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).

Actual Versus Optimal Radiotherapy Utilisation for Metastatic Cancer Patients in the 45 and Up Study Cohort, New South Wales.

AIMS: Radiotherapy can provide quality of life and/or survival benefits to patients with metastatic cancer on diagnosis (MCOD). However, little is known about radiotherapy utilisation in this population. We compared the optimal radiotherapy rates with actual uptake for people who present with MCOD in the 45 and Up Study cohort, and examined factors associated with utilisation. MATERIALS AND METHODS: In total, 267 153 individuals aged ≥45 enrolled in the Sax Institute's 45 and Up Study completed a baseline questionnaire during 2006-2009, providing sociodemographic and health information and consent for linkage to administrative health databases. Participants diagnosed up to December 2013 with MCOD were identified in the New South Wales Cancer Registry. Radiotherapy receipt was determined from claims to the Medicare Benefits Schedule and/or records in the New South Wales Admitted Patient Data Collection (2006 to June 2016). The Collaboration for Cancer Outcomes, Research and Evaluation optimal utilisation model was adapted for patients with MCOD to provide a benchmark. RESULTS: Of 17 687 participants diagnosed with cancer after completion of the baseline questionnaire, 2392 had MCOD. Of patients with MCOD, 25% had primary lung cancer, which was the most common site. The actual radiotherapy utilisation rate for all patients was 32.3%, lower than the optimal of 45.0%. From multivariable analysis, patients who were aged ≥80 years and/or needed help with daily tasks and/or had a Charlson Comorbidity Index ≥2 were less likely to receive radiotherapy. CONCLUSIONS: Actual uptake of radiotherapy was below optimal. Elderly patients and/or those with more comorbidities were less likely to receive radiotherapy. These results suggest a potential role for advocacy and education around radiotherapy for these patient groups.

Factors Associated With Radiotherapy Utilisation In New South Wales, Australia: Results From The 45 and Up Study.

AIMS: Actual radiotherapy utilisation rates tend to be lower than the estimated optimal rates. Little is known about the factors contributing to this difference. Our aim was to identify factors associated with radiotherapy receipt for a cohort of cancer patients in New South Wales (NSW), Australia. MATERIALS AND METHODS: In total, 267 153 participants in the NSW 45 and Up Study completed a questionnaire during 2006-2009 providing detailed health and socio-demographic information and consented to record linkage with administrative health datasets. Single primary cancers diagnosed after study enrolment were identified through linkage with the NSW Cancer Registry to December 2013. Radiotherapy receipt was determined from claims to the Medicare Benefits Schedule and/or records in the NSW Admitted Patient Data Collection (2006 to June 2016). Competing risks regression was used to examine associations between health and socio-demographic characteristics and radiotherapy treatment. RESULTS: Of 17 873 patients with an incident cancer, 5414 (30.3%) received radiotherapy during follow-up (median 5.3 years). Patients less likely to receive radiotherapy were aged <60 or 80+ years, female, had a Charlson co-morbidity index of 1+, needed help with daily tasks or lived ≥100 km from the nearest radiotherapy centre. CONCLUSION: Distinct subgroups of patients are less likely to receive radiotherapy. Advocacy and/or policy changes are needed to improve access.

Barriers to lung cancer care: health professionals' perspectives.

PURPOSE: Globally, lung cancer is the most common cancer and the leading cause of cancer death. Problematically, there is a wide variation in the management and survival for people with lung cancer and there is limited understanding of the reasons for these variations. To date, the views of health professionals across relevant disciplines who deliver such care are largely absent. The present study describes Australian health professionals' views about barriers to lung cancer care to help build a research and action agenda for improving lung cancer outcomes. METHODS: Qualitative semi-structured interviews were undertaken with a multidisciplinary group of 31 Australian health professionals working in lung cancer care for an average of 16 years (range 1-35 yrs.; SD = 10.2) seeing a mean of 116 patients annually. RESULTS: Three superordinate themes were identified: illness representations, cultural influences, and health system context. Illness representations included three themes: symptoms attributed as smoking-related but not cancer, health-related stigma, and therapeutic nihilism. Cultural influence themes included Indigenous health care preferences, language and communication, and sociodemographic factors. Health system context included lack of regional services and distance to treatment, poor care coordination, lack of effective screening methods, and health professional behaviours. CONCLUSIONS: Fractured and locally isolated approaches routinely confound responses to the social, cultural and health system complexities that surround a diagnosis of lung cancer and subsequent treatment. Improving outcomes for this disadvantaged patient group will require government, health agencies, and the community to take an aggressive, integrated approach balancing health policy, treatment priorities, and societal values.

