title: Effects of COVID-19 in Care Homes - A Mixed Methods Review

abstract:
IntroductionThe report provides an up-to-date review of the global effects of the COVID-19 pandemic in care homes. We used a mixed methods approach to assess care home mortality by country, how the deaths compared with previous periods, and how excess deaths may be explained. We retrieved national datasets for 25 countries on mortality, 17 cohort studies assessing deaths compared to a previous period, and 16 cohort studies reporting interventions or factors associated with excess mortality.

The COVID-19 pandemic disproportionately impacted those living in care homes at the highest risk for severe outcomes. However, the pandemic only highlighted and exacerbated a long-running problem: underfunding, poor structural layout, undertraining, under-skilling, under-equipping, and finally, lack of humanity in dealing with the most vulnerable members of society.

The 17 cohort studies point to excess mortality worsening during the pandemic. Despite involving vast numbers of care homes around the globe, the quality of the evidence is not good. For example, the majority of the studies infer the cause of extra deaths from the observation window (mainly the spring of 2020) rather than through detailed investigations. This is why we do not draw any clear conclusions about the specific causes of death, apart from noting their significantly high numbers. In addition, we did not review all policy actions since 2020 but note there has been a scarcity of studies since then - an indicator that interest in this problem has waned and likely not been addressed.

Analysis of national datasets for 25 countries shows that care home deaths were, on average, 30% of the total COVID-19 deaths (range: 9-64%). The quality of the current evidence base is limited, short term, and lacks standardised methods to prevent robust countrywide comparisons. Residual excess deaths were also observed, with excess mortality being reported for both COVID-19 positive and negative patients.

Several reported interventions or factors suggest the potential to mitigate the risk in care homes substantially. Interventions that could reduce mortality include improving the care home quality, increasing staffing levels, reducing the number of beds in the facility, employing staff confinement strategies with residents, and improving clinical care such as implementing daily examinations. Some care home solutions like US  Green House homes, which usually have fewer than 12 beds, may provide crucial insights into the care home problem compared with larger homes. Furthermore, care home residents faced barriers accessing emergency treatments during the pandemic waves. Finally, interventions targeting care homes should be subject to smaller trials given large effect sizes in some studies.

Approximately one per cent of the global population resides in care homes, while care home residents account for nearly one-third of deaths attributed to COVID-19 in the 25 countries studied. Reducing this ratio requires analysing current care home infrastructures, funding models, and incentives for providing high-quality care. The scale of the problem in care homes requires robust evaluation and coordinated strategies to improve outcomes for those most vulnerable to COVID-19. Failure to address these systemic problems could mean global care home populations will be similarly affected by future crises and pandemics.


title: The statistical analysis of daily data associated with different parameters of the New Coronavirus COVID-19 pandemic in Georgia and their monthly interval prediction from January 1, 2022 to March 31, 2022

abstract:
In this work results of the next statistical analysis of the daily data associated with New Coronavirus COVID-19 infection of confirmed (C), recovered (R), deaths (D) and infection rate (I) cases of the population of Georgia in the period from January 01, 2022 to March 31, 2022 are presented. It also presents the results of the analysis of monthly forecasting of the values of C, D and I. As earlier, the information was regularly sent to the National Center for Disease Control & Public Health of Georgia and posted on the Facebook page https://www.facebook.com/Avtandil1948/.

The analysis of data is carried out with the use of the standard statistical analysis methods of random events and methods of mathematical statistics for the non-accidental time-series of observations. In particular, the following results were obtained.

Georgias ranking in the world for Covid-19 monthly mean values of infection and deaths cases in investigation period (per 1 million population) was determined. Among 157 countries with population [≥] 1 million inhabitants in February 2022 Georgia was in the 4 place on new infection cases, in the 2 place on death. Georgia took the best place in terms of confirmed cases of diseases (thirty fifth) and in mortality (tenth) - in March.

A comparison between the daily mortality from Covid-19 in Georgia from January 01, 2022 to March 31, 2022 with the average daily mortality rate in 2015-2019 shows, that the largest share value of D from mean death in 2015-2019 was 43.1 % (January 04, 2022), the smallest 2.12 % (March 23, 2022).

As in previous works [10-13] the statistical analysis of the daily and decade data associated with coronavirus COVID-19 pandemic of confirmed, recovered, deaths cases and infection rate of the population of Georgia are carried out. Maximum daily values of investigation parameters are following: C = 26320 (February 2, 2022), R = 48486 (February 12, 2022), D = 67 (January 4,2022), I = 41.58 % (February 14, 2022). Maximum mean decade values of investigation parameters are following: C = 22214 (1 Decade of February 2022), R = 23408 (2 Decade of February 2022), D = 45 (2 Decade of February 2022), I = 32.12% (1 Decade of February 2022).

It was found that as in spring, summer and from September to December 2021 [10,11,13], in investigation period of time the regression equations for the time variability of the daily values of C, R, D and I have the form of a tenth order polynomial.

Mean values of speed of change of confirmed - V(C), recovered - V(R), deaths - V(D) and infection rate V(I) coronavirus-related cases in different decades of months for the indicated period of time were determined. Maximum mean decade values of investigation parameters are following: V(C) = +1079 cases/day (3 Decade of January 2022), V(R) = +1139 cases/day (1 Decade of February 2022), V(D) = +0.8 cases/day (1 Decade of February 2022), V(I) = + 1.16 %/ day (3 decades of January 2022).

Cross-correlations analysis between confirmed COVID-19 cases with recovered and deaths cases shows, that from January 1, 2022 to March 31, 2022 the maximum effect of recovery is observed on 3-6 days after infection (CR=0.83-0.84), and deaths - after 2 and 4 days (CR=0.60). The impact of the omicron variant of the coronavirus on people (recovery, mortality) could be up to19 and 16 days respectively.

Comparison of daily real and calculated monthly predictions data of C, D and I in Georgia are carried out. It was found that in investigation period of time daily and mean monthly real values of C, D and I mainly fall into the 67% - 99.99% confidence interval of these predicted values. Exception - predicted values of I for January 2022 (alarming deterioration, violation of the stability of a time-series of observations).

Traditionally, the comparison of data about C and D in Georgia (GEO) with similar data in Armenia (ARM), Azerbaijan (AZE), Russia (RUS), Turkey (TUR) and in the World (WRL) is also carried out.

category: epidemiology


title: Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD

abstract:
BackgroundWhite matter hyperintensities (WMHs) are pathological changes that develop with increased age and are associated with cognitive decline. Most research on WMHs has neglected to examine regional differences and instead focuses on using a whole-brain approach. This study examined regional WMH differences between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimers disease (AD). Another goal was to examine whether WMH burden was associated with declines in different cognitive domains in each of the groups.

MethodsParticipants were selected from the Alzheimers Disease Neuroimaging Initiative and included if they had at least one WMH measurement and cognitive scores examining global cognition, executive functioning, and memory. MCI and AD participants were included only if they were amyloid positive. A total of 1573 participants with 7381 follow-ups met inclusion criteria. Linear mixed-effects models were completed to examine group differences in WMH burden and the association between WMH burden and cognition in aging, MCI, and AD.

ResultsPeople with MCI and AD had increased total and regional WMH burden compared to cognitively healthy older adults. An association between WMH and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions of interest. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region.

ConclusionThese results suggest WMH burden increases from aging to AD. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between WMH and memory and WMH and global cognition. These findings suggest that WMH burden is associated with changes in cognition in healthy aging and early cognitive decline, but other biological changes may have a stronger impact on cognition with AD.

category: geriatric medicine


title: POPULATION ANALYSIS OF MORTALITY RISK: PREDICTIVE MODELS USING MOTION SENSORS FOR * 100,000 PARTICIPANTS IN THE UK BIOBANK NATIONAL COHORT

abstract:
We have developed novel technology for health monitoring, which inputs motion sensors to predictive models of health status. We have validated these models in clinical experiments with carried smartphones, using only their embedded accelerometers. Using smartphones as passive monitors for population measurement is critically important for health equity, since they are ubiquitous in high-income countries already and will become ubiquitous in low-income countries in the near future. Our study simulates smartphones by using accelerometers as sensor input.

We analyzed 100,000 participants in UK Biobank who wore activity monitors with motion sensors for 1 week. This national cohort is demographically representative of the UK population, and this dataset represents the largest such available sensor record. We performed population analysis using walking intensity, with participants whose motion during normal activities included daily living equivalent of timed walk tests. We extract continuous features from sensor data, for input to survival analysis for predictive models of mortality risk.

Simulating population monitoring, we validated predictive models using only sensors and demographics. This resulted in C-index of 0.76 for 1-year risk decreasing to 0.73 for 5-year. A minimum set of sensor features achieves similar C-index with 0.72 for 5-year risk, which is similar accuracy to previous studies using methods not achievable with phone sensors. The minimum model uses average acceleration, which has predictive value independent of demographics of age and sex, as does the physical measure of gait speed. Our digital health methods achieve the same accuracy as activity monitors measuring total activity, despite using only walking sessions as sensor input, orders of magnitude less than existing methods.

AUTHOR SUMMARYSupporting healthcare infrastructure requires screening national populations with passive monitors. That is, looking for health problems without intruding into daily living. Digital health offers potential solutions if sensor devices of adequate accuracy for predictive models are already widely deployed. The only such current devices are cheap phones, smartphone devices with embedded sensors. This limits the measures to motion sensors when the phones are carried during normal activities. So measuring walking intensity is possible, but total activity is not.

