Effect of a general practitioner management plan on health outcomes and hospitalisations in older patients with diabetes.

BACKGROUND: Little is known about the impact of a general practitioner management plan (GPMP) on health outcomes of patients with diabetes. AIM: To examine the impact of a GPMP on the risk of hospitalisation for diabetes. METHODS: A retrospective study using administrative data from the Australian Government Department of Veterans' Affairs was conducted (1 July 2006 to 30 June 2014) of diabetes patients either exposed or unexposed to a GPMP. The primary end-point was the risk of first hospitalisation for a diabetes-related complication and was assessed using Cox proportional hazard regression models with death as a competing risk. Secondary end-points included rates of receiving guideline care for diabetes, with differences assessed using Poisson regression analyses. RESULTS: A total of 16 214 patients with diabetes were included; 8091 had a GPMP, and 8123 did not. After 1 year, 545 (6.7%) patients with a GPMP and 634 (7.8%) of patients without a GPMP were hospitalised for a diabetes complication. There was a 22% reduction in the risk of being hospitalised for a diabetes complication (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.87, P < 0.0001) for those who received a GPMP by comparison to those who did not. Increased rates of diabetes guideline care, HbA1c claims (adjusted HR 1.29, 95% CI 1.25-1.33) and microalbuminura claims (adjusted HR 1.65, 95% CI 1.58-1.72) were observed after a GPMP. CONCLUSION: Provision of a GPMP in older patients with diabetes resulted in improved health outcomes, delaying the risk of hospitalisation at 12 months for diabetes complications. GPMP should be included as part of routine primary care for older patients with diabetes.

Cost driver analysis of statin expenditure on Australia's Pharmaceutical Benefits Scheme.

INTRODUCTION: The Australian Pharmaceutical Benefits Scheme (PBS) provides universal access to subsidized medicines. In 2013, statins as a class had the highest expenditure on the PBS. OBJECTIVES: To assess the influence of policies and drivers affecting PBS statin utilization and expenditure between 1992 and 2013. METHODS: Analyses conducted from 1992 to 2013 and over three distinct time periods, including monthly expenditure/prescription, annual utilization (calculated as Defined Daily Doses/1000 inhabitants/day) and statin strengths dispensed. RESULTS: The major driver of increased PBS expenditure for statins was increased volumes. After adjusting for inflation, the average PBS expenditure on statin prescriptions was the major negative driver. Other influential drivers included the increased use of newer statins and increased strength of statins dispensed. DISCUSSION: Whilst the inflation-adjusted reimbursed price of statins decreased, increased utilization, including increased use of patented statins, increased total statin expenditure. Successful measures adopted by other countries could be applied to Australia to decrease total medicines expenditure.

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison.

WHAT IS KNOWN AND OBJECTIVE: Endocrine therapy is an effective treatment for post-menopausal women with 'oestrogen receptor-positive' invasive breast cancers. There are two main types of endocrine therapies: selective oestrogen receptor modulators (tamoxifen) and aromatase inhibitors (anastrozole, letrozole and exemestane). The aim of this study was to compare the patterns of use of endocrine therapies for breast cancer in women between nine developed countries. METHODS: A longitudinal, cross-national drug utilization study was conducted. The endocrine therapies included were tamoxifen and the aromatase inhibitors: anastrozole, letrozole and exemestane. Annual drug utilization data were collected from Australia, Denmark, England, Finland, France, Iceland, the Netherlands, Norway and Sweden over the period 2001-2012. Utilization was measured in DDD/1000 inhabitants/day and was also adjusted for breast cancer incidence and female population statistics. RESULTS AND DISCUSSION: Total use of endocrine therapies either increased or remained steady in all countries. Total endocrine therapy usage was consistently highest in England and France. Norway showed the lowest usage of endocrine therapies overall, using only 1.80 DDD/1000 inhabitants/day in 2012. Downward trends in tamoxifen use and upward trends in aromatase inhibitors were seen across all countries over the study period. By 2012, aromatase inhibitors represented over half of total endocrine therapy use in all countries, and as high as 74% and 80% in France and Denmark, respectively. WHAT IS NEW AND CONCLUSION: Our analysis found a shift in use of endocrine therapy from tamoxifen to aromatase inhibitors. This trend is consistent with major clinical guidelines endorsing preferential use of aromatase inhibitors in post-menopausal women. Stabilization or small increase in tamoxifen use in the recent years may reflect the recognition of tamoxifen as still an appropriate first-line treatment. The similarity in utilization patterns may be due to the relatively comparable healthcare systems in the countries, namely universal health insurance and pharmaceutical coverage. Differences in utilization observed could be due to differences in breast cancer incidence, prescribing behaviours, interpretation of new trial evidence, and timing of drug marketing approval and reimbursement between countries.

