focus, and participants were able to escape living with respiratory disease when playing. The group was a priority in the weekly lives of participants, even though the buzz of being part of a group was lost.

DiscussionPlaying the harmonica requires a different way of breathing and offers a breathing control strategy. Participants also reported the harmonica helped airway clearance and enabled a continued, regular social interaction through COVID-19. The results of this study compliment previous quantitative results and are relevant to physiotherapy. Further mechanistic studies and randomised controlled trials are needed to investigate the biopsychosocial benefits of playing the harmonica with COPD.

category: respiratory medicine


title: Impaired SARS-CoV-2 mRNA vaccine antibody response in chronic medical conditions: a real-world data analysis

abstract: This study is to investigate whether certain medical conditions may impair antibody response to the mRNA vaccines. In this unique study, participants were drawn from patients in National Jewish Health, a pulmonary specialty outpatient clinic.Our study highlights fact that 26% of our patients (n=226) who had spike protein ab measured at least 14 days post 2nd vaccine had negative spike protein ab testing. We found interstitial lung disease (ILD) to be an independent risk factor for impaired antibody response. While the exact antibody level that confers protection against SARS-CoV-2 is unknown and there may be other non-B cell-mediated protection (e.g. T cell-mediated), our study raises concerns that SARS-CoV-2 vaccination may not result in protective immunity in all populations and may have implications for some as masking and distancing strategies are abandoned.


title: Removal of the race coefficient and adjustment to individual BSA provide the most accurate estimation for GFR in Black adolescents

abstract:
IntroductionObesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG).

MethodsWe created a cohort of women and girls ages 12-21 from the New York Metropolitan area using electronic health records. Glomerular filtration rate (GFR) was estimated in three ways: I) using the standard age recommended formulae, II) eGFRr - without a race-specific coefficient, and III) Absolute eGFRr - combing removal of the race coefficient and adjusting to individual body surface area. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of [≥]135ml/min/1.73m2. Bland Altman analysis and Pearsons coefficient assessed the correlation of each formula with creatinine clearance (CrCl).

Results7315 Black and 15,102 non-Black women and girls had simultaneous evaluation of kidney function and body measures. CrCl was available in 207 non-Black and 107 Black individuals as an internal validation. Simultaneous removal of the race coefficient and adjustment to individual BSA estimated GFR most accurately compared to CrCl, across BMI groups and between races. Hyperfiltration was more frequent in obese Black compared to non-Black individuals when using standard eGFR (20% vs. 6.5% respectively) but had a lower frequency after eliminating the race-specific coefficient (4.5% vs. 6.5%). Black race was independently associated with a higher risk of hyperfiltration with standard eGFR calculations (OR=3.43, 95% CI 2.95-3.99) and with lower risk when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Simultaneous removal of the race coefficient from GFR calculation and adjustment to individual BSA attenuated the difference in risk between races (OR=0.8, 95% CI 0.68-0.94). The combined correction agreed well with creatinine clearance (Pearsons correlation coefficient r=0.64, 0.52 and 0.52 for absolute eGFRr, eGFR and eGFRr respectively.

ConclusionsRemoval of the race coefficient from GFR estimating equations obscures obesity associated hyperfiltration among Black adolescents. This correction should be accompanied by adjustment to individual BSA to improve estimation of GFR to avoid misclassification of obesity related hyperfiltration.

category: nephrology


title: Depression, Anxiety and Stress among the Patient of Chronic Kidney Disease at Nadiad Gujarat, A Cross sectional study

abstract:
IntroductionChronic kidney disease is considered as a public health problem worldwide [1]. It is defined by kidney tissue injury with or without a decrease in glomerular filtration rate and /or a decrease in kidney function over a period of three or more months. When the glomerular filtration rate [GFR] is below 15ml./min./1.73m2, the patient is in the terminal stage or dialysis, requiring renal replacement therapy [RRT], dialysis or transplant as alternative treatments. Renal failure is the inability of the kidney to excrete wastes, concentrate urine, and conserve electrolytes. Renal failure is precipitated from a variety of etiological factors. It is treatable but not curable, which means that the patient needs a long term therapies or transplantation [2].

The overall prevalence of depression, anxiety and stress in this study found to be 22.9%, 19.2%, and 28.2%, respectively. Forty nine (13.84%) respondents had mild depression twenty eight (7.91%) has moderate depression[2].

