title: Antibiotic resistance profile of E. coli isolates in 17 municipal wastewater utilities across Oregon

abstract: Wastewater treatment utilities are considered one of the main sources and reservoirs of antimicrobial resistance. The objective of this study was to determine the diversity and prevalence of antibiotic-resistant Escherichia coli in wastewater treatment systems across the state of Oregon. Influent, secondary effluent, final effluent, and biosolids were collected from 17 wastewater treatment utilities across Oregon during the winter and summer seasons of 2019 and 2020 (n = 246). E. coli strains were recovered from samples by culturing on mTEC, followed by confirmation with MacConkey with MUG agar plates. Antibiotic susceptibility of 1143 E. coli isolates against 8 antibiotics were determined, and resistance profiles and indices were analyzed between utilities, seasons, and flows. Antibiotic resistance phenotypes were detected in 31.6% of the collected E. coli isolates. Among those antibiotic-resistant E. coli isolates, multi-drug resistance (i.e., resistance to three or more classes of antibiotics) was harbored by 27.7% with some strains showing resistance to up to six classes of antibiotics. The most prevalent resistance was to ampicillin (n = 207) and the most common combinations of multi-drug resistance included simultaneous resistances to ampicillin, streptomycin, and tetracycline (n = 49), followed by ampicillin, streptomycin, and sulfamethoxazole/trimethoprim (n = 46). Significant correlations were observed between resistance to sulfamethoxazole/trimethoprim and resistances to ampicillin, ciprofloxacin, and tetracycline (p < 0.001). A small percentage (1.1%) of the E. coli isolates displayed extended-spectrum beta lactamase (ESBL) activity and a single isolate carried resistance to imipenem. Compared to wastewater influent, ciprofloxacin resistance was significantly more prevalent in biosolids (p <0.05) and tetracycline resistance was significantly lower in effluent (p <0.05). Seasonal impact on antibiotic-resistant E. coli in wastewater influent was observed through significantly higher multiple antibiotic resistance (MAR) index, ampicillin resistance prevalence, and ciprofloxacin resistance prevalence in summer compared to winter (p < 0.05). This state-wide study confirms the widespread distribution of antibiotic-resistant, multi-drug resistant, and extended-spectrum beta lactamase-producing E. coli in wastewater systems across different flows and seasonal variations, making them the recipients, reservoirs, and sources of antimicrobial resistance.


title: A neonatal ward strengthening program improves survival for neonates treated with CPAP at district hospitals in Malawi

abstract:
IntroductionFrom 2013-2015, a CPAP quality improvement program (QIP) was implemented to introduce and monitor CPAP usage and outcomes in the neonatal wards at all government district and central hospitals in Malawi. In 2016 the CPAP QIP was extended into healthcare facilities operated by the Christian Health Association of Malawi. Although clinical outcomes improved, ward assessments indicated that many rural sites lacked other essential equipment and a suitable space to adequately treat sick neonates, which likely limited the impact of improved respiratory care. The aim of this study was to determine if a ward strengthening program improved outcomes for neonates treated with CPAP.

MethodsTo address the needs identified from ward assessments, a ward strengthening program was implemented from 2017-2018 at rural hospitals in Malawi to improve the care of sick neonates. The ward strengthening program included the distribution of a bundle of equipment, supplemental training, and, in some cases, health facility renovations. Survival to discharge was compared for neonates treated with CPAP at 12 rural hospitals for one year before and for one year immediately after implementation of the ward strengthening program.

ResultsIn the year prior to ward strengthening, 189 neonates were treated with CPAP; in the year after, 232 neonates received CPAP. The overall rate of survival for those treated with CPAP improved from 46.6% to 57.3% after ward strengthening (p=0.03). For the subset of neonates with admission weights between 1.00 - 2.49 kg diagnosed with respiratory distress syndrome, survival increased from 39.4% to 60.3% after ward strengthening (p=0.001).

ConclusionA ward strengthening program including the distribution of a bundle of equipment, supplemental training, and some health facility renovations, further improved survival among neonates treated with CPAP at district-level hospitals in Malawi.

category: public and global health


title: Sexual Behaviours and Sexual Health Among Middle-Aged and Older Adults in Britain: A Latent Class Analysis of The Natsal-3

abstract:
ObjectivesPopulation-representative studies of the sexual health of middle-aged and older adults are lacking in aging societies. This study aimed to identify latent patterns of sexual behaviours and health of people aged 45-74.

MethodsWe conducted a latent class analysis of the National Attitudes and Sexual Lifestyles Survey (Natsal-3), a nationally representative survey conducted in Britain in 2011.

ResultsOf the 5260 respondents aged 45-74, 49% of men and 45% of women belonged to the Content Caseys class who reported good sexual health. The Infrequent Indigos (31% of men, 44% of women) were characterized by a lack of sexual activity, reported some dissatisfaction, and were more likely to have a disability. The Low-Functioning Lees (12% of men, 8% of women) reported some more disability and had issues with sexual functioning and higher levels of distress. The Multiple-Partnered Morgans (9% of men, 2% of women) were characterized by a greater number of sexual partners and several risk behaviours.

ConclusionsThe use of these four classes can aid in improved targeting of tailored sexual health services to improve sexual function, sexual satisfaction, reduce distress and risky behaviours among middle-aged and older adults. These services should be inclusive of the disabled community.

Bullet pointsO_LIAbout half of these respondents were classified as Content Caseys who reported few issues concerning their sex lives.
C_LIO_LIOver a third who reported no recent sexual activity, the vast majority of whom are single, were classified as Infrequent Indigos.
C_LIO_LINearly 10% were classified Low-Functioning Lees due to the greater probability of reporting sexual function issues and distress.
C_LIO_LIThe rest were classified as Multiple Partner Morgans as a result of a high likelihood of having multiple partners and unsafe sex.
C_LI

category: sexual and reproductive health


title: Gut-bladder axis syndrome associated with recurrent UTIs in humans

abstract: Recurrent urinary tract infections (rUTIs) are a major health burden worldwide, with history of infection being a significant risk factor. While the gut is a known reservoir for uropathogenic bacteria, the role of the microbiota in rUTI remains unclear. We conducted a year-long study of women with and without history of rUTIs, from whom we collected urine, blood and monthly fecal samples for multi-omic interrogation. The rUTI gut microbiome was significantly depleted in microbial richness and butyrate-producing bacteria compared to controls, reminiscent of other inflammatory conditions, though Escherichia coli gut and bladder dynamics were comparable between cohorts. Blood samples revealed signals of differential systemic immunity, leading us to hypothesize that rUTI susceptibility is in part mediated through a syndrome involving the gut-bladder axis, comprising gut dysbiosis and differential immune response to bacterial bladder colonization, manifesting in symptoms. This work highlights the potential for microbiome therapeutics to prevent and treat rUTIs.

category: urology


title: Automated Detection of Cerebral Microbleeds on MR images using Knowledge Distillation Framework

abstract: Cerebral microbleeds (CMBs) are associated with white matter damage, various neu-rodegenerative and cerebrovascular diseases. CMBs occur as small, circular hypointense lesions on T2*-weighted gradient recalled echo (GRE) and susceptibility weighted imaging (SWI) images, and hyperintense on quantitative susceptibility mapping (QSM) images due to their paramagnetic nature. Accurate detection of CMBs would help to determine the CMB lesion count and distribution, which would be further useful to understand the clinical impact of CMBs and to obtain quantitative imaging biomarkers. In this work, we propose a fully automated, deep learning-based, 2-step algorithm, using structural and anatomical properties of CMBs from any single input image modality (e.g. GRE / SWI / QSM) for their accurate detection. Our method consists of an initial candidate detection step, that detects CMBs with high sensitivity and a candidate discrimination step using a knowledge distillation framework to classify CMB and non-CMB instances, followed by a morphological clean-up step. We used 4 datasets consisting of different modalities specified above, acquired using various protocols and with a variety of pathological and demographic characteristics. On cross-validation within datasets, our method achieved a cluster-wise true positive rate (TPR) over 90% with an average of less than 2 false positives per subject. Our method is flexible in terms of the input modality and provides comparable cluster-wise TPR and a better cluster-wise precision compared to existing state-of-the-art methods. When evaluated across different datasets, our method showed good generalisability with a cluster-wise TPR greater than 80% with different modalities.

category: neurology


title: Developing a taxonomy of care coordination for people living with rare conditions: A qualitative study

abstract:
BackgroundImproving care coordination is particularly important for individuals with rare conditions (who may experience multiple inputs into their care, across different providers and settings). To develop and evaluate strategies to potentially improve care coordination, it is necessary to develop a method for organising different ways of coordinating care for rare conditions. Developing a taxonomy would help to describe different ways of coordinating care and in turn facilitate development and evaluation of pre-existing and new models of care coordination for rare conditions. To the authors knowledge, no studies have previously developed taxonomies of care coordination for rare conditions. This research aimed to develop and refine a care coordination taxonomy for people with rare conditions.

MethodsThis study had a qualitative design and was conducted in the United Kingdom. To develop a taxonomy, six stages of taxonomy development were followed. We conducted interviews (n=30 health care professionals/charity representatives/commissioners) and focus groups (n=4 focus groups, 22 patients/carers with rare/ultra-rare/undiagnosed conditions). Interviews and focus groups were audio-recorded with consent, and professionally transcribed. Findings were analysed using thematic analysis. Themes were used to develop a taxonomy, and to identify which types of coordination may work best in which situations. To refine the taxonomy, we conducted two workshops (n=12 patients and carers group; n=15 professional stakeholder group).

