title: Burden and bacteriological profile of sepsis among adult medical emergencies presenting to a national referral hospital in Kampala, Uganda

abstract:
IntroductionSepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection can result from any infection. In 2017, an estimated 48.9 million incident cases of sepsis and 11.8 million sepsis-related deaths were reported globally. Bacterial infection is the major cause of sepsis. Data about sepsis burden is derived almost exclusively from studies in high-income countries yet mortality from sepsis is disproportionately higher in low- and middle-income countries. We aimed to determine the prevalence of sepsis, bacteriological profile of causes, antimicrobial susceptibility patterns, and in-hospital outcomes among adult medical emergencies presenting to Kiruddu National Referral Hospital in Kampala, Uganda.

MethodsWe conducted a prospective cohort study between December 2018 and July 2019 in which patients presenting to the medical emergency ward with sepsis were consecutively enrolled; blood was drawn for aerobic blood cultures, antimicrobial susceptibility patterns were determined and patients were followed up for in-hospital outcomes.

ResultsOf 1,657 patients screened during the study period, 243(14.7%) had sepsis, the median age was 45 years (IQR 32,65) and the majority were female (55.6%). Among patients with sepsis; 46 (18.9%) had positive aerobic blood cultures. Staphylococcus aureus was the most common isolate (31/46, 67.4%) with a predominance of Methicillin-Resistant Staphylococcus aureus (MRSA) (20/31, 64.5%). Of the 243 patients followed up, 143 (58.9%) died in hospital with an average length of stay of 4.9 days (SD 5.5) for those who died and 10.2 (SD 7.6) for those that were discharged alive. None of the patients was admitted to ICU.

ConclusionsSepsis was common (14.7%) among adult medical emergencies and it was associated with a high in-hospital mortality rate (58.9%). Positive blood cultures were predominantly Staphylococcus aureus and nearly a third of these were Methicillin-Resistant.


title: Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

abstract:
BackgroundThe coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion because it harbors mutations even in individuals with complete vaccination. Here, we examine the capability of the booster vaccination to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses.

MethodsA total of 167 participants primed with heterologous CoronaVac/AZD1222 were enrolled to receive AZD1222, BNT162b2, or mRNA-1273 as a booster dose. Reactogenicity was recorded. Binding antibody, neutralizing antibody (NAb) titers against omicron BA.1 and BA.2, and total interferon gamma (IFN-{gamma}) post-booster responses were measured.

ResultsA substantial loss in neutralizing potency to omicron variant was found at 4 to 5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. Notably, boosted individuals with mRNA vaccines could induce T cell response. Reactogenicity was mild to moderate without serious adverse events.

ConclusionsOur findings highlight that the booster vaccination could overcome immunity wanes and provide adequate NAbs coverage against omicron BA.1 and BA.2.

category: allergy and immunology


title: Factors affecting oral health problems among school children in Kaski District, Nepal

abstract:
IntroductionSchool children have a high prevalence of oral health problems in Nepal. Socio-demographic factors such as gender, parents socioeconomic status, and individual awareness of oral health may have an influence on the occurrence of oral health problems. However, little evidence is available about the oral health problems and their associated factors among school children. Therefore, this study aimed to assess the factors associated with oral health problems among school children in Nepal.

MethodologyA cross-sectional study was conducted among school children of grade 7 in 12 schools of Kaski district, Gandaki Province, Nepal. The schools were randomly chosen from urban and semi-urban areas in the district. A total of 669 students participated in the study. Data were collected using a set of questionnaires covering dental health knowledge, socio-demographic characteristics, oral health condition and practices. The factors of poor oral health condition and practices were examined using t-test, one-way Anova, and multiple linear regression.

ResultsSchool children who visited health institutions for oral health services and those with parents having higher level education had higher dental health knowledge scores. Total decayed score was higher among those who did not have knowledge that fluoride prevents decay compared to those who had knowledge about it (Have knowledge about fluoride prevents decay: Mean=1.21 (SD=1.54) Vs No knowledge: mean=2.13 (SD=2.13). Females were more likely to have higher DMFT score compared to males ({beta}-coefficient=0.43, 95% CI=0.13, 0.73, P value=0.005) and increase in knowledge score was associated a with a decrease in DMFT score ({beta}-coefficient=-0.09, 95% CI= -0.20, -0.10, P value=0.047).

ConclusionThis study found that gender, knowledge score, and parents socioeconomic status were the major factors contributing to higher DMFT scores. School children should be provided with regular oral health counseling and promotion activities in schools and oral health screening in schools.

category: dentistry and oral medicine


title: COVID-19 third wave experience in India, a survey of 5971 adults

abstract:
BackgroundThe third wave of the pandemic in India lasted from January till March 2022, and breakthrough infections were common. Third dose of vaccine was rolled out to priority groups in the beginning of 2022. There is no published information available about the clinical outcomes in this context.

AimsO_LITo assess the community level experience of the pandemic, with focus on the third wave and vaccination in India.
C_LIO_LITo describe the experience of the boosted and non-boosted population during the 3rd wave.
C_LIO_LITo study the public perception about the precautionary (3rd) dose in India.
C_LI

ResultsAmong 5971 respondents, 98.6% were vaccinated, 40% of whom had also received the 3rd dose. Age range: 24% were below 40, 50% were 40-59, 26% were >60 years.

45% were women, 53% were healthcare workers.

COVID-19 was reported by 3361 (56%) respondents. Among those who reported COVID-19, 2311 (70%) were infected during the third wave. Severe symptoms occurred in <1%, while moderate severity was reported by 42%. Repeated bouts of infection were common; 15% of those with a history of COVID-19 had been infected at least twice. 44% of the respondents (2610/5971) did not report a history of COVID-19.

The third dose was taken by 2383 individuals, of whom 30% reported COVID-19 during the 3rd wave. The boosted group also had higher N95 use, and a greater proportion of healthcare workers. Among those who did not take a 3rd dose, 45% reported COVID-19 in the 3rd wave. COVID-19 incidence was lower at 27% among those in this group who had recently received their second dose. Longer gap after the second dose correlated with higher chance of infection during 3rd wave. Giving a 3rd dose before a 6-month gap since the second dose did not make a difference in infection rate.

Covaxin and Covishield recipients had the same incidence of COVID-19 during the third wave.

While 35% of the respondents believed it was helpful, 65% of the respondents were either uncertain or disapproving of the benefit of a 3rd dose.

ConclusionsO_LI30% of respondents who received a 3rd dose went on to get COVID-19 during the 3rd wave.
C_LIO_LIYounger adults were more likely to be affected during 3rd wave.
C_LIO_LIAlthough severe disease was rare, 42% reported having symptoms of moderate severity that could temporarily incapacitate people, affecting their routine and productivity.
C_LIO_LIThe proportion of different grades of severity was similar among all vaccinated people, regardless of whether they received a 3rd dose.
C_LIO_LIReinfections occurred in 15%, and were not always milder.
C_LIO_LIAmong those who did not receive a 3rd dose, 45% reported COVID-19 in the 3rd wave. However, this group had lower use of N95 masks (50%) than the 3rd dose group (68%) which may have reduced the overall protection.
C_LIO_LIThe longer the gap after the second dose, the greater was the chance of reporting COVID-19.
C_LIO_LIPeople who received their second dose recently had the same incidence of third wave COVID-19 as following a 3rd dose.
C_LIO_LIThe 3rd dose, given too close to the second dose, made no difference in the infection rate.
C_LIO_LICovaxin and Covishield recipients had the same rate of COVID-19 in the third wave.
C_LIO_LIAlthough the respondents were 98.6% vaccinated at baseline, there was considerable uncertainty (65%) amongst them about the benefit of a 3rd dose.
C_LI

category: epidemiology


title: Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017-2021

abstract: COVID-19 pandemic-related shifts in healthcare utilization, in combination with trends in non-COVID-19 disease transmission and NPI use, had clear impacts on infectious and chronic disease hospitalization rates. Using a national healthcare billing database (C19RDB), we estimated the monthly incidence rate ratio of hospitalizations between March 2020 and June 2021 according to 19 ICD-10 diagnostic chapters and 189 subchapters. The majority of hospitalization causes showed an immediate decline in incidence during March 2020. Hospitalizations for diagnoses such as reproductive neoplasms, hypertension, and diabetes returned to pre-pandemic norms in incidence during late 2020 and early 2021, while others, like those for infectious respiratory disease, never returned to pre-pandemic norms. These results are crucial for contextualizing future research, particularly time series analyses, utilizing surveillance and hospitalization data for non-COVID-19 disease. Our assessment of subchapter level primary hospitalization codes offers new insight into trends among less frequent causes of hospitalization during the COVID-19 pandemic.


title: The primary care annual dementia review: a qualitative study of the views and experiences of service users and providers

abstract:
BackgroundIn England and Wales, the Quality and Outcomes Framework (QOF) financially rewards GP practices for long-term conditions management, including completion of annual dementia reviews. There is limited evidence about how this works in practice and whether it meets patients and carers needs.

MethodsData from five qualitative datasets were integrated and analysed thematically. Data comprised interviews, focus groups, and observations with 209 participants, including commissioners, managers and frontline staff in dementia services; people with dementia; carers; and policy experts.

FindingsFour main themes were developed: (i) perceived benefits of annual review; (ii) variability and (in)visibility of annual review; (iii) logistics; and (iv) external influences and constraints.

Variability in both the completion and quality of QOF annual dementia reviews was attributed by some to limited nuance in the current QOF dementia indicator. Many patients and carers were unaware that an annual dementia review had occurred. Participants suggested that many GPs lack the required competencies and/or capacity for successful dementia reviews.

