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1.
JAMA Pediatr ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843971

RESUMO

Importance: In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non-evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care. Objective: To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis. Design, Setting, and Participants: This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020. Interventions: Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback. Main Outcomes and Measures: The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions. Results: A total of 26 hospitals were randomized without dropouts. Analysis was by intention to treat. Baseline data collected on 8003 infants for 3 bronchiolitis seasons (2014-2016) before the implementation period were similar between intervention and control hospitals. Implementation period data were collected on 3727 infants, including 2328 boys (62%) and 1399 girls (38%), with a mean (SD) age of 6.0 (3.2) months. A total of 459 (12%) were Maori (New Zealand), and 295 (8%) were Aboriginal/Torres Strait Islander (Australia). Compliance with recommendations was 85.1% (95% CI, 82.6%-89.7%) in intervention hospitals vs 73.0% (95% CI, 65.3%-78.8%) in control hospitals (adjusted risk difference, 14.1%; 95% CI, 6.5%-21.7%; P < .001). Conclusions and Relevance: Targeted interventions led to improved treatment of infants with bronchiolitis. This study has important implications for bronchiolitis management and the development of effective interventions to deimplement low-value care. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.

2.
PLoS One ; 16(3): e0248983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765016

RESUMO

Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.

3.
PLoS One ; 16(3): e0249000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765036

RESUMO

BACKGROUND: The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. MATERIAL AND METHODS: This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. RESULTS: The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68). CONCLUSION: Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

4.
Hemodial Int ; 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779046

RESUMO

INTRODUCTION: Hemodialysis (HD) with medium cut-off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25-60 kDa). However, the impact of MCO dialyzers on long-term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) provided an opportunity to assess the effect of MCO dialyzers on protein-bound uremic toxins and novel markers of mineral metabolism. METHODS: This exploratory sub-study of REMOVAL-HD evaluated changes in protein-bound solutes (total and free indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor-23 [iFGF23], fetuin-A and endogenous calciprotein particles [CPP-1 and CPP-2]). Mid-week, pre-HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models. FINDINGS: Eighty-nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (-26.8% [95%CI -39.7, -11.1], p = 0.001), which was sustained at Week 24 (-21.7% [95%CI -35.7, -4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin-A, CPP-1, or CPP-2. DISCUSSION: The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.

5.
Clin Kidney J ; 14(3): 735-738, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33779659

RESUMO

Relapsing, recurrent or repeat peritonitis is a devastating complication for peritoneal dialysis (PD) patients and is usually associated with poor outcomes including prolonged hospitalization, catheter removal, hemodialysis transfer and even death. Despite its critical importance and frequent occurrence, there is limited available evidence to facilitate evidence-informed treatment of PD peritonitis. This editorial comments on the findings and limitations of a randomized controlled study published in this journal, which reported that extending antibiotic treatment duration for an additional week beyond that recommended by the International Society for PD did not reduce the risk of relapsing, recurrent or repeat peritonitis, and may have increased the risk of repeat peritonitis. These results are explored in the context of the existing literature and recommendations for practice and research are provided.

6.
Curr Opin Nephrol Hypertens ; 30(3): 346-352, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33767063

RESUMO

PURPOSE OF REVIEW: Several observational studies have shown that hyperuricemia is associated with chronic kidney disease (CKD) progression and is a potential therapeutic target in people with CKD. This review discusses the results of three recently published placebo-controlled randomized trials evaluating the effect of urate-lowering treatment on the progression of CKD with at least 2 years of follow-up. RECENT FINDINGS: The Febuxostat versus Placebo Randomized Controlled Trial Regarding Reduced Renal Function in Patients with Hyperuricemia Complicated by Chronic Kidney Disease Stage 3 trial evaluated the effect of febuxostat in 443 patients with stage 3 CKD (mean estimated glomerular filtration rate [eGFR] 45 mL/min/1.73 m2) and asymptomatic hyperuricemia (mean serum urate 7.8 mg/dL). The Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Loss in Diabetes trials respectively evaluated the effect of allopurinol in 369 adults with stage 3 or 4 CKD (mean eGFR 31.7 mL/min/1.73 m2, mean serum urate 8.2 mg/dL) with high progression risk and 530 patients with type 1 diabetes and diabetic kidney disease (mean eGFR 74.7 mL/min/1.73 m2, mean serum urate 6.1 mg/dL). Despite the large and sustained reductions in serum urate levels in all 3 trials, urate-lowering treatment with febuxostat or allopurinol did not result in clinically meaningful improvement in kidney outcomes. SUMMARY: The results of large and well-designed placebo-controlled trials do not support the use of urate-lowering therapy to slow the progression of CKD.