Determinants of survival and attempted resection in patients with non-metastatic pancreatic cancer: An Australian population-based study.

BACKGROUND: There are indications that pancreatic cancer survival may differ according to sociodemographic factors, such as residential location. This may be due to differential access to curative resection. Understanding factors associated with the decision to offer a resection might enable strategies to increase the proportion of patients undergoing potentially curative surgery. METHODS: Data were extracted from medical records and cancer registries for patients diagnosed with pancreatic cancer between July 2009 and June 2011, living in one of two Australian states. Among patients clinically staged with non-metastatic disease we examined factors associated with survival using Cox proportional hazards models. To investigate survival differences we examined determinants of: 1) attempted surgical resection overall; 2) whether patients with locally advanced disease were classified as having resectable disease; and 3) attempted resection among those considered resectable. RESULTS: Data were collected for 786 eligible patients. Disease was considered locally advanced for 561 (71%) patients, 510 (65%) were classified as having potentially resectable disease and 365 (72%) of these had an attempted resection. Along with age, comorbidities and tumour stage, increasing remoteness of residence was associated with poorer survival. Remoteness of residence and review by a hepatobiliary surgeon were factors influencing the decision to offer surgery. CONCLUSIONS: This study indicated disparity in survival dependent on patients' residential location and access to a specialist hepatobiliary surgeon. Accurate clinical staging is a critical element in assessing surgical resectability and it is therefore crucial that all patients have access to specialised clinical services.

The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.

INTRODUCTION: The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design. MATERIAL AND METHODS: Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases. RESULTS: 10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer. DISCUSSION: This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.

Estimating the proportion cured of cancer: some practical advice for users.

BACKGROUND: Cure models can provide improved possibilities for inference if used appropriately, but there is potential for misleading results if care is not taken. In this study, we compared five commonly used approaches for modelling cure in a relative survival framework and provide some practical advice on the use of these approaches. PATIENTS AND METHODS: Data for colon, female breast, and ovarian cancers were used to illustrate these approaches. The proportion cured was estimated for each of these three cancers within each of three age groups. We then graphically assessed the assumption of cure and the model fit, by comparing the predicted relative survival from the cure models to empirical life table estimates. RESULTS: Where both cure and distributional assumptions are appropriate (e.g., for colon or ovarian cancer patients aged <75 years), all five approaches led to similar estimates of the proportion cured. The estimates varied slightly when cure was a reasonable assumption but the distributional assumption was not (e.g., for colon cancer patients ≥75 years). Greater variability in the estimates was observed when the cure assumption was not supported by the data (breast cancer). CONCLUSIONS: If the data suggest cure is not a reasonable assumption then we advise against fitting cure models. In the scenarios where cure was reasonable, we found that flexible parametric cure models performed at least as well, or better, than the other modelling approaches. We recommend that, regardless of the model used, the underlying assumptions for cure and model fit should always be graphically assessed.

Second primary colorectal cancers (SPCRCs): experiences from a large Australian Cancer Registry.

BACKGROUND: We examined the rate of second primary colorectal cancer (SPCRC) in a cohort of 29 471 patients first diagnosed with colorectal cancer (CRC) from 1987 to 1996, in New South Wales (NSW), Australia. METHODS: The 5-year age group, date and site of first and subsequent CRC diagnoses as well as death dates were obtained from the NSW Central Cancer Registry. The time to SPCRC and standardised incidence ratios (SIRs) were generated. RESULTS: Six hundred and sixty patients (2.1%) developed SPCRCs and the cumulative incidence at 18 years was 5.5%, 95% confidence interval (CI) 4.9% to 6.3%. The risk of SPCRC was increased in patients with a CRC history compared with the general population (SIR = 1.5, 95% CI 1.4-1.6) and inversely related to age at first diagnosis (30-49 years, SIR = 5.1, 95% CI 3.6-7.1 versus >/=80 years, SIR = 1.1, 95% CI 0.9-1.4). The excess absolute risk of SPCRC was greater for females aged 50-69 years at first diagnosis than for males in the same age group. SPCRC was also increased in individuals with right-sided first primaries (SIR = 2.0, 95% CI 1.6-2.4). CONCLUSIONS: The SPCRC rate was increased during the first 5 years after first diagnosis but remained increased for up to 10 years in females, in patients with right-sided cancers and in patients <60 years at first diagnosis. These findings support active surveillance up to 10 years in these risk groups.