Our study simulates smartphone sensors to predict mortality risk in the largest national cohort with sensor records, the demographically representative UK Biobank. Death is the most definite outcome, accurate death records are available for 100,000 participants who wore sensor devices some five years ago. We analyzed this dataset to extract walking sessions during daily living, then used these to predict mortality risk. The accuracy achieved was similar to activity monitors measuring total activity and even to physical measures such as gait speed during observed walks. Our scalable methods offer a potential pathway towards national screening for health status.

category: health informatics


title: Effects of multiple-dose intranasal oxytocin treatment on social responsiveness in children with autism: A randomized, placebo-controlled trial

abstract: In the past decade, intranasal administration of the neuropeptide oxytocin is increasingly explored as a new treatment for reducing the core symptoms of autism spectrum disorder (ASD). The efficacy of continual oxytocin treatment in school-aged children with ASD is, however, not well established. Using a double-blind, randomized, placebo-controlled, parallel design, the current trial explored the effects of four weeks of intranasal oxytocin treatment (12 IU, twice daily) on social functioning in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). The double-blind phase was followed by a four-week single-blind extension phase during which all participants received intranasal oxytocin. In the double-blind phase, no treatment-specific effects were identified in the primary outcome assessing social functioning (parent-rated Social Responsiveness Scale), as well as on secondary outcomes assessing repetitive behaviors, anxiety, and attachment. Exploratory moderator analyses revealed that children who received the oxytocin treatment in combination with concomitant psychosocial treatment displayed a greater benefit than those who received psychosocial treatment or oxytocin alone. A modulating effect of parents beliefs about allocated treatment was also identified, indicating that parents who believed their child assigned to the active treatment reported greater benefit than those who believed their child received placebo, particularly in the actual oxytocin group. Finally, participants who were allocated to receive the placebo treatment during the double-blind phase of the trial and later crossed-over to receive the active treatment during the single-blind extension phase, displayed a significant within-group improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. While no overall treatment-specific improvements were identified, our results provide important indications that clinical efficacy can be augmented when oxytocin administration is paired with targeted psychosocial interventions that similarly stimulate socio-communicative behaviors. Future trials are urged to further elucidate the potential of embedding oxytocin treatment within a socially stimulating context.

category: psychiatry and clinical psychology


title: "Younger women had more access to COVID-19 information": An Intersectional Analysis of Factors Influencing Women and Girls' Access to COVID-19 Information in Rohingya and Host Communities in Bangladesh

abstract:
IntroductionThe Rohingya and Bangladeshi host communities live at a heightened risk of COVID-19 impact due to their pre-existing vulnerabilities, religious beliefs, and strict socio-cultural and gender norms that render primarily women and girls vulnerable. However, the extent of this vulnerability varies within and across population groups in the host and Rohingya communities. The intersectionality lens helps identify, recognize, and understand these factors that create inequities within populations. This study explored the factors that influenced the women and girls access to information during the COVID-19 pandemic through an intersectional lens.

MethodologyThis paper presents partial findings from the exploratory qualitative part of mixed-method research conducted in ten Rohingya camps and four wards of the adjacent host communities in Coxs Bazar, Bangladesh. Data were extracted from 24 in-depth interviews (12 in each community) conducted from November 2020 to March 2021 with diverse participants, including adolescent girls, younger women, adult women, pregnant and lactating mothers, persons with disabilities, older adults, and single female-household heads. All participants provided verbal informed consent before the interviews. In the case of the adolescents, assent was taken from the participants, and verbal informed consent was taken from their parents/guardians. The ethical clearance of this study was sought from the institutional review board of BRAC James P Grant School of Public Health, BRAC University.

ResultWe find that the women and girls living in Rohingya communities exhibit a more profound structural interplay of factors within their socio-ecological ecosystem depending on their age, power, and position in the society, physical (dis)abilities, and pre-existing vulnerabilities stemming from their exodus, making them more vulnerable to COVID-19 impact by hindering their access to information. Unlike Rohingya, the host women and girls explain the impact of the COVID-19 pandemic on their access to information through the lens of intergenerational poverty and continuous strain on existing resources, thereby highlighting shrinking opportunities due to the influx, COVID-19 infodemic and misinformation, access to digital devices amongst the adolescents, and restricted mobility mainly due to transport, school closures, and distance-related issues. Moreover, the socio-cultural beliefs and the gender norms imposed on women and adolescent girls played an essential role in accessing information regarding the COVID-19 pandemic and consequently influenced their perception of and response to the disease and its safety protocols. Socio-cultural gender norms led to mobility restrictions, which compounded by lockdowns influenced their access to information resulting in dependency on secondary sources, usually from male members of their families, which can easily mislead/provide mis/partial information. The younger age groups had more access to primary sources of information and a broader support network. In comparison, the older age groups were more dependent on secondary sources, and their social networks were limited to their family members due to their movement difficulty because of age/aging-related physical conditions.

ConclusionThis study explored and analyzed the intersectional factors that influenced the women and girls access to information during the COVID-19 pandemic from two contexts with varying degrees of pre-existing vulnerability and its extent. These include gender, age, state of vulnerability, power and privilege, socio-economic status, and physical (dis)ability. It is imperative that services geared towards the most vulnerable are contextualized and consider the intersectional factors that determine the communities access to information.

category: public and global health


title: Specific gait changes in prodromal hereditary spastic paraplegia type 4 - The preSPG4 study

abstract:
BackgroundIn hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.

ObjectivesIdentification of specific movement abnormalities before manifestation of gait impairment and quantification of disease progression in the prodromal phase.

Methods70 subjects participated in gait assessment, including 30 prodromal SPAST mutation carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy controls. Gait was assessed by an infrared-camera-based motion capture system to analyze features like range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale (SPRS) and neurofilament light chain (NfL) as a fluid biomarker indicating neurodegeneration.

ResultsCompared to healthy controls, we found an altered gait pattern in prodromal mutation carriers during the swing phase in segmental angles of the lower leg (p<0.05) and foot (p<0.01), and in heel ground clearance (p<0.01). Furthermore, ranges of motion of segmental angles were reduced for foot (p<0.001) and lower leg (p<0.01). These changes occurred in prodromal mutation carriers without quantified leg spasticity in clinical examination. Gait features correlated with NfL levels and SPRS score.

ConclusionGait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages.

category: neurology


title: School Feeding Programmes and Physical Nutrition Outcomes of Primary School Children in Developing Countries

abstract:
ContextSchool feeding programmes have been widely implemented and particularly in developing countries with the aim to improve school enrolment and attendance especially of girls and to reduce short term hunger to improve childrens performance in school.

Beyond the first 1000 days of the lives of children, school feeding programmes remain one of the critical interventions that have used schools as a platform to contribute to the fulfilment of their nutritional needs though the evidence to this effect is little and mixed.

ObjectiveThis review focused on assessing the impact of school feeding programmes on reduction in underweight, thinness, and stunting among primary school children in developing countries.

Data sourcesElectronic searches were carried out in PUBMED, SCORPUS and Cochrane library. The WHO clinical trials registry as well as reference lists of relevant articles were also hand searched.

Data ExtractionData was extracted from included studies which have been published in the past 10 years (2010 - August 2021) from original research where the main intervention was the provision of school based meals.

Data analysisMeta-analysis was conducted to determine changes in height-for-age (HAZ), weight-for-age (WAZ) and BMI-for-age (BAZ) z scores. A random effects model was applied to determine the mean difference in all outcomes of interest which were evaluated as continuous variables.

ResultsChildren aged 3 - 16 years were enrolled in the included studies and the number of participants ranged between 321 and 2,869 across studies. Of the included studies, the feeding intervention provided for a minimum of 30% RDA for the age group with the intervention lasting up to a maximum of 34 weeks. The impact of school feeding intervention on HAZ, BAZ and WAZ showed statistically non-significant (p>0.05) mean differences of 0.02 (95% CI, -0.06 to 0.10), 0.11 (95% CI, -0.01 to 0.23) and 0.06 (95% CI, -0.04 to 0.16) respectively

ConclusionSchool feeding interventions have not shown any significant positive effect on the physical nutrition outcomes of primary school children. Short duration of intervention of studies, poor compliance to feeding and substitution of school meals could have accounted for the weak effect sizes.

category: nutrition


title: Incorporating Genetic Determinants of Prostate-Specific Antigen Levels Improves Prostate Cancer Screening

abstract: Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. We evaluated the potential of genetic determinants of PSA levels to improve screening utility by accounting for variation in PSA not due to cancer. A multi-ancestry genome-wide meta-analysis of 95,768 men without prostate cancer discovered 128 PSA-associated index variants (P<5x10-8), including 82 novel signals. The resulting 128-variant polygenic score for PSA (PGSPSA) explained 7.3-8.8% of PSA variation in external validation cohorts. Adjusting PSA values using PGSPSA enabled more accurate diagnostic decisions, such as avoiding 17-20% of negative prostate biopsies. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR)=3.04, P=3.3x10-7; AUC=0.716) than unadjusted PSA (OR=2.80, P=3.2x10-6; AUC=0.684) and improved detection of aggressive disease when combined with a prostate cancer PGS (AUC: 0.732 vs. 0.645, P=3.3x10-4). We further showed that PSA-related selection bias distorts genetic associations with prostate cancer and hampers PGS performance. Our findings provide a roadmap towards personalizing cancer biomarkers and screening.

