bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound examination for a heel scar: seeing/treating the painful superficial fascia
Authors: Pirri Carmelo , Stecco Carla , Pirri Nina , De Caro Raffaele , Özçakar Levent
Published: May 2022

.
Stochastic defect removal coating for high-performance extreme ultraviolet lithography
Authors: Choi Young Joo , Namgung Ran , Kim Jun Soo , Song Dae Seok , Park Hyeon , Bae Shin-hyo , Chon Min-Ki , Kim Min Soo , Song Hyun-Ji , Kim Hyun-Woo , Hong Suk Koo
Published: May 2022

To reduce the stochastic defect caused by insufficient photon numbers of extreme ultraviolet lithography, a simple additional process has been designed and experimented. The additional process consists of one coating and washing process after pattern formation by lithography. The coating material was named stochastic defect removal coating and was carefully designed to reduce the stochastic defects without harming the lithographic margin. The defect reduction up to 48% was accomplished by failure-free latitude measurement and defect inspection.
E-site drug specificity of the human pathogen
Candida albicans
ribosome
Authors: Zgadzay Yury , Kolosova Olga , Stetsenko Artem , Wu Cheng , Bruchlen David , Usachev Konstantin , Validov Shamil , Jenner Lasse , Rogachev Andrey , Yusupova Gulnara , Sachs Matthew S. , Guskov Albert , Yusupov Marat
Published: May 2022

Candida albicans
is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds to the E–transfer RNA binding site of the ribosome. Because of lack of structural information, it is neither possible to understand the nature of the resistance nor to develop novel inhibitors. To overcome this issue, we determined the structure of the vacant
C. albicans
80
S
ribosome at 2.3 angstroms and its complexes with bound inhibitors at resolutions better than 2.9 angstroms using cryo–electron microscopy. Our structures reveal how a change in a conserved amino acid in ribosomal protein eL42 explains CHX resistance in
C. albicans
and forms a basis for further antifungal drug development.
Identification and characterization of BEND2 as a key regulator of meiosis during mouse spermatogenesis
Authors: Ma Longfei , Xie Dan , Luo Mengcheng , Lin Xiwen , Nie Hengyu , Chen Jian , Gao Chenxu , Duo Shuguang , Han Chunsheng
Published: May 2022

The chromatin state, which undergoes global changes during spermatogenesis, is critical to meiotic initiation and progression. However, the key regulators involved and the underlying molecular mechanisms remain to be uncovered. Here, we report that mouse BEND2 is specifically expressed in spermatogenic cells around meiotic initiation and that it plays an essential role in meiotic progression.
Bend2
gene knockout in male mice arrested meiosis at the transition from zygonema to pachynema, disrupted synapsis and DNA double-strand break repair, and induced nonhomologous chromosomal pairing. BEND2 interacted with chromatin-associated proteins that are components of certain transcription-repressor complexes. BEND2-binding sites were identified in diverse chromatin states and enriched in simple sequence repeats. BEND2 inhibited the expression of genes involved in meiotic initiation and regulated chromatin accessibility and the modification of H3K4me3. Therefore, our study identified BEND2 as a previously unknown key regulator of meiosis, gene expression, and chromatin state during mouse spermatogenesis.
Quantitative and ultrasensitive in situ immunoassay technology for SARS-CoV-2 detection in saliva
Authors: Chen Yuchao , Liu Fei , Lee Luke P.
Published: May 2022

The coronavirus disease 2019 (COVID-19) pandemic has become an immense global health crisis. However, the lack of efficient and sensitive on-site testing methods limits early detection for timely isolation and intervention. Here, we present a quantitative and ultrasensitive in situ immunoassay technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in saliva (QUIT SARS-CoV-2). Our nanoporous membrane resonator generates a rapid oscillating flow to purify and concentrate fully intact SARS-CoV-2 virus in saliva by 40-fold for in situ detection of viral antigens based on chemiluminescent immunoassay within 20 min. This method can not only achieve a detection sensitivity below 100 copies/ml of virus, comparable to the bench-top PCR equipment; it can also improve detection specificity via direct monitoring of viral loads. The integrated portable QUIT SARS-CoV-2 system, which enables rapid and accurate on-site viral screening with a high-throughput sample pooling strategy, can be performed in primary care settings and substantially improve the detection and prevention of COVID-19.
Submillimeter-scale multimaterial terrestrial robots
Authors: Han Mengdi , Guo Xiaogang , Chen Xuexian , Liang Cunman , Zhao Hangbo , Zhang Qihui , Bai Wubin , Zhang Fan , Wei Heming , Wu Changsheng , Cui Qinghong , Yao Shenglian , Sun Bohan , Yang Yiyuan , Yang Quansan , Ma Yuhang , Xue Zhaoguo , Kwak Jean Won , Jin Tianqi , Tu Qing , Song Enming , Tian Ziao , Mei Yongfeng , Fang Daining , Zhang Haixia , Huang Yonggang , Zhang Yihui , Rogers John A.
Published: May 2022

