National Health Service Information Centre Research Articles

Heavy Lifetime Cannabis Use and Mortality by Sex

The association between mortality and cannabis use remains unclear. To examine sex-stratified associations of cumulative lifetime cannabis use with all-cause, cardiovascular disease (CVD), and cancer mortality in the UK Biobank population. This cohort study used data from volunteers in the UK Biobank population. Participant monitoring for mortality in the UK Biobank study commenced from the point of their inclusion between 2006 and 2010 and continued until December 19, 2020. Data regarding the causes of death were sourced from the National Health Service Information Centre. Data were analyzed from inception of study inclusion to December 2020. Cannabis use status was assessed by questionnaire and categorized as heavy, moderate, low, and never. The main outcomes were all-cause, CVD, and cancer mortality. Sex-stratified associations of cumulative lifetime cannabis use with mortality were estimated using Cox proportional hazards regression with adjustment for demographic and clinical variables. Among 121 895 participants (54.51% females with mean [SD] age of 55.15 [7.64] years; 45.49% males with mean [SD] age of 56.46 [7.79] years) during an overall median of 11.80 years (IQR, 10.53-13.22 years) of follow-up, 2375 total deaths occurred, including 1411 deaths from CVD and 440 from cancer. In males, after full adjustment, the hazard ratios (HRs) were 1.28 (95% CI, 0.90-1.81) for all-cause mortality, 0.98 (95% CI, 0.43-2.25) for CVD mortality, and 1.09 (95% CI, 0.71-1.67) for cancer mortality among heavy cannabis users compared with never users. In females, after full adjustment, the HRs were 1.49 (95% CI, 0.92-2.40) for all-cause mortality, 2.67 (95% CI, 1.19-4.32) for CVD mortality, and 1.61 (95% CI, 0.91-2.83) for cancer mortality among heavy cannabis users compared with never users. In female current tobacco users, after full adjustment, heavy cannabis use was associated with all-cause mortality (HR, 2.25; 95% CI, 1.12-4.53), CVD mortality (HR, 2.56; 95% CI, 1.43-15.36), and cancer mortality (HR, 3.52; 95% CI, 1.50-8.33) and among never tobacco users was associated with CVD mortality (HR, 2.98; 95% CI, 1.67-6.61). In male current tobacco users, heavy cannabis use was associated with cancer mortality (HR, 2.44; 95% CI, 1.14-5.23). In this study, a positive association between CVD mortality and heavy lifetime cannabis use was observed among females. Longitudinal studies are needed in general populations to investigate the potential effects of cannabis on mortality.

Ratio of Red Blood Cell Distribution Width to Albumin Level and Risk of Mortality.