category: genetic and genomic medicine


title: Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy

abstract: The neuronal SNARE complex drive synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring rare variants in STX1A who present with a spectrum of intellectual, autism and epilepsy. Causative variants comprise a homozygous splice variant, three de novo missense variants and two inframe deletions of a single amino acid. We observed a phenotype mainly driven by epilepsy in the individuals with missense variants in contrast to intellectual disability and autistic behavior in individuals with single amino acid deletions and the splicing variant. In silico modeling of missense variants and single amino acid deletions show different impaired protein-protein interactions. We hypothesize the two phenotypic courses of affected individuals to be dependent on two different pathogenic mechanisms: (1) a weakened inhibitory STX1A-STXBP1 interaction due to missense variants results in an STX1A-related developmental epileptic encephalopathy and (2) a hampered SNARE complex formation due to inframe deletions causes an STX1A-related intellectual disability and autism phenotype.


title: SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy

abstract: Introductory ParagraphElevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and epilepsy1-5. We performed a genome-wide association, colocalization and pathway analysis of impulsivity in juvenile myoclonic epilepsy (JME). We identify genome-wide associated SNPs at 8q13.3 (p=7.5 x 10-9) and 10p11.21 (p=3.6 x 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (p=9.5 x 10-3). SLCO5A1 codes for a membrane-bound organic anion transporter6 and upregulates synapse assembly/organisation genes7. Pathway analysis also demonstrates 9.3-fold enrichment for synaptic assembly genes (p=0.03) including NRXN1, NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila homolog of SLCO5A1, causes both over-reactive startling behaviour (p=8.7 x 10-3) and increased seizure-like events (p=6.8 x 10-7). Polygenic risk score for ADHD correlates with impulsivity scores (p=1.60 x 10-3), demonstrating shared genetic contributions. SLCO5A1 loss-of-function represents a novel impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.


title: Minimal algorithms for knowledge representation in clinical decision support systems research: a theoretical and empirical analysis

abstract: Clinical decision support systems (CDSS) figures out as one of the most promising technologies for data-centered and AI-prompted healthcare. Its current developments are mainly guided by two disparate mindsets, namely a machine learning-centered framework and a classical rule-based framework. These respective approaches presents contrastive pros and cons. In the present study we provide an analysis showing that these two mindsets are actually related to each other, and straightforward algorithms are feasible by combining current standards for machine learning and classic decision tables algorithms. A theoretical analysis are provided, as well a computational implementation (in python). A real case scenario on radiological immaging exam prescription is used to ilustrate the successfully application of our results. Future work on benchmarking the proposed algorithms embodied in a fully operational clinical decision support system could extend our findings towards daily used systems.


title: Reporting of patient involvement: A mixed-methods analysis of current practice in health research publications

abstract:
ObjectivesTo evaluate the extent and quality of patient involvement reporting in examples of current practice in health research.

DesignMixed-methods study. We used a targeted search strategy across three cohorts to identify health research publications that reported patient involvement: publications published in The BMJ, publications listed in the PCORI database, and publications citing the GRIPP2 reporting checklist for patient involvement or a critical appraisal guideline for user involvement. Publications were coded according to three coding schemes: "Phase of involvement", the GRIPP2-SF reporting checklist, and the critical appraisal guideline.

Outcome measuresThe phase of the study in which patients were actively involved. For the BMJ sample, the proportion of publications that reported patient involvement. The quality of reporting based on the GRIPP2 short form reporting guideline. The quality of patient involvement based on the critical appraisal guideline. Quantitative and qualitative results are reported.

ResultsWe included 87 publications that reported patient involvement. Patients were most frequently involved in study design (90% of publications, n=78), followed by study conduct (70%, n=61), and dissemination (40%, n=35). Reporting of patient involvement was often incomplete, e.g., only 39% of publications (n=34) reported the aim of patient involvement. While the methods (56%, n=49) and results (59%, n=51) of involvement were reported more frequently, qualitative analyses showed that reporting was often unspecific and the influence of patients input remained vague. Therefore, a systematic assessment of the quality and impact of patient involvement according to the critical appraisal guideline was not feasible across samples.

ConclusionsAs patient involvement is increasingly seen as an integral part of the research process and requested by funding bodies, it is essential that researchers receive specific guidance on how to report patient involvement activities. Complete reporting builds the foundation for assessing the quality of patient involvement and its impact on research.

PROTOCOLThe protocol was published on the Open Science Framework: https://osf.io/vntgu/

STRENGTHS AND LIMITATIONSO_LIA targeted search strategy was used to identify examples of patient involvement reporting in a variety of publication types and study designs in health research
C_LIO_LIA mixed-methods approach allowed for an analysis of both the completeness and quality of patient involvement reporting
C_LIO_LIIn this study, we coded statements reporting on patient involvement in 87 health research publications that may be adapted for further use
C_LIO_LIReporting of patient involvement was insufficiently detailed to allow for a systematic assessment of the quality of patient involvement
C_LI

category: health systems and quality improvement


title: The Prevalence of Mental Health Disorders in people with HIV and the effects on the HIV Care Continuum

abstract:
ObjectiveTo describe the prevalence of diagnosed depression, anxiety, bipolar disorder, and schizophrenia in people with HIV (PWH) and the differences in HIV care continuum outcomes in those with and without mental health disorders (MHD).

DesignObservational study of participants in the NA-ACCORD.

MethodsPWH ([≥]18 years) contributed data on prevalent schizophrenia, anxiety, depressive, and bipolar disorders from 2008-2018 based on ICD code mapping. MH multimorbidity was defined as having [≥] 2 MHD. Log binomial models with generalized estimating equations estimated adjusted prevalence ratios (aPR) and 95% confidence intervals for retention in care ([≥] 1 visit/year) and viral suppression (HIV RNA [≤] 200 copies/mL) by presence vs. absence of each MHD between 2016-2018.

ResultsAmong 122,896 PWH, 67,643 (55.1%) were diagnosed with [≥] 1 MHD: 39% with depressive disorders, 28% with anxiety disorders, 10% with bipolar disorder, and 5% with schizophrenia. The prevalence of depressive and anxiety disorders increased between 2008-2018, while bipolar disorder and schizophrenia remained stable. MH multimorbidity affected 24% of PWH. From 2016-2018 (N=64,684), retention in care was marginally lower among PWH with depression or anxiety, however those with MH multimorbidity were more likely to be retained in care. PWH with bipolar disorder had marginally lower prevalence of viral suppression (aPR=0.98 [0.98-0.99]) as did PWH with MH multimorbidity (aPR=0.99 [0.99-1.00]) compared with PWH without MHD.

ConclusionThe prevalence of MHD among PWH was high, including MH multimorbidity. Although retention and viral suppression were similar to people without MHD, viral suppression was lower in those with bipolar disorder and MH multimorbidity.

category: hiv aids


title: The impact of community asymptomatic rapid antigen testing on COVID-19 hospital admissions: a synthetic control study

abstract:
ObjectiveTo analyse the impact on hospital admissions for COVID-19 of large-scale, voluntary, public open access rapid testing for SARS-CoV-2 antigen in Liverpool (UK) between 6th November 2020 and 2nd January 2021.

DesignSynthetic control analysis comparing hospital admissions for small areas in the intervention population to a group of control areas weighted to be similar in terms of prior COVID-19 hospital admission rates and socio-demographic factors.

InterventionCOVID-SMART (Systematic Meaningful Asymptomatic Repeated Testing), a national pilot of large-scale, voluntary rapid antigen testing for people without symptoms of COVID-19 living or working in the City of Liverpool, deployed with the assistance of the British Army from the 6th November 2020 in an unvaccinated population. This pilot informed the UK roll-out of SARS-CoV-2 antigen rapid testing, and similar policies internationally.

Main outcome measureWeekly COVID-19 hospital admissions for neighbourhoods in England.

ResultsThe intensive introduction of COVID-SMART community testing was associated with a 43% (95% confidence interval: 29% to 57%) reduction in COVID-19 hospital admissions in Liverpool compared to control areas for the initial period of intensive testing with military assistance in national lockdown from 6th November to 3rd December 2020. A 25% (11% to 35%) reduction was estimated across the overall intervention period (6th November 2020 to 2nd January 2021), involving fewer testing centres, before Englands national roll-out of community testing, after adjusting for regional differences in Tiers of COVID-19 restrictions from 3rd December 2020 to 2nd January 2021.

ConclusionsThe worlds first voluntary, city-wide SARS-CoV-2 rapid antigen testing pilot in Liverpool substantially reduced COVID-19 hospital admissions. Large scale asymptomatic rapid testing for SARS-CoV-2 can help reduce transmission and prevent hospital admissions.

Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABS- Previous studies on managing the spread of SARS-CoV-2 have identified asymptomatic transmission as significant challenges for controlling the pandemic.
- Along with non-pharmaceutical measures, many countries rolled out population-based asymptomatic testing programmes to further limit transmission.
- Evidence is required on whether large scale voluntary testing of communities for COVID-19 reduces severe disease, by breaking chains of transmission.