Depression and anxiety are frequent comorbid disorders among chronic kidney disease (CKD) patients, with estimated prevalence of approximately 25% in this population, [3] and are associated with worse outcomes, such as progression to end-stage renal disease (ESRD) and mortality [4,5,6,7]. The transition from predialysis management to renal replacement therapy (RRT) is a stressful event in the course of CKD, leading to challenges and decisions that might increase their susceptibility to anxiety, mood disorders or even exacerbate psychological issues that already exist [8].

AimsThe researcher aim to assess the level of depression, anxiety and stress among chronic kidney disease patient in selected hospital of Nadiad City, Gujarat. The research wants to explore the actual psychological status of the patients who were suffering from chronic illness like CKD, because due to long term suffering from the illness disturbed the everyone mind and cause various psychological changes in the body. Hence research want to assess what kind of changes take place due to chronic kidney diseases.

ObjectivesO_LITo assess the level of depression among CKD patients at selected hospital, Nadiad.
C_LIO_LITo assess the level of anxiety among CKD patients at selected hospital, Nadiad.
C_LIO_LITo assess the level of stress among the CKD patients at selected hospital, Nadiad.
C_LI

MethodologyO_ST_ABSDesign and SettingC_ST_ABSDescriptive cross sectional survey research design was adopted for the study and non-probability purposive sampling method was used to drawn samples from the participants. For the data collection researcher has used modified The DASS-42 is a 42 item self-report scale designed to measure the negative emotional states of depression, anxiety and stress, it is a standardized tool.

Prior to data collection written setting permission obtain from the head of the hospital as well prior inform consent form was obtain from the study participants, the objectives and methods of the study were appropriately explain to the samples. For data collection researcher has select MPUH kidney hospital situated Nadiad City. The total sample size was 30 chronic kidney disease patients.

The research data collection tool consist of following Section I Demographic variables of the CKD patients section II DASS 42 questionnaire self rating scale.

Statistical AnalysisDescriptive statistics applied where, data were analyzed by using SPSS software, and Frequency, percentage, tables etc. were used to represent the statistical data in the tables and graph and figure.

ResultThe majority of participants (30%) were 41-50 years, sample (36.67%) belong age group of above 50 years, majority 56.67% were Male, (43.33%) were graduate, (67%) Having 5000-10000 Monthly Income, (60%) were living in Joint family, (56.67%) were belong to 0-3 years, (23.33%) were belong above 9 years if illness. Duration of hospitalization (80%) 0-15 days.

Prevalence rate of depression, anxiety and stress among Chronic Kidney Disease the most of patient have 50%, had moderate symptoms of depression, anxiety and stress, 30% had mild and only 20% have severe symptoms of depression, anxiety and stress which was measured by DASS self rating scale.

ConclusionsThe currents study ended to assess the prevalence rate of the depression, anxiety and stress among Chronic Kidney Disease patients, the study result concluded that the majority (50%) of Patients having moderate level of depression, anxiety and stress. The people in age group 41-50 or above 50 are having higher rate of depression, anxiety, and stress during chronic kidney disease.

category: nursing


title: Assessment of Quadriceps Muscle Weakness in Association with Symptomatic and Radiological Osteoarthritis of the Knee

abstract:
BackgroundPrimary knee osteoarthritis is a significant cause of impairment of the lower limbs mobility, making effective rehabilitation particularly important. This study aimed to identify the association of quadriceps strength with pain and disability in comparison to its association with increasing severity of radiological grades of knee osteoarthritis.

Methods50 subjects above the age of 40 years with different grades of knee osteoarthritis were evaluated for their radiological grade of osteoarthritis using Kellgren-Lawrence grading criteria for the knee radiographs, isometric quadriceps muscle strength using a modified hand-held dynamometer, pain, and disability using WOMAC questionnaire, all on the same day in this cross-sectional study.

ResultsThere is a significant negative correlation between K/L grade and maximum strength of the quadriceps muscle, r (50) = -0.28 (p<0.05). We found a highly significant negative correlation between WOMAC score and strength of the quadriceps muscle, r (50) = -0.41 (p<0.05).