ConclusionsWork is urgently needed to improve the quality of annual dementia reviews. Potential strategies include changing the financial reimbursement to reflect both quality and quantity, so the review is tailored to the needs of the individual and their family; the creation of standardised templates; collaborative working within primary care and across sectors; and integrating dementia reviews into other long-term conditions.

Key pointsO_LIQOF annual dementia reviews are a key opportunity for providing support for people with dementia in England and Wales
C_LIO_LICurrent provision of annual reviews varies both in completion rates and quality
C_LIO_LIStrategies for improvement include improving quality indicators, implementing standardised templates, and improving primary care capacity and capability to carry out reviews
C_LI

category: primary care research


title: Comprehensive assessment of Age-Specific Mortality Rate and its incremental changes using a composite measure: A sub-national analysis of rural Indian women

abstract:
BackgroundDiverse socio-economic and cultural issues contribute to adverse health outcomes and increased mortality rates among rural Indian women across different age categories. The present study aims to comprehensively assess age-specific mortality rates and their temporal trends using a composite measure at the sub-national level for rural Indian females to capture cross-state differences.

MethodsA total of 19 states were included in the study to construct a composite age-specific mortality index for 2011 (base year) and 2018 (reference year) and examine the incremental changes in the index values across these years at the sub-national level in India. Sub-index values were calculated for each component age group and were subsequently used to compute the composite ASMR index using the geometric mean method. Based on the incremental changes, the performance of states was categorized into four different typologies.

ResultsImprovement in mortality index scores in the 0-4 years age group was documented for all states. The mortality rates for the 60+ age group were recorded to be high for all states. Kerela emerged as the overall top performer in terms of mortality index scores, while Bihar and Jharkhand were at the bottom of the mortality index table. The overall mortality composite score has shown minor improvement from base year to reference year at all India level.

ConclusionsAn overall reduction in the mortality rates of rural Indian women has been observed over the years in India. The success of public health interventions to reduce the under-five mortality rate is evident as the female rural mortality rates have reduced sizably for all states. Nevertheless, there is still sizable scope for reducing mortality rates for other component age groups. Additionally, there is a need to divert attention toward the female geriatric (60+ years) population as the mortality rates are still high.

category: public and global health


title: Characterization of Autonomic Symptom Burden in Long COVID: A Global Survey of 2,314 Adults

abstract:
BackgroundAutonomic dysfunction is a common complication of post-acute sequalae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity rates are unknown.

ObjectiveThe primary goal of this study was to assess the frequency and severity of autonomic symptoms in PASC. We also aimed to assess symptom burden in PASC though well-validated questionnaires, evaluate which pre-existing conditions are associated with an increased risk of developing autonomic dysfunction, and determine whether the severity of acute COVID-19 illness is associated with the severity of autonomic dysfunction in this population.

MethodsWe conducted an online survey of 2,314 adults with PASC using several validated questionnaires including the COMPASS-31 to evaluate for autonomic dysfunction. We included both participants who had tested positive for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone (test-unconfirmed). Additional analyses were performed on test-confirmed participants, comparing hospitalized to non-hospitalized participants.

Results67% of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and non-hospitalized participants (28.95{+/-}30.98 vs 26.4{+/-}28.35, p=0.06). Both hospitalized and non-hospitalized participants reported significant functional disability across all quality-of-life domains.

ConclusionsModerate to severe autonomic dysfunction was seen in all PASC groups in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and not necessarily dependent on the severity of acute COVID illness.

category: neurology


title: A Novel Application of Neural Networks to Identify Potentially Effective Combinations of Biologic Factors for Enhancement of Bone Fusion/Repair

abstract:
IntroductionThe use of biologic adjuvants (orthobiologics) is becoming commonplace in orthopaedic surgery. Amongst other applications, biologics are often added to enhance fusion rates in spinal surgery and to promote bone healing in complex fracture patterns. Generally, orthopaedic surgeons use only one biomolecular agent (ie allograft with embedded bone morphogenic protein-2) rather than several agents acting in concert. Bone fusion, however, is a highly multifactorial process and it likely could be more effectively enhanced using biologic factors in combination, acting synergistically. We used artificial neural networks to identify combinations of orthobiologic factors that potentially would be more effective than single agents.

MethodsAvailable data on the outcomes associated with various orthopaedic biologic agents, electrical stimulation, and pulsed ultrasound were curated from the literature and assembled into a form suitable for machine learning. The best among many different types of neural networks was chosen for its ability to generalize over this dataset, and that network was used to make predictions concerning the expected efficacy of 2400 medically feasible combinations of 9 different agents and treatments.

ResultsThe most effective combinations were high in the bone-morphogenic proteins (BMP) 2 and 7 (BMP2, 15mg; BMP7, 5mg), and in osteogenin (150ug). In some of the most effective combinations, electrical stimulation could substitute for osteogenin. Some other effective combinations also included bone marrow aspirate concentrate. BMP2 and BMP7 appear to have the strongest pairwise linkage of the factors analyzed in this study.

ConclusionsArtificial neural networks are powerful forms of artificial intelligence that can be applied readily in the orthopaedic domain, but neural network predictions improve along with the amount of data available to train them. This study provides a starting point from which networks trained on future, expanded datasets can be developed. Yet even this initial model makes specific predictions concerning potentially effective combinatorial therapeutics that should be verified experimentally. Furthermore, our analysis provides an avenue for further research into the basic science of bone healing by demonstrating agents that appear to be linked in function.

CLINICAL RELEVANCEBone healing is a highly multifactorial process, and it likely could be more effectively enhanced using combinations of factors rather than single factors in isolation. This study provides a starting point for an integration of biomedical experimentation and computational AI that ultimately could lead to highly sophisticated combinatorial treatments for bone repair and other applications in orthopaedic medicine.

category: orthopedics


title: Human Germline Heterozygous Gain-of-Function STAT6 Variants Cause Severe Allergic Disease

abstract: STAT6 (Signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. STAT6 mediates the biological effects of IL-4, a cytokine necessary for type 2 differentiation of T cells and B cell survival, proliferation and class switching to IgE. We have identificated two unrelated patients with a phenotype notable for their early-life onset of profound allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic esophagitis, elevated serum IgE, IgE-mediated food allergies, and vascular anomalies of the brain. Both patients harbored heterozygous de novo missense variants in the DNA binding domain of STAT6 (c.1144G>C, p.E382Q; and c.1256A>G, p.D419G). Functional studies established that both variants caused a gain-of-function (GOF) phenotype associated with enhanced phosphorylation and transcriptional activity of STAT6, in addition to increased transcript abundance of known STAT6 target genes and other genes implicated in allergic disease. JAK inhibitors decreased the enhanced STAT6 responses associated with both these STAT6 GOF variants. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of the first humans with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

category: genetic and genomic medicine


title: The Helping Older People Engage (HOPE) Study: Protocol & COVID Modifications for a Randomized Trial

abstract:
ObjectivesEvidence-based strategies to reduce loneliness in later life are needed because loneliness impacts all domains of health, functioning, and quality of life. Volunteering is a promising strategy, as a large literature of observational studies documents associations between volunteering and better health and well-being. However, relatively few studies have used randomized controlled trials (RCTs) to examine benefits of volunteering, and none have examined loneliness. The primary objective of the Helping Older People Engage (HOPE) study is to examine the social-emotional benefits of a social volunteering program for lonely older adults. This manuscript describes the rationale and design of the trial.

DesignRandomized controlled trial examining an existing community volunteering program available nationwide. We are randomly assigning adults aged 60 or older (up to 300) who report loneliness to 12 months of either AmeriCorps Seniors volunteering program or an active control (self-guided life review). Co-primary outcomes are assessed via self-report--loneliness (UCLA Loneliness Scale) and quality of life (WHOQOL-Bref). This trial is registered at clinicaltrials.gov (NCT03343483)

SettingLifespan of Greater Rochester, a non-medical, community-based aging services agency (volunteering) and participants homes (control).

ParticipantsAdult ages [≥]60 years who endorsed feelings of loneliness (score of 6 or greater on the 3-item UCLA Loneliness Scale).

InterventionThe interventions are 12-months of volunteer service with the AmeriCorps Seniors program or self-guided life review writing (active control).

MeasurementsData were collected at baseline, 3-, 6-, and 12-months (loneliness) and baseline and 12-months (quality of life).

