How social engagement against Covid-19 in a Brazilian Slum helped mitigate rising statistics ObjectivesFor many underdeveloped countries, strategies implemented by social communities allied to scientific knowledge may be a rote to attenuate the rapid spread of Covid-19 cases and allow services to the population. This work presents a joint effort collaboration between scientists and underserved community groups from a Brazilian slum/Santa Marta in Rio de Janeiro City in the fight against Covid-19. Measurements of contamination in the air near the ground, georeferencing of data of infected people, were regressed with sanitization activities aiming at reducing the Covid-19 incidence.

MethodsWe monitored aerosol containing SARS-Cov-2 virus in outdoor ambient air using various virus collection mediums (solid, liquid, and gelatinous substrates) at different aerodynamic sizes. We implemented a local statistics survey for the Covid-19 database correlated with varying sanitization levels between April 2020 and June 2021 developed in the Santa Marta slum.

FindingsWe detected the SARS-CoV-2 virus in the air near the ground in diameters ranging from 0.25 to 0.5 {micro}m, demonstrating that there is a circulation of the virus in the slum atmosphere. We demonstrate that Covid-19 cases for the Santa Marta slum were significatively lowered with improved sanitization levels (r = -0.74).

ConclusionsDespite previous publications that discarded the use of sanitization as a relevant tool in the fight against Covid-19, our results suggest that profits can be achieved in mitigating Covid-19 in underserved community sites. Furthermore, a permanent sanitization activity may induce positive social behavior for the sake of combating Covid-19.
"If somebody had told me I'd feel like I do now, I wouldn't have believed them"    Older adults' experiences of the BELL trial: a qualitative study ObjectivesThis study examined older adults experiences of participating in the BELL trial, involving 12-weeks of group-based hardstyle kettlebell training.

MethodsIn the BELL trial, 28 insufficiently active older adults (15 women, 13 men, 59-79 years) completed 6 weeks of face-to-face group training, and 6 weeks of home-based training. In-depth semi-structured interviews were audio recorded and transcribed, inductively coded, with themes constructed thematically from patterns of shared meaning.

ResultsFour higher-order themes were developed that reflect older adults experiences participating in a group-exercise program of hardstyle kettlebell training. These included: (1) "Its one of the best things weve done" - enjoying the physical and psychosocial benefits, (2) "Its improved it tremendously!" - change in a long-term health condition, (3) "It put me on a better course" - overcoming challenges, (4) "I wasnt just a number" - feeling part of a group/community.

DiscussionFindings highlight the perceived physical and psychological benefits of participating in hardstyle group kettlebell training, the value attributed to being part of an age-matched community of like-minded people engaged in group-exercise, as well as the challenges participants faced, and the sense of achievement in overcoming them. Implications for program design and delivery, and future research are discussed.
Comparative profiles of SARS-CoV-2 Spike-specific human milk antibodies elicited by mRNA- and adenovirus-based COVID-19 vaccines Numerous COVID-19 vaccines are authorized globally. To date, [~]71% of doses are comprised of the Pfizer/BioNTech vaccine, and [~]17% the Moderna/NIH vaccine, both of which are mRNA-based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises [~]9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks 4th at [~]2% [1]. No COVID-19 vaccines are yet available for children 0-4. One method to protect this population may be passive immunization via antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work [2] and other reports [3-5] have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG-dominant. In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86% -100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12 - 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33%-38% of recipients. Specific IgA was measured in 52%-71% of mRNA vaccine recipient milk and 17%-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. <50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit >2-fold increases in specific secretory Ab titer relative to pre-vaccine sample. These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response. The effects of modifiable maternal pregnancy exposures on offspring molar-incisor hypomineralisation: A negative control study ObjectivesO_LITo explore the associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH).
C_LIO_LITo explore for the presence of residual confounding using negative control analyses.
C_LI

MethodsThis study used data from Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective birth cohort. We defined offspring MIH using prospectively collected questionnaire data. We used logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We included negative control exposure (paternal BMI, smoking and alcohol around the time of pregnancy) and outcome (offspring dental trauma) analyses to explore for the presence of residual confounding.

Results5536 mother/offspring pairs were included (297 MIH cases [5.4%]). We found a positive association between maternal mean BMI and offspring MIH (OR per 1-kg/m2 difference in maternal BMI: 1.04, 95% CI: 1.00, 1.08). In subsequent analyses, we found evidence that this effect was non-linear and being driven by women in the highest BMI quintiles. In negative control analyses, we found no evidence of association between paternal BMI and offspring MIH (OR: 0.94, 95% CI: 0.89, 1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95% CI: 0.96, 1.02). There was no clear evidence of an association for maternal pregnancy smoking (OR: 0.76, 95%CI: 0.46, 1.22) and alcohol consumption (OR: 0.79, 95% CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated.