No improvement in lung cancer care: the management of lung cancer in 1996 and 2002 in New South Wales.

BACKGROUND: Patterns-of-care studies emphasize significant variation in the management of lung cancer. The aim of the study was to compare the patterns of care for patients diagnosed with lung cancer in 1996 and 2002 within three health areas in New South Wales. METHODS: Treatment data were collected from medical records and treating doctors for the calendar year 1996 and between 1 November 2001 and 31 December 2002. Patients were residents of either south-western Sydney, Hunter or Northern Sydney health areas at the time of diagnosis. chi(2)-tests were used to investigate changes in treatment patterns between the two time periods. An adjusted odds ratio for treatment in 2002 relative to 1996 was calculated using logistic regression. RESULTS: Data were available for 738 and 567 cases in 1996 and 2002, respectively. Cancer-specific therapy was given within 6 months of diagnosis to 62 and 64% of patients, respectively. Adjusting for health area, age, sex, pathology and performance status, the odds ratio (OR) of treatment in 2002 relative to 1996 was 1.03 (95% confidence interval (CI) 0.78-1.35). When stage was included, the odds of treatment in 2002 relative to 1996 for non-small-cell lung cancer (n = 950) was 1.21 (95%CI 0.87-1.68). After adjustment for potential confounders, patients diagnosed with small-cell lung cancer (n = 176) were substantially less likely to receive treatment in 2002 compared with patients diagnosed in 1996 (OR = 0.11; 95%CI 0.04-0.34). CONCLUSION: The odds of receiving treatment in 2002 and 1996 were similar. However, patients diagnosed with small-cell lung cancer in 2002 were significantly less likely to receive treatment. Overall, this study suggests there has been no change in lung cancer care in New South Wales. Further work is required to determine what proportion of persons with lung cancer should receive cancer-specific treatment so that clinical practices can be judged appropriately.

Cell salvage for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood, have prompted reconsideration of the use of allogeneic (blood from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents and the websites of international health technology assessment agencies. The reference lists in identified trials and review articles were also searched, and study authors were contacted to identify additional studies. The searches were updated in January 2004. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed methodological quality. The main outcomes measures were the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction, renal failure), mortality, and length of hospital stay (LOS). MAIN RESULTS: Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (relative risk [RR] = 0.61: 95% confidence interval [CI] 0.52 to 0.71). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 23% (95% CI 16% to 30%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.42 (95% CI 0.32 to 0.54) compared to 0.77 (95% CI 0.68 to 0.87) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.67 units of allogeneic RBC per patient (weighted mean difference was -0.64; 95% CI -0.89 to -0.45). Cell salvage did not appear to impact adversely on clinical outcomes. AUTHORS' CONCLUSIONS: The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective surgery. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients' treatment status biasing the results in favour of cell salvage.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Vitamin D and related compounds have been used to prevent fractures. OBJECTIVES: To determine the effects of vitamin D or analogues, with or without calcium, in the prevention of fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: March 2005. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, reporting fracture outcomes, in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if the relative risks were heterogeneous. MAIN RESULTS: Vitamin D alone showed no statistically significant effect on hip fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41), vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13, 95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR 0.99, 95% CI 0.91 to 1.09). Vitamin D with calcium marginally reduced hip fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96), non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78 to 0.97), but there was no evidence of effect of vitamin D with calcium on vertebral fractures. The effect appeared to be restricted to those living in institutional care. Hypercalcaemia was more common when vitamin D or its analogues was given compared with placebo or calcium (14 trials, 8035 participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61). There was no evidence that vitamin D increased gastro-intestinal symptoms (seven trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip and other non-vertebral fractures if given vitamin D with calcium supplements. Effectiveness of vitamin D alone in fracture prevention is unclear. There is no evidence of advantage of analogues of vitamin D compared with vitamin D. Calcitriol may be associated with an increased incidence of adverse effects. Dose, frequency, and route of administration of vitamin D in older people require further investigation.

Blood transfusion and autologous donation: a survey of post-surgical patients, interest group members and the public.

Before planned surgery, patients may choose autologous donation in order to avoid the small, but potential, risks of receiving an allogeneic blood transfusion. This study examined the perceived risks of allogeneic blood transfusions, preferences and willingness to pay for autologous donation and the desired role in the decision-making process in three populations: post-surgical patients, special interest group members and the general public. Quantitative and qualitative data were collected from 206 respondents with the help of computer-assisted semi-structured telephone interviews. Thirty-three per cent of the sample voiced concerns about receiving allogeneic blood transfusions. The risks of hepatitis C virus, human immunodeficiency virus, variant Creutzfeldt-Jakob disease and a haemolytic reaction were perceived as being low, but were rated as numerically higher than those of other life events that have equal probability. Autologous donation was perceived as removing all the risks associated with transfusion, and respondents were willing to pay a median $976 AUD ($664 US) to use this technique. Over 80% of respondents preferred to be involved in making the decision about whether to use autologous donation. Even though autologous donation is not 'risk-free' and the blood supply is very safe, people overestimate the associated risks and have a preference for their own blood. Decision aids presenting balanced information on the advantages and disadvantages of both allogeneic and autologous blood may be required.

Comparison of cancer survival in UK and Australia: rates are higher in Australia for three major sites.

Relative survival of patients diagnosed with cancers of the colorectum, lung and female breast from Yorkshire, UK and New South Wales (NSW), Australia in 1992-2000 were compared using multiple regression models to adjust for various factors. Statistically significant differences were observed for all sites, Yorkshire patients having a 47-58% higher risk of excess death than those of NSW.

Cell salvage for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood, have prompted reconsideration of the use of allogeneic (blood from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: Articles were identified by: computer searches of MEDLINE, EMBASE, Current Contents (to July 2002), the Cochrane Controlled Trials Register (Issue 2, 2002) and websites of international health technology assessment agencies. References in the identified trials and review articles were searched and authors contacted to identify additional studies. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al. (Jadad 1996). Main outcomes measured were: the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were: re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction, renal failure), mortality, and length of hospital stay (LOS). MAIN RESULTS: Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 40% (relative risk [RR] = 0.60: 95% confidence interval [CI] = 0.51 to 0.70). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 23% (95%CI = 16% to 30%). In orthopaedic procedures the relative risk (RR) of exposure to RBC transfusion was 0.42 (95%CI = 0.32 to 0.54) compared to 0.78 (95%CI = 0.68 to 0.88) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.64 units of allogeneic RBC per patient (weighted mean difference [WMD] = -0.64: 95%CI = -0.86 to -0.46). Cell salvage did not appear to impact adversely on clinical outcomes. REVIEWER'S CONCLUSIONS: The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective surgery. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patient's treatment status biasing the results in favour of cell salvage.

The impact of specialists on prescribing by general practitioners.

OBJECTIVE: To investigate the direct impact of specialists on prescribing by general practitioners. DESIGN: Cross-sectional, prescription-based study. SUBJECTS AND SETTING: 88 GPs in the Hunter Urban Division of General Practice, Hunter Valley, NSW. MAIN OUTCOME MEASURE: Proportions of specialist-initiated prescriptions for eight commonly prescribed drug classes. RESULTS: The proportion of specialist-initiated prescriptions was greatest for proton pump inhibitors (85%), and lowest for diuretics (8%), newer antidepressants (10%) and H2-receptor antagonists (13%). Specialists initiated 29% of prescriptions for beta-blockers, 26% for calcium-channel blockers, 20% for statins and 19% for angiotensin-converting enzyme inhibitors or angiotensin II antagonists. Specialists were more likely to have been involved in starting therapy with metoprolol than other beta-blockers (51% v 23%) and diltiazem than other calcium-channel blockers (48% v 19%), and this was related to indication for treatment. In contrast, prescriptions for the more recently introduced drugs (angiotensin II antagonists and atorvastatin) were not more likely to have been specialist-initiated than prescriptions for established angiotensin-converting enzyme inhibitors and statins. CONCLUSIONS: The direct impact of specialists on prescribing in the Hunter Urban Division of General Practice is substantial and varies with the drug class. This highlights the need to engage both GPs and specialists in efforts to improve prescribing practices.

Personal formularies. An index of prescribing quality?

