Gliptins - do they increase cardiovascular risk or benefit?

INTRODUCTION: In 2008, the US FDA required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase-4 inhibitors ('gliptins'). AREAS COVERED: The cardiovascular safety trials of saxagliptin and alogliptin have recently been published and are the subject of this evaluation. EXPERT OPINION: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care were both multicentre, randomised, double-blind, placebo-controlled, Phase IV clinical trials. These trials showed that saxagliptin and alogliptin did not increase the primary end point, which was a composite of cardiovascular outcomes that did not include hospitalisations for heart failure. However, saxagliptin significantly increased hospitalisation for heart failure, which was a component of the secondary end point. The effect of alogliptin on hospitalisations for heart failure has not been reported. Neither agent improved cardiovascular outcomes. As there is no published evidence of improved outcomes with gliptins, it is unclear to us why these agents are so widely available for use. We suggest that the use of gliptins be restricted to Phase IV clinical trials until such time as cardiovascular safety and benefits/superiority are clearly established

The association between the measurement of adherence to anti-diabetes medicine and the HbA1c

BACKGROUND: Adherence to medicines is important in subjects with diabetes, as nonadherence is associated with an increased risk of morbidity and mortality. However, it is not clear whether there is an association between adherence to medicines and glycaemic control, as not all studies have shown this. One of the reasons for this discrepancy may be that, although there is a standard measure of glycaemic control i.e. HbA1c, there is no standard measure of adherence to medicines. Adherence to medicines can be measured either qualitatively by Morisky or non-Morisky methods or quantitatively using the medicines possession ratio (MPR). AIMS OF THE REVIEW: The aims of this literature review are (1) to determine whether there is an association between adherence to anti-diabetes medicines and glycaemic control, and (2) whether any such association is dependent on how adherence is measured. Methods A literature search of Medline, CINAHL and the Internet (Google) was undertaken with search terms; 'diabetes' with 'adherence' (or compliance, concordance, persistence, continuation) with 'HbA1c' (or glycaemic control). RESULTS: Twenty-three studies were included; 10 qualitative and 12 quantitative studies, and one study using both methods. For the qualitative methods measurements of adherence to anti-diabetes medicines (non-Morisky and Morisky), eight out of ten studies show an association with HbA1c. Nine of ten studies using the quantitative MPR, and two studies using MPR for insulin only, have also shown an association between adherence to anti-diabetes medicines and HbA1c. However, the one study that used both Morisky and MPR did not show an association. Three of the four studies that did not show a relationship, did not use a range of HbA1c values in their regression analysis. The other study that did not show a relationship was specifically in a low income population. CONCLUSIONS: Most studies show an association between adherence to anti-diabetes medicines and HbA1c levels, and this seems to be independent of method used to measure adherence. However, to show an association it is necessary to have a range of HbA1c values. Also, the association is not always apparent in low income populations.

Dapagliflozin – do we need it registered for type 2 diabetes?

INTRODUCTION: Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) promote the excretion of glucose to reduce glycated hemoglobin (HbA1c) levels. Canagliflozin was the first SGLT2 inhibitor to be approved by the US FDA for use in the treatment of type 2 diabetes, and recently dapagliflozin has also been approved. AREAS COVERED: We evaluated a recent Phase III clinical trial with dapagliflozin. EXPERT OPINION: Dapagliflozin was studied as add-on therapy to sitagliptin with or without metformin, and was shown to lower HbA1c levels and body weight. The incidence of hypoglycaemia was low with dapagliflozin, but it did increase the incidence of urogenital infections. As no clear benefits have been identified for dapagliflozin over canagliflozin, which was the first gliflozin registered by the FDA, we do not fully understand why it was necessary to register dapagliflozin. Given that there are no completed cardiovascular/clinical outcome studies with dapagliflozin, and therefore no evidence of beneficial effect, it also seems premature to be using it extensively or considering it as an alternative to the clinically proven metformin.

The effect of the addition of hip strengthening exercises to a lumbopelvic exercise programme for the treatment of non-specific low back pain : a randomized controlled trial

Objectives To compare the efficacy of two exercise programs in reducing pain and disability for individuals with non-specific low back pain and to examine the underlying mechanical factors related to pain and disability for individuals with NSLBP. Design A single-blind, randomized controlled trial. Methods: Eighty participants were recruited from eleven community-based general medical practices and randomized into two groups completing either a lumbopelvic motor control or a combined lumbopelvic motor control and progressive hip strengthening exercise therapy program. All participants received an education session, 6 rehabilitation sessions including real time ultrasound training, and a home based exercise program manual and log book. The primary outcomes were pain (0-100mm visual analogue scale), and disability (Oswestry Disability Index V2). The secondary outcomes were hip strength (N/kg) and two-dimensional frontal plane biomechanics (°) measure during the static Trendelenburg test and while walking. All outcomes were measured at baseline and at 6-week follow up. Results There was no statistical difference in the change in pain (xˉ = -4.0mm, t= -1.07, p =0.29, 95%CI -11.5, 3.5) or disability (xˉ = -0.3%, t= -0.19, p =0.85, 95%CI -3.5, 2.8) between groups. Within group comparisons revealed clinically meaningful reductions in pain for both Group One (xˉ =-20.9mm, 95%CI -25.7, -16.1) and Group Two (xˉ =-24.9, 95%CI -30.8, -19.0). Conclusion Both exercise programs had similar efficacy in reducing pain. The addition of hip strengthening exercises to a motor control exercise program does not appear to result in improved clinical outcome for pain for individuals with non-specific low back pain.