TimelineEnrollment for this trial is underway and expected to finish by May 2022, with completion of follow-up assessments through April, 2023, and completion of primary outcomes soon thereafter.

category: geriatric medicine


title: Can accurate demographic information about people who use prescription medications non-medically be derived from Twitter big data?

abstract: Traditional surveillance mechanisms for nonmedical prescription medication use (NPMU) involve substantial lags. Social media-based approaches have been proposed for conducting close-to-real-time surveillance, but such methods typically cannot provide fine-grained statistics about subpopulations. We address this gap by developing methods for automatically characterizing a large Twitter NPMU cohort (n=288,562) in terms of age-group, race, and gender. Our methods achieved 0.88 precision (95%-CI: 0.84-0.92) for age-group, 0.90 (95%-CI: 0.85-0.95) for race, and 0.94 accuracy (95%-CI: 0.92-0.97) for gender. We compared the automatically-derived statistics for the NPMU of tranquilizers, stimulants, and opioids from Twitter to statistics reported in traditional sources (eg., the National Survey on Drug Use and Health). Our estimates were mostly consistent with the traditional sources, except for age-group-related statistics, likely caused by differences in reporting tendencies and representations in the population. Our study demonstrates that subpopulation-specific estimates about NPMU may be automatically derived from Twitter to obtain early insights.

category: health informatics


title: Acceptability and Feasibility of Genetic Testing to Assess Risk of HIV-Associated Neurocognitive Impairment among Thai Adolescents and Young Adults

abstract: Host genetic factors may modify the risk of developing HIV-associated neurocognitive impairment (HIV-NCI), and genetic research has the potential to inform novel treatments for HIV-NCI. However, there is a need to better understand the acceptability of genetic testing among distinct populations of people living with HIV at increased risk for HIV-NCI, such as young people living with perinatally-acquired HIV (PHIV) in low- and middle-income countries (LMICs), to gauge the feasibility of genetic research within these populations. This pilot study evaluated the acceptability and feasibility of genetic testing to assess risk of future neurocognitive problems in fifty Thai adolescents and young adults (12-24 years; Mage=19.16; 52% female) with PHIV and demographically similar HIV-negative controls. Participants completed a survey assessing acceptability of and concerns about genetic testing and were asked to provide blood samples for genetic testing. Descriptive statistics and blood draw completion rates were produced and calculated. Reported concerns about genetic testing were grouped thematically and tallied. Independent t tests and chi-squares explored demographic differences between participants who reported concerns and peers. Results indicated 46 participants (92%) rated genetic testing as "acceptable" or "completely acceptable." Eight participants (16%) reported concerns about genetic testing. The most common concerns were related to genetic information being shared or misused. Compared to peers, participants who reported concerns had more years of education and were more likely to have post-secondary schooling. Regarding completion rates, 49 participants (98%) agreed to genetic testing and provided blood samples. Overall, results support the acceptability and feasibility of incorporating genetic testing into research investigating HIV-NCI among adolescents and young adults in Thailand. Findings provide important considerations for planning future genetic studies among young people in Thailand and perhaps other LMICs.

category: hiv aids


title: Assessing clinical outcomes of vancomycin treatment in adult patients with penicillin-resistant Enterococcus faecium bacteremia

abstract: Enterococcal bacteremia is associated with high mortality and long-term hospitalization. Here, we aimed to investigate the clinical outcomes and evaluate risk factors for mortality in adult patients treated with vancomycin (VCM) for penicillin-resistant Enterococcus faecium (E. faecium) bacteremia. Data were collected from inpatients at a single university hospital between January 2009 and December 2020. The area under the curve (AUC) of VCM was calculated using the Bayesian approach. The primary outcome was 30-day in-hospital mortality. Univariate analysis showed significant differences in the combined use of vasopressors, history of the use of inactive antimicrobial agents against E. faecium, VCM plasma trough concentration, and renal dysfunction during VCM administration between 30-day mortality and survival groups. However, the AUC/minimum inhibitory concentration (MIC) was not significantly different. Multivariate analysis revealed that concomitant vasopressors were an independent risk factor for 30-day all-cause mortality (odds risk, 7.81; 95% confidence interval, 1.16-52.9; P = 0.035). VCM plasma trough concentrations and AUC/MIC in the mortality group were higher than those in the surviving group. Depending on the drug-susceptibility results of E. faecium, it is considered that the AUC/MIC is calculated at a double AUC value. No association between AUC/MIC and treatment effect in E. faecium bacteremia was assumed because the known target AUC/MIC was sufficiently achieved in the mortality group. When an immunocompromised host develops E. faecium bacteremia with septic shock, especially in situations where the hemodynamics of using a pressor agent is unstable, treating it exclusively by sufficient exposure to antibacterial agents may be difficult.

category: infectious diseases


title: WHEN SEX MATTERS: A COMPARATIVE GENERALISED STRUCTURAL EQUATION MODEL (GSEM) FOR THE DETERMINANTS OF STUNTING AMONGST UNDER-FIVES IN UGANDA

abstract:
The main aim of this study was to establish the differences in both the determinants of stunting and the causal mechanism through which the identified determinants influence stunting amongst male and female under-fives in Uganda. Literature shows that male children below the age of five years are at a higher risk of being stunted than their female counterparts. Specifically, studies in Uganda indicate that being a male child is positively associated with stunting while being a female is negatively associated with stunting.

Data for 904 male and 829 female under-fives was extracted form UDHS-2016 survey dataset. Key variables for this study were identified and used in generating relevant models and paths. Structural equation modeling techniques was used in its generalized form (GSEM). The generalized nature necessitated specifying both the family and link functions for each response variables in the system of the model. Sex of the child (b4) was used as a grouping factor and the height for age (HAZ) scores were used to construct the status for stunting of under-fives.

The estimated models and path clearly indicated that the set of underlying factors that influence male and female under-fives respectively were different and the path through which they influence stunting were different. However, some of the determinants that influenced stunting amongst male under-fives also influenced stunting amongst the female under-fives.

To reduce the stunting problem to the desirable state, it is important to consider the multifaceted and complex nature of the risk factors that influence stunting amongst the under-fives but more importantly consider the different sex specific factors and their causal mechanism or paths through which they influence stunting.


title: Diagnosis and treatment of opioid use disorder in a South African private sector medical insurance scheme: a cohort study

abstract:
BackgroundThe use of opioids is increasing globally, but data on opioid use disorder (OUD) in South Africa are scarce. This study examines the incidence of diagnosed OUD, opioid agonist use, and excess mortality among persons with OUD in South Africas private healthcare sector.

MethodsWe conducted a cohort study of beneficiaries ([≥] 11 years) of a South African medical insurance scheme using reimbursement claims from Jan 1, 2011, to Jul 1, 2020. Beneficiaries were classified as having OUD if they received opioid agonists (buprenorphine or methadone), an ICD-10 F11 diagnosis for a mental and behavioural disorder due to opioid use, or an ICD-10 T40 diagnosis for opioid poisoning. We calculated adjusted hazard ratios (aHR) for factors associated with OUD, estimated the cumulative incidence of opioid agonist use after receiving an ICD-10 F11 diagnosis, and examined excess mortality among beneficiaries with OUD.

ResultsOf 1,251,458 beneficiaries, 1,313 (0.1%) had OUD. Between 2011 and 2020, the incidence of OUD increased by 12% (95% CI 9%-14%) per year. Men, young adults in their twenties, and beneficiaries with co-morbid mental health or other substance use disorders were at increased risk of OUD. The cumulative incidence of opioid agonist use was 10.6% (95% CI 8.3-13.2) at 3 years after receiving an F11 diagnosis. After adjusting for age, sex, year, medical insurance coverage, and population group, OUD was associated with an increased risk of mortality (aHR 2.29, 95% CI 1.85-2.82). OUD was associated with a 7.63-year shorter life expectancy (95% CI 4.08-10.70).

ConclusionsThe incidence of patients diagnosed with or treated for OUD in the private sector is increasing rapidly. People with OUD in the private sector are a vulnerable population with substantial psychiatric comorbidity who often die prematurely. Evidence-based management of OUD is urgently needed to improve the health outcomes of people with OUD.


title: Did Norwegian adolescents suffer more violence and sexual abuse during the Covid-19 pandemic? Violence and sexual abuse rates the year before the pandemic compared to rates one year into the pandemic.

abstract:
BackgroundThe Covid-19 pandemic is a public health crisis which may cause unintended additional societal costs such as child maltreatment. Considerable concern is raised as to whether the pandemic has led to an increase in violence and sexual abuse against children.

ObjectiveThe present study objective is to provide rates of violence and sexual abuse against adolescents the year before the pandemic compared to one year into the pandemic.

Participants and settingTwo samples of Norwegian 12-16-year-olds were approached. A representative pre-pandemic sample of 9240 adolescents (M age= 14.11), and a sample recruited one year into the pandemic resulting in 3540 responses (M age (SD) = 14.5).

MethodsAn online survey was administered during school hours including established measures of violence and sexual abuse exposure. Sociodemographic characteristics were assessed.

ResultsThere was 1.4 percentage point increase in sexual abuse by an adult, and a 3.9 percentage point decrease in psychological violence by a parent during the pandemic compared to the year before the pandemic. Otherwise, violence and sexual abuse rates remained stable across these two time periods. Risk factors for violence and sexual abuse were amplified during the pandemic.

ConclusionNorway, a high-income welfare state, imposed measures to counteract the burden of the pandemic mitigation actions for adolescents. This might partly explain the absence of the feared increase in violence towards adolescents. The disproportionate risk for violence and sexual abuse for some groups of adolescents is however concerning, and should be followed up over time.


title: Artificial Intelligence Model for Detecting Duodenal Endoscopic Changes on Images of Functional Dyspepsia

abstract:
Introduction and AimsRecently, it has been suggested that the duodenum may be the pathological locus of functional dyspepsia (FD), but there are few reports on the presence of duodenal changes on imaging in FD.

MethodsDuodenal images acquired at our hospital with the presence or absence of the term "functional dyspepsia" on the electronic medical record, and H. pylori (HP) infection status on the Japan Endoscopy Database were obtained. The Google Cloud Platform AutoML Vision (single-label classification) was used to classify FD/HP current infection, versus FD/HP uninfected patients. We constructed an AI model to distinguish four groups, which included FD/HP current infection, FD/HP uninfected, non-FD/current infection, and non-FD/HP uninfected, and calculated the sensitivity, specificity, and AUC. Patient images with other organic diseases such as gastrointestinal cancer, peptic ulcer, postoperative abdominal organs, and gastroesophageal reflux disease were excluded. Narrow band imaging and dye-spread images were also excluded.

