What is the future for rimonabant in the treatment of obesity

Orlistat and sibutramine only cause modest reductions in body weight. Rimonabant, a cannabinoid receptor 1 antagonist, is a new approach to weight reduction, but is it safe, efficacious, and better than the existing agents?

New findings with old drugs for osteoporosis

Background : Postmenopausal osteoporosis is common and is associated with stooped posture, loss of height, back pain and fractures. Objectives/methods : This evaluation is of clinical outcome trials with tibolone (Long-Term Intervention of Fractures with Tibolone) and strontium ranelate (Spinal Osteoporosis Therapeutic Intervention) in postmenopausal osteoporosis. Results : Although the Long-Term Intervention of Fractures with Tibolone trial established that tibolone decreased the incidence of vertebral and non-vertebral fractures in postmenopausal osteoporosis, it also showed that tibolone caused a small increase in the incidence of stoke. The Spinal Osteoporosis Therapeutic Intervention trial established that strontium ranelate decreased the incidence of vertebral fractures, but had little effect on the incidence of non-vertebral fractures. Conclusions : As some of the bisphosphonates (alendronate, risedronate, zoledronic acid) have been shown to prevent hip fractures without increasing the incidence of stroke, they should be preferred to tibolone and strontium in the treatment of postmenopausal osteoporosis.

Telcagepant is a new oral treatment for migraine

Background : Migraine is a common cause of disability. Many subjects (30 – 40%) do not respond to the 5-HT 1B/1D agonists (the triptans) commonly used in the treatment of migraine attacks. Calcitonin gene-related protein (CGRP) receptor antagonism is a new approach to the treatment of migraine attacks. Objectives/methods : This evaluation is of a Phase III clinical trial comparing telcagepant, an orally active CGRP receptor antagonist, with zolmitriptan in subjects during an attack of migraine. Results : Telcagepant 300 mg has a similar efficacy to zolmitriptan in relieving pain, phonophobia, photophobia, and nausea. Telcagepant was better tolerated than zolmitriptan. Conclusions : The initial Phase III clinical trial results with telcagepant are promising but several further clinical trials are needed to determine the place of telcagepant in the treatment of migraine attacks

Anti-cancer activity of zoledronic acid in breast cancer

Background: Zoledronic acid is used to prevent the bone loss associated with antioestrogen treatments in subjects with breast cancer. Preclinical studies suggest that zoledronic acid may have anticancer activity in its own right. This anticancer possibility with zoledronic acid has not been investigated extensively in clinical trials. Objectives/methods: This evaluation is of a large clinical trial that investigated the effect of zoledronic acid on cancer outcomes in premenopausal women with breast cancer. Results: The trial showed that after 4 years, 94.0% of subjects who were treated with zoledronic acid were disease-free compared with 90.8% of those not treated with zoledronic acid. Recurrence survival was a secondary end point; this occurred in 94.0% with, and 90.9% without, zoledronic acid treatment. Conclusions: Zoledronic acid does have anticancer activity in premenopausal women with cancer.

Is liraglutide or exenatide better in type 2 diabetes?

Background: Subjects with type 2 diabetes have high circulating levels of glucose. Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that has a major role in glucose homeostasis. Exenatide and liraglutide are both agonists at the GLP-1 receptor, and are effective at reducing circulating glucose levels (measured as HbA1c levels), but they have not been compared. Objectives/methods: This evaluation is of a clinical trial comparing liraglutide once a day with exenatide twice a day in subjects with type 2 diabetes. Results: In the Liraglutide Effect and Action in Diabetes (LEAD)-6 trial, subcutaneous liraglutide 1.8 mg once a day was compared with exenatide 10 μg twice a day. The primary efficacy outcome was change in HbA1c levels, and this was significantly greater with liraglutide (1.12%) than with exenatide (0.79%). Liraglutide and exenatide had similar small abilities to reduce body weight, blood pressure and LDL-cholesterol. Conclusions: Liraglutide was more effective than exenatide for overall glycaemic control in subjects with type 2 diabetes. However, this is only true for the preparations and doses tested, that is liraglutide 1.8 mg once weekly and exenatide 10 μg b.i.d., and may not apply when the comparison is undertaken with the new longer-lasting preparation of exenatide once weekly.

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

Adherence to medicines in the older-aged with chronic conditions : does an intervention concerning adherence by an allied health professional help?

Adherence to medicines is a major determinant of the effectiveness of medicines. However, estimates of non-adherence in the older-aged with chronic conditions vary from 40 to 75%. The problems caused by non-adherence in the older-aged include residential care and hospital admissions, progression of the disease, and increased costs to society. The reasons for non-adherence in the older-aged include items related to the medicine (e.g. cost, number of medicines, adverse effects) and those related to person (e.g. cognition, vision, depression). It is also known that there are many ways adherence can be increased (e.g. use of blister packs, cues). It is assumed that interventions by allied health professions, including a discussion of adherence, will improve adherence to medicines in the older aged but the evidence for this has not been reviewed. There is some evidence that telephone counselling about adherence by a nurse or pharmacist does improve adherence, short- and long-term. However, face-to-face intervention counselling at the pharmacy, or during a home visit by a pharmacist, has shown variable results with some studies showing improved adherence and some not. Education programs during hospital stays have not been shown to improve adherence on discharge, but education programs for subjects with hypertension have been shown to improve adherence. In combination with an education program, both counselling and a medicine review program have been shown to improve adherence short-term in the older-aged. Thus, there are many unanswered questions about the most effective interventions to promote adherence. More studies are needed to determine the most appropriate interventions by allied health professions, and these need to consider the disease state, demographics, and socio-economic status of the older-aged subject, and the intensity and duration of intervention needed.

