Pharmacist-Managed Therapeutic Drug Monitoring Programs within Australian Hospital and Health Services-A National Survey of Current Practice.

Pharmacist-managed therapeutic drug monitoring (TDM) services have demonstrated positive outcomes in the literature, including reduced duration of therapy and decreased incidence of the adverse effects of drug therapy. Although the evidence has demonstrated the benefits of these TDM services, this has predominately been within international healthcare systems. The extent to which pharmacist-managed TDM services exist within Australia, and the roles and responsibilities of the pharmacists involved compared to their counterparts in other countries, remains largely unknown. A cross-sectional online survey was conducted evaluating pharmacist-managed TDM programs within Australian hospital and healthcare settings. Pharmacist perceptions were also explored about the strengths, weaknesses, opportunities, and barriers associated with implementing a pharmacist-managed TDM service. A total of 92 surveys were returned, which represents a response rate of 38%. Pharmacist-managed TDM programs were present in 15% of respondents. It is only in the minority of hospitals where there is a pharmacist-managed service, with pharmacists involved in recommending pathology and medication doses. The programs highlighted improved patient outcomes but had difficulty maintaining the educational packages and training. For hospitals without a service, a lack of funding and time were highlighted as barriers. Based on the findings of this survey, there is minimal evidence of pharmacist-managed TDM models within Australian hospital and health services. A standardized national approach to pharmacist-managed TDM services and recognition of this specialist area for pharmacists could be a potential solution to this.

Acceptability and barriers to implementation of N-of-1 tests in Ethiopia - a qualitative study.

BACKGROUND: Locally produced generic drugs offer a cost-effective alternative to imported drugs to treat patients in Ethiopia. However, due to a lack of bioequivalence testing, additional assurance tests are needed to build trust in cheaper, locally made drugs. By testing bioequivalence of local drugs to gold standard, N-of-1 tests have the potential to promote patient centred quality use of medicines. METHOD: We sought to assess the acceptability of, and explore barriers to, conducting N-of-1 tests to evaluate local medicines in a resource limited clinical setting. We conducted a descriptive qualitative study, analysing four focus group discussions and five key informant interviews. Participants were senior drug regulatory authority members, institutional review board members, physicians and patients. All interviews were audio taped and transcribed verbatim. Patient interviews were conducted in Amharic and translated to English prior to analysis. Data analysis used an inductive, thematic process. RESULTS: Five major themes were identified; (1) Appropriateness of N-of-1 tests to determine the therapeutic equivalence of local drugs, (2) N-of-1 therapeutic equivalence tests: clinical care or research? (3) Ethical and regulatory requirements (IRB), (4) Potential barriers to implementing N-of-1 tests and (5) Possible solutions to identified challenges. The study demonstrated considerable support for using N-of-1 tests for clinical equivalence studies between local and imported medicines, but important impediments were very likely to impact the feasibility of conducting N-of-1 tests in Ethiopia. Key informants from the regulatory authority did not support additional tests of local drugs. There were also mixed opinions regarding ethical requirements for conducting N-of-1 tests. The Institutional Review Board (IRB) members believed that IRB approval was sufficient to conduct N-of-1 tests, however, the regulatory authority members considered that N-of-1 tests constituted a clinical trial, and required approval at the regulatory level. CONCLUSION: This study showed that there were key uncertainties that could impact the feasiblity of using N-of-1 testing local drugs in Ethiopia. Therefore, a number of protocol amendments to address contextual threats and regulatory challenges, would be needed before progressing to conducting these tests.

A series of N-of-1 trials to assess the therapeutic interchangeability of two enalapril formulations in the treatment of hypertension in Addis Ababa, Ethiopia: study protocol for a randomized controlled trial.