DiscussionQuadriceps strength reduced progressively in subjects with more significant radiographic changes, questioning whether quadriceps muscle weakness precedes the onset of osteoarthritis and progressively results in further damage or osteoarthritis itself reduces the quadriceps strength. Though patients may have greater joint destruction on knee radiographs, increasing the strength of quadriceps might reduce the pain and functional disability.

category: orthopedics


title: Does Robotic-Assisted Surgery improve outcomes of total hip arthroplasty compared to manual technique? A protocol for systematic review and meta-analysis

abstract:
BackgroundRobot-assisted total hip arthroplasty (THA) is an emerging technology that claims to position THA components with a very high degree of accuracy. It is unclear if this increase in accuracy leads to improved long-term functional outcomes of the patient.

ObjectivesThis systematic review aims to compare robot-assisted THA to those done using conventional manual techniques, in terms of both short-term radiographic outcomes, as well as long-term clinical outcomes.

MethodsThis systematic review will be conducted according to the PRISMA guidelines. A literature search will be conducted on the electronic databases of PubMed, Embase, Scopus, and Ovid with a pre-determined search strategy. A manual bibliography search of included studies will also be done. Original articles in English that directly compare robot-assisted THA to manual THA will be included. Data on outcomes will be extracted from included studies and analysis carried out with the help of appropriate software.


title: Data-driven Testing Program Improves Detection of COVID-19 Cases and Reduces Community Transmission

abstract: AO_SCPLOWBSTRACTC_SCPLOWCOVID-19 remains a global threat in the face of emerging SARS-CoV-2 variants and gaps in vaccine administration and availability, and organizations must be prepared to detect and mitigate its risk to their people and activities. In this report we share key lessons learned from an adaptive COVID-19 testing program implemented at a mid-sized university in the Midwest. The program utilized two simple, diverse, and easily interpretable machine learning models to quickly and accurately predict which students were at elevated risk for contracting COVID-19 and should be called proactively for testing. Our adaptive testing cohorts produced positivity rates that were 26% higher than the random cohort: 0.58% positivity (95% CI 0.47% to 0.68%) from 19,171 tests, and 0.46% positivity (95% CI 0.41% to 0.51%) from 64,003 tests, respectively. Within 14 days of their selection, 2.94% of the adaptive cohort tested positive, compared to 1.27% of the random cohort. Close contacts who were predicted by the adaptive testing models received a COVID-19 test within an average of 0.94 days (95% CI 0.78 to 1.11) of the source testing positive, while those who were manually contact traced were tested in an average of 1.92 days (95% CI 1.81 to 2.02). These results suggest that machine learning strategies can improve surveillance testing effectiveness, especially in a university setting, by effectively distributing testing resources and potentially reducing community transmission.

category: health informatics


title: Outbreak of SARS-CoV-2 in a prison: Low effectiveness of a single dose of the adenovirus vector ChAdOx1 vaccine in recently vaccinated inmates.

abstract:
IntroductionTo analyse the effectiveness of a dose of adenovirus vector ChAdOx1 vaccine (AVChOx1) in an outbreak of SARS-CoV-2 detected in a prison.

MethodsObservational study carried out at Brians-1 Prison, Barcelona. After detecting a case of infection, rt-PCR was administered to all prisoners (some of whom had been vaccinated 21-23 days previously with a dose of AVChOx1) and to staff. Infection rates in vaccinated and unvaccinated populations were calculated, as was vaccine effectiveness.

ResultsOne hundred and eighty-four asymptomatic prisoners (50.3% vaccinated) and 33 staff were screened. Forty-eight (25.9%) infections by the SCV-B.1.17 variant were recorded in prisoners and none in staff. Infection rates were higher in younger prisoners, immigrants, and those admitted [≥]7 days previously. In all, 22.6% of vaccinated subjects were infected vs. 29.3% of unvaccinated. Vaccine effectiveness was 23%. Only 6.2 cases would have been prevented by vaccinating the unvaccinated individuals. At seven days, the rt-PCR was negative in 46.2% of vaccinated subjects vs. 13.6% of unvaccinated (p = 0.02).

DiscussionIn a prison outbreak, a dose of AVChAdOx1 administered 21-23 days earlier did not significantly prevent the occurrence of infections, but did reduce the duration of rt-PCR positivity. Maintaining post-vaccination preventive measures is essential.


title: Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): a longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection

abstract:
BACKGROUNDReports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

METHODSINSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.

RESULTSParticipating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.

