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BMC Nephrology May 2024Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD.... (Comparative Study)
Comparative Study
BACKGROUND
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
METHODS
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
RESULTS
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
CONCLUSIONS
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Topics: Humans; Female; Citrulline; Male; Protein Carbamylation; Biomarkers; Middle Aged; Renal Insufficiency, Chronic; Aged; Prospective Studies; Risk Assessment; Kidney Failure, Chronic; Prognosis; Proportional Hazards Models; Serum Albumin
PubMed: 38816682
DOI: 10.1186/s12882-024-03619-6 -
RMD Open May 2024To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs.
OBJECTIVE
To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.
METHODS
Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.
RESULTS
A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.
CONCLUSION
Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Topics: Humans; Purines; Sulfonamides; Arthritis, Rheumatoid; Pyrazoles; Azetidines; Male; Female; Middle Aged; Antirheumatic Agents; Aged; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Treatment Failure; Adult; Patient Reported Outcome Measures; Severity of Illness Index
PubMed: 38816210
DOI: 10.1136/rmdopen-2024-004291 -
BMJ Open May 2024Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a...
INTRODUCTION
Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.
METHODS AND ANALYSIS
SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2-6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.
ETHICS AND DISSEMINATION
The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.
TRIAL REGISTRATION NUMBER
NCT04680910.
Topics: Humans; Propofol; Cognitive Dysfunction; Aged; Sleep, Slow-Wave; Electroencephalography; Male; Anesthetics, Intravenous; Depressive Disorder, Treatment-Resistant; Female; Middle Aged; Clinical Trials, Phase I as Topic
PubMed: 38816055
DOI: 10.1136/bmjopen-2024-087516 -
BMJ Open May 2024To map the evidence and scope of physical rehabilitation services delivered by community health workers (CHWs) in sub-Saharan Africa (SSA). (Review)
Review
OBJECTIVES
To map the evidence and scope of physical rehabilitation services delivered by community health workers (CHWs) in sub-Saharan Africa (SSA).
DESIGN
Scoping review DATA SOURCES: PubMed, Scopus, Cochrane Central and databases within the EBSCOhost platform. We also searched other literature sources including reference lists, conference presentations and organisational websites such as WHO, Ministries of Health and non-governmental organisations in SSA.
ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES
Articles presenting evidence on CHWs' delivery of physical rehabilitation services in SSA from September 1978 to June 2023.
DATA EXTRACTION AND SYNTHESIS
Screening was conducted by two reviewers and was guided by the inclusion criteria. Thematic content analysis of data was employed. The results are presented according to the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews.
RESULTS
A total of 6996 articles were identified through various databases, with only 20 studies qualifying for data extraction. Evidence was presented by Eritrea, Ethiopia, Malawi, Mauritius, Namibia, South Africa and Uganda. Assessments, case management, health education, community liaison with support, health systems linkage and administration were the CHWs' scope of practice identified. The review identified home-based, community-based, community and facility-based, home and community-based and facility-based as modes of delivery. The barriers experienced are resources, societal and community attitudes, governance, geographical barriers and delivery capacity, while proximity to the community, positive job attitude and support with collaboration facilitated service delivery.
CONCLUSION
Training and integrating CHWs in national health care systems, with careful selection of existing CHWs, would minimise the barriers faced.
Topics: Humans; Community Health Workers; Africa South of the Sahara; Delivery of Health Care; Rehabilitation
PubMed: 38816054
DOI: 10.1136/bmjopen-2023-079738 -
BMJ Open May 2024Hospital electronic patient records (EPRs) offer the opportunity to exploit large-scale routinely acquired data at relatively low cost and without selection. EPRs...
BACKGROUND
Hospital electronic patient records (EPRs) offer the opportunity to exploit large-scale routinely acquired data at relatively low cost and without selection. EPRs provide considerably richer data, and in real-time, than retrospective administrative data sets in which clinical complexity is often poorly captured. With population ageing, a wide range of hospital specialties now manage older people with multimorbidity, frailty and associated poor outcomes. We, therefore, set-up the Oxford and Reading Cognitive Comorbidity, Frailty and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR) to facilitate clinically meaningful research in older hospital patients, including algorithm development, and to aid medical decision-making, implementation of guidelines, and inform policy.