ConclusionIn summary we found evidence of a possible intrauterine effect of high maternal pre-pregnancy BMI on offspring MIH. We did not find robust evidence for an intrauterine effect of maternal pregnancy smoking or alcohol consumption on offspring MIH. Our findings provide further support for women of reproductive age to maintain a healthy weight. Future studies are warranted to explore possible mechanisms on how the pregnancy environment may relate to offspring MIH. Seasonal pattern COVID-19 and Flu-Like Illnesses comparable BackgroundDuring the first wave of COVID-19 it was hypothesized that COVID-19 is subject to multi-wave seasonality, similar to Influenza-Like Illnesses since time immemorial. One year into the pandemic, we aimed to test the seasonality hypothesis for COVID-19.

MethodsWe calculated the average annual time-series for Influenza-Like Illnesses based on incidence data from 2016 till 2019 in the Netherlands, and compared these with two COVID-19 time-series during 2020/2021 for the Netherlands. We plotted the time-series on a standardized logarithmic infection scale. Finally, we calculated correlation coefficients and used univariate regression analysis to estimate the strength of the association between the time-series of COVID-19 and Influenza-Like Illnesses.

ResultsThe time-series for COVID-19 and Influenza-Like Illnesses were strongly and highly significantly correlated. The COVID-19 peaks were all during flu season, and lows were all in the opposing period. Finally, COVID-19 meets the multi-wave characteristics of earlier flu-like pandemics, namely a short first wave at the tail-end of a flu season, and a longer and more intense second wave during the subsequent flu season.

ConclusionsWe conclude that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands. Further, the COVID-19 pandemic satisfies the criteria of earlier respiratory pandemics, namely a first wave that is short-lived at the tail-end of flu season, and a second wave that is longer and more severe.

This seems to imply that the same factors that are driving the seasonality of Influenza-Like Illnesses are causing COVID-19 seasonality as well, such as solar radiation (UV), temperature, relative humidity, and subsequently seasonal allergens and allergies.

HIGHLIGHTSO_LITime-series analysis shows that COVID-19 and historic of Influenza-Like illnesses have highly similar seasonal patterns in the Netherlands.
C_LIO_LICOVID-19 satisfies the criteria of earlier flu-like pandemics, namely a short cycle at the end of flu season, and a longer, more intense cycle during the subsequent flu season.
C_LIO_LIThe implication is that the seasonal factors driving flu season, are also responsible for COVID-19 seasonality.
C_LIO_LIWe developed and applied a new method to determine seasonality, encompassing comparative time-series analysis, a standardized logarithmic infection scale, and qualitative seasonality criteria.
C_LI Treatment interruption is a risk factor for sickness presenteeism: a large-scale cross-sectional study during the COVID-19 pandemic ObjectivesThis study examined the relationship between interruption to routine medical care during the coronavirus disease 2019 pandemic and sickness presenteeism among workers in Japan.

MethodsA cross-sectional study using data obtained from an internet monitor questionnaire was conducted. Interruption to medical care was defined based on the response "I have not been able to go to the hospital or receive treatment as scheduled." The fraction of sickness presenteeism days in the past 30 days was employed as the primary outcome. A fractional logit model was used for analysis to treat bounded data.

ResultsOf the 27,036 participants, 17,526 (65%) were workers who did not require routine medical care, 8,451 (31%) were using medical care as scheduled, and 1,059 (4%) experienced interrupted medical care. The adjusted odds ratio (aOR) of sickness presenteeism was significantly higher among workers who experienced interrupted medical care (3.44; 95% confidence interval [CI]: 3.04-3.89) than those who did not require routine medical care. In terms of symptoms, the highest aOR was observed among workers with mental health symptoms (aOR: 5.59, 95%CI: 5.04-6.20).