CONCLUSIONSThis study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.


title: Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria

abstract: There are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case-control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacterium Neisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1, UniProtKB - P00915, CAH1_HUMAN) and hemoglobin subunit beta (HBB, UniProtKB - P68871, HBB_HUMAN) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.

category: dentistry and oral medicine


title: Factors affecting aerosol size distribution during various dental procedures

abstract:
ObjectivesTo determine the impact of various aerosol mitigation interventions and establish duration of aerosol persistence in a variety of dental clinic configurations.

MethodsWe performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (e.g, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies [ventilation and high-volume evacuation (HVE)] and prevalence of particulate matter in the dental clinic environment before, during and after high-speed drilling, slow speed drilling and ultrasonic scaling procedures.

ResultsConical and ISOVAC(R) HVE were superior to standard tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics - regardless of configuration - when conical and ISOVAC(R) HVE were used.

ConclusionsDentists should consider using conical or ISOVAC(R) HVE rather than standard tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients as aerosols are rapidly dispersed.

Clinical SignificanceISOVAC(R) HVE is highly effective in reducing aerosol emissions, with adequate ventilation and HVE use, dental fallow time can be reduced to 5 minutes.


title: The 3p21.31 genetic locus promotes progression to type 1 diabetes through the CCR2/CCL2 pathway

abstract:
ObjectiveMultiple cross-sectional and longitudinal studies have shown that serum levels of the chemokine ligand 2 (CCL-2) are associated with type 1 diabetes (T1D), although the direction of effect differs. We assessed CCL-2 serum levels in a longitudinal cohort to clarify this association, combined with genetic data to elucidate the regulatory role of CCL-2 in T1D pathogenesis.

Research design and methodsThe Diabetes Autoimmunity Study in the Young (DAISY) followed 310 subjects with high risk of developing T1D. Of these, 42 became persistently seropositive for islet autoantibodies but did not develop T1D (non-progressors); 48 did develop T1D (progressors). CCL-2 serum levels among the three study groups were compared using linear mixed models adjusting for age, sex, HLA genotype, and family history of T1D. Summary statistics were obtained from the CCL-2 protein quantitative trait loci (pQTL) and CCR2 expression QTL (eQTL) studies. The T1D fine mapping association data were provided by the Type 1 Diabetes Genetics Consortium (T1DGC).

ResultsSerum CCL-2 levels were significantly lower in both progressors (p=0.004) and non-progressors (p=0.005), compared to controls. Two SNPs (rs1799988 and rs746492) in the 3p21.31 genetic locus, which includes the CCL-2 receptor, CCR2, were associated with increased CCR2 expression (p = 8.2e-5 and 5.2e-5, respectively), decreased CCL-2 serum level (p = 2.41e-9 and 6.21e-9, respectively), and increased risk of T1D (p = 7.9e-5 and 7.9e-5, respectively).

ConclusionsThe 3p21.31 genetic region is associated with developing T1D through regulatory control of the CCR2/CCL2 immune pathway.

category: endocrinology


title: CandyCodes: Simple universally unique edible identifiers for confirming the authenticity of pharmaceuticals

abstract: Counterfeit or substandard medicines adversely affect the health of millions of people and cost an estimated $200 billion USD annually. Their burden is greatest in developing countries, where the World Health Organization estimates that one in ten medical products are fake. In this work, I describe a simple addition to the existing drug manufacturing process that imparts an edible universally unique physical identifier to each pill, tablet, capsule, caplet, etc. This technique uses nonpareils (also called sprinkles and "hundreds and thousands"), tiny inexpensive multicolor candy spheres that are normally added to other candies or desserts as decorations. If nonpareils are applied at random to a pill immediately after manufacture, the specific pattern they form is unlikely to ever be repeated by random chance; this means that the pattern (or "CandyCode") can be used to uniquely identify the pill and distinguish it from all other pills. By taking a photograph of each CandyCoded pill after manufacture and recording the location and color of each nonpareil, a manufacturer can construct a database containing the CandyCodes of all known-authentic pills they produce. A consumer can then simply use a cellphone to photograph a pill and transfer its image to the manufacturers server, which determines whether the pills CandyCode matches a known-good CandyCode in their database (meaning that the pill is authentic) or does not have a match in the database (in which case the consumer is warned that the pill may be counterfeit and should not be consumed). To demonstrate the feasibility of using random particles as universal identifiers, I performed a series of experiments using both real CandyCodes (on commercially produced chocolate candies) and simulated CandyCodes (generated by software). I also developed a simple method for converting a CandyCode photo to a set of strings for convenient storage and retrieval in a database. Even after subjecting CandyCodes to rough handling to simulate shipping conditions, the CandyCodes were still easily verifiable using a cellphone camera. A manufacturer could produce at least 1017 CandyCoded pills--41 million for each person on Earth--and still be able to uniquely identify each CandyCode. By providing universally-unique IDs that are easy to manufacture but hard to counterfeit, require no alteration of the existing drug formation and minimal alteration of the manufacturing process, and need only a cameraphone for verification, CandyCodes could play an important role in the fight against fraud in pharmaceuticals and many other products.

