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10.1101/2022.04.25.22274288 | Predictors of Survival among 6-59 Months Old Children with Severe Acute Malnutrition: A Retrospective Cohort | BackgroundUndernutrition among children is a significant contributor to the global disease burden and a leading cause of child mortality. Ethiopia, home to more than 16 million children under 5 years old, is one of the countries that have high levels of wasting. The aim of this study was to assess survival status and predictors of mortality among children with severe acute malnutrition admitted to Dubti Zonal Referral hospital from January 1/2017 to September 30/2019.
MethodsFacility-based retrospective cohort was conducted among 331 severely acutely malnourished children. Data were collected from SAM management registration, individual patient cards and multi-charts admitted from January 1/2017 to September 30/2019. Cox-regression was used to characterize survival within the cohort and to estimate the effect of specific variables while controlling for potential confounders. The hazard ratio was used as a measure of the outcome. P-value less than 0.05 was considered statistically significant to identify independent predictors in multivariable analysis.
ResultThe median age of study participants was 18 months and males were 187(56%). About half of 160 (48.3%) respondents were with co-morbidities during admission: diarrhea (44%) and pneumonia (26%) were the major co-morbidities. From a total of 331 SAM children, 255(77%) were recovered, 34(10%) died, and 40(12%) have defaulted from treatment. The main risk factors for earlier death of severely malnourished children were rural residence (AHR=1.6, 95% CI= 0.745-3.493), being on IV Infusion (AHR=2.5, 95% CI= 1.12-4.18), anemia during admission (AHR= 6.27, 95% CI =2.41-16.36) & pneumonia (AHR=0.27, 95% CI = 0.11-0.68)
ConclusionsThe death rate was 10% which is close to the minimum SPHERE standard & national management protocol for SAM. Predictors for earlier hospital deaths were rural residence, IV infusion, Anemia, and Pneumonia. | nutrition |
10.1101/2022.04.26.22274224 | A systematic review of the effects of traditional East Asian medicine on symptom clusters during the menopausal transition | ImportanceGiven that many midlife women use evidence-based non-pharmacologic interventions for symptom management during the menopausal transition and early postmenopause and that many women experience two or more symptoms (symptom cluster), it is important to review recent evidence on said interventions for symptom clusters. This review focuses on randomized clinical trials (RCTs) of traditional East Asian Medicine (TEAM), including acupuncture, acupressure, moxibustion, and Chinese herbal medicine, for hot flashes and one or more co-occurring symptoms experienced during peri- or post-menopause.
ObjectiveThe primary objective of the study was to review RCTs (published 2011-2021) of TEAM interventions for hot flashes and at least one other co-occurring symptom, including sleep problems, cognitive function, mood, and pain.
Evidence ReviewWe searched Medline, CINAHL Plus, and PsychINFO for RCTs reported in English from July 7, 2011, to December 31, 2021. We included RCTs that assessed women in the menopausal transition or early postmenopause with masking as appropriate; TEAM interventions were studied as the treatment with one or more comparison groups; hot flushes and at least one additional symptom from at least one of the symptom clusters were reported as an outcome (from sleep, mood, cognition, pain symptom groups). Bias was assessed.
FindingsOf 409 abstracts identified, 9 RCTs examined the effectiveness of therapies for hot flashes and at least one additional co-occurring symptom. One study reported separately on two TEAM interventions. The maximum trial duration was 6 months (range: 5 weeks - 6 months). Statistically significant improvement was reported in 2 or more symptoms: 5 of 6 studies of acupuncture, one acupressure study, one moxibustion study, 1 of 2 studies of Chinese herbal medicine.
Conclusions and RelevanceOur systematic review summarizes the recent literature on TEAM interventions for symptom clusters during the MT and EPM. A majority of studies reported symptom reduction. Overall, our findings highlight the need for further investigation with studies that include whole systems TEAM as each intervention was studied separately in the reviewed trials. Clinical practice often includes concurrent use of acupuncture, moxibustion, CHM, and advice to patients to use self-acupressure. Studying each modality separately is a scientific abstraction that does not reflect clinical practice.
Key PointsO_ST_ABSQuestion/ObjectiveC_ST_ABSWhat is the effect of traditional East Asian medicine (TEAM) therapeutics, including acupuncture, acupressure, Chinese herbal medicine, or moxibustion for hot flashes and one or more co-occurring symptoms during the menopausal transition (MT)?
FindingsNine RCTs (n=811) evaluating the effects of TEAM therapeutics on MT symptoms were included. Statistically significant improvement was reported in these studies: acupuncture (5 of 6), 1 acupressure study, 1 moxibustion study, and Chinese herbal medicine (1 of 2).
MeaningBased on the results of this systematic review, TEAM interventions demonstrate promising improvement of hot flashes and co-occurring symptoms experienced during the MT. | obstetrics and gynecology |
10.1101/2022.04.26.22274264 | Pilot study on the use of low molecular weight heparins in the prevention of thromboembolic disease during pregnancy and puerperium. | A pregnant woman is 4 to 5 times more likely to suffer a thromboembolic event than a non-pregnant woman. Furthermore, an increase in these episodes has been observed in women infected with SARS-CoV-2. Consequently, the prophylactic prescription of low-molecular-weight heparins (LMWH) in pregnant women is undergoing an increase that has not been evaluated yet. The aim of this study was to determine the prevalence of LMWH prescription in pregnant women at the Hospital Universitario Puerta de Hierro Majadahonda (HUPHM), according to their level of risk and its variation due to SARS-CoV-2 infection. To answer this question, a retrospective cohort of 113 women who gave birth during the month of February at the HUPHM was designed. The level of individual risk of thromboembolism, according to the Royal College guidelines (37a), was calculated with an interview to complete a questionnaire and the analysis of their clinical records. 53.6% of the women were prescribed LMWH as indicated in the guidelines. This high prevalence is explained by the high age of the pregnant women (over 35 years), the wave of the omicron variant (December 2021) and a high rate of cesarean sections (25%). On the other hand, the percentage of patients with COVID-19 was 17.6% but only 53% of them had received LMWH. In conclusion, LMWH is a very common prescription in obstetrics, mostly during puerperium, and has become even more relevant due to the COVID-19 pandemic | obstetrics and gynecology |
10.1101/2022.04.25.22274276 | Exploring U.S. food system workers' intentions to work while ill during the early COVID-19 pandemic: a national survey analysis | BackgroundAs "stay at home" orders were in effect, many US food workers attended in-person work during early phases of the COVID-19 pandemic, charged with maintaining normal operation of the national food supply chain. Despite establishment of a novel national paid sick leave policy, anecdotal evidence suggests that many U.S. food system workers encountered barriers to staying home when ill.
MethodsUsing quantitative and free-text analyses from a national, cross-sectional, online survey deployed from July to October 2020 among 2,535 respondents, we explored workplace and non-workplace factors associated with U.S. food system workers intentions to attend work while ill (i.e. presenteeism intentions) during the first four to six months of the COVID-19 pandemic.
ResultsOverall, 8.8% of workers surveyed reported intentions to attend work while ill. Both quantitative data and free-text responses suggest that aspects of workplace culture influenced workers decisions to attend work while ill. Workers reporting a high workplace safety climate score had half the odds of reporting presenteeism intentions (adjusted odds ratio [aOR] 0.52, 95% confidence interval (CI) 0.37, 0.75) relative to those reporting low scores. Workers described cultural barriers, including retaliation and penalties, that reduced paid sick leave access. Workers reporting low (aOR 2.06, 95% CI 1.35, 3.13) or very low (aOR 2.31, 95% CI 1.50, 3.13) levels of household food security had more than twice the odds of reporting presenteeism intentions.
ConclusionsThis study offers insights into opportunities for reducing presenteeism related to illness among food workers both during the COVID-19 pandemic and in other infectious disease scenarios. Addressing vulnerabilities like food insecurity and empowering food system workers to make health-protective decisions is important both for optimal worker health outcomes and maintaining a functioning food system. | occupational and environmental health |
10.1101/2022.04.25.22274276 | Exploring U.S. food system workers' intentions to work while ill during the early COVID-19 pandemic: a national survey analysis | BackgroundAs "stay at home" orders were in effect, many US food workers attended in-person work during early phases of the COVID-19 pandemic, charged with maintaining normal operation of the national food supply chain. Despite establishment of a novel national paid sick leave policy, anecdotal evidence suggests that many U.S. food system workers encountered barriers to staying home when ill.
MethodsUsing quantitative and free-text analyses from a national, cross-sectional, online survey deployed from July to October 2020 among 2,535 respondents, we explored workplace and non-workplace factors associated with U.S. food system workers intentions to attend work while ill (i.e. presenteeism intentions) during the first four to six months of the COVID-19 pandemic.
ResultsOverall, 8.8% of workers surveyed reported intentions to attend work while ill. Both quantitative data and free-text responses suggest that aspects of workplace culture influenced workers decisions to attend work while ill. Workers reporting a high workplace safety climate score had half the odds of reporting presenteeism intentions (adjusted odds ratio [aOR] 0.52, 95% confidence interval (CI) 0.37, 0.75) relative to those reporting low scores. Workers described cultural barriers, including retaliation and penalties, that reduced paid sick leave access. Workers reporting low (aOR 2.06, 95% CI 1.35, 3.13) or very low (aOR 2.31, 95% CI 1.50, 3.13) levels of household food security had more than twice the odds of reporting presenteeism intentions.