METHODS AND ANALYSIS
ORCHARD-EPR uses routinely acquired individual patient data on all patients aged ≥65 years with unplanned admission or Same Day Emergency Care unit attendance at four acute general hospitals serving a population of >800 000 (Oxfordshire, UK) with planned extension to the neighbouring Berkshire regional hospitals (>1 000 000). Data fields include diagnosis, comorbidities, nursing risk assessments, frailty, observations, illness acuity, laboratory tests and brain scan images. Importantly, ORCHARD-EPR contains the results from mandatory hospital-wide cognitive screening (≥70 years) comprising the 10-point Abbreviated-Mental-Test and dementia and delirium diagnosis (Confusion Assessment Method-CAM). Outcomes include length of stay, delayed transfers of care, discharge destination, readmissions and death. The rich multimodal data are further enhanced by linkage to secondary care electronic mental health records. Selection of appropriate subgroups or linkage to existing cohorts allows disease-specific studies. Over 200 000 patient episodes are included to date with data collection ongoing of which 129 248 are admissions with a length of stay ≥1 day in 64 641 unique patients.
ETHICS AND DISSEMINATION
ORCHARD-EPR is approved by the South Central Oxford C Research Ethics Committee (ref: 23/SC/0258). Results will be widely disseminated through peer-reviewed publications and presentations at conferences, and regional meetings to improve hospital data quality and clinical services.
Topics: Humans; Electronic Health Records; Aged; Comorbidity; Databases, Factual; Frailty; Female; Aged, 80 and over; Male; Aging; United Kingdom; Geriatric Assessment
PubMed: 38816052
DOI: 10.1136/bmjopen-2024-085126 -
BMJ Open May 2024Understanding what general practice (GP) registrars consider as distinctive in their consultations with Aboriginal and Torres Strait Islander patients may help bridge...
BACKGROUND AND OBJECTIVE
Understanding what general practice (GP) registrars consider as distinctive in their consultations with Aboriginal and Torres Strait Islander patients may help bridge the gap between patient-determined cultural safety and current medical and behavioural practice. This project seeks to explore what GP registrars perceive as distinctive to their consultations with Aboriginal and Torres Strait Islander patients.
METHODS
This mixed-methods study involved a survey considering demographic details of GP registrars, questionnaire regarding attitude and cultural capability, and semistructured interviews.
RESULTS
26 registrars completed the survey. 16 registrars completed both the survey and the interview. Despite recognising a need to close the gap on health outcomes for Aboriginal and Torres Strait Islander peoples and wanting to do things differently, most registrars adopted a generic approach to all consultations.
DISCUSSION
This study suggests that overall, GP registrars want to improve the health of Aboriginal and Torres Strait Islander patients, but do not want their consultations with Aboriginal and Torres Strait Islander patients to be distinctive. Registrars appeared to approach all consultations in a similar manner using predominantly patient-centred care principles. Given the importance of a culturally safe consultation, it is important for us to consider how to increasingly transform these learners and teach cultural safety in this context.
Topics: Humans; Native Hawaiian or Other Pacific Islander; Male; Female; Attitude of Health Personnel; Adult; Surveys and Questionnaires; Health Services, Indigenous; Australia; Middle Aged; Cultural Competency; Referral and Consultation; General Practice; General Practitioners; Physician-Patient Relations; Patient-Centered Care; Australian Aboriginal and Torres Strait Islander Peoples
PubMed: 38816050
DOI: 10.1136/bmjopen-2023-082137 -
BMJ Open May 2024This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically... (Meta-Analysis)
Meta-Analysis
Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.
OBJECTIVES
This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically important outcomes, in people of any age.
METHODS
We searched different electronic databases and other resources for randomised clinical trials that had compared vitamin A supplements versus placebo or no intervention (last search 16 April 2024). We used Cochrane methodology. We used the random-effects model to calculate risk ratios (RRs), with 95% CIs. We analysed individually and cluster randomised trials separately. Our primary outcomes were mortality, adverse events and quality of life. We assessed risks of bias in the trials and used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of the evidence.