category: pharmacology and therapeutics


title: Development of Goal Management Training+ (GMT+) for methamphetamine use disorder through collaborative design: A process description

abstract:
BackgroundMethamphetamine use disorder (MUD) is associated with executive dysfunctions, which are linked with poorer treatment outcomes including earlier drop out and relapse. However, current treatments for MUD do not address executive functions. Goal Management Training (GMT) is an evidence-based cognitive remediation program for executive dysfunction but required modifications to enhance its relevance and application within addiction treatment settings. This study aimed to 1) tailor GMT to the key cognitive deficits and typical treatment duration of MUD; 2) explore consumers (people with MUD) engagement with the revised program; 3) implement a protocol of the program with consumers; and 4) present the manualised standard administration to clinical service providers.

MethodsWe followed the Medical Research Council Complex Interventions Framework and employed an evidence- and person-based intervention development process. We used a four-phased approach and collaborated with neuropsychology experts, design researchers in healthcare, consumers with MUD, and clinical service providers. Each aim was addressed in a separate study phase; including content refinement and review with neuropsychology experts (phase 1), intervention design and collaboration with consumers (phase 2), prototype development and review with consumers (phase 3), and final program modifications and review with clinical stakeholders (phase 4).

ResultsFindings from phase 1 indicated support for targeting four cognitive processes (attention, impulse control, goal setting, and decision-making). Key feedback included the need to help habitualise program strategies and guide consumers in applying them in emotionally salient situations. Findings from phases 2 and 3 indicated consumer support for the program strategies and materials but highlighted the need to further enhance the personal relevance of specific content and journal activities. Findings from phase 4 provided overall clinical support for the revised program but indicated an opportunity to minimise unintended effects. We present the intervention materials for the revised program, Goal Management Training+ (GMT+), in line with TIDieR guidelines.

ConclusionsGMT+ targets tailored cognitive processes, includes reimagined materials and activities, and is sensitive to the clinical needs of people with MUD. Our intervention development process was important for informing the training components, design and intervention materials, and indicating initial acceptability prior to conducting a clinical trial.

category: psychiatry and clinical psychology


title: Multiple-time measurements of multidimensional psychiatric states from immediately before the COVID-19 pandemic to one year later: A longitudinal online survey of the Japanese population

abstract: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the mental health of both infected and uninfected people. Although most psychiatric disorders have highly overlapping genetic and pathogenic backgrounds, most studies investigating the impact of the pandemic have examined only single psychiatric disorders. It is necessary to examine longitudinal trajectories of factors that modulate psychiatric states across multiple dimensions. 2274 Japanese citizens participated in online surveys presented in December 2019 (before the pandemic), August 2020, Dec 2020, and April 2021. These surveys included nine questionnaires on psychiatric symptoms, such as depression and anxiety. Multi-dimensional psychiatric time series data were then decomposed into four principal components. We used generalized linear models to identify modulating factors for effects of the pandemic on these components. The four principal components can be interpreted as general psychiatric burden, social withdrawal, alcohol-related problems, and depression/anxiety. Principal components associated with general psychiatric burden and depression/anxiety peaked during the initial phase of the pandemic. They were further exacerbated by the economic burden of the pandemic. In contrast, principal components associated with social withdrawal showed a delayed peak, with human relationships as an important risk modulating factor. In addition, being elderly and female were risk factors shared across all components. Our results show that COVID-19 has imposed a large and varied burden on the Japanese population since the commencement of the pandemic. Although components related to the general psychiatric burden remained elevated, peak intensities differed between components related to depression/anxiety and those related to social anxiety. These results underline the importance of using flexible monitoring and mitigation strategies for mental problems, according to the phase of the pandemic.


title: Characterising COVID-19 empirical research production in Latin America and the Caribbean: a scoping review

abstract:
IntroductionThe Coronavirus Disease 2019 (COVID19) pandemic has struck Latin America and the Caribbean (LAC) particularly hard. One of the crucial areas in the international communitys response relates to accelerating research and knowledge sharing. The aim of this article is to map and characterise the existing empirical research related to COVID-19 in LAC countries and contribute to identify opportunities for strengthening future research.

