Cohort profile: the Mexico City Prospective Study.
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Adult↗
Biomedical subjects
Jonathan Emberson
Publications and source records attributed to Jonathan Emberson.
Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease.
AIMS: To estimate the potential effectiveness of different "high-risk" and "population" approaches to the primary prevention of cardiovascular disease (CVD) in middle-aged British men, after correction for regression dilution bias. METHODS AND RESULTS: We used a combination of cohort and randomised controlled trial evidence to estimate the effectiveness of high-risk strategies, based on the identification of high-risk factors or high absolute risk, and strategies based on population-wide reductions in cholesterol and blood pressure. High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population. Aggressive pharmacological treatment (using statins, beta-blockers, ACE-inhibitors and aspirin) in individuals with a 10-year Framingham event risk of >or=30% (6% of population) would have reduced major CVD by at most 11%. This figure increased to 34% at a >or=20% treatment threshold (26% of population). In contrast, modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD. Taking regression dilution bias into account, 10% reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45%. CONCLUSIONS: If high-risk strategies are to have a major impact on CVD in the population, they need to be more widely used than previously envisaged. Population-wide reduction of major risk factors is needed if CVD is to be substantially reduced.
Cardiovascular Diseases↗
The number needed to treat (NNT) can be adjusted for bias when the outcome is measured with error.
BACKGROUND AND OBJECTIVE: We consider the number needed to treat (NNT) when the event of interest is defined by dichotomizing a continuous response at a threshold level. If the response is measured with error, the resulting NNT is biased. We consider methods to reduce this bias. METHODS: Bias adjustment was studied using simulations in which we varied the distributions of the underlying response and measurement error, including both normal and nonnormal distributions. We studied a maximum likelihood estimate (MLE) based on normality assumptions, and also considered a simulation-extrapolation estimate (SIMEX) without such assumptions. The treatment effect across all potential thresholds was summarized using an NNT threshold curve. RESULTS: Crude NNT estimation was substantially biased due to measurement error. The MLE performed well under normality, and it continued to perform well with nonnormal measurement error, but when the underlying response was nonnormal the MLE was unacceptably biased and was outperformed by the SIMEX estimate. The simulation results were also reflected in empirical data from a randomized study of cholesterol-lowering therapy. CONCLUSION: Ignoring measurement error can lead to substantial bias in NNT, which can have an important practical effect on the interpretation of analyses. Analysis methods that adjust for measurement error bias can be used to assess the sensitivity of NNT estimates to this effect.
Bias↗
Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study.
OBJECTIVE: To establish the predictive accuracy of the Framingham risk score for coronary heart disease in a representative British population. DESIGN: Prospective cohort study. SETTING: 24 towns in the United Kingdom. PARTICIPANTS: 6643 British men aged 40-59 years and free from cardiovascular disease at entry into the British regional heart study. MAIN OUTCOME MEASURES: Comparison of observed 10 year coronary heart disease mortality and event rates with predicted rates for each individual, using the relevant Framingham risk equation. RESULTS: Of 6643 men, 2.8% (95% confidence interval 2.4% to 3.2%) died from coronary heart disease compared with 4.1% predicted (relative overestimation 47%, P < 0.0001). A fatal or non-fatal coronary heart disease event occurred in 10.2% (9.5% to 10.9%) of the men compared with 16.0% predicted (relative overestimation 57%, P < 0.0001). These relative degrees of overestimation were similar at all levels of coronary heart disease risk, so that overestimation of absolute risk was greatest for those at highest risk. A simple adjustment provided an improved level of accuracy. In a "high risk score" approach, most cases occur in the low risk group. In this case, 84% of the deaths from coronary heart disease and non-fatal events occurred in the 93% of men classified at low risk (< 30% in 10 years) by the Framingham score. CONCLUSION: Guidelines for the primary prevention of coronary heart disease advocate offering preventive measures to individuals at high risk. Currently recommended risk scoring methods derived from the Framingham study significantly overestimate the absolute coronary risk assigned to individuals in the United Kingdom.
Adult↗
A randomized controlled trial of exercise and manipulative therapy for cervicogenic headache.
STUDY DESIGN: A multicenter, randomized controlled trial with unblinded treatment and blinded outcome assessment was conducted. The treatment period was 6 weeks with follow-up assessment after treatment, then at 3, 6, and 12 months. OBJECTIVES: To determine the effectiveness of manipulative therapy and a low-load exercise program for cervicogenic headache when used alone and in combination, as compared with a control group. SUMMARY OF BACKGROUND DATA: Headaches arising from cervical musculoskeletal disorders are common. Conservative therapies are recommended as the first treatment of choice. Evidence for the effectiveness of manipulative therapy is inconclusive and available only for the short term. There is no evidence for exercise, and no study has investigated the effect of combined therapies for cervicogenic headache. METHODS: In this study, 200 participants who met the diagnostic criteria for cervicogenic headache were randomized into four groups: manipulative therapy group, exercise therapy group, combined therapy group, and a control group. The primary outcome was a change in headache frequency. Other outcomes included changes in headache intensity and duration, the Northwick Park Neck Pain Index, medication intake, and patient satisfaction. Physical outcomes included pain on neck movement, upper cervical joint tenderness, a craniocervical flexion muscle test, and a photographic measure of posture. RESULTS: There were no differences in headache-related and demographic characteristics between the groups at baseline. The loss to follow-up evaluation was 3.5%. At the 12-month follow-up assessment, both manipulative therapy and specific exercise had significantly reduced headache frequency and intensity, and the neck pain and effects were maintained (P < 0.05 for all). The combined therapies was not significantly superior to either therapy alone, but 10% more patients gained relief with the combination. Effect sizes were at least moderate and clinically relevant. CONCLUSION: Manipulative therapy and exercise can reduce the symptoms of cervicogenic headache, and the effects are maintained.
Adult↗
Standardized mortality ratios and fatal pulmonary embolism rates following total knee replacement: a cohort of 936 consecutive cases.
Mortality and fatal pulmonary embolism rates in 936 consecutive primary total knee replacements (TKR) were determined during a 3-month postoperative period. Postmortem examinations verified the cause of death in all but 3 patients, and follow-up was performed on all but 1 patient. All patients had elastic stockings as mechanical prophylaxis. No deaths occurred from pulmonary embolism confirmed by postmortem examinations. At worst, the fatal pulmonary embolism rate was 0.43% (4/936; confidence interval [CI]=0.14%-1.17%). The all-cause mortality rate was 0.64% (6/936; CI=0.26%-1.46%). The patient mortality was compared with the population mortality of England and Wales using standardized mortality ratios. The standardized mortality ratios for both sexes combined was 0.74 (CI=0.29-1.52). A lower mortality was observed in women (0.67) than in men (0.84) during the first 3 postoperative months compared to the general population. Fatal pulmonary embolism after TKR with the routine use of graded elastic stockings and early mobilization is rare. In this series, the death rate in patients undergoing TKR appears to be lower than that in the general population.
Aged↗