RESULTS
We included 120 randomised trials (1 671 672 participants); 105 trials allocated individuals and 15 allocated clusters. 92 trials included children (78 individually; 14 cluster randomised) and 28 adults (27 individually; 1 cluster randomised). 14/105 individually randomised trials (13%) and none of the cluster randomised trials were at overall low risk of bias. Vitamin A did not reduce mortality in individually randomised trials (RR 0.99, 95% CI 0.93 to 1.05; I=32%; p=0.19; 105 trials; moderate certainty), and this effect was not affected by the risk of bias. In individually randomised trials, vitamin A had no effect on mortality in children (RR 0.96, 95% CI 0.88 to 1.04; I=24%; p=0.28; 78 trials, 178 094 participants) nor in adults (RR 1.04, 95% CI 0.97 to 1.13; I=24%; p=0.27; 27 trials, 61 880 participants). Vitamin A reduced mortality in the cluster randomised trials (0.84, 95% CI 0.76 to 0.93; I=66%; p=0.0008; 15 trials, 14 in children and 1 in adults; 364 343 participants; very low certainty). No trial reported serious adverse events or quality of life. Vitamin A slightly increased bulging fontanelle of neonates and infants. We are uncertain whether vitamin A influences blindness under the conditions examined.
CONCLUSIONS
Based on moderate certainty of evidence, vitamin A had no effect on mortality in the individually randomised trials. Very low certainty evidence obtained from cluster randomised trials suggested a beneficial effect of vitamin A on mortality. If preventive vitamin A programmes are to be continued, supporting evidence should come from randomised trials allocating individuals and assessing patient-meaningful outcomes.
PROSPERO REGISTRATION NUMBER
CRD42018104347.
Topics: Humans; Vitamin A; Randomized Controlled Trials as Topic; Dietary Supplements; Primary Prevention; Secondary Prevention; Quality of Life; Vitamins
PubMed: 38816049
DOI: 10.1136/bmjopen-2023-078053 -
BMJ Open May 2024Electronic health record (EHR) systems are used extensively in healthcare; their design can influence clinicians' behaviour. We conducted a systematic review of...
OBJECTIVES
Electronic health record (EHR) systems are used extensively in healthcare; their design can influence clinicians' behaviour. We conducted a systematic review of EHR-based interventions aimed at changing the clinical practice of general practitioners in the UK, assessed their effectiveness and applied behaviour change theory to identify lessons for other settings.
DESIGN
Mixed methods systematic review.
DATA SOURCES
MEDLINE, EMBASE, CENTRAL and APA PsycINFO were searched up to March 2023.
ELIGIBILITY CRITERIA
Quantitative and qualitative findings from randomised controlled trials (RCTs) controlled before-and-after studies and interrupted time series of EHR-based interventions in UK general practice were included.
DATA EXTRACTION AND SYNTHESIS
Quantitative synthesis was based on Cochrane's Synthesis without Meta-analysis. Interventions were categorised using the Behaviour Change Wheel and MINDSPACE frameworks and effectiveness determined by vote-counting using direction of effect. Inductive thematic synthesis was used for qualitative studies.
RESULTS
Database searching identified 3824 unique articles; 10 were included (from 2002 to 2021), comprising eight RCTs and two associated qualitative studies. Four of seven quantitative studies showed a positive effect on clinician behaviour and three on patient-level outcomes. Behaviour change techniques that may trigger emotions and required less cognitive engagement appeared to have positive effects. Qualitative findings indicated that interventions reassured clinicians of their decisions but were sometimes ignored.
CONCLUSION
Despite widespread use, there is little high quality, up-to-date experimental evidence evaluating the effectiveness of EHR-based interventions in UK general practice. The evidence suggested EHR-based interventions may be effective at changing behaviour. Persistent, simple action-oriented prompts appeared more effective than complex interventions requiring greater cognitive engagement. However, studies lacked detail in intervention design and theory behind design choices. Future research should seek to optimise EHR-based behaviour change intervention design and delineate limitations, providing theory-based justification for interventions. This will be of increasing importance with the growing use of EHRs to influence clinicians' decisions.
