What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies.

Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.

Implementing a web-based oncology protocol system in Australia: evaluation of the first 3 years of operation.

BACKGROUND: EviQ is a web-based oncology protocol system launched across Australia in 2005 (http://www.eviq.org.au). We evaluated eviQ use at the point-of-care and determined the factors impacting on its uptake and routine use in the first three years of operation. METHODS: We conducted a suite of qualitative and quantitative studies with over 200 Australian oncology physicians, nurses and pharmacists working at treatment centres in diverse geographical locations. RESULTS: EviQ was part of routine care at many hospitals; however, the way in which it was used at the point-of-care varies according to clinician roles and hospital location. We identified a range of factors impacting on eviQ uptake and routine use. Infrastructure, such as availability of point-of-care computers, and formal policies endorsing eviQ are fundamental to increasing uptake. Furthermore, the level of clinical and computer experience of end-users, the attitudes and behaviour of clinicians, endorsement and promotion strategies, and level and type of eviQ education all need to be considered and managed to ensure that the system is being used to its full potential. CONCLUSION: Our findings show that the dissemination of web-based treatment protocols does not guarantee widespread use. Organisational, environmental and clinician-specific factors play a role in uptake and utilisation. The deployment of sufficient computer infrastructure, implementation of targeted training programmes and hospital policies and investment in marketing approaches are fundamental to uptake and continued use. This study highlights the value of ongoing monitoring and evaluation to ensure systems like eviQ achieve their primary purpose - reducing treatment variation and improving quality of care.

Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer.

BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.

Governance approval for multisite, non-interventional research: what can Harmonisation of Multi-Centre Ethical Review learn from the New South Wales experience?

BACKGROUND: In 2007, New South Wales Health mandated the separation of ethical and scientific review from research governance at all New South Wales public health sites based on their distinction in the National Health and Medical Research Council National Statement. This separation allowed for single-site ethical review of multicentre studies. AIMS: To investigate the time taken for governance approval of multicentre studies through the site-specific approval (SSA) process. METHODS: A retrospective audit of the SSA process for five non-interventional studies proposed by a university cancer research unit. RESULTS: The median total governance approval time for all submissions (n= 28) was 12 weeks (range 2.5-64); median time from starting the SSA to submission was 8 weeks (range 1-48) and median time for governance approval was 5 weeks (range 0.3-40). Approval times were shorter for public compared to private institutions. Reasons for delays in finalising submissions for approval were the absence of institutional governance officers, lack of clarity regarding signatories, the need to identify a principal investigator employed by the institution, and lack of recognition of ethical approval by private institutions. The need to develop legal agreements between the university and hospital was the main reason for lengthy delays in obtaining approval. CONCLUSIONS: The advantages of a harmonised single ethical review process were undermined by the coexistence of a fragmented, complex and lengthy governance approval process. This experience has implications for the success of the national Harmonisation of Multi-Centre Ethical Review (HoMER) model. A harmonised and fully supported national approach to research governance should be developed contemporaneously with HoMER.

De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

BACKGROUND: Advances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC). METHODS: We searched MEDLINE 01/01/1995-12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups. FINDINGS: We identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005-2009, the median OS was 26 months (range 24-30), a median gain of 6 months since 1995-1999 (range 0-9, 4 studies). Median 5-year OS was 23% in 2005-2009, a median gain of 7% since 1995-1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007-2013 (median OS 23 months). For combined MBC, 76-89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995-1999 19·1; 2000-2004 22·3 months) but not >60 years (12·7, 11·6 months). INTERPRETATION: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. FUNDING: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21-001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

The quality of web-based oncology guidelines and protocols: how do international sites stack up?

