bluuebunny/crossref_metadata_2025 huggingface dataset:
Urine tenofovir-monitoring predicts HIV viremia in patients treated with high genetic-barrier regimens
Authors: van Zyl Gert , Jennings Lauren , Kellermann Tracy , Nkantsu Zukisa , Cogill Dolphina , van Schalkwyk Marije , Spinelli Matthew , Decloedt Eric , Orrell Catherine , Gandhi Monica
Published: October 2022

Objective:

Access to viral load measurements is constrained in resource-limited settings. A lateral flow urine tenofovir (TFV) rapid assay (UTRA) for patients whose regimens include TFV offers an affordable approach to frequent adherence monitoring.

Design:

We conducted a cross-sectional study of patients to assess the utility of UTRA to predict virologic failure, defined as a viral load greater than 400 copies/ml.

Methods:

We assessed urine TFV among 113 participants at increased risk of viral failure (who had previous viral failure on this regimen or had previously been ≥30 days out of care), comparing low genetic-barrier efavirenz (EFV) regimens (n = 60) to dolutegravir (DTG)-boosted or ritonavir-boosted protease inhibitor (PI/r)-based high genetic-barrier regimens (n = 53). Dried blood spots (DBS) for TFV-diphosphate and plasma for TFV concentrations were collected, with drug resistance assessed if viral failure present.

Results:

Among 113 participants, 17 of 53 received DTG or PI/r had viral failure at the cross-sectional visit, with 11 (64.7%) demonstrating an undetectable urine TFV; the negative-predictive value (NPV) of undetectable UTRA for viral failure was 85% (34/40); none of the 16 sequenced had dual class drug resistance. In those treated with EFV regimens the sensitivity was lower, as only 1 (4.8%) of 21 with viral failure had an undetectable UTRA (P < 0.001).

Conclusions:

Urine tenofovir-testing had a high negative-predictive value for viral failure in patients treated with DTG or ritonavir-boosted protease inhibitor regimens, where viral failure was largely explained by poor drug adherence. Frequent monitoring with inexpensive lateral flow urine TFV testing should be investigated prospectively in between viral load visits to improve viral load suppression on DTG-based first-line therapy in resource-limited settings.
Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy
Authors: Milne Ross S. , Beck Ingrid A. , Levine Molly , So Isaac , Andersen Nina , Deng Wenjie , Panpradist Nuttada , Kingoo James , Kiptinness Catherine , Yatich Nelly , Kiarie James N. , Sakr Samah R. , Chung Michael H. , Frenkel Lisa M.
Published: October 2022

Objective(s):

Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART).

Design:

Prospective observational study.

Methods:

Participants’ pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1–9%) or high-frequency drug-resistant variants (10–100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters.

Results:

Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants.

Conclusion:

We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants’ frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.
HIV transmission among acutely infected participants of a Dutch cohort study 2015–2021 is not associated with large, clustered outbreaks
Authors: Prins Henrieke A.B. , Rokx Casper , Verbon Annelies , van Sighem Ard , de Bree Godelieve J. , Dijkstra Maartje , Prins Jan M. , Reiss Peter , van Kampen Jeroen J.A. , van de Vijver David A.M.C.
Published: October 2022

Objective:

Timely identification of acute or early HIV infection (AEHI) is important to help prevent onward transmission, and understanding the number of secondary infections resulting from individuals with AEHI is key to planning HIV prevention services and case finding.

Design:

We performed a phylogenetic investigation of a dense sample of individuals with AEHI who took part in the Netherlands Cohort Study on Acute HIV infection (NOVA) in the Netherlands during 2015-2021.

Methods:

Transmission clusters were identified using phylogenetic analyses based on HIV pol sequences. The Tamura-Nei model was used to estimate genetic distance. A number of 1000 bootstraps was used to check the reliability of clustering using maximum likelihood. A cluster was defined as having a bootstrap value of at least 95% and a genetic distance of at most 1.5%. Sensitivity analyses using different values for the bootstrap and genetic distance were performed to study the reproducibility of the clustering.

Results:

Of the 156 participants included in NOVA between July 2015 and April 2021, 134 individuals for whom baseline characteristics and genotypic resistance data at baseline were available could be included. We identified 10 clusters, but the majority of persons (111/134) were not part of a cluster, suggesting mainly independent transmission events.

Conclusion:

Mainly independent transmission events among a study population consisting predominantly of MSM in a low-incidence high-resource setting is likely the result of active AEHI case finding and direct start of treatment, and the roll-out over recent years of preventive measures such as preexposure prophylaxis.
Development and validation of a pentaplex assay for identification of antibodies against underdiagnosed diseases in cattle
Authors: Rodriguez Ana , Alonso-Morales Rogelio , Lassala Arantzatzu , Rangel P Lucia , Ramírez-Andoney Vianey , Gutierrez Carlos G
Published: October 2022

