bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccines against sexually transmitted infections: an update
Authors: Fatima Farhat , Kumar Satarupa , Das Anupam
Published: April 2022

Sexually transmitted infections (STI) constitute a major share of the diseases encountered by physicians. Although science has made considerable progress in terms of diagnosing and treating such infections, development of effective and safe vaccines is still needed. Syphilis, viral warts, gonorrhoea, genital herpes, chlamydia and trichomoniasis are the most common infections that are transmitted sexually. In this review, we have attempted to summarize the current status, lacunae and avenues for future research, with reference to the development of STI vaccines.
Successful use of rituximab, an anti-CD20 monoclonal antibody, to treat IgA nephropathy in a patient with recessive dystrophic epidermolysis bullosa
Authors: Hunjan Manrup Kaur , Bardhan Ajoy , Harper Natasha , Langman Gerald , Ajayi Bamidele , Suresh Vijay , Heagerty Adrian H. M.
Published: April 2022

We describe the successful use of rituximab for the treatment of IgA nephropathy in a patient with recessive dystrophic epidermolysis bullosa. To our knowledge, this is the first reported case in the literature.
Supportive mobility device use across the life span by individuals with cerebral palsy: A qualitative study
Authors: Feldner Heather A. , Gaebler‐Spira Deborah , Awasthi Varun , Bjornson Kristie
Published: April 2022

Aim

To understand the mobility experiences, supportive mobility device (SMD) use, and desired participation outcomes of individuals with cerebral palsy (CP) across the life span, and describe how perspectives of rehabilitation care and professional resources may influence mobility decision‐making processes and outcomes.

Method

In the second phase of an overarching study, focus groups were conducted with 164 participants (68 individuals with CP; 32 females, 36 males; mean age 17y 8mo, SD 11y 11mo, range 3–68y), 74 caregivers (50 females, 24 males), and 22 healthcare providers (14 females, eight males) across four US cities. Sessions were audio‐recorded, transcribed, and analysed using constant comparison.

Results

Six themes emerged. Five presented across all stakeholder groups: (1) the system is broken; (2) equipment is simultaneously liberating and restricting; (3) adaptation across the life span; (4) designed for transport, not for living; and (5) sharing our stories and sharing resources. One theme (theme 6) was specific to healthcare providers: caught in the middle.

Interpretation

This qualitative study underscores the simultaneous value and frustration associated with SMDs as described by the community with CP, and recognition among all stakeholders of the need to improve connections and resource networks within the community with CP to improve SMD design and provision processes across device types and across the life span for individuals with CP.

What this paper adds

Supportive mobility devices (SMDs) were most often equated with freedom, participation, and independence.

Frustration with SMDs across the life span persisted with regard to design, function, cost, and maintenance.

Stakeholders in the community with cerebral palsy are seeking greater networking and resource sharing to enhance SMD provision processes.

Access to appropriate SMDs across the life span and the need for system improvement are critical.
Relative protein intake and associations with markers of physical function in those with type 2 diabetes
Authors: Henson Joseph , Arsenyadis Frank , Redman Emma , Brady Emer M. , Coull Nicole A. , Edwardson Charlotte L. , Hall Andrew P. , James Lewis J. , Khunti Kamlesh , Rowlands Alex V. , Stevenson Emma J. , West Daniel J. , Davies Melanie J. , Yates Thomas
Published: April 2022

Aims

To examine the independent associations between relative protein intake (g kg−1 day1) and markers of physical function in those with type 2 diabetes, while also comparing with current guidelines for protein intake.

Methods

This analysis reports data from the ongoing Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) study. Functional assessments included: Short Physical Performance Battery (SPPB), 60 s sit‐to‐stand (STS‐60), 4‐m gait speed, time to rise from a chair (×5) and handgrip strength. Participants also completed a self‐reported 4 day diet diary. Regression analyses assessed whether relative protein intake was associated with markers of physical function. Interaction terms assessed whether the associations were modified by sex, age, HbA1c or body mass index (BMI).

Results

413 participants were included (mean ± SD:age = 65.0 ± 7.7 years, 33% female, BMI = 30.6 ± 5.1 kg/m2). The average total protein intake was 0.88 ± 0.31 g kg−1 day−1. 33% of individuals failed to meet the reference nutrient intake for the United Kingdom (≥0.75 g kg−1 day−1), and 87% for European recommendations (≥1.2 g kg−1 day−1). After adjustment, each 0.5 g/kg of protein intake was associated with an 18.9% (95% CI: 2.3, 35.5) higher SPPB score, 22.7% (1.1, 44.3) more repetitions in STS‐60, 21.1% (4.5, 37.7) faster gait speed and 33.2% (16.9, 49.5) lower chair rise time. There were no associations with handgrip strength or any interactions.

Conclusions

Relative protein intake was positively associated with physical function outcomes, even after consideration of total energy intake. As a number of individuals were below the current guidelines, protein intake may be a modifiable factor of importance for people with type 2 diabetes.
Invisible work at work and the reproduction of gendered social service organizations
Authors: Lavee Einat , Kaplan Amit
Published: April 2022

Studies demonstrate that the convergence of neoliberalism and New Public Management imperatives creates conditions wherein social service providers undertake various types of unpaid work, reemphasizing the role of gender in service provision. Drawing on these arguments, this study explores the process through which unpaid practices restructure gender in social service organizations, using the concept of “invisible work.” Applying the institutional ethnography method of inquiry, we examine experiences of social service workers in the Israeli public sector and operationalize unpaid work as informal personal resources that workers provide to clients. Analysis of 185 in‐depth interviews revealed three main discursive frames workers use to justify provision of personal resources. Through these frames, informal practices become invisible as work in multiple layers—to the self, the organization, and the society. Similar to invisible work in the household, its invisibility in the workplace constitutes a main force in the reproduction of gendered social service organizations.
Stem Cell‐based therapies for COVID‐19‐related acute respiratory distress syndrome
Authors: Ngai Hoi Wa , Kim Dae Hong , Hammad Mohamed , Gutova Margarita , Aboody Karen , Cox Christopher D.
Published: April 2022

As the number of confirmed cases and resulting death toll of the COVID‐19 pandemic continue to increase around the globe ‐ especially with the emergence of new mutations of the SARS‐CoV‐2 virus in addition to the known alpha, beta, gamma, delta and omicron variants ‐ tremendous efforts continue to be dedicated to the development of interventive therapeutics to mitigate infective symptoms or post‐viral sequelae in individuals for which vaccines are not accessible, viable or effective in the prevention of illness. Many of these investigations aim to target the associated acute respiratory distress syndrome, or ARDS, which induces damage to lung epithelia and other physiologic systems and is associated with progression in severe cases. Recently, stem cell‐based therapies have demonstrated preliminary efficacy against ARDS based on a number of preclinical and preliminary human safety studies, and based on promising outcomes are now being evaluated in phase II clinical trials for ARDS. A number of candidate stem cell therapies have been found to exhibit low immunogenicity, coupled with inherent tropism to injury sites. In recent studies, these have demonstrated the ability to modulate suppression of pro‐inflammatory cytokine signals such as those characterizing COVID‐19‐associated ARDS. Present translational studies are aiming to optimize the safety, efficacy and delivery to fully validate stem cell‐based strategies targeting COVID‐19 associated ARDS for viable clinical application.
Predictive models for clinical decision making: Deep dives in practical machine learning
Authors: Eloranta Sandra , Boman Magnus
Published: April 2022

The deployment of machine learning for tasks relevant to complementing standard of care and advancing tools for precision health has gained much attention in the clinical community, thus meriting further investigations into its broader use. In an introduction to predictive modelling using machine learning, we conducted a review of the recent literature that explains standard taxonomies, terminology and central concepts to a broad clinical readership. Articles aimed at readers with little or no prior experience of commonly used methods or typical workflows were summarised and key references are highlighted. Continual interdisciplinary developments in data science, biostatistics and epidemiology also motivated us to further discuss emerging topics in predictive and data‐driven (hypothesis‐less) analytics with machine learning. Through two methodological deep dives using examples from precision psychiatry and outcome prediction after lymphoma, we highlight how the use of, for example, natural language processing can outperform established clinical risk scores and aid dynamic prediction and adaptive care strategies. Such realistic and detailed examples allow for critical analysis of the importance of new technological advances in artificial intelligence for clinical decision‐making. New clinical decision support systems can assist in prevention and care by leveraging precision medicine.
Cancer testis antigen (PRAME) as an independent marker for survival in oral squamous cell carcinoma (OSCC)
Authors: Haidari Selgai , Tröltzsch Matthias , Fliefel Riham , Jungbluth Achim A. , Otto Sven , Fegg Florian , Liokatis Paris , Ahmadi Nima , Eberl Marian , Probst Florian Andreas , Knösel Thomas
Published: April 2022

Background

The objective was to assess the expression patterns of the cancer testis antigen PRAME, NY‐ESO1, and SSX2 in oral squamous cell carcinoma (OSSC) and to correlate the expression with clinical and histopathological parameters including progression‐free survival analysis.

Methods

The study variables of this retrospective cohort study (n = 83) included demographic data, histopathological data, and information on progression‐free survival. PRAME expression patterns were rated based on immunohistochemistry on tissue microarrays (TMA). The survival rate was assessed by Kaplan–Meier method and Cox regression model. The primary predictor variable was defined as the expression of PRAME and the outcome variable was progression‐free survival.

Results

Analysis of progression‐free survival using Kaplan–Meier method showed that patients with positive expression of PRAME had lower probabilities of progression‐free survival (p < 0.001). According to the Cox regression model, the level of PRAME expression had a considerable and significant independent influence on progression‐free survival (positive PRAME expression increasing the hazards for a negative outcome by 285% in our sample; HR = 3.85, 95% CI: 1.45–10.2, p = 0.007). The expression of SSX2 (n = 1) and NY‐ESO‐1 (n = 5) in our samples was rare.

