Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis

Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ]

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Impact of home telemonitoring and management support on blood pressure control in non-dialysis CKD: a systematic review protocol

Introduction Hypertension is a common public health problem and a key modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD). Home blood pressure (BP) telemonitoring (HBPT) and management is associated with improved BP control, accelerated delivery of care and decision-making strategies that can reduce adverse outcomes associated with hypertension. The aim of this paper is to describe the protocol for a systematic review to assess the impact of HBPT interventions used for improving BP control and reducing CV and kidney outcomes in non-dialysis CKD patients.Methods We developed this protocol using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO and grey literature for studies conducted in non-dialysis CKD patients on interventions using HBPT and reporting outcomes related to BP control and other outcomes such as CV events and kidney disease progression. All studies meeting these criteria, in adults and published from inception until 2020 with no language barrier will be included.Ethics and dissemination Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of HBPT on BP control in non-dialysis CKD patients, evidence gathered through it will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate government agencies.PROSPERO registration number CRD42020190705)

ASSESSING THE IMPACT OF SCREENING, EARLY IDENTIFICATION AND INTERVENTION PROGRAMMES FOR CHRONIC KIDNEY DISEASE: PROTOCOL FOR A SCOPING REVIEW

Chronic kidney disease (CKD) is a major threat to public health, especially in low-income and lower middle-income countries, where resources for treating patients with advanced CKD are scarce. Although early CKD identification and intervention hold promise for reducing the burden of CKD and risk factors, it remains unclear if an uniform strategy can be applicable across all income groups. The aim of this scoping review is to synthesise available evidence on early CKD identification programmes in all world regions and income groups. The study will also identify efforts that have been made to use interventions and implementation of early identification programmes for CKD across countries and income groups. Methods and analysis This review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O’Malley. Empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be searched to identify studies on CKD screening, early identification and interventions across all populations. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. We will use a general descriptive overview, tabular summaries and content analysis on extracted data. Ethics and dissemination The findings from our planned scoping review will enable us to identify items in early identification programmes that can be used in developing screening toolkits for CKD. We will disseminate our findings using traditional approaches that include open access peer-reviewed publication, scientific presentations and a white paper (call to action) report. Ethical approval will not be required for this scoping review as the data will be extracted from already published studie

EARLY IDENTIFICATION OF CKD—A SCOPING REVIEW OF THE GLOBAL POPULATIONS

Introduction: Decisions on whether to screen for chronic kidney disease (CKD) or not remain contentious in nephrology. This study provides a global overview of early CKD identification efforts. Methods: Guidelines for scoping reviews were followed and studies were identified by searching MEDLINE, EMBASE, Cochrane Library, CINAHL, ISI Web of Science, and PsycINFO. Data extracted from included studies focused on the following 4 themes: study population, measurement methods, interventions used, and available policies. Results: We identified 290 CKD screening and detection programs from 83 countries. Overall sample size was 3.72 million (North East Asia: 1.19 million), detection of CKD was the aim in 97.6%, 63.1% used populationbased screening methods, and only 12.4% were in rural populations. Reported CKD prevalence (stages 3– 5) was higher in targeted- (14.8%) than population-based studies (8.0%). Number of persons needed to screen (NNS) to identify 1 case was also lower in targeted studies (7 vs. 13). Single measurements (80%) and the combination of estimation of glomerular filtration rate with a urine test (albuminuria/proteinuria) (71.4%) were frequently used to detect CKD. Only 2.8% of studies included an intervention such as pharmacotherapy in identified cases. Policies on early identification were available in 30.1% of countries included. Conclusion: Methods for early CKD identification vary worldwide, often leading to wide variations in the reported prevalence. Efforts to standardize measurement methods for early detection focusing on highrisk populations and ensuring appropriate interventions are available to those identified with CKD will improve the value of programs and improve patient outcomes

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia