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.

Scaling concept II rowing ergometer performance for differences in body mass to better reflect rowing in water.

We investigated whether the concept II indoor rowing ergometer accurately reflects rowing on water. Forty-nine junior elite male rowers from a Great Britain training camp completed a 2000 m concept II model C indoor rowing ergometer test and a water-based 2000 m single-scull rowing test. Rowing speed in water (3.66 m/s) was significantly slower than laboratory-based rowing performance (4.96 m/s). The relationship between the two rowing performances was found to be R2=28.9% (r=0.538). We identified that body mass (m) made a positive contribution to concept II rowing ergometer performance (r=0.68, P<0.001) but only a small, non-significant contribution to single-scull water rowing performance (r=0.039, P=0.79). The contribution that m made to single-scull rowing in addition to ergometer rowing speed (using allometric modeling) was found to be negative (P<0.001), confirming that m has a significant drag effect on water rowing speed. The optimal allometric model to predict single-scull rowing speed was the ratio (ergometer speed xm(-0.23))1.87 that increased R2 from 28.2% to 59.2%. Simply by dividing the concept II rowing ergometer speed by body mass (m0.23), the resulting "power-to-weight" ratio (ergometer speed xm(-0.23)) improves the ability of the concept II rowing performance to reflect rowing on water.

The bone-anchored hearing aid in the rehabilitation of single-sided deafness: experience with 58 patients.

OBJECTIVES: To assess the efficacy of the bone-anchored hearing aid (BAHA) in the rehabilitation of single-sided deafness (SSD). STUDY DESIGN: Retrospective case-control series review. SETTING: Tertiary referral unit. PATIENTS: Fifty-eight consecutive patients that had a bone-anchored hearing aid for single-sided deafness completed outcome questionnaires, building upon earlier audiological assessment of 19 patients. Single-sided deafness controls (n = 49) were mainly acoustic neuroma patients. MAIN OUTCOME MEASUREMENTS: speech discrimination testing in directional noise, speech and spatial qualities of hearing questionnaire and the Glasgow Benefit Inventory (GBI). RESULTS: The mean follow-up time was 28.4 months. Five (13%) of the bone-anchored hearing aid patients were non-users because of lack of benefit. The audiometric testing confirmed that when noise was on the bone-anchored hearing aid side speech perception was reduced but benefited when noise was on the side of the hearing ear. There was no difference between the Speech and Spatial Qualities of Hearing Scores in bone-anchored hearing aid users and controls. In particular there was no difference in the spatial subscores. In the bone-anchored hearing aid users the median Glasgow Benefit Inventory score was 11. If the non-users are included then 13 (22%) patients had no or detrimental (negative) Benefit scores. No or negative benefit scores were more frequent in those deaf for <10 years. In open-field questions, patients felt the bone-anchored hearing aid was most useful in small groups or in 'one-to-one' conversation. CONCLUSIONS: Bone-anchored hearing aid rehabilitation for single-sided deafness is less successful than for other indications, reflected here by relatively low median Glasgow Benefit Inventory scores. There was also no significant difference between controls and bone-anchored hearing aid users in the Speech and Spatial Qualities of Hearing Questionnaire. Patients with a longer duration of deafness report greater subjective benefit than those more recently deafened, perhaps due to differing expectations.

Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism.

