Rapid genomic sequencing (rGS) in critically ill infants with suspected genetic disorders has high diagnostic and clinical utility. However, rGS has primarily been available at large referral centres with the resources and expertise to offer state-of-the-art genomic care. Critically ill infants from racial and ethnic minority and/or low-income populations disproportionately receive care in safety-net and/or community settings lacking access to state-of-the-art genomic care, contributing to unacceptable health equity gaps. VIrtual GenOme CenteR is a ‘proof-of-concept’ implementation science study of an innovative delivery model for genomic care in safety-net neonatal intensive care units (NICUs).
We developed a virtual genome centre at a referral centre to remotely support safety-net NICU sites predominantly serving racial and ethnic minority and/or low-income populations and have limited to no access to rGS. Neonatal providers at each site receive basic education about genomic medicine from the study team and identify eligible infants. The study team enrols eligible infants (goal n of 250) and their parents and follows families for 12 months. Enrolled infants receive rGS, the study team creates clinical interpretive reports to guide neonatal providers on interpreting results, and neonatal providers return results to families. Data is collected via (1) medical record abstraction, (2) surveys, interviews and focus groups with neonatal providers and (3) surveys and interviews with families. We aim to examine comprehensive implementation outcomes based on the Proctor Implementation Framework using a mixed methods approach.
This study is approved by the institutional review board of Boston Children’s Hospital (IRB-P00040496) and participating sites. Participating families are required to provide electronic written informed consent and neonatal provider consent is implied through the completion of surveys. The results will be disseminated via peer-reviewed publications and data will be made accessible per National Institutes of Health (NIH) policies.
NCT05205356/clinicaltrials.gov.
To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome.
A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022.
The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID.
Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred.
During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life.
Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms.
In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients’ comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI: 1.01 to 1.04), COVID-19 severity (OR=0.42, 95% CI: 0.21 to 0.82), number of comorbidities (OR=1.22, 95% CI: 1.01 to 1.5), metabolic (OR=2.52, 95% CI: 1.25 to 5.27), pulmonary (OR=1.87, 95% CI: 1.10 to 3.32) and autoimmune diseases (OR=4.57, 95% CI: 1.57 to 19.41) increased the risk of the physical macro symptoms.
Being male was the unique protective factor in both waves. Other factors reflected different medical behaviours and the impact of comorbidities. Evidence of the effect of therapies adds valuable information that may drive future medical choices.
Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC).
This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1–3 and one meal/day in months 4–6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1–2 pounds per week.
The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563).
The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key BVAB (ie, Prevotella bivia, Fannyhessea vaginae) into the biofilm that alter the transcriptome of the polymicrobial consortium. This study will investigate the sequence of microbiologic events preceding iBV.
This study will enrol 150 women aged 18–45 years with normal vaginal microbiota and no sexually transmitted infections at a sexual health research clinic in Birmingham, Alabama. Women will self-collect twice daily vaginal specimens up to 60 days. A combination of 16S rRNA gene sequencing, qPCR for Gardnerella spp, P. bivia and F. vaginae, and broad range 16S rRNA gene qPCR will be performed on twice daily vaginal specimens from women with iBV (Nugent score 7–10 on at least 2 consecutive days) and controls (with comparable age, race, contraceptive method and menstrual cycle days) maintaining normal vaginal microbiota to investigate changes in the vaginal microbiota over time for women with iBV. Participants will complete daily diaries on multiple factors including sexual activity.
This protocol is approved by the University of Alabama at Birmingham Institutional Review Board (IRB-300004547) and written informed consent will be obtained from all participants. Findings will be presented at scientific conferences and published in peer-reviewed journals as well as disseminated to providers and patients in communities of interest.
Mental health disorders (MHD) rank third for US adult hospitalisations. Given the substantial prevalence of ‘Long COVID’ in SARS-CoV-2 survivors, this study aims to assess its association with increased MHD risk using extensive real-world data.