ResultsThe overall AUC of the four groups was 0.47 (FD/HP current infection 0.20, FD/HP uninfected 0.35, non-FD/current infection 0.46, non-FD/HP uninfected 0.74). Next, using the same images, we constructed a model to determine the presence or absence of FD in HP infected patients only. The sensitivity, specificity, positive predictive value, negative predictive value, and AUC were 71.4%, 66.7%, 50.0%, 83.3%, and 0.84, respectively. However, when we constructed a model to determine the presence of FD only in uninfected HP patients, the sensitivity, specificity, positive predictive value, negative predictive value, and AUC were 58.3%, 100%, 100%, 77.3%, and 0.85, respectively.

ConclusionThe results suggest that the duodenal imaging AL model may be able to determine the presence or absence of FD to a certain degree in HP-infected or uninfected patients.

category: gastroenterology


title: Measuring Autonomic Symptoms with the Body Perception Questionnaire Short Form (BPQ-SF): Factor Analysis, Derivation of U.S. Adult Normative Values, and Association with Sensor-Based Physiological Measures

abstract:
ObjectiveAutonomic regulation of organ and tissues may give rise to disruptions of typical functions. The Body Perception Questionnaire Short Form (BPQ-SF) includes items that were developed to assess autonomic symptoms in daily life. This pair of studies aimed to establish previously unexplored psychometric properties of the BPQ-SF, develop normative values for clinical and research use, and validate the self-reports with sensor-based measures.

MethodsStudy 1 reports exploratory and confirmatory factor analysis (CFA) on BPQ-SF autonomic reactivity items from a large U.S. population-based online study (n = 2048). In study 2, BPQ-SF scores were examined for associations with heart period, respiratory sinus arrhythmia (RSA), and skin conductance (SC) during seated leg lifts in a community sample (n = 62).

ResultsStudy 1 results supported a 2-factor supra- and sub-diaphragmatic autonomic symptom solution (CFA: RMSEA = .040, CFI = .99, TLI = .99), though a 1-factor solution also fit the data well (RMSEA = .080, CFI = .99, TLI = .99). In study 2, flexible HP responses to lifts and rests were demonstrated at all autonomic symptom levels. However, low self-reported autonomic symptoms were associated with flexible dynamic RSA and SC, moderate symptoms with prolonged SC responses during rest periods, and high symptoms with little systematic changes in RSA and SC during leg lifts.

ConclusionResults support the validity of self-reports of autonomic symptoms in research and clinical applications, with higher symptoms likely indicating impairment in autonomic flexibility.

category: psychiatry and clinical psychology


title: CRISIS AFAR: An International Collaborative Study of the Impact of the COVID-19 Pandemic on Youth with Autism and Neurodevelopmental Conditions.

abstract:
ImportanceHeterogeneous mental health outcomes during the COVID-19 pandemic are recognized in the general population, but it has not been systematically assessed in youth with neurodevelopmental disorders (NDD), including autism spectrum (ASD).

ObjectiveIdentify subgroups of youth with ASD/NDD based on the pandemic impact on symptoms and service changes, as well as predictors of outcomes.

Design, Setting, and ParticipantsThis is a naturalistic observational study conducted across 14 North American and European clinical and/or research sites. Parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) adapted for Autism and Related Neurodevelopmental Conditions (AFAR) were cross-sectionally collected from April to October 2020. The sample included 1275, 5-21 year-old youth with ASD and/or NDD who were clinically well-characterized prior to the pandemic.

Main Outcomes and MeasuresTo identify impact subgroups, hierarchical clustering analyzed eleven AFAR factors measuring pre- to pandemic changes in clinically relevant symptoms and service access. Random forest classification assessed the relative contribution in predicting subgroup membership of 20 features including socio-demographics, pre-pandemic service, and clinical severity along with indices of COVID-19 related experiences and environments empirically-derived from AFAR parent responses and global open sources.

ResultsClustering analyses revealed four ASD/NDD impact subgroups. One subgroup - broad symptom worsening only (20% of the aggregate sample) - included youth with worsening symptoms that were above and beyond that of their ASD/NDD peers and with similar service disruptions as those in the aggregate average. The three other subgroups showed symptom changes similar to the aggregate average but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Pre-pandemic factors (e.g., number of services), pandemic environments and experiences (e.g., COVID-19 cases, related restrictions, COVID-19 Worries), and age emerged in unique combinations as distinct protective or risk factors for each subgroup. Together they highlighted the role of universal risk factors, such as risk perception, and the protective role of services before and during the pandemic, in middle childhood.

Conclusions and RelevanceConcomitant assessment of changes in both symptoms and services access is critical to understand heterogeneous impact of the pandemic on ASD/NDD youth. It enabled the delineation of pathways to risk and resilience that include universal and ASD/NDD specific contributors.


title: Using Explainable-AI to Find Geospatial Environmental and Sociodemographic Predictors of Suicide Attempts

abstract: Despite a global decrease in suicide rates in recent years, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts in order to combat this growing epidemic. In this study, we use an explainable artificial intelligence (X-AI) method, iterative Random Forest (iRF), to predict suicide attempts using data from the Million Veteran Program (MVP). Our predictive model incorporates multiple environmental variables (e.g., elevation, light wavelength absorbance, temperature, humidity, etc) at ZIP code-level geospatial resolution. We additionally consider demographic variables from the American Community Survey as well as the number of firearms and alcohol vendors per 10,000 people in order to assess the contributions of proximal environment, access to means, and restraint decreasement to suicide attempts. Our results show that geographic areas with higher concentrations of married males living with spouses are predictive of lower rates of suicide attempts, whereas geographic areas where males are more likely to live alone and to rent housing are predictive of higher rates of suicide attempts. We also identified climatic features that were associated with suicide attempt risk by age group. Additionally, we observed that firearms and alcohol vendors were associated with increased risk for suicide attempts irrespective of the age group examined, but that their effects were small in comparison to the top features. Taken together, our findings highlight the importance of social determinants and contextual factors in understanding suicide risk among veterans.


title: Which countries need COVID-19 vaccines the most? Development of a prioritisation tool

abstract:
BackgroundAssessing relative needs for COVID-19 vaccines across countries has been challenging. The objective of this study was to identify the most important factors for assessing countries needs for vaccines, and to weight each, generating a scoring tool for prioritising countries.

MethodsThe study was conducted between March and November 2021. The first stage involved a Delphi survey with a purposive and snowball sample of public health experts, to reach consensus on country-level factors for assessing relative needs for COVID-19 vaccines. The second stage involved a discrete choice experiment (DCE) to determine weights for the factors.

ResultsThe study included 28 experts working across 13 different countries and globally. The Delphi survey found 37 factors related to needs. Nine of the most important factors were included in the DCE. Among these, the most important factor was the  proportion of overall population not fully vaccinated with a mean weight of 19.5, followed by  proportion of high-risk population not fully vaccinated (16.1),  health system capacity (14.2),  capacity to purchase vaccines (11.9) and the  proportion of the population clinically vulnerable (11.3).

ConclusionsBy assessing relative needs, this scoring tool can build on existing methods to further the role of equity in global COVID-19 vaccine allocation.


title: Arbovirus risk perception as a predictor of mosquito-bite preventive behaviors in Ponce, Puerto Rico

abstract:
Mosquito-borne arboviruses are an important cause of morbidity and mortality in the Caribbean. In Puerto Rico, chikungunya, dengue, and Zika viruses have each caused large outbreaks during 2010-2022. To date, the majority of control measures to prevent these diseases focus on mosquito control and many require community participation. In 2018, the U.S. Centers for Disease Control and Prevention launched the COPA project, a community-based cohort study in Ponce, Puerto Rico, to measure the impact of novel vector control interventions in reducing arboviral infections. Randomly selected households from 38 designated cluster areas were offered participation, and baseline data were collected from 2,353 households between May 2018 and May 2019. Household-level responses were provided by one representative per home. Cross-sectional analyses of baseline data were conducted to estimate 1) the association between arboviral risk perception and annual household expenditure on mosquito control, and 2) the association between arboviral risk perception and engagement in [≥]3 household-level risk reduction behaviors. In this study, 27% of household representatives believed their household was at high risk of arboviruses and 36% of households engaged in at least three of the six household-level preventive behaviors. Households where the representative perceived their household at high risk spent an average of $35.9 (95% confidence interval: $23.7, $48.1) more annually on mosquito bite prevention compared to households where the representative perceived no risk. The probability of engaging in [≥]3 household-level mosquito-preventive behaviors was 10.2 percentage points greater (7.2, 13.0) in households where the representatives perceived high risk compared to those in which the representatives perceived no risk. Paired with other research, these results support investment in community-based participatory approaches to mosquito control and providing accessible information for communities to accurately interpret their risk.

