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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 Diabetes Research & Care May 2024The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged... (Randomized Controlled Trial)
Randomized Controlled Trial
Within and post-trial effects of an intensive lifestyle intervention on kidney disease in adults with overweight or obesity and type 2 diabetes mellitus: a secondary analysis of the Look AHEAD clinical trial.
INTRODUCTION
The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45-76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial's secondary outcome of kidney disease.
RESEARCH DESIGN AND METHODS
We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to <45 mL/min/1.73 m or need for kidney replacement therapy (KRT: dialysis or kidney transplant) during intervention and post-intervention follow-up (median 15.6 years overall).
RESULTS
Incidence of eGFR <45 mL/min/1.73 m was lower in ILI during the intervention (HR=0.80, 95% CI=0.66 to 0.98) but not post-intervention (HR=1.03, 0.86 to 1.23) or overall (HR=0.92, 0.80 to 1.04). There were no significant treatment group differences in KRT. In prespecified subgroup analyses, age×treatment interactions were significant over total follow-up: p=0.001 for eGFR <45 mL/min/1.73 m and p=0.01 for KRT. The 2205 participants aged >60 years at baseline had benefit in both kidney outcomes during intervention and overall (HR=0.75, 0.62 to 0.90 for eGFR <45 mL/min/1.73 m; HR=0.62, 0.43 to 0.91 for KRT). The absolute treatment effects were greater post-intervention: ILI reduced the rate of eGFR <45 mL/min/1.73 m by 0.46 and 0.76 cases/100 person-years during and post-intervention, respectively; and reduced KRT by 0.15 and 0.21 cases/100 person-years. The younger participants experienced no such post-intervention benefits.
CONCLUSIONS
ILI reduced kidney disease progression during and following the active intervention in persons aged ≥60 years. ILI should be considered for reducing kidney disease incidence in older persons with type 2 diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Middle Aged; Male; Female; Aged; Obesity; Glomerular Filtration Rate; Overweight; Life Style; Follow-Up Studies; Disease Progression; Diabetic Nephropathies; Risk Reduction Behavior; Prognosis
PubMed: 38816203
DOI: 10.1136/bmjdrc-2024-004079 -
BMJ Open May 2024Although adolescents make treatment gains in psychiatric residential treatment (RT), they experience significant difficulty adapting to the community and often do not...
Families in transition (FIT) study protocol: feasibility, acceptability and preliminary effects of a group-based parent training in parents of youth in psychiatric residential treatment.
INTRODUCTION
Although adolescents make treatment gains in psychiatric residential treatment (RT), they experience significant difficulty adapting to the community and often do not sustain treatment gains long term. Their parents are often not provided with the necessary support or behaviour management skillset to bridge the gap between RT and home. Parent training, a gold standard behaviour management strategy, may be beneficial for parents of these youth and web-based parent training programmes may engage this difficult-to-reach population. This study focuses on a hybrid parent training programme that combines Parenting Wisely (PW), a web-based parent training with facilitated discussion groups (Parenting Wisely for Residential Treatment (PW)). This study aims to: (1) establish the feasibility and acceptability of PW, (2) evaluate whether PW engages target mechanisms (parental self-efficacy, parenting behaviours, social support, family function) and (3) determine the effects of PW on adolescent outcomes (internalising and externalising behaviours, placement restrictiveness).
METHODS AND ANALYSIS
In this randomised control trial, parents (n=60) will be randomly assigned to PW or treatment as usual. Each week for 6 weeks, parents in the PW condition will complete two PW modules (20 min each) and attend one discussion group via Zoom (90 min). Adolescents (n=60) will not receive intervention; however, we will evaluate the feasibility of adolescent data collection for future studies. Data from parents and adolescents will be collected at baseline, post intervention (6 weeks post baseline) and 6 months post baseline to allow for a robust understanding of the longer-term effects of PW on treatment gain maintenance.
ETHICS AND DISSEMINATION
The study has been approved by The Ohio State University Institutional Review Board (protocol number 2022B0315). The outcomes of the study will be shared through presentations at both local and national conferences, publications in peer-reviewed journals and disseminated to the families and organisations that helped to facilitate the project.
TRIAL REGISTRATION NUMBER
NCT05764369 (V.1, December 2022).
Topics: Humans; Adolescent; Parents; Feasibility Studies; Residential Treatment; Parenting; Female; Male; Mental Disorders; Randomized Controlled Trials as Topic; Social Support
PubMed: 38816058
DOI: 10.1136/bmjopen-2023-080603 -
BMJ Open May 2024Compulsory admissions are associated with feelings of fear, humiliation and powerlessness. The number of compulsory admissions in Germany and other high-income countries... (Randomized Controlled Trial)
Randomized Controlled Trial
Effectiveness of a peer-supported crisis intervention to reduce the proportion of compulsory admissions in acute psychiatric crisis interventions in an outreach and outpatient setting: study protocol for an exploratory cluster randomised trial combined with qualitative methods.