Robots with submillimeter dimensions are of interest for applications that range from tools for minimally invasive surgical procedures in clinical medicine to vehicles for manipulating cells/tissues in biology research. The limited classes of structures and materials that can be used in such robots, however, create challenges in achieving desired performance parameters and modes of operation. Here, we introduce approaches in manufacturing and actuation that address these constraints to enable untethered, terrestrial robots with complex, three-dimensional (3D) geometries and heterogeneous material construction. The manufacturing procedure exploits controlled mechanical buckling to create 3D multimaterial structures in layouts that range from arrays of filaments and origami constructs to biomimetic configurations and others. A balance of forces associated with a one-way shape memory alloy and the elastic resilience of an encapsulating shell provides the basis for reversible deformations of these structures. Modes of locomotion and manipulation span from bending, twisting, and expansion upon global heating to linear/curvilinear crawling, walking, turning, and jumping upon laser-induced local thermal actuation. Photonic structures such as retroreflectors and colorimetric sensing materials support simple forms of wireless monitoring and localization. These collective advances in materials, manufacturing, actuation, and sensing add to a growing body of capabilities in this emerging field of technology.
Robots are taming the wild
Authors: Lee Michael M.
Published: May 2022

Advances in computer science and bioinspired robotics are ushering machines out of the lab.
Schwann cells in the subcutaneous adipose tissue have neurogenic potential and can be used for regenerative therapies
Authors: Stavely Rhian , Hotta Ryo , Picard Nicole , Rahman Ahmed A. , Pan Weikang , Bhave Sukhada , Omer Meredith , Ho Wing Lam N. , Guyer Richard A. , Goldstein Allan M.
Published: May 2022

Stem cell therapies for nervous system disorders are hindered by a lack of accessible autologous sources of neural stem cells (NSCs). In this study, neural crest–derived Schwann cells are found to populate nerve fiber bundles (NFBs) residing in mouse and human subcutaneous adipose tissue (SAT). NFBs containing Schwann cells were harvested from mouse and human SAT and cultured in vitro. During in vitro culture, SAT-derived Schwann cells remodeled NFBs to form neurospheres and exhibited neurogenic differentiation potential. Transcriptional profiling determined that the acquisition of these NSC properties can be attributed to dedifferentiation processes in cultured Schwann cells. The emerging population of cells were termed SAT-NSCs because of their considerably distinct gene expression profile, cell markers, and differentiation potential compared to endogenous Schwann cells existing in vivo. SAT-NSCs successfully engrafted to the gastrointestinal tract of mice, migrated longitudinally and circumferentially within the muscularis, differentiated into neurons and glia, and exhibited neurochemical coding and calcium signaling properties consistent with an enteric neuronal phenotype. These cells rescued functional deficits associated with colonic aganglionosis and gastroparesis, indicating their therapeutic potential as a cell therapy for gastrointestinal dysmotility. SAT can be harvested easily and offers unprecedented accessibility for the derivation of autologous NSCs from adult tissues. Evidence from this study indicates that SAT-NSCs are not derived from mesenchymal stem cells and instead originate from Schwann cells within NFBs. Our data describe efficient isolation procedures for mouse and human SAT-NSCs and suggest that these cells have potential for therapeutic applications in gastrointestinal motility disorders.
Lysine acylation causes collateral damage in inborn errors of metabolism
Authors: Goetzman Eric S. , Vockley Jerry
Published: May 2022

Posttranslational modifications contribute to the pathology of methylmalonic acidemia and may be targetable via an acylation-resistant sirtuin (Head
et al.
, this issue).
Machine Learning for Antimicrobial Resistance Prediction: Current Practice, Limitations, and Clinical Perspective
Authors: Kim Jee In , Maguire Finlay , Tsang Kara K. , Gouliouris Theodore , Peacock Sharon J. , McAllister Tim A. , McArthur Andrew G. , Beiko Robert G.
Published: May 2022

Antimicrobial resistance (AMR) is a global health crisis that poses a great threat to modern medicine. Effective prevention strategies are urgently required to slow the emergence and further dissemination of AMR.
Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies
Authors: Wong Marcus P. , Meas Michelle A. , Adams Cameron , Hernandez Samantha , Green Valerie , Montoya Magelda , Hirsch Brett M. , Horton Mary , Quach Hong L. , Quach Diana L. , Shao Xiaorong , Fedrigo Indro , Zermeno Alexandria , Huffaker Julia , Montes Raymond , Madden Alicia , Cyrus Sherri , McDowell David , Williamson Phillip , Contestable Paul , Stone Mars , Coloma Josefina , Busch Michael P. , Barcellos Lisa F. , Harris Eva
Published: May 2022

Estimation of community-level antibody responses to SARS-CoV-2 from infection or vaccination is critical to inform public health responses. Traditional studies of antibodies rely on collection of blood via venipuncture, an invasive procedure not amenable to pandemic-related social-distancing measures.
Detached structural model of the Keweenaw fault system, Lake Superior region, North America: Implications for its origin and relationship to the Midcontinent Rift System
Authors: DeGraff James M. , Carter Brad T.
Published: May 2022

