Overweight across the life course and adipokines, inflammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort.

BACKGROUND/OBJECTIVES: There is growing evidence that early development of obesity increases cardiovascular risk later in life, but less is known about whether there are effects of long-term excess body weight on the biological drivers associated with the atherosclerotic pathway, particularly adipokines, inflammatory and endothelial markers. This paper therefore investigates the influence of overweight across the life course on levels of these markers at retirement age. SUBJECTS/METHODS: Data from the Medical Research Council National Survey of Health and Development (n=1784) were used to examine the associations between overweight status at 2, 4, 6, 7, 11, 15, 20, 26, 36, 43, 53 and 60-64 years (body mass index (BMI)⩾25 kg m(-2) for adult ages and gender-specific cut-points for childhood ages equivalent to BMI⩾25 kg m(-2)) and measurements of adipokines (leptin and adiponectin), inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6)) and endothelial markers (E-selectin, tissue plasminogen activator (t-PA) and von Willebrand factor) at 60-64 years. In addition, the fit of different life course models (sensitive periods/accumulation) were compared using partial F-tests. RESULTS: In age- and sex-adjusted models, overweight at 11 years and onwards was associated with higher leptin, CRP and IL-6 and lower adiponectin; overweight at 15 years and onwards was associated with higher E-selectin and t-PA. Associations between overweight at all ages earlier than 60-64 with leptin, adiponectin, CRP and IL-6 were reduced but remained apparent after adjustment for overweight at 60-64 years; whereas those with E-selectin and t-PA were entirely explained. An accumulation model best described the associations between overweight across the life course with adipokines and inflammatory markers, whereas for the endothelial markers, the sensitive period model for 60-64 years provided a slightly better fit than the accumulation model. CONCLUSIONS: Overweight across the life course has a cumulative influence on adipokines, inflammatory and possibly endothelial markers. Avoidance of overweight from adolescence onwards is likely important for cardiovascular disease prevention.

Is screening for AF worthwhile? Stroke risk in a screened population from the SAFE study.

INTRODUCTION: Atrial fibrillation (AF) is an important independent risk factor for stroke and oral anticoagulation therapy provides a highly effective treatment to reduce this risk. Active screening strategies improve detection of AF in comparison with routine care; however, whether screen-detected patients have stroke risk profiles favouring anticoagulation is unclear. Using data derived from the screening for AF in the elderly (SAFE) study, the aim of this article was to determine if patients with AF detected via active screening have stroke risk profiles that warrant prophylactic anticoagulation. METHODS: Secondary analysis of data derived from 25 general practices within which cohorts of 200 patients were randomly allocated to opportunistic [pulse and electrocardiogram (ECG)] or systematic screening (postal invitation for ECG). Stroke risk assessment was undertaken using baseline data extracted from medical records and CHADS2 criteria. CHADS2 scores were compared between the screening groups. RESULTS: One hundred and forty-nine new cases of AF were detected, 75 via opportunistic screening and 74 via systematic screening. CHADS2 scores were ≥1 in 83% [95% confidence interval (CI) 72.6-89.6] of patients detected via opportunistic screening and 78% (95% CI 67.7-86.2) detected via systematic screening. There were no significant differences in stroke risk profiles of patients detected via opportunistic and systematic screenings. CONCLUSION: Stroke risk profiles of patients detected via opportunistic and systematic screenings were similar. Data derived from the SAFE study suggest that active screening for AF in patients aged ≥65 years in primary care is a useful screening programme with 78-83% of patients identified eligible for anticoagulation treatment according to the CHADS2 criteria.

Quality assurance for oral anticoagulation self management: a cluster randomized trial.

BACKGROUND AND AIMS: External quality assessment (EQA) should be an inherent component of patient self management (PSM) of oral anticoagulation. The aim of this study was to evaluate methods of EQA for patients within a cluster randomized trial. METHOD: After development of methods, general practises were randomly allocated to a formal EQA scheme of patients performing the test independently at home or at their practise with supervision. The supervised group of practises was further sub divided to test two other EQA methods: (i) venous sample compared with patients' point of care (POC) device; and (ii) patients POC compared with reference POC. Primary trial outcome measure was reliability of results from the formal scheme taking into account adherence and test errors. RESULTS: Proportion of EQA scheme tests in range was 633/836 (75.7%). Proportion in range was significantly higher in group performing independently compared with supervised group, 80.1% vs. 71.5% respectively, P = 0.02. Sixty-six percent of tests were in range with venous compared with patients POC, and 88% in patients POC compared with reference POC. CONCLUSION: Patients are able to undertake a formal EQA scheme and perform more reliably at home independently. There are satisfactory alternatives if a formal scheme is not acceptable.

