A Fuller

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data

BACKGROUND Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

Effect of 3 to 5 Years of Scheduled CEA and CT Follow-up to Detect Recurrence of Colorectal Cancer: The FACS Randomized Clinical Trial

IMPORTANCE Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence. OBJECTIVE To assess the effect of scheduled blood measurement of carcinoembryonic antigen (CEA) and computed tomography (CT) as follow-up to detect recurrent colorectal cancer treatable with curative intent. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial in 39 National Health Service hospitals in the United Kingdom; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer, including adjuvant treatment if indicated, with no evidence of residual disease on investigation. INTERVENTIONS Participants were randomly assigned to 1 of 4 groups: CEA only (n = 300), CT only (n = 299), CEA+CT (n = 302), or minimum follow-up (n = 301). Blood CEA was measured every 3 months for 2 years, then every 6 months for 3 years; CT scans of the chest, abdomen, and pelvis were performed every 6 months for 2 years, then annually for 3 years; and the minimum follow-up group received follow-up if symptoms occurred. MAIN OUTCOMES AND MEASURES The primary outcome was surgical treatment of recurrence with curative intent; secondary outcomes were mortality (total and colorectal cancer), time to detection of recurrence, and survival after treatment of recurrence with curative intent. RESULTS After a mean 4.4 (SD, 0.8) years of observation, cancer recurrence was detected in 199 participants (16.6%; 95% CI, 14.5%-18.7%) overall; 71 of 1202 participants (5.9%; 95% CI, 4.6%-7.2%) were treated for recurrence with curative intent, with little difference according to Dukes staging (stage A, 5.1% [13/254]; stage B, 6.1% [34/553]; stage C, 6.2% [22/354]). Surgical treatment of recurrence with curative intent was 2.3% (7/301) in the minimum follow-up group, 6.7% (20/300) in the CEA group, 8% (24/299) in the CT group, and 6.6% (20/302) in the CEA+CT group. Compared with minimum follow-up, the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4% (95% CI, 1.0%-7.9%; adjusted odds ratio [OR], 3.00; 95% CI, 1.23-7.33), in the CT group was 5.7% (95% CI, 2.2%-9.5%; adjusted OR, 3.63; 95% CI, 1.51-8.69), and in the CEA+CT group was 4.3% (95% CI, 1.0%-7.9%; adjusted OR, 3.10; 95% CI, 1.10-8.71). The number of deaths was not significantly different in the combined intensive monitoring groups (CEA, CT, and CEA+CT; 18.2% [164/901]) vs the minimum follow-up group (15.9% [48/301]; difference, 2.3%; 95% CI, -2.6% to 7.1%). CONCLUSIONS AND RELEVANCE Among patients who had undergone curative surgery for primary colorectal cancer, intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up; there was no advantage in combining CEA and CT. If there is a survival advantage to any strategy, it is likely to be small. TRIAL REGISTRATION isrctn.org Identifier: 41458548.

Health checks in general practice: another example of inverse care?

OBJECTIVE--To assess attendance at and the characteristics of patients attending health checks for cardiovascular disease offered in a general practice over a period of five years (1984-9). DESIGN--Medical record audit and postal questionnaire survey. SETTING--One general practice in Oxfordshire with a socially diverse population. PARTICIPANTS--1101 Men and 1110 women aged 35-64 registered with the practice. MAIN OUTCOME MEASURES--Age, sex, marital state, social class, smoking habits, alcohol consumption, and diet. RESULTS--Of the 2211 men and women in the target age group (35-64) in 1989, 1458 (65.9%) had been offered screening and 963 (43.6%) had attended for a health check. Attenders were more likely to be women, aged greater than or equal to 45, married, non-smokers, and of higher social class than patients who did not respond to the invitation. The relative likelihood of non-attendance was 1.24 for smokers, 1.20 for the overweight, 1.16 for heavy drinkers, and 1.28 for those with a less healthy diet, even after adjustment for age, sex, marital state, and social class. CONCLUSIONS--After five years of offering health checks, opportunistically (to men) and in the context of cervical smear tests (to women), less than half of the eligible patients had attended. The likelihood of acceptance of an invitation to attend was inversely related to the patients cardiovascular risk for all factors measured except age. A coherent strategy to reduce cardiovascular disease depends on more careful targeting of scarce health service resources and more emphasis on public health measures (such as dietary regulation and tobacco taxation). Doctors should be careful not to absolve the government of its public health obligations by substituting unproved preventive interventions aimed at the individual patient.