OBJECTIVES: (1) To determine the extent to which Australian general practitioners (GPs) restrict the numbers of agents they prescribe within a drug class ('personal formularies'); (2) To assess concordance of these drug choices with standards based on established guidelines or recognised good prescribing practices; (3) To assess the potential of these measures as indicators of the quality of prescribing. METHODS: Australian Health Insurance Commission (HIC) prescription data (1994 1997) for around 15,400 GPs providing 1500 or more Medicare services per year were analysed. Measures of an individual GP's use of a personal formulary (determined by number of agents) and concordance with prescribing criteria based on specified drugs for five classes of commonly prescribed drugs were derived. RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs): GP concordance was higher with a non-specified personal formulary (any five NSAIDs) than with a list of specified drugs (five NSAIDs of 'low' or 'medium' risk of gastrointestinal toxicity), and concordance with both increased over time. In 1997, around 70% of GPs used five or fewer NSAIDs for 90% of their prescribing; 47% of GPs had 90% of prescribing from five selected agents. Angiotensin converting enzyme inhibitors/angiotensin-II receptor antagonists: The introduction of new agents appeared to increase the size of the GPs' personal formularies, and concordance with defined standards decreased over time. Antibacterial agents: Concordance with a specified drug standard (nine drugs listed in the Australian Antibiotic Guidelines) increased substantially over time but was largely due to increased prescribing of two heavily promoted drugs. Beta-blocking agents: Over time, GPs restricted most prescribing to two agents, atenolol and metoprolol. Calcium channel blockers: GPs did not appear to restrict prescribing of these drugs; most GPs prescribed all five agents available. CONCLUSIONS: Australian GPs use 'personal formularies'. Formulary size varies with the drug class, can change over time as new agents become available, and its contents can be influenced by promotional activities. Prescribing standards based on numbers of drugs used may not always reflect rational prescribing choices. Criteria based on specified drugs provide more rigorous prescribing standards, but may give a misleading picture of prescribing quality in the absence of information on patients and the indications for treatment. Personal formulary measures are potentially useful prescribing indicators but need to be carefully defined and interpreted. GPs should be encouraged to identify their personal formularies and review the drugs included in them.

Risk factors for mastitis in breastfeeding women: results of a prospective cohort study.