ResultsOur taxonomy has six domains, each with different options. The six domains are: 1) Ways of organising care (local, hybrid, national), 2) Ways of organising professionals involved in care (collaboration between many or all professionals, collaboration between some professionals, a lack of collaborative approach), 3) Responsibility for coordination (administrative support, formal roles and responsibilities, supportive roles and no responsibility), 4) How often appointments and coordination take place (regular, on demand, hybrid), 5) Access to records (full or filtered access), and 6) Mode of care coordination (face-to-face, digital, telephone).

ConclusionsFindings indicate that there are different ways of coordinating care across the six domains outlined in our taxonomy. This may help to facilitate the development and evaluation of existing and new models of care coordination for people living with rare conditions.

category: health systems and quality improvement


title: The hospital burden of intergenerational contact with the welfare system: A whole-of-population liked data study

abstract:
BackgroundIntergenerational welfare contact (IWC) is a policy issue because of the personal and social costs of intergenerational disadvantage. We estimated the hospital burden of IWC for children aged 11-20 years.

MethodsThis linked data study of children born in South Australia, 1991-1995 (n=94,358), and their parent/s (n=143,814) used de-identified data from the Better Evidence Better Outcomes Linked Data platform. Using Australian Government Centrelink data, welfare contact (WC) was defined as parent/s receiving a means-tested welfare payment (low-income, unemployment, disability or caring) when children were aged 11-15, or children receiving payment at ages 16-20. IWC was WC occurring in both parent and child generations. Children were classified as: No WC, parent only WC, child only WC, or IWC. Hospitalisation rates and cumulative incidence were estimated by age and WC group.

FindingsIWC affected 34.9% of children, who had the highest hospitalisation rate (133.5 per 1,000 person-years) compared to no WC (46.1 per 1,000 person-years), parent only WC (75.0 per 1,000 person-years), and child only WC (87.6 per 1,000 person-years). Of all IWC children, 43.0% experienced at least one hospitalisation between 11-20, frequently related to injury, mental health, and pregnancy.

InterpretationChildren experiencing IWC represent a third of the population aged 11-20. Compared to children with parent-only WC, IWC children had 78% higher hospitalisation rates from age 11 to 20, accounting for over half of all hospitalisations in this age group. Frequent IWC hospitalisation causes were injuries, mental health, and pregnancy.

FundingMedical Research Future Fund, National Health and Medical Research Council, Westpac Scholars Trust.

category: epidemiology


title: Global Prevalence of Post-Acute Sequelae of COVID-19 (PASC) or Long COVID: A Meta-Analysis and Systematic Review

abstract:
ImportanceAs SARS-CoV-2 pervades worldwide, considerable focus has been placed on the longer lasting health effects of the virus on the human host and on the anticipated healthcare needs.

ObjectiveThe primary aim of this study is to examine the prevalence of post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, across the world and to assess geographic heterogeneities through a systematic review and meta-analysis. A second aim is to provide prevalence estimates for individual symptoms that have been commonly reported as PASC, based on the existing literature.

Data SourcesPubMed, Embase, and iSearch for preprints from medRxiv, bioRxiv, SSRN, and others, were searched on July 5, 2021 with verification extending to August 12, 2021.

Study SelectionStudies written in English that consider PASC (indexed as ailments persisting at least 28 days after diagnosis or recovery for SARS-CoV-2 infection) and that examine corresponding prevalence, risk factors, duration, or associated symptoms were included. A total of 40 studies were included with 9 from North America, 1 from South America, 17 from Europe, 11 from Asia, and 2 from other regions.

Data Extraction and SynthesisData extraction was performed and separately cross-validated on the following data elements: title, journal, authors, date of publication, outcomes, and characteristics related to the study sample and study design. Using a random effects framework for meta-analysis with DerSimonian-Laird pooled inverse-variance weighted estimator, we provide an interval estimate of PASC prevalence, globally, and across regions. This meta-analysis considers variation in PASC prevalence by hospitalization status during the acute phase of infection, duration of symptoms, and specific symptom categories.

Main Outcomes and MeasuresPrevalence of PASC worldwide and stratified by regions.

ResultsGlobal estimated pooled PASC prevalence derived from the estimates presented in 29 studies was 0.43 (95% confidence interval [CI]: 0.35, 0.63), with a higher pooled PASC prevalence estimate of 0.57 (95% CI: 0.45, 0.68), among those hospitalized during the acute phase of infection. Females were estimated to have higher pooled PASC prevalence than males (0.49 [95% CI: 0.35, 0.63] versus 0.37 [95% CI: 0.24, 0.51], respectively). Regional pooled PASC prevalence estimates in descending order were 0.49 (95% CI: 0.21, 0.42) for Asia, 0.44 (95% CI: 0.30, 0.59) for Europe, and 0.30 (95% CI: 0.32, 0.66) for North America. Global pooled PASC prevalence for 30, 60, 90, and 120 days after index test positive date were estimated to be 0.36 (95% CI: 0.25, 0.48), 0.24 (95% CI: 0.13, 0.39), 0.29 (95% CI: 0.12, 0.57) and 0.51 (95% CI: 0.42, 0.59), respectively. Among commonly reported PASC symptoms, fatigue and dyspnea were reported most frequently, with a prevalence of 0.23 (95% CI: 0.13, 0.38) and 0.13 (95% CI: 0.09, 0.19), respectively.

Conclusions and RelevanceThe findings of this meta-analysis suggest that, worldwide, PASC comprises a significant fraction (0.43 [95% CI: 0.35, 0.63]) of COVID-19 tested positive cases and more than half of hospitalized COVID-19 cases, based on available literature as of August 12, 2021. Geographic differences appear to exist, as lowest to highest PASC prevalence is observed for North America (0.30 [95% CI: 0.32, 0.66]) to Asia (0.49 [95% CI: 0.21, 0.42]). The case-mix across studies, in terms of COVID-19 severity during the acute phase of infection and variation in the clinical definition of PASC, may explain some of these differences. Nonetheless, the health effects of COVID-19 appear to be prolonged and can exert marked stress on the healthcare system, with 237M reported COVID-19 cases worldwide as of October 12, 2021.

Key Points

QuestionAmong those infected with COVID-19, what is the global and regional prevalence of post-acute sequelae COVID-19 (PASC)?

FindingsGlobally, the pooled PASC prevalence estimate was 0.43, whereas the pooled PASC prevalence estimate for patients who had to be hospitalized due to COVID-19 was 0.57. Regionally, estimated pooled PASC prevalence from largest to smallest effect size were 0.49 for Asia, 0.44 for Europe, and 0.30 for North America. Global pooled PASC prevalence for 30, 60, 90, and 120 days after index date were estimated to be 0.36, 0.24, 0.29, and 0.51, respectively. Among commonly reported PASC symptoms, fatigue and dyspnea were reported most frequently, with a prevalence of 0.23 and 0.13.

MeaningIn follow-up studies of patients with COVID-19 infections, PASC was common both globally and across geographic regions, with studies from Asia reporting the highest prevalence.


title: Investigating the source of increased bipolar and major depressive disorder polygenic risk in multiplex schizophrenia families

abstract: Psychotic and affective disorders often aggregate in the relatives of probands with schizophrenia (SCZ), and genetic studies show substantial genetic correlation among SCZ, bipolar disorder (BIP) and major depressive disorder (MDD). However, the nature of this genetic overlap in polygenic risk score (PRS) analyses of multiplex families has not been fully dissected. In the current study, we investigated the polygenic risk burden of BIP and MDD in a sample of 257 multiplex SCZ families (N=1,005) and population controls (N=2,205). Furthermore, due to the strong genetic correlation among SCZ, BIP, and MDD, we examined whether increased BIP or MDD PRS in members of multiplex SCZ families can be attributed to latent genetic factors unique to BIP or MDD, or latent genetic factors that each of these two disorders share with SCZ. Our results indicate that members of multiplex SCZ families have an increased PRS for BIP and MDD, however, this observation is largely attributable to latent genetic factors that BIP or MDD share with SCZ, rather than latent genetic factors unique to them. These results provide new insight for cross-disorder PRS analyses of psychiatric disorders, by cautioning that for complete interpretation of observed cross-disorder PRS enrichment, we should account for genetic correlations across psychiatric disorders. Our findings further indicates that members of multiplex SCZ families may have an increased genetic vulnerability to both psychotic and affective disorders, and for full assessment of an individuals genetic risk, familial backgrounds should be taken into consideration.

category: psychiatry and clinical psychology


title: Resistome characterization of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolated from wastewater treatment utilities in Oregon

abstract: Infections resistant to broad spectrum antibiotics due to the emergence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is of global concern. This study characterizes the resistome (i.e., entire ecology of resistance determinants) of 11 ESBL-producing Escherichia coli isolates collected from eight wastewater treatment utilities across Oregon. Whole genome sequencing was performed to identify the most abundant antibiotic resistance genes including ESBL-associated genes, virulence factors, as well as their sequence types. Moreover, the phenotypes of antibiotic resistance were characterized. ESBL-associated genes (i.e., blaCMY, blaCTX, blaSHV, blaTEM) were found in all but one of the isolates with five isolates carrying two of these genes (4 with blaCTX and blaTEM; 1 with blaCMY and blaTEM). The ampC gene and virulence factors were present in all the E. coli isolates. Across all the isolates, 31 different antibiotic resistance genes were identified. Additionally, all E. coli isolates harbored phenotypic resistance to beta-lactams (penicillins and cephalosporins), while eight of the 11 isolates carried multi-drug resistance phenotypes (resistance to three or more classes of antibiotics). Findings highlight the risks associated with the presence of ESBL-producing E. coli isolates in wastewater systems that have the potential to enter the environment and may pose direct or indirect risks to human health.


title: Seasonal variation in blood pressure recorded in routine primary care

abstract:
ObjectiveSeasonal variations in blood pressure (BP) exist. There is limited information about important clinical factors associated with increased BP and the strength and amplitude of seasonal variation in primary care.