All-Cause and Cardiovascular Mortality in Middle-Aged People With Type 2 Diabetes Compared With People Without Diabetes in a Large U.K. Primary Care Database

OBJECTIVE Middle-aged people with diabetes have been reported to have significantly higher risks of cardiovascular events than people without diabetes. However, recent falls in cardiovascular disease rates and more active management of risk factors may have abolished the increased risk. We aimed to provide an up-to-date assessment of the relative risks associated with type 2 diabetes of all-cause and cardiovascular mortality in middle-aged people in the U.K. RESEARCH DESIGN AND METHODS Using data from the General Practice Research Database, from 2004 to 2010, we conducted a cohort study of 87,098 people, 40–65 years of age at baseline, comparing 21,798 with type 2 diabetes and 65,300 without diabetes, matched on age, sex, and general practice. We produced hazard ratios (HRs) for mortality and compared rates of blood pressure testing, cholesterol monitoring, and use of aspirin, statins, and antihypertensive drugs. RESULTS People with type 2 diabetes, compared with people without diabetes, had a twofold increased risk of all-cause mortality (HR 2.07 [95% CI 1.95–2.20], adjusted for smoking) and a threefold increased risk of cardiovascular mortality (3.25 [2.87–3.68], adjusted for smoking). Women had a higher relative risk than men, and people <55 years of age had a higher relative risk than those >55 years of age. Monitoring and medication rates were higher in those with diabetes (all P < 0.001). CONCLUSIONS Despite efforts to manage risk factors, administer effective treatments, and develop new therapies, middle-aged people with type 2 diabetes remain at significantly increased risk of death.

The "Help Your Patient Stop" initiative. Evaluation of smoking prevalence and dissemination of WHO/UICC guidelines in UK general practice.

The World Health Organisation and the International Agency against Cancer in 1988 published joint guidelines on smoking cessation for primary health care teams. A booklet entitled Help Your Patient Stop was produced in the United Kingdom as a model for the international dissemination of these guidelines. This booklet was sent to UK general practitioners by post; about 4 weeks later, a random sample of 5000 were asked to complete a postal questionnaire about the booklet and their smoking habits. The response rate was 75%. About half (50.5%) remembered receiving the booklet, 27.7% had read it, and only 8.8% could write down any of the three essential activities in smoking cessation which the booklet was intended to promote and which were printed in bold letters on the inside back cover. Although the booklet itself might be an adequate model for other countries, unless dissemination and marketing of the information it contains can be improved, its achievement will be limited. However, the survey did have one optimistic feature: only 13.5% of general practitioners reported that they smoke; and only a third of those who gave full details of their smoking habit smoke cigarettes.

The dopamine D2 receptor C32806T polymorphism (DRD2 Taq1A RFLP) exhibits no association with smoking behaviour in a healthy UK population

A single nucleotide polymorphism (SNP) in the Taq1A site near the DRD2 gene has been associated in several studies with smoking behaviour. We genotyped 732 current smokers (241 low, one to nine cigarettes a day, 250 mid, 10 ‐ 19 cigarettes, 241 high, 20 + cigarettes) and 243 never‐smokers at this site (C32806T), to test for effects on smoking initiation and amount of tobacco consumed. No significant association between minor allele frequency and smoking status was detected. Multiple regression analysis including DRD2 genotype, sex, age and alcohol consumption as predictors showed that level of cigarette consumption was associated with sex (p  = 0.003) and age (p  = 0.002) but not with alcohol consumption (p  = 0.25) or DRD2 genotype (p  = 0.76).

