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Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review

Por: Benade · M. · Maskew · M. · Juntunen · A. · Flynn · D. B. · Rosen · S.
Objectives

As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation.

Design

Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa.

Data sources

PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences.

Eligibility criteria

Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure.

Data extraction and synthesis

We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature.

Results

Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret.

Conclusions

The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%–50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure.

PROSPERO registration number

CRD42022324136.

Association of antecedent statin use on 30-day, 60-day and 90-day mortality among Mississippi Medicaid beneficiaries diagnosed with COVID-19

Por: Rong · Y. · Goswami · S. · Eriakha · O. · Ramachandran · S. · Bentley · J. · Banahan · B. F. · Kirby · T. · Smith · D. · Pittman · E. · Bhattacharya · K.
Objective

To assess if the antecedent statin use was associated with all-cause death among COVID-19 patients enrolled in Medicaid.

Design

Cohort study.

Setting

Mississippi Medicaid population.

Participants

This study included 10 792 Mississippi Medicaid-enrolled patients between 18 and 64 years of age with a confirmed COVID-19 diagnosis from March 2020 to June 2021.

Intervention

Antecedent statin use, which was determined by a record of statin prescription in the 90-day period prior to the COVID diagnosis.

Main outcome measures

The outcomes of interest included mortality from all cause within 30 days, 60 days and 90 days after index.

Results

A total of 10 792 patients with COVID-19 met the inclusion and exclusion criteria, with 13.1% of them being antecedent statin users. Statin users were matched 1:1 with non-users based on age, sex, race, comorbidities and medication use by propensity score matching. In total, the matched cohort consisted of 1107 beneficiaries in each group. Multivariable logistic regression showed that statin users were less likely to die within 30 days (adjusted OR: 0.51, 95% CI: 0.32 to 0.83), 60 days (OR: 0.56, 95% CI: 0.37 to 0.85) and 90 days (OR: 0.55, 95% CI: 0.37 to 0.82) after diagnosis of COVID-19. Those with low-intensity/moderate-intensity statin use had significantly lower mortality risk in the 60-day and the 90-day follow-up period, while the high intensity of statin use was only found to be significantly associated with a lower odd of mortality within 30 days post index.

Conclusion

After COVID infection, Medicaid beneficiaries who had taken statins antecedently could be at lower risk for death. For patients with chronic conditions, continuity of care is crucial when interruptions occur in their medical care. Further research is required to further investigate the potential mechanisms and optimal use of statins in COVID-19 treatment.

Predictors of outcome in sciatica patients following an epidural steroid injection: the POiSE prospective observational cohort study protocol

Por: Stynes · S. · Snell · K. I. · Riley · R. D. · Konstantinou · K. · Cherrington · A. · Daud · N. · Ostelo · R. · O'Dowd · J. · Foster · N. E.
Introduction

Sciatica can be very painful and, in most cases, is due to pressure on a spinal nerve root from a disc herniation with associated inflammation. For some patients, the pain persists, and one management option is a spinal epidural steroid injection (ESI). The aim of an ESI is to relieve leg pain, improve function and reduce the need for surgery. ESIs work well in some patients but not in others, but we cannot identify these patient subgroups currently. This study aims to identify factors, including patient characteristics, clinical examination and imaging findings, that help in predicting who does well and who does not after an ESI. The overall objective is to develop a prognostic model to support individualised patient and clinical decision-making regarding ESI.

Methods

POiSE is a prospective cohort study of 439 patients with sciatica referred by their clinician for an ESI. Participants will receive weekly text messages until 12 weeks following their ESIand then again at 24 weeks following their ESI to collect data on leg pain severity. Questionnaires will be sent to participants at baseline, 6, 12 and 24 weeks after their ESI to collect data on pain, disability, recovery and additional interventions. The prognosis for the cohort will be described. The primary outcome measure for the prognostic model is leg pain at 6 weeks. Prognostic models will also be developed for secondary outcomes of disability and recovery at 6 weeks and additional interventions at 24 weeks following ESI. Statistical analyses will include multivariable linear and logistic regression with mixed effects model.

Ethics and dissemination

The POiSE study has received ethical approval (South Central Berkshire B Research Ethics Committee 21/SC/0257). Dissemination will be guided by our patient and public engagement group and will include scientific publications, conference presentations and social media.

Incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first seven days in Northwest Ethiopia Comprehensive Specialized Hospitals, 2023: A retrospective follow-up study

Por: Wondie · W. T. · Legesse · B. T. · Mekonnen · G. B. · Degaga · G. T. · Zemariam · A. B. · Gedefaw · G. D. · Abebe · D. E. · Kassie · Y. T. · Gonete · A. T. · Belay · A. E. · Wubneh · C. A.
Introduction

Respiratory distress syndrome is a catastrophic respiratory problem among low birth weight neonates. It increases the suffering of neonates and the economic expenditure of the countries. Notably, it is a major public health issue in low-income and middle-income countries such as Ethiopia. Despite this, studies regarding respiratory distress syndrome among low birth weight neonates were limited in Ethiopia.

Objective

To assess the incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first 7 days in Northwest Ethiopia Comprehensive Specialized Hospitals.

Method

Multicentred institution-based retrospective follow-up study was conducted from 19 September 2021 to 1 January 2023, among 423 low birthweight neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.6. and analysed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Weibull regression was carried out to identify predictors of respiratory distress syndrome. Statistical significance was declared at a p≤0.05.

Result

The incidence rate of respiratory distress syndrome was found to be 10.78 (95% CI 9.35 to 12.42) per 100 neonate days. Fifth minute Appearance, Pulse, Grimace, Activity, Respiration (APGAR score)

Conclusion

The incidence of respiratory distress syndrome was higher than other studies conducted on other groups of neonates. Multiple pregnancy, fifth minute APGAR score, caesarean section, prematurity, extremely low birth weight and very low birth weight were predictors of respiratory distress syndrome. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention for these predictors.

Impact of deintensifying hypoglycaemic drugs in older adults with type 2 diabetes: protocol for an emulation of a target trial

Por: Christiaens · A. · Simon-Tillaux · N. · Thompson · W. · Sinclair · A. J. · Henrard · S. · Boland · B. B. · Slaouti-Jegou · Y. · Lekens · B. · Bonnet-Zamponi · D. · Tubach · F. · Zerah · L.
Introduction

In older adults with type 2 diabetes (T2D), overtreatment with hypoglycaemic drugs (HDs: sulfonylureas, glinides and/or insulins) is frequent and associated with increased 1-year mortality. Deintensification of HD is thus a key issue, for which evidence is though limited. The primary objective of this study will be to estimate the effect of deintensifying HD on clinical outcomes (hospital admission or death) within 3 months in older adults (≥75 years) with T2D.

Methods

We will emulate with real-world data a target trial, within The Health Improvement Network cohort, a large-scale database of data collected from electronic medical records of 2000 general practitioners in France. From 1 January 2010 to 28 February 2019, we will include eligible patients ≥75 years who will have T2D, a stable dose of HDs, glycated haemoglobin A1c (HbA1c) value 75 mmol/mol within 1 year. Participants will be followed from baseline to 12 months after randomisation, administrative censoring, or death, whichever occurs first. A pooled logistic regression will be used to estimate the treatment effect on the incidence of the outcomes.

Dissemination and ethics

No ethical approval is needed for using retrospectively this fully anonymised database. The results will be disseminated during conferences and through publications in scientific journals.

Cohort profile: the United Kingdom Childhood Cancer Study (UKCCS) - a UK-wide population-based study examining the health of cancer survivors

Por: Roman · E. · Kane · E. · Smith · A. · Howell · D. · Sheridan · R. · Simpson · J. · Bonaventure · A. · Kinsey · S.
Purpose

The United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age, comparing future healthcare patterns in 5-year cancer survivors to baseline activity seen in age- and sex-matched individuals from the general population.

Participants

Predicated on a national childhood cancer case-control study conducted in the early 1990s (4430 cases, 9753 controls) in England, Scotland and Wales, the case population comprises 3125 cancer survivors (>5 years), and the control population 7156 age- and sex-matched individuals from the general population who did not have cancer as a child. Participants are now being followed up via linkage to national administrative healthcare databases (deaths, cancers and secondary care hospital activity).

Findings to date

Enabling the creation of cohorts with minimal selection bias and loss to follow-up, the original case-control study registered all newly diagnosed cases of childhood cancer and their corresponding controls, regardless of their family’s participation. Early findings based on the registered case population found marked survival variations with age and sex across subtypes and differences with deprivation among acute lymphoblastic leukaemia (ALL) survivors. More recently, comparing the health-activity patterns of the case and control populations revealed that survivors of childhood ALL experienced excess outpatient and inpatient activity across their teenage/young adult years. Adding to increased risks of cancer and death and involving most clinical specialties, excesses were not related to routine follow-up monitoring and showed no signs of diminishing over time.

