Introduction The Safer Prescribing and Care for the Elderly (SPACE) cluster randomised controlled trial in 39 general practices found that a search of the practice database to identify and generate for each general practitioner (GP) a list of patients with high-risk prescribing, pharmacist-delivered one-on-one feedback to GPs, and electronic tick-box for GPs to select action for each patient (Patient letter; No letter but possible medication review when patient next in; No action), prompted safer prescribing at 6 months but not at 1 year. Aim This process evaluation explores research participation, intervention uptake and effect on GPs. Methods Mixed methods were used including quantitative data (log of practice recruitment, demographic data, intervention delivery and GP responses including tick-box selections) and qualitative data (trial pharmacist reflective journal). Data were analysed using descriptive statistics and general inductive analysis, respectively. Results Recruitment of general practices was challenging, with only 39% of eligible practices agreeing to participate. Those who declined were often ‘too busy’. Engagement was also challenging, especially in larger practices, with the trial pharmacist managing to meet with only 64% of GPs in the intervention group. The GPs who did engage were positive about the intervention, but elected to send letters to only 23% of patients with high-risk prescribing, either because the high-risk prescribing had already stopped, the GP did not agree the prescribing was ‘high-risk’ or the GP was concerned a letter would upset the patient. Conclusions Effectiveness of the SPACE cluster randomised controlled trial could be improved by changes including ensuring searches are current and relevant, repeating cycles of search and feedback, and integrating pharmacists into general practices.

BACKGROUND:Safer prescribing in general practice may help to decrease preventable adverse drug events (ADE) and related hospitalisations.AIM:To test the effect of the Safer Prescribing and Care for the Elderly (SPACE) intervention on high-risk prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) and/or antiplatelet medicines and related hospitalisations.DESIGN & SETTING:A pragmatic cluster randomised controlled trial in general practice. Participants were patients at increased risk of ADEs from NSAIDs and/or antiplatelet medicines at baseline. SPACE comprises automated search to generate for each GP a list of patients with high-risk prescribing; pharmacist outreach to provide education and one-on-one review of list with GP; and automated letter inviting patients to seek medication review with their GP.METHOD:The primary outcome was the difference in high-risk prescribing of NSAIDs and/or antiplatelet medicines at 6 months. Secondary outcomes were high-risk prescribing for gastrointestinal, renal, or cardiac ADEs separately, 12-month outcomes, and related ADE hospitalisations.RESULTS:Thirty-nine practices were recruited with 205 GPs and 191 593 patients, of which 21 877 (11.4%) were participants. Of the participants, 1479 (6.8%) had high-risk prescribing. High-risk prescribing improved in both groups at 6 and 12 months compared with baseline. At 6 months, there was no significant difference between groups (odds ratio [OR] 0.99; 95% confidence intervals [CI] = 0.87 to 1.13) although SPACE improved more for gastrointestinal ADEs (OR 0.81; 95% CI = 0.68 to 0.96). At 12 months, the control group improved more (OR 1.29; 95% CI = 1.11 to 1.49). There was no significant difference for related hospitalisations.CONCLUSION:Further work is needed to identify scalable interventions that support safer prescribing in general practice. The use of automated search and feedback plus letter to patient warrants further exploration.

Rationale & Objective: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design: Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations: 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction: Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results: The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [ 95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m(2)), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations: Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Abstract Objective To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. Design Individual participant data meta-analysis. Setting Cohorts from 40 countries with data collected between 1970 and 2017. Participants Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). Main outcome measures GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. Results Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. Conclusions Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Background Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Methods In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Findings Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (p interaction < 0.0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed. Interpretation Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows:•African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr.; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Rachel J. Middleton, Donal J. O’Donoghue; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Köttgen, Florian Kronenberg, Barbara Bärthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Ontario Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis and Transplantation program (ICES KDT): Amit X. Garg, Eric McArthur, Danielle M. Nash; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study (NephroTest): Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Verónica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agées (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schön, Mårten Segelmark, Karl-Göran Prütz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.•CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Köttgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.•CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).•Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director). Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rateKidney InternationalVol. 93Issue 6PreviewPatients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Full-Text PDF Open Archive

High-risk prescribing, adverse drug events, and avoidable adverse drug event hospitalizations are common. The single greatest risk factor for high-risk prescribing and adverse drug events is the number of medications a person is taking. More people are living longer and taking more medications for multiple long-term conditions. Most on-going prescribing occurs in primary care. The most effective, cost-effective, and practical approach to safer prescribing in primary care is not yet known. To test the effect of the Safer Prescribing And Care for the Elderly (SPACE) intervention on high-risk prescribing of nonsteroidal anti-inflammatory and antiplatelet medicines, and related adverse drug event hospitalizations. This is a protocol of a cluster randomized controlled trial. The clusters will be primary care practices. Data collection and analysis will be at the level of patient. Recruitment started in 2018. Six-month data collection will be in 2018. This study addresses an important translational gap, testing an intervention designed to prompt medicines review and support safer prescribing in routine primary care practice. Australian New Zealand Clinical Trials Registry: ACTRN12618000034235 http://www.ANZCTR.org.au/ACTRN12618000034235.aspx (Archived with Webcite at http://www.webcitation.org/6yj9RImDf)

Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0–1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. Conclusions Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.