[Acquired haemophilia A: two cases]. / Deux observations d'hémophilie A acquise.

BACKGROUND: Acquired haemophilia A (AH) is an uncommon bleeding disorder that presents as multiple, disseminated spontaneous subcutaneous bleeds. Diagnosis may be made on the basis of prolonged activated partial thromboplastin time (aPTT). The severity of the disease is associated with the low risk of haemoglobin levels and with potential links with other diseases. OBSERVATIONS: Two men were hospitalized for extensive and spontaneous subcutaneous hematoma. In both cases, the International Normalized Ratio (INR) was normal, but aPTT was 3 times higher than normal. Autoantibodies against coagulation factor VIII confirmed the diagnosis of AH. The patients received immunomodulatory treatment. In one patient, diffuse large B-cell lymphoma was discovered one year after successful treatment of AH. DISCUSSION: AH may be revealed by areas of bruising, subutaneous haematomas mimicking erythema nodosum, and muscle pain. APTT results alone can prompt the biologist to screen for factor VIII inhibitors. Aside from the risk of fatal bleeding, in half of all cases, the prognosis is determined by associated disorders such as blood dyscrasias, solid tumours, autoimmune diseases, use of certain medicines and pregnancy. After treatment for bleeding complications, therapy focuses on restoring the coagulation time. The aim of immunomodulatory therapy is to stem production of autoantibodies against coagulation factor VIII. CONCLUSION: AH must be considered rapidly in order to reduce the risk of bleeding emergencies and to screen for potential related diseases.

General practitioner management plans delaying time to next potentially preventable hospitalisation for patients with heart failure.

BACKGROUND: Several studies have shown that the Australian Medicare-funded chronic disease management programme can lead to improvements in care processes. No study has examined the impact on long-term health outcomes. AIMS: This retrospective cohort study assessed the association between provision of a general practitioner management plan and time to next potentially preventable hospitalisation for older patients with heart failure. METHODS: We used the Australian Government Department of Veterans' Affairs (DVA) claims database and compared patients exposed to a general practitioner management plan with those who did not receive the service. Kaplan-Meier analysis and Cox proportional hazards models were used to compare time until next potentially preventable hospitalisation for heart failure between the exposed and unexposed groups. RESULTS: There were 1993 patients exposed to a general practitioner management plan and 3986 unexposed patients. Adjusted results showed a 23% reduction in the rate of potentially preventable hospitalisation for heart failure at any time (adjusted hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.92; P = 0.0051) among those with a general practitioner management plan compared with the unexposed patients. Within one year, 8.6% of the exposed group compared with 10.7% of the unexposed group had a potentially preventable hospitalisation for heart failure. CONCLUSIONS: A general practitioner management plan is associated with delayed time to next potentially preventable hospitalisation for heart failure.

Serious statin-associated myotoxicity and rhabdomyolysis in Aboriginal and Torres Strait Islanders: a case series.