7.
Nephrology (Carlton) ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33715269

RESUMO

AIM: With improved life expectancy over time, the burden of kidney failure resulting in kidney replacement therapy (KRT) in older persons is increasing. This study aimed to describe the age distribution at dialysis initiation in Australia and New Zealand (ANZ) across centres and over time. METHODS: Adults initiating dialysis as first KRT in ANZ from 1999 to 2018 reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry were included. The primary outcomes were the age distribution and the proportion of older persons (75 years and older) initiating dialysis across centres and over time. Secondary outcomes were characterization of the older population compared with younger people and differences in dialysis modality and treatment trajectories between groups. RESULTS: Over the study period, 55 382 people initiated dialysis as first KRT, including 10 306 older persons, in 100 centres. Wide variation in age distribution across states/countries was noted, although the proportion of older persons at dialysis initiation did not significantly change over time (from 13% in 1999 to 19% in 2003, then remaining stable thereafter). Older persons were less likely to be treated with home therapies compared with younger people. Older persons were mostly Caucasians; had higher socioeconomic position, more cardiovascular comorbidities and higher eGFR at baseline; and resided in major cities. Higher proportions of older persons per centre were noted in privately funded facilities. CONCLUSION: Wide variations were noted in the proportions of older persons initiating dialysis across centres and states/country, which were associated with different case-mix across regions, particularly in terms of ethnicity, remoteness and socioeconomic advantage.

8.
Cochrane Database Syst Rev ; 3: CD013119, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33782940

RESUMO

BACKGROUND: Obesity and chronic kidney disease (CKD) are highly prevalent worldwide and result in substantial health care costs. Obesity is a predictor of incident CKD and progression to kidney failure. Whether weight loss interventions are safe and effective to impact on disease progression and clinical outcomes, such as death remains unclear. OBJECTIVES: This review aimed to evaluate the safety and efficacy of intentional weight loss interventions in overweight and obese adults with CKD; including those with end-stage kidney disease (ESKD) being treated with dialysis, kidney transplantation, or supportive care. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 14 December 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of more than four weeks duration, reporting on intentional weight loss interventions, in individuals with any stage of CKD, designed to promote weight loss as one of their primary stated goals, in any health care setting. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and extracted data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess the certainty of evidence. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised mean difference (SMD) for continuous outcomes or in descriptive format when meta-analysis was not possible. MAIN RESULTS: We included 17 RCTs enrolling 988 overweight or obese adults with CKD. The weight loss interventions and comparators across studies varied. We categorised comparisons into three groups: any weight loss intervention versus usual care or control; any weight loss intervention versus dietary intervention; and surgical intervention versus non-surgical intervention. Methodological quality was varied, with many studies providing insufficient information to accurately judge the risk of bias. Death (any cause), cardiovascular events, successful kidney transplantation, nutritional status, cost effectiveness and economic analysis were not measured in any of the included studies. Across all 17 studies many clinical parameters, patient-centred outcomes, and adverse events were not measured limiting comparisons for these outcomes. In studies comparing any weight loss intervention to usual care or control, weight loss interventions may lead to weight loss or reduction in body weight post intervention (6 studies, 180 participants: MD -3.69 kg, 95% CI -5.82 to -1.57; follow-up: 5 weeks to 12 months, very low-certainty evidence). In very low certainty evidence any weight loss intervention had uncertain effects on body mass index (BMI) (4 studies, 100 participants: MD -2.18 kg/m², 95% CI -4.90 to 0.54), waist circumference (2 studies, 53 participants: MD 0.68 cm, 95% CI -7.6 to 6.24), proteinuria (4 studies, 84 participants: 0.29 g/day, 95% CI -0.76 to 0.18), systolic (4 studies, 139 participants: -3.45 mmHg, 95% CI -9.99 to 3.09) and diastolic blood pressure (4 studies, 139 participants: -2.02 mmHg, 95% CI -3.79 to 0.24). Any weight loss intervention made little or no difference to total cholesterol, high density lipoprotein cholesterol, and inflammation, but may lower low density lipoprotein cholesterol. There was little or no difference between any weight loss interventions (lifestyle or pharmacological) compared to dietary-only weight loss interventions for weight loss, BMI, waist circumference, proteinuria, and systolic blood pressure, however diastolic blood pressure was probably reduced. Furthermore, studies comparing the efficacy of different types of dietary interventions failed to find a specific dietary intervention to be superior for weight loss or a reduction in BMI. Surgical interventions probably reduced body weight (1 study, 11 participants: MD -29.50 kg, 95% CI -36.4 to -23.35), BMI (2 studies, 17 participants: MD -10.43 kg/m², 95% CI -13.58 to -7.29), and waist circumference (MD -30.00 cm, 95% CI -39.93 to -20.07) when compared to non-surgical weight loss interventions after 12 months of follow-up. Proteinuria and blood pressure were not reported. All results across all comparators should be interpreted with caution due to the small number of studies, very low quality of evidence and heterogeneity across interventions and comparators. AUTHORS' CONCLUSIONS: All types of weight loss interventions had uncertain effects on death and cardiovascular events among overweight and obese adults with CKD as no studies reported these outcome measures. Non-surgical weight loss interventions (predominately lifestyle) appear to be an effective treatment to reduce body weight, and LDL cholesterol. Surgical interventions probably reduce body weight, waist circumference, and fat mass. The current evidence is limited by the small number of included studies, as well as the significant heterogeneity and a high risk of bias in most studies.