What this study adds- The findings of this study suggest that large scale rapid antigen testing of communities for SARS-CoV-2, within an agile local public health campaign, can reduce transmission and prevent hospital admissions.
- The results indicate that policy makers should integrate such testing into comprehensive, local public health programmes targeting high risk groups, supporting those required to isolate and adapting promptly to prevailing biological, behavioural and environmental circumstances.

category: infectious diseases


title: MICNet: Prediction of antibiotic susceptibility from microscopic images using transfer learning

abstract: Rapid susceptibility testing of bacterial isolates is crucial for anti-infective therapy, especially in critical cases such as bacteriaemia and sepsis. Nevertheless, empiric therapy is often initiated immediately and without testing because two days and more pass between a positive blood culture and a susceptibility profile, so in the meantime, the most likely pathogens are treated. However, current empiric recommendations are very generic. They often remain unmodified even in light of incoming, early data specific to a patients case, such as positive blood culture microscopy. Part of the hesitancy to change treatments presumably stems from a lack of systematic integration of early information beyond expert intuition. To enable targeted antimicrobial therapy earlier in a cases progression, we developed a method to predict antimicrobial susceptibility from microscopy images of bacteria alone. Our proof-of-concept MICNet combines two neural nets in a new chimerical architecture. It is pre-trained on about 100 thousand antibiograms and fine-tuned with only five thousand microscopic images through transfer learning. Predicting susceptibility profiles of four representative species, we show high predictive performance with a mean F-score of nearly 85%. In addition, several qualitative assessments show that our chimerical net has learned substantial expert knowledge. Therefore, MICNet is the first step towards personalized empiric therapy, combining prior pathogen probabilities with patient-specific data.


title: Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy

abstract:
IMPORTANCEMonoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19. However, no studies have evaluated adverse events and effectiveness of mAbs in pregnant persons compared to no mAb treatment.

OBJECTIVETo determine the frequency of drug-related adverse events and obstetric-associated safety outcomes after treatment with mAb compared to no mAb treatment, and the association between mAb treatment and a composite of 28-day COVID-19-related hospital admission or emergency department visit, COVID-19-associated delivery, or mortality.

DESIGN, SETTING, PARTICIPANTSPropensity-score matched cohort study of persons aged 12 years of age or older with a pregnancy episode and any documented positive SARS-CoV-2 test (polymerase chain reaction or antigen test) in the UPMC health system from April 30, 2021 to January 21, 2022.

EXPOSURESBamalanivmab and etesevimab, casirivimab and imdevimab, or sotrovimab treatment compared to no mAb treatment.

MAIN OUTCOMES AND MEASURESDrug-related adverse events, obstetric-associated safety outcomes among persons who delivered, and a risk-adjusted composite of 28-day COVID-19-related hospital admission or ED visit, COVID-19-associated delivery, or mortality.

RESULTSAmong 944 pregnant persons (median [IQR] age 30 [26, 33] years, White (79.5%, N=750), median [IQR] Charlson Comorbidity Index Score 0 (0,0)), 552 persons received mAb treatment (58%). Median gestational age at COVID-19 diagnosis or treatment was 179 days (IQR: 123, 227), and most persons received sotrovimab (69%, N=382). Of those with known vaccination status, 178 (62%) were fully vaccinated. Drug-related adverse events were uncommon (N=8, 1.4%), and there were no differences in any obstetric-associated outcome among 276 persons who delivered. After propensity score matching, the frequency of the composite 28-day COVID-19-associated outcome was 4.0 per 100 persons (95% CI 1.9, 6.2) in mAb-treated compared to 3.7 per 100 persons (95% CI 1.7, 5.8) in non-treated controls (risk difference = 0.31 per 100 persons [95% CI -2.6, 3.3). There were no deaths among mAb-treated patients compared to 1 death in the non-treated controls (p = 0.24). There were more non-COVID-19-related hospital admissions in the mAb-treated persons (risk difference 2.8 per 100 persons (95% CI 1.1, 4.5)).

CONCLUSIONS AND RELEVANCEIn pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment among persons who delivered. MAb treatment was associated with similar 28-day COVID-19-associated outcomes and more non-COVID-19-related hospital admissions compared to no mAb treatment.

Key PointsO_ST_ABSQUESTIONC_ST_ABSAmong pregnant persons with COVID-19, is monoclonal antibody (mAb) treatment associated with drug-related adverse events, similar frequency of obstetric-associated safety outcomes, and improved COVID-19-related clinical outcomes compared to no mAb treatment?

FINDINGSIn 944 pregnant persons with COVID-19, drug-related adverse events were mild and infrequent. Obstetric-associated safety outcomes were similar between mAb treatment and no treatment. There was no evidence of difference in risk of COVID-19-related hospital admission, COVID-19-associated delivery, or mortality between mAb treatment and no mAb treatment.

MEANINGIn pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were uncommon, and there was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment. MAb treatment was associated with similar 28-day risk of a COVID-19-associated outcome and more non-COVID-19-related hospital admissions compared to no mAb treatment.


title: Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants

abstract:
BackgroundUnderstanding immunological responses to SARS-CoV-2 vaccinations is integral to the management of SARS-CoV-2. We aimed to investigate determinants of antibody response to the BNT162b2 vaccine.

MethodsA cross-sectional analysis of anti-spike binding antibodies in serum samples from healthcare workers after one or two doses. Post-vaccination interval was restricted to [≥]21 days after dose 1, [≥]14 days after dose 2. The primary outcome was anti-S titres with explanatory variables dose, previous infection, dosing interval, age, ethnicity, and comorbidities. Multivariable linear regression was also conducted.

ResultsParticipants (n=5,871) included 3,989 post-dose 1, 1,882 post-dose 2. In SARS-CoV-2 infection naive, 99.65% seroconverted after dose 1 and >99.9% seroconverted after dose 2. Geometric mean anti-S titre in the naive cohort was 75.48 Binding Antibody Units/ml after dose 1, 7,049 BAU/ml after dose 2. Anti-S titres were higher in those with previous infection (2,111 BAU/ml post-dose 1, 16,052 BAU/ml post-dose 2), and increased with time between infection and vaccination: 3 months 1,970 (1,506-2,579) vs 9 months; 13,759 (8,097-23,379). Longer dosing intervals increased antibody response post-dose 2: 11-fold higher with a longer interval (>10 weeks) than those with shorter intervals, across all age-groups. Younger participants had higher mean titres (>2.2-fold higher). Multivariable regression modelling corroborated the above associations, and also found higher titres associated with being female or from an ethnic minority but lower titres among immunocompromised participants.

ConclusionThe number of antigen exposures and timing between vaccinations plays a significant role in the magnitude of the post-vaccination antibody response, with implications for long-term protection and post-booster antibody responses.


title: Variation in the Incidence of ventriculostomy related infection in critically ill patients

abstract:
IntroductionVentriculostomy related infection (VRI) or ventriculitis is a common and serious complication related to the placement of an external ventricular drain. Numerous sets of diagnostic criteria for VRI have been reported. We sought to estimate the variation in the incidence of VRI in a cohort of patients according to published diagnostic criteria.

Materials and MethodsWe conducted a retrospective cohort study. We included adult patients admitted to the Neuroscience intensive care unit with traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) who required an EVD. We estimated the incidence of VRI according to published diagnostic criteria. We compared the incidence to clinicians diagnoses of VRI. The primary outcome was the estimated incidence of VRI.

ResultsThere were 190 study participants, median age (interquartile range) of 58 (48 - 72), 106 (55.8%) were female. Admitting diagnoses was ICH in 30 (15.8%), TBI in 49 (25.8%) and SAH in 111 (58.4%) of cases respectively. There were 158 (83.2%) who required mechanical ventilation for a median of 6 (2-13) days. There were 29 (15.3%) who were treated for VRI by clinicians, with 6 (3.2%) having a positive culture. Variation in the diagnostic criteria led to an estimated incidence of VRI that ranged from 1 (0.5%) to 178 (93.7%).

ConclusionIn this critically ill cohort, the estimated incidence of VRI varied widely depending on which diagnostic criteria for VRI were applied. A comprehensive, consistent, objective and universal set of diagnostic criteria for ventriculostomy related infection is needed.

category: intensive care and critical care medicine


title: Elevated plasma Complement Factor H Regulating Protein 5 is associated with venous thromboembolism and COVID-19 severity

abstract: Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activation in vitro. Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.

category: cardiovascular medicine


title: Assessing Depression and Suicidality Among Recently Unemployed Persons with Obstructive Sleep Apnea and Socioeconomic Inequality

abstract:
BackgroundObstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder that often is associated with several psychiatric conditions. Job loss is a stressful life event that can also affect mental health and socioeconomic status (SES). We investigated whether there was an association between the prevalence of OSA and several psychiatric conditions within a cohort of persons who recently became unemployed and whether SES was a contributing factor.

MethodsData from 292 participants who completed the screening evaluation of the Assessing Daily Activity Patterns through occupational Transitions (ADAPT) Study were used to assess the association between the prevalence of OSA, and current and past depression, and past suicidality. A type III sleep home sleep monitor was used to identify the presence of OSA and assess its severity. Depression and suicidality were ascertained using the Mini-international neuropsychiatric interview. Years of education was used as a proxy for SES.

ResultsThere were no significant associations between severity of OSA, SES and current depression, past depression, and suicidality. Past suicidality was noted to be more common among those who were single/widowed (17.4%) or those who were divorced or separated (11.1%) (p=0.027). Current depression was more common among Hispanics in comparison to non-Hispanics. Furthermore, prevalence rates of both depression and past suicidality were higher than previous reports in general populations.