MethodsThis was a repeated cross-sectional observational study of routinely measured BPs in primary care using data from electronic medical records in the greater Toronto region, from January 2009 to June 2019. We used time-series models and mean monthly systolic BPs (SBPs) and diastolic BPs (DBPs) to estimate the strength and amplitude of seasonal oscillations, as well as their associations with patient characteristics.

Results314,518 patients were included. Mean SBPs and DBPs were higher in winter than summer. There was strong or perfect seasonality for all characteristics studied, except for BMI less than 18.5 (underweight). Overall, the mean maximal amplitude of the oscillation was 1.51mmHg for SPB (95% CI 1.30mmHg to 1.72mmHg) and 0.59mmHg for DBP (95% CI 0.44mmHg to 0.74mmHg). Patients aged 81 years or older had larger SBP oscillations than younger patients aged 18 to 30 years; the difference was 1.20mmHg (95% CI 1.15mmHg to 1.66mmHg). Hypertension was also associated with greater oscillations, difference 0.53mmHg (95% CI 0.18mmHg to 0.88mmHg). There were no significant differences in SBP oscillations by other patient characteristics, and none for DBP.

ConclusionStrong seasonality was detected for almost all patient subgroups studied and was greatest for older patients and for those with hypertension. The variation in BP between summer and winter should be considered by clinicians when making BP treatment decisions.

category: primary care research


title: Memory perfectionism is associated with persistent memory complaints after concussion

abstract:
ObjectiveThe etiology of persistent memory complaints after concussion is poorly understood. Memory perfectionism (highly valuing memory ability and intolerance of minor memory lapses) may help explain why some people report persistent subjective memory problems in the absence of corresponding objective memory impairment. The present study investigated the relationship between memory perfectionism and persistent memory complaints after concussion.

MethodsAdults (N=77; 61% women) with persistent symptoms following concussion were recruited from outpatient specialty clinics. Participants completed the National Institutes of Health Toolbox Cognition Battery, Test of Memory Malingering-Trial 1, and questionnaires measuring memory perfectionism (Memory in Adulthood-Achievement subscale), forgetfulness and other post-concussion symptoms (Rivermead Postconcussion Symptoms Questionnaire; RPQ), and depression (Patient Health Questionnaire-2) at M=17.8 weeks post-injury. Patients with vs. without severe memory complaints (based on the RPQ) were compared.

ResultsMemory perfectionism was associated with severe memory complaint, after controlling for objective memory ability, overall cognitive ability, and depression (95% confidence interval for odds ratio = 1.11 to 1.40). Sensitivity analyses showed that this relationship did not depend on use of specific objective memory tests nor on inclusion of participants who failed performance validity testing. In a control comparison to test the specificity of identified relationships, memory perfectionism was not associated with severe fatigue (95% confidence interval for odds ratio = 0.91 to 1.07).

DiscussionMemory perfectionism may predispose people to experience persistent memory symptoms and/or contribute to their perpetuation after concussion, with potential relevance to the spectrum of functional cognitive disorders more broadly.


title: Details of "conversion therapy" practices and concordance with legislative definition: Findings from a non-probability community-based survey in Canada, 2020

abstract:
Background"Conversion therapy" practices (CTP) refer to a heterogeneous set of treatments and activities that share the common goal of suppressing, "repairing," or otherwise preventing expressions of transgender, lesbian, gay, bisexual, or queer identities. This study aimed to elicit details from those with direct experience and assess concordance between CTP experiences and the definition of CTP included in federal legislation aiming to deter CTP.

MethodsWe conducted an anonymous online survey of adults (>18 years) in Canada between August 18 and December 2, 2020. Participants were recruited through social media, CTP survivor networks, and word-of-mouth.

ResultsOf 51 respondents with direct experience of CTP, 16 were transgender, 34 were cisgender. Most respondents lived in Alberta, British Columbia, Ontario, or Quebec. 49% experienced CTP in a licensed healthcare provider office, 45% at a faith-based organization, and 36% at an unlicensed counselor office (categories not mutually exclusive). Age at first CTP experience ranged from 2 to 44 years of age (mean: 17.8 years; median: 17 years). Respondents experienced CTP for <1 year to 33 years (mean: 4.6 years; median: 2 years). Fifty percent of those with direct experience of CTP indicated that the proposed legislative definition of CTP did not fully encompass their personal experience.

InterpretationResults from this Canadian survey of adults with experience of CTP indicate that legislative attempts to ban CTP must be expanded (e.g., to include adults and practices that do not concord with previously drafted definitions) and paired with other prevention efforts.


title: Continued Effectiveness of COVID-19 Vaccination among Urban Healthcare Workers during Delta Variant Predominance

abstract:
BackgroundData on COVID-19 vaccine effectiveness (VE) among healthcare workers (HCWs) during periods of delta variant predominance are limited.

MethodsWe followed a population of urban Massachusetts HCWs (45% non-White) subject to epidemiologic surveillance. We accounted for covariates such as demographics and community background infection incidence, as well as information bias regarding COVID-19 diagnosis and vaccination status.

Results and DiscussionDuring the study period (December 16, 2020 to September 30, 2021), 4615 HCWs contributed to a total of 1,152,486 person-days at risk (excluding 309 HCWs with prior infection) and had a COVID-19 incidence rate of 5.2/10,000 (114 infections out of 219,842 person-days) for unvaccinated person-days and 0.6/10,000 (49 infections out of 830,084 person-days) for fully vaccinated person-days, resulting in an adjusted VE of 82.3% (95% CI: 75.1-87.4%). For the secondary analysis limited to the period of delta variant predominance in Massachusetts (i.e., July 1 to September 30, 2021), we observed an adjusted VE of 76.5% (95% CI: 40.9-90.6%). Independently, we found no re-infection among those with prior COVID-19, contributing to 74,557 re-infection-free person-days, adding to the evidence base for the robustness of naturally acquired immunity.


title: LightOCT: Exploring the depth for Retinal disease detection

abstract: With the advancement in technology and computation capabilities, identifying retinal damage through state-of-the-art CNNs architectures has led to the speedy and precise diagnosis, thus inhibiting further disease development. In this study, we focus on the classification of retinal damage caused by detecting choroidal neovascularization (CNV), diabetic macular edema (DME), DRUSEN, and NORMAL in optical coherence tomography (OCT) images. The emphasis of our experiment is to investigate the component of depth in the neural network architecture. We introduce a shallow convolution neural network - LightOCT, outperforming the other deep model configurations, with the lowest value of LVCEL and highest accuracy (+98% in each class). Next, we experimented to find the best fit optimizer for LightOCT. The results proved that the combination of LightOCT and Adam gave the most optimal results. Finally, we compare our approach with transfer learning models, and LightOCT outperforms the state-of-the-art models in terms of computational cost, least training time and gives comparable results in the criteria of accuracy. We would direct our future work to improve the accuracy metrics with shallow models such that the trade-off between training time and accuracy is reduced.

category: ophthalmology


title: On The Dynamics of Interstate Diffusion of Firearm Violence and Impact of Firearm Regulations

abstract:
ObjectivesOur purpose was to test the impact of firearm regulations on the firearm violence flow across US state borders. Further we assessed the spatial variations in these impacts across different regions with the goal of identifying state-groups that are especially vulnerable to cross-border firearm violence.

MethodsIncidence of firearm violence (2000-2017) has been modelled as an inhomogeneous diffusion process whose parameters depend on state firearm regulations. Firearm regulations measurement for a state accounted for all 14 law categories across 54 states since 1991 as per State Firearm Law Database. The effects of regulations and other covariates were estimated across all states.

ResultsSix clusters of states were identified based on the variations of effects within and across those clusters. For 3 of these clusters the diffusive flow parameters were statistically significant. In all of these clusters the deterring effect of regulations on incidence and flow of crime was statistically significant.

ConclusionThe clusters can be assigned to 5 descriptive categories based on their roles in the flow of firearm violence - Source states, Transitive states, Destination states, Isolated issue states and Stable. It was found that flow of firearm violence indeed does follow a diffusive process for most categories of states. It has also been recommended that while in-state regulations are important to curb firearm violence flowing into Destination states, they are not adequate unless regulatory stringency is also applied to neighboring Source and Transitive States.

category: health policy


title: From online data collection to identification of disease mechanisms: The IL-1beta, IL-6 and TNF-alpha; cytokine triad is associated with post-acute sequelae of COVID-19 in a digital research cohort

abstract: Post-acute sequelae of COVID-19 (PASC) emerge as a global problem with unknown molecular drivers. In a digital epidemiology approach, we rapidly recruited 8,077 individuals out of 129,733 households in Halle (Saale) to the cohort study for digital health research in Germany (DigiHero). These responded to a basic questionnaire followed by a PASC-focused survey and blood sampling in case of prior positive SARS-CoV-2 testing in their household. The presented analysis is based on the first 318 DigiHero participants, the majority thereof after mild infections. PASC were reported in 67.8% of cases, consisted predominantly in fatigue, dyspnea and concentration deficit, persisted in 60% over the follow-up period of on average eight months and their resolution was unaffected by post-infection vaccination. PASC was not associated with post-COVID-19 autoantibodies, but with elevated levels of IL-1{beta}, IL-6 and TNF-. Blood profiling and single-cell data from validation cohorts with early infection suggested the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop. Our data indicate a long-lasting cytokine triad -potentially underlying PASC symptoms - to be driven by macrophage primed during infection. We demonstrate how the combination of digital epidemiology with selective biobanking can rapidly generate hints towards disease mechanisms.