BACKGROUND:High-risk prescribing places patients at increased risk of adverse drug events (ADEs). High-risk prescribing and ADE hospitalisations are increasingly common as people are living longer and taking more medicines for multiple chronic conditions. The Safer Prescribing and Care for the Elderly (SPACE) intervention is designed to foster patient engagement in medicines management and prompt medicines review.AIM:To pilot the SPACE intervention in preparation for a larger cluster randomised controlled trial (RCT).DESIGN & SETTING:A pilot study in two general practices. Study participants were all patients at increased risk of an adverse drug reaction (ADE) from non-steroidal anti-inflammatory drugs (NSAIDs) and/or antiplatelet medicines. The primary outcome was the proportion of participants receiving high-risk prescribing at 6 months and 12 months compared with baseline.METHOD:The SPACE intervention comprised automated practice audit to identify and generate for each GP a list of patients with high-risk prescribing for these medicines; an outreach visit by clinical advisory pharmacist to deliver education and to go through with each GP their list of at-risk patients and indicate in a tick-box the intended action for each patient; and a mail-out from GPs to selected patients containing a medicines information brochure and a letter encouraging patients to discuss their medicines when they next see their GP.RESULTS:SPACE can be delivered within existing primary care infrastructure. The rate of high-risk prescribing was reduced at 6 months following the delivery of the intervention, but these improvements were not evident at 12 months.CONCLUSION:SPACE prompts medicines review and shows promising signs of supporting safer prescribing in general practice in the short term. A randomised trial of SPACE started in 2018.

Background The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0‐to‐9‐point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events ( MACE ) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting. Methods and Results We evaluated the performance of TRS2°P for predicting MACE in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of MACE across 5 cohorts over a mean follow‐up of 5 years, and the overall MACE rate ranged from 5.0 to 18.4 (per 100 person‐years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C‐statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C‐statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher MACE risk, with strongest associations observed (meta‐analyzed adjusted hazard ratio 1.6–1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3–1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1). Conclusions TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings.

AimLower limb amputation is a serious complication of diabetic foot disease and there are unexplained ethnic variations in incidence. This study investigates the risk of amputation among different ethnic groups after adjusting for demographic, socio-economic status and clinical variables.MethodsWe used primary care data from a large national multi-ethnic cohort of patients with Type2 diabetes in New Zealand and linked hospital records. The primary outcome was time from initial data collection to first lower limb amputation. Demographic variables included age of onset and duration since diabetes diagnosis, gender, ethnicity and socio-economic status. Clinical variables included smoking status, height and weight, blood pressure, HbA(1c), total cholesterol/HDL ratio and albuminuria. Cox proportional hazards models were used.ResultsThere were 892 lower limb amputations recorded among 62002 patients (2.11 amputations per 1000person-years), followed for a median of 7.14years (422357person-years). After adjusting for demographic and socio-economic variables and compared with Europeans, Maori had the highest risk [hazard ratio (HR) 1.84 (95%CI:1.54-2.19)], whereas East Asians [HR 0.18, (0.08-0.44)] and South Asians [HR 0.39 (0.22-0.67)] had the lowestrisk. Adjusting for available clinical variables reduced the differences but they remained substantial [HR 1.61 (1.35-1.93), 0.23 (0.10-0.56) and 0.48 (0.27-0.83), respectively].ConclusionsEthnic groups had significantly different risk of lower limb amputation, even after adjusting for demographic and some major clinical risk factors. Barriers to care should be addressed and intensive prevention strategies known to reduce the incidence of lower limb amputations could be prioritized to those at greatest risk.

