Reducing adverse events in older Australians taking newly released drugs

The number of older Australians with one or multiple chronic diseases is increasing. This thesis presents a model to assist in identifying current older patients with multiple illnesses and taking multiple medications who are at risk of experiencing an adverse drug reaction if they are prescribed a newly released drug.

Evaluation of an internet-based psychological intervention for the treatment of erectile dysfunction

Recent research on the treatment of erectile dysfunction (ED) has focused on medical interventions, in particular oral medications. The current study examined the effectiveness of an internet-based psychological intervention for this condition. In total, 31 men (12 in treatment group, 19 in control group) completed the program. The results demonstrated that men who completed the program reported improved erectile functioning and sexual relationship satisfaction and quality. The implications of these findings for the treatment of ED are discussed.

An appraisal of the histopathological assessment of liver fibrosis.

One of the most important aspects of the histopathological assessment of liver biopsies in the setting of chronic liver disease is determination of the degree of fibrosis and architectural change. Most of the work in this regard has been concerned with chronic viral hepatitis. This article attempts to assess critically our current and historical biopsy practice, from subjective fibrosis scoring systems to biopsy sample size; and the appropriate use of the data that scoring systems
generate in the research and clinical setting. An understanding of the limitations of each of the components of the fibrosis assessment process can help to devise appropriate protocols to ensure that the information obtained is optimised, and its degree of reliability appreciated. It is only from this starting point that recently promulgated antifibrotic medications and ‘‘non-invasive’’ liver fibrosis assessment techniques can be evaluated properly.

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

Background
The majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).

Methods/Design
The HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense®). The pharmacies have been randomised to either 'Pharmacist Care Group' (PCG) or 'Usual Care Group' (UCG). To check for 'Hawthorne effect' in the UCG, a third group of patients 'Hidden Control Group' (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.

Discussion
To our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the 'Hawthorne effect' in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.

Trial Registration
Australian New Zealand Clinical Trial Registry ACTRN12609000705280

Identification of depression in diabetes the efficacy of PHQ-9 and HADS-D

Background
Clinical guidelines advise screening for depression in patients with diabetes. The Patient Health Questionnaire (PHQ-9) and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) are commonly used in primary care.

Aim
To compare the efficacy of HADS-D and PHQ-9 in identifying moderate to severe depression among primary care patients with type 2 diabetes.

Design of study
Self-report postal survey, clinical records assessed by GPs.

Setting
Seven metropolitan and rural general practices in Victoria, Australia.

Method
Postal questionnaires were sent to all patients with diabetes on the registers of seven practices in Victoria. A total of 561 completed postal questionnaires were returned, giving a response rate 47%. Surveys included demographic information, and history of diabetes and depression. Participants completed both the PHQ-9 and HADS-D. Clinical data from patient records included glycosylated hemoglobin (HbA1c) levels and medications.

Results
The proportion of the total sample completing HADS-D was 96.8% compared with 82.4% for PHQ-9. Level of education was unrelated to responses on the HADS-D but was related to completion of the PHQ-9. Using complete data (n = 456) from both measures, 40 responders showed HADS-D scores in the moderate to severe range, compared with 103 cases identified by PHQ-9. Only 35 cases were classified in the moderate to severe category by both the PHQ-9 and HADS-D. Items with the highest proportions of positive responses on the PHQ-9 were related to tiredness and sleeping problems and, on the HADS-D, feeling slowed down.

Conclusion
It may be that the items contributing to the higher prevalence of moderate to severe depression using the PHQ-9 are due to diabetes-related symptoms or sleep disorders.

Medical error and decision making : learning from the past and present in intensive care

Background : Human error occurs in every occupation. Medical errors may result in a near miss or an actual injury to a patient that has nothing to do with the underlying medical condition. Intensive care has one of the highest incidences of medical error and patient injury in any specialty medical area; thought to be related to the rapidly changing patient status and complex diagnoses and treatments.

Purpose : The aims of this paper are to: (1) outline the definition, classifications and aetiology of medical error; (2) summarise key findings from the literature with a specific focus on errors arising from intensive care areas; and (3) conclude with an outline of approaches for analysing clinical information to determine adverse events and inform practice change in intensive care.