ConclusionsThis study offers insights into opportunities for reducing presenteeism related to illness among food workers both during the COVID-19 pandemic and in other infectious disease scenarios. Addressing vulnerabilities like food insecurity and empowering food system workers to make health-protective decisions is important both for optimal worker health outcomes and maintaining a functioning food system. | occupational and environmental health |
10.1101/2022.04.26.22274346 | Cancer-associated Lactobacillus iners are genetically distinct and associated with chemoradiation resistance in cervical cancer | This study identifies a novel pathotype of cervical cancer-associated Lactobacillus iners (L. iners) that results in chemoradiation resistance in vitro and is associated with poor patient survival. Cervical cancer affects over half a million women a year around the world. Treatment for women with locally advanced cancer is delivered with definitive chemoradiation (CRT) but is curative for only 60% of patients. There are few validated molecular markers to identify patients who will respond poorly to treatment. Tumor microbiome features are associated with treatment resistance in patients with colon and pancreatic cancers, and thus we investigated their role in the response of cervical cancer to therapy. We identified a strong association between poor clinical response to CRT and tumors dominated by L. iners. Cancer-associated L. iners promoted in vitro resistance of cervical cancer cells and modified the local tumor immunologic microenvironment, while non-cancer-associated L. iners did not. Assembly of genomes from cancer-derived L. iners also demonstrated pathogenic, metabolic, and immune functions not found in healthy patients. | oncology |
10.1101/2022.04.26.22274275 | Prostate cancer androgen receptor activity dictates efficacy of Bipolar Androgen Therapy | Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), entitled Bipolar Androgen Therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer [1-5]. However, predictors and mechanisms of response and resistance have been ill-defined. Here we show that growth inhibition of prostate cancer models by SPA requires high androgen receptor (AR) abundance and activity and is driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pre-treatment AR activity predicts downregulation of MYC, clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance can be overcome by alternating SPA with the AR inhibitor enzalutamide, which induces adaptive upregulation of AR and re-sensitizes prostate cancer to SPA. This work identifies a predictive biomarker of response to BAT and supports a new treatment paradigm for prostate cancer involving alternating between AR inhibition and activation. | oncology |
10.1101/2022.04.26.22274298 | Computational Image Analysis Techniques, Programming Languages and Software Platforms Used in Cancer Research: A Scoping Review | BackgroundCancer-related research, as indicated by the number of entries in Medline, the National Library of Medicine of the USA, has dominated the medical literature. An important component of this research is based on the use of computational techniques to analyse the data produced by the many acquisition modalities. This paper presents a review of the computational image analysis techniques that have been applied to cancer. The review was performed through automated mining of Medline/PubMed entries with a combination of keywords. In addition, the programming languages and software platforms through which these techniques are applied were also reviewed.
MethodsAutomatic mining of Medline/PubMed was performed with a series of specific keywords that identified different computational techniques. These keywords focused on traditional image processing and computer vision techniques, machine learning techniques, deep learning techniques, programming languages and software platforms.
ResultsThe entries related to traditional image processing and computer vision techniques have decreased at the same time that machine learning and deep learning have increased significantly. Within deep learning, the keyword that returned the highest number of entries was convolutional neural network. Within the programming languages and software environments, Fiji and ImageJ were the most popular, followed by Matlab, R, and Python. Within the more specialised softwares, QuPath has had a sharp growth overtaking other platforms like ICY and CellProfiler.
ConclusionsThe techniques of artificial intelligence techniques and deep learning have grown to overtake most other image analysis techniques and the trend at which they grow is still rising. The most used technique has been convolutional neural networks, commonly used to analyse and classify images. All the code related to this work is available through GitHub: https://github.com/youssefarafat/Scoping-Review. | oncology |
10.1101/2022.04.26.22274147 | Missense variants in the voltage sensing and pore domain of KCNH5 cause neurodevelopmental phenotypes including epilepsy | ObjectiveKCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.
MethodsWe screened 893 individuals with developmental and epileptic encephalopathies (DEEs) for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included three previously published individuals including additional phenotypic details.
ResultsWe report a cohort of 17 patients, including nine with a recurrent de novo missense variant p.Arg327His, four with a recurrent missense variant p.Arg333His, and four additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using American College of Medical Genetics and Genomics (ACMG) criteria. All individuals presented with epilepsy with a median seizure onset at six months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalised epilepsy and normal intellect, while the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore-domain were more severely affected, with neonatal-onset DEE, profound disability, and childhood death.
ConclusionsWe report the first cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders (NDDs) and epilepsy. | genetic and genomic medicine |
10.1101/2022.04.26.22274312 | Factors Influencing Health Impacts among Smartphone Users in New Normal Situation: A Case Study among University Students in Thailand | BackgroundNowadays, smartphone users are increasing across the world. Smartphones have become a necessary thing in peoples life. Using smartphones have both benefits and health effects. Therefore, this study mainly aims to develop an appropriate mobile application to be the tool for health effects and finding factors associated with a health risk from smartphone usage.
MethodsThis study was a cross-sectional descriptive study. The data was conducted in Thailand. The sample size was 500 university students. The Smartphone U Health mobile application was developed and shown in the Play Store and App Store. The self-administration was used for data collection throughout the Smart U Health. Data were entered and analyzed with licensed SPSS version 22.
ResultsThe participants, including 328 females (65.6%) and 172 males (34.4%) with an average age was 20.3{+/-}1.5 years old. The average period of using smartphones was 7.9{+/-}2.0 years. The average time spent was 8.6{+/-}3.4 hours/day. The primary physical, mental, and social health effects from smartphone usage over three months were eye pain (93.8%), feeling bored (90.4%), the participants had a communication problem with other people (84.0%), respectively. In the multivariate analysis, the significant factors associated with a health risk from smartphone usage were faculty, income, using smartphones in the classroom, experience of resting their eyes before continuing. Moreover, knowledge and practice levels were significantly associated with health risk levels from smartphone usage.
ConclusionOveruse of smartphones had many health effects. The Smart U Health mobile application might be the appropriate tool to assess smartphone users health risk levels. In the future, it may consider an intervention study to reduce health risks from smartphone usage. | health informatics |
10.1101/2022.04.25.22274285 | Evaluating diagnostic accuracies of Panbio™ COVID-19 rapid antigen test and RT-PCR for the detection of SARS-CoV-2 in Addis Ababa, Ethiopia using Bayesian Latent-Class Models (BLCM) | BackgroundRapid diagnostics are vital for curving the transmission and control of COVID-19 pandemic. Although many commercially available antigen-based rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 are recommended by the WHO, their diagnostic performance has not yet been assessed in Ethiopia. So far, the vast majority of studies assessing diagnostic accuracies of rapid antigen tests considered RT-PCR as a gold standard, which inevitably leads to bias when RT-PCR is not 100% sensitive and specific. Thus, this study aimed to evaluate the diagnostic performance of Panbio COVID-19 rapid antigen test jointly together with the RT-PCR for the detection of SARS-CoV-2.
MethodsA prospective cross-sectional study was done from July to September 2021 in Addis Ababa, Ethiopia, during the third wave of the pandemic involving two health centers and two hospitals. Diagnostic sensitivity and specificity of Panbio rapid antigen test and RT-PCR were obtained using Bayesian Latent-Class Models (BLCM).
Results438 COVID-19 presumptive clients were enrolled, 239 (54.6%) were females, of whom 196 (44.7%) had a positive RT-PCR and 158 (36.1%) were Ag-RDT positive. The Ag-RDT and RT-PCR had a sensitivity (95% CrI) of 99.6 (98.4-100), 89.3 (83.2-97.6) and specificity (95% CrI) of 93.4 (82.3 - 100), 99.1 (97.5-100) respectively. Most of the study participants, 318 (72.6) exhibited COVID-19 symptoms and the most reported was cough 191 (43.6).
ConclusionThe diagnostic performance of Panbio COVID-19 Ag RDT is coherent with the WHO established criteria of having a sensitivity [≥]80% for Ag-RDTs. Superior performance of the Panbio RDT was documented in samples with the lowest cycle-threshold RT-PCR values and clients with confirmed clinical symptoms. Thus, we recommend the use of the Panbio RDT for both symptomatic and asymptomatic individuals in clinical settings for screening purposes. | health systems and quality improvement |
10.1101/2022.04.26.22274345 | Identifiability of parameters in mathematical models of SARS-CoV-2 infections in humans | Determining accurate estimates for the characteristics of the severe acute respiratory syndrome coronavirus 2 in the upper and lower respiratory tracts, by fitting mathematical models to data, is made difficult by the lack of measurements early in the infection. To determine the sensitivity of viral predictions to the noise in the data, we developed a novel two-patch within-host mathematical model and investigated its ability to match population level data. We proposed several approaches that can improve practical identifiability of parameters, including an optimal experimental approach, and found that availability of viral data early in the infection is of essence for improving the accuracy of the estimates. Our findings can be useful for designing interventions. | infectious diseases |
10.1101/2022.04.26.22274196 | Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections | The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics analysis of an immunologically naive SARS-CoV-2 clinical cohort from the plasma of uninfected controls, mild, and severe infections. A comparison of healthy controls and patient samples showed activation of neutrophil degranulation pathways and formation of neutrophil extracellular trap (NET) complexes that were activated in a subset of the mild infections and more prevalent in severe infections (containing multiple NET proteins in individual patient samples). As a potential mechanism to suppress NET formation, multiple redox enzymes were elevated in the mild and severe symptom population. Analysis of metabolites from the same cohort showed a 24- and 60-fold elevation in plasma L-cystine, the oxidized form of cysteine, which is a substrate of the powerful antioxidant glutathione, in mild and severe patients, respectively. Unique to patients with mild infections, the carnosine dipeptidase modifying enzyme (CNDP1) was up-regulated. The strong protein and metabolite oxidation signatures suggest multiple compensatory pathways working to suppress oxidation and NET formation in SARS-CoV-2 infections. | infectious diseases |
10.1101/2022.04.26.22274311 | Burden and bacteriological profile of sepsis among adult medical emergencies presenting to a national referral hospital in Kampala, Uganda | 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. | infectious diseases |
10.1101/2022.04.25.22274294 | Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination | 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. | allergy and immunology |
10.1101/2022.04.25.22274284 | Factors affecting oral health problems among school children in Kaski District, Nepal | 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. | dentistry and oral medicine |
10.1101/2022.04.26.22274273 | COVID-19 third wave experience in India, a survey of 5971 adults | 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 | epidemiology |
10.1101/2022.04.26.22274301 | Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017-2021 | 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. | epidemiology |
10.1101/2022.04.26.22274255 | The primary care annual dementia review: a qualitative study of the views and experiences of service users and providers | 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 | primary care research |
10.1101/2022.04.25.22274281 | Comprehensive assessment of Age-Specific Mortality Rate and its incremental changes using a composite measure: A sub-national analysis of rural Indian women | 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. | public and global health |
10.1101/2022.04.25.22274300 | Characterization of Autonomic Symptom Burden in Long COVID: A Global Survey of 2,314 Adults | 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. | neurology |