Animal welfare and economic implications of infectious disease occurrence in cattle demand an efficient epidemiological monitoring as the foundation for the establishment of control and eradication programs. Bovine respiratory syncytial virus (BRSV), Parainfluenza virus type 3 (PI3V), Bovine Herpes virus-1 (BoHV-1), Bovine viral diarrhoea virus (BVDV), and Enzootic Bovine Leukosis virus (EBLV) cause common and underdiagnosed diseases in cattle that are endemic in most countries (WAHIS 2020). A hallmark of individual exposure to a viral pathogen is the presence of antibodies directed towards that virus. The aim of this study was to develop and validate a pentaplex assay to simultaneously detect and quantify serum antibodies against BRSV, PI3V, BoHV-1, BVDV and EBLV, as an efficient tool to yield epidemiological data. Monoplex assays were initially developed using either complete BRSV or BoHV-1 viral particles, or recombinant proteins for BVDV, EBLV or PI3V as capture antigens. In addition, 125 sera samples from unvaccinated cattle, which were classified as positive or negative towards each of the viruses by commercial ELISA kits, were used for validation. Conditions established for the monoplex assays were adopted for the pentaplex assay. The accuracy, determined by the area under the ROC curve, was greater than 0.97, and assay sensitivities and specificities were over 95% and 90% respectively for all antigens. Intra (r) and interassay (R) coefficients of variation were under 10% and 20%, respectively. Selectivity towards target viruses was shown by binding inhibition assays where unbound viruses reduced fluorescence intensities. Diagnoses agreement for samples analysed simultaneously in the monoplex and multiplex assays was almost perfect. In conclusion, a highly sensitive pentaplex assay was validated for the simultaneous identification of serum antibodies directed against BVDV, BOHV-1, PI3V, BRSV, and EBLV. The developed pentaplex assay complies with performance characteristics established by international guidelines for diagnostic tests (AOAC, Eurochem).
JMM Profile: Staphylococcus epidermidis
Authors: Skovdal Sandra Maria , Jørgensen Nis Pedersen , Meyer Rikke Louise
Published: October 2022

Staphylococcus epidermidis

is the most abundant commensal bacterium of human skin. Despite protecting us from foreign invaders,

S. epidermidis

itself exploits human vulnerability when given the opportunity. Such opportunities arise when patients are immunocompromised or when biomedical implants present an opportunity to colonize the surface and form biofilms.

S. epidermidis

is one of the most frequently isolated organisms from implanted devices and from bloodstream infections. However,

S. epidermidis

infections are often recalcitrant to antibiotics because of biofilm-associated antibiotic tolerance. Furthermore, the emergence and spread of nearly pan-resistant strains is a considerable health concern. Symptoms can be subclinical, making diagnosis challenging, and treatment with antibiotics is inefficient. For now, infection prevention remains the best strategy available.
Estimating the effectiveness of shielding during pregnancy against SARS-CoV-2 in New York City during the first year of the COVID-19 pandemic
Authors: Chen Siyu , Murphy Elisabeth A , Pendergrass Angeline G , Sukhu Ashley C , Eng Dorothy , Jurkiewicz Magdalena , Mohammed Iman , Rand Sophie , White Lisa J , Hupert Nathaniel , Yang Yawei J
Published: October 2022

Pregnant patients have increased morbidity and mortality in the setting of SARS-CoV-2 infection. The exposure of pregnant patients in New York City to SARS-CoV-2 is not well understood due to early lack of access to testing and the presence of asymptomatic COVID-19 infections. Before the availability of vaccinations, preventative (shielding) measures, including but not limited to wearing a mask and quarantining at home to limit contact, were recommended for pregnant patients. Using universal testing data from 2196 patients who gave birth from April through December 2020 from one institution in New York City, and in comparison, with infection data of the general population in New York City, we estimated the exposure and real-world effectiveness of shielding in pregnant patients. Our Bayesian model shows that patients already pregnant at the onset of the pandemic had a 50% decrease in exposure compared to those who became pregnant after the onset of the pandemic and to the general population.
Deep reinforcement learning framework for controlling infectious disease outbreaks in the context of multi-jurisdictions
Authors: Khatami Seyedeh Nazanin , Gopalappa Chaitra
Published: October 2022

In the absence of pharmaceutical interventions, social distancing and lockdown have been key options for controlling new or reemerging respiratory infectious disease outbreaks. The timely implementation of these interventions is vital for effectively controlling and safeguarding the economy.

Motivated by the COVID-19 pandemic, we evaluated whether, when, and to what level lockdowns are necessary to minimize epidemic and economic burdens of new disease outbreaks. We formulated the question as a sequential decision-making Markov Decision Process and solved it using deep Q-network algorithm. We evaluated the question under two objective functions: a 2-objective function to minimize economic burden and hospital capacity violations, suitable for diseases with severe health risks but with minimal death, and a 3-objective function that additionally minimizes the number of deaths, suitable for diseases that have high risk of mortality. A key feature of the model is that we evaluated the above questions in the context of two-geographical jurisdictions that interact through travel but make autonomous and independent decisions, evaluating under cross-jurisdictional cooperation and non-cooperation.