Future plans

With annual linkage updates, the UKCCS’s maturing population-based matched cohorts provide the foundation for tracking the health of individuals through their lifetime. Comparing the experience of childhood cancer survivors to that of unaffected general-population counterparts, this will include examining subsequent morbidity and mortality, secondary care hospital activity and the impact of deprivation on longer term outcomes.

Can online and app-based interventions be used by people with diabetes to reduce diabetes distress? A protocol for a scoping review

Por: Andersen · C. M. · Mathiesen · A. S. · Pouwer · F. · Mouritsen · J. D. · Mathiasen · K. · Rothmann · M. J.
Introduction

Diabetes distress has been defined as "the negative emotional or affective experience resulting from the challenge of living with the demands of diabetes". Diabetes distress affects 20%–25% of individuals living with diabetes and can have negative effects on both diabetes regulation and quality of life. For people living with diabetes distress, innovative tools/interventions such as online or app-based interventions may potentially alleviate diabetes distress in a cost-effective way. The specific research questions of this scoping review are: (1) what are the effects of online or app-based interventions on diabetes distress for adults with type 1 or type 2 diabetes, and (2) what are the characteristics of these interventions (eg, type of intervention, duration, frequency, mode of delivery, underlying theories and working mechanisms)?

Methods and analysis

A scoping review will be conducted, using the methodological framework of Arksey and O’Malley along with Levac et al. Eligible studies are: studies of adults ≥18 years old with type 1 or 2 diabetes using an online or app-based intervention and assessing diabetes distress as the primary or secondary outcome. Five databases (Medline, EMBASE, CINAHL, PsycINFO and Scopus) will be searched and is limited to articles written in English, Danish, Norwegian, Swedish or Dutch. Two reviewers will independently screen potentially eligible studies in Covidence, select studies, and together chart data, collate, summarise, and report the results. We will adhere to the Preferred reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR).

Ethics and dissemination

The scoping review has been exempt from full ethical review by the Regional Committees on Health Research Ethics for Southern Denmark (case number: S-20232000-88). The results of the review will be published in a peer-reviewed journal and presented at relevant conferences and workshops with relevant stakeholders.

Hospital variations in failure to rescue after abdominal surgery: a nationwide, retrospective observational study

Por: Augestad · K. M. · Skyrud · K. D. · Lindahl · A. K. · Helgeland · J.
Objectives

This study aims to determine hospital variation and intensive care unit characteristics associated with failure to rescue after abdominal surgery in Norway.

Design

A nationwide retrospective observational study.

Setting

All 52 hospitals in Norway performing elective and acute abdominal surgery.

Participants

All 598 736 patients undergoing emergency and elective abdominal surgery from 2011 to 2021.

Primary outcome measure

Primary outcome was failure to rescue within 30 days (FTR30), defined as in-hospital or out-of-hospital death within 30 days of a surgical patient who developed at least one complication within 30 days of the surgery (FTR30). Other outcome variables were surgical complications and hospital FTR30 variation. Statistical analysis was conducted separately for general surgery and abdominal surgery.

Results

The 30-day postoperative complication rate was 30.7 (183 560 of 598 736 surgeries). Of general surgical complications (n=25 775), circulatory collapse (n=6127, 23%), cardiac arrhythmia (n=5646, 21%) and surgical infections (n=4334, 16 %) were most common and 1507 (5.8 %) patients were reoperated within 30 days. One thousand seven hundred and forty patients had FTR30 (6.7 %). The severity of complications was strongly associated with FTR30. In multivariate analysis of general surgery, adjusted for patient characteristics, only the year of surgery was associated with FTR30, with an estimated linear trend of –0.31 percentage units per year (95% CI (–0.48 to –0.15)). The driving distance from local hospitals to the nearest referral intensive care unit was not associated with FTR30. Over the last decade, FTR30 rates have varied significantly among similar hospitals.

Conclusions

Hospital factors cannot explain Norwegian hospitals’ significant FTR variance when adjusting for patient characteristics. The national FTR30 measure has dropped around 30% without a corresponding fall in surgical complications. No association was seen between rural hospital location and FTR30. Policy-makers must address microsystem issues causing high FTR30 in hospitals.

