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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 -
ESC Heart Failure May 2024This study aimed to investigate the prevalence, risk factors and prognostic implications of cognitive impairment in young and middle-aged patients with acute heart...
AIMS
This study aimed to investigate the prevalence, risk factors and prognostic implications of cognitive impairment in young and middle-aged patients with acute heart failure (HF).
METHODS
In a prospective cohort of patients with acute HF, we assessed cognitive function by the Mini-Cog, predictors of the cognitive impairment and its associations with 30 day and 1 year cardiovascular death or HF rehospitalization among young and middle-aged patients (<65 years old).
RESULTS
Among 1958 young and middle-aged patients, the prevalence of cognitive impairment was 19.6%. Predictors of cognitive impairment included older age, females, lower education levels and prior strokes. Compared with patients having normal cognitive function, cognitive impairment was associated with a higher risk of 30 day cardiovascular death or HF rehospitalization [hazard ratio (HR), 1.52, 95% confidence interval (CI), 1.07-2.17, P = 0.02], but not for 1 year cardiovascular death or HF rehospitalization (HR, 1.06, 95% CI, 0.87-1.30, P = 0.55).
CONCLUSIONS
Cognitive impairment is present in a notable proportion of young and middle-aged patients with acute HF and is associated with an increased risk of short-term adverse outcomes. Strategies for screening and intervention for cognitive impairment at a younger age are necessary, particularly for those at high risk.
PubMed: 38816208
DOI: 10.1002/ehf2.14885 -
BMJ Open Diabetes Research & Care May 2024ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing...
INTRODUCTION
ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
RESEARCH DESIGN AND METHODS
Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
RESULTS
The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
CONCLUSIONS
Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.
TRIAL REGISTRATION NUMBER
UMIN000011525.
Topics: Humans; Male; Female; Diabetic Nephropathies; Angiotensin-Converting Enzyme 2; Biomarkers; Middle Aged; Glomerular Filtration Rate; Peptidyl-Dipeptidase A; Aged; Prognosis; Disease Progression; Follow-Up Studies
PubMed: 38816205
DOI: 10.1136/bmjdrc-2024-004237 -
BMJ Open Diabetes Research & Care May 2024We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus...
INTRODUCTION
We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.
RESEARCH DESIGN AND METHODS
Using the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.
RESULTS
At baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was -0.80 mL/min/1.73 m/year (95% CI -1.05 to -0.54) among SGLT2 inhibitors group and -1.78 mL/min/1.73 m/year (95% CI -2.08 to -1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.
CONCLUSIONS
The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Female; Male; Aged; Japan; Glomerular Filtration Rate; Diabetic Nephropathies; Databases, Factual; Renal Insufficiency, Chronic; Aged, 80 and over; Diabetes Mellitus, Type 2; Follow-Up Studies; Disease Progression; Hypoglycemic Agents; Prognosis; Treatment Outcome
PubMed: 38816204
DOI: 10.1136/bmjdrc-2024-004115 -
BMJ Open May 2024Multiple sclerosis (MS) is an immune-mediated demyelinating disease with a significant burden of neuropsychiatric sequelae. These symptoms, including depression and...
INTRODUCTION
Multiple sclerosis (MS) is an immune-mediated demyelinating disease with a significant burden of neuropsychiatric sequelae. These symptoms, including depression and anxiety, are predictors of morbidity and mortality in people with MS. Despite a high prevalence of obsessive-compulsive disorder in MS, potentially shared pathophysiological mechanisms and overlap in possible treatments, no review has specifically examined the clinical dimensions of people with obsessive-compulsive and related disorders (OCRD) and MS. In this scoping review, we aim to map the available knowledge on the clinical dimensions of people with co-occurring OCRD and MS. Understanding the characteristics of this population in greater detail will inform more patient-centred care and create a framework for future studies.
