title: DermoExpert: Skin lesion classification using a hybrid convolutional neural network through segmentation, transfer learning, and augmentation

abstract:
Background and ObjectiveAlthough automated Skin Lesion Classification (SLC) is a crucial integral step in computeraided diagnosis, it remains a challenging task due to inconsistency in texture, color, indistinguishable boundaries, and shapes.

MethodsIn this article, we propose an automatic and robust framework for the dermoscopic SLC named Dermoscopic Expert (DermoExpert). The DermoExpert consists of a preprocessing, a hybrid Convolutional Neural Network (hybrid-CNN), and transfer learning. The proposed hybrid-CNN classifier consists of three distinct feature extractors, with the same input images, which are fused to achieve better-depth feature maps of the corresponding lesion. Those distinct and fused feature maps are classified using the different fully connected layers, which are then ensembled to get a final prediction probability. In the preprocessing, we use lesion segmentation, augmentation, and class rebalancing. For boosting the lesion recognition, we have also employed geometric and intensity-based augmentation as well as the class rebalancing by penalizing the loss of the majority class and adding extra images to the minority classes. Additionally, we leverage the knowledge from a pre-trained model, also known as transfer learning, to build a generic classifier, although small datasets are being used. In the end, we design and implement a web application by deploying the weights of our DermoExpert for automatic lesion recognition.

ResultsWe evaluate our DermoExpert on the ISIC-2016, ISIC-2017, and ISIC-2018 datasets, where our DermoExpert has achieved the area under the receiver operating characteristic curve (AUC) of 0.96, 0.95, and 0.97, respectively. The experimental results outperform the recent state-of-the-art by a margin of 10.0 % and 2.0 % respectively for ISIC-2016 and ISIC-2017 datasets in terms of AUC. The DermoExpert also outperforms, in concerning a balanced accuracy, by a margin of 3.0 % for ISIC-2018 dataset.

ConclusionSince our framework can provide better-classification on three different test datasets, even with limited training data, it can lead to better-recognition of melanoma to aid dermatologists. Our source code, and segmented masks, for ISIC-2018 dataset, will be made publicly available for the research community for further improvements.

category: dermatology


title: Lifetime depression and age-related changes in body composition, cardiovascular function, grip strength and lung function: sex-specific analyses in the UK Biobank

abstract: Individuals with depression, on average, die prematurely, have high levels of physical comorbidities and may experience accelerated biological ageing. A greater understanding of age-related changes in physiology could provide novel biological insights that may help inform strategies to mitigate excess mortality in depression. We used generalised additive models to examine age-related changes in 15 cardiovascular, body composition, grip strength and lung function measures, comparing males and females with a lifetime history of depression to healthy controls. The main dataset included 342,393 adults (mean age = 55.87 years, SD = 8.09; 52.61% females). We found statistically significant case-control differences for most physiological measures. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in depression. These differences did not uniformly narrow or widen with age and differed by sex. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in depression cases at age 45 and this difference widened to 2.5 mmHg at age 65. These findings suggest that targeted screening for physiological function in middle-aged and older adults with depression is warranted to potentially mitigate excess mortality.

category: epidemiology


title: GPS-estimated foot traffic data and venue selection for COVID-19 serosurveillance studies

abstract: The initial phase of the COVID-19 pandemic in the US was marked by limited diagnostic testing, resulting in the need for seroprevalence studies to estimate cumulative incidence and define epidemic dynamics. In lieu of systematic representational surveillance, venue-based sampling was often used to rapidly estimate a communitys seroprevalence. However, biases and uncertainty due to site selection and use of convenience samples are poorly understood. Using data from a SARS-CoV-2 serosurveillance study we performed in Somerville, Massachusetts, we found that the uncertainty in seroprevalence estimates depends on how well sampling intensity matches the known or expected geographic distribution of seropositive individuals in the study area. We use GPS-estimated foot traffic to measure and account for these sources of bias. Our results demonstrated that study-site selection informed by mobility patterns can markedly improve seroprevalence estimates. Such data should be used in the design and interpretation of venue-based serosurveillance studies.


title: Recruitment location influences bias and uncertainty in SARS-CoV-2 seroprevalence estimates


title: ACTIVE SURVEILLANCE OF THE SPUTNIK V VACCINE IN HEALTH WORKERS

abstract:
IntroductionThe World Health Organization (WHO) recommends vaccination against Sars Cov-2 coronavirus to mitigate COVID-19 pandemic. On December 29th, the Argentine Ministry of Health started a vaccination plan with the Sputnik V vaccine emphasizing the registration of the Events Supposedly Attributed to Vaccines and Immunizations (ESAVI) in the National Surveillance System. The aim of this study is to determine the safety of this vaccine.

MethodsIn an ongoing cohort study, health professionals from Hospital Italiano de Buenos Aires vaccinated with the first component of the Sputnik V vaccine (a rAd26 vector-based) were followed up. Safety at 72 hs was analysed from a self-report form. Local and systemic reactions were characterized as mild, moderate and severe. Incident rates were calculated per 1000 person-hours by age groups and gender. Adjusted hazard ratio and 95% Confidence Interval (HR; 95%CI) is obtained by Cox Regression Model.

Results707 health professionals (mean age 35, 67% female) were vaccinated, response rate was 96,6% and 71,3% reported at least one ESAVI. Rate was 6.3 per 1.000 person-hours. Among local reactions, 54% reported pain at the injection site, 11% redness and swelling. Among systemic reactions 40% reported fever, 5% diarrhea and 68% new or worsened muscle pain. Five percent had serious adverse events that required medical evaluation and one inpatient.

ESAVI rate was higher among females (65.4% vs 50%; HR 1.38, 95%CI 1.13-5.38) and in younger than 55 years-old (72.8% vs 32%; HR 2.66, 95%CI 1.32-1.68).

ConclusionActive surveillance on safety for vaccines with emergency approval is mandatory. This study shows high rates of local and systemic reactions however early serious events were rare. Short term safety is supported by these preliminary findings. Studies on long term safety and efficacy, accoding sex and age, are needed.


title: Machine learning to predict retention and viral suppression in South African HIV treatment cohorts

abstract:
BackgroundTo optimize South Africas HIV response and reach PEPFARs 95:95:95 targets require same day initiations and patients successfully remaining on antiretroviral therapy, and remaining virally suppressed. Much effort and resources with HIV programmes have centred on tracking and tracing for those lost to follow-up (LTFU), through various back to care strategies to ensure retention of patients. However, programmes have noted the need for targeted, data driven and predictive approaches for identifying most at risk of patients for LTFU and viral unsuppression outcomes using available phenotypic data.

MethodsWe applied predictive machine learning algorithms to anonymised, patient-level HIV programmatic data from two districts in South Africa, January 2016 - July 2019. We developed patient risk scores for two outcomes: 1) visit attendance within 28 days of next scheduled clinic visit and 2) suppression of next HIV viral load (VL). Demographic, clinical, behavioural (e.g. visit patterns) and laboratory data were investigated in multiple models as potential predictor variables of attending next scheduled visit and VL result at next visit.

FindingsLongitudinal data was analysed using combinations of predictor features and classification algorithms. 445,636 Patients were included in the retention model and 363,977 in the VL model. Predictive accuracy, summarized by Area Under the Curve (AUC), ranged from 0.69 for attendance at next scheduled visit to 0.76 for VL suppression, suggesting the model correctly classified patients to whether a scheduled visit would be attended in 2 out of 3 patients and whether the VL result at next test would be suppressed in approximately 3 out of 4 patients. Key predictors for both retention & VL suppression include metrics on prior late or LTFU visits, the number of prior VL tests, the time since their last visit, the number of visits on their current regimen, the patients age, and their time on treatment. For retention, the number of visits at the current facility and the details of the next appointment date were also predictors. For VL suppression, other predictors included the range of thee previous VL value.

ConclusionMachine learning can be used to identify HIV patients at risk for defaulting on treatment and not being virally suppressed. Predictive modelling can improve targeting of interventions through differentiated models of care, increasing cost-effectiveness and improving patient outcomes.


title: COVID19-related and all-cause mortality among middle-aged and older adults across the first epidemic wave of SARS-COV-2 infection in the region of Tarragona, Spain: results from the COVID19 TARRACO Cohort Study, March-June 2020.

abstract:
BackgroundDirect and indirect COVID19-related mortality is uncertain. This study investigated COVID19-related and all-cause deaths among middle-aged and older adults during the first wave of COVID19 epidemic period, assessing mortality risks by pre-existing socio-demographic and medical underlying conditions.