In the 2-objective function under cross-jurisdictional cooperation, the optimal policy was to aim for shutdowns at 50% and 25% per day. Though this policy avoided hospital capacity violations, the shutdowns extended until a large proportion of the population reached herd immunity. Delays in initiating this optimal policy or non-cooperation from an outside jurisdiction required shutdowns at a higher level of 75% per day, thus adding to economic burdens. In the 3-objective function, the optimal policy under cross-jurisdictional cooperation was to aim for shutdowns of up to 75% per day to prevent deaths by reducing infected cases. This optimal policy continued for the entire duration of the simulation, suggesting that, until pharmaceutical interventions such as treatment or vaccines become available, contact reductions through physical distancing would be necessary to minimize deaths. Deviating from this policy increased the number of shutdowns and led to several deaths.

In summary, we present a decision-analytic methodology for identifying optimal lockdown strategy under the context of interactions between jurisdictions that make autonomous and independent decisions. The numerical analysis outcomes are intuitive and, as expected, serve as proof of the feasibility of such a model.
Waist circumference and glycaemia are strong predictors of progression to diabetes in individuals with prediabetes in sub-Saharan Africa: 4-year prospective cohort study in Malawi
Authors: Nakanga Wisdom P. , Crampin Amelia C. , Mkandawire Joseph , Banda Louis , Andrews Rob C. , Hattersley Andrew T. , Nyirenda Moffat J. , Rodgers Lauren R.
Published: October 2022

Introduction

Sub-Saharan Africa is projected to have the highest increase in the number of people with diabetes worldwide. However, the drivers of diabetes in this region have not been clearly elucidated. The aim of this study was to evaluate the incidence of diabetes and the predictors of progression in a population-based cohort with impaired fasting glucose (IFG) in Malawi.

Methods

We used data from an extensive rural and urban non-communicable disease survey. One hundred seventy-five, of 389 individuals with impaired fasting glucose (IFG) at baseline, age 48 ±15 years and body mass index 27.5 ±5.9 kg/m2 were followed up for a median of 4.2 years (714 person-years). Incidence rates were calculated, and predictors of progression to diabetes were analysed using multivariable logistic regression models, with overall performance determined using receiver operator characteristics (ROC) curves.

Results

The median follow-up was 4.2 (IQR 3.4 – 4.7) years. Forty-five out of 175 (26%) progressed to diabetes. Incidence rates of diabetes were 62.9 per 1000 person-years 95% CI, 47.0-84.3. The predictors of progression were higher; age (odds ratio [OR] 1.48, 95% CI 1.01-2.19, P=0.046), BMI (OR 1.98, 95% CI 1.34-2.94,P=0.001), waist circumference (OR 2.50, 95% CI 1.60-3.91,P<0.001), waist-hip ratio (OR 1.40, 95%CI 0.98-2.01,P=0.03), systolic blood pressure (OR 1.56, 95% CI 1.10-2.21,P=0.01), fasting plasma glucose (OR 1.53, 95%CI 1.08-2.16,P=0.01), cholesterol (OR 1.44, 95% CI 1.00-2.08,P=0.05) and low-density lipoprotein cholesterol (OR 1.80, 95% 1.23-2.64,P=0.002). A simple model combining fasting plasma glucose and waist circumference was predictive of progression to diabetes (ROC area under the curve=0.79)

Conclusion

The incidence of diabetes in people with IFG in Malawi is higher than those seen in Europe (35.0 per 1,000 person-years) but similar to those seen in India (61.0 per 1,000 person-years). Predictors of progression are like those seen in other populations. A simple chart with probabilities of progression to diabetes based on waist circumference and fasting plasma glucose could be used to identify those at risk of progression in clinical settings in sub-Saharan Africa.
Nonlinear relationship between systolic blood pressure and diabetic retinopathy in type 2 diabetic patients in southern China: a single-center observational study
Authors: Luo Yisheng , Zhang Chen , Zhou Chaochao , Yan Zhisong , Ouyang Zezhong , Zhu Wenbin
Published: October 2022

Background

Blood pressure (BP) control has been shown in clinical trials to reduce the risk of diabetic retinopathy (DR). To some extent, systolic blood pressure (SBP) has been shown to have a positive correlation with DR. However, there are no studies that have standardized SBP thresholds for DR prevention. Our goal was to use threshold analysis to further investigate the relationship between SBP and DR, identifying safe levels of SBP that contribute to DR prevention

Methods

We analyzed data from a cross-sectional study (December 2017-November 2018, n = 426, mean age 59.15±13.68) of patients with type 2 diabetes mellitus in the endocrinology department of Guangdong Provincial People’s Hospital, which is publicly available in the Dryad database. DR severity was assessed by retinal photographs. The International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scale was used to classify DR severity and divide it into two groups: with DR and without DR. SBP was analyzed as a continuous variable. Multivariate logistic regression models, smoothed curve fitting, threshold analysis, and interaction tests were used to assess the relationship between SBP and DR.