10.1101/2022.04.26.22274343 | A Novel Application of Neural Networks to Identify Potentially Effective Combinations of Biologic Factors for Enhancement of Bone Fusion/Repair | 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. | orthopedics |
10.1101/2022.04.25.22274265 | Human Germline Heterozygous Gain-of-Function STAT6 Variants Cause Severe Allergic Disease | 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. | genetic and genomic medicine |
10.1101/2022.04.25.22274283 | The Helping Older People Engage (HOPE) Study: Protocol & COVID Modifications for a Randomized Trial | 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. | geriatric medicine |
10.1101/2022.04.27.22274390 | Can accurate demographic information about people who use prescription medications non-medically be derived from Twitter big data? | 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. | health informatics |
10.1101/2022.04.28.22274059 | Acceptability and Feasibility of Genetic Testing to Assess Risk of HIV-Associated Neurocognitive Impairment among Thai Adolescents and Young Adults | 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. | hiv aids |
10.1101/2022.04.27.22274384 | Assessing clinical outcomes of vancomycin treatment in adult patients with penicillin-resistant Enterococcus faecium bacteremia | 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. | infectious diseases |
10.1101/2022.04.25.22274287 | WHEN SEX MATTERS: A COMPARATIVE GENERALISED STRUCTURAL EQUATION MODEL (GSEM) FOR THE DETERMINANTS OF STUNTING AMONGST UNDER-FIVES IN UGANDA | 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. | epidemiology |
10.1101/2022.04.28.22274253 | Diagnosis and treatment of opioid use disorder in a South African private sector medical insurance scheme: a cohort study | 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. | epidemiology |
10.1101/2022.04.26.22274316 | 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. | 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. | epidemiology |
10.1101/2022.04.26.22274340 | Artificial Intelligence Model for Detecting Duodenal Endoscopic Changes on Images of Functional Dyspepsia | 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. | gastroenterology |
10.1101/2022.04.27.22274391 | 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 | 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. | psychiatry and clinical psychology |
10.1101/2022.04.27.22274269 | CRISIS AFAR: An International Collaborative Study of the Impact of the COVID-19 Pandemic on Youth with Autism and Neurodevelopmental Conditions. | 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. | psychiatry and clinical psychology |
10.1101/2022.04.26.22274333 | Using Explainable-AI to Find Geospatial Environmental and Sociodemographic Predictors of Suicide Attempts | 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. | public and global health |
10.1101/2022.04.27.22274377 | Which countries need COVID-19 vaccines the most? Development of a prioritisation tool | 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. | public and global health |
10.1101/2022.04.27.22274353 | Arbovirus risk perception as a predictor of mosquito-bite preventive behaviors in Ponce, Puerto Rico | 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. | public and global health |
10.1101/2022.04.27.22274356 | 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 | 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. | public and global health |
10.1101/2022.04.27.22274355 | Classifying sex with MRI | 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. | radiology and imaging |
10.1101/2022.04.27.22274369 | High-Dimensional Multinomial Multiclass Severity Scoring of COVID-19 Pneumonia Using CT Radiomics Features and Machine Learning Algorithms | 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. | radiology and imaging |
10.1101/2022.04.25.22274289 | Postural control telerehabilitation with a low-cost virtual reality protocol for children with cerebral palsy: Protocol for a clinical trial. | 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. | rehabilitation medicine and physical therapy |
10.1101/2022.04.27.22273623 | Augmenting gait in a population exhibiting foot drop with adaptive functional electrical stimulation | 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. | rehabilitation medicine and physical therapy |
10.1101/2022.04.25.22274293 | Characteristics of health-related quality of life and related factors in patients with brain tumors treated with rehabilitation therapy | 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. | rehabilitation medicine and physical therapy |
10.1101/2022.04.26.22274347 | Early Carotid Revascularization Rates, Procedural Distribution, and Hospital Density | 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. | surgery |
10.1101/2022.04.27.22274385 | Racial Disparities in Post-Transplant Stroke and Mortality Following Stroke in Adult Cardiac Transplant Recipients in the United States | 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. | transplantation |
10.1101/2022.04.28.22274328 | 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 | 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) | neurology |
10.1101/2022.04.28.22274418 | Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis | 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. | neurology |
10.1101/2022.04.27.22273598 | Circulating Low Density Neutrophils Mediate Resistance to First Line Anti-PD1/PDL1 Immunotherapy in Non-Small Cell Lung Cancer | 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. | oncology |
10.1101/2022.04.27.22274374 | Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis of multiple-center populations | 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. | oncology |
10.1101/2022.04.27.22274394 | A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial | 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. | health informatics |
10.1101/2022.04.27.22274400 | Using Primary Care Text Data And Natural Language Processing To Monitor COVID-19 In Toronto, Canada | 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. | health informatics |
10.1101/2022.04.27.22274397 | Diagnostic delay of Myositis: protocol for an integrated systematic review | 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 | epidemiology |
10.1101/2022.04.25.22274035 | Critical interventions for demand generation in Zambia, Nepal, and Senegal with regards to the 5C psychological antecedents of vaccination | 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. | epidemiology |
10.1101/2022.04.27.22274375 | Mapping the emergence of SARS-CoV-2 Omicron variants on a university campus | 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. | epidemiology |
10.1101/2022.04.27.22274371 | Urban greenspace and anxiety symptoms during the COVID-19 pandemic: A 20-month follow up of 19,848 participants in England | 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. | public and global health |
10.1101/2022.04.27.22274371 | Urban greenspace and anxiety symptoms during the COVID-19 pandemic: A 20-month follow up of 19,848 participants in England | 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. | public and global health |
10.1101/2022.04.28.22274381 | RISKS OF NEONATAL MORTALITY IN NEONATES WITH NEONATAL ENCEPHALOPATHY IN A TERTIARY NEWBORN CARE UNIT IN ZIMBABWE OVER A 12-MONTH PERIOD | 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 | public and global health |
10.1101/2022.04.28.22274416 | 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 | 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. | public and global health |
10.1101/2022.04.27.22274359 | The Physical Exercise and Cardiovascular Adaptation Monitoring in Pregnancy (PE-CAMP) Randomised Controlled Trial Protocol. | 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 | sports medicine |
10.1101/2022.04.27.22274388 | Prior Optic Neuritis Detection on Peripapillary Ring Scans using Deep Learning | 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. | neurology |
10.1101/2022.04.28.22274370 | Neuropsychological assessments for dementia research in the COVID-19 era: comparing remote and face-to-face testing | ObjectivesWe explored whether adapting traditional neuropsychological tests for online administration against the backdrop of COVID-19 was feasible for people with diverse forms of dementia and healthy older controls. We compared face-to-face and remote settings to ascertain whether remote administration affected performance.
DesignWe used a longitudinal design for healthy older controls who completed face-to-face neuropsychological assessments between three and four years before taking part remotely. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched in age, education, and disease duration.
SettingRemote assessments were performed using video-conferencing and online testing platforms, with participants using a personal computer or tablet and situated in a quiet room in their own home. Face-to-face assessments were carried out in dedicated testing rooms in our research centre.
ParticipantsThe remote cohort comprised ten healthy older controls (also seen face-to-face 3-4 years previously) and 25 patients (n=8 Alzheimers disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive nonfluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA).
Primary and secondary outcome measuresThe outcome measures comprised the strength of evidence under a Bayesian analytic framework for differences in performances between face-to-face and remote testing environments on a general neuropsychological (primary outcomes) and neurolingustic battery (secondary outcomes).
ResultsThere was evidence to suggest comparable performance across testing environments for all participant groups, for a range of neuropsychological tasks across both batteries.
ConclusionsOur findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.
Strengths and limitations of this studyO_ST_ABSMethodological strengths of this study includeC_ST_ABSO_LIDiverse patient cohorts representing rare dementias with specific communication difficulties
C_LIO_LISampling of diverse and relevant neuropsychological domains
C_LIO_LIUse of Bayesian statistics to quantify the strength of evidence for the putative null hypothesis (no effect between remote and face-to-face testing)
C_LI
Limitations includeO_LIRelatively small cohort sizes
C_LIO_LILack of direct head-to-head comparisons of test environment in the same patients
C_LI | neurology |
10.1101/2022.04.28.22274408 | Islamic Perspective on Nursing and the Philosophy of Science | Although nursing theory developed in the modern Western scientific tradition has universal aspects, it is important to consider the different philosophies, beliefs and cultures of each different society to enrich the perspective and practice of nursing that is more sensitive to the patients background. As supported by the Transcultural Nursing Theory, in treating patients a nurse needs to pay attention to and respect the cultural preferences and beliefs of the patient. In this context, this article wants to contribute by describing the Islamic perspective on nursing in the context of nursing philosophy. Methods: This literature review uses articles published from 2018-2022 with source from databased ScienceDirect, Scopus, Sage Journals, EBSCO-Host, Springer Link, and ProQuest. The keywords used are Islamic, perspective, nursing, caring. Article selection follows "PRISMA" flow. Results: This systematic review have a total of 8 articles meet the criteria for analysis. This article has relevance both in Muslim-majority countries such as Indonesia, Malaysia and Middle Eastern countries, as well as countries where Muslims are a minority. We found 8 articles presents a number of opinions or research results that examine nursing issues and those related to it from an Islamic perspective. From a number of opinions and research findings studied, it can be concluded that although it can be said to offer universal core values, the Islamic perspective has fundamental differences with Western nursing philosophy or theory, especially in terms of the source of knowledge, the basic view of humans, and the importance of spirituality in nursing. | nursing |
10.1101/2022.04.28.22274424 | Phenotypic associations with the HMOX1 GT(n) promoter repeat in European populations | HO-1 is a key enzyme in the management of heme in humans. A GT(n) repeat length in the gene HMOX1, has previously been widely associated with a variety of phenotypes, including susceptibility and outcomes in diabetes, cancer, infections, and neonatal jaundice. However, studies are generally small and results inconsistent. In this study, we imputed the GT(n) repeat length in two European cohorts (UK Biobank, n = 463,005; and Avon Longitudinal Study of Parents and Children (ALSPAC n = 937), with the reliability of imputation tested in other cohorts (1000 Genomes, HGDP, and UK-PGP). Subsequently, we measured the relationship between repeat length and previously identified associations (diabetes, COPD, pneumonia and infection related mortality in UK Biobank; neonatal jaundice in ALSPAC) and performed a phenome-wide association study (PheWAS) in UK Biobank. Despite high quality imputation (correlation between true repeat length and imputed repeat length >0.9 in test cohorts), no clinical associations were identified in either the PheWAS or specific association studies. These findings were robust to definitions of repeat length and sensitivity analyses. Despite multiple smaller studies identifying associations across a variety of clinical settings; we could not replicate or identify any relevant phenotypic associations with the HMOX1 GT(n) repeat. | genetic and genomic medicine |
10.1101/2022.04.25.22274157 | A machine learning-based SNP-set analysis approach for identifying disease-associated susceptibility loci | IntroductionIdentifying disease-associated susceptibility loci is one of the most pressing and crucial challenges in modeling complex diseases. Existing approaches to biomarker discovery are subject to several limitations including underpowered detection, neglect for variant interactions, and restrictive dependence on prior biological knowledge. Addressing these challenges necessitates more ingenious ways of approaching the "missing heritability" problem.