MethodsPopulation-based cohort study involving 79,083 individuals [≥]50 years-old in Tarragona (Southern Catalonia, Spain). Baseline cohort characteristics (age/sex, comorbidities and medications/vaccinations history) were established at study start (01/03/2020) and main outcomes were COVID19-related deaths (occurred in patients diagnosed with the disease) and all-cause deaths occurred among cohort members between 01/03/2020-30/06/2020. Mortality risks were assessed by Cox regression analyses.

ResultsCohort members were followed for 1,356,358 persons-weeks, occurring 576 all-cause deaths (124 COVID19-related). All-cause mortality rate was 42.5 deaths per 100,000 persons-week, being 22.8 in healthy/unrelated-COVID19 subjects, 236.4 in COVID19-excluded/PCR-negative subjects, 493.7 in COVID19-compatible/PCR-unperformed subjects and 4009.1 in COVID19-confirmed patients. In multivariable analyses, increasing age, sex male, nursing-home residence, cancer, neurologic, cardiac or liver disease, receiving diuretics, systemic corticosteroids, proton-pump inhibitors and benzodiazepines were associated with increased risk of all-cause mortality; conversely, receiving renin-angiotensin inhibitors and statins were associated with reduced risk. Age/years, sex male and nursing-home residence were strong predictors for COVID19-related mortality, but none comorbidity appeared significantly associated with an increased risk.

ConclusionApart from direct COVID19-related deaths (which represented almost 22% of all-cause mortality), theoretically COVID19-excluded patients (PCR-negative) suffered considerable greater all-cause mortality than healthy/unrelated-COVID19 subjects, which could explain, in part, the large excess deaths observed across the COVID19 pandemic.


title: How did COVID-19 measures impact sexual behaviour and access to STI&HIV services in Panama? Results from a national cross-sectional online survey

abstract:
ObjectivesTo describe perceived changes in sexual behaviours, including virtual sex (sexting and cybersex), and access to HIV/STI testing and care during COVID-19 measures in Panama. Methods We conducted an online cross-sectional survey from August 8 to September 12, 2020, among adults ([≥]18 years) residing in Panama. Participants were recruited through social media. Questions included demographics, access to HIV/STI testing and HIV care and sexual behaviours three months before COVID-19 social distancing measures and during social distancing measures (COVID-19 measures). Logistic regression was used to identify associations between variables and behavioural changes.

ResultsWe recruited 960 participants; 526 (54.8%) identified as cis-women, 366 (38.1%) cis-men, and 68 (7.1%) non-binary or another gender; median age was 28y (IQR:23-37y), 531/957 (55.5%) were of mixed-ethnicity (mixed-Indigenous/European/Afro-descendant ancestry). Before COVID-19 measures, virtual sex was reported by 38.5% (181/470) cis-women, 58.4% (184/315) cis-men and 45.0% (27/60) non-binary participants; during COVID-19 measures, virtual sex increased among 17.2% cis-women, 24.7% cis-men and 8.9% non-binary participants. During COVID-19 measures, 230/800 [28.8%] of participants reported decreased casual sex compared to pre-COVID-19 measures. Compared to pre-COVID-19 measures, decreased casual sex were reported more frequently during COVID-19 measures by cis-men compared to cis-women (39.2% versus 22.9%, urban/rural adjusted odds ratio [AOR]=2.17, 95% confidence interval [CI]:1.57-3.01); and by Afro-descendant compared to mixed-ethnicity participants (40.0% versus 29.8%, AOR=1.78, 95%CI:1.07-2.94). Compared to no change in virtual sex (16.8%), increase in virtual sex (38.5%, AOR=1.78, 95%CI:1.10-2.88); and decreased virtual sex (86.7%, AOR=16.53, 95%CI:7.74-35.27) were associated with decreased casual sex encounters. During COVID-19 measures, HIV/STI testing could not be obtained by 58.0%(58/100) participants who needed a test, and interrupted HIV care was reported by 53.3% (8/15) HIV-positive participants.

ConclusionsCOVID-19 measures in Panama were associated with a decrease in casual sex among cis-men and Afro-descendant peoples, whilst access to HIV/STI testing and care was seriously disrupted.


title: How did COVID-19 measures impact sexual behaviour and access to HIV/STI services in Panama? Results from a national cross-sectional online survey


title: Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England

abstract:
BackgroundEthnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves.

MethodsUsing data from the Office for National Statistics Public Health Data Asset on individuals aged 30-100 years living in private households, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions.

ResultsThe study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7 - 376.2] and 166.8 [141.7 - 191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4 - 390.1] and 127.1 [91.1 - 171.3] in men and women)background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves.

ConclusionBetween the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.

*VN and NI contributed equally to this paper

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA recent systematic review by Pan and colleagues demonstrated that people of ethnic minority background in the UK and the USA have been disproportionately affected by the Coronavirus (COVID-19) pandemic, compared to White populations. While several studies have investigated whether adjusting for socio-demographic and economic factors and medical history reduces the estimated difference in risk of mortality and hospitalisation, the reasons for the differences in the risk of experiencing harms from COVID-19 are still being explored during the course of the pandemic. Studies so far have analysed the ethnic differences in COVID-19 mortality in the first wave of the pandemic. The evidence on the temporal trend of ethnic inequalities in COVID-19 mortality, especially those from the second wave of the pandemic, is scarce.

Added value of this studyUsing data from the Office for National Statistics (ONS) Public Health Data Asset on 29 million adults aged 30-100 years living in private households in England, we conducted an observational cohort study to examine the differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and second wave (from 1st September to 28th December 2020). We find that in the first wave all ethnic minority groups were at elevated risk of COVID-19 related death compared to the White British population. In the second wave, the differences in the risk of COVID-19 related death attenuated for Black African and Black Caribbean groups, remained substantially higher in people from Bangladeshi background, and worsened in people from Pakistani background. We also find that some of the factors explaining these differences in mortality have changed in the two waves.

Implications of all the available evidenceThe risk of COVID-19 mortality during the first wave of the pandemic was elevated in people from ethnic minority background. An appreciable reduction in the difference in COVID-19 mortality in the second wave of the pandemic between people from Black ethnic background and people from the White British group is reassuring, but the continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy response. Focusing on treating underlying conditions, although important, may not be enough in reducing the inequalities in COVID-19 mortality. Focused public health policy as well as community mobilisation and participatory public health campaign involving community leaders may help reduce the existing and widening inequalities in COVID-19 mortality.


title: Field performance evaluation of the PanBio rapid SARS-CoV-2 antigen assay in an epidemic driven by 501Y.v2 (lineage B.1.351) in the Eastern Cape, South Africa

abstract:
BackgroundSouth Africa was the African country most severely affected by the SARS-CoV-2 pandemic during 2020, experiencing 2 waves of infection. During the first wave, diagnostics were largely based on reverse transcription-linked PCR (RT-PCR). The Abbott PanBio antigen test was deployed during the 2nd wave which was driven by emergence of the 501Y.v2 variant. At the time of evaluation in mid-November 2020, 501Y.v2 was the dominant circulating virus in Nelson Mandela Bay, in the Eastern Cape Province.

MethodsA prospective diagnostic evaluation study was undertaken, during a period of high community transmission, to evaluate the field performance of the PanBio antigen RTD. Testing was conducted at mobile community testing centres on 677 ambulant patients seeking SARS-CoV-2 testing. RT-PCR was performed on the original naso-pharyngeal antigen swabs to evaluate test performance.

ResultsOf 146 RT-PCR positive individuals, 101 were RTD positive in the clinic. The antigen RTD had an overall sensitivity of 69.2% (95%CI 61.4, 75.8) and specificity of 99.0% (95%CI 98.8, 99.3) in this clinical context. Sensitivity was strongly dependent on the amount of virus in clinical samples, as reflected by the PCR cycle threshold (CT) value, with 100% detection in samples where the CT was <20, 96% with CT between 20-25, 89% with CT between 26-30 and 64% when CT was 31-35.

ConclusionsThe assay reliably detected 501Y.v2 infections in ambulatory ill patients. Assay sensitivity was >90% in patients with high viral loads who are expected to be most infectious. Negative and positive predictive values were also >90%.

category: pathology


title: Extubation generates lung volume inhomogeneity in preterm infants

abstract:
ObjectiveTo evaluate the feasibility of EIT to describe the regional tidal ventilation (VT) and change in end-expiratory lung volume (EELV) patterns in preterm infants during the process of extubation from invasive to non-invasive respiratory support.

DesignProspective observational study

SettingSingle-centre tertiary neonatal intensive care unit

PatientsPreterm infants born <32 weeks gestation who were being extubated to nasal continuous positive airway pressure (nCPAP) as per clinician discretion.