ConclusionsThis study suggests the importance of continuing necessary treatment during a pandemic to prevent presenteeism. Airway management, procedural data, and mortality records of patients undergoing surgery for mucormycosis associated with coronavirus disease (COVID-19) In India, the second wave of coronavirus disease (COVID -19) was associated with a distinct surge in cases of invasive fungal infection with mucormycosis. This disease was seen typically in the sinonasal form in COVID-19 patients. Uncontrolled diabetes, steroid use in COVID-19 treatment, etc. were some of the postulated risk factors for the association of COVID 19 and Mucormycosis. The management plan of these cases included surgical debridement, systemic antifungal therapy, sugar control, and management of antifungal related systemic adverse effects. In this retrospective case record review, we aimed to evaluate the airway management plan, demographics, and overall outcomes in patients undergoing surgical resection for COVID-19 associated mucormycosis. Forty-one (71.9 %) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) had a diagnosis of rhino-orbital mucormycosis, and 2 patients (3.5%) were diagnosed with palatal mucormycosis. Total 44 (77.19 %) patients had co-morbidities. The most common co-morbidity was Diabetes Mellitus 42 (73.6%), followed by hypertension 21 (36.84%) and Acute kidney injury 14 (28.07%). We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 out of 57 patients. In our study, mortality occurred in 7 (12.28 %) patients. The median mortality time was 60 (range, 27-74) days. The median time to hospital discharge was 53.5 (range,10-85) days. Managing COVID-19 on its own is challenging and additional mucormycosis can lead to increased morbidity and mortality. Despite challenges and risks, timely and meticulous interventions can reduce complications. Simple risk scores to predict hospitalization or death in outpatients with COVID-19 including the Omicron variant ImportanceOutpatient physicians need guidance to support their clinical decisions regarding management of patients with COVID-19, in particular whether to hospitalize a patient and if managed as an outpatient, how closely to follow them.

ObjectiveTo develop and prospectively validate a clinical prediction rule to predict the likelihood of hospitalization for outpatients with COVID-19 that does not require laboratory testing or imaging.

DesignDerivation and temporal validation of a clinical prediction rule, and prospective validation of two externally derived clinical prediction rules.

SettingPrimary and Express care clinics in a Pennsylvania health system.

ParticipantsPatients 12 years and older presenting to outpatient clinics who had a positive polymerase chain reaction test for COVID-19.

Main outcomes and measuresClassification accuracy (percentage in each risk group hospitalized) and area under the receiver operating characteristic curve (AUC).

ResultsOverall, 7.4% of outpatients in the early derivation cohort (5843 patients presenting before 3/1/21) and 5.5% in the late validation cohort (3806 patients presenting 3/1/21 or later) were ultimately hospitalized. We developed and temporally validated three risk scores that all included age, dyspnea, and the presence of comorbidities, adding respiratory rate for the second score and oxygen saturation for the third. All had very good overall accuracy (AUC 0.77 to 0.78) and classified over half of patients in the validation cohort as very low risk with a 1.7% or lower likelihood of hospitalization. Two externally derived risk scores identified more low risk patients, but with a higher overall risk of hospitalization (2.8%).

Conclusions and relevanceSimple risk scores applicable to outpatient and telehealth settings can identify patients with very low (1.6% to 1.7%), low (5.2% to 5.9%), moderate (14.7% to 15.6%), and high risk (32.0% to 34.2%) of hospitalization. The Lehigh Outpatient COVID Hospitalization (LOCH) risk score is available online as a free app: https://ebell-projects.shinyapps.io/LehighRiskScore/. How Informative Were Early SARS-CoV-2 Treatment and Prevention Trials? A longitudinal cohort analysis of trials registered on clinicaltrials.gov BackgroundEarly in the SARS-CoV-2 pandemic, commentators warned that some COVID trials were inadequately conceived, designed and reported. Here, we retrospectively assess the prevalence of informative COVID trials launched in the first 6 months of the pandemic.

MethodsWe created a cohort of SARS-CoV-2 treatment and prevention efficacy trials that were initiated from 2020-01-01 to 2020-06-30 using ClinicalTrials.gov registration records. We evaluated trials on 3 criteria of informativeness: potential redundancy, design quality and feasibility of patient-participant recruitment. The study protocol was prospectively registered with the Open Science Framework (https://osf.io/fp726/).

ResultsWe included 500 trials in our cohort, 58% of which were Phase 2 and 84.8% were directed towards the treatment of SARS-CoV-2. Close to one third of trials met all three criteria and were deemed informative (29.0% (95% Confidence Interval 23.7 - 36.9)). The proportion of potentially redundant trials in our cohort was 4.1%. Over half of the trials in our cohort (56.2%) did not meet our criteria for high quality trial design. The proportion of trials with infeasible patient-participant recruitment was 22.6%.

ConclusionsLess than one third of COVID-19 trials registered on ClinicalTrials.gov during the first six months met all three criteria for informativeness. Shortcomings in trial design, recruitment feasibility and redundancy reflect longstanding weaknesses in the clinical research enterprise that were likely amplified by the exceptional circumstances of a pandemic. Anti-CELA1 KF4 Antibody Prevents Emphysema by Inhibiting Stretch-Mediated Remodeling Emphysema is a major contributor to the morbidity and mortality of chronic obstructive pulmonary disease (COPD), and there are no disease modifying therapies. Three leading pathophysiologic models are the altered protease/antiprotease balance model, the biomechanical model in which loss of one alveolar wall increases strain on adjacent wall predisposing them to failure, and the accelerated aging model. Chymotrypsin-like elastase 1 (CELA1) is a novel serine protease with a physiological role in reducing postnatal lung elastance that mechanistically links these three models. CELA1 is expressed by alveolar type 2 (AT2) cells and is found adjacent to lung elastin fibers. The KF4 antibody neutralizes CELA1 by binding to its catalytic triad. CELA1 binding to lung elastin fibers increases 4-fold with strain, and application of biaxial strain induces lung elastase activity which is blocked with the KF4 anti-CELA1 antibody. Cela1-/- mice were protected from airspace simplification in hyperoxia, elastase and cigarette-smoke induced emphysema, and age-related airspace simplification. CELA1 mRNA was correlated with human lung elastolytic activity, and anti-CELA1 KF4 antibody protected mice from hyperoxia-induced alveolar simplification and elastase emphysema. CELA1-mediated lung matrix remodeling in response to strain is an important contributor to postnatal airspace simplification. Matrix stabilization by KF4 represents a potential therapeutic approach to preventing emphysema progression.

One Sentence SummaryNeutralization of chymotrypsin-like elastase 1 prevents strain-induced emphysema. Impact of HIV Infection on COVID-19 Outcomes Among Hospitalized Adults in the U.S. BackgroundWhether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID-19 is uncertain.

ObjectiveTo evaluate the impact of HIV infection on COVID-19 outcomes among hospitalized patients.

MethodsUsing the American Heart Associations COVID-19 Cardiovascular Disease registry, we used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics and comorbidities and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS).

ResultsThe registry included 21,528 hospitalization records of people with confirmed COVID-19 from 107 hospitals in 2020, including 220 people living with HIV (PLWH). PLWH were younger (56.0+/-13.0 versus 61.3+/-17.9 years old) and more likely to be male (72.3% vs 52.7%), Non-Hispanic Black (51.4% vs 25.4%), on Medicaid (44.5% vs 24.5), and active tobacco users (12.7% versus 6.5%).

Of the study population, 36 PLWH (16.4%) had in-hospital mortality compared with 3,290 (15.4%) without HIV (Risk ratio 1.06, 95%CI 0.79-1.43; risk difference 0.9%, 95%CI -4.2 to 6.1%; p=0.71). After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.13; 95%CI 0.77-1.6; p 0.54) even after adding body mass index and comorbidities (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91), severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86), or LOS (aOR 1.03; 95% CI 0.76-1.66, p=0.21).

ConclusionHIV was not associated with adverse outcomes of COVID-19 including in-hospital mortality, MACE, or severity of illness.

Condensed AbstractWe studied 21,528 patients hospitalized with COVID-19 at 107 hospitals in AHAs COVID-19 registry to examine the association between HIV and COVID-19 outcomes. More patients with HIV were younger, male, non-Hispanic Black, on Medicaid and current smokers. HIV was not associated with worse COVID-19 in-hospital mortality (Risk ratio 1.06, 95%CI 0.79-1.43; p=0.71) even after adjustment (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was also not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91) or severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86. Our findings do not support that HIV is a major risk factor for adverse COVID-19 outcomes. Complementary frailty and mortality prediction models on older patients as a tool for assessing palliative care needs BackgroundPalliative care (PC) has demonstrated benefits for life-limiting illnesses. Cancer patients have mainly accessed these services, but there is growing consensus about the importance of promoting access for patients with non-malignant disease. Bad survival prognosis and patients frailty are usual dimensions to decide PC inclusion.

ObjectivesThe main aim of this work is to design and evaluate three quantitative models based on machine learning approaches to predict frailty and mortality on older patients in the context of supporting PC decision making: one-year mortality, survival regression and one-year frailty classification.