'Women on a Wiki’ : the role of interactive websites in reflective learning practices for undergraduate women’s health students

Aim Our pedagogical research addressed the following research questions: 1) Can shared ‘cyber spaces’, such as a ‘wiki’, be occupied by undergraduate women’s health students to improve their critical thinking skills? 2) What are the learning processes via which this occurs? 3) What are the implications of this assessment trial for achieving learning objectives and outcomes in future public health undergraduate courses? Methods The students contributed written, critical reflections (approximately 250 words) to the Wiki each week following the lecture. Students reflected on a range of topics including the portrayal of women in the media, femininity, gender inequality, child bearing and rearing, domestic violence, mental health, Indigenous women, older women, and LGBTIQ communities. Their entries were anonymous, but visible to their peers. Each wiki entry contained a ‘discussion tab’ wherein online conversations were initiated. We used a social constructivist approach to grounded theory to analyse the 480 entries posted over the semester. (http://pub336womenshealth.wikispaces.com/) Results The social constructivist approach initiated by Vygotsky (1978) and further developed by Jonasson (1994) was used to analyse the students’ contributions in relation to four key thematic outcomes including: 1) Complexities in representations across contexts; 2) Critical evaluation in real world scenarios; 3) Reflective practice based on experience, and; 4) Collaborative co-construction of knowledge. Both text and image/visual contributions are provided as examples within each of these learning processes. A theoretical model depicting the interactive learning processes that occurred via discussion of the textual and visual stimulus is presented.

'Bacon - hold the eggs' for uncontrollable nose bleeds

Almost everyone experiences a nosebleed at some time during their lives. In many cases, these nosebleeds are self-limiting, resolve without medical attention, and tend to be nothing more than a minor nuisance. However, in some instances they can be life threatening and urgent medical attention is required. One of these instances is when people who have Glanzmann's thrombasthenia (GT) experience a nosebleed...

A puff of fluticasone for eosinophilic oesophagitis

Eosinophilic oesophagitis (EEl is most commonly observed in children and young males, and is estimated to affect one per 10,000 children, and lo/o of adults in Australia. EE causes inflammation of the oesophagus; and an endoscopy, and biopsy showing an increase in eosinophils through the oesophagus is used for diagnosis. People with EE often present with non-specific symptoms to varying degrees of severity that could also suggest swallowing difficulties, or acid reflux; the feeling of food sticking to the throat on the way down (sometimes completely), choking on food, regurgitation of food, and severe acid reflux that does not respond to stomach acid suppression treatment...

Simvastatin - from cholesterol to venous ulcers?

It is estimated that up to three per 1,000 of the Australian adult population are affected by leg ulcers. Venous ulcers are the most common cause of ulceration in the lower extremities, accounting for approximately 80-85% of leg ulcers. These debilitating, and often painful ulcers recur frequently and can affect people of all ages, though the risk increases dramatically with age (approximately 99% of those with venous ulcers in Australia are over 65 years of age). Other risk factors include a family history of leg ulceration, varicose veins, venous disease, phlebitis, deep vein thrombosis, congestive heart failure, obesity, immobility, and previous leg injury. The chronic and recurring nature of venous ulcers, in addition to reduced quality of life for the patient, and ongoing costs of care place a significant burden of disease on the patient, and health system...

Smoothing out the breathlessness

An estimated one in 10 Australians has asthma. In 2010, the burden of disease for asthma was ranked 7th highest for the overall population in Australasia. A less well-known condition that also affects breathing, is vocal cord dysfunction (VCD). People with asthma and VCD can both present with similar symptoms such as coughing, difficulty breathing, wheezing and throat tightness. Asthma and VCD attacks also share similar triggers such as breathing in lung irritants, exercising or having an upper respiratory infection. Asthma and VCD frequently coexist. They affect different parts of the respiratory system and appear to have separate aetiologies. Asthma is essentially a condition of airway inflammation, even though the most prominent clinical presentation is bronchoconstriction. which is responsible for symptoms such as wheezing and shortness of breath. The cause of VCD is not well understood, though the abnormal closing of the vocal cords during breathing does not appear to involve an immune reaction, or the lower airways...