category: infectious diseases


title: COVID-19 vaccination, risk-compensatory behaviours, and social contacts in four countries in the UK

abstract: The physiological effects of vaccination against SARS-CoV-2 (COVID-19) are well documented, yet the behavioural effects are largely unknown. Risk compensation suggests that gains in personal safety, as a result of vaccination, are offset by increases in risky behaviour, such as socialising, commuting and working outside the home. This is potentially problematic because transmission of SARS-CoV-2 is driven by contacts, which could be amplified by vaccine-related risk compensation behaviours. Here, we show that behaviours were overall unrelated to personal vaccination, but - adjusting for variation in mitigation policies - were responsive to the level of vaccination in the wider population: individuals in the UK were risk compensating when rates of vaccination were rising. This effect was observed across four nations of the UK, each of which varied policies autonomously.


title: Assessment of breakthrough infections among post-vaccinated healthcare workers in a Tertiary Dental Hospital in New Delhi, India

abstract:
BackgroundCOVID-19 vaccination in India has been rolled out on a national level, with healthcare workers (HCWs) becoming the first recipient of both Covishield and Covaxin. However, concerns over efficacy of vaccines have been much debated. This study highlights COVID-19 infections among vaccinated HCWs in a teaching dental hospital in Delhi, India.

MethodologyThis cross-sectional survey was conducted using a pretested, validated, self-instituted questionnaire assessing COVID-19 like symptoms and/or confirmed infections among partially or fully vaccinated HCWs (all faculty, staff and students) of the institute from 16th January to 31st July 2021. The number of infections was also matched with hospital records.

ResultsOut of 397 HCWs, 386 (97.2%) were vaccinated and 355 (89.4%) had received both doses. COVID-19 like symptoms appeared in 21 HCWs (5.4%) post any dose of vaccine. Symptomatic breakthrough infections >14 days after second dose occurred was seen in 16 HCWs (4.5%). Except one (required hospitalization), all other cases had mild infection. No significant difference was observed between Covishield and Covaxin. Most common symptom was fever and body ache.

ConclusionThe study identifies the possibility of breakthrough infections among vaccinated HCWs, and ensures the impact of vaccination in limiting disease severity. The findings suggest that COVID-19 preventive measures should be continued even among vaccinated individuals.


title: Experience with open schools and preschools in periods of high community transmission of COVID-19 in Norway during the academic year of 2020/2021.

abstract:
BackgroundSchools and preschools have largely remained open in Norway throughout the pandemic, with flexible mitigation measures in place. This contrasts with many other high-income countries that closed schools for long periods of time. Here we describe cases and outbreaks of COVID-19 in schools and preschools during the academic year 2020/2021, to evaluate the strategy of keeping these open with infection prevention control measures in place.

MethodsIn this descriptive study, the Norwegian Institute of Public Health initiated systematic surveillance for COVID-19 cases and outbreaks in schools and preschools in October 2020. Data was compiled from the national outbreak alert system VESUV, municipality websites, and media scanning combined with the national emergency preparedness register Beredt C-19. An outbreak was defined as [≥] 2 cases among pupils or staff within 14 days at the same educational setting. Settings were categorized as preschool (1-5-years), primary school (6-12-years), lower secondary school (13-15-years) and upper secondary school (16-18-years). We reported the incidence rate among preschool and school-aged pupils and gave a descriptive overview of outbreaks and included cases per educational setting.

ResultsDuring the whole academic year, a total of 1203 outbreaks in preschools and school settings were identified, out of a total of 8311 preschools and schools nationwide. The incidence of COVID-19 in preschool- and school-aged children and the rates of outbreaks in these settings largely followed the community trend. Most of the outbreaks occurred in primary schools (40%) and preschools (25%). Outbreaks across all settings were mostly small (median 3 cases, range 2 to 72), however, 40 outbreaks (3% of total) included 20 or more cases. The larger outbreaks were predominantly seen in primary schools (43%).

ConclusionsWe observed few large outbreaks in open schools and preschools in Norway during the academic year of 2020/2021, also when the Alpha variant was predominant. This illustrates that it is possible to keep schools and preschools open even during periods of high community transmission of COVID-19. Adherence to targeted IPC measures adaptable to the local situation has been essential to keep educational settings open, and thus reduce the total burden on children and adolescents.


title: COVID-19 in Elderly Patients with Acute Kidney Injury

abstract:
ObjectiveCoronavirus disease 2019 (Covid 19) started in China in December 2019 and spread all over the world, is more progressive in patients who are elderly and with chronic diseases. Especially kidney involvement affects the survival of patients. In this study, we analyzed Covid 19 patients who developed acute kidney injury treated in our unit, retrospectively.

MatherialsThe clinical and laboratory data of 610 patients who hospitalized due to Covid 19 pandemic between 01.06.2020 and 30.06.2021 in the intensive care and other clinics of our hospital evaluated from the records, retrospectively. One hundred-fourty patients diagnosed with AKI according to the criteria of KDIGO (Kidney Disease Global Outcomes). The patients divided into two groups as KDIGO stage 1 and 2, 3.

ResultsThe median age in both groups was 70 (35-92) and 73 (35-90) years. Approximately seventy percent of them were over 65 years old. Almost all of the patients had hypertension. Most of the patients were using angiotensin converting enzyme inhibitors (ACE inh) or angiotensin receptor blockers (ARB) (84%). AKI was present at the time of admission (61.9%) in the KDIGO 1 group and at the time of hospitalization (64.3%) in the KDIGO 2, 3 group. The mortality rate was higher in stage 2-3 AKI patients (35.7%). Ferritin and fibrinogen levels were high in the KDIGO 2, 3 group, while lymphocyte levels were low.

ConclusionAKI can be seen at the time of admission and during treatment in patients who are hospitalized and treated due to Covid 19. Covid 19 is more mortal in patients with advanced AKI.

category: nephrology


title: COVID-19 in the Republic of Belarus: pandemic features and the interim safety and efficacy assessment of the Gam-COVID-Vac vaccine

abstract:
ObjectiveTo study the COVID-19 pandemic features among the population of the Republic of Belarus from February 2020 to September 2021 and assess the safety (tolerance) and epidemiological efficacy of the Gam-COVID-Vac vaccine (Sputnik V).

Materials and methodsA retrospective analysis of COVID-19 cases in the Republic of Belarus from the beginning of registration (February 28, 2020) to September 12, 2021 was performed. To assess the COVID-19 case detection dynamics, official registration data available on the website of the Ministry of Health of the Republic of Belarus were used.

Vaccine safety (tolerance) and efficacy were assessed in an observational study. Safety (tolerance) was assessed by presence/absence of adverse reactions: general and local ones.

The efficacy rate (E) and the epidemiological efficacy index (K) was calculated according to the formula: E(%)=100*(b-a)/b, K=b/a.

ResultsOur data show that The COVID-19 pandemic in the Republic of Belarus is characterized by successive development stages: the first is the absence of COVID-19 cases in the country; the second is the registration of individual infection cases that came from abroad followed by local pathogen spread among the countrys population; the third is a local spread of COVID-19 among individuals who had contact with infected people; the fourth is the detection of cases where patients had no history of exposure to COVID-19 patients.

As of calendar week 26, 2021 Delta variant of SARS-CoV-2 has become the prevalent in the country.

Follow-up results in January-August 2021 showed that the Sputnik V vaccine was well tolerated, with 80,832 adverse reactions reported (2.99% (95% CI 2.9-3.0) of the total number of vaccine doses administered). In terms of severity, adverse reactions were mild (91.4% (95% CI 91.2-91.6)) and moderate (8.6% (95% CI 8.6-8.8)). The epidemiological efficacy rate was 96.3%, the epidemiological efficacy index was 26.7. Thus, the results obtained testify to high prophylactic efficacy of the Sputnik V vaccine.

ConclusionsThe COVID-19 pandemic in the Republic of Belarus is characterized by successive development stages: from no cases in early 2020 to detected cases where most individuals had no history of contact with COVID-19 patients; periods of rising and falling incidence. The Sputnik V vaccine has demonstrated a high safety profile and epidemiological efficacy throughout mass vaccination in the Republic of Belarus.


title: Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron recycling and erythrocyte morphology

abstract: Aging, and the pathogenesis of many common diseases, involves iron homeostasis. A key role in iron homeostasis is played by the spleen, which is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this important role, spleen iron content has not been measured previously in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank using magnetic resonance imaging (MRI). We find that epidemiologic and environmental factors such as increased age, higher red meat consumption and lower alcohol intake correlate with higher spleen iron. Through genome-wide association study, we identify genetic associations between spleen iron and common variation at seven loci, including in two hereditary spherocytosis (HS) genes, ANK1 and SPTA1. HS-causing mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while our common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes observed in some HS allele carriers. Further, we identify an association between spleen iron and MS4A7, which colocalizes with a quantitative trait locus for MS4A7 alternative splicing in whole blood, and with monocyte count and fraction. Through quantification of spleen iron in a large human cohort, we extend our understanding of epidemiological and genetic factors associated with iron recycling and erythrocyte morphology.

category: hematology


title: Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology


title: Attenuation of antibody titres during 3-6 months after the second dose of the BNT162b2 vaccine depends on sex, with age and smoking as risk factors for lower antibody titres at 6 months

abstract:
ObjectiveWe aimed to determine antibody titres at 6 months and their rate of change during 3-6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) and to explore clinical variables associated with titres in Japan.