ObjectivesThis study aims to discover disease-associated susceptibility loci by augmenting previous genome-wide association study (GWAS) using the integration of random forest and cluster analysis.
MethodsThe proposed integrated framework is applied to a hepatitis B virus surface antigen (HBsAg) seroclearance GWAS data. Multiple cluster analyses were performed on (1) single nucleotide polymorphisms (SNPs) considered significant by GWAS and (2) SNPs with the highest feature importance scores obtained using random forest. The resulting SNP-sets from the cluster analyses were subsequently tested for trait-association.
ResultsThree susceptibility loci possibly associated with HBsAg seroclearance were identified: (1) SNP rs2399971, (2) gene LINC00578, and (3) locus 11p15. SNP rs2399971 is a biomarker reported in the literature to be significantly associated with HBsAg seroclearance in patients who had received antiviral treatment. The latter two loci are linked with diseases influenced by the presence of hepatitis B virus infection.
ConclusionThese findings demonstrate the potential of the proposed integrated framework in identifying disease-associated susceptibility loci. With further validation, results herein could aid in better understanding complex disease etiologies and provide inputs for a more advanced disease risk assessment for patients. | genetic and genomic medicine |
10.1101/2022.04.28.22274405 | Updating mortality risk estimation in intensive care units from high-dimensional electronic health records with incomplete data | ContextIntensive care units (ICU) are subject to a high mortality rate, currently addressed by the implementation of scores (SAPS II, SOFA, APACHE II) assessing the risk of in-hospital mortality from admission data. Their performances are satisfactory to predict death when complications occur early after admission; however, they may become irrelevant in the case of long hospital stays.
MethodsUsing the MIMIC-III database, we developed predictive models of short-term mortality in ICU from longitudinal data collected throughout patients stays of at least 48 hours. Several statistical learning approaches were compared, including deep neural networks and penalized regression. Missing data were handled using either complete case analysis or multiple imputation. Models performances were evaluated via repeated 5-fold cross-validation.
ResultsPredictions relying on longitudinal data were more accurate than those relying solely on admission data. Complete case analyses from 19 predictors showed good discrimination (area under the ROC curve [AUC] > 0.77 for several statistical learning approaches) to predict death between 12 and 24 hours onwards, while keeping only 25% of patients in the sample. Multiple imputation allowed to include 70 predictors and keep 95% of patients, with similar performances, hence allowing predictions in patients with incomplete data. Calibration was satisfactory for all models.
DiscussionThis proof of concept supports that automated analysis of electronic health records can be of great interest throughout patients stays, as a surveillance tool likely to detect lethal complications in ICU soon enough to take corrective measures. Though this framework relies on a large set of predictors, it is robust to data imputation and may be effective early after admission, as data is still scarce. | health informatics |
10.1101/2022.04.26.22274351 | Heterogeneity of Provider Preferences for HIV Care Coordination Program Features: Latent Class Analysis of a Discrete Choice Experiment | BackgroundThe PROMISE study was launched in 2018 to assess revisions to an HIV care coordination program (CCP) designed to address gaps in care and treatment engagement among people living with HIV in New York City (NYC). We report on the heterogeneity of provider preferences regarding a revised CCP elicited from a discrete choice experiment (DCE).
MethodsFrom January to March 2020, 152 CCP providers in NYC completed a DCE with 4 program attributes: 1) help with adherence to antiretroviral therapy, 2) help with primary care appointments, 3) help with issues other than primary care, and 4) program visit location. Each attribute had 3-4 levels. Latent class analysis (LCA) was used to detect subgroups with differing attribute importance and part-worth utility patterns. Choice simulation was used to estimate providers endorsement of eight hypothetical CCPs.
ResultsLCA identified three subgroups. The two larger subgroups (n = 133) endorsed more intensive attribute levels, particularly clients receiving directly observed therapy, and home visits. The remaining smaller subgroup (n = 19) endorsed clients receiving medication reminders and meeting with clients at the program. Simulation showed that intensive medical case management programs had the highest degree of endorsement (62%).
ConclusionWhile our results indicate high endorsement among providers for intensive CCP features, overall, they also suggest the need for flexible service delivery options to meet the needs of the clients that these programs serve. Additional information sharing across and within agencies may be warranted to improve the fidelity with which the CCP is implemented. | hiv aids |
10.1101/2022.04.26.22274330 | Interest of seroprevalence surveys for the epidemiological surveillance of the SARS-CoV-2 pandemic in African populations: insights from the ARIACOV Project in Benin | BackgroundMany SARS-CoV-2 seroprevalence surveys since the end of 2020 have disqualified the first misconception that Africa had been spared by the pandemic. Through the analysis of three SARS-CoV-2 seroprevalence surveys carried out in Benin as part of the ARIACOV project, we argue that the integration of epidemiological serosurveillance of the SARS-COV2 infection in the national surveillance package would be of great use to refine the understanding of the COVID-19 pandemic in Africa.
MethodsThree repeated cross-sectional surveys have been carried out in Benin, two in Cotonou, the economic capital in March and May 2021, and one in Natitingou, a semi-rural city in North in August 2021. The global and by age-groups weighted seroprevalences have been estimated and the risk factors of the infection by SARS-COV-2 have been assessed by using logistic regression.
ResultsIn Cotonou, a slight increase in overall age-standardized SARS-CoV-2 seroprevalence from 29.77% (95% CI: 23.12-37.41%) at the first survey to 34.86% (95% CI: 31.57-38.30%) at the second survey was observed. In Natitingou the global adjusted seroprevalence was 33.34% (95% CI: 27.75-39.44%), much higher than expected. Adults over 40 seemed to be more at risk than the youngest during the first survey in Cotonou but no longer in the second survey, showing the persistence of the SARS-COV-2 virus circulation outside the epidemic waves.
ConclusionsA routine serological surveillance on strategic sentinel sites and / or populations could constitute a cost / effective compromise to better anticipate the onset of new waves and define public health strategies. | infectious diseases |
10.1101/2022.04.25.22274187 | Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 | Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas(R) SARS-CoV-2 assays, defined by a [≥]2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities. | infectious diseases |
10.1101/2022.04.27.22274378 | "Utilization of health insurance by patients with diabetes or hypertension in urban hospitals in Mbarara, Uganda" | BackgroundDiabetes and hypertension are among the leading contributors to global mortality and require life-long medical care. However, many patients cannot access quality healthcare due to high out-of-pocket expenditures, thus health insurance would help provide relief. This paper examines factors associated with utilization of health insurance by patients with diabetes or hypertension at two urban hospitals in Mbarara, southwestern Uganda.
MethodsWe used a cross-sectional survey design to collect data from patients with diabetes or hypertension attending two hospitals located in Mbarara. Logistic regression models were used to examine associations between demographic factors, socio-economic factors and awareness of scheme existence and health insurance utilization.
ResultsWe enrolled 370 participants, 235 (63.5%) females and 135 (36.5%) males, with diabetes or hypertension. Patients who were not members of a microfinance scheme were 76% less likely to enrol in a health insurance scheme (OR = 0.34, 95% CI: 0.15 - 0.78, p = 0.011). Patients diagnosed with diabetes/hypertension 5 - 9 years ago were more likely to enrol in a health insurance scheme (OR = 2.99, 95% CI: 1.14 - 7.87, p = 0.026) compared to those diagnosed 0 - 4 years ago. Patients who were not aware of the existing schemes in their areas were 99% less likely to take up health insurance (OR = 0.01, 95% CI: 0.0 - 0.02, p < 0.001) compared to those who knew about health insurance schemes operating in the study area. Majority of respondents expressed willingness to join the proposed national health insurance scheme although concerns were raised about high premiums and misuse of funds which may negatively impact decisions to enrol.
ConclusionBelonging to a microfinance scheme positively influences enrolment by patients with diabetes or hypertension in a health insurance program. Although a small proportion is currently enrolled in health insurance, the vast majority expressed willingness to enrol in the proposed national health insurance scheme. Microfinance schemes could be used as an entry point for health insurance programs for patients in these settings. | cardiovascular medicine |
10.1101/2022.04.27.22274380 | Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study | NAD+ precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have failed to report positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months (clinicaltrials.gov entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI. | endocrinology |
10.1101/2022.04.28.22274413 | Life stage-specific effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study | Background/ObjectivesSeparate genetic variants are associated with larger body size in childhood and adulthood. Whether these variants predominantly influence adiposity, and whether these truly differ by life stage is unknown. We examined how genetic variants influence total body fat and total lean mass trajectories from childhood to young adulthood.
MethodsData were from the Avon Longitudinal Study of Parents and Children birth cohort. Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans were used to measure total body fat and lean mass 6 times between ages 9-25y. We used mutually-adjusted multilevel linear spline models to examine the independent sex-specific associations of childhood and adulthood body size GRSs with fat and lean mass trajectories from 9 -25y.
ResultsIn males, the childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18y; 8.3% (95% confidence interval (CI): 5.1,11.6)) and 7.5% (95% CI: 4.3,10.8) higher fat mass at 18y per standard deviation (SD) higher childhood and adulthood GRS respectively. At 25y, childhood GRS associations with fat mass attenuated while adulthood GRS associations remained similar to those at 18y for males. Among females, associations for the childhood GRS were almost two-fold stronger than the adulthood GRS from 9 to 18y: 10.5% (95% CI: 8.5, 12.4) higher fat mass at 9y per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per SD higher adulthood GRS. At 25y, associations of the childhood and adulthood GRS with fat mass were similar; 5.0% (95% CI: 2.5, 7.5) and 5.8% (95% CI: 3.3, 8.3) higher fat mass per SD higher childhood and adulthood GRS respectively: Lean mass effect sizes were much smaller.