BACKGROUND: Statins are associated with skeletal muscle adverse effects. These are generally considered mild and reversible, with more severe toxicity occurring rarely. There is little known regarding statin myotoxicity in Aboriginal and Torres Strait Islander Australians who are at high cardiovascular risk and likely to receive statins. AIMS: To describe features of serious statin-associated myotoxicity (SSAM) occurring in Indigenous Australians and increase awareness of this condition. METHODS: Observational case series of SSAM in Aboriginal or Torres Strait Islanders. Cases were identified from personal clinical experience, referrals, reports to the Therapeutic Goods Administration, medical literature, an Internet search and reports from a histopathology laboratory. Information was collected onto a standardised data collection form. RESULTS: Fifteen cases of serious myotoxicity in Aboriginal or Torres Strait Islanders exposed to statins were identified from 2006 to 2012. The mean age was 55 (range 35-69). Painless weakness was the most common presentation. Interacting drugs were involved in seven cases. Biopsies were done in eight cases, three showed inflammatory polymyositis and five necrotising myositis. Three patients died and two had permanent severe disability. Resolution of symptoms after statin cessation was variable. CONCLUSIONS: SSAM has occurred in the Indigenous Australian population with some fatalities. Awareness of the potential for SSAM is essential for early recognition and effective management to reduce probability of avoidable catastrophic harm. Safe, as well as effective use of medication, is essential for optimum health outcomes. Effective pharmacovigilance and therapeutic risk management are important for Aboriginal and Torres Strait Islander Australians.

Time and geographical variations in utilization of endocrine therapy for breast cancer in Australia.

BACKGROUND: Endocrine therapies, aromatase inhibitors and tamoxifen, are commonly used as an adjuvant treatment in women with breast cancer. AIMS: This study examined the trends in use of endocrine therapies in Australia between 1996 and 2008, including a comparison between Australian states. METHODS: Prescription and expenditure data for tamoxifen and aromatase inhibitors (1996-2008) were obtained from the Drug Utilisation Sub-Committee. We converted prescription data to defined daily doses (DDD)/1000 population/day, the international unit of drug utilization. Utilization data in each state/territory (2003-2008) were adjusted for female population and age-standardized incidence rates of breast cancer. RESULTS: Total utilization of endocrine therapies increased by 30% from 1.66 to 2.14 DDD/1000/day between 1996 and 2008. Over this period, there was a shift in use from tamoxifen to aromatase inhibitors which became the highest used products in 2008. Anastrozole was the most used aromatase inhibitor and its use increased markedly after being listed on Australia's national Pharmaceutical Benefits Scheme (PBS) for early breast cancer in 2005 (average increase of 0.14 DDD/1000/day per annum between 2005 and 2008). PBS expenditure for endocrine therapies increased by 265% from $16 million to $58 million between 1996 and 2008. Utilization of endocrine therapies was overall comparable between regions except that it was substantially lower in the Northern Territory. CONCLUSIONS: Use of aromatase inhibitors has overtaken use of tamoxifen in 2008. Further real-world effectiveness data are required to evaluate whether large associated increases in expenditures partly because of the higher costs of aromatase inhibitors are actually justified.

Prasugrel vs. clopidogrel for cytochrome P450 2C19-genotyped subgroups: integration of the TRITON-TIMI 38 trial data.

BACKGROUND: Prasugrel is a newly marketed antiplatelet drug with improved cardiac outcomes as compared with clopidogrel for acute coronary syndromes involving percutaneous coronary intervention (PCI). Analysis of a subset of the TRITON-TIMI 38 trial demonstrated that cytochrome P450 2C19 (CYP2C19) reduced-function genotypes are associated with differential clinical responses to clopidogrel, but not prasugrel. Whether the CYP2C19 genotype has the potential to influence clinical choice of these drugs prior to PCI for individuals with unstable angina or non-ST segment elevation myocardial infarction is currently uncertain. METHODS AND RESULTS: An exploratory, secondary analysis was undertaken to estimate the clinical benefit of prasugrel over clopidogrel in subgroups defined by CYP2C19 genotype, by integrating the published results of the genetic substudy and the overall TRITON-TIMI 38 trial. Individuals with a CYP2C19 reduced-metabolizer genotype were estimated to have a substantial reduction in the risk of the composite primary outcome (cardiovascular death, myocardial infarction, or stroke) with prasugrel as compared with clopidogrel [relative risk (RR) 0.57; 95% confidence interval (CI) 0.39-0.83]. For CYP2C19 extensive metabolizers (∼70% of the population), however, the composite outcome risks with prasugrel and clopidogrel were not substantially different (RR 0.98; 95% CI 0.80-1.20). CONCLUSIONS: Integration of the TRITON-TIMI 38 data suggests that the CYP2C19 genotype can discriminate between individuals who receive extensive benefit from using prasugrel instead of clopidogrel, and individuals with comparable clinical outcomes with prasugrel and clopidorel. Thus, CYP2C19 genotyping has the potential to guide the choice of antiplatelet therapy, and further research is warranted to validate this estimate.