BACKGROUND: The Internet is a popular medium for disseminating information relevant to oncology practitioners. Despite the widespread use of web-based guidelines and protocols, the quality of these resources has not been evaluated. This study addresses this gap. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument was used to assess the quality of breast and sarcoma guidelines and protocols according to six independent domains. The oncology resources were selected from eight websites developed for healthcare settings in North America, the United Kingdom, Europe, and Australia. RESULTS: Mean quality scores across domains were highly variable for both guidelines (29-73%) and protocols (31-71%). Guidelines scored highly in terms of articulating their Scope and Purpose (72.6 ± 11.2%) but poorly with respect to Applicability in clinical practice (29.0 ± 17.3%). Protocols scored highly on Clarity of Presentation (70.6 ± 17.6%) but poorly in terms of the processes used to synthesise underlying evidence, develop, and update recommendations (30.8 ± 20.0%). CONCLUSION: Our evaluation provides a quick reference tool for clinicians about the strengths and limitations of oncology resources across several major websites. Further, it supports resource developers in terms of where to direct efforts to enhance guideline and protocol development processes or the communication of these processes to end-users.

Identifying incident cancer cases in dispensing claims: A validation study using Australia's Repatriation Pharmaceutical Benefits Scheme (PBS) data.

INTRODUCTION: Dispensing claims are used commonly as proxy measures in pharmacoepidemiological studies; however, their validity is often untested. OBJECTIVES: To assess the performance of a proxy for identifying cancer cases based on the dispensing of anticancer medicines and estimate the misclassification of cancer status and potential for bias researchers may encounter when using this proxy. METHODS: We conducted our validation study using Department of Veterans' Affairs (DVA) client data linked with the New South Wales (NSW) Cancer Registry and Repatriation Pharmaceutical Benefits Scheme data. We included DVA clients aged ≥65 years residing in NSW between July 2004 and December 2012. We matched clients with a cancer diagnosis to clients without a diagnosis based on demographic characteristics and available observation time. We used dispensing claims for anticancer medicines dispensed between July 2004 and December 2013 as a proxy to identify clients with cancer and calculated sensitivity, specificity, positive predictive values and negative predictive values compared with cancer registrations (gold standard), overall and by cancer site. We illustrated misclassification by the proxy in a cohort of people initiating opioid therapy. Using the proxy, we excluded people with cancer from the cohort, in an attempt to delineate people potentially using opioids for cancer rather than chronic non-cancer pain. RESULTS: We identified 15,679 new cancer diagnoses in 14,112 DVA clients from the cancer registry and 62,663 clients without a diagnosis. Sensitivity of the proxy based on dispensing claims was 30% for all cancers and around 20% for specific cancers (range: 10-67%). Specificity was above 90% for all cancers. The dispensing proxy correctly identified 26% of people with a cancer diagnosis who initiated opioid therapy and failed to identify 74% those with a cancer diagnosis; the proxy was most robust for clients with breast cancer where 61% were correctly identified by proxy. CONCLUSIONS: Using dispensing of anticancer medicines to identify people with a cancer diagnosis performed poorly. Excluding patients with evidence of anticancer medicine use from cohort studies may result removal of a disproportionate number of women with breast cancer. Researchers excluding or otherwise using anticancer medicine dispensing to identify people with cancer in pharmacoepidemiological studies should acknowledge the potential biases introduced to their findings. KEYWORDS: cancer, diagnosis, proxy, dispensing records, validation study.

Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. METHODS: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. CONCLUSION: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.

Demographic, social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. METHODS: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. CONCLUSION: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

Patterns of analgesic and anti-inflammatory medicine use by Australian veterans.

