Attentional bias retraining in cigarette smokers attempting smoking cessation (ARTS): study protocol for a double blind randomised controlled trial.

BACKGROUND: Smokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking. Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation. METHODS/DESIGN: This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training. Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal nicotine patches for 8-12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at 4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months and 6 months post-quit. DISCUSSION: This is the first randomised controlled trial of attentional retraining in smokers attempting cessation. This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN54375405.

Iodine status of UK schoolgirls: a cross-sectional survey.

BACKGROUND: Iodine deficiency is the most common cause of preventable mental impairment worldwide. It is defined by WHO as mild if the population median urinary iodine excretion is 50-99 µg/L, moderate if 20-49 µg/L, and severe if less than 20 µg/L. No contemporary data are available for the UK, which has no programme of food or salt iodination. We aimed to assess the current iodine status of the UK population. METHODS: In this cross-sectional survey, we systematically assessed iodine status in schoolgirls aged 14-15 years attending secondary school in nine UK centres. Urinary iodine concentrations and tap water iodine concentrations were measured in June-July, 2009, and November-December, 2009. Ethnic origin, postcode, and a validated diet questionnaire assessing sources of iodine were recorded. FINDINGS: 810 participants provided 737 urine samples. Data for dietary habits and iodine status were available for 664 participants. Median urinary iodine excretion was 80·1 µg/L (IQR 56·9-109·0). Urinary iodine measurements indicative of mild iodine deficiency were present in 51% (n=379) of participants, moderate deficiency in 16% (n=120), and severe deficiency in 1% (n=8). Prevalence of iodine deficiency was highest in Belfast (85%, n=135). Tap water iodine concentrations were low or undetectable and were not positively associated with urinary iodine concentrations. Multivariable general linear model analysis confirmed independent associations between low urinary iodine excretion and sampling in summer (p<0·0001), UK geographical location (p<0·0001), low intake of milk (p=0·03), and high intake of eggs (p=0·02). INTERPRETATION: Our findings suggest that the UK is iodine deficient. Since developing fetuses are the most susceptible to adverse effects of iodine deficiency and even mild perturbations of maternal and fetal thyroid function have an effect on neurodevelopment, these findings are of potential major public health importance. This study has drawn attention to an urgent need for a comprehensive investigation of UK iodine status and implementation of evidence-based recommendations for iodine supplementation. FUNDING: Clinical Endocrinology Trust.

The relationship between serum TSH and free T4 in older people.

The frequency distribution of serum thyroid stimulating hormone (TSH) shows a skewed pattern that may change with age. The set point of the hypothalamic-pituitary-thyroid axis for an individual is thought to be genetically determined and has been described as a log-linear relationship of serum TSH to free thyroxine (T4); however, the validity of this hypothesis has yet to be established in older people. The aim of the study was to describe the relationship between serum TSH and free T4 in older people and define factors influencing this relationship. We conducted a cross-sectional, observational study of thyroid function in a community population of older subjects over 65 years of age. The relationship between serum TSH and free T4 was not linear as previously described, but is best described as a fourth-order polynomial. Both gender and smoking status affected the relationship. This suggests that more complex modelling is required when investigating the hypothalamic-pituitary-thyroid axis.

Does self-management of oral anticoagulation therapy improve quality of life and anxiety?