MethodsWe enrolled 365 healthcare workers (250 women, 115 men) whose 3-month antibody titres were analyzed in our previous study and whose blood samples were collected 183 {+/-} 15 days after the second dose. Participant characteristics collected previously were used. The relationships of these factors with antibody titres at 6 months and rates of change in antibody titres during 3-6 months were analyzed.

ResultsMedian age was 44 years. Median antibody titre at 6 months was 539 U/mL. Older participants had significantly lower antibody titres (20s, 752 U/mL; 60s-70s, 365 U/mL). In age-adjusted analysis, smoking was the only factor associated with lower antibody titres. Median rate of change in antibody titres during 3-6 months was -29.4%. The only factor significantly associated with the rate of change in Ab titres was not age or smoking, but sex (women, -31.6%; men, -25.1%).

ConclusionThe most important factors associated with lower antibody titres at 6 months were age and smoking, as at 3 months, probably reflecting their effect on peak antibody titres. However, antibody titres significantly attenuated during 3-6 months in women alone, which reduced the sex difference in antibody titres seen during the first 3 months. Antibody titres may be affected by different factors at different time points.


title: Family-Assisted Severity of Illness Monitoring for Hospitalized Children in Low-resource settings: a two-arm interventional pilot study

abstract:
IntroductionPediatric mortality remains unacceptably high in many low-resource settings, with inpatient deaths often associated with delayed recognition of clinical deterioration. The Family-Assisted Severe Febrile Illness ThERapy (FASTER) tool has been developed for caregivers to assist in monitoring their hospitalized children and alert clinicians. While utilization of the tool is feasible, the impact on outcomes in low-resource settings has not been studied.

MethodsRandomized controlled pilot study at Kenyatta National Hospital, Kenya. Children hospitalized with acute febrile illness with a caregiver at the bedside for 24 hours were enrolled. Caregivers were trained using the FASTER tool (monitors work of breathing, mental status, perfusion, producing color-coded flags to signal illness severity). The primary outcome was the frequency of clinician reassessments between intervention (FASTER) and control (standard care) arms. Secondary outcomes included survey assessments of clinician and caregiver experiences with the tool. The study was registered with ClinicalTrials.gov NCT03513861.

Results150 patient/caregiver pairs were enrolled, 139 included in the analysis, 74 in the intervention, 65 in the control arm. Patients median age was 0.9 (range 0.2-10) and 1.1 years (range 0.2-12) in intervention versus control arms. The most common diagnoses were pneumonia (80[58%]), meningitis (58[38%]) and malaria (34[24%]). 134(96%) caregivers were patients mothers. Clinician visits/hour increased with patients illness severity in both arms, but without difference in frequency between arms (point estimate for the difference -0.2%, p=0.99). Of the 16 deaths, 8 (four/arm) occurred within 2 days of enrollment. Forty clinicians were surveyed, 33(82%) reporting that FASTER could improve outcomes of very sick children in low-resource settings; 26(65%) rating caregivers as able to adequately capture patients severity of illness. Of 70 caregivers surveyed, 63(90%) reported that FASTER training was easy to understand; all(100%) agreed that the intervention would improve care of hospitalized children and help identify sick children in their community.

DiscussionAlthough we observed no difference in recorded frequency of clinician visits with FASTER monitoring, the tool was rated positively by caregivers and clinicians. Further research to refine implementation with additional input from all stakeholders might increase the effectiveness of FASTER in detecting and responding to clinical deterioration in low-resource settings.

category: emergency medicine


title: The Direct and Indirect Effects of a Global Pandemic on US Fishers and Seafood Workers

abstract: The United States seafood industry experienced major shifts in consumer demand and COVID-19 social-distancing restrictions starting in March 2020, when the early stages of the pandemic were unfolding. However, the specific effects on workers across seafood value chains are less well known. According to the US Centers for Disease Control and Protection (CDC), fishers and seafood workers face an increased risk of workplace exposure to COVID-19 given the close proximity to others in processing facilities and on fishing vessels, long work hours, and communal housing, living, and transportation arrangements associated with seasonal employment. To explore this hypothesis, and given a lack of data on the sector, we reviewed news articles, scientific articles, and white papers to identify the various effects of COVID-19 on US seafood workers and to track COVID-19 cases and outbreaks. Here, we show that most COVID-19 cases among seafood workers were reported during the summer of 2020 and during the beginning of 2021 with outbreaks primarily occurring in seafood processing. COVID-19 cases were documented throughout coastal areas, with Alaska experiencing the largest number of cases and outbreaks. Based on news reports, seafood workers were about twice as likely to contract COVID-19 as workers in other parts of the overall US food system. By examining news articles and scientific literature, we also documented several indirect effects of the pandemic. Social-distancing restrictions limited crew size and number of workers on processing lines, resulting in longer work hours and more physical and mental taxation. Economic consequences of the pandemic were reportedly a primary concern for fishers and aquaculture businesses, including changes in markets, supply, and demand, in addition to revenue loss, price fluctuations, supply chain issues, and labor shortages. Fewer outlets interviewed workers in seafood processing; however, concerns about workplace safety, contracting COVID-19, access to medical services, vaccination, and paid sick leave were all noted. We also highlight several inequities in COVID-19 responses within the seafood sector, both along racial and gender lines. Peer-reviewed studies and news coverage all point to diverse direct and indirect effects of the COVID-19 pandemic on workers across seafood value chains. The summary of these effects can serve as a foundation for future work on infection control and occupational outreach to workers in the seafood sector.


title: Unraveling the spatiotemporal spread of COVID-19 in Brazil through spatial network connectivity

abstract:
BackgroundDescribing and understanding the process of diffusion can allow local managers better plan emergence scenarios. Thus, the main aim of this study was to describe and unveil the spatiotemporal patterns of diffusion of the COVID-19 in Brazil from February 2020 until April 2021.

MethodsThis is a retrospective purely observational ecologic study including all notified cases and deaths. We used satellite-derived night light imagery and spatiotemporal Empirical Orthogonal Function analysis to quantify the spatial network structure of lighted development and the spatiotemporal transmission of the pathogen through the network.

ResultsThe more populous state capitals within the largest network components presented higher frequency of deaths and earlier onset compared to the increasing numbers of smaller, less populous municipalities trending toward lower frequency of deaths and later onset. By week 48 2020, the full network was almost completely affected. Cases and deaths showed a distinct second wave of wider geographic expansion beginning in early November 2020.

ConclusionsThe spatiotemporal diffusion in Brazil was characterized by an intertwined process of overseas relocation, hierarchical network transmission and contagious effects. A rapid response as the immediate control of all ports, airports and borders combined with mandatory quarantine are critical to retard disease diffusion.


title: Frequency and phenotype associations of rare variants in five monogenic cerebral small vessel disease genes in 200,000 UK Biobank participants with whole exome sequencing data

abstract:
Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extra-cerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of rare variants in cSVD genes in UK Biobank (UKB), a large population-based study.

We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in CTSA, TREX1, HTRA1, COL4A1/2. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in UKBs linked health data from UK hospital admissions, death records and primary care. Among 199,313 exome-sequenced UKB participants, we assessed: the proportion of participants carrying [≥]1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach.

Among UKB participants, 0.5% had [≥]1 variant(s) in studied genes. Using hospital admission and death records, 4-20% of variant carriers per gene had an associated phenotype. This increased to 7-55% when including primary care records. Only COL4A1 variant carrier-status was significantly associated with having [≥]1 phenotype-of-interest and a higher phenotype score (OR=1.29, p=0.006).

While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only around half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity and/or limited statistical power.

category: genetic and genomic medicine


title: A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

abstract:
BackgroundCoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac(R), but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac(R) on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile.

MethodsVolunteers immunized with two doses of CoronaVac(R) in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose.

FindingsWe observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4+ T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron.

InterpretationOur results show that a booster dose of CoronaVac(R) increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac(R) is active against VOC, suggesting an effective protection.


title: A booster dose of an inactivated SARS-CoV-2 vaccine increases neutralizing antibodies and T cells that recognize Delta and Omicron variants of concern


title: COVID-19 first and delta waves in relation to ACEI, ARB, Influenza vaccination, and comorbidity in a North Metropolitan Barcelona Health Consortium

abstract:
BACKGROUNDSome authors have reported that angiotensin converter enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improve clinical outcomes in hypertensive COVID-19 patients, and others have proposed cross-protection for influenza vaccination. This study explores the impact of these variables on the evolution of hospitalized patients, focusing in the first wave and the Delta wave.

METHODSHospitalizations (n=1888) from March 1, 2020, to July 31, 2021, in the Hospital of Terrassa, the referral center for the free access Terrassa Health Consortium in the North Metropolitan Barcelona Health Region (population=167,386) were studied. The number of chronic treatments and conditions of patients from the initial outbreak (n=184) and the Delta outbreak (n=158) were recorded.

RESULTSOf the non-survivors, 96.3% were aged >60 years in the first wave and 100% were aged >70 years in the Delta wave. In non-survival hospitalized patients aged >60 years, the percentage treated with ACEI was similar to general population but was significantly different for ARB treatments of influenza vaccination, although associated to a higher comorbidity and age. In July 2021, the number of hospitalizations for patients aged <50 years was higher than March 2020 and 22% of hospitalized patients without chronic treatments and conditions needed admission to the intensive care unit. Mortality was reduced in the groups with most comorbidities who received influenza and SARS-CoV2 vaccination.

