"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.
Do school closures and school reopenings affect community transmission of COVID-19? A systematic review of observational studies BackgroundSchool closures are associated with significant negative consequences and exacerbate inequalities. They were implemented worldwide to control SARS-CoV-2 in the first half of 2020, but their effectiveness, and the effects of lifting them, remain uncertain. This review summarises observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission.

MethodsThe study protocol was registered on Prospero (ID:CRD42020213699). On 07 January 2021 we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index, and Google. We included observational studies with quantitative estimates of the effect of school closures/reopenings on SARS-CoV-2 community transmission. We excluded prospective modelling studies and intra-school transmission studies. We performed a narrative synthesis due to data heterogeneity. We used the ROBINS-I tool to assess risk of bias.

FindingsWe identified 7,474 articles, of which 40 were included, with data from 150 countries. Of these 32 studies assessed school closures, and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60%, and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission.

ConclusionsSchool closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures.
Macronutrient mass intake explains deferential weight and fat loss in isocaloric diets Differential weight and fat losses under isocaloric diets of distinct macronutrient composition are well-documented findings in obesity research.1-6 Such data are considered a result of inadequate methodology as it disagree with the energy balance theory.7 A recent mathematical analysis of this paradigm has found, however, serious analytical contradictions in its foundations.8 As an alternative, a mass balance model was proposed to explain the aforesaid body composition alterations. Here, we expand on this observation by contrasting both models. We show that mass balance explains a wide range of fending experiments including those concurring with the energy balance principle. The latter, however, is less flexible and results in poor forecasts in settings consistent with mass balance. The energy balance theory is thus an unsatisfactory model of body composition changes. Consequently, by shifting to a mass balance paradigm of obesity a much deeper understanding of this disease may follow in the near future. Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: A scoping review ObjectivesThe goals of this study are to identify and analyse interventions that aim to treat Post Traumatic Stress Disorder (PTSD) and complex PTSD in individuals who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care.

DesignScoping review

Search strategyWe searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science, and PTSDpubs for published literature up to March 2020 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organizations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analyzed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described.

Results26 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions; and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomized controlled trials, were generally ineffective. Of the ten studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover.

ConclusionsThis scoping review identified a lack of high-quality trials to address PTSD in the vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.

Strengths and limitations of this studyO_LIFirst review of how trauma-informed care is being operationalized in the treatment of PTSD for the vulnerably housed.
C_LIO_LIProvides a clear picture emphasizing the need to consistently utilize a trauma-informed care approach for PTSD treatment in the vulnerably housed.
C_LIO_LILargely homogenous populations (primarily women and US Veterans) included in studies, may not be representative of broader population.
C_LIO_LIOften no mention of ethnic or cultural factors to consider when providing treatment.
C_LIO_LIMany of the studies available were of low methodological quality.
C_LI Covid-19 Associated Hepatitis in children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention. Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months followup BackgroundDetermining the humoral immunogenicity of tozinameran (BNT162b2) vaccine in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, will guide risk assessment and subsequent changes in vaccination policy.

MethodsIn a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody response to vaccine or infection and infection rate during followup.

Results175 dialysis patients (40% women, 65{+/-}15 years), 252 kidney transplant patients (33% women, 54{+/-}14 years) and 71 controls (65% women, 44{+/-}14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 80% of dialysis patients, 44% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 75% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower titers in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with diminished antibody response. Vaccination associated with fewer subsequent infections (HR=0.23, p<0.05). Moreover, higher antibody titers associated with fewer events, HR 0.41 for each unit increased in log10titer (p<0.05).

ConclusionsDialysis patients, and more so kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination, and lesser humoral response associated with more infections. Measures to identify and protect non-responsive patients are urgently required.

SignificanceReports on the humoral immunogenicity of SARS-CoV-2 mRNA vaccines in patients with end stage renal disease are scarce, and association with subsequent COVID-19 morbidity is unknown. In this cohort study that included 175 patients treated with dialysis, 252 kidney transplant recipients and 71 control volunteers, the proportion achieving an antibody response was time- and group-dependent, reaching 80%, 44% and 100% at 3 months post prime inoculation. Personal history of vaccination, positive antibody responses and antibody titers associated with significantly lower risk of COVID-19 infection. Thus, in patients with end stage renal disease, SARS-CoV-2 antibody testing may be warranted after vaccination, to identify non-responders at higher risk for disease. Correction of measurement error in a commercial multiple-breath washout device RationaleNitrogen multiple-breath washout (N2MBW) is an established technique to assess functional residual capacity (FRC) and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes.