ConclusionsWithin a cohort of individuals who experienced recent job loss, there was no association between OSA and depression or past suicidality. Prevalence rates of both depression and past suicidality were higher than previous reports in the general population.


title: A Platform for Data-centric, Continuous Epidemiological Analyses

abstract: Guaranteeing durability, provenance, accessibility, and trust in open datasets can be challenging for researchers and organizations that rely on public repositories of data critical to epidemiology and other health analytics. Not only are the required repositories sometimes difficult to locate, and nearly always require conversion into a compatible format, they may move or change unpredictably. Any single change of the rules in one repository can hinder updating of a public dashboard reliant on pulling data from external sources. These concerns are particularly challenging at the international level, because systems aimed at harmonizing health and related data are typically dictated by national governments to serve their individual needs. In this paper, we introduce a comprehensive public health data platform, the EpiGraphHub, that aims to provide a single interoperable repository for open health and related data, curated by the international research community, which allows secure local integration of sensitive databases whilst facilitating the development of data-driven applications and reports for decision-makers. The platform development is co-funded by the World Health Organization and is fully open-source to maximize its value for large-scale public health studies.


title: A Statistical Argument Against Vaccine Injury

abstract:
Vaccine hesitancy is a major threat to public health. While the root causes of vaccine hesitancy are numerous, they largely revolve around some form of perceived risk to the self. In particular, the unknown long-term risks are amongst the most frequently cited concerns. In this work, we show that regardless of their peak onset following vaccination, the incidence of adverse outcomes will follow some distribution f (x| {micro}, {sigma}2) of mean onset {micro}, and standard deviation{sigma} , and variance{sigma} 2. Despite the small proportion of events at the tails of these distributions, the large-scale public deployment of vaccines would imply that any signal for a given adverse outcome would be observed soon after distribution begins, even in cases where tx < t{micro}-3{sigma}. The absence of such an early signal, however low, would suggest that long term effects are unlikely and that vaccine safety is therefore likely. Indeed, when enough individuals have been exposed to a new therapy - even if the majority of adverse outcomes only manifest at a future time t{micro}, the number of adverse outcomes given by the cumulative density function (CDF) near t0 + dt > 0. Otherwise stated:

O_FD O_INLINEFIG[Formula 1]C_INLINEFIGM_FD(1)C_FD

We evoke the theory behind normal (Gaussian) and skew-normal distributions and use Chebyshevs Theorem to evaluate the COVID-19 vaccine data as an example. The findings of this study are not vaccine-specific and can be applied to assess the health effects of the mass distribution of any good, treatment or policy at large.


title: Genetic diversity and spatiotemporal distribution of SARS-CoV-2 alpha variant in India

abstract: After the spill to humans, in the timeline of SARS-CoV-2, several positively selected variants have emerged. A phylogeographic study on these variants can reveal their spatial and temporal distribution. In December 2020, the alpha variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has been designated as a variant of concern (VOC) by WHO, was discovered in the southeastern United Kingdom (UK). Slowly, it expanded across India, with a considerable number of cases, particularly in North India. The study focuses on determining the prevalence and expansion of the alpha variants in various parts of India. The genetic diversity estimation helped us understand various evolutionary forces that have shaped the spatial distribution of this variant during the peak. Overall, our study paves the way to understand the evolution and expansion of a virus variant.


title: Association of Sedentary and Physical Activity Behaviors with Body Composition: a Genome-Wide Association and Mendelian Randomization Study

abstract:
ObjectivesStudies suggest that body composition can be independently improved through physical activity (PA). We performed a Mendelian randomization (MR) study to test the incremental benefits of sedentary behavior and various physical activity (PA) exposures on body composition outcomes as assessed by anthropometric indices, lean body mass (LBM) (kg), body fat (%), and visceral adipose tissue (VAT) (kg).

MethodsGenetic instruments were identified for both self-reported and accelerometer-measured sedentary behavior and PA. Outcomes included anthropometric and dual-energy X-ray absorptiometry measures of adiposity, extracted from the UK Biobank and the largest available consortia. Multivariable MR (MVMR) included educational attainment as a covariate to address potential confounding. Sensitivity analyses were evaluated for weak instrument bias and pleiotropic effects.

ResultsWe did not identify consistent associations between genetically-predicted self-reported and accelerometer-measured sedentary behavior and body composition outcomes. All analyses for self-reported moderate PA were null for body composition outcomes. Genetically-predicted PA at higher intensities was protective against VAT in MR and MVMR analyses of both accelerometer-measured vigorous PA (MVMR {beta} = -0.15, 95% Confidence Interval (CI): -0.24, -0.07, p<0.001) and self-reported participation in strenuous sports or other exercises (MVMR {beta} = -0.27, 95%CI: -0.52, -0.01, p=0.034) was robust across several sensitivity analyses.

ConclusionsWe did not identify evidence of a causal relationship between genetically-predicted PA and body composition, with the exception of a putatively protective effect of higher-intensity PA on VAT. Protective effects of PA against VAT may support prior evidence of biological pathways through which PA decreases risk of downstream cardiometabolic diseases.


title: An epidemiological and intervention assessment of the malaria epidemic in Bolivar, Venezuela: a modelling study

abstract:
BackgroundVenezuela has experienced an explosive resurgence in Plasmodium falciparum and Plasmodium vivax malaria incidence over the last decade due to various social, political, and economic factors. To ensure national and regional progress towards malaria elimination, there is an urgent need to better understand the epidemiological dynamics of this malaria outbreak at its epicenter in the southern state of Bolivar and to identify the sets of interventions that may be necessary to reduce transmission and incidence.

MethodsWe fitted transmission models of P. falciparum and P. vivax to weekly incidence data in Bolivar, Venezuela during 2000-2018. We estimated the magnitude of local transmission for both Plasmodium spp. and inferred the contribution of relapses and reinfections to P. vivax incidence in the region. Compared to a business-as-usual scenario, we projected the impact of different interventions on Plasmodium spp. incidence during the period 2021-2023.

FindingsWe estimated that 63{middle dot}7 - 73{middle dot}3% of all P. vivax infections in Bolivar are relapses, leading to as many as 51,800 observed relapses misclassified per year as reinfections in the routine surveillance data. Our estimates suggest that the reproduction number remains close to one for both Plasmodium spp., pointing towards the feasibility of control. Long-lasting insecticidal nets (LLINs) were projected to cause greater proportional reductions in P. falciparum incidence than P. vivax incidence, and mass drug administration (MDA) with an 8-aminoquinoline and a blood-stage partner drug was projected to cause the greatest reduction in P. vivax incidence, provided that adherence rates were high.

InterpretationControl of the malaria outbreak in Southeastern Venezuela is feasible, should appropriate resources to support surveillance and control be brought to bear. Coupling the distribution of LLINs and a focal MDA with an 8-aminoquinoline and a blood-stage partner drug may lead to the greatest reduction in malaria incidence.

FundingNational Science Foundation and the University of Notre Dame

RESEARCH IN CONTEXTO_ST_ABSEvidence before the studyC_ST_ABSWe searched PubMed, bioRxiv, and medRxiv for articles in English published on or before May 25th, 2021 using the following keywords: "Venezuela", "malaria", AND "model*". Previous studies have applied statistical models to characterize the relationship between malaria incidence and climate in Venezuela, concluding that the reproduction number is low and suggesting the feasibility of control. A study fitting a mechanistic transmission model to epidemiological data to allow for projecting the impact of alternative approaches to control has not been performed.

Added value of the studyWe fitted Plasmodium falciparum and Plasmodium vivax transmission models to 20 years of weekly incidence data to estimate the transmission of both Plasmodium spp. and characterize the contribution of relapses and reinfections to P. vivax incidence in Bolivar, Venezuela. We also projected the likely impact of interventions in the region under alternative scenarios about control.

Implications of the available evidenceThe burden of Plasmodium vivax relapses in Bolivar is underestimated from routine surveillance data, so control interventions must target the hypnozoite reservoir in the region. Mass drug administration (MDA) is projected to be impactful for both Plasmodium spp., though tradeoffs between coverage and adherence suggest that a focal MDA with an 8-aminoquinoline and a blood-stage partner drug may yield the greatest impact.


title: Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study

abstract: It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged [≥]16 years 35{+/-}8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.


title: Weakly supervised and transfer learning for adenocarcinoma classification in transurethral resection of the prostate whole slide images

abstract: The transurethral resection of the prostate (TUR-P) is generally considered an option for benign prostatic diseases especially nodular hyperplasia patients who have moderate to severe urinary problems that have not responded to medication. Importantly, incidental prostate cancer are diagnosed at the time of TUR-P for benign prostatic disease. Since diagnosing a large number of cases containing TUR-P specimens which are characterized by a very large volume of tissue fragments by pathologists using a conventional microscope is time-consuming and limited in terms of human resources. Thus, it is necessary to develop new techniques which can rapidly and accurately screen large numbers of TUR-P specimens. Computational pathology applications which can assist pathologists in detecting prostate adenocarcinoma from TUR-P whole slide images (WSIs) would be of great benefit for routine histopathological workflow. In this study, we trained deep learning models to classify TUR-P WSIs into prostate adenocarcinoma and benign (non-neoplastic) lesions using transfer and weakly supervised learning. We evaluated the models on TUR-P, needle biopsy, and The Cancer Genome Atlas (TCGA) public dataset test sets, achieving an ROC-AUC up to 0.984 in TUR-P test sets for adenocarcinoma. The results demonstrate the high promising potential of deployment in a practical TUR-P histopathological diagnostic workflow system.

category: pathology


title: Diabetes and neuroaxonal damage in Parkinson's disease

abstract: Patients with Parkinsons disease (PD) with coexistent type 2 diabetes (T2DM) can manifest with more severe motor and cognitive phenotypes. The precise reasons for this remain unclear though underlying pathophysiological differences are increasingly implicated. More severe neuroaxonal injury in PD patients with T2DM was recently proposed as a potential mechanism for this. We explored this in the tracking Parkinsons study and confirmed these findings. Cases with T2DM had higher serum neurofilament light levels and this remained significant after correction for age and vascular risk factor burden. Disentangling the underlying mechanism for more rapid axonal damage will be important in the development of disease modifying therapies for PD.


title: Optical coherence tomography assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis

abstract:
ObjectiveOptical coherence tomography (OCT) assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis.