OBJECTIVES: To identify potential risk factors for the development of mastitis in breastfeeding women. METHODS: A prospective cohort study with questionnaire and telephone follow-up was conducted. Women were recruited after delivery at either the teaching hospital or the only private hospital with an obstetric service during May to December 1994 in Newcastle, New South Wales and were followed up at home for six months. 1,075 breastfeeding women were recruited and were sent follow-up questionnaires at three, eight and 26 weeks post-delivery. RESULTS: Mastitis occurred in 20% (95% CI 18-22%) of women during the first six months. Factors that were statistically significantly and independently related to mastitis were: past history of mastitis (adjusted Hazard Ratio=1.74, 1.07-2.81), university or college education (HR=1.93, 1.18-3.16), blocked duct (HR=2.43, 1.68-3.49), cracked nipples (HR=1.44, 1.00-2.07), use of creams on nipples (HR=1.83, 1.22-2.73), particularly papaya cream (Relative Risk = 1.83, 1.36-2.47), and always starting with the alternate breast on consecutive feeds (HR=2.28, 1.50-3.44). CONCLUSIONS: Women with a past history of mastitis had an increased risk of developing mastitis. Blocked ducts and cracked nipples serve as warning signs for mastitis. Use of some creams may increase the risk of mastitis and their value should be tested in clinical trials. IMPLICATIONS: We have identified several pre-natal and post-natal markers for increased risk of mastitis that may assist in its early identification and treatment. The use of creams on nipples may introduce pathogens that cause mastitis and should be avoided.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, LILACS, CABNAR, BIOSIS, HEALTHSTAR, Current Contents, The Cochrane Database of Systematic Reviews, the Cochrane Musculoskeletal Injuries Group trials register, and bibliographies of identified trials and reviews. Date of the most recent search: September 2000. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared vitamin D or a vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with eligible fracture outcomes, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a nine item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. Pooling of data, where it was admissible, used pooled relative risk and fixed effects model. MAIN RESULTS: Almost all estimates of treatment effects are based on single studies. Administration of vitamin D3 alone without calcium co-supplementation was not associated with any reduction in incidence of hip fracture (relative risk (RR) 1.20, 95% confidence interval (CI) 0.83, 1.75) or other non-vertebral fracture. Administration of vitamin D3 with calcium co-supplementation to frail elderly people in sheltered accommodation was associated with a reduction in incidence of hip fracture (RR 0.74, 95% CI 0.60, 0.91). In healthy younger, ambulant participants the effect on hip fracture is unknown (RR 0.36, 95% CI 0.01, 8.78), although there appears to be a significant overall effect on non-vertebral fracture incidence in this group ( RR 0.46, 95% CI 0.23,0.90). Calcitriol (1,25 dihdyroxy vitamin D) was effective in reducing the incidence of vertebral deformity (RR 0.49, 95% CI 0.25, 0.95). Calcitriol was more effective than calcium in reducing the frequency of new vertebral deformities during the third year of treatment (RR 0.28, 95% CI 0.15, 0.52). 1-alpha-hydroxy vitamin D was effective in reducing the incidence of non-vertebral fractures in a single small study of elderly people whose mobility was impaired by neurological disease (RR 0.12, 95% CI 0.02, 0.95). No statistically significant effects were found for other comparisons of vitamin D or its analogues against each other, with and without calcium supplementation. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further large randomised trials are currently being conducted to clarify the effectiveness of community fracture prevention programmes employing vitamin D supplementation.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Due to their known effects on bone metabolism, Vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. OBJECTIVES: To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE, EMBASE, BIOSIS, CINAHL, HealthPLAN, Dissertation Abstracts, Index to UK Theses, Current Contents, and bibliographies of identified trials and reviews. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: December 1995. SELECTION CRITERIA: Any randomised or quasi-randomised trial which compared Vitamin D or a Vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with fracture as an outcome, in elderly men or women with involutional or post-menopausal osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a seven item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. MAIN RESULTS: Fourteen trials recording 13 different comparisons were included. In the only trial of Vitamin D alone, protection against hip fracture was not confirmed. Two regimens, each represented by one large trial, which showed limited evidence of efficacy in reducing the incidence of hip or other appendicular skeleton fractures were: 1) Oral Vitamin D when accompanied by calcium supplementation. 2) 1,25 dihydroxy Vitamin D (calcitriol). This appeared more effective than calcium in a direct comparison. Regimens showing limited evidence of efficacy in reducing the incidence of vertebral deformity were: 1) 1,25 dihydroxy Vitamin D (calcitriol), which appeared more effective than calcium in one large trial, and more effective than placebo from pooled results of two small trials. 2) Oral 1-alpha hydroxy Vitamin D (alfacalcidol), when administered with calcium supplements (two small trials, which lacked power to confirm a possible effect). Hypercalcaemia and gastro-intestinal symptoms, reported in less than 5% of participants, were slightly more common when Vitamin D analogues were taken. However, the risk of death was marginally less. REVIEWER'S CONCLUSIONS: Uncertainty remains about the efficacy of regimens which include Vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further randomised trials with economic evaluation are desirable before community fracture prevention programmes employing Vitamin D supplementation can be confidently introduced.

Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose.

BACKGROUND: The evidence for efficacy of gastric lavage and activated charcoal for gastrointestinal decontamination in poisoning has relied entirely on volunteer studies and/or pharmacokinetic studies and evidence for any clinical benefits or resource savings is lacking. AIM OF STUDY: To investigate the value of gastrointestinal decontamination using gastric lavage and/or activated charcoal in acetaminophen (paracetamol) poisoning. PATIENTS AND METHODS: We analyzed a series of 981 consecutive acetaminophen poisonings. These patients were treated with gastric lavage and activated charcoal, activated charcoal alone, or no gastrointestinal decontamination. The decision as to which treatment was received was determined by patient cooperation, the treating physician, coingested drugs, and time to presentation after the overdose. RESULTS: Of 981 patients admitted over 10 years, 10% (100) had serum concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The risk of toxic concentrations for patients ingesting less than 10 g of acetaminophen was very low. In patients presenting within 24 hours, who had ingested 10 g or more, those who had been given activated charcoal were significantly less likely to have probable or high risk concentrations (Odds ratio 0.36, 95% CI 0.23-0.58, p < 0.0001). Gastric lavage, in addition to activated charcoal, did not further decrease the risk (Odds ratio 1.12, 95% CI 0.57-2.20, p = 0.86). CONCLUSIONS: Toxic concentrations of serum acetaminophen (paracetamol) are uncommon in patients ingesting less than 10 g. In those ingesting more, activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay.