Reallocating time spent in sleep, sedentary behavior and physical activity and its association with pain: a pilot sleep study from the Osteoarthritis Initiative.

OBJECTIVE: Being physically active has broad health benefits for people with osteoarthritis (OA), including pain relief. Increasing physical activity (PA) requires reducing time in other behaviors within a fixed 24-h day. We examined the potential benefits in relation to pain from trading time in one type of wake or sleep behavior for another. METHOD: In this cross-sectional study, we used isotemporal logistic regression models to examine the estimated effect on pain from replacing time in one behavior with equal time in another, controlling for sociodemographic and health factors. Stratified analysis was conducted by the report of restless sleep. Sleep and wake behaviors [sedentary behavior (SB), light PA, moderate PA] were monitored by accelerometer in a pilot study of 185 Osteoarthritis Initiative (OAI) participants. Outcomes were bodily pain interference and knee pain. RESULTS: Moderate PA substituted for an equivalent time in sleep or other types of wake behaviors was most strongly associated with lower odds of pain (bodily pain interference odds reduced 21-25%, knee pain odds reduced 17-20% per 10-min exchange). These beneficial associations were particularly pronounced in individuals without restless sleep, but not in those with restless sleep, especially for bodily pain interference. CONCLUSION: Interventions promoting moderate physical activities may be most beneficial to address pain among people with or at high risk for knee OA. In addition to encouraging moderate-intensity PA, pain management strategies may also include the identification and treatment of sleep problems.

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.

Antithrombotic use following transient ischaemic attack or ischaemic stroke among older Australians with atrial fibrillation.

Hospital audits may underestimate anticoagulant use among acute ischaemic stroke patients with atrial fibrillation (AF), as treatment may commence after discharge. To account for this, antithrombotic use in the 4 months after hospitalisation for transient ischaemic attack or ischaemic stroke among AF patients was assessed using claims data. Results suggest that treatment may be commenced soon after discharge and should be considered when assessing prevalence of use.

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.

Prenatal exposure to selective serotonin reuptake inhibitors and risk of childhood overweight.

The objective was to investigate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and overweight in offspring at 4-5 years of age. We conducted a retrospective cohort study using linked records from the Women's and Children's Health Network in South Australia, Australia. Women were eligible to participate if they gave birth to singleton, live-born infants between September 2000 and December 2005. Women were excluded if they received a dispensing for an antidepressant other than SSRIs or an antipsychotic or an anti-epileptic or had a chronic medical condition. Of the 6560 eligible women, 71 received a dispensing for an SSRI (exposed), 204 had a reported psychiatric illness but did not receive a dispensing for any antidepressant (untreated psychiatric illness) and 6285 did not have a reported psychiatric illness and did not receive a dispensing for any antidepressant (unexposed). Childhood overweight was classified as a body mass index >85th percentile, based on age and sex. At 4-5 years of age, female offspring of exposed mothers were less likely to be overweight compared with female offspring of mothers with an untreated psychiatric illness [adjusted Prevalence Ratio (aPR) 0.23; 95% confidence interval (CI) 0.05-0.98] and female offspring of unexposed mothers (aPR 0.27; 0.07-0.99). No association with overweight was observed among male offspring of exposed mothers compared with male offspring of mothers with an untreated psychiatric illness (aPR 1.17; 0.54-2.51) and male offspring of unexposed mothers (aPR 0.93; 0.52-1.67). Further research is required to confirm these findings and examine the potential mechanisms behind the sex-specific differences.

Continuity of care: when do patients visit community healthcare providers after leaving hospital?