INTRODUCTION
Compulsory admissions are associated with feelings of fear, humiliation and powerlessness. The number of compulsory admissions in Germany and other high-income countries has increased in recent years. Peer support has been shown to increase the self-efficacy of individuals with mental health conditions in acute crises and to reduce the use of coercive measures in clinical settings. The objective of this study is to reduce the number of compulsory admissions by involving peer support workers (PSWs) in acute mental health crises in outreach and outpatient settings.
METHODS AND ANALYSIS
This one-year intervention is an exploratory, cluster randomised study. Trained PSWs will join the public crisis intervention services (CIS) in two of five regions (the intervention regions) in the city of Bremen (Germany). PSWs will participate in crisis interventions and aspects of the mental health services. They will be involved in developing and conducting an antistigma training for police officers. The remaining three regions will serve as control regions. All individuals aged 18 and older who experience an acute mental health crisis during the operating hours of the regional CIS in the city of Bremen (around 2000 in previous years) will be included in the study. Semistructured interviews will be conducted with PSWs, 30 patients from control and intervention regions, as well as two focus group discussions with CIS staff. A descriptive comparison between all participants in the intervention and control regions will assess the proportion of compulsory admissions in crisis interventions during the baseline and intervention years, including an analysis of temporal changes.
ETHICS AND DISSEMINATION
This study was approved by the Ethics Committee of the University of Bremen (file 2022-09) on 20 June 2022. The results will be presented via scientific conferences, scientific journals and communicated to policy-makers and practitioners.
TRIAL REGISTRATION NUMBER
DRKS00029377.
Topics: Humans; Crisis Intervention; Peer Group; Germany; Qualitative Research; Mental Disorders; Randomized Controlled Trials as Topic; Commitment of Mentally Ill; Male; Adult; Female; Mental Health Services
PubMed: 38816053
DOI: 10.1136/bmjopen-2023-083385 -
BMJ Open May 2024Prevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother's milk helps prevent NEC. Rates of own mother's milk feeding...
Effects of implementation of a care bundle on rates of necrotising enterocolitis and own mother's milk feeding in the East Midlands: protocol for a mixed methods impact and process evaluation study.
INTRODUCTION
Prevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother's milk helps prevent NEC. Rates of own mother's milk feeding in the East Midlands are lower than the national average and the incidence of NEC is higher. The East Midlands Neonatal Operational Delivery Network (EMNODN) has created a care bundle to improve these in babies born at <32 weeks' gestation, the group at the highest risk of NEC. The bundle was introduced in September 2022 and embedded by December 2022. We will evaluate its effectiveness and conduct a process evaluation to understand barriers and facilitators to implementation.
METHODS AND ANALYSIS
We will conduct a retrospective cohort study (workstream 1) using data from the National Neonatal Research Database (NNRD). We will identify infants receiving any own mother's milk on day 14 and at discharge, and cases of severe NEC. We will aggregate outcomes by birth month and use interrupted time series analysis to estimate an incidence rate ratio for changes after the care bundle was embedded, relative to pre-implementation. We will model data from all other NNRD units and assess whether there are any concurrent changes to exclude confounding due to other events.We will apply the RE-AIM framework (workstream 2), supplemented by the Consolidated Framework for Implementation Research and Framework for Implementation Fidelity, to conduct a mixed methods evaluation in EMNODN units. We will triangulate data from several sources, including questionnaires and semistructured interviews with parents and healthcare professionals, and data from patient records.
ETHICS AND DISSEMINATION
The study has approval from the South East Scotland Research Ethics Committee 01 and the Health Research Authority and Health and Care Research Wales (IRAS 323099). Results will be disseminated via scientific journals and conferences, to neonatal service commissioners and through public-facing infographics.
TRIAL REGISTRATION NUMBER
NCT05934123.
Topics: Enterocolitis, Necrotizing; Humans; Infant, Newborn; Retrospective Studies; Patient Care Bundles; Female; Milk, Human; Breast Feeding; Infant, Premature; Research Design; Incidence
PubMed: 38816042
DOI: 10.1136/bmjopen-2023-078633 -
BMJ Open Quality May 2024This service evaluation describes the rapid implementation of self-monitoring of blood pressure (SMBP) into maternity care at a tertiary referral centre during the...
BACKGROUND
This service evaluation describes the rapid implementation of self-monitoring of blood pressure (SMBP) into maternity care at a tertiary referral centre during the COVID-19 pandemic. It summarises findings, identifies knowledge gaps and provides recommendations for further research and practice.