ObjectivesWe investigated the accuracy of oxygen and carbon dioxide measurements used for the indirect calculation of nitrogen concentration in a commercial MBW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on FRC and lung clearance index (LCI).

MethodsHigh precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on FRC and LCI in a dataset of healthy children and children with cystic fibrosis using custom analysis software.

ResultsWe found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently FRC and LCI outcomes. Breath-by-breath correction of this error reduced mean (SD) FRC by 8.9 (2.2)% and LCI by 11.9 (4.0)%. It also resulted in almost complete disappearance of the tissue nitrogen signal at the end of measurements.

ConclusionsInadequate correction for cross sensitivity between the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of FRC and LCI. Correction of this error is possible and could be applied by re-analysing the measurements breath-by-breath in an updated software version.

Grants, Gifts, Equipment, DrugsEco Medics AG (Duernten, Switzerland) provided a research version of their commercial software Spiroware 3.2.1 including insight on signal processing algorithms and helped with the acquisition of mass spectrometry measurements. This project was funded by the Swiss National Science Foundation, Grant Nr. 182719 (P. Latzin) and 168173 (K. Ramsey) Structural disconnectome mapping of cognitive function in post-stroke patients Sequalae following stroke represents a significant challenge in current rehabilitation. The location and size of focal lesions are only moderately predictive of the diverse cognitive outcome after stroke. One explanation building on recent work on brain networks proposes that the cognitive consequences of focal lesions are caused by damages to anatomically distributed brain networks supporting cognition rather than specific lesion locations. To investigate the association between post-stroke structural disconnectivity and cognitive performance, we estimated individual level whole-brain disconnectivity probability maps based on lesion maps from 102 stroke patients using normative data from healthy controls. Cognitive performance was assessed in the whole sample using Montreal Cognitive Assessment, and a more comprehensive computerized test protocol was performed on a subset (n=82). Multivariate analysis using Partial Least Squares on the disconnectome maps revealed that higher disconnectivity in right insular and frontal operculum, superior temporal gyrus and putamen was associated with poorer MoCA performance, indicating that lesions in regions connected with these brain regions are more likely to cause cognitive impairment. Furthermore, our results indicated that disconnectivity within these clusters was associated with poorer performance across multiple cognitive domains. These findings demonstrate that the extent and distribution of structural disconnectivity following stroke are sensitive to cognitive deficits and may provide important clinical information predicting post stroke cognitive sequalae. 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/. 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
C_LI

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
C_LI

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
C_LI A Randomised Trial of a Wearable UV dosimeter for Skin Cancer Prevention BackgroundNon-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States, affecting 5 million people and costing $8.1 billion per year. Despite well-defined guidelines on ultraviolet radiation (UVR) avoidance, it remains difficult for people to assess their individual exposure, as UVR is invisible and the onset of symptoms due to UVR damage are delayed.

MethodsIn a prospective, randomized-controlled trial, 97 patients with a history of actinic keratoses were enrolled from March 2018 to July 2018 and followed over 6 months. 50 patients were given a wearable device that measured UV exposure and a smartphone application that provided both real-time and cumulative UV exposure information, and 47 patients were provided with UV protection counseling by a dermatologist.

ResultsWe observed a significant decrease in the incidence rate of NMSC in the intervention group compared to the control group over 3 months (p = 0.02). We did not observe a significant decrease in the incidence rate of actinic keratoses (AK) in the intervention group compared to the control group. The observed clinical benefit was not accompanied by psychological side effects such as anxiety and depression.

