Effectiveness of social prescribing for chronic disease prevention in adults: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Social prescribing (SP) enables healthcare professionals to link patients with non-medical interventions available in the community to address underlying socioeconomic and behavioural determinants. We synthesised the evidence to understand the effectiveness of SP for chronic disease prevention. METHODS: A systematic literature search was conducted using five databases and two registries. Eligible studies included randomised controlled trials of SP among community-dwelling adults recruited from primary care or community setting, investigating any chronic disease risk factors defined by the WHO (behavioural factors: smoking, physical inactivity, unhealthy diet and excessive alcohol consumption; metabolic factors: raised blood pressure, overweight/obesity, hyperlipidaemia and hyperglycaemia). Random effect meta-analyses were performed at two time points: completion of intervention and follow-up after trial. RESULTS: We identified nine reports from eight trials totalling 4621 participants. All studies evaluated SP exercise interventions which were highly heterogeneous regarding the content, duration, frequency and length of follow-up. Majority of studies had some concerns for risk of bias. Meta-analysis revealed that SP likely increased physical activity (completion: mean difference (MD) 21 min/week, 95% CI 3 to 39, I2=0%; follow-up ≤12 months: MD 19 min/week, 95% CI 8 to 29, I2=0%). However, SP may not improve markers of adiposity, blood pressure, glucose and serum lipid. There were no eligible studies that primarily target unhealthy diet, smoking and excessive alcohol drinking behaviours. CONCLUSIONS: SP exercise interventions probably increased physical activity slightly; however, no benefits were observed for metabolic factors. Determining whether SP is effective in modifying the determinants of chronic diseases and promotes sustainable healthy behaviours is limited by the current evidence of quantification and uncertainty, warranting further rigorous studies. PROSPERO REGISTRATION NUMBER: CRD42022346687.

Aspirin for primary prevention of cardiovascular events in the elderly: current status and future directions.

The role of aspirin in the secondary prevention of occlusive cardiovascular events has now been well established. Given this, aspirin in primary prevention has been the focus of several large trials and subsequent meta-analyses over the past 3 decades, and yet the issue remains controversial. Recent studies in populations with high baseline risk - such as diabetics and those with asymptomatic peripheral arterial disease - have not found the expected benefits of aspirin on cardiovascular endpoints, which contrasts with earlier studies that reported a reduced relative risk for outcomes such as myocardial infarction and ischaemic stroke, but not for mortality. Furthermore, in healthy populations, the absolute risk reduction conferred by aspirin is small and needs to be balanced against the risk of a major haemorrhage. Older adults have a higher risk for cardiovascular events and therefore might represent the group in which aspirin for primary prevention could deliver the greatest absolute benefit, yet at the same time, the elderly bear an increased vulnerability to major haemorrhage, including haemorrhagic stroke. It is also not known whether older adults experience the same risk reduction from aspirin as middle-aged individuals. The current evidence base does not sufficiently clarify whether aspirin for primary prevention confers a meaningful net benefit in the elderly.

Pharmacotherapies for obesity: past, current, and future therapies.

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs.

Smoking cessation-recent advances.

BACKGROUND: Smoking continues to be a major contributor to the burden of disease across the world although there has been a decrease in some developed countries such as USA and Australia. In countries of South-East Asia with a high prevalence of smoking, the incidence of tobacco-related diseases will continue to increase. METHODS: We reviewed the literature in relation to the pharmacology of nicotine, the measures used to determine the efficacy of anti-smoking therapies, and the randomised controlled trials and systematic reviews of pharmacotherapies published between 2004 and 2010. We focused primarily on the three first line therapies that are currently available: nicotine replacement therapy (NRT), bupropion and varenicline. RESULTS: Randomised controlled trials and meta-analyses have demonstrated that single therapy with either NRT, bupropion or varenicline are all more effective than placebo for smoking cessation. Abstinence rates for monotherapies varies from 13.3% to 19% for NRT compared to 7.5% to 14% for placebo, 19% to 19.7% for bupropion versus 10.9% to 11% for placebo and 25.5% to 25.6% for varenicline versus 11.2% to 14.8% for placebo. Of current therapies varenicline appears to be more effective at achieving abstinence. Some combination therapies with one or two formulations of NRT or NRT plus bupropion have demonstrated superior results to monotherapy. To date there are no randomised controlled trials of varenicline in combination with NRT or bupropion. CONCLUSION: Further studies are required to address the uncertainty that exists on the most appropriate duration of therapy as well as the effectiveness and safety of combination pharmacotherapy. Post-marketing surveillance continues to play an important role in monitoring the adverse effects events associated with these therapies.