Patient self management of oral anticoagulation in routine care in the UK.

BACKGROUND: Self management of anticoagulation: a randomised trial (SMART) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management (PSM) of oral anticoagulation therapy compared to routine care. SMART showed that while PSM was as clinically effective as routine care, it was not as cost effective. SMART adds to the growing body of trial data to support PSM; however there are no data on clinical effectiveness and cost of PSM in routine care. AIM: To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions. METHODS: A retrospective multicentre matched control study. 63 PSM patients from primary care in the West Midlands were matched by age and international normalised ratio (INR) target with controls. INR results were collected for the period 1 July 2003-30 June 2004. The primary outcome measure was INR control. RESULTS: 38 PSM and 40 control patients were recruited. INR percentage time in range was 70% PSM vs 64% controls. 60% PSM were having a regular clinical review, 45% were performing an internal quality control (IQC) test and 82% were performing external quality assurance (EQA) on a regular basis. CONCLUSION: PSM outside trial conditions is as clinically effective as routine UK care.

An evidence-based review and guidelines for patient self-testing and management of oral anticoagulation.

There is a limited evidence base for self-testing and -management for oral anticoagulation management. Available data suggest that these are credible models for a significant minority of patients if underpinned by structured training and follow-up. The guidelines presented are necessarily consensual and outline procedures for patient selection, training, product procurement, product maintenance, quality assurance procedures, dosage adjustment and clinical supervision. The cost-effectiveness of these models remains to be elucidated within the UK. Further data on both health economic and clinical outcomes are required from UK based studies before widespread implementation of self-testing and management can be recommended on a wider scale.

Self management of oral anticoagulation: randomised trial.

OBJECTIVE: To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. DESIGN: Multicentre open randomised controlled trial. SETTING: Midlands region of the UK. PARTICIPANTS: 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. INTERVENTION: Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. MAIN OUTCOME MEASURE: Percentage of time spent within the therapeutic range of international normalised ratio. RESULTS: No significant differences were found in percentage of time in the therapeutic range between self management and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (chi2(df = 1) = 0.02, P = 0.89). CONCLUSION: With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375.

Point of care testing for INR monitoring: where are we now?

Point of care (POC, or near patient) testing for measurement of the international normalized ratio (INR) has facilitated the devolution of service delivery from the traditional hospital outpatient setting. However it must be undertaken within the confines of safe practice involving quality control procedures. The evaluation of INR POC tests should be closely related to the clinical issues of management and, specifically, improving the quality of care. One benefit of POC testing is in the increased motivation that some practitioners feel, being able to perform diagnostic tests without sending samples to a laboratory. POC for INR testing within primary care eliminates the delay in waiting for the result to be processed by the hospital laboratory, and the subsequent delay in informing the patient of their dosing advice. This review describes the utilization of POC testing outside the laboratory setting to develop models of care for oral anticoagulation management.

Patient self-management of oral anticoagulation and external quality assessment procedures.

The role of external quality assessment (EQA) is a contentious issue for patient self-management (PSM) of oral anticoagulation. Patients from general practices in the West Midlands undertaking PSM were recruited to compare efficacy of patients' and health professionals' EQA procedure using the UK National External Quality Assessment Scheme (NEQAS). Patients using Coaguchek (Roche Diagnostics) were trained to perform EQA as part of their PSM training. They undertook PSM for 26 weeks and were asked to perform EQA using material provided by the UK NEQAS twice at home without supervision and twice at the practice with supervision. Patients' results were compared with health care professional users of Coaguchek S. Twenty-three PSM patients were compared with 75 health care professional users of the NEQAS scheme. The PSM group international normalized ratio (INR) percentage time in range was 74%. There was no significant difference in the median results on NEQAS samples obtained by the patients and those obtained by professionals. Three patients were outwith consensus (results > 15% from the median INR) on more than one occasion. Patients were able to perform the EQA tests competently. The data show that good agreement can be achieved between patients analysing the same EQA samples, with coefficients of variation ranging from 22.3% to as low as 5.4%. Further study is required to determine how precision within these EQA schemes relates to the stability of treatment in patients' management of their own anticoagulation.

External quality assessment for warfarin dosing using computerised decision support software.