A retrospective cohort study with propensity score matching was conducted. We used the International Classification of Diseases, 10th Revision codes to identify individuals with Long COVID status and COVID-19 histories. Multivariable stratified Cox proportional hazards regression analysis was conducted to determine the association of Long COVID status with MHD.
Data were sourced from the TriNetX database, spanning records from 1 October 2021 to 16 April 2023.
Two distinct cohorts were established: one comprising individuals diagnosed with Long COVID and another comprising individuals with no history of Long COVID or COVID-19. At the start of the study, none of the participants had a recorded MHD.
The main outcome of interest was a composite diagnosis of MHD. Secondary outcomes were individual mental health conditions.
The study included 43 060 control participants without Long COVID and 4306 Long COVID participants, demonstrating well-balanced distribution across all covariates. After adjusting for 4 demographic factors and 10 comorbidities, Long COVID was associated with MHD (adjusted HR, aHR 2.60; 95% CI 2.37 to 2.85). In subgroup analysis, Long COVID was associated with major depression disorder (aHR 3.36; 95% CI 2.82 to 4.00) and generalised anxiety disorder (aHR 3.44; 95% CI 2.99 to 3.96).
In this retrospective large real-world cohort study, Long COVID was associated with an increased risk of incident MHD. The MHD impact is significant considering the vast number of patients with Long COVID. Enhanced MHD screening among COVID-19 survivors should be a priority.
Diagnosing invasive cutaneous melanoma (CM) can be challenging due to subjectivity in distinguishing equivocal nevi, melanoma in situ and thin CMs. The underlying molecular mechanisms of progression from nevus to melanoma must be better understood. Identifying biomarkers for treatment response, diagnostics and prognostics is crucial. Using biomedical data from biobanks and population-based healthcare data, translational research can improve patient care by implementing evidence-based findings. The BioMEL biobank is a prospective, multicentre, large-scale biomedical database on equivocal nevi and all stages of primary melanoma to metastases. Its purpose is to serve as a translational resource, enabling researchers to uncover objective molecular, genotypic, phenotypic and structural differences in nevi and all stages of melanoma. The main objective is to leverage BioMEL to significantly improve diagnostics, prognostics and therapy outcomes of patients with melanoma.
The BioMEL biobank contains biological samples, epidemiological information and medical data from adult patients who receive routine care for melanoma. BioMEL is focused on primary and metastatic melanoma, but equivocal pigmented lesions such as clinically atypical nevi and melanoma in situ are also included. BioMEL data are gathered by questionnaires, blood sampling, tumour imaging, tissue sampling, medical records and histopathological reports.
The BioMEL biobank project is approved by the national Swedish Ethical Review Authority (Dnr. 2013/101, 2013/339, 2020/00469, 2021/01432 and 2022/02421-02). The datasets generated are not publicly available due to regulations related to the ethical review authority.
The qualities of primary healthcare (PHC) make it a very relevant environment for research; however, there is still work to be done to enhance the research capabilities of family physicians in healthcare units. Considering there is no ongoing review that specifically addresses this objective, the proposed goal of this scoping review is to determine the depth of the literature on the current strategies that support research capacity building among family physicians in the context of PHC.
The scoping review will include studies from PubMed, Scopus, Web of Science, Cochrane Library and grey literature, published from 2008 to 2023, that address strategies to promote research capacity building among family physicians in the context of PHC. Only studies published in English, Portuguese or Spanish will be considered. All study designs, including quantitative, qualitative and mixed-methods studies, will be eligible for inclusion. The literature search will be performed from January to March of 2024 and data charting will employ a descriptive-analytical method, systematically summarising study objectives, methodologies, findings and implications. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and the review will employ the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews.
This review does not need ethical approval. Peer-reviewed publications, policy summaries, presentations at conferences and involvement with pertinent stakeholders are all part of our outreach approach.
To provide an overview of existing instruments measuring patient-perceived quality of nursing care and to develop and psychometrically evaluate a new multidimensional scale applicable to the German acute care sector.
We conducted a scale development and validation study involving the following phases: (1) performing a structured literature search to identify existing scales, (2) generating an initial pool of items using the results of the literature search and expert interviews, (3) coding/categorising the item pool, (4) organising a peer researcher workshop to select relevant items, (5) drafting the survey questionnaire and conducting cognitive pretesting, (6) pilot testing the survey questionnaire, (7) administering the survey to a large sample of hospital patients and (8) conducting a psychometric evaluation comprising exploratory factor analysis using the survey results, followed by confirmatory factor analysis and reliability and validity assessment of the resulting draft scale.
17 859 recently hospitalised patients discharged from non-intensive care in non-paediatric and non-psychiatric hospital units in Germany between May and October 2019.
We identified 32 instruments comprising 635 items on nursing care quality. Alongside 135 indicators derived from expert interviews, these formed our initial item pool, which we coded into 15 categories. From this pool, 36 items were selected in the peer researcher workshop for pretesting and psychometric evaluation. Based on the results of our exploratory and confirmatory factor analyses, we propose a second-order scale to measure Patients’ Experience of Nursing Quality in Acute Hospitals (PENQuAH), including the two higher-order dimensions ‘patients’ perception of direct nursing care activities’ and ‘patients’ perception of guidance provided by nurses’. The results of various tests suggest the scale has sufficient goodness of fit, reliability and validity.
The PENQuAH scale is promising in terms of its psychometric properties, the plausibility and meaningfulness of its dimensions, and its ease of use.
Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.
In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.
The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.
To our knowledge, this study is the first to identify and describe current sepsis policies, clinical practice guidelines, and health professional training standards in Canada to inform evidence-based policy recommendations.
This study will be designed and reported according to the Arksey and O’Malley framework for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. EMBASE, CINAHL, Medline, Turning Research Into Practice and Policy Commons will be searched for policies, clinical practice guidelines and health professional training standards published or updated in 2010 onwards, and related to the identification, management or reporting of sepsis in Canada. Additional sources of evidence will be identified by searching the websites of Canadian organisations responsible for regulating the training of healthcare professionals and reporting health outcomes. All potentially eligible sources of evidence will be reviewed for inclusion, followed by data extraction, independently and in duplicate. The included policies will be collated and summarised to inform future evidence-based sepsis policy recommendations.
The proposed study does not require ethics approval. The results of the study will be submitted for publication in a peer-reviewed journal and presented at local, national and international forums.
The study sought to explore the perceptions and attitudes of women in the perinatal period towards the reproductive health services of male midwives.
The study adopted an in-depth exploratory descriptive design for data collection and themes extracted using thematic analysis.
Antenatal and postpartum units of two primary healthcare facilities in the Kwabre-East District of Ghana.
20 women in the perinatal period who were receiving antenatal care and delivery services from the facilities included in the study were recruited through purposive sampling.
Divergent views emerged among our participants regarding the acceptability and utilisation of perinatal services provided by male midwives. Some participants perceived male midwives as patient, supportive, caring, compassionate and skilful at their work while the negative attitude related to some participants perceiving their interactions with male midwives as an opportunity for sexual violation. Positive attitudes emanated from male midwives’ empathetic behaviour, reception, privacy and confidentiality of information. Conversely, negative attitudes arose from a lack of awareness of the changing female gender domination in midwifery, fear and misconceptions. Finally, participants faced various challenges, rooted in culture, which impacted their acceptance of male midwifery services.
Factors influencing participants’ negative perceptions and attitudes towards male midwives were born out of culturally motivated and gender-sensitive stereotyping rather than male professional midwifery competencies. The study outcome provides the basis and the need for a community-based intervention to effect changes in the perception and attitude of women in the perinatal period towards male midwifery practice in the affected communities. Increasing awareness of the existence of male midwives in the communities would contribute to increasing acceptance and utilisation of their services among women in the perinatal period in Ghana.