Measuring under-5 mortality and fertility through mobile phone surveys: an assessment of selection bias in 34 low-income and middle-income countries

Por: Sanchez-Paez · D. A. · Masquelier · B. · Menashe-Oren · A. · Baruwa · O. J. · Reniers · G.
Objectives

This study aims to assess sample selection bias in mobile phone survey estimates of fertility and under-5 mortality.

Design

With data from the Demographic and Health Surveys, we use logistic regressions to identify sociodemographic correlates of mobile phone ownership and access, and Poisson regressions to estimate the association between mobile phone ownership (or access) and fertility and under-5 mortality estimates. We evaluate the potential reasons why estimates by mobile phone ownership differ using a set of behavioural characteristics.

Setting

34 low-income and middle-income countries, mostly in sub-Saharan Africa.

Participants

534 536 women between the ages of 15 and 49.

Outcome measures

Under-5 mortality rate (U5MR) and total fertility rate (TFR).

Results

Mobile phone ownership ranges from 23.6% in Burundi to 96.7% in Armenia. The median TFR ratio and U5MR ratio between the non-owners and the owners of a mobile phone are 1.48 and 1.29, respectively. Fertility and mortality rates would be biased downwards if estimates are only based on women who own or have access to mobile phones. Estimates of U5MR can be adjusted through poststratification using age, educational level, area of residence, wealth and marital status as weights. However, estimates of TFR remain biased even after adjusting for these covariates. This difference is associated with behavioural factors (eg, contraceptive use) that are not captured by the poststratification variables, but for which there are also differences between mobile phone owners and non-owners.

Conclusions

Mobile phone surveys need to collect data on sociodemographic background characteristics to be able to weight and adjust mortality estimates ex post facto. Fertility estimates from mobile phone surveys will be biased unless further research uncovers the mechanisms driving the bias.

Tight perioperative blood pressure management to reduce complications: a randomised feasibility trial

Por: Li · K. · Hu · Z. · Li · W. · Shah · K. · Sessler · D.
Objective

Evaluate the feasibility of a trial of perioperative hypotension and serious complications.

Design

A patient and assessor-blinded randomised feasibility trial.

Setting

We included patients in a tertiary university hospital.

Participants

We enrolled 80 adults scheduled for major non-cardiac surgery.

Interventions

In patients randomised to tight blood pressure control, intraoperative mean arterial pressure (MAP) was targeted to ≥85 mm Hg maintained with norepinephrine infusion, and restarting chronic antihypertensive medications was delayed until the third postoperative day. In the reference group, intraoperative blood pressure was managed per routine and antihypertensive medications were restarted immediately after surgery.

Primary and secondary outcome measures

Our first co-primary outcome was the fraction of time when intraoperative MAP was >85 mm Hg, intraoperative area (time integral) of MAP >85 mm Hg and MAP

Results

Forty patients in each group were analysed. The median for intraoperative area of MAP >85 mm Hg was 1303 (772–2419) mm Hg*min in routine blood pressure (BP) cases and 2425 (1926–3545) mm Hg*min in tight BP control. The area for intraoperative MAP 85 mm Hg was 0.52 (0.25) and 0.87 (0.15). Antihypertensive medications were restarted 2 (1–3) days later in tight BP control cases. However, postoperative SBPs were similar.

Conclusions

Tight BP management markedly increased intraoperative MAP and reduced the amount of hypotension. In contrast, delaying chronic antihypertensive medications had little effect on postoperative SBP. The full trial appears feasible and remains necessary but should not include postoperative antihypertensive management.

Trial registration

NCT04789733.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic

Por: Kennalley · A. L. · Fanelli · J. L. · Furst · J. A. · Mynarski · N. J. · Jarvis · M. A. · Nichols · S. D. · McCall · K. L. · Piper · B. J.
Objectives

Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic.

Design

Retrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases.

Setting

USA.

Participants

Patients who were dispensed methadone at US opioid treatment programmes (OTPs).

Primary and secondary outcome measures

The primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone.

Results

Methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p

Conclusions

There have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.

