Healthcare services use by patients with heart failure in Australia: Findings from the SHAPE study.

BACKGROUND AND OBJECTIVES: General practitioners (GPs) play a central role in healthcare, serving as the first point of contact, making appropriate referrals and coordinating care for chronic conditions such as heart failure (HF). We sought to determine healthcare use by people with HF in primary care. METHOD: In this Study of Heart failure in the Australian Primary carE setting (SHAPE), we analysed records of 1.93 million adult patients who attended a total of 43 practices between 1 July 2013 and 30 June 2018. We identified and examined the data of 20,219 patients with HF to describe the frequency of visits and use of Medicare Benefits Schedule items. RESULTS: Patients with HF saw GPs 14.4 times per annum on average; 59.5% had a General Practice Management Plan (GPMP), 2.9% of GPMPs were reviewed annually or more frequently, and 46.8% of patients had been referred to a cardiologist. A total of 3761 had coexisting anxiety or depression, and of these 37.1% had a mental health plan. DISCUSSION: Patients with HF visit their GP frequently, with many not reaching guideline therapy nor referred to cardiologists. Low use of care planning and reviews presents an opportunity for GPs to improve care.

Estimating the economic impact of acute coronary syndrome in New Zealand over time (ANZACS-QI 64): a national registry-based cost burden study.

OBJECTIVES: To estimate the changes in costs associated with acute coronary syndrome (ACS) admissions in New Zealand (NZ) public hospitals over a 12-year period. DESIGN: A cost-burden study of ACS in NZ was conducted from the NZ healthcare system perspective. SETTING: Hospital admission costs were estimated using relevant diagnosis-related groups and their costs for publicly funded casemix hospitalisations, and applied to 190 364 patients with ACS admitted to NZ public hospitals between 2007 and 2018 identified from routine national hospital datasets. Trends in the costs of index ACS hospitalisation, hospital admissions costs, coronary revascularisation and all-cause mortality up to 1 year were evaluated. All costs were presented as 2019 NZ dollars. PRIMARY OUTCOME MEASURES: Healthcare costs attributed to ACS admissions in NZ over time. RESULTS: Between 2007 and 2018, there was a 42% decrease in costs attributed to ACS (NZ$7.7 million (M) to NZ$4.4 M per 100 000 per year), representing a decrease of NZ$298 827 per 100 000 population per year. Mean admission costs associated with each admission declined from NZ$18 411 in 2007 to NZ$16 898 over this period (p<0.001) after adjustment for key clinical and procedural characteristics. These reductions were against a background of increased use of coronary revascularisation (23.1% (2007) to 38.1% (2018)), declining ACS admissions (366-252 per 100 000 population) and an improvement in 1-year survival post-ACS. Nevertheless, the total ACS cost burden remained considerable at NZ$237 M in 2018. CONCLUSIONS: The economic cost of hospitalisations for ACS in NZ decreased considerably over time. Further studies are warranted to explore the association between reductions in ACS cost burden and changes in the management of ACS.

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes.

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were 'Alive without type 2 diabetes', 'Alive with type 2 diabetes' and 'Dead'. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

Applying a framework to assess the impact of cardiovascular outcomes improvement research.

BACKGROUND: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research. METHODS: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients. RESULTS: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery. CONCLUSIONS: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.

Coronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.

OBJECTIVES: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. DESIGN, SETTING, PARTICIPANTS: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. MAIN OUTCOME MEASURES: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). RESULTS: 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. CONCLUSIONS: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN 12614001294640; 11 December 2014 (prospective).

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care. METHODS: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634. FINDINGS: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group. INTERPRETATION: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder. FUNDING: None.

Carnosine and histidine-containing dipeptides improve dyslipidemia: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required. OBJECTIVE: Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines. DATA SOURCES: The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls. DATA EXTRACTION: Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome. DATA ANALYSIS: A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], -0.32 mmol/L [95%CI, -0.57 to -0.07], P = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, -0.14 mmol/L [95%CI, -0.20 to -0.08], P < 0.001) compared with controls. In studies using carnosine, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups. CONCLUSIONS: Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases. SYSTEMIC REVIEW REGISTRATION: PROSPERO registration no.: CRD42017075354.

An economic evaluation of the All New Zealand Acute Coronary Syndrome Quality Improvement Registry programme-subanalyses for Maori (ANZACS-QI 42).