Conclusion

PRAME is expressed in OSCC and appears to be a suitable marker of progression‐free survival, correlates with severe course, and may allow identification of high‐risk patients with aggressive progression.
Factors contributing to neonatal readmissions to a level 4 hospital within 28 days after birth
Authors: Jarrett Olivia , Gim Daeun , Puusepp‐Benazzouz Helen , Liu Anthony , Bhurawala Habib
Published: April 2022

Aim

To identify maternal and neonatal factors associated with neonatal readmissions.

Methods

A case controlled, cross‐sectional, retrospective review of neonatal readmissions within 28 days from birth to a level 4 hospital in Western Sydney was conducted from January to December 2018. Maternal and neonatal factors for readmission were assessed. A control group of 122 neonates were randomly selected. Comparative statistics and logistic regression analysis were used to analyse the data.

Results

Of the 3914 neonatal discharges following birth, there were 129 neonatal readmissions (3.3%). Following regression analysis, gestational age (odds ratio 0.82, 95% confidence interval 0.7–0.97, P = 0.02) and intrapartum intravenous (IV) fluids (odds ratio 2.78, 95% confidence interval 1.66–4.67, P < 0.001) were associated with readmission. The majority of readmissions were feeding‐related (72.9%). Of these readmissions, 29.8% had feeding concerns noted by nursing or midwifery staff during the initial hospital stay. During the initial hospital stay following birth, neonatal feeding issues were significantly associated with primiparous mothers (P = 0.005). Mothers who did not receive IV fluids during labour were also more likely to experience feeding issues (P = 0.015).

Conclusion

Our findings indicate that hospital discharge prior to established feeding patterns may be associated with an increased incidence of neonatal readmission. The factors associated with neonatal readmission are earlier gestational age and intrapartum IV fluid administration. These findings suggest that more comprehensive feeding assessment prior to discharge, flexibility of discharge timing and increased community support may reduce neonatal readmission.
Multidrug‐resistant organisms in paediatric palliative care patients – Prevalence, risk factors and the impact of a liberal hygiene concept
Authors: Schmidt Pia , Hasan Carola , Mauritz Maximilian D , Simon Arne , Stening Kathrin , Hartenstein‐Pinter Almut , Zernikow Boris , Wager Julia
Published: April 2022

Aim

Multidrug‐resistant organisms (MDRO) deserve special attention in health‐care facilities for children with life‐limiting conditions because these children have an increased risk for colonisation. To avoid nosocomial transmissions to other inpatients, single‐room isolation is usually recommended. In the context of paediatric palliative care (PPC), such isolation counters the aim of participation in social activities for the patients. This study aimed to determine the prevalence of MDRO, the predictive value of risk factors and the incidence of nosocomial infections and nosocomial colonisations on a PPC inpatient unit applying a special hygiene concept that enables participation in social activities through risk‐adaption and barrier nursing.

Methods

Two‐year surveillance with MDRO screening of all intakes (N = 386) of a PPC unit on the day of admission and discharge. To determine the predictive value of pre‐defined risk factors, logistic regression analyses were calculated. Receiver operating characteristic analyses were performed to determine the predictive power of the number of risk factors on the presence of MDRO.

Results

The rate of MDRO colonisation at admission was 12.7%; previous positive MDRO screening was the only significant individual risk factor. Over the 2‐year period, no MDRO‐related nosocomial infections occurred; nosocomial colonisation incidence density was 0.6.

Conclusion

Results demonstrate that patients with at least one risk factor have to be cared for by barrier nursing until MDRO screening results are negative. Following these guidelines prevents nosocomial MDRO transmission.
Peaks, gaps, and time‐reversibility of economic time series
Authors: Proietti Tommaso
Published: April 2022

By locating the running maxima and minima of a time series, and measuring the current deviation from them, it is possible to generate processes that are relevant for the analysis of the business cycle and for characterizing bull and bear phases in financial markets. First, the measurement of the time distance from the running peak originates a first‐order Markov chain, whose characteristics can be used for testing time‐reversibility of economic dynamics and specific types of asymmetries in financial markets. Second, the gap processes can be combined to provide a non‐parametric measure of the growth cycle. The article derives the time series properties of the gap process and other related processes that arise from the same measurement context, and proposes new non‐parametric tests of time‐reversibility and new measures of the output gap.
ANGUSTIFOLIA negatively regulates resistance to Sclerotinia sclerotiorum via modulation of PTI and JA signalling pathways in Arabidopsis thaliana
Authors: Gao Xiuqin , Dang Xie , Yan Fengting , Li Yuhua , Xu Jing , Tian Shifu , Li Yaling , Huang Kun , Lin Wenwei , Lin Deshu , Wang Zonghua , Wang Airong
Published: April 2022