Community perceptions matter: a mixed-methods study using local knowledge to define features of success for a community intervention to improve quality of care for children under-5 in Jigawa, Nigeria

Por: Iuliano · A. · Shittu · F. · Colbourn · T. · Salako · J. · Bakare · D. · Bakare · A. A. A. · King · C. · Graham · H. · McCollum · E. D. · Falade · A. G. · Uchendu · O. · Haruna · I. · Valentine · P. · Burgess · R.
Objectives

In this study, we used the information generated by community members during an intervention design process to understand the features needed for a successful community participatory intervention to improve child health.

Design

We conducted a concurrent mixed-methods study (November 2019–March 2020) to inform the design and evaluation of a community–facility linkage participatory intervention.

Setting

Kiyawa Local Government Area (Jigawa State, Nigeria)—population of 230 000 (n=425 villages).

Participants

Qualitative data included 12 community conversations with caregivers of children under-5 (men, older and younger women; n=9 per group), 3 focus group discussions (n=10) with ward development committee members and interviews with facility heads (n=3). Quantitative data comprised household surveys (n=3464) with compound heads (n=1803) and women (n=1661).

Results

We analysed qualitative data with thematic network analysis and the surveys with linear regression—results were triangulated in the interpretation phase. Participants identified the following areas of focus: community health education; facility infrastructure, equipment and staff improvements; raising funds to make these changes. Community involvement, cooperation and empowerment were recognised as a strategy to improve child health, and the presence of intermediate bodies (development committees) was deemed important to improve communication and solve problems between community and facility members. The survey showed functional community relations’ dynamics, with high levels of internal cohesion (78%), efficacy in solving problems together (79%) and fairness of the local leaders (82%).

Conclusions

Combining the results from this study and critical theories on successful participation identified community-informed features for a contextually tailored community–facility link intervention. The need to promote a more inclusive approach to future child health interventions was highlighted. In addition to health education campaigns, the relationship between community and healthcare providers needs strengthening, and development committees were identified as an essential feature for successfully linking communities and facilities for child health.

Trial registration number

ISRCTN39213655.

Relationship between diabetic knowledge, attitudes and practices among patients with diabetes in China: a structural equation model

Por: Zhu · W. · Liang · D. · Petersen · J. D. · Zhang · W. · Huang · J. · Dong · Y.
Objectives

Whether the routine delivery of diabetes-related knowledge can change patients’ attitudes and hence influence their self-management activities remains unknown in primary healthcare settings in China. Thus, this study aims to explore the complex transformation process between knowledge, attitude and practice (KAP) among patients with diabetes in a city in China.

Design

A cross-sectional study.

Setting

Yuhuan City, Zhejiang Province, China.

Participants

A total of 803 patients with diabetes were invited to attend a questionnaire survey and 782 patients with type 2 diabetes completed the survey. The average age of participants was 58.47 years old, 48.21% of whom only attended primary school or below.

Primary and secondary outcome measures

A questionnaire based on existing scales and expert consultation was applied to assess patients’ socio-demographic information (SI), disease progression risk and diabetes-related KAP. A structural equation model was built to analyse the relationships between patients’ characteristics and KAP.

Results

No significant association was found between patients’ knowledge and attitude (β=0.01, p=0.43). Better knowledge and attitude were both found to be associated with better diet and physical activities (β=0.58, p

Conclusions

While successful KAP transformation has been achieved in practice for diet and physical activities, there is a need to improve foot care practice. Health education should also prioritise the prevention, detection and care of diabetic foot. Also, appropriate methods should be adopted to deliver health education to vulnerable patients, such as the elderly, those living in rural areas, those with minimal education, the unemployed and low-income patients.

In silico exploration of <i>Serratia</i> sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin

by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Altered serum TNF-α and MCP-4 levels are associated with the pathophysiology of major depressive disorder: A case-control study results

by Jannatul Nayem, Rapty Sarker, A. S. M. Roknuzzaman, M. M. A. Shalahuddin Qusar, Sheikh Zahir Raihan, Md. Rabiul Islam, Zobaer Al Mahmud

Background

Major Depressive Disorder (MDD) is a debilitating mental health condition with complex etiology, and recent research has focused on pro-inflammatory cytokines and chemokines as potential contributors to its pathogenesis. However, studies investigating the roles of TNF-α and MCP-4 in MDD within the Bangladeshi population are scarce. This study aimed to assess the association between serum TNF-α and MCP-4 levels and the severity of MDD, exploring their potential as risk indicators for MDD development.

