Numerous glucose-lowering drugs are used to treat type 2 diabetes.
To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin.
Cochrane Library Central ...Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016.
Randomized clinical trials of 24 weeks' or longer duration.
Random-effects network meta-analysis.
The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight.
A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference SMD, 0.18 95% CI, 0.01 to 0.34), thiazolidinedione (SMD, 0.16 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD, 0.33 95% CI, 0.13 to 0.52), and α-glucosidase inhibitor (SMD, 0.35 95% CI, 0.12 to 0.58) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio OR, 3.13 95% CI, 2.39 to 4.12; risk difference RD, 10% 95% CI, 7% to 13%) and basal insulin (OR, 17.9 95% CI, 1.97 to 162; RD, 10% 95% CI, 0.08% to 20%) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 95% CI, 0.08 to 0.18; RD, -22% -27% to -18%). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 95% CI, 0.39 to 0.94; RD, -10% 95% CI, -18% to -2%).
Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.
Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some ...patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014.
This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.
The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov.
All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded.
Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables.
This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.Neutral pH, low GDP versus conventional glucose PD solutionUse of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m
(95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).Glucose polymer (icodextrin) versus conventional glucose PD solutionIn moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m
higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death.
This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.
Peritoneal Dialysis-Related Infections Cho, Yeoungjee; Chow, Kai-Ming; Kam-Tao Li, Philip ...
Clinical journal of the American Society of Nephrology,
05/2024, Letnik:
19, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Peritoneal dialysis (PD) represents an important treatment choice for patients with kidney failure. It allows them to dialyze outside the hospital setting, facilitating enhanced opportunities to ...participate in life-related activities, flexibility in schedules, time and cost savings from reduced travel to dialysis centers, and improved quality of life. Despite its numerous advantages, PD utilization has been static or diminishing in parts of the world. PD-related infection, such as peritonitis, exit-site infection, or tunnel infection, is a major concern for patients, caregivers, and health professionals-which may result in hesitation to consider this as treatment or to cease therapy when these complications take place. In this review, the definition, epidemiology, risk factors, prevention, and treatment of PD-related infection on the basis of the contemporary evidence will be described.
The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes.
The study included ...all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data.
365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived <100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p = 0.001), whilst overall peritonitis rates were higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio OR 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p < 0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable between the two groups.
Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients.
Peritoneal dialysis (PD) is an important home-based treatment for kidney failure and accounts for 11% of all dialysis and 9% of all kidney replacement therapy globally. Although PD is available in ...81% of countries, this provision ranges from 96% in high-income countries to 32% in low-income countries. Compared with haemodialysis, PD has numerous potential advantages, including a simpler technique, greater feasibility of use in remote communities, generally lower cost, lesser need for trained staff, fewer management challenges during natural disasters, possibly better survival in the first few years, greater ability to travel, fewer dietary restrictions, better preservation of residual kidney function, greater treatment satisfaction, better quality of life, better outcomes following subsequent kidney transplantation, delayed need for vascular access (especially in small children), reduced need for erythropoiesis-stimulating agents, and lower risk of blood-borne virus infections and of SARS-CoV-2 infection. PD outcomes have been improving over time but with great variability, driven by individual and system-level inequities and by centre effects; this variation is exacerbated by a lack of standardized outcome definitions. Potential strategies for outcome improvement include enhanced standardization, monitoring and reporting of PD outcomes, and the implementation of continuous quality improvement programmes and of PD-specific interventions, such as incremental PD, the use of biocompatible PD solutions and remote PD monitoring.
Shared decision-making about clinical care options in end-stage kidney disease is limited by inconsistencies in the reporting of outcomes and the omission of patient-important outcomes in trials. ...Here we generated a consensus-based prioritized list of outcomes to be reported during trials in peritoneal dialysis (PD). In an international, online, three-round Delphi survey, patients/caregivers and health professionals rated the importance of outcomes using a 9-point Likert scale (with 7–9 indicating critical importance) and provided comments. Using a Best-Worst Scale (BWS), the relative importance of outcomes was estimated. Comments were analyzed thematically. In total, 873 participants (207 patients/caregivers and 666 health professionals) from 68 countries completed round one, 629 completed round two and 530 completed round three. The top outcomes were PD-related infection, membrane function, peritoneal dialysis failure, cardiovascular disease, death, catheter complications, and the ability to do usual activities. Compared with health professionals, patients/caregivers gave higher priority to six outcomes: blood pressure (mean difference, 0.4), fatigue (0.3), membrane function (0.3), impact on family/friends (0.1), peritoneal thickening (0.1) and usual activities (0.1). Four themes were identified that underpinned the reasons for ratings: contributing to treatment longevity, preserving quality of life, escalating morbidity, and irrelevant and futile information and treatment. Patients/caregivers and health professionals gave highest priority to clinical outcomes. In contrast to health professionals, patients/caregivers gave higher priority to lifestyle-related outcomes including the impact on family/friends and usual activities. Thus, prioritization will inform a core outcome set to improve the consistency and relevance of outcomes for trials in PD.
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Concern regarding technique failure is a major barrier to increased uptake of peritoneal dialysis (PD), and the first year of therapy is a particularly vulnerable time.
A cohort study using ...competing-risk regression analyses to identify the key risk factors and risk periods for early transfer to hemodialysis therapy or death in incident PD patients.
All adult patients who initiated PD therapy in Australia and New Zealand in 2000 through 2014.
Patient demographics and comorbid conditions, duration of prior renal replacement therapy, timing of referral, PD modality, dialysis era, and center size.