Methods45 patients with familial MS (fMS), 58 patients with sporadic MS (sMS) and 35 healthy controls were included in the study. OCT was performed with the spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Germany). The retinal nerve fiber layer (RNFL) thickness and macular volume (MV) were measured.

ResultsA significant thinning of the global RNFL thickness was detected in both forms of MS compared to control group, (86,61 (+/- 14,74) {micro}m in sMS, 85,8 (+/- 12,7) {micro}m in fMS, 97,96 (+/- 7,6) {micro}m in control group; p <0,001). There was no significant difference in the global RNFL thickness between sMS and fMS. A significant reduction of the MV was shown in sMS and fMS compared to control group (8,12 (+/- 1,14) mm3 in sMS, 8,1 (+/- 1,12) mm3 in fMS, and 8,81 (+/- 0,31) mm3 in control group; p = 0,003). No difference in MV between sMS and fMS was found. However, in eyes with history of optic neuritis (ON) MV was significantly reduced in sMS versus fMS (8,12 (+/- 2,87) mm3 vs. 8,42 (+/- 0,54) mm3; p=0,05).

ConclusionWe confirmed the presence of axonal and neuronal damage of the retina in sMS and fMS. ON induced a significantly greater reduction of MV in sMS compared to fMS, indicating a stronger neuronal damage in ON eyes in sMS than in fMS.

KEY MESSAGESThe familial MS accounts for a significant proportion of MS patients and there is still ongoing discussion on the distinction between familial (fMS) and sporadic (sMS) forms of this disease. Using OCT, we confirmed the presence of axonal and neuronal damage in the retina in both forms of MS. We found that optic neuritis (ON) induced a greater retinal neuronal damage in sMS than in fMS. These results support the conclusion that there are some discrete differences in pathological processes occurring in the retina in sMS and fMS.


title: Geospatial distribution of Hepatitis B prevention services in Wakiso District, Central Uganda

abstract:
IntroductionDespite global and national efforts in place for the prevention and control of Hepatitis B, there remains a gap in access to hepatitis B prevention services such as testing and vaccination. Nonetheless, there is limited evidence of the geospatial distribution of Hepatitis B services. This study established the geospatial distribution of HBV vaccination services in Wakiso District, Uganda.

Materials and methodsA cross-sectional quantitative descriptive study was conducted among 55 healthcare facilities including 6 hospitals, and 49 primary care facilities in Wakiso district. Data were collected using the KoboCollect application. Quantitative data were analysed using STATA 14.0. A chi-square test was performed to establish the relationship between healthcare facility characteristics and the availability of hepatitis B services. ArcGIS (version 10.1) was used for analysis of geospatial data.

ResultsThe hepatitis B vaccine was available in only 27.3 % (15) of the facilities, and 60% (33) had testing services. Receipt of the hepatitis B vaccine doses in the last 12 months was associated with the level of healthcare facility (p=[≤]0.001) and location (p=0.030). Availability of the Hepatitis B vaccines at the time of the survey was associated with the level of healthcare facility (p=0.002) and location (p=0.010). Availability of hepatitis B testing services was associated with level of healthcare facility (p=0.031), ownership (p[≤]0.001) and location (p=0.010). Healthcare facilities offering vaccination and testing services were mostly in urban healthcare facilities, and close to Kampala, Ugandas capital.

ConclusionHepatitis B services were sub-optimal across all healthcare facility levels, locations, and ownership. The majority of the hepatitis B prevention services were provided in urban settings, close to major towns, municipalities, and the city. This calls a extension of hepatitis B prevention services to rural, public and PNFP healthcare facilities.


title: COVID-19 outcomes by cancer status, type, treatment, and vaccination

abstract:
BackgroundObservational studies have identified patients with cancer as a potential subgroup of individuals at elevated risk of severe SARS-CoV-2 (COVID-19) disease and mortality. Early studies showed an increased risk of COVID-19 mortality for cancer patients, but it is not well understood how this association varies by cancer site, cancer treatment, and vaccination status.

MethodsUsing electronic health record data from an academic medical center, we identified 259,893 individuals who were tested for or diagnosed with COVID-19 from March 10, 2020, to February 2, 2022. Of these, 41,218 tested positive for COVID-19 of whom 10,266 had a past or current cancer diagnosis. We conducted Firth-corrected, covariate-adjusted logistic regression to assess the association of cancer status, cancer type, and cancer treatment with four COVID-19 outcomes: hospitalization, intensive care unit (ICU) admission, mortality, and a composite "severe COVID-19" outcome which is the union of the first three outcomes. We examine the effect of the timing of cancer diagnosis and treatment relative to COVID diagnosis, and the effect of vaccination.

ResultsCancer status was associated with higher rates of severe COVID-19 infection [OR (95% CI): 1.18 (1.08, 1.29)], hospitalization [OR (95% CI): 1.18 (1.06, 1.28)], and mortality [OR (95% CI): 1.22 (1.00, 1.48)]. These associations were driven by patients whose most recent initial cancer diagnosis was within the past three years. Chemotherapy receipt was positively associated with all four COVID-19 outcomes (e.g., severe COVID [OR (95% CI): 1.96 (1.73, 2.22)], while receipt of either radiation or surgery alone were not associated with worse COVID-19 outcomes. Among cancer types, hematologic malignancies [OR (95% CI): 1.62 (1.39, 1.88)] and lung cancer [OR (95% CI): 1.81 (1.34, 2.43)] were significantly associated with higher odds of hospitalization. Hematologic malignancies were associated with ICU admission [OR (95% CI): 1.49 (1.11, 1.97)] and mortality [OR (95% CI): 1.57 (1.15, 2.11)], while melanoma and breast cancer were not associated with worse COVID-19 outcomes. Vaccinations were found to reduce the frequency of occurrence for the four COVID-19 outcomes across cancer status but those with cancer continued to have elevated risk of severe COVID [cancer OR (95% CI) among those fully vaccinated: 1.69 (1.10, 2.62)] relative to those without cancer even among vaccinated.

ConclusionOur study provides insight to the relationship between cancer diagnosis, treatment, cancer type, vaccination, and COVID-19 outcomes. Our results indicate that it is plausible that specific diagnoses (e.g., hematologic malignancies, lung cancer) and treatments (e.g., chemotherapy) are associated with worse COVID-19 outcomes. Vaccines significantly reduce the risk of severe COVID-19 outcomes in individuals with cancer and those without, but cancer patients are still at higher risk of breakthrough infections and more severe COVID outcomes even after vaccination. These findings provide actionable insights for risk identification and targeted treatment and prevention strategies.


title: Public attitudes towards COVID-19 vaccines in Africa: a systematic review

abstract:
BackgroundAs COVID-19 vaccine acquisition and deployment accelerates, tensions also increase. This review aims to identify and understand the significance of population attitudes toward COVID-19 vaccines in Africa.

MethodsA systematic review was conducted. Searches were conducted in MEDLINE, CINAHL, EMBASE, and Global Health databases. Database searches began on June 23, 2021, and the last search date was June 30, 2021. The methodological quality of the studies included in this review was assessed using the Mixed methods appraisal tool.

ResultsA total of 609 articles were retrieved, and 23 met the eligibility criteria. All 23 included studies were cross-sectional. Three attitudes were identified: acceptance, reluctance, and refusal to be vaccinated. Acceptance of vaccination was motivated by confidence in the accuracy of the governments response to COVID-19 and the fact that relatives had been diagnosed with or died from COVID-19. Reluctance was based on fear of vaccine quality and side effects, and insufficient clinical trials. Finally, refusal to be vaccinated was justified by reasons such as the unreliability of clinical trials and insufficient data regarding the vaccines adverse effects.

ConclusionThis review revealed common attitudes of African populations toward COVID-19 vaccines. The results indicate that research needs to focus more on identifying facilitators of COVID-19 vaccination. However, they also provide essential elements for health personnel in charge of vaccination to develop strategies to achieve satisfactory coverage rates


title: Systematic review of food insecurity and violence against women and girls: mixed methods findings from low- and middle-income settings

abstract:
IntroductionViolence against women and girls (VAWG) is a global human rights and public health concern. Food insecurity is a sign of severe poverty, and likely to heighten womens vulnerability to VAWG and mens perpetration of it. However, the extent of the association and the multiple pathways between food insecurity and VAWG are not well understood.

MethodsWe systematically assessed peer reviewed quantitative and qualitative literature to explore this in low- and middle-income countries (LMIC). Fixed effects meta-analysis was used to synthesize quantitative evidence. Qualitative data was analyzed using thematic analysis.

ResultsWe identified 23 quantitative and 19 qualitative or mixed-methods peer-reviewed manuscripts. In a meta-analysis of 21 cross-sectional studies with 20,378 participants, food insecurity was associated with doubled odds of reported VAWG (odds ratio [OR]=2.38, 95% confidence interval [CI]=1.82-3.10). This finding was consistent for both womens experience or male perpetration of VAWG. Qualitative and mixed-methods papers offered insight that underlying conditions of inequitable gender norms, economic deprivation, and social isolation frame both food insecurity and VAWG. Food insecurity may trigger survival behaviors due to household stress and lack of meeting expected gender roles, which leads to VAWG. VAWG exposure may lead to food insecurity if women are more impoverished after leaving a violent household. Potential protective factors include financial stability, the involvement of men in VAWG programming, transformation of gender norms, and supporting women to develop new networks and social ties.