Reporting of studies on new medicines in major medical journals: a case study in breast cancer.

A comparison of the results of pivotal trials on three new medicines for advanced breast cancer published in medical journals with those presented in the US Food and Drug Administration (FDA) reviews showed that analyses reported in journals were of lower quality and were given a favorable interpretation by minimizing toxicity and ignoring methodological shortcomings. Several proposals to strengthen the quality of reporting of clinical trials in medical journals and to support reliable assessment of the therapeutic value of new medicines are discussed.

Co-morbidity and the utilization of health care for Australian veterans with diabetes.

OBJECTIVE: To examine the impact of co-morbidity on health service utilization by Australian veterans with diabetes. METHODS: A retrospective cohort study was undertaken including veterans aged >or= 65 years dispensed medicines for diabetes in 2006. Data were sourced from the Australian Department of Veterans' Affairs health claims database. Utilization of preventive health services for diabetes was assessed, including claims for glycated haemoglobin (HbA(1c)) test, microabuminuria, podiatry services, diabetes care plans, medication reviews, case conferences, general practitioner (GP) management plans and ophthalmology/optometry services. RESULTS: Among the 17,095 veterans dispensed medicines for diabetes, more than 80% had four or more co-morbid conditions. Those with a higher number of co-morbidities were more likely to have had claims for optometry/ophthalmology services and podiatry services, but not for other services. Veterans with at least one diabetes-related hospital admission had no more claims for diabetes health services than those who had no diabetics-related hospital admission, except for endocrinology services (relative risk = 1.26, 95% confidence intervals 1.15-1.37). Veterans with dementia were less likely to have had claims for diabetes health services while patients with renal failure were more likely to have had claims for the services. CONCLUSIONS: Low utilization of preventive diabetes care services is apparent in all co-morbidity groups. Patients with renal failure or dementia used more and less health services resources, respectively. Given the high mean age of this population, there may be valid reasons for the low use, such as competing health demands and patients' preferences.

Comorbid chronic diseases, discordant impact on mortality in older people: a 14-year longitudinal population study.

OBJECTIVES: To determine the impact of comorbid chronic diseases on mortality in older people. DESIGN: Prospective cohort study (1992-2006). Associations between numbers of chronic diseases or mutually exclusive comorbid chronic diseases on mortality over 14 years, by Cox proportional hazards model adjusting for sociodemographic variables or Kaplan-Meier analyses, respectively. SETTING: Population based, Australia. PARTICIPANTS: 2087 randomly selected participants aged ≥65 years old, living in the community or institutions. MAIN RESULTS: Participants with 3-4 or ≥5 diseases had a 25% (95% CI 1.05 to 1.5, p=0.01) and 80% (95% CI 1.5 to 2.2, p<0.0001) increased risk of mortality, respectively, by comparison with no chronic disease, after adjusting for age, sex and residential status. When cardiovascular disease (CVD), mental health problem or diabetes were comorbid with arthritis, there was a trend towards increased survival (range 8.2-9.5 years) by comparison with CVD, mental health problem or diabetes alone (survival 5.8-6.9 years). This increase in survival with arthritis as a comorbidity was negated when CVD and mental health problems or CVD and diabetes were present in disease combinations together. CONCLUSION: Older people with ≥3 chronic diseases have increased risk of mortality, but discordant effects on survival depend on specific disease combinations. These results raise the hypothesis that patients who have an increased likelihood of opportunity for care from their physician are more likely to have comorbid diseases detected and managed.

Advertising of antihypertensive medicines and prescription sales in Australia.