Methods

This case-control study enrolled 58 MDD patients from Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh, alongside 30 age, sex, and BMI-matched healthy controls. MDD diagnosis followed DSM-5 criteria and disease severity using the 17-item Hamilton Depression Rating Scale (Ham-D). We measured serum TNF-α and MCP-4 levels using ELISA assays according to the supplied protocols.

Results

The study revealed significantly elevated serum TNF-α levels in MDD patients (47±6.6 pg/ml, mean±SEM) compared to controls (28.06±1.07 pg/ml). These increased TNF-α levels positively correlated with Ham-D scores (Pearson’s r = 0.300, p = 0.038), suggesting a potential association between peripheral TNF-α levels and MDD pathology. Additionally, MDD patients exhibited significantly higher serum MCP-4 levels (70.49±6.45 pg/ml) than controls (40.21±4.08 pg/ml). However, serum MCP-4 levels showed a significant negative correlation (r = -0.270, P = 0.048) with Ham-D scores in MDD patients, indicating a more complex role for MCP-4 in MDD pathogenesis.

Conclusion

This study highlights that Bangladeshi MDD patients exhibit heightened inflammatory and immune responses compared to controls, supporting the cytokine hypothesis in MDD pathogenesis. Serum TNF-α, but not MCP-4, shows promise as a potential biomarker for assessing the risk of MDD development, which could aid in early detection. Future investigations involving larger populations and longitudinal studies are essential to confirm the utility of these cytokines as biomarkers for MDD.

Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR)

Por: Mishra · N. K. · Kwan · P. · Tanaka · T. · Sunnerhagen · K. S. · Dawson · J. · Zhao · Y. · Misra · S. · Wang · S. · Sharma · V. K. · Mazumder · R. · Funaro · M. C. · Ihara · M. · Nicolo · J.-P. · Liebeskind · D. S. · Yasuda · C. L. · Cendes · F. · Quinn · T. J. · Ge · Z. · Scalzo · F. · Zela
Introduction

Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research.

Methods and analysis

We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE.

Ethics and dissemination

Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials.

Trial registration number

NCT06108102

Determinants of practice for providing decision coaching to facilitate informed values-based decision-making: protocol for a mixed-methods systematic review

Por: Berger-Höger · B. · Lewis · K. B. · Cherry · K. · Finderup · J. · Gunderson · J. · Kaden · J. · Kienlin · S. · Rahn · A. C. · Sikora · L. · Stacey · D. · Steckelberg · A. · Zhao · J.
Introduction

Decision coaching is a non-directive approach to support patients to prepare for making health decisions. It is used to facilitate patients’ involvement in informed values-based decision-making and use of evidence-based health information. A recent systematic review revealed low certainty evidence for its effectiveness with and without evidence-based information. However, there may be opportunities to improve the study and use of decision coaching in clinical practice by systematically investigating its determinants of practice. We aim to conduct a systematic review to identify and synthesise the determinants of practice for providing decision coaching to facilitate patient involvement in decision-making from multiple perspectives that influence its use.

Methods and analysis

We will conduct a mixed-methods systematic review guided by the Cochrane’ Handbook of Systematic Reviews. We will include studies reporting determinants of practice influencing decision coaching with or without evidence-based patient information with adults making a health decision for themselves or a family member. Systematic literature searches will be conducted in Medline, EMBASE, Cochrane CENTRAL and PsycINFO via Ovid and CINAHL via EBSCO including quantitative, qualitative and mixed-methods study designs. Additionally, experts in the field will be contacted.

Two reviewers will independently screen and extract data. We will synthesise determinants using deductive and inductive qualitative content analysis and a coding frame developed specifically for this review based on a taxonomy of barriers and enablers of shared decision-making mapped onto the major domains of the Consolidated Framework for Implementation Research. We will assess the quality of included studies using the Mixed Methods Appraisal Tool.

Ethics and dissemination

Ethical approval is not required as this systematic review involves only previously published literature. The results will be published in a peer-reviewed journal, presented at scientific conferences and disseminated to relevant consumer groups.

PROSPERO registration number

CRD42022338299.

Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial

Por: Molina Hidalgo · C. · Collins · A. M. · Crisafio · M. E. · Grove · G. · Kamarck · T. W. · Kang · C. · Leckie · R. L. · MacDonald · M. · Manuck · S. B. · Marsland · A. L. · Muldoon · M. F. · Rasero · J. · Scudder · M. R. · Velazquez-Diaz · D. · Verstynen · T. · Wan · L. · Gianaros · P. J
Introduction

Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk.