BACKGROUND: Hypertension is one of the leading causes of morbidity and mortality in Ethiopia. Treatment usually involves lifelong medication use. Enalapril is a common drug for the treatment of hypertension in Ethiopia. However, the drug is expensive and, therefore, there is limited capacity for people to afford the treatment. Locally produced Enalapril is a cost-effective solution to treat the disease. However, as local medicines regulation does not include bioequivalence tests on locally produced drugs, physicians and patients need assurance about the effectiveness and safety of local generics. Evidence on therapeutic equivalence is needed on these untested local drugs. METHODS: This is a hospital-based, randomized, partially blinded, three-cycle crossover trial in single patients, comparing a locally produced version of enalapril with enalapril imported from Europe. Patients involved in this trial are not blinded, as there is no local facility to produce relatively small numbers of placebos or encapsulated drugs. To ensure blinding of study investigators and data analysts, study medications are prepared by an independent pharmacy unit using opaque medication packaging. The importance of maintaining blinding is also part of patient pre-trial education. Each N-of-1 trial will consist of three successive 14-day treatment pairs, each pair comprising 7 days of 5-20 mg local and 7 days of 5-20 mg imported enalapril taken once daily in the morning. The primary outcome will be the average difference in systolic blood pressure as measured by home blood pressure measurements. DISCUSSION: The number of locally produced products, such as enalapril, being approved without proof of bioequivalence is dramatically increasing. By bridging the information gap on bioequivalence, the trial will give rigorous evidence on therapeutic equivalence of locally produced enalapril in the treatment of hypertension. If there is no difference, the hypothesized result, then patients can take the local medicine with confidence. This trial will also will determine whether aggregated N-of-1 studies are feasible to evaluate untested generic drugs in resource-limited countries where bioequivalence testing centers are unavailable. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry, ID: ACTRN12616001088437p . Registered on 12 August 2016.

Do Participants With Different Patterns of Loss to Follow-Up Have Different Characteristics? A Multi-Wave Longitudinal Study.

BACKGROUND: To identify patterns of loss to follow-up and baseline predictors of each pattern. METHODS: The Mater-University Study of Pregnancy collected baseline information for 7718 pregnant women who attended Mater Hospital in Brisbane, Australia, from 1981 through 1983. Follow-up data for 6753 eligible participants were collected at 6 months, 5 years, 14 years, 21 years, and 27 years after giving birth. Participants were partitioned into groups of 'Always Responders', 'Returners', 'Leavers', 'Intermittents', and 'Never Responders'. Multinomial logistic regression was used to simultaneously compare baseline characteristics of the last four groups with 'Always Responders'. RESULTS: Being younger, less educated, having no partner, and living in rented housing were associated with being a 'Returner'. Not owning housing, receiving welfare benefits, and being younger, less educated, not married, a smoker, an Aboriginal/Islander, and born in a non-English-speaking country were associated with being a 'Leaver', an 'Intermittent', or a 'Never-responder'. Having higher mental health score and drinking before pregnancy were associated with being a 'Leaver' or an 'Intermittent'. Being unemployed and not physically active were associated with being a 'Leaver' or 'Never Responder'. The groups 'Leavers' and 'Never Responders' were the most different from the 'Always Responders'. The group that was most similar to 'Always Responders' was the 'Returners'. CONCLUSIONS: Patterns of loss to follow-up should be considered in the application of missing data techniques, where researchers make assumptions about the characteristics of those subjects who do not respond to assess the type of missing data. This information can be used to prevent individuals who are at high risk of dropping out of a study from doing so.

Cannabis use and quality of life of adolescents and young adults: findings from an Australian birth cohort.

Cannabis is generally used to enhance mood (quality of life), but it is not known whether it has this effect in the medium to longer term. Little is currently known about the temporal sequence between cannabis use and the quality of life (QOL). Data are taken from a prospective longitudinal study of pregnant women recruited at their first antenatal visit in Brisbane, Australia. Offspring data from the follow-ups with 14-year-olds and 21-year-olds are used here. Indicators of QOL, happiness, and satisfaction at 14 years are considered as predictors of subsequent cannabis use. The association between cannabis use and QOL at 21 years, adjusting for prior QOL (14 years), is also examined. Socio-demographic characteristics were included as potential confounders relevant to QOL assessments. In this cohort, lower QOL in the early teenage years predicted subsequent onset of cannabis use in young adulthood. After adjustment for socio-demographic characteristics and for QOL pre-cannabis use, participants who used cannabis more frequently had a lower QOL at the 21-years follow-up. Frequent use of cannabis does not appear to enhance the user's QOL and appears to be associated with a reduced QOL into young adulthood.

Cohort Profile Update: The Mater-University of Queensland Study of Pregnancy (MUSP).

The Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes began in 1981 with data collected on 7223 pregnant woman-child pairs (6753 mothers, of whom 520 had 2 study children, less 50 who had multiple births). These women, and their children, were initially followed for up to 21 years. Since then there have been additional follow-ups of the mothers (27 years) and their children (30 years). There has also been a substantial increase in the breadth of topics addressed, with the collection of biological samples, the administration of structured clinical assessments of mental health and cognitive capacity, and markers of physical health such as lung function and blood pressure. MUSP was originally developed as a birth cohort study. It has become a longitudinal study of growth, development and ageing with an emphasis on the generational transmission of a wide range of factors impacting on adult health outcomes. We welcome interest in our study; for study background and publications visit [www.socialscience.uq.edu.au/musp] or contact [j.najman@uq.edu.au].