ConclusionStrong evidence exists for a relationship between food security and IPV. Future funding should target causal directions and preventive options through longitudinal and interventional research. Strategies to ensure households have access to sufficient food and safe relationships are urgently needed to prevent VAWG.


title: A pipeline for tabular dataset formation from unstructured data provided by ACR Appropriateness Criteria guidelines

abstract: Currently, data performns a critical concept for disparate human activities, from law to technology. Among data-centric technologies, clinical decision support systems (CDSS) figures out as one of the most promising for healthcare. Despite the technological advances facilitating its implementation, the maintainance of knowledge base for CDSS remains open to improvements. Here, we argue that the Appropriateness Criteria provided by ACR guidelines can be used as a open data-source that, combined with appropriate algorithms, can push forward basic research and technological developments regarding knowledge base for CDSS. Therefore, we developed a pipeline capable of forming tabular datasets from ACR guidelines, stored in a web site as textual PDF files. We also experimentally demonstrate that the proposed pipeline successfully recorvers the interested contents, and the best composition, in terms of its component algorithms, is discussed. Future research focused on algorithms flexibility in the face of PDF template updates could improve our work.


title: Accuracy of US CDC COVID-19 Forecasting Models

abstract: Accurate predictive modeling of pandemics is essential for optimally distributing resources and setting policy. Dozens of case predictions models have been proposed but their accuracy over time and by model type remains unclear. In this study, we analyze all US CDC COVID-19 forecasting models, by first categorizing them and then calculating their mean absolute percent error, both wave-wise and on the complete timeline. We compare their estimates to government-reported case numbers, one another, as well as two baseline models wherein case counts remain static or follow a simple linear trend. The comparison reveals that more than one-third of models fail to outperform a simple static case baseline and two-thirds fail to outperform a simple linear trend forecast. A wave-by-wave comparison of models revealed that no overall modeling approach was superior to others, including ensemble models, and error in modeling has increased over time during the pandemic. This study raises concerns about hosting these models on official public platforms of health organizations including the US-CDC which risks giving them an official imprimatur and further raising concerns if utilized to formulate policy. By offering a universal evaluation method for pandemic forecasting models, we expect this work to serve as the starting point towards the development of more sophisticated models.


title: Investigating Attitudes, Motivations and Key Influencers for vaccine uptake among late adopters of COVID-19 vaccination in Africa

abstract:
BackgroundThe rapid development of vaccines in response to the COVID-19 pandemic has provided an effective tool for the management of COVID-19. However, in Africa there has been a poor uptake of COVID-19 vaccines with only 15% vaccine coverage compared to the WHO global target of 70%. One of the important drivers has been vaccine hesitancy, understanding late adopters of vaccination can provide insights into the attitudes, motivations and influences that can enhance vaccine uptake.

MethodsBetween January 4 - February 11, 2022, we conducted a survey among adults presenting for their first dose of a COVID-19 vaccine almost 12-months after the vaccination program began. Vaccines were free and provided at clinics and outreach centers in Harare, Zimbabwe. The questionnaire assessed environmental and individual factors (attitudes, barriers, motivations, key influencers, and information sources) that influenced the decision to present for vaccination. Baseline socio-demographic data and responses to survey questions were summarized using descriptive statistics. Binary logistic regression models were developed to understand factors associated with vaccine confidence.

Results1016 adults were enrolled into the study, 508 (50%) were female, 126 (12.4%) had HIV co-infection. The median age was 30 years (IQR 22 - 39). Women were more likely to have negative views about the COVID-19 vaccine compared to men (OR 1.51 (95%CI 1.16, 1.97, p=0.002). Women compared to men and older adults ([≥] 40 years) compared with youth (18-25 years) were more likely to have  major concerns about vaccines. Most concerns were about safety with 602 (59.3%) concerned about immediate and 520 (51.2%) about long-term health effects of vaccines. People living with HIV (PLWH) were more likely to perceive vaccines as safe (OR 1.71 (95%CI: 1.07, 2.74, p=0.025), effective (1.68 (95%CI: 1.07, 2.64, p=0.026) and to trust regulatory systems for approving vaccines (OR 1.79 (95% CI: 1.11, 2.89, p=0.017) compared to those without HIV. Internet users were less likely to perceive vaccines as safe (OR 0.72 (95% CI: 0.55, 0.95, p=0.021), effective (OR 0.61 (95% CI: 0.47, 0.80, p<0.001) or trust regulatory processes for approving vaccines (OR 0.64 (95% CI: 0.48, 0.85, p=0.002) compared to non-internet users. Social influence was a key factor in the decision to be vaccinated with family members being the primary key influencers for 560 (55.2%) participants. The most important reason for receiving the COVID-19 vaccine today for 715 (70.4%) participants was the protection of individual health. The most trusted source of information regarding the vaccine was the Ministry of Health (79.7%) and the radio, television and social media were the preferred sources for obtaining this information. Social media was a more likely source for youth and those with higher levels of education.

ConclusionImproving vaccine coverage will need targeted communication strategies that address negative perceptions of vaccines and associated safety and effectiveness concerns. Leveraging normative behavior as a social motivator for vaccination will be important as close social networks are key influences of vaccination. Traditional media remains important for health communication in Africa and should be strengthened to counter social media-based misinformation that drives concerns about safety and effectiveness particularly among internet users.


title: Assessing the effectiveness of malaria interventions at the regional level in Ghana using a mathematical modelling Application

abstract:
BackgroundSupporting malaria control with interfaced applications of mathematical models that enables investigating effectiveness of various interventions as well as their cost implications could be supportive. Through their usage for planning, these applications may improve the chances of attaining various set targets such as those of the National Strategic Plan policy for malaria control 2014-2020 in Ghana. This approach could boost the fight against malaria and accelerate the achievement of pre-elimination in a shorter time

MethodsA single patch malaria model was adapted and used for simulating the incidence of malaria in all ten administrative regions of Ghana. The model and its application were developed by the Modelling and Simulation Hub Africa (MASHA) and calibrated using aggregated district level data captured on the District Health Information Management System (DHIMS) in Ghana from 2012 to 2018. Average monthly rainfall at the zonal level was fitted to trigonometric functions for each zone using least squares approach. These zonal functions were then used as forcing functions for all the regions within their respective zones. Various intervention packages such as increasing insecticide treated bednets coverage and usage, increasing indoor residual spraying coverage and effectiveness, improving the health system effectiveness, increasing seasonal malaria chemotherapy coverage among children were investigated to observe the their impact on averting malaria incidence by 2030.

ResultsIncreased usage of bednets but not only coverage levels, predicted to lead to significant proportion of cases of malaria averted in all regions. Whereas, improvements in the health systems by way of health seeking, testing and treatment predicted to lead to a decline in incidence largely in all regions, it allows more incidence cases to be detected in the Upper East, Upper West and Brong-Ahafo regions. With an increased coverage of SMC, to include higher age groups, a modest proportion of cases could be averted in populations of the Guinea savannah. Indoor residual spraying could also benefit populations of the Transitional forest and Coastal savannah as its impact is significant in averting incidence.

ConclusionsHaving achieved relatively high bednet coverage, enhancing bednet usage to at least a doubling of the current usage levels and deployed in combination with various interventions in all the regions predicted a significant reductions, ranging from 44.0% - 97.0%, in malaria incidence. Regions of the Transitional forest and Coastal savannah could also benefit from a drastic decline in incidence following a gradual introduction of indoor residual spraying on a sustained basis. A much improved health system in all regions could potentially cater for all incident cases that were not prevented through vector control activities. The modelling application has shown to be beneficial given the opportunity to be able to study in relatively more detail, the regional differences in malaria morbidity in Ghana.


title: Spinal cord damage in Friedreich's ataxia: Results from ENIGMA-Ataxia

abstract:
ObjectiveSpinal cord damage is a hallmark of Friedreich ataxia (FRDA), but its progression and clinical correlates remain unclear. Here we performed a characterization of cervical spinal cord structural abnormalities in a large multisite FRDA cohort.

MethodsWe performed a cross-sectional analysis of cervical spinal cord (C1 to C4) cross-sectional area (CSA) and eccentricity using MRI data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched controls. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age.

ResultsIndividuals with FRDA, relative to controls, had significantly reduced CSA at all examined levels, with large effect sizes (d>2.1) and significant correlations with disease severity (r<-0.4). Similarly, we found significantly increased eccentricity (d>1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, while CSA appears to decrease progressively, eccentricity remains stable over time.

InterpretationPrevious research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage or both. Hence, our data support the hypothesis that damage to DC and CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, whereas CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression.


title: Improving the Diagnosis of SIBO Using an At-Home Handheld App Connected Breath Analysis Device (AIRE)

abstract:
INTRODUCTIONSmall Intestinal Bacterial Overgrowth (SIBO) is a common yet underdiagnosed condition. Lactulose hydrogen breath tests (LHBT) are typically used to detect SIBO; however, current breath testing methods require specialised, expensive equipment and technical support and are either done at a point-of-care facility and/or have to be mailed to a central laboratory. To address these issues a novel hand-held breath analyzer (AIRE(R), FoodMarble) was tested. The aims of this study were first, to perform a technical assessment of the AIRE device, second to compare the performance of the AIRE device against a commercially available mail-in LHBT kit using a zero-inflated negative binomial mixed effect model.

METHODSThree AIRE devices were tested with certified test gases covering a diagnostically meaningful range (hydrogen mixed with air at 3 ppm, 10 ppm and 50 ppm). For the clinical study, 36 patients suspected to have SIBO presenting to a tertiary level clinic were provided with an AIRE device and performed concurrent LHBTs at home with a mail-in LHBT kit.

RESULTSThe overall average readings (mean {+/-} SD) for the AIRE devices tested at 3 ppm, 10 ppm and 50 ppm H2 were: 3.5 {+/-} 0.7 ppm; 10.7 {+/-} 1.1 ppm and 49.5 {+/-} 2.6 ppm respectively. The overall mean absolute error across the tested devices was 1.2 ppm. A significant positive correlation (r = 0.78, p < 0.001) was demonstrated between AIRE and mail-in kit H2 values.