MethodsThe dataset used in this study is composed of 39,310 hospital admissions for 19,753 older patients (age >= 65) from January 1st, 2011 to December 30th, 2018. All prediction models were based on Gradient Boosting Machines. From the initial pool of variables at hospital admission, 20 were selected by a recursive feature elimination algorithm based on the random forests GINI importance criterion. Besides, we run an independent grid search to find the best hyperparameters in each model. The evaluation was performed by 10-fold cross-validation and area under the receiver operating characteristic curve and mean absolute error were reported. The Cox proportional-hazards model was used to compare our proposed approach with classical survival methods.

ResultsThe one-year mortality model achieved an AUC ROC of 0.87 {+/-} 0.01; the mortality regression model achieved an MAE of 329.97 {+/-} 5.24 days. The one-year frailty classification reported an AUC ROC of 0.9 {+/-} 0.01. The Spearmans correlation between the admission frailty index and the survival time was -0.1, while the point-biserial correlation between one-year frailty index and survival time was -0.16.

ConclusionsOne-year mortality model performance is at a state-of-the-art level. Frailty Index used in this study behaves coherently with other works in the literature. One-year frailty classifier demonstrated that frailty status within the year could be predicted accurately. To our knowledge, this is the first study predicting one-year frailty status based on a frailty index. We found mortality and frailty as two weakly correlated and complementary PC needs assessment criteria. Predictive models are available online at http://demoiapc.upv.es. Precision MRI Phenotyping Enables Detection of Small Changes in Body Composition for Longitudinal Cohorts Longitudinal studies provide unique insights into the impact of environmental factors and lifespan issues on health and disease. Here we investigate changes in body composition in 3,088 free-living participants, part of the UK Biobank in-depth imaging study. All participants underwent neck-to-knee MRI scans at the first imaging visit and after approximately two years (second imaging visit). Image-derived phenotypes for each participant were extracted using a fully-automated image processing pipeline, including volumes of several tissues and organs: liver, pancreas, spleen, kidneys, total skeletal muscle, iliopsoas muscle, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), as well as fat and iron content in liver, pancreas and spleen. Overall, no significant changes were observed in BMI, body weight, or waist circumference over the scanning interval, despite some large individual changes. A significant decrease in grip strength was observed, coupled to small, but statistically significant, decrease in all skeletal muscle measurements. Significant increases in VAT and intermuscular fat in the thighs were also detected in the absence of changes in BMI, waist circumference and ectopic-fat deposition. Adjusting for disease status at the first imaging visit did not have an additional impact on the changes observed. In summary, we show that even after a relatively short period of time significant changes in body composition can take place, probably reflecting the obesogenic environment currently inhabited by most of the general population in the United Kingdom. Deceased donor kidney degradomics indicates cytoskeletal proteolytic alterations impacting post-transplant function. BackgroundIn brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction.

Material & MethodsUsing mass spectrometry and immunoblotting analyses, we profiled degradation patterns of cytoskeletal proteins in deceased (n=55) and living (n=10) donor kidneys.

ResultsWe found that in DBD kidneys, key podocyte cytoskeletal proteins had been proteolytically cleaved. Generated degradation profiles were not associated to donor related demographic and clinical factors but were associated to suboptimal post-transplant function. Strikingly, -actinin -4 and Talin-1 degradation profiles were not observed in circulatory-death or living-donor kidneys. As Talin-1 is a specific proteolytic target of Calpain-1, we investigated a potential trigger of Calpain activation and Talin-1 degradation using ex-vivo precision-cut human kidney slices and in-vitro immortalised human podocytes. Notably, we found that Transforming-Growth Factor-{beta} (TGF-{beta}) activated Calpain-1 and proteolytically cleaved Talin-1 to generate distinct peptide fragments. These peptide fragments were of similar size and matched the degradation patterns observed in DBD kidneys. Talin-1 degradation was prevented in vitro by Calpain-1 inhibition.

ConclusionsHere, we provide initial evidence that DBD kidneys are susceptible to cytoskeletal protein degradation that impacts posttransplant kidney function. Subsequent studies should aim to further investigate the link between brain death and activation of proteolytic pathways exploring new therapeutic opportunities. Feasibility of an online Langerian mindfulness program for stroke survivors and caregivers BackgroundMindfulness is promising for individuals with neurological disorders and their caregivers to improve psychological well-being. The potential application of a Langerian mindfulness intervention, focused on attention to variability, however, is still unknown.

ObjectiveTo determine the feasibility (usability, satisfaction, and potential effectiveness on psychological well-being) of an online mindfulness intervention for stroke survivors and caregivers.

MethodologyUsing mixed-methods, 11 stroke survivors and 3 caregivers participated in a 3-week, online, Langerian mindfulness intervention. A semi-structured interview assessed the interventions usability and gathered feedback. Self-reported measures about psychological well-being were documented remotely three times (pre, post, one-month follow-up).