The ratio of red blood cell distribution width (RDW) to albumin concentration (RAR) has emerged as a reliable prognostic marker for mortality in patients with various diseases. However, whether RAR is associated with mortality in the general population remains unknown. To explore whether RAR is associated with all-cause and cause-specific mortality and to elucidate their dose-response association. This population-based prospective cohort study used data from participants in the 1998-2018 US National Health and Nutrition Examination Survey (NHANES) and from the UK Biobank with baseline information provided from 2006 to 2010. Included participants had complete data on serum albumin concentration, RDW, and cause of death. The NHANES data were linked to the National Death Index records through December 31, 2019. For the UK Biobank, dates and causes of death were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland) to November 30, 2022. Potential associations between RAR and the risk of all-cause and cause-specific mortality were evaluated using Cox proportional hazards regression models. Restricted cubic spline regressions were applied to estimate possible nonlinear associations. In NHANES, 50 622 participants 18 years of age or older years were included (mean [SD] age, 48.6 [18.7] years; 26 136 [51.6%] female), and their mean (SD) RAR was 3.15 (0.51). In the UK Biobank, 418 950 participants 37 years of age or older (mean [SD], 56.6 [8.1] years; 225 038 [53.7%] female) were included, and their mean RAR (SD) was 2.99 (0.31). The NHANES documented 7590 deaths over a median (IQR) follow-up of 9.4 (5.1-14.2) years, and the UK Biobank documented 36 793 deaths over a median (IQR) follow-up of 13.8 (13.0-14.5) years. According to the multivariate analysis, elevated RAR was significantly associated with greater risk of all-cause mortality (NHANES: hazard ratio [HR], 1.83 [95% CI, 1.76-1.90]; UK Biobank: HR, 2.08 [95% CI, 2.03-2.13]), as well as mortality due to malignant neoplasm (NHANES: HR, 1.89 [95% CI, 1.73-2.07]; UK Biobank: HR, 1.93 [95% CI, 1.86-2.00]), heart disease (NHANES: HR, 1.88 [95% CI, 1.74-2.03]; UK Biobank: HR, 2.42 [95% CI, 2.29-2.57]), cerebrovascular disease (NHANES: HR, 1.35 [95% CI, 1.07-1.69]; UK Biobank: HR, 2.15 [95% CI, 1.91-2.42]), respiratory disease (NHANES: HR, 1.99 [95% CI, 1.68-2.35]; UK Biobank: HR, 2.96 [95% CI, 2.78-3.15]), diabetes (NHANES: HR, 1.55 [95% CI, 1.27-1.90]; UK Biobank: HR, 2.83 [95% CI, 2.35-3.40]), and other causes of mortality (NHANES: HR, 1.97 [95% CI, 1.86-2.08]; UK Biobank: HR, 2.40 [95% CI, 2.30-2.50]) in both cohorts. Additionally, a nonlinear association was observed between RAR levels and all-cause mortality in both cohorts. In this cohort study, a higher baseline RAR was associated with an increased risk of all-cause and cause-specific mortality in the general population. These findings suggest that RAR may be a simple, reliable, and inexpensive indicator for identifying individuals at high risk of mortality in clinical practice.

Association of circulating vitamin D and omega 3 fatty acid with all-cause mortality in patients with rheumatoid arthritis: A large population-based cohort study.

To assess the associations of both the level of circulating vitamin D and the ratio of omega-3 fatty acids to total fatty acids (omega-3%) with mortality among participants with rheumatoid arthritis. This study included 4,293 and 1,157 adults with rheumatoid arthritis identified by self-report from the UK Biobank for the analysis of vitamin D and omega-3%, respectively. Death outcomes were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland). Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for mortality. The medians (25th-75th percentiles) of serum 25(OH)D and omega-3% were 45.8 (31.4-62.9) nmol/L and 4.1% (3.3%-5.1%), respectively. During 52,612 person-years of follow-up in the 25(OH)D group, 502 all-cause deaths occurred; and during 14,192 person-years of follow-up in the omega-3% group, 122 all-cause deaths occurred. Rheumatoid arthritis patients with vitamin D levels of at least 20nmol/L had an approximately 40-50% lower risk of all-cause mortality than those with severe vitamin D deficiency (hazard ratio ranging from 0.51 to 0.62, all P values<0.05). Each unit increase in natural log-transformed 25(OH)D was associated with a 22% reduction in the risk of all-cause mortality, and a U-shaped association between serum 25(OH)D and all-cause mortality was found. However, the association between omega-3% and mortality was not significant. Lower serum 25(OH)D concentration, but not omega-3%, was significantly associated with higher all-cause mortality in patients with rheumatoid arthritis. Optimizing serum vitamin D levels may be an important factor in reducing mortality risk in this population.

Associations between handgrip strength and skeletal muscle mass with all-cause mortality and cardiovascular mortality in people with type 2 diabetes: A prospective cohort study of the UK Biobank.