BACKGROUND: Research related to service requirements for anticoagulation management has focussed on clinical and health economic outcomes and paid little attention to the impact of treatment and service delivery on patients' quality of life. This was the first large UK study to evaluate the effect of patient self-management (PSM) of oral anticoagulation on treatment-related quality of life (TRQoL) and anxiety in comparison with routine care (RC) and to explore the effect of level of therapeutic control on TRQoL and anxiety across and within each model of care. METHODS: A quantitative survey, set in primary care in the West Midlands. The subjects were 517 randomized controlled trial participants, 242 receiving PSM and 275 RC. Postal questionnaires at baseline and 12 months comprised the State Trait Anxiety Inventory and a treatment-specific measure of positive (satisfaction and self-efficacy) and negative aspects (daily hassles, strained social network and psychological distress) of TRQoL. Change in anxiety and TRQoL scores were compared between PSM and RC. Subgroup analysis was based upon level of therapeutic control (high, medium and low). RESULTS: Overall, 83% (n = 202) PSM and 55% (n = 161) RC patients contributed data. Anxiety scores were similar in both groups. PSM demonstrated greater improvement in self-efficacy than RC across the study period. A statistically significant between-group difference (PSM versus RC) in the self-efficacy also existed in subgroups with medium and high levels of therapeutic control. CONCLUSIONS: PSM is not associated with increased anxiety and has a positive effect upon some aspects of TRQoL compared to RC.

Inverted BMI rather than BMI is a better proxy for percentage of body fat.

BACKGROUND: Percentage of body fat (BF%) is a known risk factor for a range of healthcare problems but is difficult to measure. An easy to measure proxy is the weight/height(2) ratio known as the Body Mass Index (BMI kg/m(2)). However, BMI does have some inherent weaknesses which are readily overcome by its inverse iBMI (1000/BMI, cm(2)/kg). METHODS: The association between BF% and both BMI and iBMI together with their distributional properties was explored using previously published data from healthy (n = 2993) and diseased populations (n = 298). RESULTS: BMI is skewed whereas iBMI is symmetrical and so is better approximated by the normal distribution. The relationship between BF% and BMI is curved, but that of iBMI and BF% is linear and thus iBMI explains more of the variation in BF% than BMI. For example a unit increase in BMI for a group of thin women represents an increase of 2.3% in BF, but for obese women this represents only a 0.3% increase in BF-a 7-fold difference. The curvature stems from body mass being the numerator in BMI but the denominator in BF% resulting in a form of hyperbolic curve which is not the case with iBMI. Furthermore, BMI and iBMI have different relationships (interaction) with BF% for men and women, but these differences are less marked with iBMI. CONCLUSIONS: Overall, these characteristics of iBMI favour its use over BMI, especially in statistical models.

Comparison of imputation methods for handling missing covariate data when fitting a Cox proportional hazards model: a resampling study.

BACKGROUND: The appropriate handling of missing covariate data in prognostic modelling studies is yet to be conclusively determined. A resampling study was performed to investigate the effects of different missing data methods on the performance of a prognostic model. METHODS: Observed data for 1000 cases were sampled with replacement from a large complete dataset of 7507 patients to obtain 500 replications. Five levels of missingness (ranging from 5% to 75%) were imposed on three covariates using a missing at random (MAR) mechanism. Five missing data methods were applied; a) complete case analysis (CC) b) single imputation using regression switching with predictive mean matching (SI), c) multiple imputation using regression switching imputation, d) multiple imputation using regression switching with predictive mean matching (MICE-PMM) and e) multiple imputation using flexible additive imputation models. A Cox proportional hazards model was fitted to each dataset and estimates for the regression coefficients and model performance measures obtained. RESULTS: CC produced biased regression coefficient estimates and inflated standard errors (SEs) with 25% or more missingness. The underestimated SE after SI resulted in poor coverage with 25% or more missingness. Of the MI approaches investigated, MI using MICE-PMM produced the least biased estimates and better model performance measures. However, this MI approach still produced biased regression coefficient estimates with 75% missingness. CONCLUSIONS: Very few differences were seen between the results from all missing data approaches with 5% missingness. However, performing MI using MICE-PMM may be the preferred missing data approach for handling between 10% and 50% MAR missingness.

Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study.

BACKGROUND: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. METHODS: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. RESULTS: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. CONCLUSION: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR.

Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines.