ConclusionsThis study suggests that providing real-time UV exposure data using a wearable UV dosimeter is a safe and effective behavioral change strategy to prevent NMSC. (Funded by the National Cancer Institute, contract HHSN261201700005C; ClinicalTrials.gov number NCT03315286.) Prospectively validated disease-agnostic predictive medicine with augmented intelligence Despite numerous superhuman achievements in complex challenges1,2, standalone AI does not free life science from the long-term bottleneck of linearly extracting new knowledge from exponentially growing new data3, severely limiting the success rate of drug discovery4. Inspired by the state-of-the-art AI training methods, we trained a human-centric hybrid augmented intelligence5 (HAI) to learn a foundation model6 that extracts all-encompassing knowledge of human physiology and diseases. To evaluate the quality of HAIs extracted knowledge, we designed the public, prospective prediction of pivotal ongoing clinical trial outcomes at large scale (PROTOCOLS) challenge to benchmark HAIs real-world performance of predicting drug clinical efficacy without access to human data. HAI achieved a 10.5-fold improvement from the baseline with 99% confidence7 in the PROTOCOLS validation, readily increasing the average clinical success rate of investigational new drugs from 7.9%8 to 90% for almost any human diseases9,10. The validated HAI confirms that exponentially extracted knowledge alone is sufficient for accurately predicting drug clinical efficacy, effecting a total reversal of Erooms law4. HAI is also the worlds first clinically validated model of human aging that could substantially speed up the discovery of preventive medicine for all age-related diseases11. Our results demonstrate that disruptive breakthroughs necessitate the smallest team size to attain the largest HAI for optimal knowledge extraction from high-dimensional low-quality data space, thus establishing the first prospective proof of the previous discovery that small teams disrupt12. The global adoption of training HAI provides a well-beaten economic path to mass-produce scientific and technological breakthroughs via exponential knowledge extraction and better designs of data labels for training better-performing AI13. Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS BackgroundHIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 p26 amino acid variations are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific CTL responses common in slower disease progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. We therefore aimed to determine if intrahost evolution of HIV-2 p26 is associated with disease progression.

MethodsTwelve treatment-naive, HIV-2 mono-infected participants from the Guinea-Bissau Police cohort with longitudinal CD4+ T cell data and clinical follow-up were included in the analysis. CD4% change over time was analysed via linear regression models to stratify participants into relative faster and slower disease progressor groups. Gag amplicons of 735 nucleotides which spanned the p26 region were amplified by PCR and sequenced. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Amino acid polymorphisms were mapped to existing p26 protein structures.

ResultsIn total, 369 heterochronous HIV-2 p26 sequences from 12 male patients with a median age of 30 (IQR: 28-37) years at enrolment were analysed. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates ({rho} = -0.8, P=0.02), but not CD4% level. However, Bayes factor (BF) testing indicated that the association between evolutionary rates and CD4% kinetics was supported by weak evidence (BF=0.5). The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5/p26 hexamer interface surface.

ConclusionsFaster p26 evolutionary rates were associated with faster progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate the HIV-2 p26 may be an attractive vaccine or therapeutic target. 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. Macular vascular complexity analysis of diabetes mellitus by swept-source optical coherence tomographic angiography PurposeTo evaluate the associations of retinal vascular complexity features, including fractal dimension (FD) and blood vessel tortuosity (BVT), with the severity of diabetic retinopathy (DR) by using noninvasive optical coherence tomographic angiography (OCTA).

MethodsThis prospective cross-sectional study recruited ocular-treatment-naive patients with type 2 diabetes mellitus (DM) registered in the community of Guangzhou, China. OCTA was used to obtain the measurements of FD and BVT in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Univariate and multivariate linear regression was used to analyse the correlation of FD and BVT in different layers with DR severity.

ResultsA total of 1282 patients with DM (1282 eyes), with a mean age of 64.2{+/-}7.8 years, were included. FD in the DCP decreased and BVT in the DCP increased in DR patients compared to non-DR patients, even after adjusting for confounding factors (P< 0.05). Trend analysis showed a significant decrease in the FD values as the DR progressed, while the BVT progressively increased with worsening DR severity (P< 0.01). The FD in DCP had a statistically significant positive correlation with FD in SCP and a negative correlation with BVT in SCP and BVT in DCP in all of the participants, including the non-DR group, moderate DR group and severe DR group (P< 0.01).