The Keweenaw fault system along Lake Superior’s south shore in Michigan, USA is one of the most significant fault systems associated with North America’s Midcontinent Rift System. Reverse slip has thrust Portage Lake Volcanics (ca. 1.1 Ga) southeastward over Jacobsville Sandstone (ca. 1.0 Ga). Growing consensus in the 1970s about a major rift beneath Lake Superior led to the idea that reverse movement on the Keweenaw fault involved inversion of a rift-bounding normal fault. To test this idea, we integrated bedrock geology maps, subsurface mining data, and geophysical data to build a wellconstrained cross-section from the Minnesota, USA-Ontario, Canada border to central Upper Michigan. The cross-section shows the Keweenaw and Hancock faults to be parts of a reverse, listric system detached deep within the layered volcanic section. Correlation of offshore seismic units with onshore stratigraphic units defines a gradual change in stratal dip from 55° NW near the faults to horizontal near the center of Lake Superior. This stratal geometry implies that onshore listric fault geometry continues offshore and that the fault system soles into a basal detachment at 12–15 km depth. Absence of second-order folds northwest of the peninsula indicates that the fault system does not ramp downward from the basal detachment through the lower crust. The observations and model preclude ideas that the Keweenaw fault was a rift-bounding normal fault inverted by post-rift crustal shortening, or that it formed by upward propagation of a deeper normal fault undergoing inversion. Instead, our results imply that the fault initiated as a detached thrust in relatively brittle upper crust and that shortening of relatively ductile lower crust occurred on other structures.
Supplemental Material: Silurian wildfire proxies and atmospheric oxygen
Authors: Glasspool Ian J. , Gastaldo Robert A.
Published: May 2022

Localities and age assignments, observations on charcoal, methods, Figure 3 locality details, data tables, and supporting figures. 
Supplemental Material: Crustal transpressional fault geometry influenced by viscous lower crustal flow
Authors: Yang Haibin , al. et
Published: May 2022

Methods and supplemental figures. 
Supplemental Material: Evidence for a lithospheric step and pervasive lithospheric thinning beneath southern New England, northeastern USA
Authors: Goldhagen Gillian B. , al. et
Published: May 2022

Detailed description of methods and negative phase interpretation and k
Supplemental Material: The influence of Late Ordovician volcanism on the marine environment based on high-resolution mercury data from South China
Authors: Wang Yong , Tan Jingqiang , al. et
Published: May 2022

Supplemental Data Set 1. Organic carbon isotopes from the first round of sampling in the Muchanggou section. Supplemental Data Set 2. Elemental data from the second round of sampling in the Muchanggou section. Supplemental Text. Carbon isotope mass balance calculations and numerical simulation of the global carbon cycle.
Rare case of multiple and perforating pilomatrixomas in a young girl with lymphovascular malformation reveals a potential new disease association
Authors: Smith Clara , Hamilton David , Waterston Stuart
Published: May 2022

This report details the case of a girl of primary school age who was referred to our plastic surgery department with an ulcerating lesion on the nape of her neck. A firm mass was palpable in the underlying subcutaneous tissue. This lesion was accompanied by two smaller firm nodules: one in the adjacent tissue and another in the left preauricular region. Ultrasound and MRI demonstrated multiple calcified nodules confined to the subcutaneous tissue. An incisional biopsy of the ulcerating lesion confirmed a diagnosis of perforating pilomatrixoma; the lesion was subsequently excised, with no sign of recurrence at 3-month follow-up. The patient had a history of lymphovascular malformation (LVM) and a paternal history of Gardner’s syndrome. Pilomatrixoma and Gardner’s syndrome have a well-documented association in existing literature; aberrant Wnt/beta-catenin signalling is common to both. Recent laboratory studies suggest this pathway is also implicated in the pathogenesis of LVM.
Treatment ofCapnocytophaga sputigenameningitis in a neurosurgical patient
Authors: Evans Terry John , Fernando Samitha , Uberti Micaela , Martin Andrew J , Basarab Marina
Published: May 2022

A woman in her 50s developed meningitis following an endoscopic, endonasal resection of a clival meningioma which was complicated by a cerebrospinal fluid (CSF) leak through the nose. CSF analysis showed a raised white cell count, andCapnocytophaga sputigenawas isolated. This organism is an oral commensal and is implicated in periodontal disease; the CSF leak explains the portal of entry.C. sputigenais rarely isolated, and this is the first report of a central nervous system (CNS) infection caused by this organism. A worsening of our patient’s dermatological condition, urticaria pigmentosa, coincided with empiric treatment with vancomycin and meropenem, which were therefore discontinued. Treatment was continued with chloramphenicol for 3 weeks, and the patient made a full recovery. Systemic chloramphenicol is uncommonly used in contemporary UK practice, but remains an excellent antibiotic for CNS penetration and it has excellent bioavailability. We anticipate increased chloramphenicol use as the number of multiresistant Gram-negative infection increases.
Machine learning identifying peripheral circulating metabolites associated with intraocular pressure alterations
Authors: Qian Chaoxu , Nusinovici Simon , Thakur Sahil , Soh Zhi Da , Majithia Shivani , Chee Miao Li , Zhong Hua , Tham Yih-Chung , Sabanayagam Charumathi , Hysi Pirro G , Cheng Ching-Yu
Published: May 2022

Aims

To identify blood metabolite markers associated with intraocular pressure (IOP) in a population-based cross-sectional study.