BACKGROUND: Multiple imputation (MI) provides an effective approach to handle missing covariate data within prognostic modelling studies, as it can properly account for the missing data uncertainty. The multiply imputed datasets are each analysed using standard prognostic modelling techniques to obtain the estimates of interest. The estimates from each imputed dataset are then combined into one overall estimate and variance, incorporating both the within and between imputation variability. Rubin's rules for combining these multiply imputed estimates are based on asymptotic theory. The resulting combined estimates may be more accurate if the posterior distribution of the population parameter of interest is better approximated by the normal distribution. However, the normality assumption may not be appropriate for all the parameters of interest when analysing prognostic modelling studies, such as predicted survival probabilities and model performance measures. METHODS: Guidelines for combining the estimates of interest when analysing prognostic modelling studies are provided. A literature review is performed to identify current practice for combining such estimates in prognostic modelling studies. RESULTS: Methods for combining all reported estimates after MI were not well reported in the current literature. Rubin's rules without applying any transformations were the standard approach used, when any method was stated. CONCLUSION: The proposed simple guidelines for combining estimates after MI may lead to a wider and more appropriate use of MI in future prognostic modelling studies.

Self-testing for cancer: a community survey.

BACKGROUND: Cancer-related self-tests are currently available to buy in pharmacies or over the internet, including tests for faecal occult blood, PSA and haematuria. Self-tests have potential benefits (e.g. convenience) but there are also potential harms (e.g. delays in seeking treatment). The extent of cancer-related self-test use in the UK is not known. This study aimed to determine the prevalence of cancer-related self-test use. METHODS: Adults (n = 5,545) in the West Midlands were sent a questionnaire that collected socio-demographic information and data regarding previous and potential future use of 18 different self-tests. Prevalence rates were directly standardised to the England population. The postcode based Index of Multiple Deprivation 2004 was used as a proxy measure of deprivation. RESULTS: 2,925 (54%) usable questionnaires were returned. 1.2% (95% CI 0.83% to 1.66%) of responders reported having used a cancer related self test kit and a further 36% reported that they would consider using one in the future. Logistic regression analyses suggest that increasing age, deprivation category and employment status were associated with cancer-related self-test kit use. CONCLUSION: We conclude that one in 100 of the adult population have used a cancer-related self-test kit and over a third would consider using one in the future. Self-test kit use could alter perceptions of risk, cause psychological morbidity and impact on the demand for healthcare.

Standardisation of rates using logistic regression: a comparison with the direct method.

BACKGROUND: Standardisation of rates in health services research is generally undertaken using the direct and indirect arithmetic methods. These methods can produce unreliable estimates when the calculations are based on small numbers. Regression based methods are available but are rarely applied in practice. This study demonstrates the advantages of using logistic regression to obtain smoothed standardised estimates of the prevalence of rare disease in the presence of covariates. METHODS: Step by step worked examples of the logistic and direct methods are presented utilising data from BETS, an observational study designed to estimate the prevalence of subclinical thyroid disease in the elderly. Rates calculated by the direct method were standardised by sex and age categories, whereas rates by the logistic method were standardised by sex and age as a continuous variable. RESULTS: The two methods produce estimates of similar magnitude when standardising by age and sex. The standard errors produced by the logistic method were lower than the conventional direct method. CONCLUSION: Regression based standardisation is a practical alternative to the direct method. It produces more reliable estimates than the direct or indirect method when the calculations are based on small numbers. It has greater flexibility in factor selection and allows standardisation by both continuous and categorical variables. It therefore allows standardisation to be performed in situations where the direct method would give unreliable results.

Different faecal sampling methods alter the acceptability of faecal occult blood testing: a cross sectional community survey.