ResultsQualitatively, participants were highly satisfied with the intervention, reported subjective benefits, but the usability of the online platform was poor. None of the self-reported measures changed over time.

ConclusionThis study provided evidence of feasibility of an online Langerian mindfulness intervention in a new population: stroke survivors and caregivers. Impact of a Multidisciplinary Nutritional Support Team on Quality Improvement in Home Parenteral Nutrition IntroductionHPN is essential for patients requiring long term nutritional support. This Quality Improvement Project for HPN Patients (QIP-PN) studied the effect of a Physician Nutrition Expert (PNE)- led multidisciplinary nutritional support team (MNST) on HPN care.

ObjectiveTo test the effect of an MNST on adherence to protocols, outcomes and QOL in HPN.

MethodsData review was conducted in phases 1a and 1b, observation in phase 2 and intervention in phase 3. In Phase 3 the MNST made recommendations to treating physicians. All long-term HPN patients were offered study participation. 75 signed consent forms. Treating physician study participation agreements were signed for 42 patients (the study group). A random sample of 30 long-term HPN patients comprised the case-matched control group (control). Data were collected on demographics, treating physicians PNE status, HPN care variables, recommended interventions, quality-of-life assessment, adverse outcomes and hospitalizations. Independent samples t-test was used for continuous data between study group and control group. Paired t-test was used for phase 2 and phase 3 patient data. Comparison between the study and control group utilized a negative binomial regression model. Statistical analysis utilized R (https://www.r-project.org/).

Results34 patients were reviewed retrospectively in phase 1a and 197 prospectively in phase 1b. 40 study patients completed phase 2 and progressed into phase 3, of whom 30 completed [&ge;]60 therapy days. Improvements in weight, BMI and QOL were seen in the study patients during intervention. Recommendations made and accepted by treating physicians differed based on PNE status. Study patients had fewer adverse outcomes and related hospitalizations than case matched controls.

ConclusionMNST recommendations improved clinical, biochemical parameters and patients self-reported overall health. It reduced adverse outcomes, hospitalization and hospital length of stay. MNST input could have a significant impact on the quality and cost of HPN care. Heading for personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization.

ObjectiveThe aim was to investigate the test-retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus.

MethodsThree short verum (1Hz, 10Hz, 20Hz; 200 pulses) and one sham (0.1Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG) together with behavioral tinnitus loudness ratings. RTMS individualization was executed by dint of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/ gamma responders) in accordance to the prevalent neurophysiological models for tinnitus.

ResultsIt was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder) respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. Contrary, test-retest correlation analyses per protocol on a group-level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were given.

ConclusionRTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability on group-level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability. Spatial Allocation of Scarce COVID-19 Vaccines The COVID-19 Vaccines Global Access (COVAX) is an initiative led by the World Health Organization (WHO) and other partners that aims for an equitable access of COVID-19 vaccines. Despite a potential heterogeneous disease burden across space, countries receiving allotments of vaccines via COVAX may want to follow WHOs allocation rule and distribute vaccines to their jurisdictions based on the jurisdictions relative population size. Utilizing economic-epidemiological modeling, we benchmark the performance of this ad hoc allocation rule by comparing it to the rule that minimizes the economic damages and expenditures over time, including a penalty cost representing the social costs of deviating from the ad hoc allocation. Under different levels of vaccine scarcity and different demographic characteristics, we consider scenarios where length of immunity and compliance to travel restrictions vary, and consider the robustness of the rules when assumptions regarding these factors are incorrect. The benefits from deviating are especially high when immunity is permanent, when there is compliance to travel restrictions, when the supply of vaccine is low, and when there is heterogeneity in demographic characteristics. Interestingly, a lack of compliance to travel restrictions pushes the optimal allocations of vaccine towards the ad hoc and improves the relative robustness of the ad hoc rule, as the mixing of the populations reduces the spatial heterogeneity in disease burden.

JEL ClassificationC61, H12, H84, I18, Q54 Precision Diagnostic Approach to Predict 5-Year Risk for Microvascular Complications in Type 1 Diabetes BackgroundIndividuals with long standing diabetes duration can experience damage to small microvascular blood vessels leading to diabetes complications (DCs) and increased mortality. Precision diagnostic tailors a diagnosis to an individual by using biomedical information. Blood small molecule profiling coupled with machine learning (ML) can facilitate the goals of precision diagnostics, including earlier diagnosis and individualized risk scoring.