The aim of this study was to refine a draft of the ACTiON FALLS LD programme based on the views of adults with an intellectual disability (AWID), carers and healthcare professionals (HCPs).
The semistructured interview study included HCP as well as AWID and carers supporting AWID living in the community. Community settings included sheltered living, supported living, AWID living at home with family carers or independently. The interview study explored the first draft of the ACTiON FALLS LD programme as well as the wider falls management for AWID. Interviews with AWID were developed to include a range of approaches (eg, case studies, pictures) to support inclusive participation. Individual interviews were digitally recorded and transcribed. Researcher notes were used during interviews with AWID. All data were analysed using the principles of framework analysis.
14 HCP, 8 carers and 13 AWID took part in the interview process. Five key themes were identified: programme components, programme design, programme approach, who would use the programme and programme delivery.
The views of AWID, HCP and carers showed the need to consider the impact of risk perception, anxiety and fear of falling in the adaption of the ACTiON FALLS programme. The programme needs to be accessible and support the inclusion of AWID in managing falls and ultimately fulfil the requirement for a proactive and educational tool by all.
Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual’s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia.
This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes.
The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals.
by Stephanie E. Martinez, Amit V. Pandey, Tania E. Perez Jimenez, Zhaohui Zhu, Michael H. Court
Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds. However, CYP2B11 gene variants associated with decreased CYP2B11 expression do not fully explain reduced CYP2B11 activity in this breed. P450 oxidoreductase (POR) is an essential redox partner for all CYPs. POR protein variants can enhance or repress CYP enzyme function in a CYP isoform and substrate dependent manner. The study objectives were to identify POR protein variants in greyhounds and determine their effect on coexpressed CYP2B11 and CYP2D15 enzyme function. Gene sequencing identified two missense variants (Glu315Gln and Asp570Glu) forming four alleles, POR-H1 (reference), POR-H2 (570Glu), POR-H3 (315Gln, 570Glu) and POR-H4 (315Gln). Out of 68 dog breeds surveyed, POR-H2 was widely distributed across multiple breeds, while POR-H3 was largely restricted to greyhounds and Scottish deerhounds (35% allele frequencies), and POR-H4 was rare. Three-dimensional protein structure modelling indicated significant effects of Glu315Gln (but not Asp570Glu) on protein flexibility through loss of a salt bridge between Glu315 and Arg519. Recombinant POR-H1 (reference) and each POR variant (H2-H4) were expressed alone or with CYP2B11 or CYP2D15 in insect cells. No substantial effects on POR protein expression or enzyme activity (cytochrome c reduction) were observed for any POR variant (versus POR-H1) when expressed alone or with CYP2B11 or CYP2D15. Furthermore, there were no effects on CYP2B11 or CYP2D15 protein expression, or on CYP2D15 enzyme kinetics by any POR variant (versus POR-H1). However, Vmax values for 7-benzyloxyresorufin, propofol and bupropion oxidation by CYP2B11 were significantly reduced by coexpression with POR-H3 (by 34–37%) and POR-H4 (by 65–72%) compared with POR-H1. Km values were unaffected. Our results indicate that the Glu315Gln mutation (common to POR-H3 and POR-H4) reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings.by Christoph Wies, Lucas Schneider, Sarah Haggenmüller, Tabea-Clara Bucher, Sarah Hobelsberger, Markus V. Heppt, Gerardo Ferrara, Eva I. Krieghoff-Henning, Titus J. Brinker
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.by Jake V. Hinton, Calvin M. Fletcher, Luke A. Perry, Noah Greifer, Jessica N. Hinton, Jenni Williams-Spence, Reny Segal, Julian A. Smith, Christopher M. Reid, Laurence Weinberg, Rinaldo Bellomo
BackgroundPlatelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown.
MethodsWe conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005–2021 across 58 sites were included. The primary outcome was operative mortality.
ResultsOf 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P Conclusion
In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.