BACKGROUND: A bowel cancer screening programme is being introduced in the UK. The programme will screen men and women aged 60-69 using faecal occult blood testing (FOBt). Uptake rates in the pilot evaluation were <60%. This study aimed to determine whether the acceptability of FOBt is associated with the sampling method or previous exposure to FOBt. METHODS: Postal questionnaire assessing the perceived acceptability of three potential methods of FOBt sampling: (1) sterile transport swab; (2) smear card [as used in the national screening roll-out]; (3) faecal specimen pot [routinely used in the NHS for stool samples]. Study population comprised those aged 50-69. RESULTS: Response rate was 63%. FOBt was reported as acceptable by 94.5%. Acceptability fell significantly when sampling methods were detailed. The swab was rated more acceptable than the card or the pot (90.2% versus 62.9% versus 63.0%, p<0.0005). FOBt acceptability did not vary with previous experience of FOBt. CONCLUSIONS: The acceptability of FOBt varied by the sampling method described. The smear card, such as that used in the national screening programme, was the least preferred method. To increase the uptake of screening, alternative methods of faecal sampling should be considered.

Lack of attentional retraining effects in cigarette smokers attempting cessation: a proof of concept double-blind randomised controlled trial.

BACKGROUND: Observational studies have shown that attentional bias for smoking-related cues is associated with increased craving and relapse. Laboratory experiments have shown that manipulating attentional bias may change craving. Interventions to reduce attentional bias could reduce relapse in smokers seeking to quit. We report a clinical trial of attentional retraining in treatment-seeking smokers. METHODS: This was a double-blind randomised controlled trial that took place in UK smoking cessation clinics. Smokers interested in quitting were randomised to five weekly sessions of attentional retraining (N=60) or placebo training (N = 58) using a modified visual probe task from one week prior to quit day. Both groups received 21 mg nicotine patches (from quit day onwards) and behavioural support. Primary outcomes included change in attentional bias reaction times four weeks after quit day on the visual probe task and craving measured weekly using the Mood and Physical Symptoms Scale. Secondary outcomes were changes in withdrawal symptoms, time to first lapse and prolonged abstinence. RESULTS: No attentional bias towards smoking cues was found in the sample at baseline (mean difference = 3 ms, 95% CI = -2, 9). Post-training bias was not significantly lower in the retraining group compared with the placebo group (mean difference = -9 ms, 95% CI = -20, 2). There was no difference between groups in change in craving (p = 0.89) and prolonged abstinence at four weeks (risk ratio = 1.00, 95% CI = 0.70, 1.43). CONCLUSIONS: Taken with one other trial, there appears to be no effect from clinic-based attentional retraining using the visual probe task. Attentional retraining conducted out of clinic may prove more effective. CLINICAL TRIAL REGISTRATION: UK Clinical Trials ISRCTN 54375405.

Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.

The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Does lower-body BMD develop at the expense of upper-body BMD in female runners?

PURPOSE: Evidence suggests that exercise plays an important role in stimulating site-specific bone mineral density (BMD). However, what is less well understood is how these benefits dissipate throughout the body. Hence, the purpose of the present study was to compare the levels of, and the correlation between, BMD recorded at 10 sites in female endurance runners, and to investigate possible determinants responsible for any inter-site differences observed. METHODS: Repeated measures ANOVA was used to compare the BMD between sites and factor analysis was used to describe the pattern of intersite correlations. Allometric ANCOVA was used to identify the primary determinants of bone mass and how these varied between sites. RESULTS: The ANOVA and factor analysis identified systematic differences in BMD between sites, with the greatest BMD being observed in the lower-body sites, in particular the legs. An investigation into the possible mechanisms responsible for these differences revealed "distances run" (km.wk-1) as a positive, and "years of training" as a negative determinant of bone mass (P < 0.001). However, the effect of a number of determinants varied between sites (P < 0.05). Specifically, the ANCOVA identified that running further distances resulted in higher bone mass in the arms and legs. In contrast, training for additional years appeared to result in lower bone mass in the arms and lumbar spine. Calcium intake was also found to be positively associated with bone mass in the legs but negatively associated at all other sites. CONCLUSIONS: A combination of running exercise and calcium intake would appear to stimulate the bone mass of women endurance runners at lower-body sites but at the expense of bone mass at upper-body sites.