Sclerotinia sclerotiorum is a devastating pathogen that infects a broad range of host plants. The mechanism underlying plant defence against fungal invasion is still not well characterized. Here, we report that ANGUSTIFOLIA (AN), a CtBP family member, plays a role in the defence against S. sclerotiorum attack. Arabidopsis an mutants exhibited stronger resistance to S. sclerotiorum at the early stage of infection than wild‐type plants. Accordingly, an mutants exhibited stronger activation of pathogen‐associated molecular pattern (PAMP)‐triggered immunity (PTI) responses, including mitogen‐activated protein kinase activation, reactive oxygen species accumulation, callose deposition, and the expression of PTI‐responsive genes, upon treatment with PAMPs/microbe‐associated molecular patterns. Moreover, Arabidopsis lines overexpressing AN were more susceptible to S. sclerotiorum and showed defective PTI responses. Our luminometry, bimolecular fluorescence complementation, coimmunoprecipitation, and in vitro pull‐down assays indicate that AN interacts with allene oxide cyclases (AOC), essential enzymes involved in jasmonic acid (JA) biosynthesis, negatively regulating JA biosynthesis in response to S. sclerotiorum infection. This work reveals AN is a negative regulator of the AOC‐mediated JA signalling pathway and PTI activation.
“Getting caught unprepared”: A phenomenological study of Indonesian nurses dealing with difficulties when caring for patients with coronavirus disease (COVID‐19)
Authors: Sutantri Sutantri , Putri Arcellia Farosyah , Ismiyati Rini
Published: April 2022

The emergence of coronavirus disease 2019 (COVID‐19) has brought pressure and challenges to nurses worldwide. This study aims to understand the lived experiences of nurses in overcoming challenges when delivering care for patients with COVID‐19 in Indonesia. The study employed a phenomenological research design. The researchers purposely selected nine nurses who provided care for patients with COVID‐19 at an urban public hospital in Yogyakarta, Indonesia, between September and December 2020. The researchers conducted face‐to‐face interviews with participants. The interview data transcriptions were analyzed using Colaizzi's phenomenological analysis. The experiences of nurses in providing care for patients with COVID‐19 can be summarized into three themes: (1) getting caught unprepared, (2) understanding and adapting to a new working situation, and (3) finding new meaning in the nursing profession. This study suggested that nurses overcame difficulties in caring for patients with COVID‐19 by using multidimensional and culturally informed coping strategies. Hospital managers and policymakers need to consider culturally relevant coping strategies (i.e., religious‐based coping strategies) when supporting healthcare providers during public health emergencies.
Relationships between fear of COVID‐19, cyberchondria, intolerance of uncertainty, and obsessional probabilistic inferences: A structural equation model
Authors: Boysan Murat , Eşkisu Mustafa , Çam Zekeriya
Published: April 2022

The study was set out to explore the structural relationships between fear of COVID‐19, cyberchondria, intolerance of uncertainty, and obsessional probabilistic inferences. The data were recruited online from a community population (n = 1,049) subjected to a confirmatory factor analytic procedure. The structural model specified according to the previous findings in the literature showed that a general tendency to negative expectations in terms of probabilistic thinking was significantly associated with both COVID‐19‐related‐fear and intolerance of uncertainty. Fear of COVID‐19 was significantly associated with cyberchondria. Probabilistic thinking style and intolerance of uncertainty contributed to cyberchondria through fear of COVID‐19 as well. We concluded that a tendency to engage in a probabilistic thinking style and intolerance of uncertainty seems to play role in the etiology of fear of infection and cyberchondria.
COVID‐19 in vaccinated versus unvaccinated hematologic malignancy patients
Authors: DeVoe Catherine , Pandey Shraddha , Shariff Dayana , Arora Shagun , Henrich Timothy J. , Yokoe Deborah S. , Langelier Charles R. , Servellita Venice , Chiu Charles , Miller Steve , Babik Jennifer M. , Chin‐Hong Peter , Fung Monica
Published: April 2022

The effect of vaccination on severity of subsequent COVID‐19 in patients with hematologic malignancies (HMs) is unknown. In this single‐center retrospective cohort study, we found no difference in severity of COVID‐19 disease in vaccinated (n = 16) versus unvaccinated (n = 54) HM patients using an adjusted multiple logistic regression model. Recent anti‐B‐cell therapy was associated with more severe illness.

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Neutralizing antibody levels against SARS‐CoV‐2 variants of concern Delta and Omicron in vaccine breakthrough‐infected blood donors
Authors: Franchini Massimo , Focosi Daniele , Mengoli Carlo , Percivalle Elena , Sammartino Josè Camilla , Ferrari Alessandro , Zani Matteo , Glingani Claudia , Baldanti Fausto
Published: April 2022

Background

Novel SARS‐CoV‐2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID‐19 convalescent plasma (CCP) a potential frontline treatment.

Study design/methods

In this study, we investigated the kinetics of anti‐SARS‐CoV‐2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti‐SARS‐CoV‐2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS‐CoV‐2 S1/S2 and Liaison® SARS‐CoV‐2 TrimericS IgG assays, DiaSorin). Measures were correlated with different variables, including the time between last vaccine dose and CCP donation, and time between SARS‐COV‐2 infection and CCP donation.

Results

nAb titers against VOC Delta and Omicron were directly related to the time interval since last vaccine dose to CCP donation, but inversely related to time since COVID19 breakthrough infection.