INTERVENTION
Pregnant and postpartum women monitored their blood pressure (BP) at home, with instructions on actions to take if their BP exceeded pre-determined thresholds. Some also conducted proteinuria self-testing.
DATA COLLECTION AND ANALYSIS
Maternity records, app data and staff feedback were used in interim evaluations to assess process effectiveness and guide adjustments, employing a Plan-Do-Study-Act and root cause analysis approach.
RESULTS
Between March 2020 and August 2021, a total of 605 women agreed to self-monitor their BP, including 10 women with limited English. 491 registered for telemonitoring (81.2%). 21 (3.5%) took part in urine self-testing. Engagement was high and increased over time with no safety issues. Biggest concerns related to monitor supply and postnatal monitoring. In December 2020, SMBP was integrated into the standard maternity care pathway.
CONCLUSIONS
This project demonstrated successful integration of SMBP into maternity care. Early stakeholder engagement and clear guidance were crucial and community midwifery support essential. Supplying BP monitors throughout pregnancy and post partum could improve the service and fully digitised maternity records would aid data collection. More research is needed on SMBP in the postnatal period and among non-English speakers. These findings support efforts to implement app-supported self-monitoring and guide future research.
Topics: Humans; Female; Pregnancy; COVID-19; Quality Improvement; Adult; United Kingdom; SARS-CoV-2; State Medicine; Blood Pressure Monitoring, Ambulatory; Pandemics; Self Care; Telemedicine
PubMed: 38816006
DOI: 10.1136/bmjoq-2023-002383 -
The Lancet. Microbe May 2024Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of...
Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.
BACKGROUND
Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.
METHODS
In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery.
FINDINGS
The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors.
INTERPRETATION
Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment.
FUNDING
US National Institutes of Health.
PubMed: 38815595
DOI: 10.1016/S2666-5247(24)00015-6 -
Cell Genomics May 2024Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and...
Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the hyper-variable (HYP) effectors of plant-parasitic nematodes. HYP effectors are single-gene loci that potentially harbor thousands of alleles. Alleles vary in the organization, as well as the number, of motifs within a central hyper-variable domain (HVD). We dramatically expand the HYP repertoire of two plant-parasitic nematodes and define distinct species-specific "rules" underlying the apparently flawless genetic rearrangements. Finally, by analyzing the HYPs in 68 individual nematodes, we unexpectedly found that despite the huge number of alleles, most individuals are germline homozygous. These data support a mechanism of programmed genetic variation, termed HVD editing, where alterations are locus specific, strictly governed by rules, and theoretically produce thousands of variants without errors.
PubMed: 38815588
DOI: 10.1016/j.xgen.2024.100580 -
PloS One 2024The government of the Republic of Moldova, endorsed the principle of Health in All Policies (HiAP) through its health sector reforms to address the rising burden of...
BACKGROUND
The government of the Republic of Moldova, endorsed the principle of Health in All Policies (HiAP) through its health sector reforms to address the rising burden of non-communicable diseases and health inequalities. Territorial Public Health Councils (TPHCs) were created to ensure the coordination and management of the population's health in their respective district. This study assessed the capacities of the TPHCs to identify areas in need of support for strengthening their intersectoral collaboration role in public health at local level.
METHODS
A mixed-method approach, using qualitative and quantitative techniques, was used to compare the perceptions of all TPHC members (n = 112) and invitees (n = 53) to council meetings from 10 districts covering all geographical areas of Moldova. The quantitative information was obtained using a cross-sectional survey, while the qualitative aspects were assessed within focus group discussions (FGDs).
RESULTS
Half of all TPHC members, including 75% from groups with a non-medical background, did not attend a public health course within the last three years. Overall, groups with a medical background were more aware of the legislation that governs TPHC activity and intersectoral collaboration compared with those with a non-medical background. The FGDs of TPHC meetings revealed that members had an insufficient level of understanding of intersectoral collaboration to solve public health issues and lacked clarity about their place and role within the TPHC.
CONCLUSIONS
HiAP implementation was found to be suboptimal with insufficient capacity at local level. TPHC members' ability to deal with public health issues were severely impaired by a general lack of knowledge and understanding of how to utilize the TPHC platform for maximum benefit. Reforming TPHC regulation is required in addition to extensive capacity building for TPHC members to increase member understanding of their roles as intended by TPHC regulations, including the facilitation of intersectoral collaborations.
Topics: Humans; Moldova; Public Health; Intersectoral Collaboration; Cross-Sectional Studies; Health Policy; Focus Groups
PubMed: 38814932
DOI: 10.1371/journal.pone.0303821