To explore the associations between handgrip strength (HGS) and skeletal muscle mass (SMM) with all-cause and cardiovascular disease (CVD) mortality risk in type 2 diabetes (T2DM) patients. Data were obtained from the UK Biobank. Baseline survey was conducted between 2006 and 2010, and followed up for a median of 12.52 years. HGS was measured using dynamometer, and SMM was measured using bioelectrical impedance method. Mortality was available via links to the National Health Service Information Centre. Sex-specific analyses were conducted. A total of 13 392 T2DM participants were included, with a mean age of 60.39 years and 52.35% men. During the follow-up, there were 3006 (22.45%) deaths, including 746 (5.57%) CVD deaths. The risk for all-cause mortality and CVD mortality among both men and women increased progressively with decreasing HGS quartiles (p trend <.05). A 1 SD decrease in HGS was found to both increase the all-cause risk (HR: 1.31 [95% CI: 1.24-1.38]) and CVD mortality risk (HR: 1.35 [95% CI: 1.22-1.50]) for men, and all-cause risk (HR: 1.26 [95% CI: 1.11-1.42]) and CVD mortality risk (HR: 1.43 [95% CI: 1.09-1.89]) for women. There was no statistically significant trend association between SMM/height2 and mortality risk, and the restricted cubic regression splines indicated that SMM/height2 showed a U-shaped nonlinear relationship (pnonlinear <.05). Grip strength displayed a linear downward trend with mortality risk among T2DM patients, whereas muscle mass showed a U-shaped relationship. Low grip strength seemed to be a better predictor for mortality compared to low muscle mass.

Weight status and breast cancer incidence in the UK Women's Cohort Study: a survival analysis

BackgroundBreast cancer is the most common type of cancer in the UK, even though it predominantly affects women. Some research suggests that obesity before menopause can be protective against breast cancer, whereas postmenopausal obesity poses increased risk. Because of a period of latency in the development of cancer, longitudinal cohort studies are essential. The aim of this research was to investigate the association between body-mass index (BMI) and breast cancer incidence. MethodsThe UK Women's Cohort Study was established in the 1990s to investigate patterns between diet and health. 35 000 women were recruited and followed up via cancer incidence and mortality data reports from the National Health Service information centre. Self-reported height and weight were used to calculate BMI. WHO cut-off points were used to define BMI categories. Age-adjusted Cox proportional hazards regression was applied with Stata (version IC12). Findings1445 (4%) of 35 372 women developed breast cancer during a median time to follow-up of 14·9 years (IQR 1·4). Cases prevalent at baseline were excluded. There were significant differences between the observed and expected outcomes by BMI category (p=0·0003, log-rank test), with underweight and normal weight having lower observed than expected incidence. Overweight and obese women had higher observed than expected incidence. Test for trend of survivor functions showed a significant trend of increasing breast cancer incidence with increasing BMI for the whole cohort (p=0·0001) and the postmenopausal subgroup (p=0·0001), but not for premenopausal women. Hazard ratios in an age-adjusted model were significant in postmenopausal women: underweight 1·0 (reference); normal weight 1·6, 95% CI 0·8–3·2; overweight 2·0, 1·0–4·1; obese 2·1, 1·0–4·3. InterpretationWe found a clear association between BMI and breast cancer incidence, especially in postmenopausal women. We did not see an association in premenopausal women. These results are supportive of existing scientific literature and highlight the importance of maintaining a healthy weight in adulthood, especially after the menopause. Health-care professionals should consider referral of overweight and obese women to weight loss services as a protective measure before menopause. FundingThis research was funded as part of an Economic and Social Research Council/Medical Research Council interdisciplinary PhD studentship.

SAT0230 The Influence of Anti-TNF or Rituximab on Cancer Incidence in Patients with Rheumatoid Arthritis Who Have HAD A Prior Malignancy

BackgroundThe exact relationship between biologics and cancer remains unclear. Despite no evidence to date of an overall increased risk of cancer on biological therapies, concerns remain about starting therapy in...

OP0029 The Risk of Serious Infections in Patients Receiving Rituximab for Rheumatoid Arthritis

BackgroundIn the Europe, rituximab (RTX), an anti-CD20 monoclonal antibody, is reserved for patients with rheumatoid arthritis (RA) who have failed initial anti-TNF therapy. There is a concern over whether B-cell...