Results

Prevalence of DR in the study population was 39.20%. After adjusting for age, sex, DM duration, HbA1c, BUN, HDL, LDL, TRIG, CHOL, TP, DBP, PP, eGFR, and CKD stage, the association between SBP and DR appears as a threshold effect, with a inflection point of 132 mm Hg. The risk of DR did not change significantly when SBP ≤132 mm Hg (OR: 0.86; 95% CI: 0.63 to 1.17, p=0.3400). When SBP ≥132 mm Hg, each 10 mm Hg increase in SBP raise the risk of developing DR by 28% (OR:1.28; 95% CI:1.07 to 1.54, P=0.0081). In addition, a stronger association of SBP with DR in patients with TP≤60g/L (OR=1.58, 95% CI: 1.19-2.08, P=0.001) compared to those with TP>60g/L (OR=1.15, 95% CI: 1.03, 1.27, P=0.012) was discovered, with a P value for interaction=0.023.

Conclusion

In Chinese patients with type 2 diabetes, SBP was significantly associated with DR when SBP ≥132 mm Hg. Further longitudinal studies are needed to confirm our findings, especially in patients with TP≤60g/L.
Establishing attributes and corresponding levels for a discrete choice experiment on nurses’ job preferences in Iran
Authors: Emamgholipour Sara , Shahraki Mahdi , Haddadfar Amir Mohammad
Published: October 2022

Background

DCE is a widely used technique in healthcare to elicit non-market-stated preferences. This study was conducted primarily to identify the most important factors affecting the job preferences of nurses through a scoping review of literature review and qualitative methods, and finally to help select attributes and attribute levels.

Methods

This study was conducted in four stages based on Helter and Boehler’s proposed framework. The first stage was raw data collection to identify the factors influencing nurses’ job preferences. For this reason, a scoping review was performed to identify relevant attributes and their levels. In addition, 7 nurses and experts in the field of nursing were interviewed (in-depth interviews) to identify related characteristics according to the Iranian nursing workplace. Then, 19 nurses were asked to rate the attributes and levels. At this stage, all possible attributes from different sources were gathered. In the third stage, inappropriate attributes were deleted based on acquired qualitative data, and the research team decided which attributes to include in the final design. Attribute wording was done in the final stage. JMP Pro 16 was used to construct the final design. A utility-neutral design was generated and blocked into 3 versions, each consisting of 6 scenarios (choice sets). Finally, a pilot study involving 24 nurses was undertaken in April 2022.

Results

By using scoping review and qualitative methods such as semi-structured interviews, 23 potential job-related factors that affect nurses’ career choices were identified. Salary, type of employment contract, workload, type of health facility, workplace facilities, work schedule, and Expected time spent on the assigned job for promotion to a higher position were 7 attributes considered in the final design of the scenarios. Internal and face validity, intelligibility, and acceptability of the questionnaire were tested in the pilot study, and minor modifications were made. It was revealed that the respondents in the pilot study were able to understand and answer all of the choice sets with ease.

Conclusion

Some of the most significant financial and non-financial factors that affect Iranian nurses’ job preferences are mentioned in this study. This indicates that policymakers have a wide range of interventions available that can significantly improve the working conditions of nurses. Additionally, the full description of the attribute development and level selection processes makes this study valuable to the literature on DCE.
Towards Out-of-Lab Anterior Cruciate Ligament Injury Prevention and Rehabilitation Assessment: A Review of Portable Sensing Approaches
Authors: Tan Tian , Gatti Anthony A. , Fan Bingfei , Shea Kevin G. , Sherman Seth L. , Uhlrich Scott D. , Hicks Jennifer L. , Delp Scott L. , Shull Peter B. , Chaudhari Akshay S.
Published: October 2022

Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) surgery are common. Many ACL-injured subjects develop osteoarthritis within a decade of injury, a major cause of disability without cure. Laboratory-based biomechanical assessment can evaluate ACL injury risk and rehabilitation progress after ACLR; however, lab-based measurements are expensive and inaccessible to a majority of people. Portable sensors such as wearables and cameras can be deployed during sporting activities, in clinics, and in patient homes for biomechanical assessment. Although many portable sensing approaches have demonstrated promising results during various assessments related to ACL injury, they have not yet been widely adopted as tools for ACL injury prevention training, evaluation of ACL reconstructions, and return-to-sport decision making. The purpose of this review is to summarize research on out-of-lab portable sensing applied to ACL and ACLR and offer our perspectives on new opportunities for future research and development. We identified 49 original research articles on out-of-lab ACL-related assessment; the most common sensing modalities were inertial measurement units (IMUs), depth cameras, and RGB cameras. The studies combined portable sensors with direct feature extraction, physics-based modeling, or machine learning to estimate a range of biomechanical parameters (e.g., knee kinematics and kinetics) during jump-landing tasks, cutting, squats, and gait. Many of the reviewed studies depict proof-of-concept methods for potential future clinical applications including ACL injury risk screening, injury prevention training, and rehabilitation assessment. By synthesizing these results, we describe important opportunities that exist for using sophisticated modeling techniques to enable more accurate assessment along with standardization of data collection and creation of large benchmark datasets. If successful, these advances will enable widespread use of portable-sensing approaches to identify ACL injury risk factors, mitigate high-risk movements prior to injury, and optimize rehabilitation paradigms.
Global Menstrual Cycle Symptomatology as Reported by Users of a Menstrual Tracking Mobile Application
Authors: Ainsworth Alessandra J , Peven Kimberly , Bamford Ryan , Zhaunova Liudmila , Salimgaraev Rodion , Prentice Carley , Wickham Aidan , Cunningham Adam , Goddard Frederick , Ponzo Sonia , Babayev Samir N
Published: October 2022

Background

Although a shared experience throughout the world, menstrual symptomatology is underreported and often misunderstood, by both individuals who menstruate and their providers. This study aimed to investigate symptomatology throughout the menstrual cycle, including the frequency of symptoms reported for each phase of the cycle and the relationship between symptoms.