InterventionsElectrical Impedance Tomography measurements were taken in supine infants during elective extubation from synchronised positive pressure ventilation (SIPPV) before extubation, during and then at 2 and 20 minutes after commencing nCPAP. Extubation and pressure settings were determined by clinicians.

Main outcome measuresGlobal and regional {Delta}EELV and {Delta}VT were measured. Heart rate, respiratory rate and oxygen saturation were measured throughout.

ResultsThirty infants of median (range) 2 (1, 21) days were extubated to a median (range) CPAP 7 (6, 8) cmH2O. SpO2/FiO2 ratio was mean (95% CI) 50 (35, 65) lower 20 minutes after nCPAP compared with SIPPV. EELV was lower at all points after extubation compared to SIPPV, and EELV loss was primarily in the ventral lung (p=0.04). VT was increased immediately after extubation, especially in the central and ventral regions of the lung, but the application of nCPAP returned VT to pre-extubation patterns.

ConclusionsLung behaviour during the transition from invasive positive pressure ventilation to CPAP at moderate distending pressures is variable and associated with lung volume loss in the ventral lung.

category: pediatrics


title: Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination

abstract:
BackgroundMaternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.

Case presentationA vigorous, healthy, full-term female was born to a COVID-19 naive mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery.

ConclusionHere, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.


title: Affective neural signatures do not distinguish women with emotion dysregulation from healthy controls:A mega-analysis across three task-based fMRI studies

abstract: Pathophysiological models are urgently needed for personalized treatments of mental disorders. However, most potential neural markers for psychopathology are limited by low interpretability, prohibiting reverse inference from brain measures to clinical symptoms and traits. Neural signatures--i.e. multivariate brain-patterns trained to be both sensitive and specific to a construct of interest--might alleviate this problem, but are rarely applied to mental disorders. We tested whether previously developed neural signatures for negative affect and discrete emotions distinguish between healthy individuals and those with mental disorders characterized by emotion dysregulation, i.e. Borderline Personality Disorder (BPD) and complex Post-traumatic Stress Disorder (cPTSD). In three different fMRI studies, a total sample of 192 women (49 BPD, 62 cPTSD, 81 healthy controls) were shown pictures of scenes with negative or neutral content. Based on pathophysiological models, we hypothesized higher negative and lower positive reactivity of neural emotion signatures in participants with emotion dysregulation. The expression of neural signatures differed strongly between neutral and negative pictures (average Cohens d = 1.17). Nevertheless, a mega-analysis on individual participant data showed no differences in the reactivity of neural signatures between participants with and without emotion dysregulation. Confidence intervals ruled out even small effect sizes in the hypothesized direction and were further supported by Bayes factors. Overall, these results support the validity of neural signatures for emotional states during fMRI tasks, but raise important questions concerning their link to individual differences in emotion dysregulation.

category: psychiatry and clinical psychology


title: 'Breaking the silence': Sexual victimisation in an old age psychiatry patient population in Flanders

abstract:
BackgroundSexual violence (SV) is linked to mental health problems in adulthood and old age. However, the extent of sexual victimisation in old age psychiatry patients is unknown. Due to insufficient communication skills in both patients and healthcare workers, assessing SV in old age psychiatry patients is challenging.

MethodsBetween July 2019 and March 2020, 100 patients at three old age psychiatry wards across Flanders participated in a face-to-face structured interview receiving inpatient treatment. The participation rate was 58%. We applied the WHO definition of SV, encompassing sexual harassment, sexual abuse with physical contact without penetration, and (attempted) rape.

OutcomesIn 57% of patients (65% F, 42% M) SV occurred during their lifetime and 7% (6% F, 9% M) experienced SV in the past 12-months. Half of the victims disclosed their SV experience for the first time during the interview. Only two victims had disclosed SV to a mental health care professional before.

InterpretationSexual victimisation appears to be common in old age psychiatry patients, yet it remains largely undetected. Although victims did reveal SV during a face-to-face interview to a trained interviewer, they do not seem to spontaneously disclose their experiences to mental health care professionals. In order to provide tailored care for older SV victims, professionals urgently need capacity building through training, screening tools and care procedures.


title: Experience of clinical services shapes attitudes to data sharing

abstract:
BackgroundRoutinely-collected mental health data could deliver novel insights for mental health research. However, patients willingness to share their mental health data remains largely unknown. We investigated factors influencing likelihood of sharing these data for research purposes amongst people with experience of mental illness.

MethodsWe collected responses from a diverse sample of UK National Health Service (NHS) users (n = 2187) of which about half (n = 1087) had lifetime experience of mental illness. Ordinal logistic regression was used to examine the influence of demographic factors, clinical service experience, and primary mental illness on willingness to share mental health data, contrasted against physical health data.

ResultsThere was a high level of willingness to share mental (89.7%) and physical (92.8%) health data for research purposes. Higher levels of satisfaction with the NHS were associated with greater willingness to share mental health data. Furthermore, people with personal experience of mental illness were more willing than those without to share mental health data, once the effect of NHS satisfaction had been controlled for. Of the mental illnesses recorded, people with depression, obsessive-compulsive disorder (OCD), personality disorder or bipolar disorder were significantly more likely to share their mental health data than people without mental illness.

ConclusionsThese findings suggest that positive experiences of health services and personal experience of mental illness are associated with greater willingness to share mental health data. NHS satisfaction is a potentially modifiable factor that could foster public support for increased use of NHS mental health data in research.


title: Experience of clinical services shapes attitudes to mental health data sharing: Findings from a UK-wide survey


title: Intention to receive a COVID-19 vaccine: Results from a population-based survey in Canada

abstract:
BackgroundThe success of any COVID-19 vaccine program ultimately depends on high vaccine uptake. This study determined overall intention to receive a COVID-19 vaccine and identified factors that predict intentions to be vaccinated against COVID-19 in Canada, specifically in key priority groups identified by the American Committee on Immunization Practice (ACIP) and the National Advisory Committee on Immunization (NACI) for early immunization.

MethodsIndividuals from research cohorts from the general population of British Columbia aged 25-69 were invited complete an online survey based on validated scales and theoretical frameworks to explore intention to receive a COVID-19 vaccine. Two multivariable logistic regression models were conducted to determine factors associated with intention to receive the COVID-19 vaccine.

ResultsOf 4,948 respondents, 79.8% intended to receive a COVID-19 vaccine. In multivariable modeling, respondents who intended to receive the vaccine had higher vaccine attitudinal scores (p <0.001), reported greater influence of direct social norms (p = 0.001), and indirect social norms, including their family physician (p = 0.024), and Provincial Health Officer (p = 0.011). Older individuals (>60 years) were more likely to intend to receive the vaccine, while females (95%CI 0.57,0.93), those with less than high school education (95%CI 0.5,0.76), those who self-identified as non-white (95%CI 0.60,0.92), self-identified as Indigenous (95%CI 0.36,0.84) and essential non-health care workers (95%CI 0.59,0.86) had lower adjusted odds of intending to receive a COVID-19 vaccine.

ConclusionsTo optimize vaccine coverage, public health should focus on key messages around vaccine safety and benefit, and leverage trusted practitioners for messaging. As certain key populations identified by NACI and ACIP for early immunization report a lower intention to vaccinate, there is a need for in-depth education and support for these communities to ensure optimal uptake.

category: public and global health


title: The intersectional role of paternal gender-equitable attitudes and maternal empowerment on child undernutrition in India

abstract:
ObjectivesUndernutrition is a major global health concern, especially for the low- and middle-income countries. Despite several programmatic efforts by the government, prevalence of undernutrition among Indian children under five years was about 38% in 2015. While studies have extensively investigated the influence of sociodemographic and maternal related factors on child undernutrition, the paternal factors and their interactions with other causal factors are understudied. To fill this gap, we conducted an intersectional analysis to assess the relationship between maternal, paternal, and wealth related factors with stunting and severe stunting among underfives in India.

MethodsWe used a sample of 22,867 mother-father-child triads from the fourth round of Indias National Family Health Survey (2015-16). We fitted survey adjusted logistic regression models and further adjusted our models for several sociodemographic variables. Results: Our statistical models revealed that even among children from poorer households, those with either an empowered mother or a father with gender-equitable attitudes versus those with none such parents, had a lower odds of stunting (AOR: 0.92, CI: 0.84, 1.02) and severe stunting (AOR: 0.87, CI:0.77, 0.98), independent of all covariates.

ConclusionWe argue that while womens autonomy could reduce the risk of child undernutrition, focusing on mens attitudes towards gender equity also holds promise for reducing undernutrition. Our findings not only underscore how patriarchy is embodied in undernourished children, but also suggest programmatic interventions to address this deep-rooted scourge in India.


title: Ultrasound-Guided Needling and Lidocaine Plus Sterile Water Injection in Lumbar Spinal Stenosis

abstract:
ObjectiveTo study the effect of ultrasound-guided (USG) needling and lidocaine plus sterile water injections in lumbar spinal stenosis (LSS).