Screening for thyroid insufficiency in adults with Down syndrome

PurposeThe purpose of this paper is to introduce and present the first findings of a new English performance indicator in the primary healthcare of adults with Down syndrome. This is a performance target, with associated bonus payment, requiring General Practitioners (GPs) to undertake annually a screening blood test for thyroid hormone deficiency.Design/methodology/approachAnalysis and review of data collected from all GP practices and published by the National Health Service (NHS) Information Centre.FindingsIn total, 82 per cent of those identified as in the target group were screened and 10 per cent were identified as not wanting to be screened or screening inappropriate. The target group numbered just over 60 per cent of the number estimated from epidemiological and other studies. The numbers of cases involved is small (0, 1 or 2 cases in 75 per cent of GP practices), and whilst variation in coverage at local level appears important, numbers are too small for the variations seen in the first year's data to be statistically significant. The scope of the data precludes useful strategic analysis of the value of the intervention.Research limitations/implicationsData from several years need to be taken together. The NHS Information Centre should slightly increase the scope of the data to allow analysis of whether the programme is having useful public health benefits.Originality/valueThe paper examines a new data source and makes points applicable to a wider range of similar datasets in the same programme.

Use of concentration indices of Hospital Episode Statistics data to monitor inequality in English children and young people (1999–2000 to 2009–10)

BackgroundNew methods are needed to monitor inequality in child health. The National Health Service (NHS) reforms introduced a statutory duty to reduce inequality at a time when UNICEF predicts a substantial increase in child poverty. The government believes that the previous focus on infant mortality was too narrow and that inequality should be measured across a range of indicators that matter most for children and young people. We propose that the concentration index of hospital activity could be a valuable aid to monitor one aspect of inequality with routinely collected data. As illustration, inequality trends in inpatient activity among children and young people for 10 years are analysed. MethodsHospital Episode Statistics data from 1999–2000 and 2009–10 were accessed via the NHS Information Centre. Activity was measured by finished consultant episodes and socioeconomic status by index of multiple deprivation decile, derived from the patient's postcode. The proportion of inpatient activity accounted for by each deprivation decile was calculated, stratifying by sex and age (<1, 1–4, 5–9, 10–14, and 15–19 years). Age-specific population estimates and deprivation scores were then accessed from the Office of National Statistics for all 6781 medium super output areas (MSOAs) in England. Linking and ranking of these data allowed estimation of the proportion of age-specific populations within each deprivation decile. We then calculated concentration indices and standard errors in Microsoft Excel using formulae published by the World Bank (appendix). FindingsComparing the concentration indices, inequality in inpatient care increased for infants (boys in 1999: −0·046, 95% CI −0·042 to −0·050; boys in 2009: −0·071, −0·067 to −0·075; girls in 1999: −0·040, −0·036 to −0·044; girls in 2009: −0·067, −0·063 to −0·071). For children aged 1–4 years, inequality was unchanged for boys (1999: −0·067, −0·065 to −0·069; 2009: −0·066, −0·064 to −0·068) but increased for girls (1999: −0·064, −0·063 to −0·066; 2009: −0·070, −0·068 to −0·072). Inequality decreased in all other groups, most substantially in girls aged 15–19 years (1999: −0·245, −0·243 to −0·247; 2009: −0·183, −0·181 to −0·185). InterpretationThe negative concentration indices suggest that children and young people from more deprived areas account for a greater proportion of inpatient care than do those living in more affluent areas. These data show converging inequality trends in different ages of childhood and adolescence during the 10 year period. Inequality in the need for hospital treatment was lowest in the early years, but increased during the 10 years. Inequality in late adolescence was much greater than at younger ages, especially for girls, but significantly reduced. Despite the policy focus on outcomes that matter most for children and young people, financial constraints have reduced the available data. Concentration indices use routinely collected, robust data and can be calculated at national, regional, or local level. They can conveniently be adapted to assess inequality in specific activity—eg, asthma, injuries, or alcohol-related admissions. Although they are affected by access factors as well as objective patient need, they might be a valuable aid for public health professionals and commissioners who wish to reduce inequality, contain costs of acute care, or interpret regional variation in hospital activity, particularly when used in conjunction with the recently published NHS Atlas of Variation in Healthcare for Children and Young People. FundingNone.