Author SummaryMosquito-borne disease is an important cause of illness and death in the Caribbean, including Puerto Rico. Most tactics to prevent these diseases rely on stopping mosquito bites, either by reducing the mosquito population or creating barriers between mosquitos and humans. These methods vary in the degree of community involvement required. This study used data collected from 2,353 households in Ponce, Puerto Rico from May 2018 to May 2019 to understand how household perception of risk of contracting these diseases related to 1) the amount of money households spent annually to prevent mosquito bites, and 2) the number of activities their household engaged in to prevent mosquito bites. We found that 27% of households perceived themselves at high risk of contracting these diseases, and 36% of households engaged in at least three activities to reduce their risk. On average, households that perceived themselves at high risk spent more money on mosquito bite prevention and engaged in more activities to prevent mosquito bites, compared to households that perceived no risk. Paired with other research in this area, these results support investment in community-based approaches to mosquito control and ensuring that communities have accessible information to understand their risk of mosquito-borne disease.


title: A cross-sectional study of Q fever in Camels: risk factors for infection, the role of small ruminants and public health implications for desert-dwelling pastoral communities

abstract: Q fever represents an important  neglected zoonosis, with high prevalences recorded across the Middle East region. Among rural desert-dwelling communities in the region, camel milk is largely consumed raw, due to perceptions of dromedaries as a uniquely clean livestock species mentioned in the Quran and Islamic hadith, while milk from other livestock species is usually boiled. As a result, camels present a unique public health threat among such communities from milk-borne pathogens, including C. burnetii. In view of this, an epidemiological survey was conducted among dromedary herds in southern Jordan between September 2017 and October 2018, including 404 camels from 121 randomly selected herds. In addition, 510 household members associated with these herds were interviewed regarding potential high-risk practices for zoonotic transmission. Weight adjusted camel population seroprevalence for C. burnetii was 49.6% (95% CI: 44.7 - 54.5), with evidence of maternally derived immunity in calves [≤]6 months old. Adjusted herd-level prevalence was 76.0% (95%CI 72.7-80.2), with 30.4% (144/477) of individuals estimated to consume raw milk from infected herds monthly or more. Following multivariable logistic regression analysis, seropositive status in camels was found to be associated with increasing age, high herd tick burdens, keeping the herd together throughout the year including when calving, and owning larger (>50) sheep and goat flocks, with goats presenting a higher risk than sheep. Racing camel status was found to be protective. Socioculturally appropriate interventions aimed at raising awareness of potential risks associated with drinking raw camel milk, alongside appropriate livestock management interventions, should be considered.


title: Classifying sex with MRI

abstract:
Sex differences in the size of specific brain structures have been extensively studied but careful and reproducible statistical hypothesis testing to identify them produced overall small effect sizes and differences brains of males and females. On the other hand, multivariate statistical or machine learning methods that analyse MR images of the whole brain have reported respectable accuracies for the task of distinguishing males from females. However, most existing studies lacked a careful control for brain volume differences between sexes and, if done, their accuracy often declined to 70% or below. This raises questions on the relevance of accuracies achieved without careful control of overall volume. Also the potential applicability is uncertain insofar as the robustness of methods had rarely been tested or they suffered from poor accuracy when applied on a different cohort.

We examined how accurately sex can be classified with multivariate methods from gray matter properties of the human brain when correcting for overall brain volume. We also tested, how robust machine learning classifiers are when predicting cross-cohort, i.e. when they are used on a different cohort than they were trained on. Further, we studied how their accuracy depends on the size of the training set. MRI data was used from two population based data sets of 3308 mostly older adults from the Study of Health in Pomerania (SHIP) and 1113 mostly younger adults from the Human Connectome Project (HCP), respectively. Our new open source program BraiNN is based on a 3D convolutional neural network and was compared with a simple logistic regression approach.

When using the gold standard method of matching male and female participants for total intracranial volume, BraiNN achieved 86% accuracy when predicting sex on the same (SHIP) cohort and 73% accuracy when cross-predicting on the HCP cohort. Logistic regression achieved an accuracy >90% on the SHIP cohort, but required a large number of training examples to perform well and did not generalize well across cohorts. On the other hand, BraiNN lost less than 2% accuracy when the cohort size was reduced from 3308 to 1274.

category: radiology and imaging


title: High-Dimensional Multinomial Multiclass Severity Scoring of COVID-19 Pneumonia Using CT Radiomics Features and Machine Learning Algorithms

abstract: We aimed to construct a prediction model based on computed tomography (CT) radiomics features to classify COVID-19 patients into severe-, moderate-, mild-, and non-pneumonic. A total of 1110 patients were studied from a publicly available dataset with 4-class severity scoring performed by a radiologist (based on CT images and clinical features). CT scans were preprocessed with bin discretization and resized, followed by segmentation of the entire lung and extraction of radiomics features. We utilized two feature selection algorithms, namely Bagging Random Forest (BRF) and Multivariate Adaptive Regression Splines (MARS), each coupled to a classifier, namely multinomial logistic regression (MLR), to construct multiclass classification models. Subsequently, 10-fold cross-validation with bootstrapping (n=1000) was performed to validate the classification results. The performance of multi-class models was assessed using precision, recall, F1-score, and accuracy based on the 4x4 confusion matrices. In addition, the areas under the receiver operating characteristic (ROC) curve (AUCs) for multi-class classifications were calculated and compared for both models using "multiROC" and "pROC" R packages. Using BRF, 19 radiomics features were selected, 9 from first-order, 6 from GLCM, 1 from GLDM, 1 from shape, 1 from NGTDM, and 1 from GLSZM radiomics features. Ten features were selected using the MARS algorithm, namely 2 from first-order, 1 from GLDM, 2 from GLRLM, 2 from GLSZM, and 3 from GLCM features. The Mean Absolute Deviation and Median from first-order, Small Area Emphasis from GLSZM, and Correlation from GLCM features were selected by both BRF and MARS algorithms. Except for the Inverse Variance feature from GLCM, all selected features by BRF or MARS were significantly associated with four-class outcomes as assessed within MLR (All p-values<0.05). BRF+MLR and MARS+MLR resulted in pseudo-R2 prediction performances of 0.295 and 0.256, respectively. Meanwhile, there were no significant differences between the feature selection models when using a likelihood ratio test (p-value =0.319). Based on confusion matrices for BRF+MLR and MARS+MLR algorithms, the precision was 0.861 and 0.825, the recall was 0.844 and 0.793, whereas the accuracy was 0.933 and 0.922, respectively. AUCs (95% CI)) for multi-class classification were 0.823 (0.795-0.852) and 0.816 (0.788-0.844) for BRF+MLR and MARS+MLR algorithms, respectively. Our models based on the utilization of radiomics features, coupled with machine learning, were able to accurately classify patients according to the severity of pneumonia, thus highlighting the potential of this emerging paradigm in the prognostication and management of COVID-19 patients.


title: Postural control telerehabilitation with a low-cost virtual reality protocol for children with cerebral palsy: Protocol for a clinical trial.

abstract:
ObjectiveTo establish the feasibility and effectiveness of a rehabilitation programme using low-cost virtual reality aimed at improving postural control in children with cerebral type palsy spastic hemiplegia. It also seeks to compare low-cost virtual reality under two delivery modalities, telerehabilitation (TR) and face-to-face (FtF).

MethodsRandomized controlled clinical trial from the ACTRN platform ACTRN12621000117819. Eighteen sessions of low-cost virtual reality therapy will be provided through both, FtF and TR modalities using a Nintendo Wii balance board. Each programme will last for 6 weeks and will consist of 3 sessions per week of 25 minutes each. The participants will include 40 patients diagnosed with cerebral palsy type spastic hemiplegia. Twenty participants for each group. Participants will be assessed at baseline, by the end of weeks 2, 4, and 6, and at weeks 8 and 10 (post-intervention follow-ups). Clinical measures include the Modified-Modified Ashworth Scale for lower limbs, Modified Ashworth Scale for upper limbs, timed up-and-go tests, the timed one-leg standing and 6-minute walk test. Posturographic measures, including sway area and velocity, under six conditions will be used: 2 statics and 4 dynamic conditions, which include voluntary sway in the mediolateral direction following a metronome set at 30Hz and 60Hz, and sway while playing 2 different videogames.

ResultsThis study provides an assessment of the feasibility and effectiveness of an affordable rehabilitation programme using low-cost virtual reality aimed at improving postural control in children with cerebral palsy.

ConclusionRehabilitation programme using low-cost virtual reality will improve postural control in children with cerebral palsy type spastic hemiplegia and this programme delivered using TR will be as effective as a FtF modality. The TR programme has be designed to expand the coverage of physiotherapy services for children with cerebral palsy in low-resource settings and in remote areas.

category: rehabilitation medicine and physical therapy


title: Augmenting gait in a population exhibiting foot drop with adaptive functional electrical stimulation

abstract:
ObjectiveTo investigate the effects of personalized, adaptive, current-steering functional electrical stimulation (FES) of the lower leg to improve gait in people with foot drop.

DesignA one-group, pre-test post-test study.

SettingTwo gait analysis centers.

ParticipantsThirty-two participants exhibiting symptoms of foot drop.

InterventionsAdaptive, current-steering FES enables precise control over dorsiflexor and evertor muscles, allowing for personalized treatment to correct key foot drop characteristics including dorsiflexion at heel strike and ankle inversion during swing phase. All participants received adaptive FES of the dorsiflexors and evertors during back-to-back walking sets. Participants completed up to three walking sets of unstimulated walking (pre-test) followed by lower-leg stimulated walking (post-test).

Main Outcomes MeasuresThe primary outcome measures include ankle dorsiflexion at heel strike and mean ankle inversion during swing phase. Secondary outcome measures include foot angle at heel strike and single-side heel strike to toe strike time (heel-toe time).

ResultsThe differences in pre-test versus post-test primary and secondary outcome measures were statistically significant (p<0.0125) within our cohort. With adaptive, current-steering FES, ankle dorsiflexion at heel strike increased an average 5.2{degrees}, and ankle inversion during swing phase was reduced by an average -3.6{degrees}, bringing the ankle to a more neutral position for stabilization.