MethodsIn this scoping review, articles published between December 2019 and 11 November 2020 were selected if they included an empirical component (explicit scientific methods to collect and analyse primary data), LAC population was researched, and the research was about the COVID-19 pandemic, regardless of publication status or language. MEDLINE, EMBASE, LILACS, Scielo, CENTRAL and Epistemonikos were searched. All titles and abstracts, and full texts were screened by two independent reviewers. Data from included studies was extracted by one reviewer and checked by a second independent reviewer.

Results14,406 records were found. After removing duplicates, 5,458 titles and abstracts were screened, of which 2,323 full texts were revised to finally include 1,626 empirical studies. The largest portion of research came from people/population of Brazil (54.6%), Mexico (19.1%), Colombia (11.2%), Argentina (10.4%), Peru (10.3%) and Chile (10%), while Caribbean countries concentrated 15.3%. The methodologies most used were cross-sectional studies (34.7%), simulation models (17.5%) and randomized controlled trials (RCTs) (13.6%). Using a modified version of WHOs COVID-19 Coordinated Global Research Roadmap classification, 54.2% were epidemiological studies, followed by clinical management (22.3%) and candidate therapeutics (12.2%). Government and public funds support were reported in 19.2% of studies, followed by universities or research centres (9%), but 47.5% did not include any funding statement.

ConclusionDuring the first part of the COVID-19 pandemic, LAC countries have contributed to the global research effort primarily with epidemiological studies, with little participation on vaccines research, meaning that this type of knowledge would be imported from elsewhere. Research agendas could be further coordinated aiming to enhance shared self-sufficiency regarding knowledge needs in the region.


title: SCU-Net: A deep learning method for segmentation and quantification of breast arterial calcifications on mammograms

abstract:
PurposeMeasurements of breast arterial calcifications (BAC) can offer a personalized, noninvasive approach to risk-stratify women for cardiovascular disease such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications.

MethodsTo separate BAC in mammograms, we propose a light-weight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patch-wise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: Sum of Mask Probability Metric ([P][M]), Sum of Mask Area Metric ([A][M]), Sum of Mask Intensity Metric ([S][I][M]), Sum of Mask Area with Threshold Intensity Metric ([T][A][M]X) and Sum of Mask Intensity with Threshold X Metric ([T] [S][I][M]X). Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared to calcified voxels and calcium mass on breast CT for 10 subjects.

ResultsOur segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1-score/Dice Score and Jaccard Index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcifications quantification measurement, our calcification volume (voxels) results yield R2-correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the [P][M], [A][M], [S][I][M], [T][A][M]100, [T] [S][I][M]100 metrics, respectively; our calcium mass results yield comparable R2-correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics.

ConclusionsSCU-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.

category: radiology and imaging


title: Finding effective therapeutic approaches for motor rehabilitation after stroke: Insights from a thematic analysis

abstract: Despite tremendous advances in the treatment and management of stroke, restoring motor and functional outcomes after stroke continues to be a major clinical challenge. Given the wide range of approaches used in motor rehabilitation, several commentaries have highlighted the lack of a clear scientific premise for different interventions as one critical factor that has led to suboptimal study outcomes. To examine this issue in greater detail, we conducted a thematic analysis of randomized controlled trials in stroke rehabilitation over a 2-year period from 2019-2020. Our results revealed three primary findings: (i) most studies did not provide an explicit rationale for why the treatment would be expected to work, (ii) there was not a close correspondence between the active ingredients mentioned versus the active ingredients measured in the study, and (iii) multimodal approaches that involved more than one therapeutic approach tended to be combined in an ad-hoc fashion, indicating the lack of a targeted approach. These results highlight the need for strengthening cross-disciplinary connections between basic science and clinical studies, and the need for structured development and testing of therapeutic approaches to find more effective treatment interventions.

category: rehabilitation medicine and physical therapy


title: Easy-BILAG: a new tool for simplified recording of SLE disease activity using BILAG-2004 index.

abstract:
ObjectiveBILAG-2004 index is a comprehensive disease activity instrument for SLE but administrative burden and frequency of errors limits its use in routine practice. We aimed to develop a tool for more accurate, time-efficient scoring of BILAG-2004 index with full fidelity to the existing instrument.