MethodThis retrospective study examined data of LSS patients who received USG lidocaine injection to lumbar facets, medial branches to facet joints, and multifidus muscles with one needle insertion at 4 spinal levels.

ResultsA total of 213 lumbar spinal stenosis patients--104 patients received USG needling and 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml injection (Group A) and 109 patients received 1% lidocaine without adrenaline 6 ml injection (Group B)--for 4 times, once per week. The VAS of chronic low back pain, radicular pain, claudication, and walking ability of both groups at 3, 6, and 12 months were significantly better than the baseline. Group A reported significantly better chronic low back pain, radicular pain, claudication, and walking ability at 3, 6, and 12 months than Group B.

ConclusionsUSG needling and 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml injection to lumbar facets, medial branches to facet joints, and multifidus muscles with one needle insertion at 4 spinal levels, once a week for 4 weeks can improve low back pain, radicular pain and gait ability in LSS with long term pain relief at least 12 months.

HighlightsO_LIThere is evidence of the long-lasting effectiveness of local anesthetic alone for chronic spinal pain on noxious peripheral stimulation, phenotypic changes for neuronal plasticity, and neurotransmitter release responsible for secondary hyperalgesia.
C_LIO_LIUSG needling and amount of safety solution as 1% lidocaine without adrenaline 2 ml plus sterile water 10 ml is effective for treating chronic low back pain, radicular pain, and claudication in LSS at least 12 months.
C_LIO_LIThese clinical outcomes should be the effects of peripheral and central desensitization. The other possible effect is the mechanical removal of fibrosis and calcification at lumbar facets, medial branches to facet joints, and multifidus muscles.
C_LI

category: rehabilitation medicine and physical therapy


title: Effectiveness of early versus delayed rehabilitation following rotator cuff repair: systematic review and meta-analyses

abstract:
ObjectiveTo investigate the effectiveness of early rehabilitation compared with delayed/standard rehabilitation after rotator cuff repair for pain, function, range of movement, strength, and repair integrity.

DesignSystematic review and meta-analyses.

MethodsWe searched databases and included randomised controlled trials (RCTs) comparing early with delayed/standard rehabilitation for patients undergoing rotator cuff repair surgery. We assessed risk of bias of the RCTs using the Cochrane RoB 2 tool.

ResultsTwenty RCTs, with 1841 patients, were included. The majority of the RCTs were of high or unclear risk of overall bias. We found substantial variations in the rehabilitation programmes, time in the sling and timing of exercise progression. We found no statistically significant differences for pain and function at any follow-up except for the outcome measure Single Assessment Numeric Evaluation at six months (MD: 6.54; 95%CI: 2.24-10.84) in favour of early rehabilitation. We found statistically significant differences in favour of early rehabilitation for shoulder flexion at six weeks (MD: 7.36; 95%CI: 2.66-12.06), three (MD: 8.45; 95%CI: 3.43-13.47) and six months (MD: 3.57; 95%CI: 0.81-6.32) and one year (MD: 1.42; 95%CI: 0.21-2.64) and similar differences for other planes of movement. In terms of repair integrity at one year, regarding early mobilisation, the number needed to harm was 651.

DiscussionCurrent approaches to early mobilisation, based largely on early introduction of passive movement, did not demonstrate significant differences in most clinical outcomes, although we found statistically significant differences in favour of early rehabilitation for range of movement. Importantly, there were no differences in repair integrity between early and delayed/standard rehabilitation. Most rehabilitation programmes did not consider early active movement as soon as the patient feels able. With ongoing variation in rehabilitation protocols there remains a need for large high quality RCT to inform the optimal approach to rehabilitation after rotator cuff repair surgery.


title: Outcomes following out-of-hours cholecystectomy: A systematic review and meta-analysis

abstract:
BackgroundCholecystectomy is one of the most commonly performed abdominal operations. Demands on acute operating theatre availability have led to out-of-hours (evenings, nights, or weekend) cholecystectomy being performed, although it is not known whether outcomes differ between out-of-hours and in-hours (daytime on weekdays) cholecystectomy.

ObjectiveThis systematic review and meta-analysis aimed to compare outcomes following out-of-hours versus in-hours urgent cholecystectomy.

MethodsMEDLINE, EMBASE and Scopus databases were systematically searched from inception to December 2020 for studies comparing outcomes from out-of-hours and in-hours urgent cholecystectomy in adults. The outcomes of interest were rates of bile leakage, bile duct injury (BDI), overall post-operative complications, conversion to open cholecystectomy, specific intra- and post-operative complications, length of stay (LOS), readmission and mortality. Sensitivity analysis of adjusted multivariate results was also performed.

ResultsIn total, 194,135 urgent cholecystectomies (30,001 out-of-hours; 164,134 in-hours) from 11 studies were included. Most studies were of high (64%) or medium (18%) quality. There were no differences between out-of-hours and in-hours cholecystectomy for rates of bile leakage, BDI, overall post-operative complications, conversion to open cholecystectomy, operative duration, readmission, mortality, and post-operative LOS. Higher rates of post-operative sepsis (odds ratio (OR) 1.58, 95% CI: 1.04-2.41; p=0.03) and pneumonia (OR 1.55, 95% CI: 1.06-2.26; p=0.02) were observed following out-of-hours cholecystectomy on univariate meta-analysis but not on adjusted multivariate meta-analysis.

ConclusionsThere was no increased risk or difference in specific complications associated with out-of-hours compared with in-hours urgent cholecystectomy.

category: surgery


title: Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US

abstract:
Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naive baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Significance StatementThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the US. Results show high variation in accuracy between and within stand-alone models, and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public health action.


title: Variations in housing affordability and health relationships by measurement and sub-population assessment.

abstract: Past studies have shown that the more unaffordable housing is to people, the worse their health, particularly mental health. However, the commonly used housing affordability indicator, the 30% measure, has limitations. There is evidence that other indicators, including the  30/40 measure, might be more precise in characterizing housing unaffordability by taking into account absolute values of household incomes. In this paper, we use cross-sectional data from the UK Household Longitudinal Study, to evaluate relationships between two affordability measures (30%, 30/40) with 3 health measures: general, physical and mental health. We use logistic regression and effect modification to test whether relationships varied by age, ethnicity, housing tenure, urbanicity and sex. Out of 35,114 participants with complete data, housing was classified as unaffordable for 24.2% using the 30% measure and 10.2% for the 30/40 measure. In age-adjusted analyses, higher unaffordability was associated with worse health for all three health measures, with associations stronger for the 30/40 vs the 30% unaffordability measure. In models adjusted for age, sex and urbanicity, both ethnicity and tenure independently modified associations; with modification showing small differences by unaffordability and health measure. Further studies are needed to disentangle complex relationships between household income, housing costs, ethnicity and tenure.

category: health economics


title: Uncovering interpretable potential confounders in electronic medical records

abstract: Randomized clinical trials (RCT) are the gold standard for informing treatment decisions. Observational studies are often plagued by selection bias, and expert-selected covariates may insufficiently adjust for confounding. We explore how unstructured clinical text can be used to reduce selection bias and improve medical practice. We develop a framework based on natural language processing to uncover interpretable potential confounders from text. We validate our method by comparing the estimated hazard ratio (HR) with and without the confounders against established RCTs. We apply our method to four cohorts built from localized prostate and lung cancer datasets from the Stanford Cancer Institute and show that our method shifts the HR estimate towards the RCT results. The uncovered terms can also be interpreted by oncologists for clinical insights. We present this proof-of-concept study to enable more credible causal inference using observational data, uncover meaningful insights from clinical text, and inform high-stakes medical decisions.

category: health informatics


title: Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle?

abstract: AbstractCOVID-19 vaccination is being conducted in over 190 countries/regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remain a key question for policy makers. To address it, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable to keep the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.


title: To what extent do we need to rely on non-pharmaceutical interventions while COVID-19 vaccines roll out in 2021?


title: Outdoor air pollution and the risk of asthma exacerbations in single lag0 and lag1 exposure patterns: A systematic review and meta-analysis

abstract:
BackgroundAsthma exacerbations accelerate the disease progression, as well as increases the incidence of hospitalizations and deaths. There have been studies on the effects of outdoor air pollution and asthma exacerbations; however, evidence regarding single lag0 and lag1 exposure patterns is inconclusive.

ObjectiveTo synthesize evidence regarding the relationship between outdoor air pollution and the asthma exacerbation risk in single lag0 and lag1 exposure patterns.