9.
Perit Dial Int ; : 896860821993950, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706584

RESUMO

BACKGROUND: Despite the implementation of a 'Peritoneal Dialysis (PD) First' policy in Thailand since 2008, nationwide PD practices and patients' outcomes have rarely been reported. METHODS: As part of the multinational PD Outcomes and Practice Patterns Study (PDOPPS), PD patients from 22 PD centres from different geographic regions, sizes and affiliations, representing Thailand PD facilities, have been enrolled starting in May 2016. Demographic, clinical and laboratory data and patients' outcomes were prospectively collected and analysed. RESULTS: The pilot and implementation phases demonstrated excellent concordance between study data and validation data collected at enrolment. In the implementation phase, 848 PD patients (including 262 (31%) incident PD patients) were randomly sampled from 5090 patients in participating centres. Almost all participants (95%) performed continuous ambulatory PD (CAPD), and a high proportion had hypoalbuminemia (67%, serum albumin < 3.5 g/dL), anaemia (42%, haemoglobin <10 g/dL) and hypokalaemia (37%, serum potassium < 3.5 mmol/L). The peritonitis rate was 0.40 episodes/year, but the culture-negative rate was high (0.13 episodes/year, 28% of total episodes). The patients from PD clinics located in Bangkok metropolitan region had higher socio-economic status, more optimal nutritional markers, blood chemistries, haemoglobin level and lower peritonitis rates compared to the provincial regions, emphasizing the centre effect on key success factors in PD. CONCLUSIONS: Participation in the PDOPPS helps unveil the critical barriers to improving outcomes of PD patients in Thailand, including a high prevalence of hypokalaemia, anaemia, poor nutritional status and culture-negative peritonitis. These factors should be acted upon to formulate solutions and implement quality improvement on a national level.

10.
Transplantation ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33653998

RESUMO

BACKGROUND: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients were identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1 to 9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome was systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1 to 11 time points per trial. CONCLUSIONS: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability and usefulness of trial evidence.Supplemental Visual Abstract; http://links.lww.com/TP/C169.