ConclusionGait augmentation using adaptive, current-steering FES improved gait in a population exhibiting symptoms of foot drop. By significantly increasing ankle dorsiflexion at heel strike and decreasing ankle inversion during swing phase, adaptive FES enabled a more neutral ankle at heel strike, which is associated with greater ankle stability and decreased fall risk.


title: Characteristics of health-related quality of life and related factors in patients with brain tumors treated with rehabilitation therapy

abstract:
BackgroundRehabilitation therapy during hospitalization is effective in improving activities of daily living (ADL) and physical function in patients with brain tumors. However, there are few studies on the effect of rehabilitation therapy on health-related quality of life (HRQOL) in patients with brain tumors. Additionally, the EuroQol-5Dimension-5Level (EQ-5D-5L) index score has not been reported as an outcome. This study aimed to investigate the HRQOL of patients with brain tumors who underwent rehabilitation therapy and investigated the factors affecting the EQ-5D-5L index score from various perspectives, including various brain tumor types, treatment methods, and recurrence. In addition, we examined the relationship between the EQ-5D-5L index score, disease-specific HRQOL scale, and ADL.

MethodsPatients with brain tumors who underwent treatment and rehabilitation at Niigata University Medical & Dental Hospital were included in this cross-sectional study. We used the EQ-5D-5L, European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire core 30, and EORTC quality of life questionnaire brain cancer module to evaluate HRQOL. ADL were assessed using the functional independence measure (FIM). The relationship between each HRQOL assessment score and the FIM was analyzed, and the influence of related factors was assessed by multiple regression analysis.

ResultsThis study included 76 patients. The EQ-5D-5L index score was 0.689 for all patients with brain tumors and 0.574 for those with glioblastomas, which was the lowest value. There was a strong correlation between the EQ-5D-5L index score and FIM (r = 0.627, p<0.001). In addition, the EQ-5D-5L index score was significantly correlated with most of the items of the disease-specific HRQOL scale. Multiple regression analysis revealed that glioblastoma histology (coefficient: -0.570, p = 0.024) and surgery (coefficient: 0.376, p = 0.030) were independent factors affecting the EQ-5D-5L index score.

ConclusionsPatients with glioblastoma undergoing rehabilitation may have reduced HRQOL, which was influenced by glioblastoma histology and surgery.


title: Early Carotid Revascularization Rates, Procedural Distribution, and Hospital Density

abstract: Early carotid revascularization (i.e. during the index hospitalization) may help reduce the risk of additional neurologic events without excess perioperative morbidity. We evaluated the relationship between rates of early carotid endarterectomy (CEA) or stenting (CAS) and hospital density/distribution within metropolitan areas of Texas. Patients with extracranial carotid artery stenosis and either stroke, transient ischemic attacks, or amaurosis were identified among all patients admitted from 2009 to 2013 to non-federal Texas hospitals within all 24 Texas metropolitan statistical areas (MSAs). Early CEA/CAS was defined as occurring during the index hospitalization. A Gini coefficient with bias correction factor was calculated to quantify the distribution of carotid procedures within an MSA. In total, 3,330 (15.4%) of the 21,665 metropolitan patients admitted to Texas hospitals with symptomatic carotid stenosis received early CEA/CAS. Only 263 (44%) of the 600 total hospitals where patients were admitted performed early CEA/CAS. An increasing proportion receiving early carotid CEA/CAS was inversely correlated with the procedural Gini coefficient (p=0.002) and directly correlated with the number of hospitals per 100K population (p=0.01). These two factors accounted for 51% of the variability among MSAs. Early CEA/CAS rates did not correlate with hospital volume or with level 1or 2 stroke centers within an MSA. Increasing the number of hospitals performing early carotid revascularization procedures (i.e. avoiding regionalization/concentration) may help increase the number of patients receiving early carotid revascularization for symptomatic carotid artery disease.

category: surgery


title: Racial Disparities in Post-Transplant Stroke and Mortality Following Stroke in Adult Cardiac Transplant Recipients in the United States

abstract:
BackgroundBlack heart transplant recipients have a higher mortality rate than white recipients 6-12 months after transplant. Whether there are racial disparities in post-transplant stroke incidence and all-cause mortality following post-transplant stroke among cardiac transplant recipients is unknown.

Methods and FindingsUsing a nationwide transplant registry, we assessed the association between race and incident post-transplant stroke using logistic regression and the association between race and mortality among adults who survived a post-transplant stroke using Cox proportional hazards regression. We found no evidence of an association between race and the odds of post-transplant stroke (OR = 1.00, 95% CI: 0.83 - 1.21). The median survival time of those with a post-transplant stroke in this cohort was 4.1 years (95% CI: 3.0, 5.4). There were 726 deaths among the 1139 patients with post-transplant stroke, including 127 deaths among 203 Black patients and 599 deaths among 936 white patients. Among post-transplant stroke survivors, Black transplant recipients experienced a 27% higher rate of mortality compared to white recipients (HR = 1.27, 95% CI: 1.03 - 1.57). This disparity is strongest in the period beyond the first 6 months and appears to be mediated by differences in the post-transplant setting of care between Black and white patients. The racial disparity in mortality outcomes was not evident in the past decade.

ConclusionsThe improved survival of Black patients in the recent decade may reflect overall protocol improvements for heart transplant recipients irrespective of race, such as advancements in surgical techniques and immediate postoperative care as well as increased awareness about reducing racial disparities.

category: transplantation


title: Extended Effects of a Wearable Sensory Prosthesis on Gait, Balance Function and Falls After 26 Weeks of Use in Persons with Peripheral Neuropathy and High Fall Risk: The walk2Wellness Trial

abstract:
BackgroundWe recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins(R), a wearable lower limb sensory prosthesis that provides directional tactile stimuli related to plantar pressure measurements during standing and walking (RxFunction Inc., MN, USA). Here, we report 26-week outcomes and compare pre- and in-study fall rates. We expected improvements in outcomes and reduced fall rates reported after 10 weeks of use to be sustained.

MethodsParticipants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score <23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10m Gait Speed, Timed Up&Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar.

ResultsWe assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline seen in FGA scores (from 15.0 to 19.2), self-selected gait speed (from 0.89 m/s to 0.97 m/s), and 4-Stage Balance Test (from 25.6s to 28.4s), indicating a decrease in fall risk. Non-significant improvements were observed in TUG and fast gait speed. Overall, 39 falls were reported; 31 of them did not require medical treatment and four caused severe injury. Participants who reported falls over 6 months prior to the study had a 43% decrease in fall rate during the study as compared to self-report 6-month pre-study (11.8 vs. 6.7 falls/1000 patient days, respectively, p<0.004), similar to the 46% decrease reported after 10 weeks of use.

ConclusionA wearable sensory prosthesis can improve outcomes of gait and balance function and substantially decreases incidence of falls during long-term use. The sustained long-term benefits in clinical outcomes reported here lessen the likelihood that improvements are placebo effects.

Trial registrationClinicalTrials.gov (#NCT03538756)


title: Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis

abstract: The APOE-{varepsilon}4 allele is known to predispose to amyloid deposition and consequently is strongly associated with Alzheimers disease (AD) risk. There is debate as to whether the APOE gene accounts for all genetic variation of the APOE locus. Another question which remains is whether APOE-{varepsilon}4 carriers have other genetic factors influencing the progression of amyloid positive individuals to AD. We conducted a genome-wide association study in a sample of 5,390 APOE-{varepsilon}4 homozygous ({varepsilon}4{varepsilon}4) individuals (288 cases and 5,102 controls) aged 65 or over in the UK Biobank. We found no significant associations of SNPs in the APOE locus with AD in the sample of {varepsilon}4{varepsilon}4 individuals. However, we identified a novel genome-wide significant locus associated to AD, mapping to DAB1 (rs112437613, OR=2.28, CI=1.73-3.01, p=5.4x10-9). This identification of DAB1 led us to investigate other components of the DAB1-RELN pathway for association. Analysis of the DAB1-RELN pathway indicated that the pathway itself was associated with AD, therefore suggesting an epistatic interaction between the APOE locus and the DAB1-RELN pathway.


title: Circulating Low Density Neutrophils Mediate Resistance to First Line Anti-PD1/PDL1 Immunotherapy in Non-Small Cell Lung Cancer

abstract:
BackgroundSingle-agent immunotherapy has been widely accepted as frontline treatment for advanced non-small cell lung cancer (NSCLC) with high tumor PD-L1 expression, however most patients do not respond and the mechanisms of resistance are not well known. Several works have highlighted the immunosuppressive activities of myeloid subpopulations, including low-density neutrophils (LDNs), although the context in which these cells play their role is not well defined.

MethodsWe prospectively monitored LDNs in peripheral blood from patients with NSCLC treated with anti-PD-1 immune checkpoint inhibitors (ICIs) as frontline therapy, and correlated values with outcomes. We have monitored LDNs in a cohort of patients treated with anti-PD1 immunotherapy combined with chemotherapy (CT+IT). We performed ex vivo experiments, including comparative proteomics, to explore the underlying mechanisms.

ResultsElevated baseline LDNs predict primary resistance to ICI monotherapy in patients with NSCLC, with a response rate of 0% when levels are higher than 7.09%. Baseline LDNs are not associated with response to CT+IT. Quantitative proteomics of the plasma revealed an enrichment of the HGF/c-MET pathway in patients with high circulating LDNs, indicating a possible regulatory mechanism of this phenomenon.

ConclusionsCirculating LDNs mediate resistance in NSCLC receiving ICI as frontline therapy through humoral immunosuppression. A depletion of this population with CT+IT might overcome resistance, suggesting that patients with high PD-L1 tumor expression and high LDNs might benefit from this combination. The activation of the HGF/c-MET pathway in patients with elevated LDNs supports potential drug combinations targeting this pathway.

TRANSLATIONAL RELEVANCEImmunotherapy has positioned as frontline therapy for advanced non-small cell lung cancer (NSCLC), alone when PD-L1 tumor expression is high, or combined with chemotherapy otherwise. However, 50% of the patients do not respond to the treatment and the mechanisms of resistance are not well defined. Moreover, it is not clear whether chemo-immunotherapy (CT+IT) could be advantageous in some patients with high PD-L1 tumor expression.