AIMS: To evaluate the clinical and cost impacts of the All New Zealand Acute Coronary Syndrome Quality Improvement programme (ANZACS-QI) specifically for Maori with acute coronary syndrome (ACS). METHODS: Decision analytic Markov models were used to estimate the effectiveness and costs of the ANZACS-QI programme over four years of full coverage (2013 to 2016), against a hypothetical scenario in which the registry did not exist. The estimated return on investment (ROI) and incremental cost-effectiveness ratios (ICERs) are reported. RESULTS: The ROI ratio for the ANZACS-QI programme for Maori over the four-year period of full coverage was 1.51; that is, every dollar spent on the programme resulted in a return of NZD $1.51. The estimated ICER was NZD $114,786 per year of life saved (YoLS) over a one-year time horizon, but extending the benefits accrued to five years reduced the ICER to NZD $20,173 per YoLS. CONCLUSIONS: The ANZACS-QI programme represents a sound investment for improving outcomes in the setting of ACS for Maori in New Zealand. Using highly conservative assumptions, the programme would be cost-saving based on an annual ROI ratio of 1.5.

Frailty Confers High Mortality Risk across Different Populations: Evidence from an Overview of Systematic Reviews and Meta-Analyses.

We performed an overview of systematic reviews and meta-analyses to summarize available data regarding the association between frailty and all-cause mortality. Medline, Embase, CINAHL, Web of Science, PsycINFO, and AMED (Allied and Complementary Medicine) databases were searched until February 2020 for meta-analyses examining the association between frailty and all-cause mortality. The AMSTAR2 checklist was used to evaluate methodological quality. Frailty exposure and the risk of all-cause mortality (hazard ratio [HR] or relative risk [RR]) were displayed in forest plots. We included 25 meta-analyses that pooled data from between 3 and 20 studies. The number of participants included in these meta-analyses ranged between <2000 and >500,000. Overall, 56%, 32%, and 12% of studies were rated as of moderate, low, and critically low quality, respectively. Frailty was associated with increased risk of all-cause mortality in 24/24 studies where the HR/RRs ranged from 1.35 [95% confidence interval (CI) 1.05-1.74] (patients with diabetes) to 7.95 [95% CI 4.88-12.96] (hospitalized patients). The median HR/RR across different meta-analyses was 1.98 (interquartile range 1.65-2.67). Pre-frailty was associated with a significantly increased risk of all-cause mortality in 7/7 studies with the HR/RR ranging from 1.09 to 3.65 (median 1.51, IQR 1.38-1.73). These data suggest that interventions to prevent frailty and pre-frailty are needed.

An Economic Evaluation of the All New Zealand Acute Coronary Syndrome Quality Improvement Registry Program (ANZACS-QI 28).

BACKGROUND: The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) program comprises a clinical quality registry of acute coronary syndrome patients admitted to hospitals across New Zealand. Its primary purpose is to improve quality of care by promoting evidence- and guidelines-based practice, and benchmarking against performance targets. Few studies have examined the cost-effectiveness attributed to clinical quality registries. We aimed to evaluate the clinical and cost impacts of the ANZACS-QI program in New Zealand from both a societal and health care system perspective. METHODS: Using decision analytic Markov models, we estimated the effectiveness and costs of the ANZACS-QI program in each year over 4 years (2013-2016), against a hypothetical scenario where the registry did not exist. We assumed that the ANZACS-QI contributed to 15% of the temporal changes to patient mortality and hospital readmissions for myocardial infarction observed in the study period. Marginal costs of the registry and years of life saved were estimated. RESULTS: Over a one-year period, the return on investment (ROI) ratio for the ANZACS-QI program was 1.53; thus, every dollar spent on the program resulted in a return of NZD $1.53. (All dollars are in 2017 New Zealand dollars [NZD] unless otherwise stated). The estimated incremental cost-effectiveness ratio (ICER) was $113,327 per year of life saved (YoLS). Extending the time horizon to 5 years, reduced the ICER to $19,684 per YoLS. CONCLUSIONS: The ANZACS-QI program represents a sound investment for New Zealand. Even based on highly conservative assumptions, the program is cost saving for society, at a ROI ratio of about 1.5 each year.

Defining Optimal Care for Functional Gut Disorders - Multi-Disciplinary Versus Standard Care: A Randomized Controlled Trial Protocol.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are the commonest reason for gastroenterological consultation, with patients usually seen by a specialist working in isolation. There is a wealth of evidence testifying to the benefit provided by dieticians, behavioral therapists, hypnotherapists and psychotherapists in treating these conditions, yet they rarely form a part of the therapeutic team, and these treatment modalities are rarely offered as part of the therapeutic management. There has been little examination of different models of care for FGIDs. We hypothesize that multi-disciplinary integrated care is superior to standard specialist-based care in the treatment of functional gut disorders. METHODS: The "MANTRA" (Multidisciplinary Treatment for Functional Gut Disorders) study compares comprehensive multi-disciplinary outpatient care with standard hospital outpatient care. Consecutive new referrals to the gastroenterology and colorectal outpatient clinics of a single secondary and tertiary care hospital of patients with an FGID, defined by the Rome IV criteria, will be included. Patients will be prospectively randomized 2:1 to multi-disciplinary (gastroenterologist, gut-hypnotherapist, psychiatrist, behavioral therapist ('biofeedback') and dietician) or standard care (gastroenterologist or colorectal surgeon). Patients are assessed up to 12 months after completing treatment. The primary outcome is an improvement on a global assessment scale at the end of treatment. Symptoms, quality of life, psychological well-being, and healthcare costs are secondary outcome measures. DISCUSSION: There have been few studies examining how best to deliver care for functional gut disorders. The MANTRA study will define the clinical and cost benefits of two different models of care for these highly prevalent disorders. TRIAL REGISTRATION NUMBER: Clinicaltrials.govNCT03078634 Registered on Clinicaltrials.gov, completed recruitment, registered on March 13th 2017. Ethics and Dissemination: Ethical approval has been received by the St Vincent's Hospital Melbourne human research ethics committee (HREC-A 138/16). The results will be disseminated in peer-reviewed journals and presented at international conferences. Protocol version 1.2.