Methods

This study was conducted in a multiethnic Asian population (Chinese, n=2805; Indians, n=3045; Malays, n=3041 aged 40–80 years) in Singapore. All subjects underwent standardised systemic and ocular examinations, and biosamples were collected. Selected metabolites (n=228) in either serum or plasma were analysed and quantified using nuclear magnetic resonance spectroscopy. Least absolute shrinkage and selection operator regression was used for metabolites selection. Multivariable linear regression was used to evaluate the relationship between metabolites and IOP in each of the three ethnic groups, followed by a meta-analysis combining the three cohorts.

Results

Six metabolites, including albumin, glucose, lactate, glutamine, ratio of saturated fatty acids to total fatty acids (SFAFA) and cholesterol esters in very large high-density lipoprotein (HDL), were significantly associated with IOP in all three cohorts. Higher levels of albumin (per SD, beta=0.24, p=0.002), lactate (per SD, beta=0.27, p=0.008), glucose (per SD, beta=0.11, p=0.010) and cholesterol esters in very large HDL (per SD, beta=0.47, p=0.006), along with lower levels of glutamine (per SD, beta=0.17, p<0.001) and SFAFA (per SD, beta=0.21, p=0.008) were associated with higher IOP levels.

Conclusion

We identify several novel blood metabolites associated with IOP. These findings may provide insight into the physiological and pathological processes underlying IOP control.
Updated upper limit of normal for serum alanine aminotransferase value in Vietnamese population
Authors: Huong Nguyen Thi Cam , Karimzadeh Sedighe , Thanh Nguyen Thi , Thuan Tieu Minh , Sabbah Ghada Mohamed , Ismaeil Khaled , An Dang Nguyen Trung , Huong Lai To , Huy Nguyen Tien , Thi Le Hoa Pham
Published: May 2022

Background

Alanine aminotransferase (ALT) is a marker of hepatic damage and its range can be affected by viral hepatitis, alcoholic hepatitis and non-alcoholic fatty liver diseases. We aimed to study the factors associated with higher ALT level and update the upper limit of normal (ULN) in the Vietnamese population.

Methods

This cross-sectional study enrolled 8383 adults, aged 18 years and older who visited the Medical Center at Ho Chi Minh City for a health check-up. Following the exclusion criteria, 6677 subjects were included in the analysis.

Results

Age ≤40 years, male gender, body mass index >23 kg/m2, diastolic blood pressure >85 mm Hg, cholesterol >5.2 mmol/L, triglyceride >1.7 mmol/L, positivity, anti-hepatitis C virus positivity and fatty liver (p<0.05) were associated with higher ALT level (>40 U/L). Without considering age and gender, healthy group is defined after exclusion of participants with one of the mentioned contributing factors. The median ALT level in the healthy group was 18 in men and 13 in women. The ULN at the 95th percentile of the healthy group was 40 U/L in men and 28 U/L in women.

Conclusion

The ULN for ALT in healthy women was lower than in healthy men. Updated ULN for ALT level can promote the identification of unhealthy subjects. More studies that involve ethnicity and lifestyle factors are needed to confirm the new ULN in the Vietnamese population.
Are You All right (AYA)? Association of cumulative traumatic events among Danish police officers with mental health, work environment and sickness absenteeism: protocol of a 3-year prospective cohort study
Authors: Hansen Nina Beck , Møller Sara Rosenbeck , Elklit Ask , Brandt Lars , Andersen Lars L , Pihl-Thingvad Jesper
Published: May 2022

Introduction

Police officers are frequently exposed to potentially traumatic events at work that increases risk of developing mental health problems, in particular post-traumatic stress disorder (PTSD). Individual and organisational factors may influence the detrimental effects of cumulative exposure to traumatic events. Occupational stress and lack of organisational support are associated with increased risk of PTSD among police officers. The Are You All right? (AYA) project is a prospective cohort study investigating the cumulative effect of traumatic events at work on mental health problems and absenteeism among police officers. The study also investigates whether potential risk and protective factors modify the association of traumatic events at work with mental health problems and absenteeism.

Method and analysis

The AYA-study includes the entire Danish police force. Prospective survey data are collected over a 3-year period beginning in the spring of 2021. Electronic surveys are sent out at baseline with 1-year, 2-year and 3-year follow-up. Further, short surveys are sent out every third month, covering exposure to traumatic events and current mental health status. The survey data are paired with workplace register data on sickness absence. Register data on sickness absence cover the period from 2020 to 2025.

Ethics and dissemination

This study was presented for evaluation at the National Ethics Committee in Denmark (reference number: 20202000-216), but according to Danish legislation, survey studies do not require approval by official Danish scientific or ethical committees. Participation in the project is based on informed consent, and data are handled in accordance with the Danish data legislation (journal number: 20/41457). Results are published in scientific journals and disseminated at international conferences.
PHOENIX (Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays): protocol for a randomised, multicentre feasibility study
Authors: Poole Kenneth E S , Chappell Daniel D G , Clark Emma , Fleming Jane , Shepstone Lee , Turmezei Thomas D , Wagner Adam P , Willoughby Karen , Kaptoge Stephen K
Published: May 2022

Introduction

Two million out of the UK’s 5 million routine diagnostic CT scans performed each year incorporate the thoracolumbar spine or pelvic region. Up to one-third reveal undiagnosed osteoporosis or vertebral fractures. We developed an intervention, Picking up Hidden Osteoporosis Effectively during Normal CT Imaging without additional X-rays (‘PHOENIX’), to facilitate early detection and management of osteoporosis in people attending hospitals for CT scans.