BACKGROUND/AIMS: Enhanced communication and transfer of information between healthcare providers and healthcare settings can reduce medication and healthcare errors post-hospital discharge. The timeframes within which patients access community healthcare providers post-hospital discharge are not well studied. This study aimed to determine length of time from hospital discharge until a general practice, pharmacy or specialist visit, or care planning service. METHODS: We conducted a retrospective analysis of Department of Veterans' Affairs health claims data. All 109 860 veterans hospitalized in 2006 were included. Main outcome measures were time from first hospital discharge to first claim for a general practice, pharmacy, specialist visit and/or care planning service. RESULTS: Within 30 days of hospital discharge 71% of subjects visited a general practitioner (GP), 86% had medicines dispensed from a community pharmacy and 44% saw a specialist. Median time to first pharmacy visit was 6 days (interquartile range 2-14) and 12 days for a GP visit (interquartile range 4-31). Less than 2% of the cohort received a discharge plan, case conference or medication review in the month after discharge. CONCLUSIONS: With 25% of patients having a claim for a GP service within 4 days of discharge, discharge summaries need to reach community-based health professionals within this time. Most patients visited their community pharmacy within 2 weeks of hospital discharge and before they saw their GP. Pharmacists are not routinely advised of hospitalization or provided with discharge summaries. More active engagement of this professional group in the continuum of care might improve care after hospital discharge.

Collaborative home medicines review delays time to next hospitalization for warfarin associated bleeding in Australian war veterans.

WHAT IS KNOWN AND BACKGROUND: Unintended bleeds are a common complication of warfarin therapy. We aimed to determine the impact of general practitioner-pharmacist collaborative medication reviews in the practice setting on hospitalization-associated bleeds in patients on warfarin. METHOD: We undertook a retrospective cohort study using administrative claims data for the ambulatory veteran and war widow population, Australia. Participants were veterans, war widows and their dependents aged 65 years and over dispensed warfarin. The exposed groups were those exposed to a general practitioner (GP)-pharmacist collaborative home medication review. The service includes GP referral, a home visit by an accredited pharmacist to identify medication-related problems, a pharmacist report with follow-up undertaken by the GP. The outcome measure was time to next hospitalization for bleeding. RESULTS: There were 816 veterans exposed to a home medicines review and 16,320 unexposed patients, with an average age of 81.5 years, and six to seven co-morbidities. Adjusted results showed a 79% reduction in likelihood of hospitalization for bleeding between 2 and 6 months (HR, 0.21 95% CI, 0.05-0.87) amongst those who had received a home medicines reviewed compared to the unexposed patients. No effect was seen in the time period from review to 2 months, nor in the time period 6 to 12 months post a review. WHAT IS NEW AND CONCLUSION: Medicines review in the practice setting delays time to next hospitalization for bleeding in those treated with warfarin in the period 2 to 6 months after the review, but is not sustained over time. Six monthly medication reviews may be required for patients on warfarin who are considered at high risk of bleeding.

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.

Potentially inappropriate prescribing among Australian veterans and war widows/widowers.

This study examined the extent of potentially inappropriate medicine, as defined by explicit criteria, dispensed to Australian veterans using the Repatriation Pharmaceutical Benefits Scheme Pharmacy Claims database. Twenty-one per cent of the 192,363 veterans aged 70 years, with an eligible gold card, were dispensed at least one potentially inappropriate medicine in the first 6 months of 2005. Long-acting benzodiazepines, amitriptyline, amiodarone, oxybutynin and doxepin were the medicines most commonly implicated. Strategies to support quality prescribing of medicines to the elderly must include a focus on these medicines.

Further evidence that Whorfian effects are stronger in the right visual field than the left.

The Whorf hypothesis holds that differences between languages induce differences in perception and/or cognition in their speakers. Much of the experimental work pursuing this idea has focused on the domain of color and has centered on the issue of whether linguistically coded color categories influence color discrimination. A new perspective has been cast on the debate by recent results that suggest that language influences color discrimination strongly in the right visual field but not in the left visual field (LVF). This asymmetry is likely related to the contralateral projection of visual fields to cerebral hemispheres and the specialization of the left hemisphere for language. The current study presents three independent experiments that replicate and extend these earlier results by using different tasks and testing across different color category boundaries. Our results differ in one respect: although we find that Whorfian effects on color are stronger for stimuli in the right visual field than in the LVF, we find that there are significant category effects in the LVF as well. The origin of the significant category effect in the LVF is considered, and two factors that might account for the pattern of results are proposed.