We have found that baseline circulating low-density neutrophils (LDN) identify a subset of patients that are intrinsically refractory to immunotherapy. Interestingly, responses can be achieved with CT+IT, detecting a progressive depletion of LDN in those patients. Besides the potential role as predictive biomarker, through ex vivo experiments and quantitative proteomics we observed that resistance was mediated by soluble molecules related with the HGF/c-MET pathway. Our findings establish circulating myeloid cells as one of the main mediators of resistance to immunotherapy in NSCLC, and gives a rationale for potential drug combinations that might improve the outcomes.

category: oncology


title: Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis of multiple-center populations

abstract:
BackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.

MethodsThe association between IGF2 methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of IGF2 methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings.

ResultsPBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P<0.0001), and this association was validated using two independent external datasets (ORPS-adjusted, 2.21, 95% CI: 1.28 to 3.81, P=0.0042 and ORPS-adjusted, 10.65, 95% CI: 1.26 to 89.71, P=0.0295, respectively). CRC patients with IGF2 hypermethylation in PBLs had significantly improved overall survival compared to those patients with IGF2 hypomethylation (HRPS-adjusted, 0.47, 95% CI: 0.29 to 0.76, P=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HRPS-adjusted, 0.69, 95% CI: 0.37 to 1.27, P=0.2359).

ConclusionsIGF2 hypermethylation may serve as a potential blood-based predictive biomarker for the identification of individuals at high risk of developing CRC and for CRC prognosis.

FundingThis work was supported by the China Postdoctoral Science Foundation (grant number 2018M641875 to YPL); the Natural Science Foundation of Heilongjiang Province (grant number YQ2019H021 to YPL); the National Natural Science Foundation of China (grant number 81473055 to YSZ), and by grant from the SCORE Foundation (Y-MX2016-045 to YLL).

Clinical trial numberNot applicable.


title: A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial

abstract:
IntroductionAntimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+).

Methods and analysisePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measure objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses (DDD), to inform the future larger- scale trial design.

Ethics and disseminationThe qualitative research and Fidelity Index were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref:19/NS/0174). The feasibility trial and quantitative analysis were approved by the London South East Research Ethics Committee (ref:22/LO/0204). Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences.

Trial registrationISRCTN 13429325 (protocol v1.0, 15/12/2021)

Strengths and limitationsO_LIMixed-methods study, incorporating qualitative and quantitative elements, assessing feasibility of a trial evaluating the ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention.
C_LIO_LIThe feasibility trial will inform refinements of ePAMS+ intervention and its future full-scale evaluation.
C_LIO_LIDevelopment of a Fidelity Index to enable adherence to the ePAMS+ intervention to be assessed objectively.
C_LIO_LITwo study sites may limit generalisability, although inclusion of several ward types will ensure the trial covers a breadth of clinical contexts.
C_LIO_LIImplementation of ePAMS+ in the Cerner ePrescribing and Medicines Administration (EPMA) system means feasibility in other systems will still need to be established.
C_LI

Lay summaryNot all infections are caused by bacteria. For those that are, antibiotics may be a suitable treatment. When patients first come to hospital, it is sometimes not clear what is causing their illness so doctors may prescribe antibiotics just in case until results from tests to identify the presence of microbes are available. The more antibiotics a person takes the more likely they are in the future to develop bacteria in their body that antibiotics are less effective at treating. The ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention is designed to guide the appropriate use of antibiotics. ePAMS+ uses the hospital electronic patient health record to alert prescribers to situations where changing or stopping antibiotics may be a good option for a patient, consistent with existing national guidelines.

The ePAMS+ intervention will prompt healthcare professionals responsible for prescribing to review the progress and test results of a patient receiving antibiotics. After such a review:

O_LIdoctors may decide that a patient will need to carry on with antibiotics because they are right for their illness;
C_LIO_LIhealthcare staff may receive test results that can inform how long antibiotics should be prescribed for and which are best to treat the infection;
C_LIO_LIpatients may have their antibiotics stopped if the prompts alert the prescriber to decide that the illness is not caused by bacteria.
C_LI

By implementing the ePAMS+ intervention in two hospitals and interviewing staff and patients, this study will assess whether ePAMS+ and our implementation methods are acceptable. It will also confirm whether it is possible to gather the data needed to assess how well ePAMS+ works. This will help design a future larger-scale study.


title: Using Primary Care Text Data And Natural Language Processing To Monitor COVID-19 In Toronto, Canada

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectiveC_ST_ABSTo investigate whether a rule-based natural language processing (NLP) system, applied to primary care clinical text data, can be used to monitor COVID-19 viral activity in Toronto, Canada.

DesignWe employ a retrospective cohort design. We include primary care patients with a clinical encounter between January 1, 2020 and December 31, 2020 at one of 44 participating clinical sites.

Setting and ContextThe study setting is Toronto, Canada. During the study timeframe the city experienced a first wave of COVID-19 in spring 2020; followed by a second viral resurgence beginning in the fall of 2020.

Methods and DataStudy objectives are descriptive. We use an expert derived dictionary, pattern matching tools and a contextual analyzer to classify documents as 1) COVID-19 positive, 2) COVID-19 negative, or 3) unknown COVID-19 status. We apply the COVID-19 biosurveillance system across three primary care electronic medical record text streams: 1) lab text, 2) health condition diagnosis text and 3) clinical notes. We enumerate COVID-19 entities in the clinical text and estimate the proportion of patients with a positive COVID-19 record. We construct a primary care COVID-19 NLP-derived time series and investigate its correlation with other external public health series: 1) lab confirmed COVID-19 cases, 2) COVID-19 hospitalizations, 3) COVID-19 ICU admissions, and 4) COVID-19 intubations.

ResultsOver the study timeframe 1,976 COVID-19 positive documents, and 277 unique COVID-19 entities were identified in the lab text. 539 COVID-19 positive documents and 121 unique COVID-19 entities were identified in the health condition diagnosis text. And 4,018 COVID-19 positive documents, and 644 unique COVID-19 entities were identified in the clinical notes. A total of 196,440 unique patients were observed over the study timeframe, of which 4,580 (2.3%) had at least one positive COVID-19 document in their primary care electronic medical record. We constructed an NLP-derived COVID-19 time series describing the temporal dynamics of COVID-19 positivity status over the study timeframe. The NLP derived series correlates strongly with external public health series under investigation.

ConclusionsUsing a rule-based NLP system we identified hundreds of unique COVID-19 entities, and thousands of COVID-19 positive documents, across millions of clinical text documents. Future work should continue to investigate how high quality, low-cost, passively collected primary care electronic medical record clinical text data can be used for COVID-19 monitoring and surveillance.


title: Diagnostic delay of Myositis: protocol for an integrated systematic review

abstract:
Idiopathic inflammatory myopathies (IIM) described as "inflammatory myositis", are a heterogeneous group of rare muscular autoimmune diseases characterized by skeletal muscle inflammation. Its complex characteristics with lack of accurate diagnostic tests, unified classification system, and comprehensive widely used diagnostic criteria could lead to diagnostic delay. This study will review diagnostic delay in Myositis and provide an overview and clearer insight of patients experiences, causes and consequences of diagnostic delay in Myositis.

Methods and analysisThe literature source will be a systematic search of PubMed/Medline, Scopus, ProQuest, and sources of grey literature, conducted from database inception to 15th of December 2021 without restrictions on publication date. All study types (qualitative and quantitative) except review articles, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of all types of myositis in all ages will be included. Evidence of patients experiences associated with diagnostic delay will also be examined. Studies in languages other than English, German and Indonesian will be excluded. Outcomes will be diagnostic delay time, patients experiences, and causes and consequences associated with diagnostic delay in Myositis. Two review authors will independently screen the titles and abstracts of search results against the inclusion criteria. The Mixed Methods Appraisal Tool (MMAT) will be used to appraise selected studies. Two independent authors will extract data using a pre-piloted data extraction tool. If sufficient quantitative data is available, a meta-analysis will be conducted along with subgroup analysis including pooled diagnostic delay in each type of Myositis. Qualitative data will be analysed in line with meta-aggregation methods. If data is insufficient, a narrative synthesis will be conducted.

Ethics and disseminationAs a systematic review, ethical approval was not required. Findings of the study will be disseminated through publications in peer-reviewed journals, conferences, and symposia.

PROSPERO Registration numberCRD42022289830

Strengths and limitations of this studyO_LIThe protocol was developed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Handbook for Systematic Reviews.
C_LIO_LIExamination of both quantitative and qualitative literature will enable insight into the causes and consequences, and patients experiences associated with diagnostic delay of Myositis.
C_LIO_LIIn some case studies, it will be necessary to manually calculate diagnostic delay according to the date of symptom onset and the date of diagnosis.
C_LIO_LIThe primary limitation of this study is that it will not capture evidence that is not published, or from situations when an accurate diagnosis of Myositis is not made.
C_LIO_LIThe review will be limited to English, German, and Indonesian studies.
C_LI

category: epidemiology


title: Critical interventions for demand generation in Zambia, Nepal, and Senegal with regards to the 5C psychological antecedents of vaccination

abstract:
IntroductionChildhood vaccination is an effective intervention for lowering the burden of infectious disease. Progress was made to increase coverage globally, but vaccine hesitancy and refusal has threatened to erode said increases. The 5C psychological antecedents of vaccination ("5C") model provides a validated measure of "vaccine hesitancy or confidence" to assess individual thoughts and behaviors behind vaccination. Our purpose was to investigate population-level factors that contributed to high and sustained vaccination coverage via interventions in Zambia, Nepal, and Senegal, and alignment with the 5Cs.