11.
Nephrology (Carlton) ; 26(5): 454-462, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550668

RESUMO

AIM: Patient-reported outcome measures (PROM) has gained international recognition as important predictors of clinical outcomes in peritoneal dialysis (PD). We sought to understand the associations between patient-reported appetite and clinical outcomes. METHODS: In the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), 690 of 848 randomly selected PD patients from 22 facilities reported their appetite by using the short form (three items) of the Appetite and Diet Assessment Tool (ADAT), between 2016 and 2018. In this questionnaire, the patients rated their appetite as well as a change in appetite over time. Cox proportional hazards model regression was used to estimating associations between self-reported appetite and clinical outcomes, including mortality, haemodialysis (HD) transfer and peritonitis. RESULTS: Half of the PD patients reported a good appetite, whereas 34% and 16% reported fair and poor appetites, respectively. Poor appetite was more prevalent among female, diabetic, congestive heart failure, older age and patients who had worse nutritional indicators, including lower time-averaged serum albumin and serum creatinine concentrations, as well as a higher proportions of hypokalaemia and severe hypoalbuminemia (serum albumin <3 g/dl). After adjusting for age, sex, comorbidities, and PD vintage, poor appetite was associated with increased risks of peritonitis (adjusted hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.14-2.62), HD transfer (adjusted HR 2.25, 95% CI 1.24-4.10) and all-cause mortality (adjusted HR 1.60, 95% CI 1.08-2.39) compared to patients with good appetite. CONCLUSION: Patient-reported poor appetite was independently associated with higher risks of peritonitis, HD transfer and all-cause mortality. This warrants further investigation to identify effective interventions.

13.
Clin Transplant ; : e14235, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527568

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are uncommon causes of kidney failure. In kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis, disease recurrence is unlikely due to ongoing immunosuppression, and patients generally have good immunological outcomes. This study compared transplant outcomes between ANCA-associated vasculitis and other etiologies of kidney disease. All 18 901 adult kidney transplant recipients (1990-2018) were ascertained from the ANZDATA Registry. Cox proportional hazards models were used to compare allograft failure between etiologies of kidney disease. Of 254 participants whose primary disease was ANCA-associated vasculitis, 95 (37%) developed allograft failure; of those who developed graft failure, 62 (65%) died with a functioning allograft. Compared with patients with IgA nephropathy, those with ANCA-associated vasculitis had higher rates of all-cause allograft failure (HR: 1.4, 95% CI: 1.2-1.7); however, rates of death-censored allograft failure were similar (HR: 1.0, 95% CI: 0.7-1.4). The most frequent causes of death in the ANCA-vasculitis group who died with a functioning graft were infection (23%) and malignancy (36%). Kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis may have had a higher risk of dying due to complications of immunosuppression compared with most other causes of kidney failure; however, they also had lower risks of disease recurrence and rejection.

14.
PLoS One ; 16(2): e0247527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606848

RESUMO

INTRODUCTION: Adverse birth outcomes have important consequences for future lung health. We evaluated patterns of respiratory health services utilization in early childhood among children born preterm (PTB), small and large for gestational age at term (SGA and LGA, respectively), and appropriate-for-gestational age at term. MATERIALS AND METHODS: We conducted a population-based retrospective cohort study using administrative health data of all singleton live births in Alberta, Canada between 2005-2010. Data on hospitalizations and emergency department (ED) visits from birth to 5 years were collected for asthma, bronchitis, bronchiolitis, croup, influenza, pneumonia, and other acute upper and lower respiratory tract infections (other URTI and other LRTI, respectively). Adjusted rate ratios were estimated for respiratory ED visits and hospitalizations for adverse birth outcomes using the appropriate-for-gestational age at term group as reference. Age-specific trajectories of total respiratory health services utilization rates for each group were estimated in Poisson models. RESULTS: A total of 293,764 episodes of respiratory care from 206,994 children were analyzed. Very PTB children had the highest rates of health services use for all respiratory conditions, particularly for asthma, pneumonia, and bronchiolitis hospitalizations. Moderate/late PTB children also had elevated ED visits and hospitalizations for all respiratory conditions. Children born SGA showed high rates of ED visits for other LRTI, and of hospitalizations for bronchitis, bronchiolitis, and other URTI. Children born LGA had high rates of croup and other URTI ED visits, and of bronchiolitis and bronchiolitis hospitalizations. Age-specific trajectories showed a decreasing trend in the rates of total respiratory health service utilization from birth to five years of age for all groups studied. Children born PTB and LGA at term significantly required more respiratory health services over time compared to the reference group. CONCLUSION: Patterns of paediatric respiratory health services utilization vary according to gestational age and fetal growth.