MethodsWe performed a systematic literature search using PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials, China National Knowledge Internet, Chinese BioMedical, and Wanfang databases until August 1st, 2020. Additionally, we reviewed the reference lists of the relevant articles. Two authors independently evaluated the eligible articles and performed structured extraction of relevant information. Pooled relative risks (RRs) and 95% confidence intervals (CIs) of lag0 and lag1 exposure patterns were estimated using the random-effect models.

ResultsEighty-four studies met the eligibility criteria and provided sufficient information for meta-analysis. Outdoor air pollutants were associated with significantly increased risks of asthma exacerbations in both single lag0 and lag1 exposure patterns [lag0: RR (95%CI) (pollutants), 1.057(1.011, 1.103) (air quality index; AQI), 1.007(1.005, 1.010) (PM2.5), 1.009(1.005, 1.012) (PM10), 1.010(1.006, 1.014) (NO2), 1.030(1.011, 1.048) (CO), 1.005(1.002, 1.009) (O3); lag1: RR (95%CI) (pollutants), 1.064(1.022, 1.106) (AQI), 1.005(1.002, 1.008) (PM2.5), 1.007(1.004, 1.011) (PM10), 1.008(1.004, 1.012) (NO2), 1.025(1.007, 1.042) (CO), 1.010(1.006, 1.013) (O3)], except SO2 [lag0: RR (95%CI), 1.004(1.000, 1.007); lag1: RR (95%CI), 1.003(0.999, 1.006)]. Subgroup analyses revealed stronger effects in children and asthma exacerbations associated with other events (including symptoms, lung function changes, and medication use as required).

ConclusionThese findings demonstrate that outdoor air pollution significantly increases the asthma exacerbation risk in single lag0 and lag1 exposure patterns.

PROSPERO registration numberCRD42020204097 (https://www.crd.york.ac.uk/PROSPERO).

Strengths and limitations of this studyO_LIWe performed a systematic literature search of six databases (with no specified start date or language limitation).
C_LIO_LISecondary references were included.
C_LIO_LIPublication bias was assessed by applying Beggs and Eggers tests.
C_LIO_LIThis study focused on the association between outdoor air pollution and the asthma exacerbation risk in single lag0 and lag1 exposure patterns.
C_LIO_LIThere were few available studies regarding the AQI, other events, and death analyses.
C_LI

category: respiratory medicine


title: Assessing knowledge, concerns, and risk perceptions among Italian medical students during the SARS-CoV-2 pandemic.

abstract:
INTRODUCTIONDuring the first phase of COVID-19 pandemic, Italian medical students transitioned from in-person to remote learning. This study was carried out to early assess students sources of information, perceived risk of infection, knowledge and preventive practices in order to resume academic activity. The impact of training and volunteer work was also assessed.

METHODSA cross-sectional online survey was conducted in May 2020 among medical students enrolled in the School of Medicine and Surgery, Bologna University.

RESULTSThe analysis included 537 responses. On average students used seven sources of information on COVID-19. Scientific journals were considered the most trustworthy but they ranked only 6th in the frequency of use. Perceived risk of infection was higher for academic activities, especially in the hospital than daily living activities. Less than 50% of students reported being trained on biological risk and use of PPE. Training received was significantly associated with both perceived risk of infection and confidence in the use of PPE. Students engaged in volunteer work had higher confidence in PPE usage.

DISCUSSIONAccessible scientific information and students engagement in spreading correct knowledge play an important role in challenging misinformation during the pandemic crisis. Students showed suboptimal knowledge about PPE use, calling for additional training. We found a moderate-high perceived risk of infection that could be mitigated with specific educational programs and by promoting voluntary work. Students engagement in public health emergencies (PHE) could potentially be beneficial for their training and as well as for the healthcare system.

category: medical education


title: Comprehensive Study of Germline Mutations and Double-Hit Events in Esophageal Squamous Cell Cancer

abstract: Esophageal squamous cell cancer (ESCC) is the eighth most common cancer around the world. Several reports have focused on somatic mutations and common germline mutations in ESCC. However, the contributions of pathogenic germline alterations in cancer susceptibility genes (CSGs), highly frequently mutated CSGs, and pathogenically mutated CSG-related pathways in ESCC remain unclear. We obtained data on 571 ESCC cases from public databases and East Asian from the 1000 Genomes Project database and the China Metabolic Analytics Project database to characterize pathogenic mutations. We detected 157 mutations in 75 CSGs, accounting for 25.0% (143/571) of ESCC cases. Six genes had more than five mutations: TP53 (n = 15 mutations), GJB2 (n = 8), BRCA2 (n = 6), RECQL4 (n = 6), MUTYH (n = 6), and PMS2 (n = 5). Our results identified significant differences in pathogenic germline mutations of TP53, BRCA2, and RECQL4 between the ESCC and control cohorts. Moreover, we identified 84 double-hit events (16 germline/somatic double-hit events and 68 somatic/somatic double-hit events) occurring in 18 tumor suppressor genes from 83 patients. Patients who had ESCC with germline/somatic double-hit events were diagnosed at younger ages than patients with the somatic/somatic double-hit events, although the correlation was not significant. Fanconi anemia was the most enriched pathway of pathogenically mutated CSGs, and it appeared to be a primary pathway for ESCC predisposition. The results of this study identified the underlying roles that pathogenic germline mutations in CSGs play in ESCC pathogenesis; increased our awareness about the genetic basis of ESCC; and provided suggestions for using highly mutated CSGs and double-hit features in the early discovery, prevention, and genetic counseling of ESCC.

category: oncology


title: Is the quality of hospital EHR data sufficient to evidence its ICHOM outcomes performance in heart failure? A pilot evaluation

abstract:
There is increasing recognition that healthcare providers need to focus attention, and be judged against, the impact they have on the health outcomes experienced by patients. The measurement of health outcomes as a routine part of clinical documentation is probably the only scalable way of collecting outcomes evidence, since secondary data collection is expensive and error prone. However, there is uncertainty about whether routinely collected clinical data within EHR systems includes the data most relevant to measuring and comparing outcomes, and if those items are collected to a good enough data quality to be relied upon for outcomes assessment, since several studies have pointed out significant issues regarding EHR data availability and quality.

In this paper, we first describe a practical approach to data quality assessment of health outcomes, based on a literature review of existing frameworks for quality assessment of health data and multi-stakeholder consultation. Adopting this approach, we perform a pilot study on a subset of 21 International Consortium for Health Outcomes Measurement (ICHOM) outcomes data items from patients with congestive heart failure. To this end, all available registries compatible with the diagnosis of heart failure within the IMASIS-2 data repository connected to the Hospital del Mar network (142,345 visits of 12,503 patients) were extracted and mapped to the ICHOM format. We focus our pilot assessment on five commonly used data quality dimensions: completeness, correctness, consistency, uniqueness and temporal stability.

Overall, this pilot study reveals high scores on the consistency, completeness and uniqueness dimensions. Temporal stability analyses show some changes over time in the reported use of medication to treat heart failure, as well as in the recording of past medical conditions. Finally, investigation of data correctness suggests several issues concerning the proper characterization of missing data values. Many of these issues appear to be introduced while mapping the IMASIS-2 relational database contents to the ICHOM format, as the latter requires a level of detail which is not explicitly available in the coded data of an EHR.

To truly examine to what extent hospitals today are able to routinely collect the evidence of their success in achieving good health outcomes, future research would benefit from performing more extensive data quality assessments, including all data items from the ICHOM heart failure standard set, across multiple hospitals.


title: Vaccine Efficacy at a Point in Time

abstract: Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to describe a vaccines total effects, requires frequent longitudinal sampling to capture all infections. Such sampling may not always be feasible. A logistically easy approach is to collect a sample to test for infection at a regularly scheduled visit. Such point or cross-sectional sampling does not permit estimation of classic vaccine effiacy on infection, as long duration infections are sampled with higher probability. Building on work by Rinta-Kokko and others (2009) we evaluate proxies of the vaccine effect on transmission at a point in time; the vaccine efficacy on prevalent infection and on prevalent viral load, VEPI and VEPV L, respectively. Longer infections with higher viral loads should have more transmission potential and prevalent vaccine efficacy naturally captures this aspect. We apply a proportional hazards model for infection risk and show how these metrics can be estimated using longitudinal or cross-sectional sampling. We also introduce regression models for designs with multiple cross-sectional sampling. The methods are evaluated by simulation and a phase III vaccine trial with PCR cross-sectional sampling for subclinical infection is analyzed.

category: infectious diseases


title: Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood

abstract:
BackgroundTo reduce lung cancer burden in the US, a better understanding of biological mechanisms in early disease development could provide new opportunities for risk stratification.