DISCUSSIONThe AIRE device is a compelling alternative to mail-in LHBT kits for the diagnosis of SIBO. The AIRE device may also offer advantages over other traditional breath testing methods.

category: gastroenterology


title: Exploring biomarkers of processing speed and executive function: the role of the anterior thalamic radiations

abstract:
IntroductionProcessing speed and executive functioning are often impaired after stroke and in typical aging. However, there are no reliable neurological markers of these cognitive impairments. The trail making test (TMT) is a common index of processing speed and executive function. Here, we tested candidate MRI markers of TMT performance in a cohort of older adults and individuals with chronic stroke.

MethodsIn 61 older adults and 32 individuals with chronic stroke, we indexed white matter structure with region-specific lesion load (WMH and stroke lesions) and diffusion tensor imaging (DTI) from four regions related to TMT performance: the anterior thalamic radiations (ATR), superior longitudinal fasciculus (SLF), forceps minor, and cholinergic pathways. Regression modelling was used to identify the marker(s) that best predicted TMT performance.

ResultsDTI metrics of the ATR predicted processing speed in both the older adult (TMT A: {beta}=-3.431, p<0.001) and chronic stroke (TMT A: {beta}=11.282, p<0.001) groups. In the stroke group executive function was best predicted by a combination of ATR and forceps minor DTI metrics in the chronic stroke group (TMT B: adjustedR2=0.438, p<0.001); no significant predictors of executive function (TMT B) emerged in the older adult group. No imaging metrics related to set shifting (TMT B-A). For all TMT outcome measures with significant imaging predictors, regional DTI metrics predicted TMT performance above and beyond whole-brain stroke and WMH volumes and removing whole-brain lesion volumes improved model fits.

ConclusionsIn this comprehensive assessment of candidate imaging markers, we demonstrate an association between ATR microstructure and processing speed and executive function performance. Regional DTI metrics provided better predictors of cognitive performance than whole-brain lesion volumes or regional lesion load, emphasizing the importance of lesion location in understanding cognition. We propose ATR DTI metrics as novel candidate imaging biomarker of post-stroke cognitive impairment.

category: rehabilitation medicine and physical therapy


title: Physiotherapists use different motivational strategies tailored to an individual's condition: a qualitative study

abstract:
QuestionHow do physiotherapists use different motivational strategies for individuals in stroke rehabilitation?

DesignA qualitative study using in-depth semi-structured online interviews.

ParticipantsA criterion sample of 15 physiotherapists who have worked in rehabilitation for over 10 years and have an interest in an individuals motivation.

InterventionNot applicable.

Outcome measuresPhysiotherapists perspectives and experiences regarding motivational strategies used depending on the individuals condition.

ResultsA total of nine themes emerged from the data upon thematic analysis and inductive coding. The participants used different strategies to encourage individuals active participation in physiotherapy depending on their (1) mental health problems, (2) physical difficulties, (3) level of cognitive function, (4) personality, (5) activities and participation, (6) age, (7) human environment, and (8) type of rehabilitation service where the individual undergoes treatment. For example, in cases where an individual lost self-confidence, participants offered practice tasks that the individual could achieve with little effort to make them experience success. Conversely, for individuals with overconfidence, participants would provide them with a relatively difficult practice task to help them realize the necessity of practice through the experience of failure. The interviews also revealed (9) motivational strategies used regardless of the individuals condition. For instance, patient-centred communication was used to build a rapport with individuals, irrespective of their condition.

ConclusionThis qualitative study is the first to demonstrate motivational strategies that physiotherapists use based on the individuals condition. Our findings provide a deeper understanding of the selection of motivational strategies in stroke rehabilitation.


title: Clinical measures of balance and gait cannot differentiate somatosensory impairments in people with lower-limb amputation.

abstract:
BackgroundIn addition to a range of functional impairments seen in individuals with a lower-limb amputation, this population is at a substantially elevated risk of falls [1,2]. Studies postulate that the lack of sensory feedback from the prosthetic limb contributes heavily to these impairments, but the extent to which sensation affects functional measures remains unclear [3,4].

Research QuestionThe purpose of this study is to determine how sensory impairments in the lower extremities relate to performance with common clinical functional measures of balance and gait in individuals with a lower-limb amputation. Here we evaluate the effects of somatosensory integrity to both clinical and lab measures of static, reactive and dynamic balance, and gait stability.

MethodsIn 20 individuals with lower-limb amputation (AMP) and 20 age and gender-matched able-bodied controls (CON), we evaluated the relationship of measures of sensation (pressure, proprioception, and vibration) to measures of balance and gait. Static, reactive, and dynamic balance were assessed using the Sensory Organization Test (SOT), Motor Control Test (MCT), and Functional Gait Assessment (FGA), respectively. Gait stability was assessed through measures of step length asymmetry and step width variability. Sensation was categorized into intact or impaired sensation by pressure thresholds and differences across groups were analyzed.

ResultsThere were significant differences between AMP and CON groups for the reliance on vision for static balance in the SOT, MCT, and FGA (p<0.01). Despite these differences across groups, there were no significant differences within the AMP group based on intact or impaired sensation across all functional measures.

SignificanceDespite being able to detect differences between able-bodied individuals and individuals with an amputation, these functional measures are unable to distinguish between levels of impairment within participants with an amputation. These findings suggest that more challenging and robust metrics are needed to evaluate the relationship of sensation and function in individuals with an amputation.

Research reported in this publication was supported by the National Institutes of Health [NINDS Award Number UH3NS100541 and NICHD Award Number F30HD098794]. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.


title: Rasch Validation of the Revised Body Awareness Rating Questionnaire (BARQ-R) in Adults with Musculoskeletal Pain, Adults with Spinal Cord Injury, and Community-Dwelling Adults in the US

abstract:
BackgroundTo establish Rasch validation of the Revised Body Awareness Rating Questionnaire (BARQ-R) in adults with musculoskeletal pain, community-dwelling adults without pain, and adults with spinal cord injury (SCI) who have neuropathic pain.

Materials and MethodThe BARQ-R has 12 items with scores ranging from 0 (completely disagree) to 3 (completely agree). Through Rasch analysis, we evaluated unidimensionality through item and person fit, targeting of the population, person separation reliability (PSR), local item dependence (LID), and principal components analysis of residuals (PCAR).

ResultsThe BARQ-R in adults with musculoskeletal pain (n=152; average age = 52.26{+/-}16.13 years) showed good targeting (person mean location: -0.36{+/-}0.88 logits), minimal floor effect (0.01%), and no ceiling effect (0.00%) and had good reliability (PSR=0.75). The BARQ-R in community-dwelling adults (n=471; average age = 49.63{+/-}17.57 years) had a person mean location of -0.62{+/-}1.09 logits, minimal floor (2.63%), and minimal ceiling effect (0.43%) after rescoring 2 items and deleting 3 items and had good reliability (PSR=0.74). The BARQ-R in adults with SCI-related neuropathic pain (n=44; average age = 55.45{+/-}13.47 years) showed good targeting after rescoring 7 items (person mean location: -0.33{+/-}0.71 logits), no floor effect (0.00%) or ceiling effect (0.00%) but had poor reliability (PSR=0.65).

ConclusionsThe BARQ-R shows sufficient fit to be used in clinical settings for group decision-making for both adults with musculoskeletal pain and community-dwelling adults. However, in adults with SCI-related neuropathic pain, preliminary Rasch analysis of the BARQ-R showed low reliability and therefore the BARQ-R is not recommended for clinical use in that population. Validation in larger groups of adults with SCI as well as more diverse samples are needed.


title: Trends in TSH, free T4, and anti-thyroid peroxidase and treatment status: Canadian Health Measures Survey 2012 to 2015

abstract:
BackgroundPrevious studies in Canada focused on the prevalence of thyroid conditions have not reported on the levels of the thyroid-stimulating hormone (TSH) and thyroid hormones. To address this issue, the present study describes the trends in TSH, free T4, and anti-thyroid peroxidase and their treatment status for the patients who have clinically high or low levels.

MethodsWe used data from the Canadian Health Measures Survey (CHMS) cycles 3 and 4 conducted between 2012 and 2015. The thyroid measures studied were TSH, free T4, and anti-thyroid peroxidase. We used clinical reference ranges to identify abnormality in these measures. We labelled abnormality in these measures as treated if relevant conditions were diagnosed or a disease-specific prescription was reported. Untreated individuals were those with an abnormality in thyroid measures without any medication use or relevant diagnoses. We presented the trends of thyroid measures in mean values and ratios, compared to the values first measured.

ResultsThe levels of TSH, free T4, and anti-peroxidase in cycle 4 were not significantly different from those in cycle 3. The proportions of Canadians with clinically high levels of free T4, anti-thyroid peroxidase, and TSH were 0.03 to 0.017, 0.005 to 0.005, and 0.30 to 0.43 for cycles 3 to 4, respectively. The proportions of Canadians with clinically low levels of TSH and free T4 were 0.02 to 0.021 and 0.18 to 0.11 for cycles 3 to 4, respectively. The change in the proportions of treatment statuses varied across the thyroid measures of the Canadians studied.

ConclusionThis descriptive study demonstrates the trends in TSH, free T4, and anti-thyroid peroxidase; their distributions in the population; and the proportions of Canadians with clinically high or low levels. We believe the information on the treatment status of those with uncontrolled high levels can be used to design patient screening programs.

category: endocrinology