MethodsFDGs and KIIs were collected at the national, regional, district, health facility, and community levels. We assessed the demand environment, as relayed by participants, and identified interventions that key informants reported as successful for demand generation, then retroactively aligned the interventions with the 5C constructs.

ResultsDemand was positively correlated with high confidence and collective responsibility. Psychological constraints sometimes impacted demand. Physical constraints created barriers in some communities, particularly difficult to access (i.e., mountainous). Occasionally, physical constraints did not affect vaccination behavior - parents believed the benefits of vaccination worth pursuing. Factors negatively correlated with demand and intent, complacency and calculation, had limited impact. The most critical interventions were: targeted and tailored health education activities (i.e., media partnerships, school outreach); community engagement; community ownership; and involvement of community (i.e., community health workers, leaders, religious figures).

ConclusionWe found similar interventions were used to generate demand, and those strategies aligned with the 5C constructs. Categorizing interventions by drivers of demand may help strategic planning and the division of resources; decision makers may choose to implement our suggested interventions. Assessing the 5Cs allows for decision-makers to operationalize demand generation into concrete interventions and policies, and determine the individual impact of these constructs on the population and focus efforts on interventions tailored to a specific need.


title: Mapping the emergence of SARS-CoV-2 Omicron variants on a university campus

abstract: Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P=0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8) and a 1.07 (95% confidence interval: 0.58, 1.57; P<0.0001) higher mean cycle threshold value. Despite near universal vaccination and stringent mitigation measures, Omicron rapidly displaced the Delta variant to become the predominant viral strain and led to a surge in cases in a university population.


title: Urban greenspace and anxiety symptoms during the COVID-19 pandemic: A 20-month follow up of 19,848 participants in England

abstract: This study examined the association between greenspace and the growth trajectories of anxiety symptoms during the COVID-19 pandemic. Using data from 19,848 urban residents in England who were followed for 20 months between March 2020 and October 2021, we found that living in an area with higher greenspace coverage was associated with fewer anxiety symptoms over time independent of population density, area deprivation levels, socio-demographics, and health profiles. There was limited evidence that greenspace was related to the change of anxiety symptoms over time. No association with anxiety trajectories was found when using greenspace proximity.


title: RISKS OF NEONATAL MORTALITY IN NEONATES WITH NEONATAL ENCEPHALOPATHY IN A TERTIARY NEWBORN CARE UNIT IN ZIMBABWE OVER A 12-MONTH PERIOD

abstract:
BackgroundNeonatal encephalopathy (NE) accounts for [~]23% of the 2.4 million annual global neonatal deaths. Most of these deaths occur in sub-Saharan Africa. However, data from low resource settings are scarce. We reviewed risk factors of neonatal mortality in neonates admitted with NE from a tertiary neonatal unit in Zimbabwe.

MethodsA retrospective review of risk factors of short-term NE mortality was conducted at Sally Mugabe Central Hospital (SMCH) (November 2018 - October 2019). Data were gathered using a tablet-based data capture and quality improvement newborn care application (Neotree). Analyses were performed on data from all admitted neonates with a diagnosis of NE, incorporating maternal, intrapartum and neonatal risk predictors of the primary outcome, mortality.

Results494/2894 neonates had NE on admission and were included. Of these, 94 died giving a NE-case fatality rate (CFR) of 190 per 1000 admitted neonates. Caesarean section (odds ratio (OR) 2.95(95% confidence intervals (CI) 1.39-6.25), convulsions (OR 7.13 (1.41-36.1)), lethargy (OR 3.13 (1.24-7.91)), Thompson score "11-14" (OR 2.98 (1.08-8.22)) or "15-22" (OR 17.61 (1.74-178.0)) were significantly associated with neonatal death. No maternal risk factors were associated with mortality.

ConclusionNearly 1 in 5 neonates diagnosed with NE died before discharge, similar to other low-resource setting but more than in typical high resource centres. The Thompson score, a validated, sensitive and specific tool for diagnosing neonates with NE was a good predictor of worse outcomes in this setting. On univariable analysis time-period, specifically a period of staff shortages due to industrial action, had a significant impact on NE mortality. Emergency caesarean section was associated with increased mortality, suggesting perinatal care is likely to be a key moment for future interventions


title: The impact of the COVID-19 pandemic on the provision & utilisation of primary health care services in Goma, Democratic Republic of the Congo, Kambia district, Sierra Leone & Masaka district, Uganda

abstract:
IntroductionThis study aimed to determine whether the COVID-19 pandemic had an impact on the number of people seen at public facilities in Uganda, the Democratic Republic of the Congo (DRC) and Sierra Leone for essential primary healthcare services.

MethodsThe number of weekly consultations for antenatal care (ANC), outpatient (OPD), expanded programme on immunisations (EPI), family planning (FP) services and HIV, for the period of January 2018-December 2020, were collected from 25 primary healthcare facilities in Masaka district, Uganda, 21 health centres in Goma, DRC, and 29 facilities in Kambia district, Sierra Leone. Negative binomial regression models accounting for facility level clustering and season were used to analyse changes in activity levels between 2018, 2019 and 2020.

ResultsWe found no evidence that the COVID-19 pandemic affected the number of OPD, EPI or ANC consultations in Goma. Family planning consultations were 17% lower in March-July 2020 compared to 2019, but this recovered by December 2020. New diagnoses of HIV were 34% lower throughout 2020 compared to 2019. Compared to the same periods in 2019, facilities in Sierra Leone had 18-29% fewer OPD consultations throughout 2020, and 27% fewer DTP3 doses in March-July 2020, but this had recovered by Jul-Dec. There was no evidence of differences in other services. In Uganda there were 20-35% fewer under-5 OPD consultations, 21-66% fewer MCV1 doses, and 48-51% fewer new diagnoses of HIV, throughout 2020, compared to 2019. There was no difference in the number of HPV doses delivered in 2020 compared to 2019.

ConclusionsThe level of disruption appeared to correlate with the strength of lockdown measures in the different settings and community attitudes towards the risk posed by COVID-19. Mitigation strategies such as health communications campaigns and outreach services proved important to limit the impact of lockdowns on primary healthcare services.

Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSThe COVID-19 pandemic and the response measures put in place caused disruption to the provision and utilisation of primary healthcare services worldwide.

What this study addsWe document that the COVID-19 pandemic had a varied impact on different services in three distinct settings on the African continent. The extent that the pandemic impacted services correlated with the stringency of the lockdowns, community perceptions of the level of danger posed by the pandemic and communities prior exposure to Ebola epidemics and concomitant response measures.

How this study might affect research, practice, or policystrategies such as communication campaigns and outreach services limited the impact of lockdowns on essential services and would be valuable strategies to implement in future epidemics.


title: The Physical Exercise and Cardiovascular Adaptation Monitoring in Pregnancy (PE-CAMP) Randomised Controlled Trial Protocol.

abstract:
BackgroundExercise can be beneficial to cardiovascular system function, but its influence during pregnancy is less well understood. Heterogeneity in research studies has led to a lack of consensus on whether physical exercise during pregnancy can elicit cardiovascular adaptations during a period in which the cardiovascular system is already being challenged. Furthermore, little research has been conducted regarding the influence of physical exercise on foetal heart rate (FHR). This paper presents the protocol for a randomised controlled trial which will evaluate the influence of supervised antenatal physical exercise on cardiovascular adaptations during and after pregnancy, as well as the FHR response to acute and chronic maternal exercise.

MethodsThe PE-CAMP Study (Physical Exercise and Cardiovascular Adaptation Monitoring in Pregnancy) is a randomised controlled trial (RCT) in which pregnant women will be randomised into an intervention group (INT), which attended supervised physical exercise programme up to three days per week, or a comparison group (COMP) which followed standard health care. All participants were assessed at three time-points i) 18-22 weeks pregnant, time-point 1; ii) 33-37 weeks pregnant, time-point 2; and iii) 12-16 weeks postnatal, time-point 3. A standardised experimental protocol was used for data collection, including body composition assessment, upper-body flexibility and strength assessment, physical activity assessment via questionnaires and acceletometry, and haemodynamic and cardiovascular evaluation before, during and after an acute 10-minute exercise bout. Foetal heart rate will be assessed at the time-point 2 before, during and after acute exercise.

DiscussionAlthough it is necessary and informative to continue investigating the effects of exercise on maternal cardiac and haemodynamic responses using specific laboratory-based tests, it is also critical to evaluate these influences during activities that are more achievable and realistic for pregnant women. The PE-CAMP study will provide data on the cardiac and haemodynamic responses to a typical acute bout of exercise, which could help inform future decisions and policies on maternal exercise prescription made by maternity healthcare providers and exercise professionals.

Clinical Trials Registration NumberNCT03748888

category: sports medicine


title: Prior Optic Neuritis Detection on Peripapillary Ring Scans using Deep Learning

abstract:
BackgroundThe diagnosis of multiple sclerosis (MS) d requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack.

ObjectiveTo investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans.

MethodsWe included 1,033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training (728 HC and 352 ON), 15% validation (152 HC and 79 ON), and 15% test data (153 HC and 79 ON). We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve (ROC) analyses with area under the curve (AUC) were used to investigate performance.

ResultsWe used a dilated residual convolutional neural network with alternating convolutional and max pooling layers for the classification. A final network using 2-factor augmentation had an accuracy of 0.85. The network achieved an area under the curve (AUC) of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84.

ConclusionDL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.