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...

Ramipril - improving exercise tolerance in intermittent claudication?

Peripheral artery disease (PAD) is one of the most common manifestations of systemic atherosclerosis. It is estimated that 10-15% of the general population is affected by PAD, whereby the narrowed arteries lead to reduced blood flow to the extremeties - particularly the legs. While many people have mild or no systems with PAD, approximately one-third of people experience intermittent claudication (IC).

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.

The role of δ-opioid receptors in learning and memory underlying the development of addiction

Opioids are important endogenous ligands that exist in both invertebrates and vertebrates and signal by activation of opioid receptors to produce analgesia and reward or pleasure. The μ-opioid receptor is the best known of the opioid receptors and mediates the acute analgesic effects of opiates, while the δ-opioid receptor (DOR) has been less well studied and has been linked to effects that follow from chronic use of opiates such as stress, inflammation and anxiety. Recently, DORs have been shown to play an essential role in emotions and increasing evidence points to a role in learning actions and outcomes. The process of learning and memory in addiction has been proposed to involve strengthening of specific brain circuits when a drug is paired with a context or environment. The DOR is highly expressed in the hippocampus, amygdala, striatum and other basal ganglia structures known to participate in learning and memory. In this review, we will focus on the role of the DOR and its potential role in learning and memory underlying the development of addiction.

Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

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

Background The frequency of prescribing potentially inappropriate medications (PIMs) in older patients remains high regardless of the evidence of adverse outcomes from their use. This study aims to identify the prevalence and nature of PIMs at admission to acute care and at discharge to residential aged care facilities (RACFs) using the recently updated Beers’ Criteria. We also aim to identify if polypharmacy, age, gender and the frailty status of patients are independent risk factors for receiving a PIM. Methods This was a retrospective study of 206 patients discharged to RACFs from acute care. All patients were aged at least70 years and were admitted between July 2005 and May 2010; their admission and discharge medications were evaluated. Frailty status was measured as the Frailty Index (FI), adding each individual’s deficits and dividing by the total number of deficits considered, with FI 0.25 used as the cut-off between “fit” and “frail”. Results Mean patient age was 84.8 ± 6.7 years; the majority (57%) were older than 85 years and approximately 90% were frail. Patients were prescribed a mean of 7.2 regular medications at admission and 8.1 on discharge. 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 the total 187 PIMs on admission, 56 (30%) were stopped, and 131 were continued; 32 new PIMs were introduced. Commonly prescribed PIMs at both admission and discharge were central nervous system, cardiovascular and gastrointestinal drugs and analgesics. Of the potential risk factors, frailty status was the only significant predictor of PIMs at both admission and discharge (p = 0.016). Conclusion A high prevalence of unnecessary drug use was observed in frail older patients on admission to acute care hospitals and on discharge to RACFs. The only association with PIM use was the frailty status of patients. Further studies are needed to further evaluate this association.

The impact of frailty and polypharmacy on adverse outcomes in older inpatients

Background Older people are at significant risk of adverse outcomes as a result of changes in physiology, frailty, co-morbidity and polypharmacy.1 Timely identification of high-risk patients may facilitate the optimization of medication and reduce the incidence of adverse outcomes. The aims of this study were to evaluate in older inpatients the relationships between risk factors, including frailty and polypharmacy, and adverse health outcomes. Methods This is a prospective study of 1418 patients, aged 70 and older, admitted to general medical units in 11 acute care hospitals across Australia. The interRAI Acute Care (interRAI AC) assessment tool was used for data collection. Frailty status was measured using a Frailty Index (FI), adding each individual’s deficits and dividing by the total number of deficits considered. Adverse health outcomes included falls in hospital, delirium, in-hospital functional and cognitive decline, discharge to a higher level of care and inpatient mortality. Results Patients had a mean age 81 ± 6.8 years with a median length of hospital stay of 6 days (interquartile range 4 to 11 days); 701 (50%) experienced at least one adverse outcome. Polypharmacy (5-9 drugs per day) was observed in almost half of the study population (n=695, 49%) and hyper-polypharmacy (≥10 drugs) observed in about one-third of patients (n=490, 34.6%). Cognitive impairment was shown to be associated with the lower rate of prescribing. FI had a significant association with all adverse outcomes studied (p = <0.05). In contrast, no association was observed between polypharmacy categories and adverse outcomes except for those on 10 or more drugs where they were more likely to be discharged to a higher level of care (p= 0.014). Conclusions Among older inpatients, frailty status was a significant predictor of adverse outcomes. Lower rates of prescribing to patients with cognitive impairment may underpin the lack of an association between polypharmacy and adverse outcomes in this cohort. References: 1. Olsson IN, Runnamo R, Engfeldt P. Medication quality and quality of life in the elderly, a cohort study.Health Qual Life Outcomes.2011;9:95

Adolescent peer aggression and its association with mental health and substance use in an Australian cohort

Prospective longitudinal birth cohort data was used to examine the association between peer aggression at 14 years and mental health and substance use at 17 years. A sample of 1590 participants from the Western Australian Pregnancy Cohort (Raine) study were divided into mutually exclusive categories (victims, perpetrators, victim-perpetrators and uninvolved). Involvement in any type of peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim-perpetrator (8.7%) was reported by 40.2% of participants. After adjusting for confounding factors, those who were a victim of peer aggression had increased odds of later depression and internalising symptoms whilst perpetrators of peer aggression were found to be at increased risk of depression and harmful alcohol use. Victim-perpetrators of peer aggression were more likely to have externalising behaviours at 17 years. These results show an independent temporal relationship between peer aggression and later mental health and substance use problems in adolescence.

The long-term health consequences of child physical abuse, emotional abuse, and neglect : a systematic review and meta-analysis

Background Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes. Methods and Findings A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships. Conclusions This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence.

Alcohol use in South Africa : findings from the first demographic and health survey (1998)

Objective This study formed part of the 1998 South African Demographic and Health Survey, which included questions assessing the extent of alcohol use, risky drinking and alcohol problems among South Africans to obtain up-to-date baseline estimates of consumption and risky drinking and to inform intervention efforts. Method A two-stage random sample of 13,826 persons ages 15 or older (59% women) was included in the survey. Alcohol use was assessed through eight questions, including the CAGE questionnaire. Frequency analyses for different age groups, geographic setting, education level, population group and gender were calculated, as were odds ratios for these variables in relation to symptoms of alcohol problems. Results Current alcohol consumption was reported by 45% of the men and 17% of the women. White men (71%) were most likely and Asian women (9%) least likely to be current drinkers. Urban residents were more likely than nonurban dwellers to report current drinking. One third of the current drinkers reported risky drinking over weekends, and 28% of the men and 10% of the women scored above the cutoff level on the CAGE questionnaire. Symptoms of alcohol problems were significantly associated with lower socioeconomic status, no school education in women and being older than 25 years of age. Conclusions A comprehensive strategy is required to address the high levels of risky drinking and reported symptoms of alcohol problems.