Site and stage of colorectal cancer influence the likelihood and distribution of disease recurrence and postrecurrence survival: data from the FACS randomized controlled trial

Objectives:To describe patterns of recurrence and postrecurrence survival in a large cohort of accurately staged patients with Dukes’ A-C colorectal cancer. Background:Recurrence remains a frequent cause of mortality after the treatment of colorectal cancer with curative intent. Understanding the likelihood and site of recurrence informs adjuvant treatment and follow-up. Methods:Retrospective cohort analysis of data from the FACS (follow-up after colorectal cancer surgery) trial after a median 4.4 years of follow-up; postrecurrence survival was calculated using the Kaplan-Meier method. Results:Complete data were available for 94% of patients; 189 (17%) patients had experienced recurrence. Incidence of recurrence varied according to the site of the primary (right colon: 51/379, 14%; left colon: 68/421, 16%; rectum: 70/332, 21%; P = 0.023) and initial stage (Dukes’ A: 26/249, 10%; Dukes’ B: 81/537, 15%; Dukes’ C: 82/346, 24%; P < 0.0001). Pulmonary recurrence was most frequently associated with rectal tumors, and multisite/other recurrence with right-sided colonic tumors. Recurrences from lower-stage tumors were more likely to be treatable with curative intent (Dukes’ A: 13/26, 50%; Dukes’ B: 32/81, 40%; Dukes’ C: 20/82, 24%; P = 0.03). Those with rectal tumors benefited most from follow-up (proportion with treatable recurrence: rectum 30/332, 9%; left colon 23/421, 6%; right colon 12/379, 3%; P = 0.003). Both initial stage (log rank P = 0.005) and site of primary (log rank P = 0.01) influenced postrecurrence survival. Conclusions:The likelihood and site of recurrence, and survival, are influenced by the site and stage of the primary tumor. Those with rectal cancers benefited most from follow-up.ISRCTN 41458548

Evaluation of a prediction model for colorectal cancer: retrospective analysis of 2.5 million patient records

Earlier detection of colorectal cancer greatly improves prognosis, largely through surgical excision of neoplastic polyps. These include benign adenomas which can transform over time to malignant adenocarcinomas. This progression may be associated with changes in full blood count indices. An existing risk algorithm derived in Israel stratifies individuals according to colorectal cancer risk using full blood count data, but has not been validated in the UK. We undertook a retrospective analysis using the Clinical Practice Research Datalink. Patients aged over 40 with full blood count data were risk‐stratified and followed up for a diagnosis of colorectal cancer over a range of time intervals. The primary outcome was the area under the receiver operating characteristic curve for the 18–24‐month interval. We also undertook a case–control analysis (matching for age, sex, and year of risk score), and a cohort study of patients undergoing full blood count testing during 2012, to estimate predictive values. We included 2,550,119 patients. The area under the curve for the 18–24‐month interval was 0.776 [95% confidence interval (CI): 0.771, 0.781]. Performance improves as the time interval reduces. The area under the curve for the age‐matched case–control analysis was 0.583 [0.574, 0.591]. For the population risk‐scored in 2012, the positive predictive value at 99.5% specificity was 8.8% with negative predictive value 99.6%. The algorithm offers an additional means of identifying risk of colorectal cancer, and could support other approaches to early detection, including screening and active case finding.

Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality

The relative toxicity of anxiolytic and hypnotic drugs commonly used for self-poisoning was assessed using data on suicides, prescriptions and non-fatal self-poisonings in England, 2005–2012. Data on suicide by self-poisoning were obtained from the Office for National Statistics, information on intentional non-fatal self-poisoning was derived from the Multicentre Study of Self-harm in England and data on prescriptions in general practice from the Clinical Practice Research Datalink. We used two indices of relative toxicity: fatal toxicity (the number of fatal self-poisonings relative to the number of individuals prescribed each drug) and case fatality (the number of fatal relative to non-fatal self-poisonings). Diazepam was the reference drug in all analyses. Temazepam was 10 times (95% confidence interval 5.48–18.99) and zopiclone/zolpidem nine times (95% confidence interval 5.01–16.65) more toxic in overdose than diazepam (fatal-toxicity index). Temazepam and zopiclone/zolpidem were 13 (95% confidence interval 6.97–24.41) and 12 (95% confidence interval 6.62–22.17) times more toxic than diazepam, respectively (case-fatality index). Differences in alcohol involvement between the drugs were unlikely to account for the findings. Overdoses of temazepam and zopiclone/zolpidem are considerably more likely to result in death than overdoses of diazepam. Practitioners need to exercise caution when prescribing these drugs, especially for individuals who may be at risk of self-harm, and also consider non-pharmacological options.