Methods and analysis

A multicentre, randomised, pragmatic feasibility study. From the general CT-attending population, women aged ≥65 years and men aged ≥75 years attending for CT scans are invited to participate, via a novel consent form incorporating Fracture Risk Assessment (FRAX) questions. Those at increased 10-year risk (within the amber or red zones of the UK FRAX graphical outputs for further action) are block randomised (1:1:1) to (1) PHOENIX intervention, (2) active control or (3) usual care. The PHOENIX intervention comprises (i) retrieving the CT scans using the NHS Image Exchange Portal, (ii) Mindways QCT Pro software analysis of CT hip and spine none density with CT vertebral fracture assessment, (iii) sending the participants’ general practitioner (GP) a clinical report including diagnosis, necessary investigations and recommended treatment. Baseline CT scans from groups 2 and 3 are assessed with the PHOENIX intervention only at study end. Assuming 25% attrition, the study is powered to find a predicted superior osteoporosis treatment rate with PHOENIX (20%) vs 16% among patients whose GPs were sent the FRAX questionnaire only (active control) and 5% in the usual care group. Five hospitals are participating to determine feasibility. The co-primary feasibility outcome measures are (a) ability to randomise 375 patients within 10 months and (b) retention of 75% of survivors, completing their 1-year bone health outcome questionnaire. Secondary 1-year outcomes include osteoporosis/vertebral fracture identification rates and osteoporosis treatment rates. Stakeholder acceptability and economic aspects are evaluated.

Ethics and dissemination

Approved by committee (National Research Ethics Service) East of England (EE) as REF/19/EE/0176. Dissemination will be through the Royal Osteoporosis Society (to patients and public) as well as to clinician peers via national and international bone/rheumatology scientific and clinical meetings.

Trial registration number

ISRCTN14722819.
Acute kidney injury without need for dialysis, incidence, its impact on long-term stroke survival and progression to chronic kidney disease
Authors: Pande Shrikant D , Roy Debajyoti , Khine Aye Aye , Win May M , Lolong Lorecar , Shan Ni Thu , Tan Pei Ting , Tu Tian Ming
Published: May 2022

Introduction

Patients who had a stroke are at increased risk of sepsis, dehydration and fluctuations in blood pressure, which may result in acute kidney injury (AKI). The impact of AKI on long-term stroke survival has not been studied well.

Objective

We aimed to identify incidence of AKI during acute stroke, follow-up period and its impact on long-term survival and development of chronic kidney disease (CKD).

Design, setting and participants

Retrospective analysis of patients who had a stroke admitted at the rehabilitation facility in Changi General Hospital, Singapore, between June 2008 and May 2017, with median follow-up of 141 (95% CI 120 to 163) months.

Outcome measures and results of univariate analysis

Total 681 patients, median age (63.6) years, 173 (28%) died during follow-up. Elevated blood urea (3.02, 95% CI 2.17 to 4.22; p≤0.001) and creatinine (1.96, 95% CI 1.50 to 2.57; p≤0.001) during stroke affected survival adversely.

Excluding patients with CKD, we analysed the remaining 617 patients. AKI was noted in 75 (12.15%) patients during the index admission, and it affected survival adversely (2.16, 95% CI 1.49 to 3.13; p<0.001). Of the patients with AKI, 21 of 75 (28%) progressed to CKD over a median follow-up of 40.7 months.

Conclusions

We found AKI during stroke admission was associated with increased mortality as compared with those without AKI on univariate analysis. AKI without need of renal replacement therapy was also associated with progression to CKD in this cohort. This suggests that patients with AKI need to have their renal function monitored longitudinally for development of CKD.
Sociodemographic characteristics and health access associated with COVID-19 infection and death: a cross-sectional study in Malang District, Indonesia
Authors: Sujarwoto Sujarwoto , Maharani Asri
Published: May 2022

Objectives

This study aims to examine sociodemographic characteristics and health access associated with COVID-19 infection and death in Malang District, Indonesia.

Design

A non-random cross-sectional study.

Setting

Population in 390 villages in Malang District, East Java Province, Indonesia.

Participants

We used Malang District government COVID-19 contact tracing data from 14 264 individuals, spanning from 1 March 2020 to 29 July 2020.

Primary outcome measures

The outcome variables in this study are COVID-19 infections and COVID-19 deaths. The associations between sociodemographic characteristics and health access of COVID-19 infection and death were analysed using multilevel logistic regression.

Results

Among the 14 264 samples, 551 individuals were confirmed as being infected with COVID-19; 62 individuals died of COVID-19. Women, individuals with direct contact with confirmed COVID-19 cases and individuals with hypertension constituted the groups most vulnerable to COVID-19 infection. Among respondents with confirmed COVID-19 cases, men, individuals aged 61 years and older, individuals with hypertension, and those diagnosed with pneumonia and respiratory failure were at higher risk of death. The number of community-based healthcare interventions was significantly associated with lower COVID-19 infection and COVID-19 mortality. Greater distance to a COVID-19 referral hospital increased risk of COVID-19 mortality.