The British Association of Dermatologists’ Biologic Interventions Register (BADBIR): design, methodology and objectives

The British Association of Dermatologists (BAD) established a web-based pharmacovigilance register to assess the long-term safety of biologics prescribed for patients with severe psoriasis in September 2007. The BAD Biologic Interventions Register (BADBIR) also participates in the network of European psoriasis biologics registers (Psonet). This prospective observational cohort study compares adult patients with psoriasis treated with biologics vs. a comparator group exposed to conventional systemic therapies. Following baseline data acquisition, clinicians record changes in therapy, disease activity and adverse events for 5years (6-monthly for 3years, then annually thereafter). Patient details are flagged lifelong on the National Health Service Information Centre system to capture occurrence of malignancy or death. Primary study endpoints include malignancy, infection, serious adverse events and death. Collection of long-term effectiveness data is a subsidiary aim. By November 2011, the number of dermatology centres actively recruiting across the U.K. and Republic of Ireland had risen to 108 and a further 37 were actively engaged in the set-up process. Of the 3176 patients enrolled in the study to date, 2193 were registered within the biologic cohort and 983 in the conventional systemic (nonbiologic-exposed) cohort. A robust, high-quality, web-based register of biologic and conventional therapy for psoriasis has been established in the U.K. This is the largest project undertaken by the BAD. The data it will provide over the coming years will be invaluable to the safe use of biologics in clinical practice. A U.K.-wide dermatology clinical research network has been established that provides a framework for future studies in other diseases.

Risk Factors Associated With Rehospitalization in the Elderly Using Chart-Abstracted Data and the New York State Patient Data System

Hospitalization is a significant risk for the elderly (65 years or older) and is the largest component of U.S. health care spending accounting for more than 35% of health care dollars (Folland, Goodman, & Stano, 2001). It is estimated that by 2030, the number of elderly will be more than double to 70 million (Centers for Disease Control and Prevention [CDC], 2010). Because 20% of our future population will be elderly with many suffering from chronic diseases, health care and hospital costs for this group are expected to increase substantially (Lamont, Sampson, Matthias, & Kane, 1983). Compared with the general population and driving these predictions, the elderly have significantly higher rates of hospital admission and readmissions and are responsible for most hospitalization days and expenses (Parker, 2005; Victor, Healy, Thomas, & Seargeant, 2000). In the United States (Elixhauser, Yu, Steiner, & Bierman, 2000) and the United Kingdom (National Health Service Information Centre Hospital Episode Statistics, 2006), the elderly account for approximately 36% of hospital admissions; in Australia, they account for 52% (Karmel, Lloyd, & Hales, 2007). In addition to the frequency and expense of hospitalization during inpatient stays, many elderly experience deconditioning and functional decline that affects their future independence, autonomy, and quality of life (Covinsky et al., 2003; Creditor, 1993; Hoenig & Rubenstein, 1991). Published research shows that of 60 functionally independent individuals 75 years or older admitted to the hospital from their home for acute illness, 75% were no longer independent on discharge including 15% who were discharged to nursing homes (Creditor, 1993; Lamont et al., 1983). Reducing length of stay and aggressive discharge policies have become important features of the hospital experience, yet readmission following discharge has become a familiar and frustrating problem and may result from avoidable hospital, and/or community service failures (Colledge & Ford, 1994). Prior hospitalizations increase the probability of future hospitalizations and by identifying and managing patient-level risk factors for rehospitalization, patients' health care and quality of life would improve, whereas morbidity, mortality, costs, and the rate of future hospitalizations would decrease (Colledge & Ford, 1994; Creditor, 1993). Developing a predictive model for rehospitalization risk is one method to describe the factors associated with elderly rehospitalization, identify those at risk, and target individuals for appropriate preventive interventions (Blackman, Kamimoto, & Smith, 1999). Such a model may also predict hospital utilization costs more accurately allowing hospitals to better anticipate staffing and resource needs to efficiently serve elderly patients. However, research has shown that a risk factor must have a much stronger association with the outcome than we ordinarily see in etiologic and epidemiologic research if it is to provide a basis for prediction in individual patients. Despite the strong association between the risk factor and the outcome, it does not follow that the risk factor provides a basis for an effective prediction rule for individual patients (Ware, 2006). OBJECTIVES The purpose of this study is to identify demographic and clinical factors associated with nonelective, all-cause rehospitalization within 120 days of an index admission in the elderly. METHODOLOGY Our sampling frame included all patients 65 years or older admitted to Saint Vincent Catholic Medical Centers (SVCMC) of New York for nonelective admissions between June 21, 2003, and June 20, 2004. For all patients admitted more than once during the study period, we counted each admission as unique. To avoid the possibility of seasonal variation on our sample, we employed a random proportional stratified sampling strategy using the date of admission to stratify the sample by season. …