MethodsIn a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 men and women in the 1989 CLUE II cohort. Median time from blood drawn to diagnosis was 14 years for all participants. We compared DNA methylation levels by case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years based smoking methylation score. Stratification analyses were conducted by time from blood draw to diagnosis, histology, and smoking status.

ResultsWe identified sixteen single CpG sites and forty DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 x 10-7). For the DMRs, we found that CpG sites in the HOXA4 region were hypermethylated in cases compared to controls.

ConclusionThe single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing new insights into the biological processes of early lung cancer development and potential biomarkers for lung cancer risk stratification.


title: Was R<1 before the English lockdowns? On modelling mechanistic detail, causality and inference about Covid-19

abstract: Detail is a double edged sword in epidemiological modelling. The inclusion of mechanistic detail in models of highly complex systems has the potential to increase realism, but it also increases the number of modelling assumptions, which become harder to check as their possible interactions multiply. In a major study of the Covid-19 epidemic in England, Knock et al. (2020) fit an age structured SEIR model with added health service compartments to data on deaths, hospitalization and test results from Covid-19 in seven English regions for the period March to December 2020. The simplest version of the model has 684 states per region. One main conclusion is that only full lockdowns brought the pathogen reproduction number, R, below one, with R >> 1 in all regions on the eve of March 2020 lockdown. We critically evaluate the Knock et al. epidemiological model, and the semi-causal conclusions made using it, based on an independent reimplementation of the model designed to allow relaxation of some of its strong assumptions. In particular, Knock et al. model the effect on transmission of both non-pharmaceutical interventions and other effects, such as weather, using a piecewise linear function, b(t), with 12 breakpoints at selected government announcement or intervention dates. We replace this representation by a smoothing spline with time varying smoothness, thereby allowing the form of b(t) to be substantially more data driven, and we check that the corresponding smoothness assumption is not driving our results. We also reset the mean incubation time and time from first symptoms to hospitalisation, used in the model, to values implied by the papers cited by Knock et al. as the source of these quantities. We conclude that there is no sound basis for using the Knock et al. model and their analysis to make counterfactual statements about the number of deaths that would have occurred with different lockdown timings. However, if fits of this epidemiological model structure are viewed as a reasonable basis for inference about the time course of incidence and R, then without very strong modelling assumptions, the pathogen reproduction number was probably below one, and incidence in substantial decline, some days before either of the first two English national lockdowns. This result coincides with that obtained by more direct attempts to reconstruct incidence. Of course it does not imply that lockdowns had no effect, but it does suggest that other non-pharmaceutical interventions (NPIs) may have been more effective than Knock et al. imply, and that full lockdowns were probably not the cause of R dropping below one.


title: Independent associations of sleep timing, duration and quality with adiposity and weight status in a national sample of adolescents: the UK Millennium Cohort Study

abstract:
BackgroundThere is evidence that short sleep elevates obesity risk in youth, but sleep is a multidimensional construct and few studies have investigated parameters beyond duration.

ObjectivesTo investigate if sleep onset time, duration, latency, and night waking frequency are independently associated with adiposity and weight status in adolescents.

MethodsThis was a cross-sectional observational study of 10,619 13-15y olds who provided self-reported sleep characteristics and underwent an anthropometric assessment to determine adiposity (body mass index (BMI) z-score and percent body fat (%BF)) and weight status. Adjusted linear and logistic regressions were used to investigate associations.

ResultsCompared to a sleep onset time before 10pm, later sleep was associated with higher adiposity and higher likelihood of overweight and obesity in boys (after midnight, odds ratio (95% CI): 1.76 (1.19 to 2.60), p=0.004) and girls (between 11-11:59pm: 1.36 (1.17 to 1.65), p=0.002). Compared to sleeping for >9-10 hours, sleeping for [≤]8 hours was associated with higher likelihood of overweight and obesity (boys: 1.80 (1.38 to 2.35), p<0.001); girls: 1.38 (1.06 to 1.79), p=0.016); there was evidence of a U-shaped association in girls for whom >10 hours of sleep was also associated with higher likelihood of overweight and obesity (1.31 (1.06 to 1.62); p=0.014). In girls, relative to a sleep latency of 16-30 minutes, sleep latencies [≥]46 minutes were associated with higher adiposity (46-60 minutes, %BF: 1.47 (0.57 to 2.36), p=0.001) and higher likelihood of overweight and obesity (46-60 minutes: 1.39 (1.05 to 1.83); p=0.020). Often as opposed to never waking in the night was also associated with higher adiposity in girls (BMI z-score: 0.24 (0.08 to 0.41), p=0.004; %BF: 1.44 (0.44 to 2.44), p=0.005).

ConclusionsSleep duration and timing, and sleep quality in girls, are independently associated with adiposity and weight status in adolescence and may be important targets for obesity prevention.


title: Demographic and clinical characteristics of patients with functional motor disorders: the prospective Salpetriere cohort.

abstract:
Functional motor disorders (FMD) are common and disabling. They are known to affect predominantly women and to start at young or middle age but to date, large case series are lacking, and demographic and clinical characteristics of patients with FMD rely on data from small cohorts. The current study aimed at describing the demographic and clinical characteristics of a large cohort of FMD patients.

MethodsWe prospectively collected data from FMD patients who were referred to the Neurophysiology Department of the Pitie-Salpetriere University Hospital between 2008 and 2016 for treatment with repeated transcranial magnetic stimulation.

Results482 patients were included. There was a majority of women (73.7%) with a median age of 40 years old at TMS treatment. Median age at symptoms onset was 35.5 years old and symptoms were mostly characterized by an acute (47.3%) or subacute (46%) onset. Only 23% of patients were active workers while 58.3% were unemployed for medical reasons. Half of the patients suffered from functional motor weakness (n= 241) and the other half suffered from movement disorders (n=241), mainly represented by tremor (21.15%) and dystonia (20.5%). 33.6% had no psychiatric comorbidity and 17.4% reported no history of trauma. No significant differences were found in age or gender according to clinical phenotypes.

ConclusionWe present the largest cohort of patients with FMD to date. This cohort will contribute to a better understanding of FMDs and their risk factors.

category: neurology


title: Symptom Prediction and Mortality Risk Calculation for COVID-19 Using Machine Learning

abstract:
BackgroundEarly prediction of symptoms and mortality risks for COVID-19 patients would improve healthcare outcomes, allow for the appropriate distribution of healthcare resources, reduce healthcare costs, aid in vaccine prioritization and self-isolation strategies, and thus reduce the prevalence of the disease. Such publicly accessible prediction models are lacking, however.

MethodsBased on a comprehensive evaluation of existing machine learning (ML) methods, we created two models based solely on the age, gender, and medical histories of 23,749 hospital-confirmed COVID-19 patients from February to September 2020: a symptom prediction model (SPM) and a mortality prediction model (MPM). The SPM predicts 12 symptom groups for each patient: respiratory distress, consciousness disorders, chest pain, paresis or paralysis, cough, fever or chill, gastrointestinal symptoms, sore throat, headache, vertigo, loss of smell or taste, and muscular pain or fatigue. The MPM predicts the death of COVID-19-positive individuals.

ResultsThe SPM yielded ROC-AUCs of 0.53-0.78 for symptoms. The most accurate prediction was for consciousness disorders at a sensitivity of 74% and a specificity of 70%. 2440 deaths were observed in the study population. MPM had a ROC-AUC of 0.79 and could predict mortality with a sensitivity of 75% and a specificity of 70%. About 90% of deaths occurred in the top 21 percentile of risk groups. To allow patients and clinicians to use these models easily, we created a freely accessible online interface at www.aicovid.org.

ConclusionsThe ML models predict COVID-19-related symptoms and mortality using information that is readily available to patients as well as clinicians. Thus, both can rapidly estimate the severity of the disease, allowing shared and better healthcare decisions with regard to hospitalization, self-isolation strategy, and COVID-19 vaccine prioritization in the coming months.

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title: Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness

abstract: We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel agent-based modeling approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatio-temporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals degree (number of social contacts) and total social proximity time is significantly more effective than the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result in reducing an additional 56-110k infections, 3.2-5.4k hospitalizations, and 700-900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3-6 million fewer infections, 181-306k fewer hospitalizations, and 51-62k fewer deaths compared to age-based allocation. The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.


title: SARS-CoV-2 Worldwide Replication Drives Rapid Rise and Selection of Mutations across the Viral Genome: A Time-Course StudyPotential Challenge for Vaccines and Therapies

abstract:
Scientists and the public were alarmed at the first large viral variant of SARS-CoV2 reported in December 2020. We have followed the time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries on four continents. We examined complete SARS-CoV-2 nucleotide sequences in GISAID, (Global Initiative of Sharing All Influenza Data) with sampling dates extending until January 20, 2021. These sequences originated from ten different countries: United Kingdom, South Africa, Brazil, USA, India, Russia, France, Spain, Germany, and China. Among the novel mutations, some previously reported mutations waned and some of them increased in prevalence over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the so-called UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, now called P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS-CoV-2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests.