ConclusionsGenetic variants for body size are more strongly associated with adiposity than lean mass from childhood to early adulthood; childhood variants are more strongly associated with adiposity in females until early adulthood whereas childhood and adulthood variants are similarly associated with adiposity across early life in males. Findings may inform selection of instruments for life stage-specific adiposity in future Mendelian randomization studies. | epidemiology |
10.1101/2022.04.26.22274335 | Incorporating Vaccination into Compartment Models for Infectious Diseases | The standard way of incorporating vaccination into a compartment model for an infectious disease is as a spontaneous transition process that applies to the entire susceptible class. The large degree of COVID-19 vaccine refusal and initial limitations of supply and distribution require reconsideration of this standard treatment. In this paper, we address these issues for models on endemic and epidemic time scales. On an endemic time scale, we partition the susceptible class into prevaccinated and unprotected subclasses and show that vaccine refusal has a significant impact on endemic behavior, particularly for diseases where immunity is short-lived. On an epidemic time scale, we develop a supply-limited Holling type 3 vaccination model and show that it is an excellent fit to vaccination data. We also extend the Holling model to a COVID-19 scenario in which the population is divided into two risk classes, with the high-risk class being prioritized for vaccination. For both cases with and without stratification by risk, we see significant differences in epidemiological outcomes between the Holling vaccination model and naive models. Finally, we use the new model to explore implications for public health policies in future pandemics. | epidemiology |
10.1101/2022.04.26.22274256 | Feasibility of an online antigen self-testing strategy for SARS-CoV-2 addressed to health care and education professionals in Catalonia (Spain). The TESTAT- COVID Project | We aimed to implement a pilot intervention based on offering online COVID-19 selftest kits addressed to healthcare and education professionals in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.
Key findingsO_LIWe implemented a pilot intervention based on offering online COVID-19 selftest kits in Spain.
C_LIO_LIWe demonstrated the feasibility of the intervention during the peak of the 6th wave caused by Omicron variant.
C_LIO_LIThe intervention counted with high acceptability among healthcare and education professionals in Spain.
C_LIO_LIOur results may contribute to define screening strategies addressed to key populations, particularly during peaks of high community transmission of SARS-CoV-2.
C_LI | epidemiology |
10.1101/2022.04.27.22274309 | Multi-level analysis of adipose tissue reveals the relevance of perivascular subpopulations and an increased endothelial permeability in early-stage lipedema | Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on tissue level as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here we showed for the first time, that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease. | pathology |
10.1101/2022.04.27.22274363 | The global effects of alcohol consumption on Gross Domestic Product in high- and low-income countries: a systematic review and meta-analysis | Aims and objectivesThis study aims to measure the disease burden and the economic burden associated with alcohol consumption in both high- and low-income countries. To emphasise the necessity of making this issue a worldwide priority, the percentage of GDP attributable to alcohol-related costs will be stated.
DesignSystematic review and meta-analysis
Data sourcesA systematic search concerning health and social costs was conducted primarily through PubMed and subsequent citation chaining of appropriate systematic reviews. Other electronic databases such as Google Scholar was also freely searched.
Eligibility criteria for selecting studiesObservational studies examining alcohol-related harm, alcohol-related disease, and alcohol-related expenditure with all studies measuring alcohol-related harm using the alcohol-attributable fraction (AAF).
Results9 cross-sectional studies were obtained assessing the consequences of alcohol on the respective countrys economy with all studies utilising a prevalence-based approach. 5 studies were eligible for a meta-analysis in the statistically programming software, R. The pooled estimate of the economic burden of alcohol in 5 countries equated to be 0.01% of GDP. Though inconsistencies in cost estimations resulted in an underestimation, our results provide evidence to suggest that alcohol negatively affects both individuals and society. The available literature on the topic of the economic impact of alcohol is inadequate; especially when investigating concerns in poorer regions of the world.
ConclusionThough the current estimate of global GDP attributable to alcohol use is low, the evidence suggesting the global increase of alcohol consumption is paramount to avoid future calamities. Cooperative leadership from the World Health Organisation (WHO), International Monetary Fund, and the World Bank are requisite to control the harmful patterns of alcohol consumption seen across the globe.
STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis is the first systematic review assessing the detrimental consequences of alcohol on economic health with the inclusion of both lower-middle income and high-income countries.
C_LIO_LIThis study provides a pooled estimate of the global estimate of the percentage of GDP attributable to alcohol related costs using statistical package, R which has not been done before.
C_LIO_LIThe obtainment of research conducted in low-income countries proved to be difficult, and as a result no low-middle income countries were used when calculating the pooled estimate. Therefore, the accuracy of the provided estimate was decreased.
C_LI | health economics |
10.1101/2022.04.27.22274363 | The global effects of alcohol consumption on Gross Domestic Product in high- and low-income countries: a systematic review and meta-analysis | Aims and objectivesThis study aims to measure the disease burden and the economic burden associated with alcohol consumption in both high- and low-income countries. To emphasise the necessity of making this issue a worldwide priority, the percentage of GDP attributable to alcohol-related costs will be stated.
DesignSystematic review and meta-analysis
Data sourcesA systematic search concerning health and social costs was conducted primarily through PubMed and subsequent citation chaining of appropriate systematic reviews. Other electronic databases such as Google Scholar was also freely searched.
Eligibility criteria for selecting studiesObservational studies examining alcohol-related harm, alcohol-related disease, and alcohol-related expenditure with all studies measuring alcohol-related harm using the alcohol-attributable fraction (AAF).
Results9 cross-sectional studies were obtained assessing the consequences of alcohol on the respective countrys economy with all studies utilising a prevalence-based approach. 5 studies were eligible for a meta-analysis in the statistically programming software, R. The pooled estimate of the economic burden of alcohol in 5 countries equated to be 0.01% of GDP. Though inconsistencies in cost estimations resulted in an underestimation, our results provide evidence to suggest that alcohol negatively affects both individuals and society. The available literature on the topic of the economic impact of alcohol is inadequate; especially when investigating concerns in poorer regions of the world.
ConclusionThough the current estimate of global GDP attributable to alcohol use is low, the evidence suggesting the global increase of alcohol consumption is paramount to avoid future calamities. Cooperative leadership from the World Health Organisation (WHO), International Monetary Fund, and the World Bank are requisite to control the harmful patterns of alcohol consumption seen across the globe.
STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis is the first systematic review assessing the detrimental consequences of alcohol on economic health with the inclusion of both lower-middle income and high-income countries.
C_LIO_LIThis study provides a pooled estimate of the global estimate of the percentage of GDP attributable to alcohol related costs using statistical package, R which has not been done before.
C_LIO_LIThe obtainment of research conducted in low-income countries proved to be difficult, and as a result no low-middle income countries were used when calculating the pooled estimate. Therefore, the accuracy of the provided estimate was decreased.
C_LI | health economics |
10.1101/2022.04.26.22274235 | CLINICAL MANIFESTATIONS AND DIAGNOSIS OF CO-INFECTION OF COVID-19, TUBERCULOSIS AND OPPORTUNISTIC PULMONARY INFECTIONS IN LATE-STAGE HIV PATIENTS WITH IMMUNODEFICIENCY | ObjectiveThe purpose of the study was to investigate the specific features of clinical manifestations and diagnosis of co-infection of COVID-19, tuberculosis and opportunistic pulmonary infections in late-stage HIV patients.
Design27 patients with co-infection of COVID-19, tuberculosis, opportunistic pulmonary infections and late-stage HIV infection with immunodeficiency without antiretroviral therapy (group 1) and 27 patients with equivalent parameters but without COVID-19 (group 2) were examined.
ResultsThe patients of the group 1 and group 2 are the persons with social maladjustment and substance addiction. All of them have concomitant viral hepatitis B/C, COPD, opportunistic pulmonary infections and similar clinical and radiological manifestations, which can only be differentiated with microbiological and molecular genetic studies. The patients with co-infection of COVID-19, tuberculosis and HIV pose a high risk of transmission of infection to healthy persons in view of non-adherence to examination and treatment.
ConclusionTo prevent the spread of infection among the healthy population, it is necessary to arrange in a mandatory manner an active and regular COVID-19 testing of all patients with tuberculosis/HIV co-infection, especially of late-stage HIV patients without antiretroviral therapy, in the tuberculosis care unit for HIV-infected persons at the tuberculosis dispensary.
SettingThere are few data on the specific features of clinical manifestations of co-infection of COVID-19, tuberculosis (TB) and opportunistic pulmonary infections (OPI) in late-stage HIV patients with immunodeficiency.
ObjectiveStudy purpose is to investigate the specific features of clinical manifestations and diagnosis of co-infection of COVID-19, TB and OPI in late-stage HIV patients with immunodeficiency.
DesignFifty-four (54) patients admitted for inpatient treatment at the TB Clinical Hospital N 3 named after Zakharyin were enrolled in this prospective study. The participants were assigned to two groups: group 1 (main) and group 2 (comparison group). Group 1 consisted of twenty-seven (27) aged 28-52 patients (18 men (66.7 {+/-} 9.1%) and 9 women (33.3 {+/-} 9.1%)) with known co-infection of COVID-19, sputum smear-positive for M. tuberculosis (MBT) pulmonary tuberculosis (PTB) and with late-stage HIV infection in progression phase without antiretroviral therapy (ART). Group 2 included 27 patients who were selected using the "copy-pair" method and were completely identical to the patients of the main group (with virtually the same age, sex, social parameters and clinical and laboratory indicators), but without diagnosis of COVID-19. | hiv aids |
10.1101/2022.04.27.22274334 | Mortality among healthcare workers in Indonesia during 18 months of COVID-19 | The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID-19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web-based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39-59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID-19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 - 5.17). The COVID-19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rates is 5-times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and a national systematic surveillance of occupational mortality is urgently needed in this setting. | public and global health |
10.1101/2022.04.28.22274428 | Cross-sectional association of skeletal muscle mass and strength with dietary habits and physical activity among first-year university students in Japan: Results from KEIJI-U study | BackgroundRecently, the high prevalence of young Japanese people who are underweight has received attention because of its potential impact on healthy life expectancy. Sarcopenia, defined as the presence of low muscle mass and function, is often observed in the underweight. However, few reports have described the prevalence and characteristics of sarcopenia in youth.
MethodsIn this cross-sectional study, we measured skeletal muscle mass using a multifrequency bioelectrical impedance analysis device and handgrip strength (HGS) and administered questionnaires on dietary habits and physical activity to 1,264 first-year university students aged 18-20 years (838 males and 426 females). Sarcopenia was diagnosed based on the presence of both low skeletal muscle mass (SMI) and weak HGS according to the Asian Working Group for Sarcopenia.
ResultsA total of 145 males (17.3%) and 69 females (16.2%) were diagnosed as underweight. Low SMI was diagnosed in 75 males (8.9%) and 18 females (4.2%), and weak HGS was diagnosed in 28 males (3.3%) and 10 females (2.3%). Then, sarcopenia was diagnosed in 8 males (1.0%) and 5 females (1.2%). There was a significantly higher prevalence of low SMI and/or weak HGS in underweight individuals compared with individuals in the other BMI ranges. The multivariate analyses indicated that SMI and HGS were significantly associated with BMI in both sexes. Furthermore, after adjusting for BMI, both SMI and HGS were significantly associated with physical activity in males, and SMI was significantly associated with energy intake and frequency of breakfast intake in females.