Conclusions

COVID-19 infection and death were related not only to sociodemographic characteristics of individuals but also to the presence of community-based healthcare interventions and access to hospital care. Strategies in public health, including improving healthcare access, are required to reduce COVID-19 infections among the most susceptible groups in Indonesia.
Evaluation of a mental health screening tool using cross-sectional surveys in a workplace setting
Authors: Xu Joe , Willems Alexander , Li Vincy , Glozier Nick , Batterham Philip J , Malone Victoria , Morris Richard W , Rissel Chris
Published: May 2022

Objectives

The Brief Health Check (BHC) is a health screener used by the Get Healthy at Work programme, which identifies workers with chronic disease risk and provides them with advice and referrals to support services. The BHC was revised to include mental health to provide a holistic approach to workplace health. This study aimed to evaluate the acceptability and appropriateness of the revised BHC by comparing the results around psychological distress and future risk with previous research, and a participant feedback survey.

Method

Data collection took place between October 2018 and May 2019. The study used data that were collected as part of programme delivery, as well as a participant feedback survey that was administered after the health check was completed.

Results

BHCs were completed by n=912 workers, out of which, n=238 completed the feedback survey. The mean Distress Questionnaire 5 score was 10.5, and 10% of participants met the threshold for ‘high’ future risk. The feedback survey revealed that the majority of participants found the mental health advice to be useful (76%), agreed with their mental health distress and risk ratings (92%–94%) and most intended on using the referred services (62%–68%).

Conclusion

The findings around mental health risk were comparable to previous findings in employed samples. The inclusion of mental health assessments, advice and referral pathways into the BHC was found to be acceptable and the subsequent referrals were appropriate, indicating that this approach could be scaled up and implemented to help address worker’s mental ill health
Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161, allogeneic human dental pulp stem cells, in patients with Acute Ischaemic stRoke (J-REPAIR)
Authors: Suda Satoshi , Nito Chikako , Ihara Masafumi , Iguchi Yasuyuki , Urabe Takao , Matsumaru Yuji , Sakai Nobuyuki , Kimura Kazumi
Published: May 2022

Introduction

JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset.

Methods and analysis

This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5–20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95.

Ethics and dissemination

The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal.

Trial registration number

NCT04608838; JapicCTI-194570 and Clinical Trials. gov.
Implementation of the ‘Removed Injectable modified Short-course regimens for EXpert Multidrug Resistant Tuberculosis’ (RISE study) in Tanzania: a protocol for a mixed-methods process evaluation
Authors: Kalolo Albino , Lalashowi Julieth , Pamba Doreen , Shayo Pendomartha Joseph , Gitige Catherine , Mvungi Happiness , Ntagazwa Webhale , Lekule Isaac , Kisonga Riziki , Mleoh Liberate , John Johnson , Kapologwe Ntuli A , Mutayoba Beatrice , Matechi Emmanuel , Mpagama Stellah G , Ntinginya Nyanda Elias
Published: May 2022

Introduction

Tanzania is adapting a shortened injectable-free multidrug resistant tuberculosis (MDR-TB) regimen, comprising new drugs such as bedaquiline and delamanid and repurposed drugs such as clofazimine and linezolid. The regimen is implemented using a pragmatic prospective cohort study within the National TB and Leprosy Programme and is accompanied by a process evaluation. The process evaluation aims to unpack the implementation processes, their outcomes and the moderating factors in order to understand the clinical effectiveness of the regimen. This protocol describes the methods employed in understanding the implementation processes of the new MDR-TB regimen in 15 regions of Tanzania.

Methods

This study adopts a concurrent mixed-methods design. Using multiple data collection tools, we capture information on: implementation outcomes, stakeholder response to the intervention and the influence of contextual factors. Data will be collected from the 22 health facilities categorised as dispensaries, health centres, district hospitals and referral hospitals. Health workers (n=132) and patients (n=220) will fill a structured questionnaire. For each category of health facility, we will conduct five focus group discussions and in-depth interviews (n=45) for health workers. Participant observations (n=9) and review documents (n=22) will be conducted using structured checklists. Data will be collected at two points over a period of 1 year. We will analyse quantitative data using descriptive and inferential statistical methods. Thematic analysis will be used for qualitative data.

Ethics and dissemination

This study received ethical approval from National Institute of Medical research (NIMR), Ref. NIMR/HQ/R.8a/Vol.IX/3269 and from the Mbeya Medical Research and Ethics Review Committee, Ref. SZEC-2439/R.A/V.I/38. Our findings are expected to inform the wider implementation of the new MDR-TB regimen as it is rolled out countrywide. Dissemination of findings will be through publications, conferences, workshops and implementation manuals for scaling up MDR-TB treatments.
Outpatient use patterns and experiences among diabetic and hypertensive patients in fragile settings: a cross-sectional study from Lebanon
Authors: Saleh Shadi , Muhieddine Dina , Hamadeh Randa S , Dimassi Hani , Diaconu K , Noubani Aya , Arakelyan Stella , Ager Alastair , Alameddine Mohamad
Published: May 2022

Objectives

Assess and describe the health service use and delivery patterns for non-communicable disease (NCD) services in two contrasting fragility contexts and by other principal equity-related characteristics including gender, nationality and health coverage.

Setting

Primary healthcare centres located in the urbanised area of Greater Beirut and the rural area of the Beqaa Valley.

Design

This is a cross-sectional study using a structured survey tool between January and September 2020.