AIM: To establish and evaluate an external quality assessment scheme for warfarin dosing for users of a computerised decision support system, BAP-PC. DESIGN: Analysis of 12 months of clinical data from 10 primary care centres using BAP-PC within an oral anticoagulation clinic. Data were analysed for individual centres and compared with aggregated data for all practices. Individual feedback forms were provided to participating centres. RESULTS: A total patient population of 367 (range, 17-65/centre) was analysed. On average, patients spent 69% of time in the therapeutic range (range, 60-76%). Patients were seen on average every 27 days (range, 24-30). The average point prevalence was 86% (range, 76-100%). In total, 33 adverse events were reported (0-13/practice). Serious adverse events ranged from 0 to 1 for each practice. This translates into a serious adverse event rate of 1.6/100 patient years. CONCLUSIONS: Practices were successful in maintaining good therapeutic international normalised ratio control, with centres achieving 60% or higher time in range. There are some doubts about the quality of data collection at a practice level because there were no reported events in half of the participating centres. The observed event rates do concur with previously reported data, however. Further cycles of the scheme are necessary to establish it as a useful research and benchmarking tool.

A systematic review of outcome measures reported for the therapeutic effectiveness of oral anticoagulation.

AIMS: To evaluate the evidence of therapeutic international normalised ratio (INR) control reporting and to provide recommendations for future reporting, particularly for research and audit purposes. METHODS: A systematic review of literature published over a five year period describing therapeutic INR control. Papers were identified from the Medline electronic database, and those that met the quality criteria were reviewed independently by an academic general practitioner and a consultant haematologist. RESULTS: Fifteen papers were identified that met the quality criteria for review. The sample size of studies ranged from 53 to 2545 (mean, 483.9) patients. Follow up ranged from three months to 13 years. Twelve studies reported results from secondary care only, one from primary care only, and two from both primary and secondary care. Seven of the 15 papers reported percentage time in range, five of 15 papers reported mean INR, six of 15 papers reported the proportion of tests in range, and five of 15 papers reported mean warfarin dose. Additional methods of presenting INR results were: dose changes each month, distribution of INR results, deviation of INR value from mean, percentage dose changes, time between visits, and median INR value. Six papers reported only one outcome measure, six reported two outcomes, two papers reported three outcomes, and one paper reported five outcomes. CONCLUSIONS: It is recommended that at least two outcome measures should be reported and measures should be selected so that both the INR determinations and dosing advice are monitored.

A randomised controlled trial of patient self management of oral anticoagulation treatment compared with primary care management.

BACKGROUND: The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring. Patient self management for oral anticoagulation is a model new to the UK. This randomised trial was the first to compare routine primary care management of oral anticoagulation with patient self management. AIM: To test whether patient self management is as safe, in terms of clinical effectiveness, as primary care management within the UK, as assessed by therapeutic international normalised ratio (INR) control. METHOD: Patients receiving warfarin from six general practices who satisfied study entry criteria were eligible to enter the study. Eligible patients were randomised to either intervention (patient self management) or control (routine primary care management) for six months. The intervention comprised two training sessions of one to two hours duration. Patients were allowed to undertake patient self management on successful completion of training. INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed. Patients were advised to perform INR tests every two weeks, or weekly if a dose adjustment was made. Dosage adjustment was undertaken using a simple dosing algorithm. RESULTS: Seventy eight of 206 (38%) patients were eligible for inclusion and, of these, 35 (45%) declined involvement or withdrew from the study. Altogether, 23 intervention and 26 control patients entered the study. There were no significant differences in INR control (per cent time in range: intervention, 74%; control, 77%). There were no serious adverse events in the intervention group, with one fatal retroperitoneal haemorrhage in the control group. Costs of patient self management were significantly greater than for routine care (pound 90 v pound 425/patient/year). CONCLUSION: These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population. Further studies are needed to elucidate whether this model of care is suitable for a larger population.

Does the Birmingham model of oral anticoagulation management in primary care work outside trial conditions?

The effectiveness of the Birmingham model of primary care oral anticoagulation management has previously been demonstrated within a randomised controlled trial. The aim of this study was to assess the effectiveness of the Birmingham model in routine care. All patients from 12 primary care centres attending either practice-based or hospital-based anticoagulation clinics were retrospectively followed up from October 1996 to March 1998. Outcome measures were therapeutic International Normalised Ratio (INR) control, haemorrhagic and thrombotic episodes, and recall frequency; 452 patients who had two or more INR results during the follow-up period were investigated. There were no significant differences between practice-based and hospital-based populations in terms of the percentage time in range, (69% and 64% respectively). The proportion of tests in range was significantly higher in the practice-based group (61% practice-based, 57% hospital-based; P = 0.015). There was no difference between the two populations in terms of mean follow-up time (36 days in each group). There were no significant differences between groups for the number of clinical outcomes per patient. This study confirmed that, within these practices, oral anticoagulation management is safe and effective using the Birmingham model.