ConclusionsFirst-year university students showed a high incidence of being underweight with low SMI and/or weak HGS, but the prevalence of sarcopenia was low in both sexes. BMI, energy intake, frequency of breakfast intake, and physical activity were independently associated with skeletal muscle mass and strength in youth. | public and global health |
10.1101/2022.04.27.22274348 | Preclinical interstitial lung disease in relatives of familial pulmonary fibrosis patients | Family history is amongst the strongest risk factors for interstitial lung disease (ILD), with emerging evidence for a shared genetic aetiology across ILD subtypes. Recruited families comprised at least two first-degree relatives who had been previously diagnosed with an ILD. All living cases and available unaffected first-degree relatives underwent a clinical examination for evidence of ILD. Preclinical ILD was diagnosed in 47.7% of first-degree relatives who had previously self-reported as unaffected. This study highlights the strong genetic predisposition in family members of ILD cases, and supports the call for routine screening of individuals with a family history of ILD. | respiratory medicine |
10.1101/2022.04.28.22274426 | Patient satisfaction in the use of non-pharmacological therapies in the management of postoperative pain: a study in a tertiary hospital, Ghana | BackgroundNon-pharmacological therapies are the non-medicinal methods used in postoperative pain (POP) management by health care practitioners such as massage, positioning, breathing exercise, music therapy, and distraction. It has been discovered that therapies that are non-pharmacological for the relief of pain are effective with minimal side effects. Studies have also revealed that non-pharmacological interventions in the management of pain lessen or alter pain perception by decreasing intensity and intensifying the tolerance of pain. This study, therefore, seeks to determine how frequently non-pharmacological methods (NPMs) are used in the management of POP and the influence of these NPMs on patient satisfaction
MethodsThis study was a descriptive cross-sectional design. A quantitative approach was utilized with a structured questionnaire to obtain responses from patients from October to December 2019. The study was conducted in the female and male surgical wards of Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. 138 patients within the first 72 hours post-operative period who consented and fulfilled the inclusion criteria were enrolled in the study. A convenience sampling method was used to collect the data. Inferential and descriptive statistics were used in analyzing the data.
ResultsThe majority of the patients, 52.2% responded to using some form of (NPMs) for pain relief. The most widely used non-pharmacological method of pain relief was walking representing 79.2%, followed by relaxation 5 (6.8%), distraction 4 (5.6%), listening to music 3 (4.2%), deep breathing 2 (2.8%), and meditation 1 (1.4%). The male participants were observed to use more NPMs of pain relief as compared to the females. Most of the patients (51.4%) who used NPMs for their pain relief reported having their pain not relieved. A majority (90.6%) of the participants desired for more pain treatment. The type of surgery the patients underwent had a statistically significant negative correlation with the use of NPMs of pain relief (Spearman Correlation Coefficient = -0.233, p-value <0.05). A higher percentage (71%) of participants were highly satisfied with the overall pain treatment received.
ConclusionNon-pharmacological management of POP have been proven to be efficient, inexpensive, and have little or no side effect on patients. There should be continuous education on non-pharmacological management of POP to nurses and other healthcare professionals to help promote the efficiency of intervening in postoperative pain with these methods. | nursing |
10.1101/2022.04.25.22274262 | Smoking and socio-economic factors linked to acute exacerbations of COPD: analysis from an Asthma + Lung UK survey | Understanding the factors driving acute exacerbations of COPD is key to reducing their impact on human health and wellbeing. 5997 patients, mean 66 years, 64% female, completed an online survey between December 2020 and May 2021 about living with COPD developed by the charity Asthma+Lung UK. The 3731(62.2%) reporting frequent([≥]2/year) exacerbations were more likely to smoke (AOR 1.70, 95%CI 1.470-1.98), have lower annual household income ([≤]{pound}20,000, (AOR: 1.72, 1.36-2.17), live in a cold and damp home (AOR: 1.78, 1.50-2.11), and report previous occupational exposure to dust, fumes, and chemicals. Strategies to improve COPD outcomes must address issues of social justice. | respiratory medicine |
10.1101/2022.04.28.22274431 | Intraoperative calculus or hemorrhage in transurethral seminal vesiculoscopy as a risk factor for recurrent hemospermia | We summarized our experience regarding Transurethral Seminal Vesiculoscopy (TUSV) and analyzed both recurrence status and risk factors for recurrence. From January 2010 to December 2020, 48 patients with intractable hemospermia received successful TUSV at Taichung Invalids General Hospital. For the intraoperative findings, the five-year Disease-free Survival rates (DFS) were 74.1% in the no calculus group compared to 37.1% in the calculus group with a significant difference (log-rank p = 0.015), 75.0% in the no hemorrhage or no blood clot group compared to 43.2% in the hemorrhage or blood clot group with significant difference (log-rank p = 0.032). Univariate analysis showed intraoperative calculus (p = 0.040; HR: 2.94, 95% CI: 1.05-8.21) to be significantly associated with recurrence (p < 0.05). Patients with intractable hemospermia who were diagnosed with stones or blood clots found during TUSV experienced a higher rate of hemospermia recurrence. | urology |
10.1101/2022.04.25.22273876 | Abnormal synergies and associated reactions post-hemiparetic stroke reflect the neuroanatomy of brainstem motor pathways | Individuals with moderate-to-severe post-stroke hemiparesis have difficulty controlling proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called the flexion and extension synergies. Over the last three decades, we and others have quantitatively characterized these patterns and have provided evidence that they emerge because of an increased influence of diffusely-projecting brainstem motor pathways following stroke-induced damage to corticospinal and corticobulbar pathways. In our recent work that has focused on how they influence post-stroke hand function, we observed three notable aspects of synergy expression that we have never studied systematically: (1) paretic wrist and finger muscles were often activated maximally while individuals contracted muscles at a different joint, not during a maximal voluntary contraction of the wrist and finger muscles themselves; (2) there were differences in the magnitude of synergy expression when elicited via contraction of proximal muscles vs. distal muscles; (3) there was consistent movement resembling flexion or extension synergy patterns in the paretic limb during maximal efforts with the non-paretic limb (a phenomenon described clinically as an associated reaction), and the strength of these movement seemed to differ based on which muscles in the non-paretic limb were being activated. In the current study, we investigated the above behaviors systematically during maximal isometric contractions of shoulder, elbow and wrist/finger muscles, specifically focusing on differences between proximal vs. distal joints and flexor vs. extensor muscles. Our overall hypothesis is that the muscle-dependent nature of the behaviors we have observed is consistent with how the muscles are impacted by corticofugal damage and the upregulation of brainstem motor pathways that results. That is, we expected that our findings would reflect the fact that the greatest proportion of descending neural control comes from the corticospinal tract for distal muscles and from brainstem motor pathways for proximal muscles. We further expected that findings would reflect the fact that the reticulospinal tract, thought to underlie the flexion synergy, has bilateral effects in the upper limbs and favors facilitation of flexor muscles on the ipsilateral side. Supporting this hypothesis, we found that for some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions. This was more prevalent and more severe in magnitude at the wrist and fingers than at the shoulder and elbow. We also found that synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Finally, we found that associated reactions in the paretic wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the contralateral contraction was at a proximal or distal joint. Our results provide indirect evidence for how an increased reliance on brainstem motor pathways post-stroke contributes to abnormal motor behaviors and demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb. | rehabilitation medicine and physical therapy |
10.1101/2022.04.28.22274442 | A Solution to the Kermack and McKendrick Integro-Differential Equations | In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. The KMES can be cast in the form of a step function response to the input of new infections; and that response is the time series of the total infections. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for diagnosing and managing an epidemic. These include new expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections.
Since the publication of Kermack and McKendricks seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions which are putatively derived from the integro-differential equations, to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, as we explicate in this manuscript, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. Our conclusion is that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics. | epidemiology |
10.1101/2022.04.27.22274350 | Detection of M. tuberculosis in the environment as a tool for identifying high-risk locations for tuberculosis transmission | Tuberculosis (TB) remains a leading cause of infectious mortality globally, yet most cases cannot be epidemiologically linked even with extensive contact investigations and whole genome sequencing. Consequently, there remain major gaps in our understanding of where and when M. tuberculosis (Mtb) exposures occur. We aimed to investigate whether Mtb can be detected in environments where TB patients were recently present, which could serve as a tool for characterizing exposure risk. We collected 389 environment surface (ES) swabs from two high TB burden prisons in Brazil, sampling 41 (n=340) cells occupied by individuals with active TB and 7 (n=49) cells from individuals without TB. In a subset of pooled swabs (n=6) and a swab from a cigarette lighter from the cell with active TB patients, we enriched Mtb DNA using RNA-bait hybrid capture assays and performed whole genome sequencing. In prison cells, Mtb DNA was detected in 55/340 (16%) of ES swabs from cells occupied by active TB patients and none (0/49) from cells in which no active TB patients were present. Mtb was detected in 13/16 (81%) prison cells occupied by the individuals with high/medium sputum Xpert Mtb load and 8/25 (32%) with low/very low sputum Mtb load (p=0.003). Seven hybrid capture samples had a median genomic coverage of 140X. rpoB mutations conferring high-level rifampin resistance were detected in 3/7 ES swabs. Mtb was frequently detectable in environments recently occupied by individuals with active TB. This approach could be applied in congregate environments to identify and characterize high-risk settings for Mtb exposure. | epidemiology |
10.1101/2022.04.29.22274457 | Therapeutic effects of different timing for PTCD and ERCP in obstructive severe acute biliary pancreatitis | ObjectiveThis study compared the therapeutic effects of different timing for PTCD and ERCP in obstructive severe acute biliary pancreatitis.
MethodsWe evaluated the clinical data for 62 patients with obstructive severe acute biliary pancreatitis in Beijing Tiantan Hospital. The study was performed from July, 2013 to July, 2019. According to the treatment, patients were divided into three groups: conservative group (n=16), PTCD group (n=22) and ERCP group (n=24), and the PTCD and ERCP groups were divided into early (24-72 h) and delayed (>72 h) groups. Laboratory indices, recovery time of liver function, remission time of abdominal pain, hospitalization length, curability and complications were compared among groups.
ResultsThe average hospitalization length, time for abdominal pain relief and laboratory indices recovery were shorter (p <0.05) in early PTCD and ERCP groups than in the conservative group. Further, the average days of hospitalization in the ERCP group was shorter (p <0.05) than in the PTCD group. The complications were low in ERCP (33.33%) and PTCD (27.27%) groups, compared to the conservative group (62.50%).