Methods and analysis

In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain–body interactions in the context of cardiovascular health.

Ethics and dissemination

Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.

Trial registration number

NCT03841669.

Health-related quality of life and associated factors among patients with schizophrenia at comprehensive specialised hospitals in the Northwest Ethiopia: a multicentre cross-sectional study

Por: Tamene · F. B. · Sema · F. D. · Mihiretie · E. A. · Siyum · T. S. · Sendekie · A. K.
Objectives

The aim of this study was to assess the health-related quality of life (HRQoL) and associated factors among patients with schizophrenia at comprehensive specialised hospitals in Northwest Ethiopia.

Design and setting

A cross-sectional study was conducted among 422 patients with schizophrenia who were followed at comprehensive specialised hospitals in Northwest Ethiopia from 1 June to 30 August 2022.

Participants

All adult patients with schizophrenia who had regular follow-up in the outpatient departments of the selected hospitals were study participants.

Main outcome measures

The main outcome of this study was HRQoL which was measured using the WHO Quality of Life Scale–Bref Version. Data entry and analysis were done using Epi-data version 4.6.1 and SPSS version 24, respectively. Linear regression was used to assess the association between quality of life and independent variables. Variables with a p value

Results

The mean score of the overall Quality of Life Scale–Brief Version was 22.42±3.60. No formal education (ß=–1.53; 95% CI: –2.80 to –0.27), duration of treatment (ß = –3.08; 95% CI: –4.71 to –1.45), comorbidity (ß=–1.14; 95% CI: –1.99 to –0.29), substance use (ß=–0.89; 95% CI: –1.56 to –0.23), extrapyramidal side effects (ß=–2.02; 95% CI: –2.90 to –1.14), non-adherence (ß=–0.83; 95% CI: –1.44 to –0.23), and antipsychotic polypharmacy (ß=–1.77; CI: –2.57 to –0.96) were negatively associated with quality of life.

Conclusion and recommendation

In this study, the social domain was recorded as having the lowest mean score, which may indicate that patients with schizophrenia could need better psychosocial support. Patients with a longer duration of treatment, who had comorbid illnesses, were substance users, developed EPS, were non-adherent to medications and were on antipsychotic polypharmacy, needs critical follow-up to improve HRQoL.

Developing and externally validating a machine learning risk prediction model for 30-day mortality after stroke using national stroke registers in the UK and Sweden

Por: Wang · W. · Otieno · J. A. · Eriksson · M. · Wolfe · C. D. · Curcin · V. · Bray · B. D.
Objectives

We aimed to develop and externally validate a generalisable risk prediction model for 30-day stroke mortality suitable for supporting quality improvement analytics in stroke care using large nationwide stroke registers in the UK and Sweden.

Design

Registry-based cohort study.

Setting

Stroke registries including the Sentinel Stroke National Audit Programme (SSNAP) in England, Wales and Northern Ireland (2013–2019) and the national Swedish stroke register (Riksstroke 2015–2020).

Participants and methods

Data from SSNAP were used for developing and temporally validating the model, and data from Riksstroke were used for external validation. Models were developed with the variables available in both registries using logistic regression (LR), LR with elastic net and interaction terms and eXtreme Gradient Boosting (XGBoost). Performances were evaluated with discrimination, calibration and decision curves.

Outcome measures

The primary outcome was all-cause 30-day in-hospital mortality after stroke.

Results

In total, 488 497 patients who had a stroke with 12.4% 30-day in-hospital mortality were used for developing and temporally validating the model in the UK. A total of 128 360 patients who had a stroke with 10.8% 30-day in-hospital mortality and 13.1% all mortality were used for external validation in Sweden. In the SSNAP temporal validation set, the final XGBoost model achieved the highest area under the receiver operating characteristic curve (AUC) (0.852 (95% CI 0.848 to 0.855)) and was well calibrated. The performances on the external validation in Riksstroke were as good and achieved AUC at 0.861 (95% CI 0.858 to 0.865) for in-hospital mortality. For Riksstroke, the models slightly overestimated the risk for in-hospital mortality, while they were better calibrated at the risk for all mortality.

Conclusion

The risk prediction model was accurate and externally validated using high quality registry data. This is potentially suitable to be deployed as part of quality improvement analytics in stroke care to enable the fair comparison of stroke mortality outcomes across hospitals and health systems across countries

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