CONTEXT: There is little consensus regarding the most appropriate dose of radioiodine ((131)I) to be administered to patients with hyperthyroidism. OBJECTIVE: To compare the efficacy of fixed dose regimens of (131)I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients. DESIGN: Consecutive series of hyperthyroid subjects treated with (131)I. SETTING: Single Secondary/Tertiary Care Hospital Clinic. PARTICIPANTS: A total of 1278 patients (1013 females and 262 males, mean age 49.7 years) presenting with hyperthyroidism between 1984 and 2006. INTERVENTION: Treatment with (131)I using a fixed dose regimen. MAIN OUTCOME MEASURES: Probability of cure and risk of development of hypothyroidism following a single dose of (131)I. RESULTS: Patients given a single dose of (131)I of 600 MBq (n = 485) had a higher cure rate (84.1%) compared with those receiving either 370 MBq (74.9%, P < 0.001) or those given 185 Bq (63%, P < 0.001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60.4%; 370 MBq: 49.2%, P = 0.001; 185 Bq: 38.1%, P < 0.001). Binary logistic regression analysis identified a 600 Bq dose of (131)I [adjusted odds ratio, AOR 3.33 (2.28-4.85), P < 0.001], female gender [AOR 1.75 (1.23-2.47), P = 0.002], lower presenting serum free T4 concentration [AOR 1.01 (1.01-1.02), P < 0.001] and absence of a palpable goitre [AOR 3.33 (2.00-5.56), P < 0.001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3.79 (2.66-5.38), P < 0.001], female gender [AOR 1.46 (1.05-2.02), P = 0.02], younger age [AOR 1.03 (1.02-1.04), P < 0.001], absence of a palpable goitre [AOR 3.85 (2.38-5.88), P < 0.001] and presence of ophthalmopathy [AOR 1.57 (1.06-2.31), P = 0.02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived. CONCLUSIONS: Simple clinical/biochemical criteria can be used to predict outcome after (131)I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure.

Screening for dyslexia, dyspraxia and Meares-Irlen syndrome in higher education.

This study reports a comparison of screening tests for dyslexia, dyspraxia and Meares-Irlen (M-I) syndrome in a Higher Education setting, the University of Worcester. Using a sample of 74 volunteer students, we compared the current tutor-delivered battery of 15 subtests with a computerized test, the Lucid Adult Dyslexia Screening test (LADS), and both of these with data on assessment outcomes. The sensitivity of this tutor battery was higher than LADS in predicting dyslexia, dyspraxia or M-I syndrome (91% compared with 66%) and its specificity was lower (79% compared with 90%). Stepwise logistic regression on these tests was used to identify a better performing subset of tests, when combined with a change in practice for M-I syndrome screening. This syndrome itself proved to be a powerful discriminator for dyslexia and/or dyspraxia, and we therefore recommend it as the first stage in a two-stage screening process. The specificity and sensitivity of the new battery, the second part of which comprises LADS plus four of the original tutor delivered subtests, provided the best overall performance: 94% sensitivity and 92% specificity. We anticipate that the new two-part screening process would not take longer to complete.

Association between serum free thyroxine concentration and atrial fibrillation.

BACKGROUND: Previous studies have suggested that minor changes in thyroid function are associated with risk of atrial fibrillation (AF). Our objective was to determine the relationship between thyroid function and presence of atrial fibrillation (AF) in older subjects. METHODS: A population-based study of 5860 subjects 65 years and older, which excluded those being treated for thyroid dysfunction and those with previous hyperthyroidism. Main outcome measures included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin [TSH]) and the presence of AF on resting electrocardiogram. RESULTS: Fourteen subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%), subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23; P<.001). After adjusting for sex, logistic regression showed a higher prevalence of AF in those with subclinical hyperthyroidism compared with euthyroid subjects (9.5% vs 4.7%; adjusted odds ratio, 2.27; P=.01). Median serum free T(4) concentration was higher in those with AF than in those without (1.14 ng/dL; interquartile range [IQR], 1.05-1.27 ng/dL [14.7 pmol/L; IQR, 13.5-16.4 pmol/L] vs 1.10 ng/dL; IQR, 1.00-1.22 ng/dL [14.2 pmol/L; IQR, 12.9-15.7 pmol/L]; P<.001), and higher in those with AF when analysis was limited to euthyroid subjects (1.13 ng/dL; IQR, 1.05-1.26 ng/dL [14.6 pmol/L; IQR, 13.5-16.2 pmol/L] vs 1.10 ng/dL; IQR, 1.01-1.21 ng/dL [14.2 pmol/L; IQR, 13.0-15.6 pmol/L]; P=.001). Logistic regression showed serum free T(4) concentration, increasing category of age, and male sex all to be independently associated with AF. Similar independent associations were observed when analysis was confined to euthyroid subjects with normal TSH values. CONCLUSIONS: The biochemical finding of subclinical hyperthyroidism is associated with AF on resting electrocardiogram. Even in euthyroid subjects with normal serum TSH levels, serum free T(4) concentration is independently associated with AF.