Discussion

SARS‐CoV‐2 breakthrough infection in vaccinated in donors boosts nAb titers against VOCs Delta and Omicron, but such titers decay shortly after infection. Therefore, CCP must be collected early after vaccine breakthrough infection.
Biaxial Murine Vaginal Remodeling With Reproductive Aging
Authors: White Shelby E. , Kiley Jasmine X. , Visniauskas Bruna , Lindsey Sarah H. , Miller Kristin S.
Published: April 2022

Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown. Therefore, the first objective of this study was to quantify the biaxial mechanical properties of the nulliparous murine vagina with reproductive aging. Menopause is further associated with a decrease in elastic fiber content, which may contribute to vaginal stiffening. Hence, our second objective was to determine the effect of elastic fiber disruption on the biaxial vaginal mechanical properties. To accomplish this, vaginal samples from CD-1 mice aged 2–14 months underwent extension-inflation testing protocols (n = 64 total; n = 16/age group). Then, half of the samples were randomly allocated to undergo elastic fiber fragmentation via elastase digestion (n = 32 total; 8/age group) to evaluate the role of elastic fibers. The material stiffness increased with reproductive age in both the circumferential and axial directions within the control and elastase-treated vaginas. The vagina demonstrated anisotropic mechanical behavior, and anisotropy increased with age. In summary, vaginal remodeling with reproductive age included increased direction-dependent material stiffness, which further increased following elastic fiber disruption. Further work is needed to quantify vaginal remodeling during pregnancy and postpartum with reproductive aging to better understand how age-related vaginal remodeling may contribute to an increased risk of vaginal tearing.
An in-plane photoelectric effect in two-dimensional electron systems for terahertz detection
Authors: Michailow Wladislaw , Spencer Peter , Almond Nikita W. , Kindness Stephen J. , Wallis Robert , Mitchell Thomas A. , Degl’Innocenti Riccardo , Mikhailov Sergey A. , Beere Harvey E. , Ritchie David A.
Published: April 2022

Many mid- and far-infrared semiconductor photodetectors rely on a photonic response, when the photon energy is large enough to excite and extract electrons due to optical transitions. Toward the terahertz range with photon energies of a few milli–electron volts, classical mechanisms are used instead. This is the case in two-dimensional electron systems, where terahertz detection is dominated by plasmonic mixing and by scattering-based thermal phenomena. Here, we report on the observation of a quantum, collision-free phenomenon that yields a giant photoresponse at terahertz frequencies (1.9 THz), more than 10-fold as large as expected from plasmonic mixing. We artificially create an electrically tunable potential step within a degenerate two-dimensional electron gas. When exposed to terahertz radiation, electrons absorb photons and generate a large photocurrent under zero source-drain bias. The observed phenomenon, which we call the “in-plane photoelectric effect,” provides an opportunity for efficient direct detection across the entire terahertz range.
Egr1
is a 3D matrix–specific mediator of mechanosensitive stem cell lineage commitment
Authors: Baek Jieung , Lopez Paola A. , Lee Sangmin , Kim Taek-Soo , Kumar Sanjay , Schaffer David V.
Published: April 2022

While extracellular matrix (ECM) mechanics strongly regulate stem cell commitment, the field’s mechanistic understanding of this phenomenon largely derives from simplified two-dimensional (2D) culture substrates. Here, we found a 3D matrix–specific mechanoresponsive mechanism for neural stem cell (NSC) differentiation. NSC lineage commitment in 3D is maximally stiffness sensitive in the range of 0.1 to 1.2 kPa, a narrower and more brain-mimetic range than we had previously identified in 2D (0.75 to 75 kPa). Transcriptomics revealed stiffness-dependent up-regulation of early growth response 1 (
Egr1
) in 3D but not in 2D.
Egr1
knockdown enhanced neurogenesis in stiff ECMs by driving β-catenin nuclear localization and activity in 3D, but not in 2D. Mechanical modeling and experimental studies under osmotic pressure indicate that stiff 3D ECMs are likely to stimulate
Egr1
via increases in confining stress during cell volumetric growth. To our knowledge,
Egr1
represents the first 3D-specific stem cell mechanoregulatory factor.
Redefining inflammatory macrophage phenotypes across stages and tissues by single-cell transcriptomics
Authors: Loke P’ng , Lin Jian-Da
Published: April 2022

Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.
Type 2 diabetes classification: a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
Authors: Christensen Diana Hedevang , Nicolaisen Sia K , Ahlqvist Emma , Stidsen Jacob V , Nielsen Jens Steen , Hojlund Kurt , Olsen Michael H , García-Calzón Sonia , Ling Charlotte , Rungby Jørgen , Brandslund Ivan , Vestergaard Peter , Jessen Niels , Hansen Torben , Brøns Charlotte , Beck-Nielsen Henning , Sørensen Henrik T , Thomsen Reimar W , Vaag Allan
Published: April 2022

Introduction

A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort.

Research design and methods

In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes.

Results

Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m2 vs 36 kg/m2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype.