PROSPERO REGISTRATION NUMBER
CRD42022341009.
Topics: Humans; Electronic Health Records; United Kingdom; General Practitioners; Practice Patterns, Physicians'; General Practice; Behavior Therapy
PubMed: 38816046
DOI: 10.1136/bmjopen-2023-080546 -
BMJ Open Ophthalmology May 2024To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye.
OBJECTIVES
To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye.
METHODS
We searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent RAO in the present study. Ophthalmic and systemic features were analysed to identify risk factors and visual outcomes.
RESULTS
Of the 850 patients in the non-arteritic RAO cohort, 11 (1.3%) experienced a second RAO recurrence, either in the same (5 patients; 0.6%) or opposite (6 patients; 0.7%) eye. The same eye group experienced an earlier recurrence (1-2 months, median 1 month) than the opposite eye group, where the time to recurrence was notably longer (8-66 months, median 22 months). Best corrected visual acuity (BCVA) in the same eye group decreased after the recurrence of RAO. In the same eye group, initial BCVA ranged from 20/200 to counting fingers (CF), while BCVA during RAO recurrence ranged from CF to hand motion. When RAO recurred in the opposite eye, the reduction in visual acuity was less severe than the reduction of the initial episode: initial episode ranged from 20/400 to light perception and recurrent episode ranged from 20/25 to 20/400. Patients exhibited varying degrees of carotid (81.8%) and cerebral (9.1%) artery occlusions. Additionally, one patient in each group (total 2 patients, 18.2%) experienced a stroke 6 months after RAO recurrence.
CONCLUSIONS
Since the RAO recurrences could lead to devastating visual impairment, it is essential to emphasise the importance of risk factor screening to patients while collaborating with neurologists and cardiologists.
Topics: Humans; Retinal Artery Occlusion; Recurrence; Male; Female; Visual Acuity; Middle Aged; Aged; Risk Factors; Retrospective Studies; Adult; Registries; Fluorescein Angiography; Aged, 80 and over; Tomography, Optical Coherence; Follow-Up Studies
PubMed: 38816011
DOI: 10.1136/bmjophth-2024-001636 -
BMJ Open Quality May 2024Sick preterm neonates are most vulnerable to developing skin injuries. Despite sound knowledge and application of evidence-based practices for preventing medical...
INTRODUCTION
Sick preterm neonates are most vulnerable to developing skin injuries. Despite sound knowledge and application of evidence-based practices for preventing medical adhesive-related skin injury (MARSI), the incidence of MARSI was 30 events per 1000 adhesive application days in our unit.
AIMS AND OBJECTIVES
We aimed to reduce the median MARSI rate from the existing 30 per 1000 MARSI days to <5 per 1000 MARSI over 5 months from June 2023 to October 2023.
MATERIAL & METHODS
With the point-of-care quality improvement (QI) approach, a prospective study was planned to reduce the incidence of MARSI among sick very preterm newborns (<32 weeks gestational age) and eventually improve overall skin condition during hospital stay. Sequential Plan-Do-Study-Act cycles were implemented based on the identified risk factors recognised during recurring team discussions.
RESULTS
We demonstrated a reduction in the MARSI rate from 30 events per 1000 adhesive applications (during baseline assessment) to zero events per 1000 adhesive applications at the end of the study period. It was temporally related to the assessment of skin risk stratification at admission using a validated tool, regular assessment of neonatal skin condition score based on the skin risk stratification, and reinforcement of MARSI prevention bundle by application of barrier spray. Awareness regarding 'skin injury prevention' bundles was continually generated among healthcare professionals. The MARSI rate remained <5 events per adhesive application in the sustenance phase over 6 months.
CONCLUSION
Implementing evidence-based skin care practices resulted in a significant reduction in iatrogenic cutaneous injury events in very preterm neonates.
Topics: Humans; Infant, Newborn; Quality Improvement; Prospective Studies; Intensive Care Units, Neonatal; Skin; Infant, Premature; Female; Male; Adhesives; Incidence
PubMed: 38816009
DOI: 10.1136/bmjoq-2023-002697