Participants

1700 Lebanese and Syrian refugee patients seeking primary care for hypertension and diabetes.

Primary and secondary outcomes

The main outcome is the comprehensiveness of service delivery comparing differences in use and service delivery patterns by fragility setting, gender, nationality and health coverage.

Results

Compliance with routine NCD care management (eg, counselling, immunisations, diagnostic testing and referral rates) was significantly better in Beirut compared with Beqaa. Women were significantly less likely to be offered lifestyle counselling advice and referral to cardiologists (58.4% vs 68.3% in Beqaa and 58.1% vs 62% in Beirut) and ophthalmologists, compared with men. Across both settings, there was a significant trend for Lebanese patients to receive more services and more advice related to nutrition and diabetes management (89.8% vs 85.2% and 62.4% vs 55.5%, respectively). Similarly, referral rates were higher among Lebanese refugees compared with Syrian refugees. Immunisation and diagnostic testing were significantly higher in Beirut among those who have health coverage compared with Beqaa.

Conclusions

The study discovered significant differences in outpatient service use by setting, nationality and gender to differentials. A rigorous and comprehensive appraisal of NCD programmes and services is imperative for providing policy makers with evidence-based recommendations to guide the design, implementation and evaluation of targeted programmes and services necessary to ensure equity in health services delivery to diabetic and hypertensive patients. Such programmes are an ethical imperative considering the protracted crises and compounded fragility.
Socioeconomic and health factors related to polypharmacy and medication management: analysis of a Household Health Survey in North West Coast England
Authors: Downing Jennifer , Taylor Rebecca , Mountain Rachael , Barr Ben , Daras Konstantinos , Comerford Terence , Marson Anthony Guy , Pirmohamed Munir , Dondelinger Frank , Alfirevic Ana
Published: May 2022

Objectives

To examine the socioeconomic and demographic drivers associated with polypharmacy (5–9 medicines), extreme polypharmacy (9–20 medicines) and increased medication count.

Design, setting and participants

A total of 5509 participants, from two waves of the English North West Coast, Household Health Survey were analysed

Outcome measures

Logistic regression modelling was used to find associations with polypharmacy and extreme polypharmacy. A negative binomial regression identified associations with increased medication count. Descriptive statistics explored associations with medication management.

Results

Age and number of health conditions account for the greatest odds of polypharmacy. ORs (95% CI) were greatest for those aged 65+ (3.87, 2.45 to 6.13) and for those with ≥5 health conditions (10.87, 5.94 to 19.88). Smaller odds were seen, for example, in those prescribed cardiovascular medications (3.08, 2.36 to 4.03), or reporting >3 emergency attendances (1.97, 1.23 to 3.17). Extreme polypharmacy was associated with living in a deprived neighbourhood (1.54, 1.06 to 2.26). The greatest risk of increased medication count was associated with age, number of health conditions and use of primary care services. Relative risks (95% CI) were greatest for those aged 65+ (2.51, 2.23 to 2.82), those with ≥5 conditions (10.26, 8.86 to 11.88) or those reporting >18 primary care visits (2.53, 2.18 to 2.93). Smaller risks were seen in, for example, respondents with higher levels of income deprivation (1.35, 1.03 to 1.77). Polypharmic respondents were more likely to report medication management difficulties associated with taking more than one medicine at a time (p<0.001). Furthermore, individuals reporting a mental health condition, were significantly more likely to consistently report difficulties managing their medication (p<0.001).

Conclusion

Age and number of health conditions are most associated with polypharmacy. Thus, delaying or preventing the onset of long-term conditions may help to reduce polypharmacy. Interventions to reduce income inequalities and health inequalities generally could support a reduction in polypharmacy, however, more research is needed in this area. Furthermore, increased prevention and support, particularly with medication management, for those with mental health conditions may reduce adverse medication effects.
Effect of routinely assessing and addressing depression and diabetes distress on clinical outcomes among adults with type 2 diabetes: a systematic review
Authors: McMorrow Rita , Hunter Barbara , Hendrieckx Christel , Kwasnicka Dominika , Speight Jane , Cussen Leanne , Ho Felicia Ching Siew , Emery Jon , Manski-Nankervis Jo-Anne
Published: May 2022

Objectives

This study examined the effect of using patient-reported outcome measures (PROMs) routinely to assess and address depressive symptoms and diabetes distress among adults with type 2 diabetes.

Design

A systematic review of published peer-reviewed studies.

Data sources

Medline, Embase, CINAHL Complete, PsycINFO, The Cochrane Library and Cochrane Central Register of Controlled Trials were searched.

Eligibility criteria

Studies including adults with type 2 diabetes, published in English, from the inception of the databases to 24 February 2022 inclusive; and where the intervention included completion of a PROM of depressive symptoms and/or diabetes distress, with feedback of the responses to a healthcare professional.

Data extraction and synthesis

Using Covidence software, screening and risk of bias assessment were conducted by two reviewers independently with any disagreements resolved by a third reviewer.