MethodsUsing data in a cohort of 537 adults with type 1 diabetes (T1D) we predicted five-year progression to DCs. Prediction models were computed first with clinical risk factors at baseline and then with clinical risk factors and blood-derived molecular data at baseline. Progression of diabetic kidney disease and diabetic retinopathy were predicted in two complication-specific models.

FindingsThe model predicts the progression to diabetic kidney disease with accuracy: 0.96{+/-}0.25 and 0.96{+/-}0.06 area under curve, AUC, with clinical measurements and with small molecule predictors respectively and highlighted main predictors to be albuminuria, glomerular filtration rate, retinopathy status at baseline, sugar derivatives and ketones. For diabetic retinopathy, AUC 0.75{+/-}0.14 and 0.79{+/-}0.16 with clinical measurements and with small molecule predictors respectively and highlighted key predictors, albuminuria, glomerular filtration rate and retinopathy status at baseline. Individual risk scores were built to visualize results.

InterpretationWith further validation ML tools could facilitate the implementation of precision diagnosis in the clinic. It is envisaged that patients could be screened for complications, before these occur, thus preserving healthy life-years for persons with diabetes.

FundingThis study has been financially supported by Novo Nordisk Foundation grant NNF14OC0013659.

Research in context

Evidence before this studyMicrovascular diabetes complications (DCs), such as diabetic kidney disease (DKD) and diabetic retinopathy (DR), lead to increased mortality, blindness, kidney failure and overall decreased quality of life in individuals with diabetes.

Added value of this studyWe have developed four algorithms based on traditional risk factors alone and risk factors with metabolomic and lipidomic data. Two accurately predicted the future progression in individuals with type 1 diabetes. The top predictors chosen by the algorithm were hemoglobin A1c, albuminuria and retinopathy status at baseline for diabetic retinopathy. The most promising models predicted future diabetic kidney disease in which albuminuria, eGFR, retinopathy status at baseline were complemented with a number of ketones and sugar derivatives.

Implications of all the available evidenceWith further validation in several cohorts, the prediction models presented here have the potential for early diagnosis of CKD in persons with diabetes, thus enabling appropriate decisions on the available therapies. It is envisaged that these algorithms will be trialed and support clinicians with precision diagnosis and treatments. Culture and understanding the role of feedback for health professions students: Realist synthesis protocol. IntroductionClinical education has moved to a "competency-based" model with an emphasis on workplace-based learning and assessment which, in turn, depends on feedback to be effective. Further, the understanding of feedback has changed from information about a performance directed to the learner performing the task, to a dialogue, which enables the learner to act and develop.

In health professional education, feedback is a complex interaction between trainee, supervisor, and the healthcare system. Most published research on feedback in health professional education originates in Europe and North America. Our interest is on the impact of Culture on this process, particularly in the context of Asian cultures.

The (scientific) realist approach of Pawson and Tilley provides a means to examine complex interventions in social situations, and thus is an appropriate lens to use for this study. This is a protocol for a realist synthesis which asks how, why and in what circumstances do Asian Cultures influence health professional trainees to seek, respond to and use feedback given in the clinical environment, if at all.

Methods and analysisAn initial search was performed to help define the scope of the review question and develop our initial program theory. The formal electronic search was carried out in February 2020 and included: CINAHL, ERIC, MEDLINE, and PsycInfo, and repeated in October 2020.

Retrieved articles were imported into Covidence for screening and data extraction, after which components of the Context - Mechanisms - Outcomes configurations will be sought to refine the initial program theory.

Ethics and DisseminationAs this study is a literature review, ethics approval is not required.

The findings will be documented in line with the RAMESES publications standards for Realist syntheses,[41] and we plan to disseminate the findings by means of a peer-reviewed journal article and conference presentation(s).

Strengths and limitations of this studyO_LIThe synthesis aims to identify the how and why Asian Cultures may influence feedback seeking and provision to health professional trainees, if at all.
C_LIO_LITo our knowledge, there are few studies of feedback seeking and provision to health professional trainees in Asia.
C_LIO_LIA Realist approach has the potential to help explain the complex nature of Cultures impact on feedback.
C_LIO_LIOnly studies published in the English language will be included, so transferability of our findings to non-English speaking environments may be lacking.
C_LIO_LIIn addition to formal literature database searches, we will need to conduct citation mining to locate other relevant resources.
C_LI Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-Drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study BackgroundAnti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease

MethodsA nationwide multicenter retrospective cohort study was conducted by evaluating patients charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).