Methods

This study included self-reported cycle information and symptoms during ovulatory menstrual cycles in mobile application users. Symptom frequency was described overall, by phase, and by day. Relationships between symptoms were examined through correlation coefficients and term frequency-inverse document frequency analysis.

Results

437,577 unique users and 896,051 unique cycles were included in the analysis. Somatic symptoms were most frequently reported, logged in 88.3% of cycles. Of the total symptoms logged, somatic, gastrointestinal, and negative mood symptoms were most prevalent in the late luteal and bleeding days. In contrast, positive mood and discharge were most reported in the fertile window. Mood symptoms were highly correlated with each other (energetic mood and happy mood r=0.62, anxious mood and obsessive thoughts r=0.60). Fatigue was highly correlated with somatic and gastrointestinal symptoms such as bloating (r=0.62), headache (r=0.60), backache (r=0.58), and nausea (r=0.55).

Conclusions

Menstrual cycle-related symptoms are very common and vary throughout the menstrual cycle. While negative symptoms, including pain, bloating, and negative mood, are most commonly reported, women also report positive symptoms, such as energetic and happy mood. Self-reported data from cycle tracking and health apps can improve our understanding of the prevalence and variability of menstrual-related symptoms.

Plain English Summary

Our study includes data collected from users of a menstrual tracking application. We found that menstrual symtpoms are common, throughout the menstrual cycle, and include both positive and negative mood and physical symptoms. This large data set may help to normalize menstrual symptoms and provide a basis for future research and understanding.
Impact of COVID-19 related social isolation on behavioral outcomes in young adults
Authors: Patrono Alessandra , Invernizzi Azzurra , Placidi Donatella , Cagna Giuseppa , Calza Stefano , Oppini Manuela , Rechtman Elza , Papazaharias Demetrios M. , Reichenberg Abraham , Lucchini Roberto G. , Memo Maurizio , Ongaro Elisa , Rota Matteo , Wright Robert O. , Renzetti Stefano , Horton Megan K.
Published: October 2022

Social isolation strongly affects our emotions, behavior and interactions. Worldwide, individuals experienced prolonged periods of isolation during the first wave of the COVID-19 pandemic when authorities imposed restrictions to reduce the spread of the virus. In this study, we investigated the effects of social isolation on emotional and behavioral outcomes in young adults from Lombardy, Italy, a global hotspot of COVID-19. We leverage baseline (pre-social isolation) and follow-up (mid-or post isolation) data collected from young adults enrolled in the ongoing, longitudinal Public Health Impact of Metals Exposure (PHIME) study. At baseline, 167 participants completed the ASEBA questionnaires (ASR/YSR) by weblink or in person; 65 completed the ASR between 12-18 weeks after the onset of restrictions. Using the sign test and multiple linear regression models, we examined differences in ASR scores between baseline and follow-up adjusting for sex, age, pre-pandemic IQ (Kaufman Brief Intelligence Tests; K-BIT 2), and time with social restrictions (weeks). Further, we examined interactions between sex and time in social isolation. Participants completed the ASR after spending an average of 14 weeks in social isolation (range 12-18 weeks). Thought Problems increased between baseline and follow-up (median difference 1.0; 1st., 3rdquartile: -1.0, 4.0; p=0.049). Among males, a longer time with social isolation (≥ 14 weeks) was associated with increased rule-breaking behaviors of 2.8 points. These results suggest the social isolation related to COVID-19 adversely impacted mental health. In particular, males seem to externalize their condition. These findings might help future interventions and treatment to minimize the consequences of social isolation experience in young adults.
Monkeypox outbreak in the Netherlands in 2022: public health response, epidemiological and clinical characteristics of the first 1000 cases and protection of the first-generation smallpox vaccine
Authors: van Ewijk Catharina E. , Miura Fuminari , van Rijckevorsel Gini , de Vries Henry J.C. , Welkers Matthijs R.A. , van den Berg Oda E. , Friesema Ingrid H.M. , van den Berg Patrick , Dalhuisen Thomas , Wallinga Jacco , Brandwagt Diederik , van Cleef Brigitte A.G.L. , Vennema Harry , Voordouw Bettie , Koopmans Marion , van der Eijk Annemiek A. , Swaan Corien M. , te Wierik Margreet J.M. , Leenstra Tjalling , Op de Coul Eline , Franz Eelco ,   the Dutch Monkeypox Response Team
Published: October 2022

In early May 2022 a global outbreak of monkeypox (MPX) started among persons without a travel history to regions known to be enzootic for monkeypox-virus. On August 8 2022, the Netherlands reported its 1000thmonkeypox case representing a cumulative incidence of 55 per million population, one of the highest cumulative incidences worldwide. Here we describe the epidemiological characteristics and clinical presentation of the first 1000 monkeypox cases in the Netherlands, within the context of the public health response. Additionally, we explored risk factors for and estimated the protective effect of first-generation smallpox vaccine against more severe MPX.