CONCLUSIONSIn COVID-19 infection, age and comorbidity are related to survival, ACEI use is safe. A high proportion of patients without comorbidity require hospitalization and intensive care.


title: Estimating COVID-19-induced Excess Mortality in Lombardy

abstract: We compare the expected all-cause mortality with the observed one for different age classes during the pandemic in Lombardy, which was the epicenter of the epidemic in Italy and still is the region most affected by the pandemic. A generalized linear mixed model is introduced to model weekly mortality from 2011 to 2019, taking into account seasonal patterns and year-specific trends. Based on the 2019 year-specific conditional best linear unbiased predictions, a significant excess of mortality is estimated in 2020, leading to approximately 35000 more deaths than expected, mainly arising during the first wave. In 2021, instead, the excess mortality is not significantly different from zero, for the 85+ and 15-64 age classes, and significant reductions with respect to the 2020 estimated excess mortality are estimated for other age classes.


title: Extreme temperatures and mortality in 326 Latin American cities

abstract:
BackgroundClimate change and urbanization are rapidly increasing human exposure to extreme ambient temperatures, yet few studies have examined the impact of temperature on mortality across Latin America, where 80% of residents live in urban areas.

MethodsWe used distributed lag nonlinear conditional Poisson models to estimate city-specific associations between daily temperatures above ("heat") and below ("cold") each city-specific minimum mortality temperature and all-cause mortality, overall and stratified by age and cause of death. We estimated the percentage of total deaths attributable to heat or cold (excess death fraction [EDF]) and the difference in mortality per 1{degrees}C higher daily mean temperature above the 95th percentile of observed daily temperature.

ResultsWe analyzed data from 326 cities in nine Latin American countries between 2002-2015, representing 15,431,532 deaths from 249 million residents. The EDF of total deaths from heat was 0.67% (95% confidence interval [CI] 0.58%, 0.74%), and from cold was 5.09% (95% CI 4.64%, 5.47%). EDFs from heat and cold were particularly high among individuals aged 65+ years (0.81% [95% CI 0.75%, 0.86%] and 6.82% [95% CI 6.41%, 7.18%], respectively). The relative risk of death per 1{degrees}C increase above the city-specific 95th percentile daily temperature was 1.057 (95% CI 1.046, 1.067).

ConclusionsIn Latin American cities, a substantial proportion of deaths are attributable to non-optimal ambient temperatures. Older populations are particularly vulnerable. Marginal increases in observed hot temperatures are associated with steep increases in mortality risk. Projected increases in temperature from climate change may have a substantial impact on mortality.

SIGNIFICANCE STATEMENTLatin America has a large population at risk of urban heat exposure, yet little is known about the linkages between ambient temperature and health in the region. We analyzed over 15 million deaths in 326 Latin American cities to characterize the relationship between ambient temperature and mortality, overall and by age and cause of death. We found that 5.75% of all deaths are associated with non-optimal temperatures, older individuals are particularly vulnerable, and cardiorespiratory deaths are especially affected. A single degree increase (1{degrees}C) in daily temperature was associated with a 5.7% higher mortality among hot days, suggesting that projected increases in temperature from climate change may have a substantial impact on mortality.


title: Impact of SARS-CoV-2 Vaccines on Covid-19 Incidence and Mortality in the United States

abstract:
BackgroundDespite safe and effective vaccines to prevent Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infections and disease, a substantial minority of the US remains resistant to getting vaccinated. It is imperative to know if expanding vaccination rates could reduce community-wide Coronavirus 2019 (COVID-19) disease, not just among those vaccinated.

MethodsNegative binomial models were used to estimate associations between U.S. county-level vaccination rates and county-wide COVID-19 incidence and mortality between April 23rd and September 30th, 2021. A two-week lag and a four-week lag were introduced to assess vaccination rate impact on incidence and mortality, respectively. Stratified analyses were performed for county vaccination rates 40%, and before and after Delta became the dominant variant.

FindingsAmong 3,070 counties, each percentage increase in population vaccination rates reduced county-wide COVID-19 incidence by 0{middle dot}9% (relative risk (RR) 0. 9910 (95% CI: 0{middle dot}9869, 0{middle dot}9952)) and mortality by 1{middle dot}9% (RR 0{middle dot}9807 (95% CI: 0{middle dot}9745, 0{middle dot}9823)). Among counties with vaccination coverage >40%, each percentage increase in vaccination rates reduced COVID-19 disease by 1{middle dot}5%, RR 0{middle dot}9850 (95% CI: 0{middle dot}9793, 0{middle dot}9952) and mortality by 2{middle dot}7% (RR 0{middle dot}9727 (95% CI: 0{middle dot}9632, 0{middle dot}9823)). These associations were not observed among counties with <40% vaccination rates. Increasing vaccination rates from 40% to 80% would have reduced COVID-19 cases by 45{middle dot}4% (RR 0{middle dot}5458 (95% CI: 0{middle dot}4335, 0{middle dot}6873)) and deaths by 67{middle dot}0% (RR 0{middle dot}3305 (95% CI: 0{middle dot}2230, 0{middle dot}4898)). An estimated 5,989,952 COVID-19 cases could have been prevented and 127,596 lives saved had US population vaccination rates increased from 40% to 80%.

InterpretationsIncreasing U.S. SARS-CoV-2 vaccination rates results in population-wide reductions in COVID-19 incidence and mortality. Furthermore, increasing vaccination rates above 40% has protective effects among non-vaccinated persons. Given ongoing vaccine hesitancy in the U.S., increasing vaccination rates could better protect the entire community and potentially reach herd immunity.

FundingNational Cancer Institute


title: Epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus-induced asthma exacerbations and COVID-19

abstract: Rhinoviruses (RV) and inhaled allergens, such as house dust mite (HDM) are the major agents responsible for asthma onset, exacerbations and progression to the severe disease, but the mechanisms of these pathogenic reciprocal virus-allergen interactions are not well understood. To address this, we analyzed mechanisms of airway epithelial sensing and response to RV infection using controlled experimental in vivo RV infection in healthy controls and patients with asthma and in vitro models of HDM exposure and RV infection in primary airway epithelial cells. We found that intranasal RV infection in patients with asthma led to the highly augmented inflammasome-mediated lower airway inflammation detected in bronchial brushes, biopsies and bronchoalveolar lavage fluid. Mechanistically, RV infection in bronchial airway epithelium led to retinoic acid-inducible gene I (RIG-I), but not via NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which was highly augmented in patients with asthma, especially upon pre-exposure to HDM. This excessive activation of RIG-I inflammasomes was responsible for the impairment of antiviral type I/III interferons (IFN), prolonged viral clearance and unresolved inflammation in asthma in vivo and in vitro. Pre-exposure to HDM amplifies RV-induced epithelial injury in patients with asthma via enhancement of pro-IL1{beta} expression and release, additional inhibition of type I/III IFNs and activation of auxiliary proinflammatory and pro-remodeling proteins. Finally, in order to determine whether RV-induced activation of RIG-I inflammasome may play a role in the susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in asthma, we analyzed the effects of HDM exposure and RV/SARS-CoV-2 coinfection. We found that prior infection with RV restricted SARS-CoV-2 replication, but co-infection augmented RIG-I inflammasome activation and epithelial inflammation in patients with asthma, especially in the presence of HDM. Timely inhibition of epithelial RIG-I inflammasome activation may lead to more efficient viral clearance and lower the burden of RV and SARS-CoV-2 infections.


title: Rhinovirus-induced epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus-induced asthma exacerbations and COVID-19


title: Interventions in sexual and reproductive health services addressing violence against women in low- and middle- income countries: a mixed-methods systematic review

abstract:
ObjectivesTo synthesise evidence on the effectiveness, cost-effectiveness, and barriers to responding to violence against women (VAW) in sexual and reproductive health (SRH) services in low- and middle-income countries (LMICs).

DesignMixed-methods systematic review.

Data sourcesMedline, Embase, Psycinfo, Cochrane, Cinahl, IMEMR, Web of Science, Popline, Lilacs, WHO RHL, ClinicalTrials.gov, Google, Google Scholar, websites of key organisations through December 2019.

Eligibility criteriaStudies of any design that evaluated VAW interventions in SRH services in LMICs.

Data extraction and synthesisConcurrent narrative quantitative and thematic qualitative syntheses, integration through line of argument and mapping onto a logic model. Two reviewers extracted data and appraised quality.

Results26 studies of varied interventions using heterogeneous outcomes. Of ten interventions that strengthened health systems capacity to respond to VAW during routine SRH consultation, three reported no harm and reduction in some types of violence. Of nine interventions that strengthened health systems and communities capacity to respond to VAW, three reported conflicting effects on re-exposure to some types of VAW and mixed effect on SRH. The interventions increased identification of VAW but had no effect on the provision (75-100%) and uptake (0.6-53%) of referrals to VAW services. Of seven psychosocial interventions in addition to SRH consultation that strengthened womens readiness to address VAW, four reduced re-exposure to some types of VAW and improved health. Factors that disrupted the pathway to better outcomes included accepting attitudes towards VAW, fear of consequences, and limited readiness of the society, health systems, and individuals. No study evaluated cost-effectiveness.

ConclusionsSome VAW interventions in SRH services reduced re-exposure to some types of VAW and improved some health outcomes in single studies. Future interventions should strengthen capacity to address VAW across health systems, communities, and individual women. First-line support should be better tailored to womens needs and expectations.

PROSPERO protocol CRD42019137167.


title: DNA methylation of Nuclear Factor of Activated T Cells 1 mediates the prospective relation between exposure to different traumatic event types and post-traumatic stress disorder

abstract:
BackgroundThe mechanisms through which exposure to differing trauma types become biologically embedded to shape the risk for subsequent post-traumatic stress disorder (PTSD) is unclear. DNA methylation (5-mC), particularly in stress-relevant genes, may play a role in this relationship.