Achieving a sustained reduction in benzodiazepine use through implementation of an area-wide multi-strategic approach.

OBJECTIVE: This study aimed to evaluate the impact, in a regional setting, of a multi-strategic partnership approach for reducing benzodiazepine use in the management of insomnia, as recommended in Australia's National Policy on Quality Use of Medicines. METHOD: The setting was a rural region of South Australia, covering approximately 2000 km2, with a population of over 20 000. The study involved participatory action research, with qualitative and quantitative evaluations. The intervention involved a multi-strategic approach, including provision of treatment guidelines, provision of consumer information, a local media campaign and education and training of health professionals. The quantitative evaluation involved a single region before/after study with 2 years of follow-up using pharmacy-based dispensing data for benzodiazepines and antidepressants, gathered for the months of November to April in 1998/99 ('before' period) through to 2000/01 ('after' period). The data were analysed using non-parametric statistics. RESULTS: There was a 19% reduction in benzodiazepine dispensing 2 years after the intervention compared with a 6% reduction nationally. Dispensing of antidepressants increased by 33%, compared with a 28% increase nationally. CONCLUSION: It was concluded that the multi-strategic approach to the management of sleep disorders proved successful in promoting the use of non-drug alternatives, achieving sustained reduction in benzodiazepine consumption in a rural community, without therapeutic substitution of antidepressants. IMPLICATIONS: The study demonstrated that a sustainable reduction in prescribing of benzodiazepines can be achieved through the implementation of a multi-strategic approach involving local consumers, health professionals, a Division of General Practice, a government department, aged-care facilities and the local media.

Medication-related problems commonly occurring in an Australian community setting.

PURPOSE: This study characterised medication-related problems in 1000 Australian patients living in the community, and who were considered at risk of medication misadventure. METHODS: A review was undertaken of 1000 clinical case notes, developed during the delivery of medication management reviews. Patient demographics, medications used, medical conditions and medication-related problems were categorised according to established classification systems. Descriptive analyses were undertaken. RESULTS: Overall, 2222 problems were identified. Ninety per cent of patients had at least one medication-related problem. One in three people were found to require additional monitoring, one in four required additional medication, one in four were using the wrong or inappropriate medication and one in five were using insufficient medication. Cardiovascular, nervous system, alimentary and respiratory medicines were most commonly implicated, accounting for 69% of the medication-related problems. CONCLUSION: This analysis reveals the need for ongoing vigilance of, and support for, people at high risk of medication misadventure. This information is also useful for informing the design of public health or health promotion strategies aiming to reduce the prevalence of these problems.

Enzyme replacement therapy in the mouse model of Pompe disease.

Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal muscle cells took up little enzyme compared to liver and heart. Glycogen reduction was less than 50%, and some fibers showed little or no glycogen clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable levels at either dose. Skeletal muscle fibers with residual glycogen showed immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained in proliferating lysosomes. Glycogen clearance was more pronounced in type 1 fibers, and histochemical analysis suggested an increased mannose-6-phosphate receptor immunoreactivity in these fibers. Differential transport of enzyme into lysosomes may explain the strikingly uneven pattern of glycogen removal. Autophagic vacuoles, a feature of both the mouse model and the human disease, persisted despite glycogen clearance. In some groups a modest glycogen reduction was accompanied by improved muscle strength. These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle.

Possible interaction of zopiclone and nefazodone.