Authors' reply: Expanding horizons in metastatic prostate cancer treatment

We thank Fizazi & Goessl for their comments and interest in our article—Bone metastasis in prostate cancer: emerging thera peutic strategies. Nat. Rev. Clin. Oncol. 8, 357–3681 (Expanding horizons in metastatic prostate cancer treatment. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2011.67‐c1)2—in which we focus on the current and emerg‐ ing therapies for bone metastases in patients with castration‐resistant prostate cancer (CRPC). We also thank them for bringing to our attention several errors in Tables 1 and 2. These have been corrected for the HTML and PDF versions of the article.3 In our Review, we discussed the Medical Research Council (MRC) PR05 trial, which recruited men with prostate cancer and metastatic bone disease (MBD) who had started or responded to long‐term hormone therapy.4 The long‐term survival data from the final analysis included data from 278 patients (89%) of the original 311 men recruited to the study, and 258 deaths (93%) were reported. In the analysis by Dearnaley et al.,4 a total of 31 patients (10%) were excluded because they were not registered in England and Wales and a further two patients (1%) were not identified by the UK National Health Service Information Centre. Evidence does not indicate that the 11% of patients excluded would have different response rates to clodronate. We remain in agreement with Dearnaley et al.,4 who con‐ clude a significant overall survival benefit from this first‐generation bisphosphonate Authors’ reply: Expanding horizons in metastatic prostate cancer treatment

The long-term risk of premature mortality in people with epilepsy

People with epilepsy have an increased risk of premature death. The risk is highest soon after onset of seizures. We report the findings of a long-term follow-up population-based study of people with epilepsy with regards to premature mortality. The National General Practice Study of Epilepsy is a prospective study flagged at the National Health Service Information Centre in the UK. Over 1000 people with new onset seizures were followed from the mid 1980s until April 2009. Of these, 564 people were classified at 6 months as having definite epileptic seizures, 228 as having possible epileptic seizures and 220 as having febrile seizures. The remainder were excluded (n=104 because of an unknown prior diagnosis of epilepsy or neonatal seizures) or classified as not having epilepsy (n=79). At median follow-up of 22.8 years there had been 301 deaths in the cohort; 300 of these were in people with definite or possible seizures. Death certificates were obtained for all but three of those who died. The overall standardized mortality ratio for those with definite or possible epilepsy was 2.2 (95% confidence interval 1.97-2.47), and was higher in those with definite seizures (2.6). In those who were alive at 20 years follow-up, the standardized mortality ratio in the subsequent years remained significantly elevated (2.2, 95% confidence interval 1.6-3.2). Pneumonia (standardized mortality ratio 6.6, 95% confidence incidence 5.1, 8.4) was a common cause of death with a consistently elevated standardized mortality ratio throughout follow-up. The standardized mortality ratio for ischaemic heart disease was significantly elevated for the first time in the last 5 years of follow-up (3.3, 95% confidence interval 1.6-7.0). Few people died from epilepsy-related causes. The risk of premature death remains significantly elevated at 20-25 years after the index seizure despite most of the cohort being in terminal remission (defined as 5 years or more seizure-free, on or off anti-epileptic medication) at the last follow-up. Further studies are needed to explore the reasons for this long-term increase in premature mortality.

Medicines Use Review: adoption and spread of a service innovation

Abstract Background Research has shown that implementation of community pharmacy Medicines Use Review and Prescription Intervention (MUR) in the first year of the service in England and Wales was less extensive than anticipated. Several barriers to MUR becoming accepted and embedded in the National Health Service (NHS) were identified. Objective To evaluate progress in the provision of the MUR service in England and Wales in its second year (April 1, 2006-March 31, 2007) compared with the first year; and to analyse trends from available national data from the third year of provision in 2007–2008. Methods The analysis drew on the following data sources: routine data on provision of MURs for community pharmacies in a stratified random sample of 31 primary care organisations in England and Wales, and national datasets on MUR provision from the Pharmaceutical Services Negotiating Committee and NHS Information Centre. Outcome measures The percentage of community pharmacies providing the MUR service, the numbers of MURs provided in 2006–2007 at pharmacy and primary care organisation level, and the extent of, and variation in, provision. Key findings The percentage of community pharmacies providing the MUR service increased from 38 to 67.2%. Overall, 62 559 MURs were provided (a more than four-fold increase on the previous year), representing 13.8% of the possible maximum. The mean number of MURs provided (per provider) increased from 36 to 85. For existing providers the mean number increased from 36 to 111 (median 78, range 0–423). For new providers the mean number was 52 (median 17, range 1–401). More than half (52%) of the pharmacies in the sample claimed for fewer than 50 MURs. Overall, 82% of MURs were provided by multiples and this percentage was lower among new providers (62%) than existing providers (89%). Thirty-three (8.1%) existing MUR providers had no recorded MURs in the second year: almost two-thirds of these (64%) were independents. Eleven pharmacies (1.5%) provided the maximum number of 400 MURs per year: all but one were branches of multiples. Of the pharmacies not yet providing MURs, 78% were independent. Conclusions Both numbers of MURs and numbers of providers of MUR services increased markedly during the service's second year. Those newly providing the service in the second year claimed for more than twice as many MURs as did those who had been ‘new providers' the previous year. Overall just over half of all providing pharmacies claimed for the equivalent of one MUR a week or fewer. Therefore the extent of ‘successful adoption’ of MURs is debatable. Differences in the level of provision continued between independent and multiple pharmacies in terms of both adoption of the service and the number of reviews conducted. As in the previous year, independent pharmacies were less likely to provide the MUR service and when they did the numbers conducted were lower than those provided by multiples.

Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials

SummaryBackgroundBisphosphonates might modulate the development of symptomatic bone metastases in men with prostate cancer. The Medical Research Council (MRC) PR05 and PR04 randomised controlled trials assessed the use of sodium clodronate, an oral, first-generation bisphosphonate. We report the final analyses of long-term survival data with additional follow-up in both trials.Methods311 men with metastatic disease were recruited to PR05 between 1994 and 1998, and 508 men with non-metastatic disease were recruited to PR04 from 1994 to 1997. All men were treated according to the recruiting site's standard practice at the time: for metastatic disease, all men were starting or responding to long-term hormone therapy; for non-metastatic disease, most men had radiotherapy, hormone therapy, or both. Men were randomly assigned to take four tablets per day of sodium clodronate (2080 mg) or matching placebo for up to 3 years (metastatic disease) or 5 years (non-metastatic). Long-term overall survival was assessed on an intention-to-treat basis in all men at sites in England and Wales using data from the National Health Service Information Centre, which held data for 278 of 311 men in the PR05 trial and 471 of 508 men in the PR04 trial. These studies are registered International Standardised Randomised Controlled Trials, numbers ISRCTN38477744 (PR05) and ISRCTN61384873 (PR04).FindingsOf the 278 men with metastatic disease, 258 (93%) were reported to have died. Evidence of a benefit for those with metastatic disease from use of sodium clodronate compared with placebo was seen in overall survival (hazard ratio [HR] 0·77, 95% CI 0·60–0·98; p=0·032). Of the 471 men with non-metastatic disease, 281 (60%) were reported to have died, with no evidence of improvement in overall survival with clodronate compared with placebo (HR 1·12, 0·89–1·42; p=0·94).InterpretationLong-term data from these trials show that a first-generation bisphosphonate, sodium clodronate, improves overall survival in men with metastatic prostate cancer who are starting hormone therapy, but there is no evidence of an effect in men with non-metastatic prostate cancer.FundingUK MRC; and an education grant and free drug from Roche Products Ltd.