MethodsWe conducted path analysis using generalized structural equation modeling to investigate whether blood-derived 5-mC in Nuclear Factor of Activated T Cells 1 (NFATC1) mediated the prospective association between each of five different trauma types ("assaultive violence", "other injury or shocking experience", "learning of trauma to loved one", "sudden, unexpected death of a close friend or relative", and "other") and lifetime PTSD assessed prospectively in the Detroit Neighborhood Health Study (n=183).

ResultsAll five trauma types were significantly associated with reduced methylation at NFATC1 CpG site, cg17057218. Three of the five trauma types were significantly associated with increased methylation at NFATC1 CpG site, cg22324981. Moreover, methylation at cg17057218 significantly mediated 23-34% of the total effect for three of the five trauma types (assaultive violence, other injury or shocking experience, and learning of trauma to a loved one), while methylation at cg22324981 mediated 36-53% of the total effect for two of the five trauma types (other injury or shocking experience and other). These CpG sites were differentially associated with transcription factor binding sites and chromatin state signatures.

LimitationsProspective assessment of lifetime PTSD, rather than PTSD onset.

ConclusionsNFATC1 5-mC may be a potential mechanism in the relationship between some trauma types and prospective risk for PTSD. This finding may help inform treatment for trauma-specific PTSD.


title: Reduced Incidence of Long-COVID Symptoms Related to Administration of COVID-19 Vaccines Both Before COVID-19 Diagnosis and Up to 12 Weeks After

abstract: Both clinical trials and studies leveraging real-world data have repeatedly confirmed the three COVID-19 vaccines authorized for use by the Food and Drug Administration are safe and effective at preventing infection, hospitalization, and death due to COVID-19 and a recent observational study of self-reported symptoms provides support that vaccination may also reduce the probability of developing long-COVID. As part of a federated research study with the COVID-19 Patient Recovery Alliance, Arcadia.io performed a retrospective analysis of the medical history of 240,648 COVID-19-infected persons to identity factors influencing the development and progression of long-COVID. This analysis revealed that patients who received at least one dose of any of the three COVID vaccines prior to their diagnosis with COVID-19 were 7-10 times less likely to report two or more long-COVID symptoms compared to unvaccinated patients. Furthermore, unvaccinated patients who received their first COVID-19 vaccination within four weeks of SARS-CoV-2 infection were 4-6 times less likely to report multiple long-COVID symptoms, and those who received their first dose 4-8 weeks after diagnosis were 3 times less likely to report multiple long-COVID symptoms compared to those who remained unvaccinated. This relationship supports the hypothesis that COVID-19 vaccination is protective against long-COVID and that effect persists even if vaccination occurs up to 12 weeks after COVID-19 diagnosis. A critical objective of this study was hypothesis generation, and the authors intend to perform further studies to substantiate the findings and encourage other researchers to as well.


title: Coronary Artery Disease (CAD) - risk factors and causes: In Libyan patients.

abstract:
AimsCoronary artery disease (CAD) is the leading cause of death worldwide in both men and women. Accordingly, we retrospectively reviewed the effects of various risk factors on coronary angiographic outcomes.

Methods and ResultsData were collected from the catheter lab through Tripoli university hospital records, whereas the team reviewed clinical data and coronary artery diagrams for one year from 01/04/2019 to 31/03/2020. In our study, the total number of cases was 666; 401 male and 265 female, ranging in age between 27 and 91 years. Considering the data, a significantly increased incidence of coronary artery disease (CAD) among the male who smokes, and who were less than 60 years of age. Furthermore, in the present study, the total number of normal patients was predominantly female. The most common risk factors for women were diabetes mellitus (DM), hypertension (HTN) (12%,13% respectively). While the men share the significant effects of smoking on coronary angiography (C. Angio) findings (40.52%), and most of them underwent a percutaneous coronary intervention (PCI).

ConclusionsIn our study, there was evidence that CAD is a prevalent disease among the middle-aged populations with male gender preference. The risk factors including diabetes, hypertension, and smoking are the most contributing factors for the developing CAD in Libya.

category: cardiovascular medicine


title: Studies of parenchymal texture added to mammographic breast density and risk of breast cancer: a systematic review of methods used in the literature.

abstract: This systematic review aimed to assess the methods used to classify mammographic breast parenchymal features in relation to prediction of future breast cancer including the time from mammogram to diagnosis of breast cancer, and methods for the identification of texture features and selection of features for inclusion in analysis. The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov. were searched through October 2021 to extract published articles in English describing the relationship of parenchymal texture features with risk of breast cancer. Twenty-eight articles published since 2016 were included in the final review. Of these, 7 assessed texture features from film mammograms images, 3 did not report details of the image used, and the others used full field mammograms from Hologic, GE and other manufacturers. The identification of parenchymal texture features varied from using a predefined list to machine-driven identification. Reduction in number of features chosen for analysis in relation to cancer incidence then varied across statistical approaches and machine learning methods. The variation in approach and number of features identified for inclusion in analysis precluded generating a quantitative summary or meta-analysis of the value of these to improve predicting risk of future breast cancers. This updated overview of the state of the art revealed research gaps; based on these, we provide recommendations for future studies using parenchymal features for mammogram images to make use of accumulating image data, and external validation of prediction models that extend to 5 and 10 years to guide clinical risk management. By following these recommendations, we expect to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.


title: Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021

abstract:
BackgroundThe extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons.

MethodsConsenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis.

ResultsA total of 978 specimens were provided by 95 participants, of whom 78 (82%) were fully vaccinated and 17 (18%) were not fully vaccinated. No significant differences were detected in duration of RT-PCR positivity among fully vaccinated participants (median: 13 days) versus those not fully vaccinated (median: 13 days; p=0.50), or in duration of culture positivity (medians: 5 days and 5 days; p=0.29). Among fully vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p=0.048) or Janssen (p=0.003) vaccine recipients.

ConclusionsAs this field continues to develop, clinicians and public health practitioners should consider vaccinated persons who become infected with SARS-CoV-2 to be no less infectious than unvaccinated persons. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks.


title: Pathway specific polygenic risk scores identify pathways and patient clusters associated with inflammatory bowel disease risk, severity and treatment response

abstract: Crohns disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) with a strong genetic component [1,2]. Genome-wide association studies (GWAS) have successfully identified over 240 genetic loci that are statistically associated with risk of developing IBD, and these associations provide valuable insights into disease pathobiology. Building on GWAS findings, conventional polygenic risk scores (cPRS) aim to quantify the aggregated disease risk based on DNA variation, and these scores can identify individuals at high risk. While stratifying individuals based on cPRS has the potential to inform clinical care, the development of novel therapeutics requires deep insight into how aggregated genetic risk leads to disruption of specific biological pathways. Here, we developed a pathway-specific PRS (pPRS) methodology to assess IBD common variant genetic risk burden across 31 manually curated pathways. We first prioritized 206 genes based on comprehensive fine-mapping and eQTL colocalization analyses of genome-wide significant IBD GWAS loci and 58 highly penetrant genes based on their involvement in early onset IBD or autoimmunity-related colitis. These 264 genes were assigned to at least one of the 31 pathways based on Gene Ontology annotations and manual curation. Finally, we integrated these inputs into a novel pPRS model and performed an extensive investigation of IBD disease risk, severity, complications, and anti-TNF treatment response by applying our pPRS approach to three complementary datasets encompassing IBD cases and controls. Our analysis identified multiple promising pathways that can inform drug target discovery and provides a patient stratification method that offers insights into the biology of treatment response.

category: allergy and immunology


title: Assessing the Use of Prescription Drugs in Obese Respondents in the National Health and Nutrition Examination Survey

abstract:
IntroductionObesity is a common disease and a known risk factor for many other conditions such as hypertension, type 2 diabetes, and cancer. Treatment options for obesity include lifestyle changes, pharmacotherapy, and surgical interventions such as bariatric surgery. In this study, we examine the use of prescription drugs and dietary supplements by the individuals with obesity.

MethodsWe conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data 2003-2014. We used multivariate logistic regression to analyze the correlations of demographics and obesity status with the use of prescription drugs and dietary supplement use. We also built machine learning models to classify prescription drug and dietary supplement use using demographic data and obesity status.

ResultsIndividuals with obesity are more likely to take cardiovascular agents (OR=1.265, 95% CI 1.222-1.311) and metabolic agents (OR=1.398, 95% CI 1.343-1.456) than individuals without obesity. The best performing model for classifying prescription drug use had the accuracy of 74.5% and the AUROC of 0.817.

ConclusionsThis study can inform clinical practice and patient education of the use of prescription drugs and dietary supplements and their correlation with obesity.

category: endocrinology


title: Childhood Immuno-metabolic Markers and Risk of Depression and Psychosis in Adulthood: A Prospective Birth Cohort Study

abstract:
BackgroundMetabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology, are limited.

MethodsUsing data from 3875 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers, we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures.

ResultsChildhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.28; 95% CI, 1.00-1.64) and negative symptoms (aOR=1.12; 95% CI, 1.05-1.20). The general immuno-metabolic factor was associated with depressive symptoms (aOR=1.05; 95% CI, 1.01-1.08) and psychotic experiences (aOR=1.20; 95% CI, 1.01-1.42). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). All associations tended to be stronger in women, though 95% credible intervals overlapped with that for men. In women, the inflammatory factor was associated with depressive episode (aOR=1.23; 95% CI, 1.01-1.47) and atypical depressive symptoms (aOR=1.10; 95% CI, 1.02-1.19).