METHODS AND ANALYSIS
We developed a search strategy to identify all articles that include people with co-occurring OCRD and MS. The search strategy (extending to the grey literature) was applied to MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science and ProQuest Dissertations & Theses. Records will undergo title and abstract screening by two independent reviewers. Articles meeting inclusion criteria based on title and abstract screening will go on to full-text review by the two independent reviewers. After reaching a consensus about articles for inclusion in the final review, data will be extracted using a standardised extraction form. The extracted data will include clinical characteristics of patients such as age, gender, medication use and severity of MS, among others.
ETHICS AND DISSEMINATION
This scoping review does not require research ethics approval. Results will be shared at national and/or international conferences, in a peer-reviewed journal publication, in a plain language summary and in a webinar for the general public.
Topics: Humans; Multiple Sclerosis; Obsessive-Compulsive Disorder; Research Design; Review Literature as Topic; Comorbidity
PubMed: 38816059
DOI: 10.1136/bmjopen-2023-074929 -
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 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 2024To evaluate co-prescribing of sedatives hypnotics and opioids.
OBJECTIVE
To evaluate co-prescribing of sedatives hypnotics and opioids.
DESIGN
Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing.
SETTING AND PARTICIPANTS
Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA.
OUTCOME MEASURES
Coprescription of sedative-hypnotics and opioids.
RESULTS
A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date.
CONCLUSIONS
Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.
Topics: Humans; Hypnotics and Sedatives; Female; Male; Analgesics, Opioid; Retrospective Studies; Adult; Middle Aged; United States; Practice Patterns, Physicians'; Drug Prescriptions; Comorbidity; Benzodiazepines; Logistic Models
PubMed: 38816043
DOI: 10.1136/bmjopen-2023-082339 -
BMJ Open May 2024To analyse the HIV-1 subtypes and molecular transmission characteristics of HIV-infected older individuals aged 50 and above in Huzhou City, and provide a scientific...
OBJECTIVE
To analyse the HIV-1 subtypes and molecular transmission characteristics of HIV-infected older individuals aged 50 and above in Huzhou City, and provide a scientific basis for prevention and treatment strategies for them.
DESIGN
A cross-sectional study with clustered molecular transmission network cases was performed, and basic epidemiological information was retrieved from the Chinese Centres for Disease Prevention and Control (CDC) Information System.
SETTING AND PARTICIPANTS
A molecular epidemiological study was conducted in 899 newly diagnosed HIV-infected individuals from January 2019 and March 2023 in Huzhou city, Zhejiang province, Eastern China. Out of these, HIV sequences were successfully obtained from 673 individuals, including 274 who were older individuals aged 50 and above.
PRIMARY AND SECONDARY OUTCOMES
Reverse transcription-polymerase chain reaction (PCR) and nested PCR were used to amplify the polymerase gene of HIV-1, and gene sequencing was performed. We used univariate and multivariate logistic regression to describe the association of clustered molecular transmission network cases.
RESULTS
In total, 274 valid HIV sequences of older individuals were obtained, which revealed 14 subtypes. Circulating recombinant forms (CRF) 07_BC accounted for 55.8% and CRF01_AE accounted for 20.1% of the subtypes. Data of 150 older individuals were included in the molecular transmission network, and the proportion of elderly individuals in clustered cases is 52.26% (150/287). The results of multivariable logistic regression analysis showed that the older age group (60-82 years) and CRF07_BC subtype were associated with case clustering (transmission risk).
CONCLUSIONS
The key high-risk transmission network was mainly composed of the older age group (60-82 years) and CRF07_BC subtype. It is necessary to further strengthen AIDS health promotion and education for individuals aged 60 years and above, as well as for patients with the CRF07_BC subtype, to reduce HIV transmission and clustering risk.
Topics: Humans; China; Cross-Sectional Studies; HIV Infections; Male; Female; Middle Aged; Aged; HIV-1; Aged, 80 and over; Molecular Epidemiology
PubMed: 38816041
DOI: 10.1136/bmjopen-2024-085646 -
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