Cost of myocardial infarction to the Australian community: a prospective, multicentre survey.

BACKGROUND: in order to evaluate the cost effectiveness of preventive strategies for myocardial infarction (MI), direct cost estimates are required. However, Australian-specific cost estimates for MI are not available. OBJECTIVE: the CosMIC (Cost of Myocardial Infarction to the Community) in Australia study was designed to determine the resource use and estimate the direct costs associated with MI in the Australian Health Care System. This information could subsequently be used in cost-effectiveness evaluations. METHODS: a prospective, multicentre survey was undertaken to investigate the costs associated with the initial hospitalization and the 12-month sequelae for patients with a first-ever MI. During the recruitment period 312 patients with MI from ten hospitals met the eligibility criteria. Of the 141 who consented to participate and were enrolled, three were withdrawn and 138 were included in the final analysis. Detailed data were collected for 12 months after the index hospitalization from several overlapping sources. All costs were considered from the point of view of total direct cost of care, i.e. regardless of who generated or paid for the service. RESULTS: the mean length of hospital stay for the initial acute episode was 7.4 days and the mean cost was $A10 934 (95% confidence interval [CI] 9588, 12 280) based on 2005 Australian dollars. There were 127 cardiac-related readmissions for 55 (40%) patients and the mean length of stay was 2.6 days. The mean total direct cost of an MI per patient was $A20 502 (95% CI 18 428, 22 576). The majority of the costs were for hospitalizations (initial and readmissions), which accounted for 77% of the total 12-month costs, whilst hospitalization costs for the initial acute event accounted for 53% of all costs. During the 12-month follow-up period, out-of-hospital medical service costs (Medicare Benefits Schedule services) contributed to 7% of the total costs incurred, medications 6%, ambulance costs 3% and all other outpatient services and carer costs 7%. CONCLUSION: the CosMIC study addresses the significant uncertainty associated with MI cost-of-illness data in Australia by providing an estimation of direct costs associated with MI in an Australian population. These direct costs can be used to determine the cost effectiveness of prevention strategies.

Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003.

BACKGROUND: Clozapine is an antipsychotic medication associated with a lower suicide rate compared with other antipsychotic agents. Clozapine is used specifically in patients for whom previous therapy was inadequate or not tolerated, and is the only antipsychotic agent associated with the development of myocarditis. OBJECTIVE: To retrospectively review all adverse drug reaction reports voluntarily submitted to the Australian Adverse Drug Reactions Unit mentioning suspected myocarditis in clozapine-treated patients. PATIENTS AND METHODS: We accessed all electronic database entries and case reports citing suspected myocarditis associated with clozapine therapy from January 1993 through to December 2003, inclusive. RESULTS: 116 case reports of suspected myocarditis amongst clozapine-treated patients were identified during the specified time frame (incidence between 0.7% and 1.2% of treated patients). Median patient age for these cases was 30 years (SD 11.1 years) compared with 37 years from the Clopine registry. The condition developed within a median 16 days (mean 19.8 days; SD 17.3 days) of commencing clozapine for the bulk of patients developing myocarditis within 6 months (n=93, 80.2%). For all cases with known treatment commencement and cessation dates (n=106), the condition developed within a median 17 days (mean 171.7 days, SD 530.9 days). Over nine-tenths of cases were prescribed clozapine within the dose range of 100 mg/day to 450 mg/day. Sixty patients (51.8%) recovered from their episode when reported or during follow-up reports, whereas 17 patients (14.7%) had not yet recovered: 27 patients (23.3%) had unknown outcome when reported and the remaining 12 patients (10.3%) died. CONCLUSION: Clozapine is uncommonly but importantly related to myocarditis, often fatal or near fatal and sometimes in relatively young patients with early onset after treatment initiation. The most striking feature about this condition is the wide diversity of nonspecific symptoms that occur in afflicted patients. Additional pharmacovigilance, improved reporting systems and further investigation of mechanisms of drug-induced myocarditis and related cardiovascular conditions (such as heart failure) are clearly warranted. A case-control study would be suitable for investigation of baseline predictors.

The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers.

OBJECTIVE: Our aim was to evaluate whether vitamin E (500 IU) slowed the progression of carotid atherosclerosis in a population of chronic smokers over 4 years as measured by ultrasound determination of carotid intima-media thickness (IMT) and systemic arterial compliance (SAC). METHODS: The Melbourne Atherosclerosis Vitamin E Trial (MAVET) was a randomized, double-blind, placebo-controlled trial in which 409 male and female smokers aged 55 years and over were randomized to receive 500 IU per day of natural vitamin E or placebo. The primary endpoint was progression of carotid atherosclerosis determined by intima-media thickness of the right common carotid artery. Secondary outcomes were change in systemic arterial compliance and low-density lipoprotein (LDL) oxidative susceptibility over time. RESULTS: The mean increase in intima-media thickness over time in the vitamin E group was 0.0041 mm/year faster than placebo (95% confidence interval -0.0021 to 0.0102 mm/year, P = 0.20). Similarly, a non-significant difference between vitamin E and placebo was found for rate of change in systemic arterial compliance (P = 0.11). Vitamin E supplementation did, however, significantly reduce LDL oxidative susceptibility (P < 0.001). CONCLUSION: Vitamin E supplementation is ineffective in reducing the progression of carotid atherosclerosis as measured by intima-media thickness in chronic smokers. This finding extends our knowledge of lack of effectiveness of vitamin E supplementation in populations with high oxidant stress.

Safety of drug therapies used for weight loss and treatment of obesity.

Some of the medications used for weight loss in the management of obesity have been associated with unacceptable morbidity and mortality. Safety concerns have led to the withdrawal of aminorex, followed by the fenfluramines in 1997, and phenylpropanolamine (norephedrine) in 2000. Aminorex was associated with an increased prevalence of primary pulmonary hypertension (PPH), fenfluramines with an increased prevalence of PPH and valvulopathy, and phenylpropanolamine with an increased risk of haemorrhagic stroke. Several studies have investigated the safety of the fenfluramines, yet the benefit-risk profile has not been conclusively quantified. This is due to several deficiencies in the published studies, including a lack of data on the baseline prevalences of comorbid conditions in obese subjects, and potential confounders and biases in the study designs. Although several studies and systematic reviews support an increased risk of PPH and valvulopathy in patients who have taken fenfluramines, without knowledge of the background prevalence it is not possible to determine if the exposure preceded the outcome. The population at higher risk of these adverse effects includes those taking higher doses or with a longer duration of exposure to fenfluramines and those with pre-existing cardiac disease or a genetic predisposition. Patients exposed to fenfluramines continue to be monitored, with some follow-up studies indicating no overall worsening in valvulopathy over time. There are limited efficacy and safety data for amfepramone (diethylpropion) and phentermine and their approval for the management of obesity is limited to short-term use. Orlistat and sibutramine are the only currently approved medications for long-term management of obesity. Although the benefit-risk profiles of sibutramine and orlistat appear positive, sibutramine continues to be monitored because of long-term safety concerns. The safety and efficacy of currently approved drug therapies have not been evaluated in children and elderly patient populations and there is limited information in adolescents, whilst the long-term safety of current and potential new drug therapies in adults will require several years of postmarketing surveillance to fully elucidate their adverse effect profiles.

Pharmacotherapy for obesity.

Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction, and has included thyroid hormone, amphetamines, phentermine, amfepramone (diethylpropion), phenylpropanolamine, mazindol, fenfluramines and, more recently, sibutramine and orlistat. These agents decrease appetite, reduce absorption of fat or increase energy expenditure. Primary endpoints used to evaluate anti-obesity drugs most frequently include mean weight loss, percentage weight loss and proportion of patients losing >or=5% and >or=10% of initial bodyweight. Secondary endpoints may include reduction in body fat, risk factors for cardiovascular disease and the incidences of diseases such as diabetes mellitus. Most pharmacotherapies have demonstrated significantly greater weight loss in patients on active treatment than those receiving placebo in short-term (or=10% loss of initial bodyweight in 46% of patients. For patients taking orlistat, weight loss was 2.2 kg greater than those on placebo at 4 years (p<0.001), with significantly more patients achieving >or=10% loss of initial bodyweight (26.2% and 15.6%, respectively; p<0.001). Other drugs that have been evaluated for weight loss include ephedrine, the antidepressants fluoxetine and bupropion, and the antiepileptics topiramate and zonisamide. Two clinical trials with fluoxetine both reported no significant difference in weight loss compared with placebo at 52 weeks. Clinical trials evaluating ephedrine, bupropion, topiramate and zonisamide have demonstrated significantly greater weight loss than placebo but have been limited to 16-26 weeks' treatment. A major obstacle to the evaluation of the clinical trials is the potential bias resulting from low study completion rates. Completion rates varied from 52.8% of phentermine recipients in a 9-month study, to 40% of fenfluramine recipients in a 24-week comparative study with phentermine and 18% of amfepramone recipients in a 24-week study. One-year completion rates range from 51% to 73% for sibutramine and from 66% to 85% for orlistat. Other potential sources of bias include run-in periods and subsequent patient selection based on compliance or initial weight loss. Several potential new therapies targeting weight loss and obesity through the CNS pathways or peripheral adiposity signals are in early phase clinical trials. Over the next decade the drug treatment of obesity is likely to change significantly because of the availability of new pharmacotherapies to regulate eating behaviours, nutrient partitioning and/or energy expenditure.

Use of complementary and alternative medicines by patients with chronic obstructive pulmonary disease.

OBJECTIVES: To investigate complementary and alternative medicine (CAM) use by patients with chronic obstructive pulmonary disease (COPD) and to explore their beliefs about CAM. DESIGN AND PARTICIPANTS: Cross-sectional study of 173 patients with moderate to severe COPD, and in depth interviews with a purposive sample of 28 patients. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Use of CAM; beliefs about the value of CAM. RESULTS: 71 patients (41%) claimed to be using some form of CAM. Most commonly used were multivitamins and minerals, and garlic was the most commonly used herbal preparation. Patients reported that advertisements and people with prior experience of using CAM were their major sources of information. Extent of knowledge about CAM, degree of faith in CAM and personal attitudes influenced decisions to try CAM. Patients used CAM to promote general wellbeing, to counteract drug side effects, to compensate for dietary deficiencies and to ameliorate their disease. Efficacy appeared less important to users than safety. CAM practitioners were regarded as more convincing, informative, considerate and available compared with mainstream health professionals. CONCLUSIONS: Communication between patients and mainstream health professionals about CAM use could be improved by health professionals being more accepting of CAM use and having some basic knowledge about commonly used CAM preparations.

Atherosclerosis and folic acid supplementation trial in chronic renal failure: baseline results.

BACKGROUND: Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is a randomized placebo controlled trial assessing whether high-dose folic acid can reduce cardiovascular events and atherosclerosis progression in patients with chronic renal failure (CRF). Here we report the baseline results and compare indices of arterial structure (carotid intima-medial thickness (IMT)) and function (systemic arterial compliance (SAC)), pressure augmentation index (AI(x)) and pulse wave velocity (PWV a-f and PWV f-d)) to age- and sex-matched controls. METHODS: Three hundred and fifteen subjects with CRF (serum creatinine > or = 0.40 mmol/L) aged 24-79 years (mean +/- SD: 56.6 +/- 13.6 years) and 213 healthy controls (58.2 +/- 10.2 years) were studied. Fasting blood samples were assayed for lipids (both groups), total homocysteine (tHcy), red cell folate, cobalamin and fibrinogen (CRF group). Ultrasound B mode measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI(x), PWV (a-f), PWV (f-d) and central pressures. RESULTS: Ninety-six per cent of the CRF group had at least one of: hypertension, hypercholesterolaemia, diabetes or smoking; 35% had established cardiovascular disease. The mean IMT was greater in CRF patients than in controls (0.86 +/- 0.19 vs 0.68 +/- 0.11 mm, P < 0.001). The SAC was significantly lower, and PWV (a-f) and AI(x) significantly higher. The tHcy was increased in 97% of the CRF group (27.3 +/- 2.9 micromol/L (normal < 13)). Total homocysteine did not correlate with IMT or any other measure of arterial function. However, those in the upper quantile of tHcy (> or =25 micromol/L) did have higher PWV (a-f) and lower SAC than those in the lower quantile. CONCLUSIONS: Compared to normals, patients with CRF exhibited a 10-15-year shift to the right in age-related increases in carotid IMT and PWV (a-f), and significantly increased central pressure augmentation. This 5-year study is examining the impact of high-dose folic acid therapy on cardiovascular end-points, IMT progression and arterial function in CRF.

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.

Reference-based pricing schemes: effect on pharmaceutical expenditure, resource utilisation and health outcomes.

Pharmaceutical expenditure is rising more rapidly than the general inflation rate in most advanced countries. One strategy that has been introduced to control pharmaceutical costs is reference-based pricing (RBP). Its potential is restricted to those specific segments of the drug market where several drugs (and/or their generic forms) exist without substantial evidence that any particular agent is superior. Three broad approaches have been adopted. These involve the aggregation of drugs into generic groups, related drug groups (e.g. ACE inhibitors) or drugs grouped by therapeutic indication (e.g. antihypertensives). For each drug group, a single reimbursement level or reference price is set. Drugs above the reference price require part or total payment by the patient. The experience with RBP ranges from over 10 years in Germany (involving all levels of RBP) to the more recent implementation of RBP for related drug groups in Australia. This review summarises the current state of knowledge on RBP from the published experiences in the countries where RBP has been adopted. The published systematic reviews of RBP from the countries that have implemented it suggest that RBP has been successful at temporarily capping drug prices for the RBP drug groups and achieving short term cost savings. However, other factors influencing total pharmaceutical expenditure have often occurred simultaneously and make it difficult to isolate specific effects of RBP. Further investigation is required before any valid conclusions can be drawn about the net effect of RBP on healthcare costs. RBP has withstood the initial legal challenges of pharmaceutical companies and the criticisms of some clinicians. Where the reference price is based on the lowest priced drug(s) in the group, RBP appears to be one of the few strategies likely to be effective at encouraging doctors to use the least expensive agents as first-line therapy and utilise more expensive agents in those who experience side effects or poor efficacy.

Ceftriaxone and cefotaxime use in Victorian hospitals.

OBJECTIVE: To determine patterns of use of ceftriaxone and cefotaxime (CEFX) in Victorian hospitals and to identify areas for improvement. DESIGN, PATIENTS AND SETTING: A concurrent, observational evaluation of CEFX use in patients commencing a course of these drugs between 8 and 14 September, 1999, in 51 Victorian hospitals. MAIN OUTCOME MEASURES: Proportion of patients treated with CEFX; indications; duration of use; concordance with recommendations of national antibiotic guidelines (Therapeutic guidelines: antibiotic, 10th edition [AG10]). RESULTS: 671 patients were treated with CEFX. The overall rate of use was 43 patients per 1000 inpatient separations. Treatment of respiratory tract infection accounted for 352 patients (52%) and surgical prophylaxis for 99 patients (15%). Treatment of skin/soft tissue, urinary tract and gastrointestinal tract infections accounted for about 7% of patients each. The median duration of CEFX courses was 3.0 days. The overall rate of concordance with indications recommended in AG10 was 27%. The rate of concordance for empirical treatment of respiratory tract infection was 24%. Of the 195 patients treated empirically with CEFX for community-acquired respiratory tract infection and assessed as non-concordant, 64% did not have radiological evidence of pneumonia, and a further 30% did not fulfill the criteria for severe pneumonia. All courses given for surgical prophylaxis were non-concordant. CONCLUSIONS: CEFX is widely used in Victorian hospitals, mostly to treat lower respiratory tract infection and in surgical prophylaxis of infection. The rate of concordance with AG10 is low. Potential areas for intervention include empirical treatment of respiratory tract infection and use in surgical prophylaxis.