15.
Perit Dial Int ; : 896860821989878, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33588659

RESUMO

This national survey of barriers to and constraints of acute peritoneal dialysis (aPD) in acute kidney injury (AKI) was performed by distributing an online questionnaire to all medical directors of public dialysis units registered with the Nephrology Society of Thailand during September-November 2019. One hundred and thirteen adult facilities responded to the survey covering 75 from 76 provinces (99%) of Thailand. aPD was performed in 66 centres (58%). In facilities where aPD practice was available, the utilization rate was relatively low (<10 cases/year) and limited to specific conditions, including HIV seropositive patients, previous receiving dialysis education and plan and difficult vascular access creation. Only 9% of facilities performed aPD routinely, but interestingly all such units permitted bedside catheter insertion by the nephrologists or internists. The major constraints placed on aPD practice were PD catheter insertion competency, timely catheter insertion support and the medical supporting team's knowledge/competency deficits. aPD for AKI is underutilized in Thailand and limited by the inability to undertake timely PD catheter insertion and knowledge and competency deficits.

16.
BMJ ; 372: m4573, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441402

RESUMO

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Mortalidade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
17.
Br J Clin Pharmacol ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507553

RESUMO

AIMS: Early identification of patients likely to die after acetaminophen (APAP) poisoning remains challenging. We sought to compare the sensitivity and time to fulfilment (latency) of established prognostic criteria. METHODS: Three physician toxicologists independently classified every in-hospital death associated with APAP overdose from eight large Canadian cities over three decades using the Relative Contribution to Fatality scale from the American Association of Poison Control Centres. The sensitivity and latency were calculated for each of the following criteria: King's College Hospital (KCH), Model for End Stage Liver Disease (MELD) ≥33, lactate ≥3.5 mmol/L, phosphate ≥1.2 mmol/L 48+ hours post-ingestion, as well as combinations thereof. RESULTS: A total of 162 in-hospital deaths were classified with respect to APAP as follows: 26 Undoubtedly, 40 Probably, 27 Contributory, 14 Probably not, 25 Clearly not, and 30 Unknown. Cases from the first three classes (combined into n = 93 "APAP deaths") typically presented with supratherapeutic APAP concentrations, hepatotoxicity, acidaemia, coagulopathy and/or encephalopathy, and began antidotal treatment a median of 12 hours (IQR 3.4-30 h) from the end of ingestion. Among all patients deemed "APAP deaths", meeting either KCH or lactate criteria demonstrated the highest sensitivity (94%; 95% CI 86-98%), and the shortest latency from hospital arrival to criterion fulfilment (median 4.2 h; IQR 1.0-16 h). In comparison, the MELD criterion demonstrated a substantially lower sensitivity (55%; 43-66%) and longer latency (52 h; 4.4-∞ h, where "∞" denotes death prior to criterion becoming positive). CONCLUSIONS: Meeting either KCH or serum lactate criteria identifies most patients who die from acetaminophen poisoning at or shortly after hospital presentation.

18.
Nephrology (Carlton) ; 26(5): 471-478, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33501716

RESUMO

BACKGROUND: There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery. AIM: To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation. METHODS: Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing. RESULTS: The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post-transplant, reflected in reductions of the mean (±SD) richness values (156 ± 46.5 to 116 ± 38.6, p = 0.002), and Shannon diversity (3.57 ± 0.49 to 3.14 ± 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post-transplant (26-fold increase from 0.16 ± 0.0091 to 4.6 ± 0.3; p = 0.006; FDR = 0.12). Functionally, the post-transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2-fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6-fold; p = 0.006; FDR = 0.14). CONCLUSION: Live donor kidney transplantation and standard care post-transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.