MethodsFrequency of BILAG-2004 items was collated from a BILAG-biologics registry (BILAG-BR) dataset. Easy-BILAG prototypes were drafted to address known issues affecting speed and accuracy. After expert-verification, accuracy and usability of the finalised Easy-BILAG was validated against standard format BILAG-2004 index in a workbook exercise of 10 case vignettes. 33 professionals with a range of expertise from 14 UK centres completed the validation exercise.

ResultsEasy-BILAG incorporates all items present in [≥]5% BILAG-BR records, plus full constitutional and renal domains into a rapid single-page assessment. An embedded glossary and colour-coding assists scoring each domain. A second page captures rarer manifestations when needed. In the validation exercise, Easy-BILAG yielded higher median scoring accuracy (96.7%) than standard BILAG-2004 documentation (87.8%, p=0.001), with better inter-rater agreement. Easy-BILAG was completed faster (59.5min) than the standard format (80.0min, p=0.04) for 10 cases. An advantage in accuracy was observed with Easy-BILAG use among general hospital rheumatologists (91.3 vs 75.0, p=0.02), leading to equivalent accuracy as tertiary centre rheumatologists. Clinicians rated Easy-BILAG as intuitive, convenient, and well adapted for routine practice.

ConclusionEasy-BILAG facilitates more rapid and accurate scoring of BILAG-2004 across all clinical settings which could improve patient care and biologics prescribing. Easy-BILAG should be adopted wherever BILAG-2004 assessment is required.

category: rheumatology


title: Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases

abstract:
ObjectiveTo describe the characteristics of COVID-19 vaccine breakthrough infections among systemic autoimmune rheumatic disease (SARD) patients.

MethodsWe identified SARDs patients in a large healthcare system with COVID-19 vaccination [≥]14 days prior to a positive SARS-CoV-2 molecular test. Details of the patients SARD, vaccination status, and COVID-19 infection were extracted.

ResultsOf 340 confirmed COVID-19 infections among SARDs patients between December 11th, 2020 (date of first COVID-19 vaccine approval in the US) and July 30th, 2021, we identified 16 breakthrough infections. Seven (44%) received the Pfizer-BioNtech vaccine, five (31%) received the Moderna vaccine, and four (25%) received the Janssen/Johnson & Johnson vaccine. The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myopathy (3, 19%), and systemic lupus erythematosus (3, 19%). Rituximab (5, 31%), glucocorticoids (4, 25%), and mycophenolate mofetil (4, 25%) were the most frequent treatments. Among the breakthrough infections, 15 (93%) were symptomatic, six (38%) were hospitalized, one (6%) required mechanical ventilation, and two (13%) died.

ConclusionsSymptomatic, including severe, breakthrough infections were observed in SARDs patients; many were on treatments associated with attenuated antibody responses to vaccination. Further studies are needed to determine the rate of breakthrough infection associated with SARD treatments and other features.

Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSBreakthrough infections following COVID-19 vaccination are expected but some patients with systemic autoimmune rheumatic diseases (SARDs) may be at higher risk because of blunted antibody responses to vaccination associated with rheumatic disease treatments and other factors that remain poorly understood.

What does this study add?We identify and describe 16 COVID-19 vaccine breakthrough infections within the Mass General Brigham system between December 11th, 2020 and June 26th, 2021. The vast majority of cases were symptomatic and two were fatal.

How might this impact on clinical practice or future developments?This study complements observations regarding the attenuated antibody response to COVID-19 vaccination in patients with SARDs by identifying serious clinical outcomes from breakthrough infections in patients receiving DMARDs that have been reported to have blunted vaccine responses. Our study identifies characteristics of COVID-19 breakthrough infections that may guide the prioritization of booster vaccines and other risk-mitigating strategies in patients with SARDs.