OBJECTIVE:To investigate maternal and birth-related risk factors associated with infant respiratory hospitalisations in New Zealand.METHODS:A Kaupapa Māori-framed retrospective cohort analysis of public hospital maternal data linked to infant data (54,980 births 1995-2009). Primary outcome was rate of hospitalisation for respiratory disease in the first year of life. Risk variables examined included socioeconomic status (SES), age, smoking, parity, gestation, time to hospital discharge, breastfeeding and maternal ethnicity as a potential marker of differential exposure to risk factors.RESULTS:Independent risk factors for hospitalisation included low maternal SES (rate ratio: 1.33 [95% CI 1.19-1.49]); smoking (1.3 [1.19-1.41]); parity (2.77 [2.37-3.24]); preterm birth (3.14 [2.58-3.83]; 30 compared with 40 weeks); but not breastfeeding (0.99 [0.87-1.11]). After adjustment for risk factors, respiratory hospitalisations remained highest among infants of young Māori women (rate ratio 1.93 [1.46-2.55] at age 22.5 years) and Pacific women across all maternal age groups (rate ratios 2.43 to 2.55), compared with infants of European women.CONCLUSIONS:Maternal and birth factors are strongly associated with ethnic disparities in infant hospital admissions for respiratory disease.IMPLICATIONS:Interventions that begin in pregnancy and address risk factors and social determinants of health are needed to address these disparities.

Objective The purpose of this study was to investigate the consistency of the proportional effect of fixed-dose combination therapy (the polypill') on the use of recommended cardiovascular preventative medications among indigenous Maori and non-indigenous adults in New Zealand.Methods We randomised Maori and non-Maori primary care patients at high risk of cardiovascular disease (either because of a prior event or with an estimated 5-year risk of a first event of at least 15%) to a polypill (containing aspirin, statin and two antihypertensives) or usual care for a minimum of 12 months. All patients had indications for all polypill components according to their general practitioner, and all medications (including the polypill) were prescribed by the patient's general practitioner and dispensed at community pharmacies. The main outcome for this study was the use of all recommended medications (antiplatelet, statin and two antihypertensives) at 12 months. Heterogeneity in the effect of polypill-based care compared with usual care on this outcome by ethnicity was assessed by logistic regression.Results Baseline use of recommended medications was 36% (93/257) among Maori and 51% (130/156) among non-Maori participants. Polypill-based care was associated with an increase in the use of recommended medications among Maori (relative risk [RR]: 1.87; 95% confidence interval [CI]: 1.50-2.34) and non-Maori (RR: 1.66; 95% CI: 1.37-2.00) when compared with usual care at 12 months, and there was no statistically significant heterogeneity in this outcome by ethnicity (p=0.92).Conclusion Polypill-based care is likely to reduce absolute inequities between Maori and non-Maori in the use of recommended cardiovascular preventative medications given baseline absolute differences and the consistency of the proportional effect of this intervention by ethnicity in this pragmatic trial in primary care.

IMPORTANCE Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. OBJECTIVE To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. DATA SOURCES Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. STUDY SELECTION Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. DATA EXTRACTION AND SYNTHESIS Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. MAIN OUTCOMES AND MEASURES Kidney failure (treatment by dialysis or kidney transplant). RESULTS During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). CONCLUSIONS AND RELEVANCE Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

OBJECTIVE:This study assessed whether 12 weeks of chiropractic care was effective in improving sensorimotor function associated with fall risk, compared with no intervention, in community-dwelling older adults living in Auckland, New Zealand.METHODS:Sixty community-dwelling adults older than 65 years were enrolled in the study. Outcome measures were assessed at baseline, 4 weeks, and 12 weeks and included proprioception (ankle joint position sense), postural stability (static posturography), sensorimotor function (choice stepping reaction time), multisensory integration (sound-induced flash illusion), and health-related quality of life (SF-36).RESULTS:Over 12 weeks, the chiropractic group improved compared with the control group in choice stepping reaction time (119 milliseconds; 95% confidence interval [CI], 26-212 milliseconds; P = .01) and sound-induced flash illusion (13.5%; 95% CI, 2.9%-24.0%; P = .01). Ankle joint position sense improved across the 4- and 12-week assessments (0.20°; 95% CI, 0.01°-0.39°; P = .049). Improvements were also seen between weeks 4 and 12 in the SF-36 physical component of quality of life (2.4; 95% CI, 0.04-4.8; P = .04) compared with control.CONCLUSION:Sensorimotor function and multisensory integration associated with fall risk and the physical component of quality of life improved in older adults receiving chiropractic care compared with control. Future research is needed to investigate the mechanisms of action that contributed to the observed changes in this study and whether chiropractic care has an impact on actual falls risk in older adults.