ConclusionFD and BVT determined using OCTA might be useful parameters for objectively distinguishing DR from non-DR and indicating DR progression. Decoding hand and wrist movement intention from chronic stroke survivors with hemiparesis using a user-friendly, wearable EMG-based neural interface Prosthetics and orthotics have been recognized for decades as a potential means to restore hand function and independence to individuals living with impairment due to stroke. However, 75% of stroke survivors, caregivers, and health care professionals (HCP) believe current practices are insufficient, specifically calling out the upper extremity as an area where innovation is needed to develop highly usable prosthetics/orthotics for the stroke population. A promising method for controlling upper limb technologies is to infer movement intent non-invasively from surface electromyography (EMG) activity. While this approach has garnered significant attention in the literature, existing technologies are often limited to research settings and struggle to meet stated user needs. To address these limitations, we have developed the NeuroLife(R) EMG System, which consists of a wearable forearm sleeve with 150 embedded electrodes and associated hardware and software to record and decode surface EMG. Here, we demonstrate accurate decoding of 12 functional hand, wrist, and forearm movements, including multiple types of grasps from participants with varying levels of chronic impairment from stroke, with an overall accuracy of 77.1{+/-}5.6%. Importantly, we demonstrate the ability to decode a subset of 3 fundamental movements in individuals with severe hand impairment at 85.4{+/-}6.4% accuracy, highlighting the potential as a control mechanism for assistive technologies. Feedback from stroke survivors who tested the system indicates that the sleeves design meets various user needs, including being comfortable, portable, and lightweight. The sleeve is in a form factor such that it can be used at home without an expert technician and can be worn for multiple hours without discomfort. Taken together, the NeuroLife EMG System represents a platform technology to record and decode high-definition EMG for the eventual real-time control of assistive devices in a form factor designed to meet user needs. Associations of the BNT162b2 COVID-19 vaccine effectiveness with patient age and comorbidities at daily resolution Vaccinations are considered the major tool to curb the current SARS-CoV-2 pandemic. A randomized placebo-controlled trial of the BNT162b2 vaccine has demonstrated a 95% efficacy in preventing COVID-19 disease. These results are now corroborated with statistical analyses of real-world vaccination rollouts, but resolving vaccine effectiveness across demographic groups is challenging. Here, applying a multivariable logistic regression analysis approach to a large patient-level dataset, including SARS-CoV-2 tests, vaccine inoculations and personalized demographics, we model vaccine effectiveness at daily resolution and its interaction with sex, age and comorbidities. Vaccine effectiveness gradually increased post day 12 of inoculation, then plateaued, around 35 days, reaching 91.2% [CI 88.8%-93.1%] for all infections and 99.3% [CI 95.3%-99.9%] for symptomatic infections. Effectiveness was uniform for men and women yet declined mildly but significantly with age and for patients with specific chronic comorbidities, most notably type 2 diabetes. Quantifying real-world vaccine effectiveness, including both biological and behavioral effects, our analysis provides initial measurement of vaccine effectiveness across demographic groups. 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. Diagnostic Model of in-Hospital Mortality in Patients with Acute ST-Segment Elevation Myocardial Infarction Used Artificial Intelligence Methods BackgroundPreventing in-hospital mortality in Patients with ST-segment elevation myocardial infarction (STEMI) is a crucial step.

ObjectivesThe objective of our research was to to develop and externally validate the diagnostic model of in-hospital mortality in acute STEMI patients used artificial intelligence methods.

MethodsWe divide non-randomly the American population with acute STEMI into a training set, a test set,and a validation set. We converted the unbalanced data into balanc ed data. We used artificial intelligence methods to develop and externally validate the dia gnostic model of in-hospital mortality in acute STEMI patients. We used confusion matrix combined with the area under the receiver operating characteristic curve (AUC) to evaluat e the pros and cons of the above models.

ResultsThe strongest predictors of in-hospital mortality were age, gender, cardiogenic shock, atrial fibrillation(AF), ventricular fibrillation(VF),third degree atrioventricular block,in-hospital bleeding, underwent percutaneous coronary intervention(PCI) during hospitalization, underwent coronary artery bypass grafting (CABG) during hospitalization, hypertension history, diabetes history, and myocardial infarction history.The F2 score of logistic regression in the training set, the test set, and the validation data set were 0.81, 0.6, and 0.59 respectively.The AUC of logistic regression in the training set, the test set, and the validation data set were 0.77, 0.78, and 0.8 respectively. The diagnostic model built by logistic regression was the best.

ConclusionWe had used artificial intelligence methods developed and externally validated the diagnostic model of in-hospital mortality in acute STEMI patients.