Technique failure within the first year, defined as transfer to hemodialysis therapy for more than 30 days or death.
Of 16,748 patients included in the study, 4,389 developed early technique failure. Factors associated with increased risk included age older than 70 years, diabetes or vascular disease, prior renal replacement therapy, late referral to a nephrology service, or management in a smaller center. Asian or other race and use of continuous ambulatory PD were associated with reduced risk, as was initiation of PD therapy in 2010 through 2014. Although the risk for technique failure due to death or infection was constant during the first year, mechanical and other causes accounted for a greater number of cases within the initial 9 months of treatment.
Potential for residual confounding due to limited data for residual kidney function, dialysis prescription, and socioeconomic factors.
Several modifiable and nonmodifiable factors are associated with early technique failure in PD. Targeted interventions should be considered in high-risk patients to avoid the consequences of an unplanned transfer to hemodialysis therapy or death.
PD Solutions and Peritoneal Health Cho, Yeoungjee; Johnson, David W
Clinical journal of the American Society of Nephrology,
10/2018, Letnik:
13, Številka:
10
Journal Article
Urgent-start peritoneal dialysis (PD), defined as initiation of PD within two weeks of catheter insertion, has been emerging as an alternative mode of dialysis initiation for patients with chronic ...kidney disease (CKD) requiring urgent dialysis without established permanent dialysis access. Recently, several small studies have reported comparable patient outcomes between urgent-start and conventional-start PD.
To examine the benefits and harms of urgent-start PD compared with conventional-start PD in adults and children with CKD requiring long-term kidney replacement therapy.
We searched the Cochrane Kidney and Transplant Register of Studies up to 25 May 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. For non-randomised controlled trials, MEDLINE (OVID) (1946 to 27 June 2019), EMBASE (OVID) (1980 to 27 June 2019), Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov (up to 27 June 2019) were searched.
All randomised controlled trials (RCTs) and non-RCTs comparing the outcomes of urgent-start PD (within 2 weeks of catheter insertion) and conventional-start PD ( ≥ 2 weeks of catheter insertion) treatment in children and adults CKD patients requiring long-term dialysis were included. Studies without a control group were excluded.
Data were extracted and quality of studies were examined by two independent authors. The authors contacted investigators for additional information. Summary estimates of effect were examined using random-effects model and results were presented as risk ratios (RR) with 95% confidence intervals (CI) as appropriate for the data. The certainty of evidence for individual outcome was assessed using the GRADE approach.
A total of 16 studies (2953 participants) were included in this review, which included one multicentre RCT (122 participants) and 15 non-RCTs (2831 participants): 13 cohort studies (2671 participants) and 2 case-control studies (160 participants). The review included unadjusted data for analyses due to paucity of studies reporting adjusted data. In low certainty evidence, urgent-start PD may increase dialysate leak (1 RCT, 122 participants: RR 3.90, 95% CI 1.56 to 9.78) compared with conventional-start PD which translated into an absolute number of 210 more leaks per 1000 (95% CI 40 to 635). In very low certainty evidence, it is uncertain whether urgent-start PD increases catheter blockage (4 cohort studies, 1214 participants: RR 1.33, 95% CI 0.40 to 4.43; 2 case-control studies, 160 participants: RR 1.89, 95% CI 0.58 to 6.13), catheter malposition (6 cohort studies, 1353 participants: RR 1.63, 95% CI 0.80 to 3.32; 1 case-control study, 104 participants: RR 3.00, 95% CI 0.64 to 13.96), and PD dialysate flow problems (3 cohort studies, 937 participants: RR 1.44, 95% CI 0.34 to 6.14) compared to conventional-start PD. In very low certainty evidence, it is uncertain whether urgent-start PD increases exit-site infection (2 cohort studies, 337 participants: RR 1.43, 95% CI 0.24 to 8.61; 1 case-control study, 104 participants RR 1.20, 95% CI 0.41 to 3.50), exit-site bleeding (1 RCT, 122 participants: RR 0.70, 95% CI 0.03 to 16.81; 1 cohort study, 27 participants: RR 1.58, 95% CI 0.07 to 35.32), peritonitis (7 cohort studies, 1497 participants: RR 1.00, 95% CI 0.68 to 1.46; 2 case-control studies, participants: RR 1.09, 95% CI 0.12 to 9.51), catheter readjustment (2 cohort studies, 739 participants: RR 1.27, 95% CI 0.40 to 4.02), or reduces technique survival (1 RCT, 122 participants: RR 1.09, 95% CI 1.00 to 1.20; 8 cohort studies, 1668 participants: RR 0.90, 95% CI 0.76 to 1.07; 2 case-control studies, 160 participants: RR 0.92, 95% CI 0.79 to 1.06). In very low certainty evidence, it is uncertain whether urgent-start PD compared with conventional-start PD increased death (any cause) (1 RCT, 122 participants: RR 1.49, 95% CI 0.87 to 2.53; 7 cohort studies, 1509 participants: RR 1.89, 95% CI 1.07 to 3.3; 1 case-control study, 104 participants: RR 0.90, 95% CI 0.27 to 3.02; very low certainty evidence). None of the included studies reported on tunnel tract infection.
In patients with CKD who require dialysis urgently without ready-to-use dialysis access in place, urgent-start PD may increase the risk of dialysate leak and has uncertain effects on catheter blockage, malposition or readjustment, PD dialysate flow problems, infectious complications, exit-site bleeding, technique survival, and patient survival compared with conventional-start PD.
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