19.
Cochrane Database Syst Rev ; 1: CD012899, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501650

RESUMO

BACKGROUND: Patients with chronic kidney disease (CKD) who require urgent initiation of dialysis but without having a permanent dialysis access have traditionally commenced haemodialysis (HD) using a central venous catheter (CVC). However, several studies have reported that urgent initiation of peritoneal dialysis (PD) is a viable alternative option for such patients. OBJECTIVES: This review aimed to examine the benefits and harms of urgent-start PD compared to HD initiated using a CVC in adults and children with CKD requiring long-term kidney replacement therapy. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 May 2020 for randomised controlled trials through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. For non-randomised controlled trials, MEDLINE (OVID) (1946 to 11 February 2020) and EMBASE (OVID) (1980 to 11 February 2020) were searched. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and non-RCTs comparing urgent-start PD to HD initiated using a CVC. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed the quality of studies independently. Additional information was obtained from the primary investigators. The estimates of effect were analysed using random-effects model and results were presented as risk ratios (RR) with 95% confidence intervals (CI). The GRADE framework was used to make judgments regarding certainty of the evidence for each outcome. MAIN RESULTS: Overall, seven observational studies (991 participants) were included: three prospective cohort studies and four retrospective cohort studies. All the outcomes except one (bacteraemia) were graded as very low certainty of evidence given that all included studies were observational studies and few events resulting in imprecision, and inconsistent findings. Urgent-start PD may reduce the incidence of catheter-related bacteraemia compared with HD initiated with a CVC (2 studies, 301 participants: RR 0.13, 95% CI 0.04 to 0.41; I2 = 0%; low certainty evidence), which translated into 131 fewer bacteraemia episodes per 1000 (95% CI 89 to 145 fewer). Urgent-start PD has uncertain effects on peritonitis risk (2 studies, 301 participants: RR 1.78, 95% CI 0.23 to 13.62; I2 = 0%; very low certainty evidence), exit-site/tunnel infection (1 study, 419 participants: RR 3.99, 95% CI 1.2 to 12.05; very low certainty evidence), exit-site bleeding (1 study, 178 participants: RR 0.12, 95% CI 0.01 to 2.33; very low certainty evidence), catheter malfunction (2 studies; 597 participants: RR 0.26, 95% CI: 0.07 to 0.91; I2 = 66%; very low certainty evidence), catheter re-adjustment (2 studies, 225 participants: RR: 0.13; 95% CI 0.00 to 18.61; I2 = 92%; very low certainty evidence), technique survival (1 study, 123 participants: RR: 1.18, 95% CI 0.87 to 1.61; very low certainty evidence), or patient survival (5 studies, 820 participants; RR 0.68, 95% CI 0.44 to 1.07; I2 = 0%; very low certainty evidence) compared with HD initiated using a CVC. Two studies using different methods of measurements for hospitalisation reported that hospitalisation was similar although one study reported higher hospitalisation rates in HD initiated using a catheter compared with urgent-start PD. AUTHORS' CONCLUSIONS: Compared with HD initiated using a CVC, urgent-start PD may reduce the risk of bacteraemia and had uncertain effects on other complications of dialysis and technique and patient survival. In summary, there are very few studies directly comparing the outcomes of urgent-start PD and HD initiated using a CVC for patients with CKD who need to commence dialysis urgently. This evidence gap needs to be addressed in future studies.


Assuntos
Cateteres Venosos Centrais , Tratamento de Emergência/métodos , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Tempo para o Tratamento , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Viés , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Tratamento de Emergência/efeitos adversos , Tratamento de Emergência/instrumentação , Tratamento de Emergência/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Estudos Observacionais como Assunto/estatística & dados numéricos , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/instrumentação , Diálise Peritoneal/métodos , Diálise Peritoneal/mortalidade , Peritonite/epidemiologia , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Diálise Renal/mortalidade , Insuficiência Renal Crônica/mortalidade
20.
Nephrology (Carlton) ; 26(1): 62-69, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32829534

RESUMO

AIM: The management of blood pressure in patients requiring dialysis remains challenging and controversial. This study aimed to describe the perspectives of patients treated with peritoneal or haemodialysis regarding blood pressure, to inform patient-centred management. METHODS: We conducted a secondary thematic analysis of qualitative data from multiple data sets derived from the Standardised Outcomes in Nephrology (SONG) initiative. We extracted and analysed the responses of adult patients (aged 18 years or over) on haemodialysis and peritoneal dialysis, and their caregivers. Qualitative data were extracted from 26 focus groups, two international Delphi surveys and two consensus workshops completed as part of the SONG-Haemodialysis and SONG-Peritoneal dialysis projects. RESULTS: Collectively, the studies involved 644 patients and caregivers from 86 countries. We identified four themes: helpless and incapacitated (including the subthemes of disabling and debilitating symptoms, limiting ability to work, fear of "crashes" - a sudden drop in blood pressure - forced to depend on others); dismissed and ignored (disregarded as a problem, lacking information, education and reassurance); escalating medication burden; and taking control for improved self-management (determining thresholds in fluid management, establishing a routine for proactive monitoring). CONCLUSION: Blood pressure symptoms are debilitating for patients on dialysis and exacerbated by a perceived lack of information about how to understand and manage these symptoms. More patient-centred management of blood pressure, particularly symptom-causing blood pressure, in patients on dialysis is likely to substantially improve patient satisfaction and outcomes.

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