Conclusion

Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
Which actionable statements qualify as good practice statements In Covid-19 guidelines? A systematic appraisal
Authors: Dewidar Omar , Lotfi Tamara , Langendam Miranda , Parmelli Elena , Saz Parkinson Zuleika , Solo Karla , Chu Derek K , Mathew Joseph L , Akl Elie A , Brignardello-Petersen Romina , Mustafa Reem A , Moja Lorenzo , Iorio Alfonso , Chi Yuan , Canelo-Aybar Carlos , Kredo Tamara , Karpusheff Justine , Turgeon Alexis F , Alonso-Coello Pablo , Wiercioch Wojtek , Gerritsen Annette , Klugar Miloslav , Rojas María Ximena , Tugwell Peter , Welch Vivian Andrea , Pottie Kevin , Munn Zachary , Nieuwlaat Robby , Ford Nathan , Stevens Adrienne , Khabsa Joanne , Nasir Zil , Leontiadis Grigorios I , Meerpohl Joerg J , Piggott Thomas , Qaseem Amir , Matthews Micayla , Schünemann Holger J
Published: April 2022

Objectives

To evaluate the development and quality of actionable statements that qualify as good practice statements (GPS) reported in COVID-19 guidelines.

Design and setting

Systematic review . We searched MEDLINE, MedSci, China National Knowledge Infrastructure (CNKI), databases of Grading of Recommendations Assessment, Development and Evaluation (GRADE) Guidelines, NICE, WHO and Guidelines International Network (GIN) from March 2020 to September 2021. We included original or adapted recommendations addressing any COVID-19 topic.

Main outcome measures

We used GRADE Working Group criteria for assessing the appropriateness of issuing a GPS: (1) clear and actionable; (2) rationale necessitating the message for healthcare practice; (3) practicality of systematically searching for evidence; (4) likely net positive consequences from implementing the GPS and (5) clear link to the indirect evidence. We assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation II tool.

Results

253 guidelines from 44 professional societies issued 3726 actionable statements. We classified 2375 (64%) as GPS; of which 27 (1%) were labelled as GPS by guideline developers. 5 (19%) were labelled as GPS by their authors but did not meet GPS criteria. Of the 2375 GPS, 85% were clear and actionable; 59% provided a rationale necessitating the message for healthcare practice, 24% reported the net positive consequences from implementing the GPS. Systematic collection of evidence was deemed impractical for 13% of the GPS, and 39% explained the chain of indirect evidence supporting GPS development. 173/2375 (7.3%) statements explicitly satisfied all five criteria. The guidelines’ overall quality was poor regardless of the appropriateness of GPS development and labelling.

Conclusions

Statements that qualify as GPS are common in COVID-19 guidelines but are characterised by unclear designation and development processes, and methodological weaknesses.
Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance
Authors: Dewidar Omar , Lotfi Tamara , Langendam Miranda W , Parmelli Elena , Saz Parkinson Zuleika , Solo Karla , Chu Derek K , Mathew Joseph L , Akl Elie A , Brignardello-Petersen Romina , Mustafa Reem A , Moja Lorenzo , Iorio Alfonso , Chi Yuan , Canelo-Aybar Carlos , Kredo Tamara , Karpusheff Justine , Turgeon Alexis F , Alonso-Coello Pablo , Wiercioch Wojtek , Gerritsen Annette , Klugar Miloslav , Rojas María Ximena , Tugwell Peter , Welch Vivian Andrea , Pottie Kevin , Munn Zachary , Nieuwlaat Robby , Ford Nathan , Stevens Adrienne , Khabsa Joanne , Nasir Zil , Leontiadis Grigorios , Meerpohl Joerg , Piggott Thomas , Qaseem Amir , Matthews Micayla , Schünemann Holger J
Published: April 2022

An evidence-based approach is considered the gold standard for health decision-making. Sometimes, a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence is indirect. In such cases, the application of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach for grading the strength of recommendations is inappropriate. Instead, the GRADE Working Group has recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumsances they would be appropriate.

Through an evaluation of COVID-1- related recommendations on the eCOVID Recommendation Map (COVID-19.recmap.org), we found that recommendations qualifying a GPS were widespread. However, guideline developers failed to label them as GPS or transparently report justifications for their development. We identified ways to improve and facilitate the operationalisation and implementation of the GRADE guidance for GPS.

Herein, we propose a structured process for the development of GPSs that includes applying a sequential order for the GRADE guidance for developing GPS. This operationalisation considers relevant evidence-to-decision criteria when assessing the net consequences of implementing the statement, and reporting information supporting judgments for each criterion. We also propose a standardised table to facilitate the identification of GPS and reporting of their development. This operationalised guidance, if endorsed by guideline developers, may palliate some of the shortcomings identified. Our proposal may also inform future updates of the GRADE guidance for GPS.
Socioeconomic risk markers of arthropod-borne virus (arbovirus) infections: a systematic literature review and meta-analysis
Authors: Power Grace M , Vaughan Aisling M , Qiao Luxi , Sanchez Clemente Nuria , Pescarini Julia M. , Paixão Enny S. , Lobkowicz Ludmila , Raja Amber I. , Portela Souza André , Barreto Mauricio Lima , Brickley Elizabeth B.
Published: April 2022

Introduction

Arthropod-borne viruses (arboviruses) are of notable public health importance worldwide, owing to their potential to cause explosive outbreaks and induce debilitating and potentially life-threatening disease manifestations. This systematic review and meta-analysis aims to assess the relationship between markers of socioeconomic position (SEP) and infection due to arboviruses with mosquito vectors.