The first 1000 MPX cases, reported between May 20 and August 8 2022, were predominantly MSM aged 31-45 years. The vast majority of infections were acquired through sexual contact with casual partners in private or recreational settings including LGBTQIA+ venues in the Netherlands. This indicates that, although some larger upsurges occurred from point-source and/or travel related events, the outbreak is mainly characterised by sustained transmission within the Netherlands. More severe MPX was associated with having one or more comorbidities as well as having participated in more (3+) different sexual activities 21 days before symptom onset. We found a vaccine effectiveness of the prior first-generation smallpox vaccine against more severe MPX of 58% (95% CI 17-78%), suggesting moderate protection against more severe MPX symptoms on top of any possible protection by this vaccine against MPXV infection and disease.
Development and validation of the Chinese Osteoporosis Screening Algorithm (COSA) in Identification of People with High Risk of Osteoporosis
Authors: Cheung Ching-Lung , Li Gloria Hoi-Yee , Mak Constance , Tan Kathryn CB , Kung Annie WC
Published: October 2022

Osteoporosis is a prevalent but under-diagnosed disease partly due to the limited availability of dual-energy X-ray absorptiometry (DXA) machines in many countries. To enhance the public awareness and facilitate diagnosis of osteoporosis, we aimed to develop a new Chinese Osteoporosis Screening Algorithm (COSA) and compare its performance with the Osteoporosis Self-Assessment Tool for Asians (OSTA) to identify people at high risk of osteoporosis. A total of 4,747 postmenopausal women and men aged≥50 years from the Hong Kong Osteoporosis Study were randomly split into a development (N=2,373) and an internal validation cohort (N=2,374). An external validation cohort comprising 1,876 community-dwelling subjects was used to evaluate the positive predictive value (PPV). Among 11 predictors included, age, sex, weight, and history of fracture were significantly associated with osteoporosis after correction for multiple testing in the development cohort. Age- and sex-stratified models were developed separately for women aged<65 years, women aged≥65 years, and men due to the presence of significant sex and age interactions. The AUC of the COSA in the internal validation cohort was 0.761 (95% CI: 0.711-0.811), 0.822 (95% CI: 0.792-0.851), and 0.946 (95% CI: 0.908-0.984) for women aged<65 years, women aged≥65 years, and men, respectively. The COSA outperformed OSTA in identifying people with osteoporosis in all the three groups. In the external validation cohort, the PPV of COSA was 40.6%, 59.4%, and 19.4% for women aged<65 years, women aged≥65 years, and men, respectively. In conclusion, we have developed and validated a new osteoporosis screening algorithm, COSA, specific for Hong Kong Chinese.
Uptake of COVID-19 vaccines among healthcare workers within primary healthcare facilities, Entebbe municipality Uganda
Authors: Kyakuwa N , Atuhairwe C , KalutTe H , Mpooya S , Nakanjako F , Perez L , Kikaire B
Published: October 2022

Background

Routine vaccination is an essential highly successfully public health intervention in the prevention of infectious diseases that greatly depends on high coverage, and health care workers (HCWs) who play a pivotal role in ensuring the high uptake of vaccines in the population. COVID-19 vaccines have been proven efficacious, and vaccination campaigns have been ongoing, however, there is a perceived high vaccine hesitancy among health care workers in Uganda. This study describes the level and determinants of uptake of COVID-19 vaccines among HCWs in Entebbe municipality, Uganda.

Materials and methods

We conducted a health facility based cross-sectional study among HCWs from private and government health facilities in Entebbe municipality between July 2021 and August 2021. Structured questionnaires were used, and data were analysed using Stata version 12. We defined uptake as having received at least the first doze of COVID-19 vaccine or completed the two dozes.

Results

The level of vaccine uptake was 65.6%with higher uptake among males than females. HCWs aged 30-39 years were 2.7 times more likely to have been vaccinated than those less than 30 years (OR 2.72, 95% CI: 1.26-5.88, P-value <0.01), and the odds of having been vaccinated were 4 times higher among health workers above 40 years (OR 4.29, 95% CI 1.50-12.24, P-value < 0.01). Additionally, the odds of having been vaccinated were 4 times higher among health care workers that participated in COVID-19 vaccine related activities (OR 4.18, 95% CI 2.16-8.10, p-value <0.001). Healthcare workers (98%) had confidence in the vaccines although 45% of those that were not vaccinated felt that the vaccines were ineffective.