We registered this study with WHO International Clinical Trials Registry Platform (ICTRP) (registration number: ChiCTR1900027129; registered date: 1 November 2019). 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 Increase in SARS-CoV-2 RBD-specific IgA and IgG Antibodies in Human Milk from Lactating Women Following the COVID-19 Booster Vaccination The CDC recommended a booster dose of the Pfizer-BioNTech Comirnaty (BNT162b2) COVID-19 mRNA vaccine in September 2021 for high-risk individuals. Pregnant and high-risk lactating women were encouraged to receive the booster to obtain potential prolonged protection for themselves and their infants. This study investigated the ability of the booster vaccine to increase IgA and IgG antibodies specific to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein in breast milk compared to levels pre-booster. We found a significant increase in both anti-RBD-specific IgA and IgG antibodies in breast milk following the Pfizer-BioNTech booster and this increase was present in the majority of participants at the study endpoint (60 days post-booster). These results suggest the booster enhances SARS-CoV-2 specific immunity in human breast milk, which may be protective for infants. The incidence of delirium in an acute geriatric community hospital: an observational cohort feasibility study. ObjectivesDelirium in hospitalised older adults is associated with negative health outcomes. Admission to an alternative care setting may lower the incidence of delirium. The Acute Geriatric Community Hospital (AGCH) was recently opened in the Netherlands and uses a multi-component non-pharmacological intervention strategy to prevent delirium. The objective of this study was to describe the incidence of delirium at the AGCH and compare this incidence to existing rates from literature. If a possible effect on delirium is seen in this comparison this would support conducting a larger prospectively controlled study on delirium in this new care setting.

DesignProspective cohort feasibility study; exploratory meta-analysis of proportions.

Setting and ParticipantsThe AGCH is an acute geriatric unit in a skilled nursing facility for patients aged >65 years with acute medical conditions.

MethodsDelirium assessment using the Confusion Assessment Method (CAM) upon admission and on day one, two and three or until delirium had resolved. Patients charts were reviewed if CAM was missing. In an linear mixed-effects model, the delirium incidence rate in AGCH was compared to pooled delirium incidence rates from six studies found in a high-quality review.

Results214 patients from the AGCH (mean age 81.9 years, 47% male, 12% with a history of dementia) were included in the analysis. Delirium developed in 8% (18/214) (95% confidence interval [CI] 5-13%) of patients during AGCH admission compared to 16% (95% CI 12-21%) in hospitals. Admission to the AGCH was associated with a decreased delirium incidence rate compared to the hospital control group (OR[odds ratio]= 0.49, 95% CI 0.24-0.98, p-value=0.044).

Conclusions and implicationsThe delirium incidence in the AGCH was low compared to those incidences found in general hospitals in literature. Based on these findings a controlled observational or randomized study measuring delirium in this care setting is recommended. RELATIONSHIP BETWEEN ADVERSE EVENTS PREVALENCE, PATIENT SAFETY CULTURE AND PATIENT SAFETY PERCEPTION IN A SINGLE SAMPLE OF PATIENTS: A CROSS-SECTIONAL AND CORRELATIONAL STUDY ObjectiveTo assess the relationship between Adverse Events Prevalence, Patient Safety Culture and Patient Safety Perception.

DesignCross-sectional, ex post facto comparative study on a single sample of patients.

SettingFour medium-high-level hospitals were included in the study -- two public and two private from Zulia State in Venezuela.

Participants556 medical records and patients were studied for the prevalence and patient safety perception study, and 397 of the healthcare providers involved in the care of these patients were surveyed for the patient safety culture study, at two public and two private hospitals.

Outcome measurementThe primary outcome of this study was the Association between Adverse Events Prevalence, Patient Safety Culture and Patient Safety Perception, and according to hospital funding type, private and public.

ResultsAn inverse association was observed between Adverse Events Prevalence and its severity and Patient Safety Culture Index (PSCI: rho=-0.8 p=0.5) (95% CI=0.26-0.10) and Patient Safety Perception Index (PSPI: rho=-0.6 p=0.18) (95% CI=0.10-0.28), which were protective factors for patient safety. No association was identified between Patient Safety Culture and Patient Safety Perception (rho=0.0001). No statistical differences were identified by hospital type (p=0.93) (95% CI=0.70-1.2).