BACKGROUND: We examined analgesic and anti-inflammatory medicine use by Australian veterans before and after the introduction of selective Cox-2 inhibitors. METHODS: We studied cohorts of Gold Card-holding veterans using prescription data held by the Department of Veterans' Affairs for the period 1 July 1998 to 30 June 2004. Outcomes were volume dispensed, average daily quantity and cumulative incidence of use of paracetamol-containing and aspirin-containing medicines, non-selective and Cox-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and dextropropoxyphene. RESULTS: Overall, we found high levels of use of analgesic and anti-inflammatory medicines, which increased by 43% over the study period. Use of paracetamol-containing medicines was overtaken by NSAIDs in 1999/2000, corresponding to the introduction of the Cox-2-selective agents. Between 12 and 17% of Cox-2-selective medicine recipients were supplied amounts indicative of continuous use in relatively high doses and 51% of veterans received at least one relatively Cox-2-selective medicine (celecoxib, rofecoxib, meloxicam, diclofenac) by the end of the study period. Dextropropoxyphene use declined during the study and tramadol use increased 10-fold. CONCLUSION: This study shows very high levels of Cox-2 inhibitor use during the 6-year period. Cox-2-selective agents were more likely to be taken continuously and at higher doses than non-selective NSAIDs. This is relevant in view of the cardiovascular toxicity of this group of medicines. The study shows the value of using unit record dispensing data to assess drug use patterns. Linking dispensing records to hospital separation and mortality data will further enhance our ability to monitor drug safety.

Information sources used by New South Wales cancer clinicians: a qualitative study.

BACKGROUND: This study identified (i) information sources used by cancer clinicians to guide pharmacological treatments, (ii) utilization of, and opinions about, online information sources and (iii) clinicians' ability to access a specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin's Lymphoma). The work was carried out before activation of the Cancer Institute New South Wales Standard Cancer Treatment (CI-SCaT) programme. METHODS: We conducted semistructured interviews with a purposeful sample of senior and junior doctors, nurses and pharmacists treating adult cancer patients (n = 32) in eight New South Wales public hospitals. RESULTS: Information seeking processes are context specific and vary from clinician to clinician and ward to ward. Clinicians use human, electronic and printed information sources at, or close to, the point of patient care; however, experienced colleagues are preferred where information is needed quickly or in unfamiliar clinical situations. Barriers to using online cancer information are environmental (hardware, connection speeds, time), personal (poor computer literacy and lack of awareness of appropriate sites) and economic (costs of journal subscriptions). Just over half of participants were able to locate a specific cancer protocol and none of these protocols was fully consistent with CI-SCaT recommendations. CONCLUSION: There is no standardized approach to the pharmacological treatment of cancer patients in this sample of New South Wales clinicians. CI-SCaT will fill a gap with respect to standardizing oncology treatment. However, to ensure maximal CI-SCaT uptake, implementation plans should harness positive behavioural influences and attempt to modify the negative forces that act on hospital clinicians in their day-to-day work.

A comparison of eating behaviors in newly diagnosed NIDDM patients and case-matched control subjects.

OBJECTIVE: To determine whether disordered eating may be problematic in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We contrasted the eating behaviors and attitudes in 50 newly diagnosed NIDDM patients with 50 age-, sex-, and weight-matched control subjects. RESULTS: Although 14% of diabetic subjects versus 4% of nondiabetic subjects reported episodes of binge eating (P < 0.10), there was no difference between diabetic and nondiabetic subjects in the prevalence with which they met criteria for binge eating disorder. Diabetic patients with a history of binge eating were significantly heavier, had younger age at diagnosis, and had more problems with eating in response to situational and emotional cues than did diabetic patients who did not binge. CONCLUSIONS: No support was found for greater prevalence of binge eating disorder in newly diagnosed NIDDM patients than in matched nondiabetic control subjects.

Inhibition of chlorophyll synthesis in Hordeum vulgare by 3-amino 2,3-dihydrobenzoic acid (gabaculin).

Gabaculin (3-amino 2,3-dihydrobenzoic acid) is shown to be a very potent inhibitor of chlorophyll formation in Hordeum vulgare. Exposure of leaf segments to 30 microM gabaculin results in an 80% inhibition of chlorophyll synthesis, and this is paralleled by a decrease in carotenoid. Dual-inhibitor studies with dioxoheptanoic acid, which is an inhibitor of delta-amino-laevulinic acid dehydratase, show that gabaculin inhibits an earlier step than dioxoheptanoic acid and affects delta-amino-laevulinic acid synthesis rather than its subsequent metabolism.

A scale to measure attitudes toward community medicine.

A questionnaire to measure attitudes toward community medicine held by general practitioners was designed, and a 35-item scale with a Likert response formal was constructed. The Attitudes Toward Community Medicine scale consists of six subscales relating to key areas of community medicine. The final scale is valid and reliable for group comparisons, with alpha coefficients ranging from alpha = 0.54 to alpha = 0.84. The instrument may be used to evaluate the effectiveness of community medicine teaching, to describe differences in beliefs of practitioners and to estimate changes in attitudes over time.

Single and combination effects of administering salinomycin and aflatoxin to broiler chicks.

A factorial design (2 by 3) was used to evaluate the interaction between aflatoxin (0, 2.5, and 5 mg per kg) and salinomycin [0, 60 g per ton (909 kg)]. There were four replicates of 10 chicks per treatment. The chicks were maintained in batteries from 0 to 3 wk of age, with feed and water available for ad libitum intake. Aflatoxin at both levels (2.5 and 5 mg per kg) with and without salinomycin decreased body weight. The efficiency of feed utilization was affected only at the 5 mg per kg level of aflatoxin. Feeding 5 mg per kg of aflatoxin alone decreased the hemoglobin level. The inclusion of salinomycin (60 g per ton) in the diet with 2.5 or 5 mg per kg of aflatoxin initiated no significant change in body weight or feed efficiency. No significant interaction was observed between aflatoxin and salinomycin on any of the parameters measured.

Communication skills of interns in New South Wales.

OBJECTIVE: To assess communication skills of interns practising in New South Wales hospitals. METHODS: Comparisons were made between five groups of interns: those who graduated from the three New South Wales universities (Newcastle, Sydney and NSW); foreign medical graduates; and those from New Zealand and interstate. Subjects were assessed up to five times during the intern year; a supervisor rating scale was used. RESULTS: Newcastle graduates were rated more favourably, and foreign graduates less favourably, than graduates from other medical schools. In addition, women were rated better than men, and younger interns better than older interns. CONCLUSIONS: The data suggest deficits in communication skills of foreign medical graduates, and support the medical education approach at Newcastle medical school, which emphasises communication skills.

Screening recommendations in general practice: a survey of graduates from different medical schools.

OBJECTIVE: To examine the influence of sociodemographic background, medical school background, general practice characteristics and attitudes towards preventive medicine on the screening recommendations of New South Wales (NSW) general practitioners (GPs). METHODS: From the NSW Medical Board Register, a sample was obtained of all GPs who graduated between 1983 and 1987 from the University of Newcastle and a random 1-in-3 sample of GPs from the Universities of Sydney and NSW. Two questionnaires were mailed consecutively. PARTICIPANTS: 363 GPs (56% response rate) who completed questionnaires suitable for analysis. MAIN OUTCOME MEASURE: A composite screening score for assessing agreement with standard screening guidelines. The score was derived by allocating points to the screening intervals that GPs recommended for 13 screening tests. A score of 39 indicated maximum agreement with guidelines. RESULTS: 87% of GPs reported being aware of standard screening guidelines. For most screening tests, there was a discrepancy between GPs' recommendations and those of the guidelines. Composite screening scores ranged from 8-38. There were significantly higher screening scores for graduates of Newcastle versus Sydney and NSW university medical schools combined (adjusted mean, 28.0 versus 25.9; P=0.0436), group versus solo GPs (adjusted mean, 26.3 versus 25.6; P=0.0092) and GPs in rural versus urban locations (adjusted mean, 27.9 versus 25.6; P=0.0049). CONCLUSIONS: GPs' recommendations for screening are not always consistent with standard guidelines, despite an awareness of them. Research is needed into the variation with which different screening tests are ordered.