Zoledronic acid once-yearly : what role in the prevention of non-vertebral osteoporotic fractures?

Osteoporosis is the most common bone disease. Low levels of oestrogens or testosterone are risk factors for primary osteoporosis. The most common cause of secondary osteoporosis is glucocorticoid treatment, but there are many other secondary causes of osteoporosis. Osteoporosis can be secondary to anti-oestrogen treatment for hormone-sensitive breast cancer and to androgen-deprivation therapy for prostate cancer. Zoledronic is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least a year after a single intravenous administration. The efficacy and safety of extended release (once-yearly) zoledronic acid in the treatment of osteoporosis is reviewed.

Oral fingolimod for relapsing-remitting multiple sclerosis

Background: Most people with multiple sclerosis have the relapsing-remitting type. Objective/methods: The objective was to evaluate two clinical trials of fingolimod in relapsing multiple sclerosis. Results: FREEDOMS (FTY720 Research Evaluation Effects of Daily Oral therapy in Multiple Sclerosis), a Phase III placebo-controlled trial, showed that fingolimod (0.5 or 1.25 mg) reduced the relapse rate and disability in multiple sclerosis, compared to placebo. Fingolimod (0.5 or 1.25 mg) has been compared to interferon β-1a in a Phase III clinical trial (TRANSFORMS; Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis) and shown to be more efficacious than interferon β-1a in reducing relapse rates. However, fingolimod did increase the risk of infections and skin cancers. Conclusions: Only the lower dose of fingolimod (0.5 mg), which possibly has less toxicity, should be considered for prevention of relapses in relapsing-remitting multiple sclerosis.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Striving to achieve best practice in heart failure disease management

Based on a national audit of chronic heart failure (CHF) management programmes (CHF-MPs) conducted in 2006, Driscoll et al identified a disproportionate distribution ranging from 0 to 4.2 programmes/million population in the various states of Australia with many programmes not following best practice.1 We welcome their proposal to develop national benchmarks for CHF management and acknowledge the contributions of the Heart Foundation and health professionals in finalising these recommendations.2 We would like to share the Queensland experience in striving towards best practice with the number of CHF-MPs increasing from four (at the time of the 2006 survey) to 23, equating to 5.0 programmes/million population. Queensland now has a state-wide heart failure service steering committee with a focus on the development of CHF-MPs supported by a central coordinator...

Psychotropic medication use in adolescents with intellectual disability living in the community

Purpose Information on the use of psychotropic medications in adolescents with intellectual disability is scant. Such information can guide interventions to improve psychotropic medication use in this population. We investigated the prevalence of, and factors associated with, psychotropic medication use in adolescents with intellectual disability in Australia who live in the community. Methods Cross-sectional data were obtained from adolescents with intellectual disability living in the community in South East Queensland, Australia, between February 2007 and September 2010. Self-reported information on medication use was extracted from a health screening tool. Demographic and medical data were collected through parent/caregiver surveys. Medications were classified according to the Anatomical Therapeutic Chemical classification system. Psychopathology was assessed using the Developmental Behaviour Checklist Short Form. Logistic regression analysis was used to assess the association of demographic and medical characteristics with psychotropic medication use. Results There were 176 participants (median age = 16 years, range = 11–19 years; 55% male). Psychotropics were used by 20% of participants. Psychostimulants were the commonest psychotropic class, used by 9% of participants. Multipsychotropic prescribing was not common with only seven participants using more than one psychotropic agent. After adjusting for potentially confounding variables, use of psychotropic medications was significantly associated with male gender (adjusted odds ratio = 3.6; 95% confidence interval = 1.3–9.5) and having major behaviour problems (3.1; 1.1–8.9). Conclusions Adolescents with intellectual disability use a wide range of psychotropic medications. Being male and having major behaviour problems are associated with the use of psychotropic medications. Research examining the rationale for psychotropic prescribing in this population is needed. Copyright © 2013 John Wiley & Sons, Ltd.

Do we need to follow medication use-by dates?

"It’s late in the night. And after a long day at work, you have a splitting headache. You rattle around in the bottom drawer of the bathroom vanity to find a packet of paracetamol tablets you know are hiding there. Phew, relief is at hand! Then you turn the packet over and discover that the crumpled box of pills actually expired two years ago..."--http://theconversation.com/explainer-do-we-need-to-follow-medication-use-by-dates-4329