PROBLEM:There is evidence that peer-support programs can improve mental health indices and help-seeking behavior among students in some secondary school and university settings and that mindfulness can improve mental health in medical students. Peer-led programs have not been formally assessed in a medical student population, where psychological issues exist and where it has been shown that students approach peers for help in preference to staff members or professional services. INTERVENTION:Medical students elected peer leaders who underwent training and then provided the intervention. The peer leaders provided support to students in the intervention group, as well as offering teaching in mindfulness meditation. CONTEXT:An exploratory study was conducted with 2nd- and 3rd-year medical students at 1 medical school in New Zealand randomized into 2 groups. In addition to existing mental health resources, intervention participants received a program including peer support and peer-taught mindfulness practice. Study participants not offered the intervention participants could use existing mental health resources. Primary measures included depression (PHQ-9) and anxiety (GAD-7) scores. Secondary measures were quality of life, resilience (15-item resilience scale), academic self-concept, and motivation to learn, assessed at baseline and 6 months. OUTCOME:Of the 402 students eligible, 275 (68%) participated and 232 (58%) completed the study. At baseline, 53% were female and mean age was 21 years (SD = 3)-PHQ-9 score (M = 5.2, SD = 3.7) and GAD-7 score (M = 4.5, SD = 3.4). Twelve peer leaders were elected. There was good participation in the intervention. One fourth of intervention students used the face-to-face peer support and more than 50% attended a peer social event and/or participated in the mindfulness program. Although improvements in mental health were seen in the intervention group, the difference between the intervention and nonintervention groups did not reach statistical significance. LESSONS LEARNED:Although evidence exists for effectiveness of peer support and mindfulness in other contexts, this exploratory study was not able to show a statistically significant effect. Future studies could consider using a longer training period for the peer leaders, as well as targeting the study population to those most likely to benefit such as those with poorer mental health, or using a more intensive intervention or larger sample size. A cluster randomized study design would also reduce the risk of contamination.

BACKGROUND:Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. STUDY DESIGN:Meta-analysis of cohort studies. SETTING & POPULATION:8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts. SELECTION CRITERIA FOR STUDIES:Cohorts participating in the CKD Prognosis Consortium. PREDICTORS:Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions. OUTCOME:Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. RESULTS:During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension. LIMITATIONS:AKI identified by diagnostic code. CONCLUSIONS:Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

BACKGROUNDInsomnia is common in primary care. Cognitive behavioural therapy for insomnia (CBT-I) is effective but requires more time than is available in the general practice consultation. Sleep restriction is one behavioural component of CBT-I.AIMTo assess whether simplified sleep restriction (SSR) can be effective in improving sleep in primary insomnia.DESIGN AND SETTINGRandomised controlled trial of patients in urban general practice settings in Auckland, New Zealand.METHODAdults with persistent primary insomnia and no mental health or significant comorbidity were eligible. Intervention patients received SSR instructions and sleep hygiene advice. Control patients received sleep hygiene advice alone. Primary outcomes included change in sleep quality at 6 months measured by the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and sleep efficiency (SE%). The proportion of participants reaching a predefined 'insomnia remission' treatment response was calculated.RESULTSNinety-seven patients were randomised and 94 (97%) completed the study. At 6-month follow-up, SSR participants had improved PSQI scores (6.2 versus 8.4, P<0.001), ISI scores (8.6 versus 11.1, P = 0.001), actigraphy-assessed SE% (difference 2.2%, P = 0.006), and reduced fatigue (difference -2.3 units, P = 0.04), compared with controls. SSR produced higher rates of treatment response (67% [28 out of 42] versus 41% [20 out of 49]); number needed to treat = 4 (95% CI = 2.0 to 19.0). Controlling for age, sex, and severity of insomnia, the adjusted odds ratio for insomnia remission was 2.7 (95% CI = 1.1 to 6.5). There were no significant differences in other outcomes or adverse effects.CONCLUSIONSSR is an effective brief intervention in adults with primary insomnia and no comorbidities, suitable for use in general practice.

AIMS:Type 2 diabetes is common and is associated with an approximate 80% increase in the rate of mortality. Management decisions may be assisted by an estimate of the patient's absolute risk of adverse outcomes, including death. This study aimed to derive a predictive risk model for all-cause mortality in type 2 diabetes.METHODS:We used primary care data from a large national multi-ethnic cohort of patients with type 2 diabetes in New Zealand and linked mortality records to develop a predictive risk model for 5-year risk of mortality. We then validated this model using information from a separate cohort of patients with type 2 diabetes.RESULTS:26,864 people were included in the development cohort with a median follow up time of 9.1 years. We developed three models initially using demographic information and then progressively more clinical detail. The final model, which also included markers of renal disease, proved to give best prediction of all-cause mortality with a C-statistic of 0.80 in the development cohort and 0.79 in the validation cohort (7610 people) and was well calibrated. Ethnicity was a major factor with hazard ratios of 1.37 for indigenous Maori, 0.41 for East Asian and 0.55 for Indo Asian compared with European (P<0.001).CONCLUSIONS:We have developed a model using information usually available in primary care that provides good assessment of patient's risk of death. Results are similar to models previously published from smaller cohorts in other countries and apply to a wider range of patient ethnic groups.