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.

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.

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.

Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning?

BACKGROUND: The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours. AIM OF STUDY: To investigate the efficacy of intravenous or oral N-acetylcysteine. PATIENTS AND METHODS: We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We incorporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. RESULTS: Of 981 patients admitted over 10 years, 4% (40) presented later than 24 hours and 10% (100) had concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%). CONCLUSIONS: The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.

Effects of information framing on the intentions of family physicians to prescribe long-term hormone replacement therapy.

OBJECTIVE: To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy (HRT) is presented influences family physicians' intentions to prescribe this treatment. DESIGN: Family physicians were randomized to receive information on treatment outcomes expressed in relative terms, or as the number needing to be treated (NNT) with HRT to prevent or cause an event. A control group received no information. SETTING: Primary care. PARTICIPANTS: Family physicians practicing in the Hunter Valley, New South Wales, Australia. INTERVENTION: Estimates of the impact of long-term HRT on risk of coronary events, hip fractures, and breast cancer were summarized as relative (proportional) decreases or increases in risk, or as NNT. MEASUREMENTS AND MAIN RESULTS: Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales. Of 389 family physicians working in the Hunter Valley, 243 completed the baseline survey and 215 participated in the randomized trial. Baseline intention to prescribe varied across patients-it was highest in the presence of risk factors for hip fracture, but coexisting risk factors for breast cancer had a strong negative influence. Overall, a larger proportion of subjects receiving information expressed as NNT had reduced intentions, and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms, or the control group. However, the differences were small and only reached statistical significance for three hypothetical patients. Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer. CONCLUSIONS: Information framing had some effect on family physicians' intentions to prescribe HRT, but the effects were smaller than those previously reported, and they were modified by the presence of serious potential adverse treatment effects.

Development of hematopoietic cancers after implantation of total joint replacement.

The evidence from the 4 epidemiologic studies published before mid 1995, which have investigated the incidence of cancers in patients who have undergone joint implants, is conflicting. The results of the 2 earlier studies suggested a sustained increase in the risk of lymphoma and leukemia after total hip arthroplasty. The results of the 2 more recent studies have not confirmed this, although in 1 study an increased risk was observed in the first year after implantation. The heterogeneity may be statistical in origin, but could also have a biologic explanation in the greater proportion of metal on metal prostheses used before 1973. All 4 studies used national data as the comparison. Here, are presented the results of 2 matched cohort studies and a case control study set in North America and Scotland, and an overview of the 4 previous studies. Neither the results of the matched studies of patients operated on after 1973 nor the results of the latter 2 published studies suggest an increased risk of lymphoma or leukemia. If metal on metal articulations are reintroduced, careful surveillance is essential.

Evaluation of new technologies for total hip replacement. Economic modelling and clinical trials.

Cost is a factor in the choice of prosthetic components in joint replacement. For a given performance, the least expensive components are the most cost-effective. When evaluating a new prosthesis with an unknown outcome, the use of an economic model allows estimation of potential cost-effectiveness. We used published data for the survival of cemented total hip replacements from Sweden, and cost and demographic information from New South Wales, Australia, in such a model. In young active total hip recipients a new prosthetic design which offered a 90% improvement in survivorship over 15 years and a 15% reduction in the cost of revision surgery, could be sold at a price of 2 to 2.5 times that of conventional cemented components such as the Charnley Low Friction Arthroplasty and still be cost-effective. Using more likely estimates of the improved performance of new technology, however, the upper limit of cost-effectiveness is an increase of 1.5 to 1. Only a very small increase in the cost of a prosthesis could ever be justified for older patients of either sex. Most of the potential benefits of a better level of survivorship appear towards the end of the 15-year period. The results of modelling may be incorporated in clinical trial design. Given the known performance of some well-established and relatively inexpensive designs of prostheses, very large randomised studies would be required to prove an improvement in performance.

A randomised controlled trial of a dietary advice program for relatives of heart attack victims.

OBJECTIVE: To compare two interventions for reducing dietary fat intake in first degree relatives of recent heart attack victims. DESIGN: A randomised controlled trial comparing a low cost mail-out advice program; referral to a general practitioner (GP); and no intervention (control group). PARTICIPANTS: Adult children or siblings, aged less than 70 years, of survivors of definite or suspected heart attack who had been admitted to hospitals in the Lower Hunter Region of New South Wales. MAIN OUTCOME MEASURES: Dietary fat intake (evaluated with a validated short questionnaire) and measurement of blood cholesterol levels at six months. RESULTS: Of the 342 relatives who participated (36% of those invited), 109, 120 and 113, respectively, were randomly assigned to receive a mail-out intervention, advice from their GP or to be part of a control group. The six-month follow-up questionnaire was completed by only 59% of those in the mail-out intervention group compared with 71% of the GP group and 77% of the control group. Younger participants, cigarette smokers and children (compared with siblings) were less likely to return a follow-up questionnaire. The mail-out group showed a statistically significant 20% reduction in self-reported dietary fat intake, but this was not seen in either the GP group or the controls. The low response rate meant the study had insufficient power to detect hypothesised changes in blood cholesterol. CONCLUSION: Because of the poor response rate and possible biases from a differential response to follow-up, we conclude that this low intensity intervention for relatives of people with recent heart attack produces only a modest improvement in reported dietary fat intake. Alternative strategies may be more effective in reducing the risk of heart disease.