Conclusion

Vaccine uptake among HCWs was relatively high compared to the WHO recommended uptake of 70% by mid-2022, although some HCWs were still hesitant. The convenience of vaccination services was an important factor in vaccine uptake. Hence, governments should endeavour to improve access to vaccination both for HCWs and the public.
Evaluation of a camera-based monitoring solution against regulated medical devices to measure: Heart Rate, Respiratory Rate, Oxygen Saturation, and Blood Pressure
Authors: Talukdar Debjyoti , de Deus Luis Felipe , Sehgal Nikhil
Published: October 2022

Regular monitoring of common physiological signs, including heart rate, blood pressure, and oxygen saturation, can be an effective way to either prevent or detect several potential conditions. In particular, cardiovascular diseases (CVDs) are a worldwide concern. According to the World Health Organization, 31% of all deaths worldwide are from CVDs. Recently, the COVID-19 pandemic has increased the interest in remote monitoring. At present, contact devices are required to extract most of an individual’ s physiological information, which can be inconvenient for users and may cause discomfort. However, remote photoplethysmography (rPPG) technology offers a solution for this issue, which enables contactless monitoring of the blood volume pulse signal using a regular camera, and ultimately can provide the same physiological information as a contact device. In this paper we propose an evaluation of rPPG technology against medical devices in a clinical environment, with a variety of subjects in a wide range of age, height, weight, and baseline vital signs. Results have shown that rPPG technology was able to meet the initial hypothesis of mean error of +/-3 units for Heart rate, Respiration Rate, and SpO2 estimation, as well as +/-10 mmHg for Systolic and Diastolic Blood Pressure.
Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021
Authors: Embi Peter J. , Levy Matthew E. , Patel Palak , DeSilva Malini B. , Gaglani Manjusha , Dascomb Kristin , Dunne Margaret M. , Klein Nicola P. , Ong Toan C. , Grannis Shaun J. , Natarajan Karthik , Yang Duck-Hye , Stenehjem Edward , Zerbo Ousseny , McEvoy Charlene , Rao Suchitra , Thompson Mark G. , Konatham Deepika , Irving Stephanie A. , Dixon Brian E. , Han Jungmi , Schrader Kristin E. , Grisel Nancy , Lewis Ned , Kharbanda Anupam B. , Barron Michelle A. , Reynolds Sue , Liao I-Chia , Fadel William F. , Rowley Elizabeth A. , Arndorfer Julie , Goddard Kristin , Murthy Kempapura , Valvi Nimish R. , Weber Zachary A. , Fireman Bruce , Reese Sarah E. , Ball Sarah W. , Naleway Allison L.
Published: October 2022

Background

Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults.

Methods

Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19–associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation.

Results

We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups.

Conclusions

During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19–associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.

Key points

During Delta variant predominance, immunocompromised (IC) adults received moderate protection against COVID-19-associated medical events from three mRNA doses, but IC patients, especially transplant recipients, were less protected than non-IC patients, underscoring the need for additional protection beyond the primary series.
Landmark-based analysis of speech differentiates conversational from clear speech in speakers with muscle tension dysphonia
Authors: Ishikawa Keiko , Pietrowicz Mary , Charney Sara , Orbelo Diana
Published: October 2022

This study evaluated the feasibility of differentiating conversational and clear speech produced by individuals with muscle tension dysphonia (MTD) using Landmark-Based Analysis of Speech (LMBAS). Thirty-four adult speakers with MTD recorded conversational and clear speech. Of those, 27 speakers were able to produce clear speech. The recordings of these individuals were analyzed with an open-source LMBAS program, SpeechMark®, MATLAB Toolbox ver. 1.1.2.

The mixed-effect logistic regression model indicated that the burst-onset landmark differentiated conversational speech from clear speech. The LMBAS is a potential approach for detecting the difference between conversational and clear speech in individuals with mild to moderate MTD.
Legionnaires’ disease in Switzerland: Rationale and study protocol of a prospective national case-control and molecular source attribution study (SwissLEGIO)
Authors: Fischer Fabienne B. , Bigler Melina , Mäusezahl Daniel , Hattendorf Jan , Egli Adrian , Julian Timothy R. , Rölli Franziska , Gaia Valeria , Wymann Monica , Fridez Françoise , Bertschi Stefanie ,   the SwissLEGIO Hospital Network
Published: October 2022

Switzerland has one of the highest annual Legionnaires’ disease (LD) notification rates in Europe (7.8 cases/ 100,000 population in 2021). The main sources of infection and the cause for this high rate remain largely unknown. This hampers the implementation of targetedLegionellaspp. control efforts. TheSwissLEGIOnational case-control and molecular source attribution study investigates risk factors and infection sources for community-acquired LD in Switzerland. Over the duration of one year, the study is recruiting 205 newly diagnosed LD patients through a network of 20 university and cantonal hospitals. Healthy controls matched for age, sex, and residence at district level are recruited from the general population. Risk factors for LD are assessed in questionnaire-based interviews. Clinical and environmentalLegionellaspp. isolates are compared using whole genome sequencing (WGS). Direct comparison of sero- and sequence types (ST), core genome multilocus sequencing types (cgMLST), and single nucleotide polymorphisms (SNPs) between clinical and environmental isolates are used to investigate infection sources and the prevalence and virulence of differentLegionellaspp. strains detected across Switzerland. TheSwissLEGIOstudy innovates in combining case-control and molecular typing approaches for source attribution on a national level outside an outbreak setting. The study provides a unique platform for national Legionellosis andLegionellaresearch and is conducted in an inter- and transdisciplinary, co-production approach involving various national governmental and national research stakeholders.
Preventing antimalarial drug resistance with triple artemisinin-based combination therapies
Authors: Nguyen Tran Dang , Gao Bo , Amaratunga Chanaki , Dhorda Mehul , Tran Thu Nguyen-Anh , White Nicholas J , Dondorp Arjen M , Boni Maciej F , Aguas Ricardo
Published: October 2022