ConclusionsFor patients who cannot determine the severity of biliary pancreatitis in the first place and exclude patients who have performed ERCP within 24 hours, ERCP is recommended for relieving obstruction of obstructive severe acute biliary pancreatitis within 24-72 hours, however, PTCD may be considered in patients failed to be cured by ERCP. | gastroenterology |
10.1101/2022.04.28.22274339 | Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology | Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Appropriate assessment of disease activity is critical for adequate treatment decisions. In addition to endoscopic mucosal healing, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, there is no standardized definition of histologic remission, limiting the utility of histologic scoring, and manual pathologist evaluation is subject to intra-and inter-observer variability. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, and can enable sensitive assessment of clinically relevant features. Here we report a proof-of-concept study using the PathAI platform to develop ML models for identification and quantification of UC histological features directly from hematoxylin and eosin (H&E)-stained whole slide images. Model-predicted histological features were used to quantify tissue area proportions and cell count proportions and densities, which correlated with disease severity and pathologist-assigned Nancy Histological Index (NHI) scores. Moreover, using multivariate analysis based on selected model-predicted histological features, we were able to accurately predict NHI scores, with a weighted kappa (k=0.93) and Spearman correlation ({rho}=0.93, p<0.001) when compared to manual pathologist consensus NHI scores. We were also able to predict histological remission, based on the resolution of active inflammation, with high accuracy of 0.94. These results demonstrate the accuracy of ML models in quantifying histologic features of UC and predicting NHI scores, and highlight the potential of this approach to enable standardized and robust assessment of histologic remission for improved evaluation of disease activity and prognosis. | pathology |
10.1101/2022.04.29.22274480 | Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects | Alterations in gray matter (GM) and monoamine oxidase A (MAO-A) distribution across the brain have been found in various neuropsychiatric conditions. MAO-A catalyzes the oxidative degradation of various monoamines and is thus implicated in neuroplastic processes that influence GM density (GMD) and microstructure (GMM) of the brain. Sex-specific differences in these patterns are well documented, however studying the long-term effects of certain sex steroids on the brain are limited due to hormonal fluctuations under naturalistic conditions. Due to the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy represent a valuable cohort to investigate such changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term gender-affirming hormone therapy over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men were recruited. All participants underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. Between baseline and follow-up imaging, transgender subjects underwent gender-affirming hormone therapy. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. The present results are indicative of a reliable influence of gender-affirming hormone therapy on GMD and GMM following an interregional pattern. Nevertheless, future studies with larger sample sizes are needed to further investigate the relationship between sex steroids, gray matter alterations and MAO-A density. | psychiatry and clinical psychology |
10.1101/2022.04.28.22274095 | Maternal depressive symptoms, neonatal white matter, and toddler social-emotional development | Maternal prenatal depression is associated with increased likelihood of neurodevelopmental and psychiatric conditions in offspring. The relationship between maternal depression and offspring outcome may be mediated by in-utero changes in brain development. Recent advances in magnetic resonance imaging (MRI) have enabled in vivo investigations of neonatal brains, minimising the effect of postnatal influences. The aim of this study was to examine associations between maternal prenatal depressive symptoms, infant white matter, and toddler behaviour. 413 mother-infant dyads enrolled in the developing Human Connectome Project. Mothers completed the Edinburgh Postnatal Depression Scale (median = 5, range = 0-28, n=52 scores [≥] 11). Infants (n=223 male) (median gestational age at birth=40 weeks, range 32.14-42.29) underwent MRI (median postmenstrual age at scan=41.29 weeks, range 36.57-44.71). Fixel-based fibre metrics (mean fibre density, fibre cross- section, and fibre density modulated by cross-section) were calculated from diffusion imaging data in the left and right uncinate fasciculi and cingulum bundle. For n=311, internalizing and externalizing behaviour, and social-emotional abilities were reported at a median corrected age of 18 months (range 17-24). Statistical analysis used multiple linear regression and mediation analysis with bootstrapping. Maternal depressive symptoms were positively associated with infant fibre density in the left (B =.0005, p=.003, q=.027) and right (B=.0006, p=.003, q=.027) uncinate fasciculus, with the left uncinate fasciculus, in turn, positively associated with social-emotional abilities in toddlerhood (B =105.70, p=.0007, q=.004). In a mediation analysis, higher maternal depressive symptoms predicted toddler social-emotional difficulties (B=.342, t(307)=3.003, p=.003), but this relationship was not mediated by fibre density in the left uncinate fasciculus (Sobel test p=.143, bootstrapped indirect effect=.035, SE=.02, 95%CI [-.01.08]). There was no evidence of an association between maternal depressive and cingulum fibre properties. These findings suggest that maternal perinatal depressive symptoms are associated with neonatal uncinate fasciculi microstructure, but not fibre bundle size, and toddler behaviour. | psychiatry and clinical psychology |
10.1101/2022.04.28.22274372 | Adaptation and validation of a French version of the Vaccination Attitudes Examination (VAX) scale | Over the past decades, vaccination has proven to be largely beneficial to global health. Despite vaccine efficacy, the French population has been recently affected by more anti-vaccination attitudes and vaccine refusal, and it is therefore necessary to develop and validate tools to study this health issue. The Vaccination Attitudes Examination scale is a brief 12-item questionnaire targeting adults, that assesses general attitudes towards vaccination. The aims of the study were (1) to translate and adapt the original English version of the scale into French and (2) to test the psychometric properties of the scale in a French population-based sample of adults. We included 450 French speaking adults that completed the French Vaccination Attitudes Examination scale and other questionnaires in order to assess convergent and divergent validities. Exploratory and confirmatory factor analyses showed that the French version of the Vaccination Attitudes Examination scale replicated the factorial structure of the original scale. Moreover, it demonstrated high internal consistency, good convergent and divergent validities, and excellent temporal stability. Also, scores on the scale differentiated vaccinators from non-vaccinator respondents. Results on the scale provides us with insight into factors involved in vaccine hesitancy in France, therefore allowing French authorities and policy makers to address these specific concerns and by consequence improve vaccine acceptance rates in this country. | public and global health |
10.1101/2022.04.28.22274344 | Understanding Definitions and Reporting of Deaths Attributed to COVID-19 in the UK - Evidence from FOI Requests | Death is a widely used outcome to assess the severity of pandemics. Accuracy in assigning the cause of death is of vital importance to define the impact of the agent, monitor its evolution, and compare its threat with those of other agents. Throughout the COVID-19 pandemic, there has been widespread reporting of aggregate death data with little attention paid to the accuracy of the assignment of causation.
We aimed to analyse public authorities understanding of the assignment of cause of deaths during the SARS-CoV-2 pandemic in the UK by accessing Freedom of Information requests posed in three periods in 2020-21. By public authorities, we mean NHS Health Trusts, laboratories, and government agencies such as Public Health England and the Department of Health and Social Care. We searched WhatDoTheyKnow using the terms "covid and death". We excluded those requests to bodies that cannot provide an answer (e.g. Councils) and those dealing with the effects of vaccines.
We grouped questions into themes addressing the definitions and causes of death relevant to the pandemic. We looked at the responses to the questions of the definition of cause of death, the accuracy of the attribution, the role of other pre-existing pathologies and how these were reported and quantified.
We found 800 requests from over 90 individuals. There was no consistency in the definition of cause of death or contributory cause of death across national bodies and in different bodies within the same nation. Nursing home providers, as well as medical practitioners, can assign a cause of death according to the Care Quality Commission. Post-mortem examinations were uncommon, the ONS did not incorporate their results in the summary of deaths by cause during the pandemic period. The meaning of the words "test" or "swab" was never clarified by any of the respondents. In care homes in England 1,304 out of 17,264 COVID-19 (7.6%, range 0% to 63%) mentioned COVID-19 in the absence of contributory or other factors in the death certificate, making it impossible to ascertain a chain of causality. The inconsistencies already noted hinder the ascertainment of the role of each factor leading to death and the quantification of the importance of infection. Some responses indicate that SARS-CoV-2 negative individuals or those whose death was not caused by COVID-19 were classified as "COVID-19 deaths". We found 14 different ways of attributing the causes of death mentioned by respondents.
The overall lack of consistency has confused the public and likely led to erroneous conclusions. We are unable to separate the effects on deaths of SARS-CoV-2 from those of human interventions. A coherent process based on consistent definitions across the devolved nations is required. Furthermore, to enhance the accuracy of causation in pandemics a subset of deaths should be verified using autopsies with full medical documentation. | public and global health |
10.1101/2022.04.29.22274470 | Multi-center evaluation of baseline neutrophil:lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in Idiopathic Pulmonary Fibrosis | BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes for people with IPF.
MethodWe adopted a two-stage discovery and validation design using patients from the UCL partners (UCLp) cohort. For the discovery analysis, we included 71 patients from UCLH. In the validation analysis, we included 928 people with IPF, using real-life data from UCLH and 5 other UK centres. Data were collected from patients presenting over a 13-year period with a mean follow up time of 3.7 years.
FindingsIn the discovery analysis, we showed that values of NLR (<2.9 vs >/=2.9) were associated with increased risk of mortality (HR 2.04, 95% CI 1.09-3.81; p=0.025). In the validation cohort we confirmed this association of high NLR with mortality (HR 1.65, 95% CI 1.39-1.95; p<0{middle dot}0001) and showed incorporation of baseline NLR in a modified GAP-stage/index (GAP/index)-plus improved predictive ability
InterpretationWe have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines clinical GAP-staging. NLR may help ILD specialist centres prioritise at risk patients in a timely way, even in the absence of lung function. | respiratory medicine |
10.1101/2022.04.27.22274290 | Cognitive improvement after dual-task training in Parkinsons disease: a follow-up study | The reaction times of patients with Parkinsons disease (PD) in tests of simultaneous dual-task accuracy are dependent on the subjects cognitive ability. We now report that one week training on dual-task tests improved cognitive function. Forty-six PD patients were compared with 47 age matched healthy controls and 26 patients were followed for one year. Five dual-task tests consisting of a primary cognitive task to be performed simultaneously with a secondary motor task were repeated for five consecutive days. Testing was repeated after 6 and 12 months. Participants reaction times, including Hits and Misses, were quantified. Initial tests indicated slower reaction times in patients compared to controls, with fewer Hits and more Misses, especially in PD patients over 65 years of age. Training by daily repeated dual-task tests improved performance within 3 days (p < 0. 01 or p < 0.001), with no deterioration after 6 months. We conclude that dual-tasks are objective and sensitive tests for detecting early cognitive difficulties in PD, with improvements in both by repeated exposure to testing. A few days of testing produced cognitive improvement lasting many months. It is recommended that the use of simultaneous, dual-task testing is used to produce long-lasting improvement of cognitive function in PD patients. | neurology |
10.1101/2022.04.29.22274404 | Genetic risk score for intracranial aneurysms to predict aneurysmal subarachnoid hemorrhage and identify associations with patient characteristics | BackgroundRupture of an intracranial aneurysm (IA) causes aneurysmal subarachnoid hemorrhage (ASAH). There is no accurate prediction model for IA or ASAH in the general population. Recent discoveries in genetic risk for IA may allow improved risk prediction.