Methods

We conducted a systematic search on PubMed, Embase, and LILACS databases to identify studies published between 1980 and 2020 that measured the association of SEP markers with arbovirus infection. We included observational studies without geographic location or age restrictions. We excluded studies from grey literature, reviews and ecological studies. Study findings were extracted and summarised, and pooled estimates were obtained using random-effects meta-analyses.

Results

We identified 36 observational studies using data pertaining to 106 524 study participants in 23 geographic locations that empirically examined the relationship between socioeconomic factors and infections caused by seven arboviruses (dengue, chikungunya, Japanese encephalitis, Rift Valley fever, Sindbis, West Nile and Zika viruses). While results were varied, descriptive synthesis pointed to a higher risk of arbovirus infection associated with markers of lower SEP, including lower education, income poverty, low healthcare coverage, poor housing materials, interrupted water supply, marital status (married, divorced or widowed), non-white ethnicities and migration status. Pooled crude estimates indicated an increased risk of arboviral infection associated with lower education (risk ratio, RR 1.5 95% CI 1.3 to 1.9); I2=83.1%), interruption of water supply (RR 1.2; 95% CI 1.1 to 1.3; I2=0.0%) and having been married (RR 1.5 95% CI 1.1 to 2.1; I2=85.2%).

Conclusion

Evidence from this systematic review suggests that lower SEP increases the risk of acquiring arboviral infection; however, there was large heterogeneity across studies. Further studies are required to delineate the relationship between specific individual, household and community-level SEP indicators and arbovirus infection risks to help inform targeted public health interventions.

PROSPERO registration number

CRD42019158572.
Electroacupuncture versus sham electroacupuncture in the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer: study protocol for a multicentre, randomised, sham-controlled trial
Authors: Zou Xuan , Yang Ying-Chi , Wang Yu , Pei Wei , Han Jia-Gang , Lu Yun , Zhang Mao-Shen , Tu Jian Feng , Lin Lu Lu , Wang Li-Qiong , Shi Guangxia , Yan Shi-Yan , Yang Jing-Wen , Liu Cun-Zhi
Published: April 2022

Introduction

Postoperative ileus (POI) is an inevitable complication of almost all abdominal surgeries, which results in prolonged hospitalisation and increased healthcare costs. Various treatment strategies have been developed for POI but with limited success. Electroacupuncture (EA) might be a potential therapy for POI. However, evidence from rigorous trials that evaluated the effectiveness of EA for POI is limited. Thus, the aim of this study was to examine whether EA can safely reduce the time to the first defecation after laparoscopic surgery in patients with POI.

Methods and analysis

This multicentre randomised sham-controlled trial will be conducted in four hospitals in China. A total of 248 eligible participants with colorectal cancer who will undergo laparoscopic surgery will be randomly allocated to an EA group and a sham EA group in a 1:1 ratio. Treatment will be performed starting on postoperative day 1 and continued for four consecutive days, once per day. If the participant is discharged within 4 days after surgery, the treatment will cease on the day of discharge. The primary outcome will be the time to first defecation. The secondary outcome measures will include time to first flatus, tolerability of semiliquid and solid food, length of postoperative hospital stay, postoperative nausea and vomiting, abdominal distension, postoperative pain, postoperative analgesic, time to first ambulation, blinding assessment, credibility and expectancy and readmission rate.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of Beijing University of Chinese Medicine (number 2020BZHYLL0116) and the institutional review board of each hospital. The results will be disseminated through peer-reviewed publications. This study protocol (V.3.0, 6 March 2020) involves human participants and was approved by the ethics committees of Beijing University of Chinese Medicine (number 2020BZHYLL0116), Beijing Friendship Hospital Affiliated to Capital Medical University (number 2020-P2-069-01), Beijing Chao-Yang Hospital Affiliated to Capital Medical University (number 2020-3-11-2), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (number 20/163-2359), and the Affiliated Hospital of Qingdao University (number QYFYKYLL711311920). The participants gave informed consent to participate in the study before taking part.

Trial registration number

ChiCTR2000038444.
Prevalence of childhood exposure to intimate partner violence in low-income and lower-middle-income countries: a systematic review
Authors: Kieselbach Berit , Kimber Melissa , MacMillan Harriet L , Perneger Thomas
Published: April 2022

Objective

To determine the proportion of children in low-income and lower-middle-income countries exposed to intimate partner violence (IPV).

Design

Systematic review.

Data sources

PubMed, CINAHL, ERIC, PsycINFO, Web of Science, WHO Global Index Medicus, and Violence and Abuse Abstracts, hand searching of specialised journals from inception until 19 May 2019.