Data source : Database searches of articles and textbooks using keywords: medical error, patient safety, decision making and intensive care. Sociology and psychology literature cited therein.

Findings : Critically ill patients require numerous medications, multiple infusions and procedures. Although medical errors are often detected by clinicians at the bedside, organisational processes and systems may contribute to the problem. A systems approach is thought to provide greater insight into the contributory factors and potential solutions to avoid preventable adverse events.

Conclusion : It is recommended that a variety of clinical information and research techniques are used as a priority to prevent hospital acquired injuries and address patient safety concerns in intensive care.

Nutrition care for adult cardiac patients : Australian general practitioners' perceptions of their role

Background. Australia has implemented systematic managed care for patients with chronic disease. Little is known about how GPs perceive their nutrition care role in this system.
Objective. To examine GPs’ perceptions of their roles in the nutrition care of cardiac patients and to identify factors that influence their role.
Methods. Multi-methods research design. Semi-structured interviews were conducted with a sample (n = 30) GPs Victoria, Australia. The resulting narratives were used to develop a quantitative questionnaire to survey a random sample of GPs. Principal components analysis was conducted to reduce the role items to a small number of underlying dimensions. The association between roles and demographic variables were examined using stepwise multiple regressions.
Results. In all, 248 GPs (30% response) participated. Three main roles were established: Influencing, Coordinating and Nutrition Educator role. Together, the roles explained 54% of the total variance. Demographic variables were not associated with these roles. The majority (mean = 88%) endorsed the items which loaded on to the Influencing and Coordinating (mean = 49%) roles. Short consultation time, use of prescribed medications and perception of patient attendance at cardiac rehabilitation reduced the priority for nutrition education.
Conclusions. This study highlights the importance of developing more effective team care arrangements for patients with chronic disease and working with the medical education colleges to develop education resources for doctors that include an explanation of the non-pharmaceutical as well as the pharmaceutical treatment for each chronic disease condition.

General practitioners’ decision to refer patients to dietitians : insight into the clinical reasoning process

The aim of this project was to describe general practitioners’ (GPs’) decision-making process for reducing nutrition risk in cardiac patients through referring a patient to a dietitian. The setting was primary care practices in Victoria. The method we employed was mixed methods research: in Study 1, 30 GPs were interviewed. Recorded interviews were transcribed and narratives analysed thematically. Study 2 involved a survey of statewide random sample of GPs. Frequencies and analyses of variance were used to explore the impact of demographic variables on decisions to refer. We found that the referral decision involved four elements: (i) synthesising management information; (ii) forecasting outcomes; (iii) planning management; and (iv) actioning referrals. GPs applied cognitive and collaborative strategies to develop a treatment plan. In Study 2, doctors (248 GPs, 30%) concurred with identified barriers/enabling factors for patients’ referral. There was no association between GPs’ sex, age or hours worked per week and referral factors. We conclude that a GP’s judgment to offer a dietetic referral to an adult patient is a four element reasoning process. Attention to how these elements interact may assist clinical decision making. Apart from the sole use of prescribed medications/surgical procedures for cardiac care, patients offered a dietetic referral were those who were considered able to commit to dietary change and who were willing to attend a dietetic consultation. Improvements in provision of patients’ nutrition intervention information to GPs are needed. Further investigation is justified to determine how to resolve this practice gap.

A naturalistic study of treatment outcomes with aripiprazole in young people with first episode psychosis

Objective: Adequate treatment of a first psychotic episode in young people is a difficult challenge but may be of critical importance for changing the course of psychotic illness. Pharmacotherapy is the standard treatment of psychosis, however there is a paucity of data specific to first-episode psychosis.
Methods: In this study 12 young people who presented with a psychotic episode at a specialised early intervention service were commenced on treatment with aripiprazole. They were assessed at baseline and weeks 4, 6, 24 and 48 using a broad battery of outcome measures. Case notes were also examined.
Results: Data was available for 6 participants at week 48, and of those, one remained on treatment with Aripiprazole at endpoint. Case histories were typified by presentations that included illicit substance use and treatments characterised by several changes in medications. No single treatment choice predominated. Most participants tolerated treatment and showed symptomatic improvement with individualised therapy.
Conclusion: Most participants showed improvement during the treatment period. Aripiprazole was one of many medications used in this study and may have been useful for the treatment of some individuals with first episode psychosis.