Significance and New Aspects of Study - SynopsisO_LIWe examine the time course of emerging mutations in the SARS-CoV-2 genome that have rapidly been selected in the worlds populations through the beginning of 2021. A study of the prevalence of viral mutations in the GISAID database in ten different countries - United Kingdom, South Africa, Brazil, US, India, Russia, France, Spain, Germany, and China - revealed widespread mutations along the genome.
C_LIO_LIWe previously identified about 10 hotspot mutations in the SARS-CoV-2 genome that became prevalent in many of the countries studied1. Since the beginning of February, many new mutations arose in the ten countries (and worldwide). The preponderance of variants and mutations correlated with the increased spread of Covid-19.
C_LIO_LIThere was a temporal progression from about 10 predominant mutants shared by several countries up to the end of May 2020, followed by a consistent and rapid increase in the number of new mutations between June and December along with the emergence of variants of concern, first reported in December 2020.
C_LIO_LIWe examine the relative frequencies of mutations, along with variants of interest, in 10 countries up until January 20, 2021. Investigations on the pathogenic properties of individual SARS-CoV-2 mutations will be urgently needed to understand the kaleidoscopic patterns of worldwide Covid-19 outbreaks and symptoms. Monitoring the frequency and speed of mutant selection have direct relevance to diagnostic testing, vaccines and therapeutics.
C_LIO_LIAs an explanation for efficient viral mutagenesis, we hypothesize that the viral spike protein - as documented - facilitates viral entry via the cells ACE receptor2. This in turn interacts with the APOBEC polypeptide, an m-RNA editing function. The actually observed frequent C to U (T) transitions and other base exchanges are thus effected. Hence, as one of the earliest steps upon viral entry, active mutagenesis commences, since SARS-CoV-2 exploits one of the cells defenses against viral infections.
C_LI


title: The systemic inflammatory response and clinicopathological characteristics in patients admitted to hospital with COVID-19 infection: Comparison of 2 consecutive cohorts

abstract:
BackgroundIn order to manage the COVID-19 systemic inflammatory response, it is important to identify clinicopathological characteristics across multiple cohorts.

MethodsElectronic patient records for 2 consecutive cohorts of patients admitted to two urban teaching hospitals with COVID-19 during two 7-week periods of the COVID-19 pandemic in Glasgow, U.K. (cohort 1: 17th March 2020 - 1st May 2020) and (cohort 2: 18th May 2020 - 6th July 2020) were examined for routine clinical, laboratory and clinical outcome data.

ResultsCompared with cohort 1, cohort 2 were older (p<0.001), more likely to be female (p<0.05) and have less independent living circumstances (p<0.001). More patients in cohort 2 were PCR positive, CXR negative (both p<0.001) and had low serum albumin concentrations (p<0.001). 30-day mortality was similar between both cohorts (23% and 22%). Over the 2 cohorts, age [≥]70 (p<0.001), male gender (p<0.05), hypertension (p<0.01), heart failure (p<0.05), cognitive impairment (p<0.001), frailty (p<0.001), COPD (p<0.05), delirium (p<0.001), elevated perioperative Glasgow Prognostic Score (p[≤]0.001), elevated neutrophil-lymphocyte ratio (p<0.001), low haematocrit (p<0.01), elevated urea (p<0.001), creatinine (p<0.001), glucose (p<0.05) and lactate (p<0.01); and the 4C score were associated with 30-day mortality. When compared with the 4C score, greater frailty (OR 10.2, 95% C.I. 3.4 - 30.6, p<0.01) and low albumin (OR 5.6, 95% C.I. 2.0 - 15.6, p<0.01) were strongly independently associated with 30-day mortality.

ConclusionIn addition to the 4C mortality score, frailty score and a low albumin were strongly independently associated with 30-day mortality in two consecutive cohorts of patients admitted to hospital with COVID-19.

Article summaryO_LIIn two consecutive cohorts of patients with COVID-19 infection admitted to two urban teaching hospitals in Glasgow, UK, there were variations in a number of clinicopathological characteristics despite similar mortality (23 and 22%).
C_LIO_LIIn these two cohorts, in a multivariate analysis that included the 4C mortality score, clinical frailty score >3, low serum albumin concentration (<35 g/L), high neutrophil-lymphocyte ratio ([≥]5), and abnormal serum sodium concentration (<133/>145 mmol/L) remained independently associated with 30-day mortality.
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category: emergency medicine


title: Assessing the performance of a serological point-of-care test in measuring detectable antibodies against SARS-CoV-2

abstract:
ObjectiveTo investigate the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay.

MethodsSerological testing was conducted on 708 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity.

ResultsSARS-CoV-2 seroprevalence was 63.4% (449/708; 95% CI 59.8%-66.9%) using the BioMedomics assay and 71.9% (509/708; 95% CI 68.5%-75.1%) using the Elecsys assay. There were 62 discordant results between the two assays. One specimen was seropositive in the BioMedomics assay, but seronegative in the Elecsys assay, while 61 specimens were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Positive, negative, and overall percent agreements between the two assays were 88.0% (95% CI 84.9%-90.6%), 99.5% (95% CI 97.2%-99.9%), and 91.2% (95% CI 88.9%-93.1%), respectively, with a Cohens kappa of 0.80 (95% CI 0.77-0.83), indicating excellent agreement. Excluding specimens with lower antibody titers, the agreement improved with positive, negative, and overall percent concordance of 91.2% (95% CI 88.2%-93.6%), 99.5% (95% CI 97.2%-99.9%), and 93.9% (95% CI 91.7%-95.5%), respectively, and a Cohens kappa of 0.87 (95% CI 0.84-0.89). Logistic regression confirmed better agreement with higher antibody titers.

ConclusionThe BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated excellent performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and possible vaccine prioritization.


title: Time of day influences psychophysical measures in women with burning mouth syndrome

abstract:
Burning mouth syndrome (BMS) is a chronic orofacial pain condition that mainly affects postmenopausal women. BMS type I patients report little to no spontaneous pain in the morning and increases in pain through the day, peaking in the afternoon. Quantitative sensory testing (QST) findings from BMS type 1 patients are inconsistent as they fail to capture this temporal variation. We examined how QST in BMS type 1 compared to healthy participants was affected by time of day. QST of the face and forearm included warmth detection threshold (WDT), cold detection threshold (CDT), and heat pain thresholds (HPT), ratings of suprathreshold heat, and pressure pain thresholds (PPT), and was performed twice: once in the morning and once in the afternoon. BMS patients reported: no differences in morning and afternoon comparisons of the orofacial region between groups and no differences in PPTs in either orofacial or arm regions between groups; lower within group PPTs of the masseter in the afternoon; higher WDTs, and lower CDTs of the forearm in the morning compared to healthy participants; lower CDTs and higher pain intensity ratings to heat stimuli at low temperatures on the forearm in the afternoon compared to healthy participants. The findings indicate that compared to healthy participants, BMS Type I patients had altered thermal sensitivity, which depended on body area tested (forearm vs orofacial region), and higher pain sensitivity, which was slightly more pronounced in the afternoon plausibly due to a hypervigilance.

PerspectiveSomatosensory profiles in BMS type 1 can be affected by time of day, possibly as an effect of spontaneous burning pain that increases throughout the day. Our findings highlight the cyclical effect of BMS pathophysiology across a day, which may further help clinicians choose appropriate treatment strategies for BMS patients.

category: pain medicine


title: Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome: A single center experience from Pune, Western India

abstract:
BackgroundCytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednisolone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for the treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroids in COVID-19 associated CRS.

MethodsThis retrospective cohort study was conducted at a tertiary level private hospital in Pune, India between 2nd April and 2nd November 2020. All patients administered TCZ and steroids for treatment of CRS were included. The primary endpoint was incidence of all-cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of infectious complications. Baseline and time-dependent risk factors significantly associated with death were identified by Relative risk estimation.