Eligibility criteria for selecting studies

Primary quantitative studies that included a measure of self-reported exposure to IPV prior to age 18 and were conducted in low-income and lower-middle-income countries.

Data extraction and synthesis

Data were screened, extracted and appraised by two independent reviewers. The prevalence estimates were pooled using a random-effects model. Outcomes included lifetime and past-year prevalence of childhood exposure to IPV. Meta-regression was used to explore heterogeneity. Publication bias was assessed using a funnel plot and Egger’s regression test. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.

Results

Sixty-two studies with a total of 231 512 participants were included. Eighty-five lifetime prevalence estimates and 6 estimates of past-year prevalence were available for synthesis. The average lifetime prevalence of childhood exposure to IPV was 29% (95% CI 26% to 31%). The average past-year prevalence in children was 35% (95% CI 21% to 48%). The lifetime prevalence disaggregated by WHO regions ranged from 21% to 34%. There were no statistical differences in prevalence estimates between samples of men and women.

Conclusion

Almost one-third of children in low-income and lower-middle-income countries have been exposed to IPV in their lifetime. There was large heterogeneity between estimates that was not explained by available study and sample characteristics. Our findings indicate that children’s exposure to IPV in low-income and lower-middle-income countries is common and widespread; prevention of this major public health exposure should be a priority.

PROSPERO registration number

CRD42019119698.
Inclusion of informal caregivers in the palliative and end-of-life care of older adults: a scoping review protocol
Authors: Auclair Isabelle , Bourbonnais Anne , Lavoie Audrey , Leclerc-Loiselle Jérôme
Published: April 2022

Introduction

Palliative and end-of-life (EOL) care will increasingly be required in years to come as a result of an ageing population. An important component of this type of care is the inclusion of informal caregivers, who are family members or friends offering unpaid assistance to older adults with a terminal illness. Although systematic reviews were conducted on topics related to the inclusion of informal caregivers in the palliative and EOL care of older adults, several gaps remain as they were specific to a health condition and/or setting. The purpose of our scoping review is to map the extent of knowledge on this subject.

Methods and analysis

We will conduct our scoping review following Levac’s methodology. We will gather publications of various types through nine databases, manual searches in journals and search engines and reference lists. The selection process will be conducted by two independent reviewers and consist of screening by title and abstract, followed by reading the full text to confirm eligibility. An independent reviewer will then extract data and assess quality from included publications. Data extracted from different publication types will be synthesised together in the Excel software using a content analysis method, with quantitative data transformed into a qualitative description. Results will be presented through descriptive statistics and themes. During different steps of the review, we will also consult informal caregivers and health professionals for feedback as stakeholders.

Ethics and dissemination

The conduction of this scoping review requires no ethical approval. Results will provide an overview of the state of knowledge on the inclusion of informal caregivers in palliative and EOL of older adults, which could help guide clinical practice, the development of interventions and policy and further research. We will disseminate these results by publishing an article, presenting in conferences, and discussing findings with stakeholders.
Antiretroviral therapy uptake and predictors of virological failure in patients with HIV receiving first-line and second-line regimens in Johannesburg, South Africa: a retrospective cohort data analysis
Authors: Gumede Siphamandla Bonga , Venter Francois , de Wit John , Wensing Annemarie , Lalla-Edward Samanta Tresha
Published: April 2022

Objective

This study described the demographics, treatment information and identified characteristics associated with virological failure and being lost to follow-up (LTFU) for patients with HIV on first-line and second-line antiretroviral therapy (ART) regimens in a large South African cohort.

Design

A quantitative retrospective cohort study using secondary data analysis.

Setting

Seven Johannesburg inner city facilities.

Participants

Unique records of 123 002 people with HIV receiving ART at any point in the period 1 April 2004 to 29 February 2020 were included.

Measures

Demographic characteristics, ART status, CD4 count information and retention status were collected and analysed as covariates of outcomes (viral load (VL) and LTFU).

Results

Of the total study patients, 95% (n=1 17 260) were on a first-line regimen and 5% (n=5742) were on a second-line regimen. Almost two-thirds were female (64%, n=79 226). Most patients (60%, n=72 430) were initiated on an efavirenz-based, tenofovir disoproxil fumarate-based and emtricitabine-based regimen (fixed-dose combination). 91% (n=76 737) achieved viral suppression at least once since initiating on ART and 60% (n=57 981) remained in care as at the end of February 2020. Patients from the community health centre and primary healthcare clinics were not only more likely to be virally suppressed but also more likely to be LTFU. Patients on second-line regimens were less likely to reach viral suppression (adjusted OR (aOR)=0.26, CI=0.23 to 0.28) and more likely to be LTFU (aOR=1.21, CI=1.09 to 1.35). Being older (≥25 years) and having a recent CD4 cell count≥100 cells/µL were predictors of viral suppression and retention in patients on ART.

Conclusion

Patients on first-line regimens had higher VL suppression rates and were more likely to remain in care than those on a second-line regimen. Being younger and having low CD4 cell counts were associated with poor outcomes, suggesting priority groups for ART adherence support.