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.

Importance: Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level. Objective: To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older. Data Sources: MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched. Study Selection: In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible. Data Extraction and Synthesis: The methodological quality of included studies was assessed using The Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model. Main Outcomes and Measures: Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration. Results: Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death. Conclusions and Relevance: Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.

Evaluation of the Effectiveness of a Phone Based Care Coordination Pilot on Hospital Utilisation and Costs for Patients With Chest Pain.

BACKGROUND: A small percentage of the population represents a disproportionate number of attendances at emergency departments (ED). "Frequent presenters" to ED with chest pain do not always fit into established pathways for acute myocardial events. With accelerated "rule out" protocols, patients are often discharged from the ED after short lengths of stay. This research will evaluate the effectiveness of a phone based care-coordination pilot designed to meet the needs of patients attending ED with cardiac and non-cardiac chest pain. METHODS: A longitudinal, single-arm interventional study with retrospectively recruited control group. Ninety-five patients were enrolled as the intervention group; 97 patients were retrospectively identified as controls. These patients had re-presented with chest pain within 6 months of a cardiac event, or attended hospital within 12 months two or more times with chest pain and/or complex needs. Intervention group patients were holistically assessed then phone-coached to support self-management of chest pain over 6 months. Following descriptive and univariate analysis, multivariate analysis was conducted to adjust for noted differences between the intervention and control groups. RESULTS: Thirty-day representation to ED was significantly less for the intervention group (14.1%) compared to controls (27.7%). After adjusting for baseline differences, intervention patients were more than two-fold less likely to re-present compared to controls (OR=0.42, 95%CI: 0.19-0.96). After adjustment for baseline differences, the savings in subsequent inpatient costs was $1588 per person, as a result of intervention, patients were less likely to have inpatient readmissions (16.3%) compared to controls (20.2%), although this was not statistically significant (p=0.588). CONCLUSION: A phone based care-coordination pilot with targeted interventions has the potential to reduce ED presentations and hospital readmissions among patients representing with chest pain.

Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.

AIM: There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. METHODS: This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. RESULTS: Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). CONCLUSION: Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study.

Can primary care team-based transition to insulin improve outcomes in adults with type 2 diabetes: the stepping up to insulin cluster randomized controlled trial protocol.

BACKGROUND: Type 2 diabetes (T2D) brings significant human and healthcare costs. Its progressive nature means achieving normoglycaemia is increasingly difficult, yet critical to avoiding long term vascular complications. Nearly one-half of people with T2D have glycaemic levels out of target. Insulin is effective in achieving glycaemic targets, yet initiation of insulin is often delayed, particularly in primary care. Given limited access to specialist resources and the size of the diabetes epidemic, primary care is where insulin initiation must become part of routine practice. This would also support integrated holistic care for people with diabetes. Our Stepping Up Program is based on a general practitioner (GP) and practice nurse (PN) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses. Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care. METHODS: This protocol is for a cluster randomized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D. 224 patients between the ages of 18 and 80 years with T2D, on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5% in the last six months will be recruited from 74 general practices. The unit of randomization is the practice.Primary outcome is change in glycated haemoglobin HbA1c (measured as a continuous variable). We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5% lower than control group at 12 months follow up. Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of <7.0%. We will also collect data on patient psychosocial outcomes and healthcare utilization and costs. DISCUSSION: The study is a pragmatic translational study with important potential implications for people with T2D, healthcare professionals and funders of healthcare though making better use of scarce healthcare resources, improving timely access to therapy that can improve disease outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612001028897.

Eplerenone. Pharmacia.

Pharmacia Corp (formerly GD Searle & Co) is developing eplerenone, an aldosterone receptor antagonist, as a potential treatment for congestive heart failure and systemic hypertension. The compound has been registered for hypertension and Pharmacia plans to submit a supplemental NDA for congestive heart failure in the first half of 2003 based on positive results from a phase III clinical trial.