Sleepless nights: the effect of socioeconomic status, physical activity, and lifestyle factors on sleep quality in a large cohort of Australian women.

The aims of this study were to examine: (1) the association between sociodemographic and lifestyle factors and sleep quality in a population-based cohort of Australian women and (2) possible influence of reproductive status and mental and physical health factors on these associations. Data on 3,655 women (mean age = 46.6 years, range 34.3-67.4) were obtained from the Mater Hospital University of Queensland Study of Pregnancy for this cross-sectional study. Self-rated sleep quality was assessed using the Pittsburgh Sleep Quality Index. For the purpose of this study, two cutoff points (scores 5 and 10) were used to divide women into three categories: normal (65.2%), moderately poor (26.4%), and very poor sleep quality (8.5%). Other covariates were measured at 21-year follow-up as well. After adjusting for reproductive status, mental and physical health, there were significant associations between moderately poor sleep quality and education and between very poor sleep quality and unemployment, both measures of socioeconomic status. In addition, work-related exertion was associated with increased rates of moderately poor sleep quality, whereas those women undertaking moderate exercise were less likely to experience very poor sleep quality. Independent associations between sociodemographic factors and exercise with moderately poor and very poor sleep quality were identified. These findings demonstrate the dynamic nature of the association between exercise/exertion, socioeconomic status, and sleep quality and highlight the importance of taking these into consideration when dealing with issues of poor sleep quality in women.

Young adults' gambling and its association with mental health and substance use problems.

OBJECTIVE: To examine the socio-demographic characteristics of young adults' gambling and its association with mental health and substance use behaviour. METHODS: The study is based on 3,512 young adults (1648 males) for whom data from the Mater-University of Queensland Study of Pregnancy (MUSP) were available on self-report gambling, gambling expenditure, Achenbach's Young Adult Self Report and substance use at the 21-year follow-up of the MUSP. The participants' age ranged between 18.2 and 23.6 (mean = 20.6, standard deviation = 0.8) years. RESULTS: Two-fifths of the young adults reported gambling. Males reported more money spent on gambling and were significantly more likely to be at risk of problem gambling. Gambling and problem gambling were significantly more common in less-educated individuals, those who had higher income or those who had a paid job. Individuals who reported gambling were more likely to smoke cigarettes, drink more than a glass of alcohol per day, use illicit drugs, or exhibit high levels of externalising behaviour than non-gamblers. CONCLUSIONS: The findings confirm the high prevalence of gambling and gambling expenditure in young adults. Individuals who are involved in gambling are more likely to report cigarette smoking, alcohol consumption, and use of illicit drugs. There is a need for further research to explore the mechanisms of association between gambling behaviour and individuals' mental health and substance use. IMPLICATIONS: Substance abuse and mental health services are recommended to consider co-morbid gambling problems in treatment-seeking patients.

Medical costs and outcomes for Australian women with ovarian cancer: a patient-level analysis over 2.5 years.

OBJECTIVE: As treatment costs for gynecological cancer escalate, real-world data on use of resources and costs becomes increasingly important. This study investigated medical costs, quality of life, and survival end points for women with ovarian cancer in Australia. METHODS: Women with primary epithelial ovarian cancer referred for chemotherapy (n =85) were recruited through 7 hospitals in Australia. Overall survival, progression-free interval, and quality-adjusted life years were assessed by stage using the Cox proportional hazards models. Direct medical costs, including those for surgeries, hospitalizations, supportive care, chemotherapy, and adverse effects (while on chemotherapy), were calculated over 2.5 years and assessed by nonparametric bootstrapping. RESULTS: Quality-adjusted life years decreased with increased disease stage at diagnosis and ranged from 2.3 for women with stage I or II disease to 1.3 for those with stage IV disease. A total of AU $4.1 million (2008) were spent on direct medical costs for 85 women over approximately 2.5 years. Medical costs were significantly higher for women with stage III or IV disease compared with that for women with stage I or II disease ($50,945 vs $31,958, P < 0.01) and/or women who experienced surgical complications and/or adverse effects requiring hospitalization while on chemotherapy ($57,821 vs $34,781, P < 0.01). Costs after first-line chemotherapy were significantly higher for women with advanced disease (mean, $20,744) compared with those for women with early disease (mean, $5525; P < 0.01). CONCLUSIONS: Whereas for women with early-stage ovarian cancer, costs are concentrated in the period of primary treatment, cumulated costs are especially high for women with recurrent disease rising rapidly after first-line therapy.

Stakeholders' views on the routine use of n-of-1 trials to improve clinical care and to make resource allocation decisions for drug use.