Recent evidence supports that gynaecomastia may predict long-term morbidity, but evidence on the association with death and causes of death in males with gynaecomastia is lacking. The objective of this work is to estimate the risk of death in men diagnosed with gynaecomastia and evaluate whether this was conditional on underlying aetiologies of gynaecomastia.
A nationwide register-based cohort study.
Nationwide Danish national health registries.
Males were diagnosed with incident gynaecomastia (n=23 429) from 1 January 1995 to 30 June 2021, and each was age and calendar matched to five randomly population-based males without gynaecomastia (n=117 145).
Not applicable.
Gynaecomastia was distinguished between males without (idiopathic) and males with a known pre-existing risk factor. Cox regression models and Kaplan-Meier analyses estimated associations between gynaecomastia and death (all cause/cause specific).
We identified a total of 16 253 males with idiopathic gynaecomastia and 7176 with gynaecomastia and a known pre-existing risk factor. Of these, 1093 (6.7%) and 1501 (20.9%) died during follow-up, respectively. We detected a 37% increased risk of all-cause death in males with gynaecomastia in the entire cohort (HR 1.37; 95% CI 1.31 to 1.43). Death risk was highest in males diagnosed with gynaecomastia and a known pre-existing risk factor (HR 1.75; 95% CI 1.64 to 1.86) compared with males with idiopathic gynaecomastia (HR 1.05; 95% CI 0.98 to 1.13). Specific causes of increased death were malignant neoplasms and circulatory, pulmonary and gastrointestinal diseases. Of the latter, an over fivefold risk of death from liver disease was detected (HR 5.05; 95% CI 3.97 to 6.42).
Males diagnosed with gynaecomastia are at higher risk of death, observed mainly in males with a known pre-existing risk factor of gynaecomastia. These findings will hopefully stimulate more awareness among healthcare providers to potentially apply interventions that aid in alleviating underlying risk factors in males with this condition.
by Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Vijay H. Masand, Rahul G. Ingle, Vivek Digamber Rathod, Nikita Maruti Gaikwad, Summya Rashid, Pravin N. Khatale, Pramod V. Burakale, Rahul D. Jawarkar
Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R2 = 0.800–793, Q2LOO = 0.734–0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit’s docking score (-8.208 kcal/mol) and PIC50 (7.85 M) demonstrated a significant affinity for SARS-CoV-2’s main protease. Based on post-covid neurodegenerative episodes in Alzheimer’s and Parkinson’s-like disorders and MAO-B’s role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2’s primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR’s COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.by Chris Bradley, Kaihua Hou, Patrick Herbert, Mathias Unberath, Greg Hager, Michael V. Boland, Pradeep Ramulu, Jithin Yohannan
Linear regression of optical coherence tomography measurements of peripapillary retinal nerve fiber layer thickness is often used to detect glaucoma progression and forecast future disease course. However, current measurement frequencies suggest that clinicians often apply linear regression to a relatively small number of measurements (e.g., less than a handful). In this study, we estimate the accuracy of linear regression in predicting the next reliable measurement of average retinal nerve fiber layer thickness using Zeiss Cirrus optical coherence tomography measurements of average retinal nerve fiber layer thickness from a sample of 6,471 eyes with glaucoma or glaucoma-suspect status. Linear regression is compared to two null models: no glaucoma worsening, and worsening due to aging. Linear regression on the first M ≥ 2 measurements was significantly worse at predicting a reliable M+1st measurement for 2 ≤ M ≤ 6. This range was reduced to 2 ≤ M ≤ 5 when retinal nerve fiber layer thickness measurements were first “corrected” for scan quality. Simulations based on measurement frequencies in our sample—on average 393 ± 190 days between consecutive measurements—show that linear regression outperforms both null models when M ≥ 5 and the goal is to forecast moderate (75th percentile) worsening, and when M ≥ 3 for rapid (90th percentile) worsening. If linear regression is used to assess disease trajectory with a small number of measurements over short time periods (e.g., 1–2 years), as is often the case in clinical practice, the number of optical coherence tomography examinations needs to be increased.