Results

The search identified 4512 citations, of which 163 full-text citations were assessed for eligibility, and nine studies met the inclusion criteria. Five studies involved assessment of depressive symptoms only, two studies assessed diabetes distress only, and two studies assessed both. All studies had an associated cointervention. When depressive symptoms were assessed (n=7), a statistically significant between-group difference in depressive symptoms was observed in five studies; with a clinically significant (>0.5%) between-group difference in HbA1c in two studies. When diabetes distress was assessed (n=4), one study demonstrated statistically significant difference in depressive symptoms and diabetes distress; with a clinically significant between-group difference in HbA1c observed in two studies.

Conclusion

Studies are sparse in which PROMs are used to assess and address depressive symptoms or diabetes distress during routine clinical care of adults with type 2 diabetes. Further research is warranted to understand how to integrate PROMs into clinical care efficiently and determine appropriate interventions to manage identified problem areas.

PROSPERO registration number

CRD42020200246.
Agreement between self-reported and researcher-measured height, weight and blood pressure measurements for online prescription of the combined oral contraceptive pill: an observational study
Authors: McCulloch Hannah , Morelli Alessandra , Free Caroline , Syred Jonathan , Botelle Riley , Baraitser Paula
Published: May 2022

Objective(s)

To compare agreement between self-reported height, weight and blood pressure measurements submitted to an online contraceptive service with researcher-measured values and document strategies used for self-reporting.

Design

An observational study.

Setting

An online sexual health service which provided the combined oral contraceptive pill, free of charge, to users in Southeast London, England.

Participants

Between August 2017 and August 2019, 365 participants were recruited.

Primary and secondary outcome measures

The primary outcome, for which the study was powered, was the agreement between self-reported and researcher-measured body mass index (BMI) and blood pressure measurements, compared using kappa coefficients. Secondary measures of agreement included sensitivity, specificity and Bland Altman plots. The study also describes strategies used for self-reporting and classifies their clinical appropriateness.

Results

327 participants fully described their process of blood pressure measurement with 296 (90.5%) classified as clinically appropriate. Agreement between self-reported and researcher-measured BMI was substantial (0.72 (95% CI 0.42 to 1.0)), but poor for blood pressure (0.06 (95% CI −0.11 to 0.23)). Self-reported height and weight readings identified 80.0% (95% CI 28.4 to 99.5) of individuals with a researcher-measured high BMI (≥than 35 kg/m2) and 9.1% (95% CI 0.23 to 41.3) of participants with a researcher-measured high blood pressure (≥140/90 mm Hg).

Conclusion

In this study, while self-reported BMI was found to have substantial agreement with researcher-measured BMI, self-reported blood pressure was shown to have poor agreement with researcher-measured blood pressure. This may be due to the inherent variability of blood pressure, overdiagnosis of hypertension by researchers due to ‘white coat syndrome’ or inaccurate self-reporting. Strategies to improve self-reporting of blood pressure for remote prescription of the combined pill are needed.
Integrated Child and Family Hub models for detecting and responding to family adversity: protocol for a mixed-methods evaluation in two sites
Authors: Hall Teresa , Goldfeld Sharon , Loftus Hayley , Honisett Suzy , Liu Hueiming , De Souza Denise , Bailey Cate , Reupert Andrea , Yap Marie B H , Eapen Valsamma , Haslam Ric , Sanci Lena , Fisher Jane , Eastwood John , Mukumbang Ferdinand C , Loveday Sarah , Jones Renee , Constable Leanne , Forell Suzie , Morris Zoe , Montgomery Alicia , Pringle Glenn , Dalziel Kim , Hiscock Harriet
Published: May 2022

Introduction

Integrated community healthcare Hubs may offer a ‘one stop shop’ for service users with complex health and social needs, and more efficiently use service resources. Various policy imperatives exist to implement Hub models of care, however, there is a dearth of research specifically evaluating Hubs targeted at families experiencing adversity. To contribute to building this evidence, we propose to co-design, test and evaluate integrated Hub models of care in two Australian community health services in low socioeconomic areas that serve families experiencing adversity: Wyndham Vale in Victoria and Marrickville in New South Wales.

Methods and analysis

This multisite convergent mixed-methods study will run over three phases to (1) develop the initial Hub programme theory through formative research; (2) test and, then, (3) refine the Hub theory using empirical data. Phase 1 involves co-design of each Hub with caregivers, community members and practitioners. Phase 2 uses caregiver and Hub practitioner surveys at baseline, and 6 and 12 months after Hub implementation, and in-depth interviews at 12 months. Two stakeholder groups will be recruited: caregivers (n=100–200 per site) and Hub practitioners (n=20–30 per site). The intervention is a co-located Hub providing health, social, legal and community services with no comparator. The primary outcomes are caregiver-reported: (i) identification of, (ii) interventions received and/or (iii) referrals received for adversity from Hub practitioners. The study also assesses child, caregiver, practitioner and system outcomes including mental health, parenting, quality of life, care experience and service linkages. Primary and secondary outcomes will be assessed by examining change in proportions/means from baseline to 6 months, from 6 to 12 months and from baseline to 12 months. Service linkages will be analysed using social network analysis. Costs of Hub implementation and a health economics analysis of unmet need will be conducted. Thematic analysis will be employed to analyse qualitative data.

Ethics and dissemination

Royal Children’s Hospital and Sydney Local Health District ethics committees have approved the study (HREC/62866/RCHM-2020). Participants and stakeholders will receive results through meetings, presentations and publications.

Trial registration number

ISRCTN55495932.