ConclusionsWhile general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation are linked to affective (depressive, atypical, and negative) symptoms.


title: Effectiveness of digital contact tracing for COVID-19 in New South Wales, Australia

abstract:
BackgroundDigital proximity tracing applications were rolled out early in the COVID-19 pandemic in many countries to complement conventional contact tracing. Empirical evidence about their benefits for pandemic response remains scarce. We evaluated the effectiveness and usefulness of  COVIDSafe, Australias national smartphone-based proximity tracing application for COVID-19.

MethodsIn this prospective study, conducted in New South Wales, Australia between May and November 2020, we calculated the positive predictive value and sensitivity of COVIDSafe, its additional contact yield, and the number of averted public exposure events. Semi-structured interviews with public health staff were conducted to assess the applications usefulness.

ResultsThere were 619 confirmed COVID-19 cases and over 25,300 close contacts during the study period. COVIDSafe was used by 137 (22%) cases and detected 79 (0{middle dot}3%) close contacts. It had a positive predictive value of 39% and a sensitivity of 15%, and detected 17 (0{middle dot}07%) additional close contacts that were not identified by conventional contact tracing. The application generated a substantial additional workload for public health staff and was not considered useful.

ConclusionsCOVIDSafe was not sufficiently effective to make a meaningful contribution to the COVID-19 response in Australias most populous state over a 6-month period. This contrasts optimistic projections from modelling studies about the added value of digitally supported contact tracing. We found no evidence that it adds value to conventional contact tracing, and recommend that their implementation should always include comprehensive effectiveness evaluations.

category: public and global health


title: Care Models for Long COVID: A Rapid Systematic Review

abstract:
ContextMore than 18M people worldwide (150K Canadians) are living with Long COVID resulting in debilitating sequalae and disabilities that impact their quality of life and capacity to return to work. A new care model is needed for persons living with this complex and multi-systemic disease.

ObjectivesWhat is the best-available evidence about care models for persons living with Long COVID?

DesignRapid Living Systematic Review.

MethodWe systematically searched seven electronic databases (MEDLINE, Embase, Web of Science, COVID-END, L-OVE, CDRS and WHO Ovid) on May 27th, 2021. Two independent reviewers screened titles, abstracts and full text. We included studies reporting on 1- persons living with Long COVID and 2- proposing a specific care model (i.e., dedicated clinic, care pathway). We extracted characteristic of studies (e.g., countries, study design, age group), referral pathways targeted (e.g., hospitalized, community), reporting of the care model implementation with number of patients, clinical settings of care model (e.g., primary care), healthcare professions included in the care model, care model principles (e.g., person-centred care) and care model components (e.g., standardized symptoms assessment). We used descriptive statistics and frequency count.

ResultsWe screened 2181 citations, read 65 full text and included 12 eligible articles reporting on care models for Long COVID. Half studies were from the United Kingdom. 7 out of 12 models reported conceptual models without a description of implementation. All but one model was designed for discharge and long-term follow-up of hospitalized patients and half models were designed for non- hospitalized or patients who lived with the disease only in the community. Nine out of 12 care models included primary care, 8 out of 12 included specialized clinics and all studies included rehabilitation services. A total of 30 healthcare professions and medical specialties were proposed for staffing Long COVID services. More than half studies proposed multidisciplinary teams, integrated/coordination of care, evidence-based care and patient-centred care as key care model principles. Standardized symptom assessment, follow-up system and virtual care were the most frequent care model components.

ConclusionThe implementation of care models for Long COVID is underway in several countries. Care models need to include both hospitalized and non-hospitalized patients. A complete care model for this population appears to design a care pathway integrating primary care, rehabilitation services and specialized clinics for medical assessment. The entry into care pathways is likely possible through a centralized referral system. It is possible to design sustainable and equitable care pathways for Long COVID in Canada integrated in current infrastructure.

Protocol/Topic RegistrationCRD42021282266

SummaryAn estimated 150K Canadians, mostly women, are facing debilitating sequalae and disabilities from Long COVID that impact their quality of life and capacity to return to work. A new care model is needed for persons with this complex and multi-systemic disease. We identified international care models describing the integration of primary care, rehabilitation services and specialized assessment clinics for Long COVID.

ImplicationsLimited evidence from this review of international care models for Long COVID point out to a care model for the Canadian context that should be co- designed with patients, clinicians, decision makers and researchers, and include: 1- A coordination unit to centrally receive referrals from both hospitalized and community-based patients; 2- Training of primary care teams to screen and support medical needs; 3- Integrated local multidisciplinary rehabilitation services; and 4- Access to medical specialty clinics for advanced testing and diagnoses.

What is the current situation?O_LIMore than 150K Canadians are with living the affliction of Long COVID, the patient-led term to describe long-term consequences of COVID-19. Long COVID is a multi-systemic and unpredictable disease impacting quality of life and return to work in middle aged population. To avoid widespread long-term disabilities impacting public health, Canadian provinces are seeking to organize a sustainable and equitable care model for Long COVID.
C_LI

What is the objective?O_LITo provide the best-available evidence about care models for persons living with Long COVID.
C_LI

How was the review conducted?O_LIWe systematically searched seven electronic databases (MEDLINE, Embase, Web of Science, COVID-END, L-OVE, CDRS and WHO Ovid) on May 27th, 2021.
C_LIO_LITwo independent reviewers screened title, abstract and full text.
C_LIO_LIWe included studies reporting on 1- persons living with Long COVID (post- hospitalized and community based) and 2- a specific care model (i.e., dedicated clinic, care pathway).
C_LIO_LIWe extracted characteristic of studies, referral pathways, clinical settings of care model, healthcare professions included in the care models, care model principles, care model components and reporting of the care model implementation.
C_LI

What did the review find?O_LIWe found 12 international care models for Long COVID that covers follow-up of patients discharged following a hospitalization and patients who had lived the infection in the community.
C_LIO_LIMost reported elements included in these care models were a coordination unit, primary care pathways, access to multidisciplinary rehabilitation and specialized medical services.
C_LIO_LIThe impact and costs of these care models are not yet reported.
C_LI


title: Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape, South Africa

abstract:
IntroductionThe World Health Organization recommends full disclosure of HIV-positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10-19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents mental health as reasons for non-disclosure. Evidence is limited about predictors of disclosure and its association with adherence, viral suppression, and mental health outcomes among adolescents in sub-Saharan Africa.

MethodsAnalyses included three rounds (2014-2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random-effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression, and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and ART adherence between study rounds and disclosure groups with logistic regression.

Results813 APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV-positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio (aOR): 1.24; 1.07 - 1.43) and living in an urban location (aOR: 2.76; 1.67 - 4.45) were associated with disclosure between interviews. There was no association between awareness of HIV-positive status and ART adherence, viral suppression, or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N=131) and increased among those not disclosed to (N=151) (interaction aOR: 0.39; 0.19 - 0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups.

ConclusionsAwareness of HIV-positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV, however, adherence support post-disclosure is important.

category: hiv aids


title: Diagnostic accuracy of three prevailing rapid antigen tests for detection of SARS-CoV-2 infection in the general population: cross sectional study

abstract:
ObjectiveTo assess the diagnostic accuracy of three rapid antigen tests (Ag-RDTs) for detecting SARS-CoV-2 infection in the general population.

DesignCross-sectional study with follow-up using pseudonymised record linkage.

SettingThree Dutch public health service COVID-19 test sites.

ParticipantsConsecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing.

Main outcome measuresSensitivity, specificity, positive and negative predictive values of BD-Veritortm System (Becton Dickinson), PanBio (Abbott), and SD-Biosensor (Roche Diagnostics), applying routinely used sampling methods (combined oropharyngeal and nasal [OP-N] or nasopharyngeal [NP] swab), with molecular testing as reference standard. For SD-Biosensor, the diagnostic accuracy with OP-N sampling was also assessed. A viral load cut-off ([≥]5.2 log10 SARS-CoV-2 E-gene copies/mL) served as a proxy of infectiousness.

ResultsSARS-CoV-2 prevalence and overall sensitivities with 95% confidence intervals were 188/1441 (13.0%) and 129/188 (68.6% [61.5%-75.2%]) for BD-Veritor, 173/2056 (8.4%) and 119/173 (68.8% [61.3%-75.6%]) for PanBio, and 215/1769 (12.2%) and 160/215 (74.4% [68.0%-80.1%]) for SD-Biosensor with routine sampling, and 164/1689 (9.7%) and 123/164 (75.0% [67.7%-81.4%]) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72.2%-83.4% and 54.0%-55.9%, respectively. With a viral load cut-off, sensitivities were 125/146 (85.6% [78.9%-90.9%]) for BD-Veritor, 108/121 (89.3% [82.3%-94.2%]) for PanBio, 160/182 (87.9% [82.3%-92.3%]) for SD-Biosensor with routine sampling, and 118/141 (83.7% [76.5%-89.4%]) with OP-N sampling. Specificities were >99%, and positive and negative predictive values >95%, for all tests in most analyses. 61.3% of false negative Ag-RDT participants returned for testing within 14 days (median of 3 days, interquartile range 3) of whom 90.3% tested positive.

ConclusionsThe overall sensitivities of the three Ag-RDTs were 68.6%-75.0%, increasing to at least 85.6% after the viral load cut-off was applied. For SD-Biosensor, the diagnostic accuracy with OP-N and NP sampling was comparable. Over 55% of false negative Ag-RDT participants tested positive during follow-up.