ResultsOut of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. Median age of the cohort was 57 (IQR: 46.5, 66) years. Almost 72 % patients had preexisting co-morbidities. Median time to TCZ administration since onset of symptoms was 9 days (IQR: 7, 11). 63% patients needed intensive care unit (ICU) admission. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Infectious complications like hospital acquired pneumonia, bloodstream bacterial and fungal infections were observed in 2.13 %, 2.13 % and 0.06 % patients respectively. Age [≥] 60 years (p=0.014), presence of co-morbidities like hypertension (p = 0.011), IL-6 [≥] 100 pg/ml (p = 0.002), D-dimer [≥] 1000 ng/ml (p < 0.0001), CT severity index [≥] 18 (p < 0.0001) and systemic complications like lung fibrosis (p = 0.019), cardiac arrhythmia (p < 0.0001), hypotension (p < 0.0001) and encephalopathy (p < 0.0001) were associated with increased risk of death.

ConclusionsCombination therapy of TCZ and Steroids is likely to be safe and effective in the management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled clinical trials.


title: Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States

abstract: As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.


title: Investigating the impact of London's Ultra Low Emission Zone on children's health: Children's Health in London and Luton (CHILL): Protocol for a prospective parallel cohort study

abstract:
IntroductionAir pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are therefore urgently needed not only to improve public health now, but to prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver clear health benefits is lacking. We established a natural experiment design study (CHILL: Childrens Health in London and Luton) to evaluate the impacts of the introduction of Londons Ultra Low Emission Zone (ULEZ) on childrens health.

Methods and analysisCHILL is a prospective two-arm parallel longitudinal cohort study of children aged 6-9 years, attending primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site). The primary goal of the study is to examine the impact of changes in annual air pollutant exposures as oxides of nitrogen, nitrogen dioxide, particulate matter less than 2.5microns and 10microns (NOx, NO2, PM2.5, PM10 respectively) across the two sites on lung growth, measured as forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), over four consecutive years. Secondary outcomes being investigated include a range of respiratory health indicators as well as inequality and health economic measures.

Ethics and disseminationEthics approval has been given by Queen Mary University of London Research Ethics Committee (ref 2018/08). Dissemination will target audiences through a variety of channels, including research papers, conference and media presentations, web summaries and social media. CHILL is funded by National Institute for Health Research (NIHR) Public Health Research (Ref 16/139/09) with additional funding by Natural Environment Research Council, NIHR CLAHRC North Thames, NIHR ARC North Thames, and the Mayor of London. ClinicalTrials.gov: NCT04695093

Strengths and limitations of this studyO_ST_ABSStrengthsC_ST_ABSO_LICHILL uses a prospective parallel cohort design, allowing robust conclusions to be drawn on the impact of the ULEZ - a major city-wide air quality mitigation strategy - on air quality and childrens respiratory health.
C_LIO_LICHILL study cohorts include children from large and ethnically diverse populations living in urban areas characterised by poor air quality.
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LimitationsO_LIAttrition of study cohort population over time, although this has been accounted for in the original design of the study.
C_LIO_LIPotential diminution of the ULEZ air pollution signal due to pre-compliance with ULEZ restrictions in the run up to the introduction of the scheme in Central London on the 8th April 2019, and minor impacts of other pollution mitigation measures.
C_LIO_LIAdded complexity of accounting for effects of COVID-19 and related lockdowns on traffic flows, air quality and childrens health.
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title: Genetic Contributions to Alcohol Use Disorder Treatment Outcomes: A Genome-wide Pharmacogenomics Study

abstract: Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; [≥]5 drinks for men, [≥]4 drinks for women in a day), during the first three months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N=1090 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p=1.6E-08) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p=3.9E-08; acamprosate TR: rs77583603, p=3.1E-09). The top association signals for TR (p=7.7E-08) and second strongest signal in the THR (p=6.1E-08) analysis of the naltrexone-treated subset map to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p=3.7E-04) and THR (p=2.6E-04). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.

category: genetic and genomic medicine


title: Dental biofilm microbiota dysbiosis is associated with the risk of aGVHD after allogeneic HSCT

abstract: Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 20% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.

category: hematology


title: Dental biofilm microbiota dysbiosis is associated with the risk of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation


title: Morphological Patterns Of Anemia Among Under Five Children On Prevention Of Mother-To-Child Transmission (PMTCT) Programmes In Masogo Sub-County Hospital, Kisumu County, Kenya.

abstract:
BackgroundAnaemia during childhood adversely affects mental, physical and social development of the children, therefore morphological patterns of anaemia in under-five children are considered essential for classification, diagnosis and management.

AimThis study aimed at assessing morphological patterns, the prevalence and associated factors of anaemia among under-five children on Prevention of Mother-To-Child Transmission (PMTCT) programmes in Masogo sub-county hospital, Kisumu County, Kenya.

MethodA cross-sectional health facility-based study was conducted among 175 children aged 6 to 59 months who attended clinic for the PMTCT programme for the period of January 2020 to December 2020. Pretested and structured questionnaires were used to collect socioeconomic and demographic characteristics of the family and child. Capillary blood sample was collected from each child for malaria parasite and Peripheral Blood Film (PBF) examination.

ResultComplete blood counts indicate that microcytic pattern was the most common, representing 30 (42.3%) followed by microcytic hypochromic pattern 20 (28.2%), normocytic normochromic pattern with 11 (15.5%) and lastly dimorphic pattern with 10 (14.0%). High prevalence of anaemia was observed in children who were urban dwellers (50.0%), in children whose mothers aged 18-27 years (44.0%) and had no formal education (48.1%). Besides, the high prevalence rate of anaemia was found among children with a family monthly income of less than 500 Ksh. (46.9%), early (<6 months) introduction of complementary foods (71.4%)

ConclusionThis study has revealed that the prevalence of anaemia in children less than five years is high and is a severe public health problem in the study area. Therefore, the policymakers should make a strategy that can reduce poverty and increase the awareness to women on breastfeeding, nutrition, and other associated factors to reduce anaemia.


title: SARS-CoV-2 Transmission Risk from sports Equipment (STRIKE)

abstract:
OBJECTIVESTo investigate the potential of shared sporting equipment as transmission vectors of SARS-CoV-2 during the reintroduction of sports such as soccer, rugby, cricket, tennis, golf and gymnastics.

SETTINGLaboratory based live SARS-CoV-2 virus study

INTERVENTIONSTen different types of sporting equipment were inoculated with 40l droplets containing clinically relevant high and low concentrations of live SARS-CoV-2 virus. Materials were then swabbed at time points relevant to sports (1, 5, 15, 30, 90 minutes). The amount of live SARS-CoV-2 recovered at each time point was enumerated using viral plaque assays, and viral decay and half-life was estimated through fitting linear models to log transformed data from each material.

MAIN OUTCOME MEASUREThe primary outcome measure was quantification of retrievable SARS-CoV-2 virus from each piece of equipment at pre-determined time points.

RESULTSAt one minute, SARS-CoV-2 virus was recovered in only seven of the ten types of equipment with the low dose inoculum, one at five minutes and none at 15 minutes. Retrievable virus dropped significantly for all materials tested using the high dose inoculum with mean recovery of virus falling to 0.74% at 1 minute, 0.39% at 15 minutes and 0.003% at 90 minutes. Viral recovery, predicted decay, and half-life varied between materials with porous surfaces limiting virus transmission.

CONCLUSIONSThis study shows that there is an exponential reduction in SARS-CoV-2 recoverable from a range of sports equipment after a short time period, and virus is less transferrable from materials such as a tennis ball, red cricket ball and cricket glove. Given this rapid loss of viral load and the fact that transmission requires a significant inoculum to be transferred from equipment to the mucous membranes of another individual it seems unlikely that sports equipment is a major cause for transmission of SARS-CoV-2. These findings have important policy implications in the context of the pandemic and may promote other infection control measures in sports to reduce the risk of SARS-CoV-2 transmission and urge sports equipment manufacturers to identify surfaces that may or may not be likely to retain transferable virus.

O_TEXTBOXWHAT IS ALREADY KNOWN ON THIS TOPICO_LITransmission of SARS-CoV-2 between individuals playing sport may be via respiratory droplets when in close proximity to an infected person.
C_LIO_LISARS-CoV-2 remains viable on a variety of surfaces resulting in recommendations to reduce the sharing of sports equipment such as tennis balls when sports were re-opened.
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WHAT THIS STUDY ADDSO_LIThe recoverable SARS-CoV-2 viral load reduces exponentially with mean viral load of all materials less than 1% of the original inoculum after 1 minute.
C_LIO_LIThe type of material has a significant effect on SARS-CoV-2 transfer, with less virus transferred from porous materials such as bovine leather or nylon woven cloth.
C_LIO_LIPolicies on infection control measures in sport may be better directed towards areas other than reducing the sharing of sports equipment.
C_LIO_LISports equipment manufacturers may consider using materials that absorb or retain virus as a way of reducing viral transmission from sports equipment.
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