Influence of dietary modifications on the blood pressure response to antihypertensive medication

Identifying dietary modifications that potentiate the blood pressure (BP)-lowering effects of antihypertensive medications and that are practical for free-living people may assist in achieving BP reduction goals. We assessed whether two dietary patterns were effective in lowering BP in persons on antihypertensive therapy and in those not on therapy. Ninety-four participants (38/56 females/males), aged 55.6 (sd 9.9) years, consumed two 4-week dietary regimens in random order (Dietary Approaches to Stop Hypertension (DASH)-type diet and low-Na high-K (LNAHK) diet) with a control diet before each phase. Seated home BP was measured daily for the last 2 weeks in each phase. Participants were grouped based on antihypertensive drug therapy. The LNAHK diet produced a greater fall in systolic BP (SBP) in those on antihypertensive therapy ( - 6.2 (sd 6.0) mmHg) than in those not on antihypertensive therapy ( - 2.8 (sd 4.0) mmHg) (P = 0.036), and this was greatest for those on renin-angiotensin system (RAS) blocker therapy ( - 9.5 (sd 6.4) mmHg) (interaction P = 0.007). The fall in SBP on the DASH-type diet, in those on therapy (overall - 1.1 (sd 6.2) mmHg; renin-angiotensin blocker therapy - 4.2 (sd 4.7) mmHg), was not as marked as that observed on the LNAHK diet. Dietary modifications are an important part of all hypertension management regimens, and a low-Na and high-K diet enhances the BP-lowering effect of antihypertensive medications, particularly those targeting the RAS.

Developmental outcomes of children exposed to antidepressants in pregnancy

Objective: To examine the developmental outcomes in children exposed to antidepressants in utero and compare those to children not exposed to these medications
Method: A prospective case-controlled study of children exposed to antidepressants in pregnancy assessed 22 exposed and 19 not exposed children using the Bayley Scales of Infant Development, third edition. The control group was measured at a mean age of 23.09 (SD 3.82) months and the medicated group at 28.53 months (SD 6.22). Maternal variables were assessed using a purpose-designed questionnaire and the Beck Depression Inventory (II) in pregnancy and at three assessments in the postpartum.
Results: Children exposed to antidepressant medication in pregnancy scored lower on motor subscales in particular on fine motor scores than non-exposed children with a moderate effect size of Cohen ’ s d = 0.47 fi ne motor and Cohen ’ s d = 0.43 for gross motor. Due to lack of power these findings did not reach conventional criteria for statistical significance. There was no association found between maternal depression and neurodevelopment.
Conclusions: This finding of a possible effect from antidepressant exposure in pregnancy on children ’ s motor development is similar to the findings from a previous study. Future research is needed which assesses children at an older age using specific assessments of motor development.

Leptin in depressed women : Cross-sectional and longitudinal data from an epidemiologic study

Background There is conflicting evidence regarding levels of leptin in depression. In this study we aimed to investigate the relationship between serum leptin level and depression in a community sample of women using both cross-sectional and longitudinal data.

Methods From among 510 women aged 20–78 yr, 83 were identified with a lifetime history of major depressive disorder or dysthymia, ascertained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Serum leptin levels were measured by radioimmunoassay. Medication use and lifestyle were self-reported and body mass index (BMI) determined from measures of height and weight.

Results Using multiple linear regression, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression, independent of BMI. Adjusted geometric mean values of serum leptin were 16.37 (95%CI 14.70–18.23) ng/mL for depressed and 14.46 (95%CI 13.79–15.16) ng/mL for non-depressed women (P = 0.039). The hazard ratio (HR) for a de novo depressive disorder over five years increased 2.56-fold for each standard deviation increase in log-transformed serum leptin among non-smokers and this was not explained by differences in BMI, medications or other lifestyle factors (HR = 2.56, 95%CI 1.52-4.30). No association was observed for smokers.

Limitations There is potential for unrecognised confounding, recall bias and transient changes in body composition.

Conclusion Women with a lifetime history of depression have elevated levels of serum leptin, and elevated serum leptin predicts subsequent development of a depressive disorder.