N-of-1 trials are empirical formal tests using a within-patient randomised, double-blind, cross-over comparison of drug and placebo (or another drug), which we adapted to study individual patients' responses as a clinical tool to guide clinical management. We administered semi-structured interviews to gauge stakeholder perspectives on the possibility of using routine n-of-1 trials for this purpose. Stakeholders included government and non-government health care sector, and patient, clinician and consumer, organisations. Stakeholders supported more widespread implementation of n-of-1 trials, in a targeted fashion, with some caveats. Barriers to their widespread implementation included constraints on doctors' time, doctors' acceptance, drug company acceptance, patient willingness, and cost. Strategies for overcoming barriers included conditional Pharmaceutical Benefits Scheme listing if cost-effective. There was little consensus on which model of n-of-1 trial implementation would be most effective. We discuss different approaches to addressing the several concerns raised to enable widespread introduction of n-of-1 trials into routine clinical practice as a decision tool.

The impact of perceived stage of cancer on carers' anxiety and depression during the patients' final year of life.

OBJECTIVE: This paper explores the effects of perceived stage of cancer (PSOC) on carers' anxiety and depression during the patients' final year. METHODS: A consecutive sample of patients and carers (N=98) were surveyed at regular intervals regarding PSOC, and anxiety and depression using the Hospital Anxiety and Depression Scale. Means were compared by gender using the Mann-Whitney U-test. The chi-square was used to analyse categorical data. Agreement between carers' and patients' PSOC was estimated using kappa statistics. Correlations between carers' PSOC and their anxiety and depression were calculated using the Spearman's rank correlation. RESULTS: Over time, an increasing proportion of carers reported that the cancer was advanced, culminating at 43% near death. Agreement regarding PSOC was fair (kappa=0.29-0.34) until near death (kappa=0.21). Carers' anxiety increased over the year; depression increased in the final 6 months. Females were more anxious (p=0.049, 6 months; p=0.009, 3 months) than males, and more depressed until 1 month to death. The proportion of carers reporting moderate-severe anxiety almost doubled over the year to 27%, with more females in this category at 6 months (p=0.05). Carers with moderate-severe depression increased from 6 to 15% over the year. Increased PSOC was weakly correlated with increased anxiety and depression. CONCLUSIONS: Carers' anxiety exceeded depression in severity during advanced cancer. Females generally experienced greater anxiety and depression. Carers were more realistic than patients regarding the ultimate outcome, which was reflected in their declining mental health, particularly near the end.

Common symptoms during pregnancy to predict depression and health status 14 years post partum.

OBJECTIVE: To examine the prospective association between symptoms commonly experienced during pregnancy and the mental and general health status of women 14 years post partum. METHODS: Data used were from the Mater-University of Queensland Study of Pregnancy, a community-based prospective birth cohort study begun in Brisbane, Australia, in 1981. Logistic regression analyses were conducted. RESULTS: Data were available for 5118 women. Women who experienced a higher burden of symptoms during pregnancy were at greater risk of becoming depressed and reporting poorer health status 14 years post partum. Women who experienced major problems during pregnancy were 4 times more likely to be depressed and nearly 8 times more likely to report poorer health status 14 years after the index pregnancy compared with women who experienced few problems. CONCLUSIONS: Findings suggest that pregnant women who experience common symptoms during pregnancy are likely to experience poorer mental and self-reported general health 14 years after the pregnancy.

Oncology nurses' perceptions of their supportive care for parents with advanced cancer: challenges and educational needs.

Despite the emotional impact for children with a parent with advanced cancer, most families receive limited information and support to assist them. A project is underway to determine the acceptability and effectiveness of a supportive and educational intervention for parents with advanced cancer to be delivered by specially trained oncology nurses. To assess the perceptions of oncology nurses about this role, explore potential challenges, and understand their educational needs, oncology nurses were recruited from three metropolitan hospitals to participate in focus groups. This data was supplemented with data from individual interviews conducted with rurally based nurses unable to participate in focus groups held in a metropolitan location. Four focus groups were held, with 24 participants. Individual telephone interviews were conducted with five nurses. Nurses identified the emotional burden of the supportive care role as a key challenge, along with health care systems which were not attuned to the needs of families. Attention to self-care and professional confidence, and access to role-models emerged as key elements required in education, along with information about the impact of parental cancer on children and their developmental stages, and ways to promote more open parental communicate with children.

Correcting for numerator/denominator bias when assessing changing inequalities in occupational class mortality, Australia 1981 -2002.

OBJECTIVE: Comparisons of the changing patterns of inequalities in occupational mortality provide one way to monitor the achievement of equity goals. However, previous comparisons have not corrected for numerator/denominator bias, which is a consequence of the different ways in which occupational details are recorded on death certificates and on census forms. The objective of this study was to measure the impact of this bias on mortality rates and ratios over time. METHODS: Using data provided by the Australian Bureau of Statistics, we examined the evidence for bias over the period 1981 -2002, and used imputation methods to adjust for this bias. We compared unadjusted with imputed rates of mortality for manual/non-manual workers. FINDINGS: Unadjusted data indicate increasing inequality in the age-adjusted rates of mortality for manual/non-manual workers during 1981 -2002. Imputed data suggest that there have been modest fluctuations in the ratios of mortality for manual/non-manual workers during this time, but with evidence that inequalities have increased only in recent years and are now at historic highs. CONCLUSION: We found that imputation for missing data leads to changes in estimates of inequalities related to social class in mortality for some years but not for others. Occupational class comparisons should be imputed or otherwise adjusted for missing data on census or death certificates.

Using n-of-1 trials as a clinical tool to improve prescribing.

BACKGROUND: N-of-1 trials are within-patient, randomised, double-blind, placebo-controlled cross-over comparisons of two drugs for chronic illnesses. We have investigated the use of these, offered to doctors as individualised medication effectiveness tests (IMETs), as a tool to improve drug prescribing. AIM: To examine patient perspectives and experiences of n-of-1 trials. DESIGN OF STUDY: We provided n-of-1 trials for osteoarthritis (OA), comparing paracetamol and ibuprofen; and attention deficit hyperactivity disorder (ADHD), comparing dexamphetamine or methylphenidate and placebo. Patients or their carers were surveyed before and after the trials by questionnaire, and after the trial by semistructured interview with thematic analysis. SETTING: Australian community-based patients and practitioners. METHOD: Forty-two patients with OA and 21 carers of patients with ADHD, for whom the effectiveness of proposed or existing medication was uncertain, completed the questionnaires, and 25 patients/carers (11 with OA and 14 with ADHD) participated in semi-structured interviews. RESULTS: Patients in this purposive sample were generally very satisfied with the n-of-1 trial process. Their participation led to increased knowledge, awareness and understanding of their condition, their bodies' response to it, and its management. Some of this arose specifically from use of daily symptom diaries. This led to a sense of empowerment and control as well as improved individually-focused care. CONCLUSIONS: N-of-1 trials appeared to empower these patients as a result of both collecting information about their responses to different treatment options, and participating actively in subsequent therapeutic decisions. They are a patient-centred intervention that may improve medication management in suitable chronic diseases.

The view from two sides: a qualitative study of community and medical perspectives on screening for colorectal cancer using FOBT.

BACKGROUND: Population-wide screening for people at average risk of colorectal cancer (CRC) by faecal occult blood test (FOBT) is under consideration in Australia. METHODS: Qualitative methods were used to examine the views of community members who did (n = 18) or did not (n = 12) participate in a pilot program of FOBT screening. In addition, views were obtained from general practitioners (GPs) and specialist gastroenterologists directly involved in the implementation of the program. Two focus group sessions were conducted with screening participants and interviews were conducted with nonparticipants, GPs and gastroenterologists. RESULTS: The findings suggest that CRC screening by FOBT distributed to households by mail was well accepted by the community and by the medical practitioners involved in its implementation. The trial had little negative effect on general practice. Both medical practitioners and consumers raised concerns about the efficacy of FOBT screening. Medical practitioners were also concerned about the potential burden mass screening could place on the public (government-funded) health care sector. CONCLUSIONS: It would seem that CRC screening using FOBT will not enjoy unqualified support from the community or from medical practitioners involved in the continuum of screening. Information about the objectives of screening programs, in general, and the efficacy of FOBT screening in particular, needs to be provided to the community to ensure informed individual choice.

The needs of cancer patients and their families from rural and remote areas of Queensland.

This study examines the impact of travelling for treatment on cancer patients and their families. Twenty-eight consecutive cancer patients, who were receiving radiation therapy treatment and 19 family carers, completed a structured needs assessment questionnaire and an in-depth interview. Both patients and carers reported moderate to high levels of unmet psychological need. Carers were found to have higher levels of anxiety than patients, although both groups had higher anxiety levels than the general population. Taking more responsibility for household tasks and organising new living arrangements for the family were the most frequently identified demands of a dual burden of caring. Nearly 40% of carers reported some disruption to their schedule and half reported experiencing financial difficulties. The qualitative interviews highlight the disruption that parents and children experience under the present system, particularly in relation to the demands of family life and the need to maintain some level of continuity and security for children.