Background

Increasing levels of artemisinin and partner drug resistance threaten malaria control and elimination globally. Triple artemisinin-based combination therapies (TACTs) which combine artemisinin derivatives with two partner drugs are efficacious and well tolerated in clinical trials, including in areas of multidrug-resistant malaria. Whether early TACT adoption could delay the emergence and spread of antimalarial drug resistance is a question of vital importance.

Methods

Using two independent individual-based models ofPlasmodium falciparumepidemiology and evolution, we evaluated whether introduction of either artesunate-mefloquine-piperaquine or artemether-lumefantrine-amodiaquine resulted in lower long-term artemisinin-resistance levels and treatment failure rates compared with continued ACT use.

Findings

In countries with 1%P. falciparumprevalence, immediate adoption of TACTs would result in substantially lower frequency of artemisinin-resistant alleles 10 years later. Median estimates were 70%, 33%, and 18% lower allele frequency for countries currently deploying dihydroartemisinin-piperaquine, artesunate-amodiaquine, or artemether-lumefantrine, respectively. Corresponding median treatment failure rate decreases are 74%, 34%, and 17%. Delaying TACT introduction increases future resistance frequencies and treatment failure rates. The most significant threat to the success of TACTs is the emergence of a triple-resistant genotype. which if above 0.01 frequency may undermine elimination efforts in low-prevalence regions.

Interpretation

Introduction of TACTs could delay the emergence and spread of artemisinin resistance and treatment failure, extending the useful therapeutic life of current antimalarial drugs and improving the chances of malaria elimination. Immediate introduction of TACTs should be considered by policy makers in areas of emerging artemisinin resistance.
Epigenetic contributions to clinical risk prediction of cardiovascular disease
Authors: Chybowska Aleksandra D , Gadd Danni A , Cheng Yipeng , Bernabeu Elena , Campbell Archie , Walker Rosie M , McIntosh Andrew M , Wrobel Nicola , Murphy Lee , Welsh Paul , Sattar Naveed , Price Jackie F , McCartney Daniel L , Evans Kathryn L , Marioni Riccardo E
Published: October 2022

Background and Aims

Cardiovascular disease (CVD) is among the leading causes of death worldwide. Discovery of new omics biomarkers could help to improve risk stratification algorithms and expand our understanding of molecular pathways contributing to the disease. Here, ASSIGN – a cardiovascular risk prediction tool recommended for use in Scotland – was examined in tandem with epigenetic and proteomic features in risk prediction models in ý12,657 participants from the Generation Scotland cohort.

Methods

Previously generated DNA methylation-derived epigenetic scores (EpiScores) for 109 protein levels were considered, in addition to both measured levels and an EpiScore for cardiac troponin I (cTnI). The associations between individual protein EpiScores and the CVD risk were examined using Cox regression (ncasesý1,274; ncontrolsý11,383) and visualised in a tailored R application. Splitting the cohort into independent training (n=6,880) and test (n=3,659) subsets, a composite CVD EpiScore was then developed.

Results

Sixty-five protein EpiScores were associated with incident CVD independently of ASSIGN and the measured concentration of cTnI (P<0.05), over a follow up of up to 16 years of electronic health record linkage. The most significant EpiScores were for proteins involved in metabolic, immune response and tissue development/regeneration pathways. A composite CVD EpiScore (based on 45 protein EpiScores) was a significant predictor of CVD risk independent of ASSIGN and the concentration of cTnI (Hazard Ratio HR=1.32, P=3.7×10-3, 0.3% increase in C-statistic).

Conclusions

EpiScores for circulating protein levels are associated with CVD risk independent of traditional risk factors and may increase our understanding of the aetiology of the disease.

Graphical abstract

Structural graphical abstract

ASSIGN – a cardiovascular risk prediction tool recommended for use in Scotland – was examined in tandem with epigenetic and proteomic features in risk prediction models in ζ12,657 participants from the Generation Scotland cohort. Cox regression was used to model the association between individual predictors and CVD hospitalisation events ascertained over 16 years of follow-up. Finally, a composite protein EpiScore was developed (based on the protein EpiScores) and its predictive performance was tested. CVD – Cardiovascular Disease, EpiScore – Epigenetic Score, Cox PH – Cox Proportional Hazards Regression, DNAm – DNA methylation.