MethodsWe constructed a genetic risk score including genetic association data for IA and 17 traits related to IA (a metaGRS) to predict ASAH incidence and IA presence. The metaGRS was trained in 1,161 IA cases and 407,392 controls in the UK Biobank and validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68,568 controls from the Nordic HUNT study. We further assessed association between genetic risk load and patient characteristics in a cohort of 5,560 IA patients.
ResultsThe hazard ratio for ASAH incidence was 1.34 (95% confidence interval = 1.20-1.51) per SD increase of metaGRS. Concordance index increased from 0.63 [0.59-0.67] to 0.65 [0.62-0.69] upon including the metaGRS on top of clinical risk factors. The odds ratio for prediction of IA presence was 1.09 [95% confidence interval: 1.01-1.18], but did not improve area under the curve. The metaGRS was statistically significantly associated with age at ASAH ({beta}=-4.82x10-3 per year [-6.49x10-3 to -3.14x10-3], P=1.82x10-8), and location at the internal carotid artery (OR=0.92 [0.86 to 0.98], P=0.0041).
ConclusionsThe metaGRS was predictive of ASAH incidence with modest added value over clinical risk factors. Genetic risk plays a role in clinical heterogeneity of IA. Additional studies are needed to identify the biological mechanisms underlying this heterogeneity.
KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSRecent advanced in the understanding of genetic risk for IA opened and opportunity for risk prediction by combining genetic and conventional risk factors.
What this study addsHere, we developed a genetic risk score based on genetic association information for IA and 17 related traits. This risk score improved prediction compared to a model including only conventional risk factors. Further, genetic risk was associated with age at ASAH and IA location.
How this study might affect research, practice, or policyThis study emphasizes the importance of combining conventional and genetic risk factors in prediction of IA. It provides a metric to develop an accurate risk assessment method including conventional and genetic risk factors. | neurology |
10.1101/2022.04.28.22274444 | Transcriptomic meta-analysis of non-Hodgkins B-cell lymphomas reveals reliance on pathways associated with the extracellular matrix | Approximately 450,000 cases of Non-Hodgkins lymphoma are diagnosed annually worldwide, resulting in [~]240,000 deaths. An augmented understanding of the common mechanisms of pathology among relatively large numbers of B-cell Non-Hodgkins Lymphoma (BCNHL) patients is sorely needed. We consequently performed a large transcriptomic meta-analysis of available BCNHL RNA-sequencing data from GEO, consisting of 322 relevant samples across ten distinct public studies, to find common underlying mechanisms across BCNHL subtypes. The study was limited to GEOs publicly available human B-cell RNA-sequencing datasets that met our criteria, and limitations may include lack of diversity in ethnicities and age groups. We found [~]10,400 significant differentially expressed genes (FDR-adjusted p-value < 0.05) and 33 significantly modulated pathways (Bonferroni-adjusted p-value < 0.05) when comparing lymphoma samples to non-diseased samples. Our findings include a significant class of proteoglycans not previously associated with lymphomas as well as significant modulation of extracellular matrix-associated proteins. Our drug prediction results yielded new candidates including ocriplasmin and collagenase. We also used a machine learning approach to identify the BCNHL biomarkers YES1, FERMT2, and FAM98B, novel biomarkers of high predictive fidelity. This meta-analysis validates existing knowledge while providing novel insights into the inner workings and mechanisms of B-cell lymphomas that could give rise to improved diagnostics and/or therapeutics. No external funding was used for this study. | oncology |
10.1101/2022.04.27.22273901 | Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures | BackgroundMental health diseases are a major component of morbidity and health care costs. Obesity and gut disorders are comorbid with mental health, with the gut microbiome hypothesized to play a key mechanistic role in linking them. Pharmacological and behavioral interventions are currently used to treat mental health disorders, but they have limited efficacy. Dietary and weight-loss interventions have been shown to provide different benefits. Still, there exists conflicting evidence regarding their effects which may be due to an individuals genetic or microbiome factors modulating the improvement of symptoms.
ObjectiveWe aimed to identify genetic and gut microbiome factors that explain the improvement in mental health after a dietary and lifestyle intervention for weight loss.
MethodsWe recruited 369 individuals participating in the Digbi Health personalized digital care program, for which we evaluated the association between 23 genetic scores, the abundance of 178 gut microbiome genera, and 42 gut-brain modules (pathways related to neuroactive metabolites produced by gut microbes) with the presence/absence of anxiety/depression or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight.
ResultsThe mean BMI and age of the study cohort were 34.6 and 48.7, respectively, and there was an overrepresentation of individuals with functional gastrointestinal disorders (84%). On average, the individuals lost 5.4% of body weight at the time of follow-up (mean of 88 days), and more than 95% reported improvement in at least one outcome. We found significant correlations between genetic scores with anxiety and depression at baseline, gut microbial functions with sleep problems at baseline, and genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Among the gut microbial functions identified, the abundance of butyrate synthesis genes was associated with less than average improvement in depression symptoms, the abundance of kynurenine synthesis genes was associated with less than average improvement in anxiety symptoms, and the abundance of genes able to synthesize and degrade neuroactive hormones like nitric oxide was associated with greater than average improvement in depression and insomnia symptoms. Among the genetic scores identified, anxiety or depression at baseline were associated with genetic scores for alcohol use disorder and major depressive disorder, and greater than average improvement in anxiety and depression symptoms was associated with an obstructive sleep apnea genetic score. Furthermore, a type 1 diabetes genetic score was associated with a greater than average improvement of insomnia symptoms, whereas a type 2 diabetes genetic score was associated with a less than average improvement of insomnia symptoms. We compared the relative ability of demographic, genetic, and microbiome factors to explain baseline and improvement in mental health and found that genetic and microbiome factors provide value above demographic variables alone. Medication and recreational drug use do not confound microbiome associations with mental health.
ConclusionsThe digital therapeutics care program significantly decreased body weight and concomitantly decreased self-reported mental health symptom intensity. Our results provide evidence that genetic and gut microbiome factors help explain interindividual differences in mental health improvement after dietary and lifestyle interventions for weight loss. Thus, individual genetic and gut microbiome factors provide a basis for designing and further personalizing dietary interventions to improve mental health. | health informatics |
10.1101/2022.04.29.22274455 | Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination | ImportanceOmicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification.
ObjectiveTo estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine.
DesignTest-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022.
SettingPopulation-based, province of Quebec, Canada
ParticipantsCommunity-dwelling [≥]12-year-olds tested for SARS-CoV-2.
ExposuresPrior laboratory-confirmed infection with/without mRNA vaccination.
OutcomesLaboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose.
ResultsWithout vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses.
Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively).
Conclusions and relevancePrior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals. | infectious diseases |
10.1101/2022.04.29.22274455 | Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination | ImportanceOmicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification.
ObjectiveTo estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine.
DesignTest-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022.
SettingPopulation-based, province of Quebec, Canada
ParticipantsCommunity-dwelling [≥]12-year-olds tested for SARS-CoV-2.
ExposuresPrior laboratory-confirmed infection with/without mRNA vaccination.
OutcomesLaboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose.
ResultsWithout vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses.
Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively).
Conclusions and relevancePrior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals. | infectious diseases |
10.1101/2022.04.27.22274270 | Clinical Features and Outcomes of COVID-19 at a Teaching Hospital in Kingston, Jamaica | ObjectiveWe examined the demographic, clinical characteristics and indicators of poor outcomes among hospitalized adults with COVID-19 at the University Hospital of the West Indies, Jamaica.
MethodsA retrospective medical record review between March 10 and December 31, 2020 analyzed data for 362 participants.
ResultsThere were 218 males (mean age 59.5 years) and 144 females (mean age 55.7 years). Hypertension, diabetes mellitus, cardiovascular disease, obesity and chronic kidney disease were the most common comorbidities. Cough, shortness of breath, fever and malaise were the most common presenting complaints. Fifty-one percent of patients were moderately to severely ill on admission; 11% were critically ill; 18% were admitted to the Intensive Care Unit (ICU). Death occurred in 62 (17%) patients (95% CI 13.6-21.4%). Among obese participants, there were increased odds of developing respiratory failure (OR 5.2, p < 0.001), acute kidney injury (OR 4.7, p < 0.001), sepsis (OR 2.9, p =0.013) and the need for ICU care (OR 3.7, p < 0.001). Factors independently associated with increased odds of death were age (OR 1.03 per year, p = 0.013) and obesity (OR 2.26, p = 0.017). Mortality also correlated significantly with D-dimer > 1000 ng/ml (OR 2.78; p = 0.03), serum albumin < 40 g/L (OR 3.54; p = 0.03) and serum LDH > 485 U/L OR 1.92, p = 0.11).
ConclusionsTargeted interventions among these high-risk patient subgroups may reduce in-patient morbidity and mortality. | infectious diseases |
10.1101/2022.04.29.22274472 | Similar performances but markedly different triaging thresholds in three CAD4TB versions risk systematic errors in TB screening programs | Tuberculosis (TB) screening programs may apply computer-aided diagnostic (CAD) tools on chest radiographs to select people for microbiological sputum examination using a pre-selected triaging threshold. CAD software-updates are frequently introduced and it is unknown whether their use requires adjustment of triaging thresholds. In a community-based screening program in South Africa, we compared the scores between the three recent CAD4TB versions (v5, v6, and v7) and assessed their performance to identify microbiologically-confirmed TB. The performance of all versions was similar (v5: AUC 0.78, v6: AUC 0.79, v7: AUC 0.80; p-values>0.05), but along a 0-100 point scale, each had markedly different score distributions and optimal triaging thresholds (v5: 40, v6: 47, v7: 20). This has the potential to cause confusion within TB screening programs as these tools are increasingly adopted and new versions released. Independent guidance for adapting CAD triaging thresholds for frequently released software updates is needed. | infectious diseases |