OBJECTIVE: To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy. CASE REPORT: An 86-year-old white woman was treated with nefazodone for depression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopiclone in plasma was subsequently measured eight hours after administration on two occasions, during nefazodone therapy and after its withdrawal. After discontnuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plasma concentration decreased from 20.6 to 1.45 ng/mL. DISCUSSION: Nefazodone is a relatively potent inhibitor of CYP3A4, a hepatic isoenzyme thought to play a major role in the metabolic elimination of zopiclone. The substantial decrease in the plasma zopiclone concentrations observed after withdrawal of nefazodone likely reflects a drug interaction. Despite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance. CONCLUSIONS: The features observed in this case suggest the possibility of a drug-drug interaction between nefazodone and zopiclone. Further prospective investigation is required to elucidate the nature and magnitude of this effect.

Bioindication potential of carbonic anhydrase activity in anemones and corals.

Activity levels of carbonic anhydrase (CA) were assessed in anemones Condylactis gigantea and Stichodactyla helianthus with laboratory exposures to copper, nickel, lead, and vanadium, and also in animals collected from polluted vs pristine field sites. CA activity was found to be decreased with increase in metal concentration and also in animals collected from the polluted field site. Preliminary assessments to adapt the CA assay for use in the widespread coral Montastraea cavernosa show decreased CA activity in specimens from the polluted field site and provide an avenue for future research aimed at more thoroughly describing coral CA activity for potential application in bioindication.

Enteral absorption of erythropoietin in the suckling rat.

Milk contains biologically relevant concentrations of erythropoietin (Epo), the primary hormone responsible for erythrocyte production. In animals, milk-borne Epo stimulates erythropoiesis. Epo receptors have been found in nonerythropoietic tissues including gastrointestinal tract. We hypothesized that milk-borne Epo is distributed to local gastrointestinal tissues, absorbed intact, and then distributed peripherally via the systemic circulation. Rat milk protected recombinant human Epo (rhEpo) from degradation in the suckling rat gastrointestinal tract. Simulated digestion of (125)I-rhEpo in suckling rat gastrointestinal juices was performed. When measured by acid precipitation and immunoassay, rat milk protected rhEpo from gastrointestinal juices better than saline (p < 0.0001). The fate of enterally administered milk-borne (125)I-rhEpo was examined in 10-d-old rats. RhEpo fed in rat milk was better protected from in vivo proteolytic degradation than rhEpo in saline (p < 0.05). After enteral (125)I-rhEpo dosing, radiolabeled protein from gastric tissue comigrated on SDS-PAGE with intact rhEpo at 36.5 kD. To determine the local and systemic distribution of physiologic intakes of rhEpo, suckling rats were fed (125)I-rhEpo in rat milk, and tissues were harvested 1, 2, and 4 h later. Intact (125)I-rhEpo was found in gastric and small intestinal walls and lumens. Five percent of total administered dose was found intact in the plasma, whereas another 8 to 10% of total administered dose was localized to bone marrow, percentages comparable to those seen after parenteral administration. Radiolabel was also localized to liver and peripheral solid tissues. These patterns of localization and degradation of rhEpo after acute administration support both systemic absorption and gastrointestinal cellular processing.

Characteristics of tranquilizer use among Australian Vietnam War veterans.

OBJECTIVE: To examine characteristics of tranquilizer use in a cohort of Australian Vietnam War veterans. DESIGN: Prospective analysis of medication use and assessment of social and clinical variables, including tranquilizer dependence. PATIENTS: Fifty-one Australian Vietnam War veterans were recruited from the department of psychiatry of an Australian teaching hospital. All subjects were men, with a mean +/- SD age of 52.2 +/- 3.3 years. MAIN OUTCOME MEASURES: A structured interview was used to obtain details of medical and psychiatric history, medication use, substance use, forensic history, and health service utilization data. Anxiety was assessed using the Hamilton Anxiety Rating Scale (Ham-A). A validated tranquilizer dependence rating scale was administered for each patient. RESULTS: Commonly used tranquilizers included diazepam (n = 19 patients) and zopiclone (26). Most patients (44) reported the use of one or more drugs for the purpose of nighttime sedation, while exclusive daytime use of tranquilizers for anxiolytic effect was uncommon. The median time spent in the hospital during the preceding year was 21.0 +/- 56.8 days. Symptoms of anxiety were prevalent, with a mean Ham-A score of 35.5 +/- 7.8. Screening criteria suggestive of tranquilizer dependence were met in 34 subjects. Health service utilization was correlated with tranquilizer intake and overall medication use. Tranquilizer dependence was independently associated with cigarette smoking (p = 0.039; odds ratio = 5.13, 95% CI 1.08 to 24.33). CONCLUSIONS: This study provides insight into the nature of tranquilizer use in an Australian population of Vietnam War veterans. The extensive use of these drugs suggests that further research and possibly intervention in this area is needed.