BACKGROUND: Drug promotion is one of the main factors that influence prescribing practices, but there are limited data available to quantify the relationship between drug advertising and prescription sales. AIM: To investigate the relationship between advertising for antihypertensive medicines and prescription sales in Australia between 1993 and 2002. METHODS: Retrospective observational study. Advertising trends were monitored by counting the number of advertisements published in three Australian medical journals. Monthly prescription dispensing data were obtained from Drug Utilisation Sub-Committee and expressed as numbers of defined daily doses/1000 inhabitants/day. Linear regression and cross-correlations of time series were used in the analysis. RESULTS: The drug classes the most heavily advertised, angiotensin-converting enzyme inhibitors and calcium channel blockers, were also the most prescribed during the study period, while the drugs the least advertised, thiazide diuretics and beta-blockers, were the least used. In 5 of the 7 main antihypertensive classes, the product the most advertised was also the most prescribed. Other factors, such as the publication of large clinical trials, may have also influenced prescribing patterns. CONCLUSION: Prescription sales of antihypertensives in Australia are correlated with promotional advertising. The newest and most expensive medicines may be chosen over older effective drugs by prescribers. New policies on drug promotion control need to be developed.

Provision of information on regulatory authorities' websites.

BACKGROUND: Several organizations have raised concerns about the excessive secrecy maintained by regulatory authorities around the world, in particular in the European Union, France, UK, Canada and Australia. However, limited research has assessed the provision of information by regulatory authorities. This study aimed to assess the type and availability of information provided on the regulatory authorities' websites. METHODS: Regulatory authorities' websites in six countries (USA, Canada, UK, France, Australia and New Zealand) and at the European level (European Medicines Evaluation Agency) were surveyed by two reviewers between October 2005 and March 2006. The survey instrument included 16 criteria organized in 3 domains: information on marketed drugs, information on assessment of drugs and information on drug safety. RESULTS: There was a great variability in the level of information provided. Several medicine agencies did not provide basic information on marketed drugs, such as the summary of products' characteristics. Information on registration dossiers was scant on most websites except that of the US Food and Drug Administration. The European Medicines Evaluation Agency, the French agency and the Canadian agency released public assessment reports that contained only summarized information of registration data. Only one country, Canada, provided full access to pharmacovigilance data. The periodic safety update reports that companies have to provide regularly to regulatory authorities were not available in any country. CONCLUSION: Information on which regulatory authorities base their decisions for licensing new drugs and the rationales behind these decisions were often not publicly available.

Drug marketing in French-speaking African countries.

Pharmaceutical companies are often criticized for the quality of their drug advertisements in developing countries. The quantitative data we have collected on advertisements in Francophone African countries confirm these criticisms. In 1990, only 41 out of 141 advertisements published in 6 medical and paramedical journals aimed at Francophone health personnel in Africa conformed to French standards for accuracy and objectivity. Indications were absent from 5 (3.5%) advertisements and exaggerated in 42 (29.8%); side-effects were not mentioned at all in 37 (26.2%) advertisements and were incomplete in a further 20 (14.2%). Similarly, contraindications were absent from 30 (21.3%) advertisements and incomplete in 19 (13.5%). It is clear that pharmaceutical companies do not always follow a code of ethical conduct and that they frequently exploit the lack of effective controls in developing countries. This attitude creates a hazard to public health and tarnishes the image of the companies concerned.

Publicite pharmaceutique en Afrique francophone

Des critiques ponctuelles sont parfois adressees aux laboratoires pharmaceutiques sur la qualite des publicites pharmaceutiques qu'ils publient dans les pays en developpement. La presente etude; qui apporte des donnees quantitatives sur les publicites publiees en Afrique francophone; confirme ces critiques. Quarante et une publicites seulement; sur les 141 parues de maniere repetee dans six revues medicales et paramedicales diffusees en Afrique francophone en 1990 se conforment aux regles d'objectivite applicables en France. Les indications des medicaments sont absentes dans 5 publicites et elargies dans 42 autres; les effets indesirables sont absents de 37 publicites et incomplets dans 20 autres; les contre-indications sont absents de 30 publicites et incompletes dans 19 autres