ConclusionsThe analysis of the variable correlations studied (AEP, PSC and PSP) within the same sample offers an interesting and useful perspective. In this sample, although no correlation was observed between the three variables as an interacting set, some correlation patterns were observed between pairs of variables that could guide further studies.

Strengths and limitations of this studyO_LIThe association analysis of the three main variables (adverse events prevalence, patient safety culture and patient safety perception) in the same sample of patients and health professionals and over the same time period during which the care process and, consequently, the adverse events took place is an unprecedented and innovative approach, which contributes to the body of knowledge on this field of study.
C_LIO_LIThe relational theoretical framework produced provides a "map" that can facilitate decision-taking and which establishes the variables that should be considered a priority. As a result, it is highly likely to have an impact on the clinical efficiency and safety of healthcare institutions and services.
C_LIO_LIThe study was carried out at both private and public hospitals, enabling the behaviour of the aforementioned variables to be compared and analysed at each type of institution. The literature to date on this approach is scarce and offers little information.
C_LIO_LIAlthough the sample of hospitals selected is not representative of Venezuela, it is representative of the hospitals of one of the most productive and populated states in the country.
C_LIO_LIDuring stages 1 and 2, some resistance to collaborating with and completing the evaluation instruments was identified among the health professionals.
C_LI Substance Use Onset in High-Risk 9-13 Year-Olds in the ABCD Study AimA key aim of the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study is to document substance use onset, patterns, and sequelae across adolescent development. However, substance use misreporting obscures accurate drug use characterization. Hair toxicology tests provide objective historical substance use data, but are rarely investigated in youth. Here, we compare objective hair toxicology results with self-reported substance use in youth.

MethodsA literature-based substance use risk algorithm identified 696 ABCD Study(R) participants for hair sample collections between baseline and 2-year follow-up (spanning ages 9-13) for laboratory analysis. Chi-square and t-tests assessed differences between participants demographics, positive and negative hair tests, risk algorithm scores, and self-reported substance use.

ResultsHair testing confirmed that 17% of at-risk 9-13 year-olds had evidence of past 3-month use of one (n=99), two (n=17), three (n=3), or four (n=2) drug classes. After considering prescribed medication use, 11% had a positive test incongruent with self- or parent-report. No participant with a positive result self-reported substance use consistent with their toxicology results. Participants with positive tests under-reported use (p<.001), reported less sipping of alcohol (p<.001), and scored higher on the risk algorithm (p<.001) than those with negative hair toxicology.

ConclusionsAn alarming 11% of tested samples in at-risk 9-13 year-olds were positive for at least one unreported substance, suggesting underreporting in this population when participating in a national healthy development study. The degree of underreporting cannot yet be calculated, as at-risk samples were prioritized for assays. Expanded toxicology testing is key to characterize substance use in youth. Correlates of patient-reported cognitive performance with regard to disability ObjectivesThe patient-reported Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is inconsistently related to objective cognitive tests in multiple sclerosis (MS), while being strongly correlated with depression. In this study we test whether the relation between subjective and objective cognitive performance is moderated by physical disability, assessed by the Expanded Disability Status Scale (EDSS).

Materials & MethodsFrom 275 MS patients who completed the patient-report MSNQ and the two-question screening tool for depression, we collected Symbol Digit Modalities Test (SDMT) and EDSS scores, indicators of respectively objective cognitive performance and physical disability. We analysed correlations between these variables in the total group and in three EDSS subgroups: Low 0.0 - 3.0, Medium 3.5 - 6.0 and High 6.5 - 9.0. We also investigated the use of a composite measure of cognitive impairment and depression.

ResultsWe found no significant correlations between patient-reported MSNQ and SDMT scores in the total group or the EDSS subgroups. MSNQ scores correlated significantly with depression in all subgroups. After correcting for several variables, MSNQ scores contributed adversely to SDMT scores in the total group, not in any subgroup. MSNQ scores contributed significantly to the prediction of the composite measure of impairment in the total group and in all EDSS subgroups.

ConclusionsThe relationship between measures of subjective and objective cognitive performance is not influenced by the patients level of physical disability. MSNQ scores are substantially influenced by depression, and reflect cognitive function to some degree. The patient-report MSNQ can be useful to identify patients requiring further (neuro)psychological assessment.