Challenging the myth of an "epidemic" of common mental disorders : trends in the global prevalence of anxiety and depression between 1990 and 2010

Background Anxiety disorders and major depressive disorder (MDD) are common and disabling mental disorders. This paper aims to test the hypothesis that common mental disorders have become more prevalent over the past two decades. Methods We conducted a systematic review of prevalence, remission, duration, and excess mortality studies for anxiety disorders and MDD and then used a Bayesian meta-regression approach to estimate point prevalence for 1990, 2005, and 2010. We also conducted a post-hoc search for studies that used the General Health Questionnaire (GHQ) as a measure of psychological distress and tested for trends to present a qualitative comparison of study findings. Results This study found no evidence for an increased prevalence of anxiety disorders or MDD. While the crude number of cases increased by 36%, this was explained by population growth and changing age structures. Point prevalence of anxiety disorders was estimated at 3.8% (3.6-4.1%) in 1990 and 4.0% (3.7-4.2%) in 2010. The prevalence of MDD was unchanged at 4.4% in 1990 (4.2-4.7%) and 2010 (4.1-4.7%). However, 8 of the 11 GHQ studies found a significant increase in psychological distress over time. Conclusions The perceived "epidemic" of common mental disorders is most likely explained by the increasing numbers of affected patients driven by increasing population sizes. Additional factors that may explain this perception include the higher rates of psychological distress as measured using symptom checklists, greater public awareness, and the use of terms such as anxiety and depression in a context where they do not represent clinical disorders.

The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study

Aim Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease. Methods Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated. Results There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally. Conclusion Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.

Health states for schizophrenia and bipolar disorder within the Global Burden of Disease 2010 Study

A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

Health consequences of exposure to e-waste : a systematic review

Background The population exposed to potentially hazardous substances through inappropriate and unsafe management practices related to disposal and recycling of end-of-life electrical and electronic equipment, collectively known as e-waste, is increasing. We aimed to summarise the evidence for the association between such exposures and adverse health outcomes. Methods We systematically searched five electronic databases (PubMed, Embase, Web of Science, PsycNET, and CINAHL) for studies assessing the association between exposure to e-waste and outcomes related to mental health and neurodevelopment, physical health, education, and violence and criminal behaviour, from Jan 1, 1965, to Dec 17, 2012, and yielded 2274 records. Of the 165 full-text articles assessed for eligibility, we excluded a further 142, resulting in the inclusion of 23 published epidemiological studies that met the predetermined criteria. All studies were from southeast China. We assessed evidence of a causal association between exposure to e-waste and health outcomes within the Bradford Hill framework. Findings We recorded plausible outcomes associated with exposure to e-waste including change in thyroid function, changes in cellular expression and function, adverse neonatal outcomes, changes in temperament and behaviour, and decreased lung function. Boys aged 8–9 years living in an e-waste recycling town had a lower forced vital capacity than did those living in a control town. Significant negative correlations between blood chromium concentrations and forced vital capacity in children aged 11 and 13 years were also reported. Findings from most studies showed increases in spontaneous abortions, stillbirths, and premature births, and reduced birthweights and birth lengths associated with exposure to e-waste. People living in e-waste recycling towns or working in e-waste recycling had evidence of greater DNA damage than did those living in control towns. Studies of the effects of exposure to e-waste on thyroid function were not consistent. One study related exposure to e-waste and waste electrical and electronic equipment to educational outcomes. Interpretation Although data suggest that exposure to e-waste is harmful to health, more well designed epidemiological investigations in vulnerable populations, especially pregnant women and children, are needed to confirm these associations. Funding Children's Health and Environment Program, Queensland Children's Medical Research Institute, The University of Queensland, Australia.

Potentially inappropriate prescribing in older patients discharged from acute care hospitals to residential aged care facilities

Background The frequency of prescribing potentially inappropriate medications (PIMs) in older patients remains high despite evidence of adverse outcomes from their use. Little is known about whether admission to hospital has any effect on appropriateness of prescribing. Objectives This study aimed to identify the prevalence and nature of PIMs and explore the association of risk factors for receiving a PIM. Methods This was a prospective study of 206 patients discharged to residential aged care facilities (RACFs) from acute care. All patients were aged at least 70 years and were admitted between July 2005 and May 2010; their admission and discharge medications were evaluated. Results Mean patient age was 84.8 ± 6.7 years; the majority (57%) were older than 85 years and mean (SD) Frailty Index was 0.42 (0.15). At least one PIM was identified in 112 (54.4%) patients on admission and 102 (49.5%) patients on discharge. Of all medications prescribed at admission (1728), 10.8% were PIMs and at discharge of 1759 medications, 9.6% were PIMs. Of total 187 PIMs on admission, 56 (30%) were stopped and 131 were continued; 32 new PIMs were introduced. Of the potential risk factors considered, in-hospital cognitive decline and frailty status were the only significant predictors of PIMs. Conclusion Although, admission to hospital is an opportunity to review the indications for specific medications, a high prevalence of inappropriate drug use was observed. The only associations with PIM use were the frailty status and in-hospital cognitive decline. Additional studies are needed to further evaluate this association.