Outcomes of an educational-outreach service for community medical practitioners: non-steroidal anti-inflammatory drugs.

OBJECTIVE: Exploration of longer-term outcomes of an ongoing educational-outreach service for community doctors. DESIGN: Quasi-experimental, with parallel and historical comparisons. SETTING: Since 1992, a teaching-hospital-based service has been providing advice and information on drugs and therapeutic strategies to community medical practitioners. PARTICIPANTS: 210 doctors practising in a particular area of metropolitan Adelaide (79% general practitioners; 21% specialists). INTERVENTIONS: Two surgery visits during 1992 focused on better use of prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Subsequent visits on other topical therapeutic issues have occurred regularly. MAIN OUTCOME MEASURES: Doctor participation in the service; supply of prescription NSAIDs; hospital admissions for gastrointestinal (GI) effects of NSAID use. RESULTS: 89% of doctors practising within the service area received the first visit on NSAIDs and 86% received the second visit. More than 85% continue to receive the service. Relative to a comparison area, aggregate reductions of 9% and 28%, respectively, were observed in two different measures of NSAID use. During an 11-year observation period, a single change point in the number of hospital admissions for GI disorders occurred in the service area, coinciding with delivery of the NSAID program. In the five years since the visits commenced, a 70% reduction in admissions was observed. No notable changes in hospital admission rates occurred in the comparison area. CONCLUSIONS: A continuing education and support service for community medical practitioners which uses principally academic detailing methods in its contact with doctors has contributed to sustained changes in prescribed NSAID use over a five-year period. A focus on risk-minimisation in prescribing of NSAIDs appears to have contributed to reductions in hospitalisations for GI adverse events.

Improving drug use: a case study of events which led to changes in use of flucloxacillin in Australia.

Policy makers and health professionals charged with implementing policies to improve medication use require knowledge as to how to integrate and co-ordinate strategies and interventions which have been shown to be effective. Experimental methodologies are commonly used to assess the effectiveness of interventions to improve medication use and while valuable for determining the effectiveness of particular interventions, they do not add to our understanding of how to co-ordinate and integrate multiple initiatives to improve medication use. We argue that analyses of the overall system of events which are implemented to improve medication use are also needed. In this paper, we demonstrate how the case study analysed within the framework of the Transtheoretical Model of behaviour change can be used to provide an understanding of the relationship of events which result in changes in medication use. A case study of the sequence of events which led to changes in the utilisation of flucloxacillin in Australia is assessed. The analysis demonstrated that the effectiveness of individual interventions was dependent upon the initiatives which were implemented concurrently and those that had been implemented previously. Changes in the utilisation of flucloxacillin resulted from regulatory interventions and the promotion of appropriate alternative therapies. The effectiveness of this change was enhanced by previous interventions which had raised awareness amongst health professionals of the adverse hepatic reaction associated with the use of flucloxacillin. This methodology adds to those currently employed to study methods of improving use of medications. It provides an understanding of the role of each initiative in the overall system. This is valuable for policy makers, providing them with information on how to co-ordinate and orchestrate the myriad of activities which support quality use of medicines.