A comparison of Bayesian and maximum likelihood methods to determine the performance of a point of care test for Helicobacter pylori in the office setting.

OBJECTIVE: Evaluations of point of care tests (PCT) are often hampered by a lack of appropriate gold standards. This study aimed to compare the results of a Bayesian statistical analysis and a maximum likelihood method to evaluate the performance of a PCT for Helicobacter pylori in primary care. METHODS: The Helisal Rapid Blood Test (Cortecs Diagnostics) was performed in 311 patients from 6 primary care centers, and a concurrent venous sample was taken for 2 enzyme-linked immunosorbent assays (ELISA) performed at the laboratory, blind to the PCT result. The Bayesian analysis was conducted using Markov Chain Monte Carlo methods (WinBUGS). The performance characteristics of the PCT and the 2 ELISA tests were estimated together with 95% credible intervals (95% CIs). RESULTS: The estimate of prevalence of H. pylori in this population was 64% (95% CI, 59% to 70%), the sensitivity and specificity of the PCT were 89% (84% to 94%) and 84% (77% to 91%), respectively (likelihood ratios positive 5.6, negative 0.13). The equivalent maximum likelihood results were prevalence, 65%; sensitivity, 90%; and specificity, 83%. CONCLUSIONS: The Helisal Rapid Blood Test performed as well as laboratory-based ELISA tests in this cohort of patients. The Bayesian analysis and the maximum likelihood method gave similar results, the Bayesian method also simultaneously estimating 95% CIs.

The relationship between serum TSH and free T4 in older people.

The frequency distribution of serum thyroid stimulating hormone (TSH) shows a skewed pattern that may change with age. The set point of the hypothalamic-pituitary-thyroid axis for an individual is thought to be genetically determined and has been described as a log-linear relationship of serum TSH to free thyroxine (T4); however, the validity of this hypothesis has yet to be established in older people. The aim of the study was to describe the relationship between serum TSH and free T4 in older people and define factors influencing this relationship. We conducted a cross-sectional, observational study of thyroid function in a community population of older subjects over 65 years of age. The relationship between serum TSH and free T4 was not linear as previously described, but is best described as a fourth-order polynomial. Both gender and smoking status affected the relationship. This suggests that more complex modelling is required when investigating the hypothalamic-pituitary-thyroid axis.

Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease.

BACKGROUND: Common autoimmune disorders tend to coexist in the same subjects and to cluster in families. METHODS: We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents. RESULTS: The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P=.005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative "clustering" of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases. CONCLUSION: This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.

The effect of walking on fitness, fatness and resting blood pressure: a meta-analysis of randomised, controlled trials.

OBJECTIVE: The purpose of this review was to perform a meta-analysis on walking intervention studies in order to quantify the magnitude and direction of walking-induced changes that may alter selected cardiovascular risk factors. METHOD: Twenty-four randomised controlled trials of walking were assessed for quality on a three-point scale. Data from these studies were pooled and treatment effects (TEs) were calculated for six traditional cardiovascular risk variables: body weight, body mass index (BMI), percentage body fat, aerobic fitness (V(O(2) )max in ml kg(-1) min(-1)) and resting systolic and diastolic blood pressure. Weighted TEs were analysed using a random effects model with weights obtained using the inverse of the individual TE variances. Random effects models were used to investigate the influence of both study quality and exercise volume (<150 vs. > or =150 min week(-1)). RESULTS: Random effects modelling showed that walking interventions increased V(O(2) )max and decreased body weight, BMI, percent body fat and resting diastolic blood pressure in previously sedentary adults (p<0.05 for all). CONCLUSION: The results of this study provide evidence that healthy but sedentary individuals who take up a programme of regular brisk walking improves several known risk factors for cardiovascular disease.

Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study.

OBJECTIVES: This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy. BACKGROUND: Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality. METHODS: A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. RESULTS: A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months. CONCLUSIONS: Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.