ResultsIn the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30-2.27, p-value <0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44-0.88, p-value = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79-2.40, p-value = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.

ConclusionIn patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed. The Addiction Risk Factor: A Unitary Genetic Vulnerability Characterizes Substance Use Disorders and Their Associations with Common Correlates Substance use disorders commonly co-occur with one another and with other psychiatric disorders. They share common features including high impulsivity, negative affect, and lower executive function. We tested whether a common genetic factor undergirds liability to problematic alcohol use (PAU), problematic tobacco use (PTU), cannabis use disorder (CUD), and opioid use disorder (OUD) by applying genomic structural equation modelling to genome-wide association study summary statistics for individuals of European ancestry (Total N = 1,019,521; substance specific Ns range: 82,707-435,563), while adjusting for the genetics of substance use (Ns = 184,765-632,802). We also tested whether shared liability across SUDs is associated with behavioral constructs (risk taking, executive function, neuroticism; Ns = 328,339-427,037) and non-substance use psychopathology (psychotic, compulsive, and early neurodevelopmental disorders). Shared genetic liability to PAU, PTU, CUD, and OUD was characterized by a unidimensional addiction risk factor (termed The Addiction-Risk-Factor, independent of substance use. OUD and CUD demonstrated the largest loadings, while problematic tobacco use showed the lowest loading. The Addiction-Risk-Factor was associated with risk taking, neuroticism, executive function, and non-substance psychopathology, but retained specific variance before and after accounting for genetics of substance use. Thus, a common genetic factor partly explains susceptibility for alcohol, tobacco, cannabis, and opioid use disorder. The Addiction-Risk-Factor has a unique genetic architecture that is not shared with normative substance use or non-substance psychopathology, suggesting that addiction is not the linear combination of substance use and psychopathology. Factors affecting first return to work following arthroscopic rotator cuff repair: A retrospective observational study in an occupational medicine clinic and single-surgeon practice BackgroundReturn to work (RTW) following arthroscopic rotator cuff repair (aRCR) within New South Wales (NSW), Australia, under compensable schemes has not been reported.

AimsDetermine factors affecting RTW status and time in patients treated with aRCR under state-based compensation schemes, compared to those outside such schemes.

MethodsPatients undergoing aRCR by one surgeon with minimum 1-year follow-up were grouped into those under (CP) or outside (non-CP) workers or vehicle accident compensation schemes, matched by age and gender. RTW status and time were assessed using chi-square analysis and multivariable linear regression.

ResultsOf 1054 available patients, 90 CP patients were identified with 29 consented and matched to non-CP (N=29). A higher proportion of CP patients (17.2 vs 0%, P<0.001) never returned to work and a lower proportion resumed pre-injury duties at first RTW (3 vs 52%, P<0.01). Median time to first RTW did not differ between CP and non-CP groups (5.1 vs 4.4, P=0.86). Smoking (P=0.007) and post-injury activity level (P=0.004) were significantly associated with longer time to first RTW, whereas compensation status was not.

ConclusionsCP patients undergoing aRCR in NSW are at risk of not returning to work. For those that return, there is no significant difference compared to non-CP in time to first RTW. Particularly, patient and management factors associated with extended time to first RTW have been identified. Interventions aimed at modifiable factors such as smoking cessation and increasing preoperative activity may improve future outcomes.

What is already known about this subjectO_LIWork-related injury and disease present a significant financial burden to the Australian economy ($AUD61.8billion per annum), with shoulder conditions due to body stressing accounting for 7% of this total cost (>$AUD4.2billion)
C_LIO_LIPatients receiving compensation appear to have poorer outcomes and take longer to return to work than their non-compensated counterparts, but the degree to which this occurs is variably reported in the literature
C_LIO_LIThe effect of modifiable factors on return to work status and time remain unclear, and have not previously been reported for the Australian population under the New South Wales workers compensation scheme
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What this study addsO_LIPatients receiving arthroscopic rotator cuff repair under a compensable scheme in New South Wales are at increased risk of not returning to work compared to patients presenting outside of a compensable scheme and patients in equivalent schemes internationally
C_LIO_LIPatients reporting a longer duration of symptoms and smokers are at increased risk of extended time to first return to work
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What impact this may have on practice or policyO_LIThe study has identified smoking and pre-surgery activity levels as key targets for intervention in patients receiving arthroscopic rotator cuff repair under a workers compensation scheme in New South Wales
C_LIO_LIBy further investigating whether interventions designed to modify these factors are able to favourably affect patient outcomes, there is potential to return patients to their preoperative level of work sooner
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