Association of high-sensitivity C-reactive protein with de novo major depression

Background: Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking.

Aims: We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder.

Method: Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis.

Results: During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression.

Conclusions: Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.

Comparing methods for prescribing exercise for individuals with chronic heart failure

This study examined the accuracy of current recommended guidelines for prescribing exercise intensity using the methods of percentage of heart rate reserve (%HRR), percentage of VO₂ peak (%VO₂peak) and percentage of VO₂ reserve (%VO₂R) in a clinical population of chronic heart failure (CHF) patients. The precision of prescription of exercise intensity for 45 patients with stable CHF (39:6 M:F, 65±9 yrs (mean±SD)) was investigated. VO₂peak testing is relatively common among patients with cardiac disease, but the assessment of VO₂rest is not common practice and the accepted standard value of 3.5 mL/kg/min is assumed in the application of %VO2R (%VO₂R_3.5). In this study, VO₂rest was recorded for 3 min prior to the start of a symptom-limited exercise test on a cycle ergometer. Target exercise intensities were calculated using the VO₂ corresponding to 50 or 80 %HRR, VO₂peak and VO₂R. The VO₂ values were then converted into prescribed speeds on a treadmill in km/hr at 1 %grade using ACSM’s metabolic equation for walking. Target intensities and prescribed treadmill speeds were also calculated with the %VO₂R method using the mean VO₂rest value of participants (3.9 mL/kg/min) (%VO₂R_3.9). This was then compared to the exercise intensities and prescribed treadmill speeds using patient’s measured VO₂rest. Error in prescription correlates the difference between %VO₂R_3.5 and %VO₂R_3.9 compared to %VO₂R with measured VO₂rest. Prescription of exercise intensity through the %HRR method is imprecise for patients on medications that blunt the HR response to exercise. %VO₂R method offers a significant improvement in exercise prescription compared to %VO₂peak. However, a disparity of 10 % still exists in the %VO₂R method using the standard 3.5 mL/kg/min for VO₂rest in the %VO₂R equation. The mean measured VO₂rest in the 45 CHF patients was 11 % higher (3.9±0.8 mL/kg/min) than the standard value provided by ACSM. Applying the mean measured VO₂rest value of 3.9 mL/kg/min rather than the standard assumed value of 3.5 mL/kg/min proved to be closer to the prescribed intensity determined by the actual measured resting VO₂. These results suggest that the %HRR method should not be used to prescribe exercise intensity for CHF patients. Instead, VO₂ should be used to prescribe exercise intensity and be expressed as %VO₂R with measured variables (VO₂rest and VO₂peak).

Significant challenges remain to achieve risk reduction targets for cardiovascular secondary prevention and diabetes

Objective: To examine population-level evidence treatment gaps for cardiovascular risk among rural patients with existing cardiovascular disease or diabetes.

Methods: Three population surveys were undertaken in the Greater Green Triangle region of southeastern Australia 2004-2006. Adults aged 25-84 yrs were randomly selected using age/sex stratified electoral role samples. A representative 1690 participants were recruited (48% participation rate). Anthropometric, clinical and self-administered questionnaire chronic disease risk data were collected in accordance with the WHO MONICA protocol. Detailed investigation of cardiovascular and diabetes history, key cardiovascular risk factors, medication use and health behaviours were included.

Results: After adjusting for age and sex, an estimated 12% (sample n=272) of the population had one or more of coronary heart disease, stroke, or diabetes. Blood pressure was at target (<130/80 mmHg) for 26% of these individuals, and 61% were treated with antihypertensive medications. Lipid targets were achieved by 17% for total cholesterol (<4 mmol/L), 18% for LDL cholesterol (<2 mmol/L), 77% for HDL cholesterol (>1.0 mmol/L) and 44% for triglycerides (<1.5 mmol/L); overall 6% achieved all four lipid targets and 60% reported use of lipid-lowering therapy, including 51% overall using statins. Ten percent were current smokers, and four in every five patients (82%) had suboptimal BMI (outside the range 18.5 - 25.0).

Conclusions: All participants with uncontrolled blood pressure and most with uncontrolled lipids should be taking medications. The magnitude of evidence treatment gaps suggests existing models of care need fundamental reform and renewed focus on prevention.