Oral anticoagulation management in primary care with the use of computerized decision support and near-patient testing: a randomized, controlled trial.

BACKGROUND: There is increased pressure on primary care physicians to monitor oral anticoagulation. OBJECTIVE: To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic, involving near-patient testing and computerized decision support software, compared with routine hospital management based on a variety of clinical outcome measures. METHODS: A randomized, controlled trial in 12 primary care practices in Birmingham, England (9 intervention and 3 control). Two control populations were used: patients individually randomly allocated as controls in the intervention practices (intrapractice controls) and all patients in control practices (interpractice controls). Intervention practices' patients were randomized to the intervention (practice-based anticoagulation clinic) or control (hospital clinic) group. The main outcome measure was therapeutic control of the international normalized ratio. RESULTS: Three hundred sixty-seven patients were recruited (122 intervention patients, 102 intrapractice control patients, and 143 interpractice control patients). Standard measures of control of the international normalized ratio (point prevalence) showed no significant difference between the intervention and control groups. Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group (paired t test, P =.008). CONCLUSIONS: Nurse-led anticoagulation clinics can be implemented in novice primary care settings by means of computerized decision support software and near-patient testing. Care given by this model is at least as good as routine hospital follow-up. The model is generalizable to primary health care centers operating in developed health care systems.

Is the international normalised ratio (INR) reliable? A trial of comparative measurements in hospital laboratory and primary care settings.

AIM: To determine the reliability of international normalised ratio (INR) measurement in primary care by practice nurses using near patient testing (NPT), in comparison with results obtained within hospital laboratories by varied methods. METHODS: As part of an MRC funded study into primary care oral anticoagulation management, INR measurements obtained in general practice were validated against values on the same samples obtained in hospital laboratories. A prospective comparative trial was undertaken between three hospital laboratories and nine general practices. All patients attending general practice based anticoagulant clinics had parallel INR estimations performed in general practice and in a hospital laboratory. RESULTS: 405 tests were performed. Comparison between results obtained in the practices and those in the reference hospital laboratory (gold standard), which used the same method of testing for INR, showed a correlation coefficient of 0.96. Correlation coefficients comparing the results with the various standard laboratory techniques ranged from 0.86 to 0.92. It was estimated that up to 53% of tests would have resulted in clinically significant differences (change in warfarin dose) depending upon the site and method of testing. The practice derived results showed a positive bias ranging from 0.28 to 1.55, depending upon the site and method of testing. CONCLUSIONS: No technical problems associated with INR testing within primary care were uncovered. Discrepant INR results are as problematic in hospital settings as they are in primary care. These data highlight the failings of the INR to standardise when different techniques and reagents are used, an issue which needs to be resolved. For primary care to become more involved in therapeutic oral anticoagulation monitoring, close links are needed between hospital laboratories and practices, particularly with regard to training and quality assurance.

Vaginal estrogen creams: use patterns among a cohort of women.

OBJECTIVE: To assess the prevalence, amount, and duration of use of vaginal estrogen cream among several birth cohorts of women from 1983 through 1992. DESIGN: Analyses are based on automated membership, pharmacy, and hospital discharge databases from Group Health Cooperative (GHC) of Puget Sound, a large health maintenance organization in Seattle, Washington. PARTICIPANTS: A total of 33,822 women, aged 45 years and older as of December 31, 1983, who were enrolled in GHC from 1983 to 1992 or who were enrolled at baseline and died in the following decade. RESULTS: About 24% of the cohort had filled at least one prescription for vaginal estrogen cream during 1983 through 1992, and about 60% of the users had more than one prescription filled. The annual birth cohort-specific prevalence of having filled one or more prescriptions for vaginal estrogen creams ranged between 1.6 and 8.2% across birth cohorts, whereas the average annual prevalence for the cohort was between 5.3 and 6.8%. The total amount, duration of use, and proportion of total estrogen exposure from creams increased with age of the birth cohort. Among the 733 women with intact uteri who were long-term cream users, 60.4% had no progestin prescriptions while averaging 22.1 tubes of estrogen cream. CONCLUSION: The prescription-filling patterns for estrogen in this cohort show an increase in the amount, years of use, and proportion of estrogen exposure from creams with the age of the birth cohort and extensive unopposed cream use among a small proportion of women with intact uteri. The systemic effects of vaginal estrogen cream among older postmenopausal women with urogenital atrophy deserve closer scrutiny.