Conservative versus primary surgical treatment of acoustic neuromas: a comparison of rates of facial nerve and hearing preservation.

OBJECTIVES: To determine whether patients with small to medium sized acoustic neuromas managed conservatively suffer reduced rates of facial nerve and hearing preservation when compared with patients undergoing primary surgery. DESIGN: An intention-to-treat comparison between patients managed conservatively at first presentation and those managed with primary surgery. SETTING: Tertiary referral neurotological centre in Birmingham, UK. PARTICIPANTS: Data were drawn from our database of 487 sporadic acoustic neuromas managed from 1997 to present day. MAIN OUTCOME MEASURES: Facial nerve status (assessed using the House-Brackmann system) was collated for all conservatively managed patients (n = 167) and compared with that expected when calculated from primarily surgically managed tumours of equivalent size (n = 121). A chi-square test was employed to test the statistical significance of any difference. Hearing preservation (maintenance of AAO-HNS Class) in patients presenting with Class A or B hearing was compared between conservatively managed patients and those with primary surgical management. RESULTS: Observed facial nerve preservation in conservatively managed patients was significantly better (P < 0.001) than expected when calculated from rates of facial nerve preservation in surgically managed patients. Hearing preservation was also significantly more successful in conservatively managed patients (Pearson chi-square: P < 0.000). CONCLUSIONS: An initial period of conservative management is a safe and reasonable management policy in all acoustic neuromas up to 2 cm in size at the cerebello-pontine angle. Given that there are no failsafe ways of deciding potential for growth in acoustic neuromas, initial conservative management of these tumours offers superior hearing and facial nerve preservation when compared with primary surgical treatment.

Short stay emergency admissions to a West Midlands NHS Trust: a longitudinal descriptive study, 2002 2005.

OBJECTIVES: To describe changes and characteristics in emergency admissions to a West Midlands National Health Service Trust, 2002-2005, with a focus on short stay emergency admissions. METHODS: A longitudinal descriptive study using retrospective analysis of routine admissions data. Admissions were categorised as short (0/1 day) or long (>or=2 days) and examined separately using a General Linear Model. Factors favouring short stays as opposed to long stays were examined using multivariable logistic regression. RESULTS: There were 151 478 emergency admissions to the Trust between 1 April 2002 and 31 December 2005, of which 2910 (1.92%) had no discharge date recorded. Adjusted means showed a 7.76% increase in emergency admissions in winter months (October-January) and a 14.50% increase across the study period. Increases were greater in short stay (34.03%) than long stay emergency admissions (8.38%). Odds of short stays in admitted patients increased by 25%. Higher odds of short stays were also associated with younger age, winter month and medical admitting specialty (p<0.001). CONCLUSIONS: Increases in emergency admissions were greater in short stay than long stay cases. Reasons for this may be both appropriate (increased use of clinical protocols and falling average length of stay) and detrimental (pressure to meet 4 h emergency department target, changing primary care provision). Further research is needed before generalising findings to other Trusts.

Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration.

CONTEXT: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. OBJECTIVE: The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. DESIGN: The design was a prospective cohort. SETTING: The study was conducted at a single secondary/tertiary care clinic. PARTICIPANTS: One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURES: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting after 1988 (n = 1183). The final cytological or histological diagnosis was determined after surgery (n = 553) or a minimum 2-yr clinical follow-up period (mean 9.5 yr, range 2-18 yr). RESULTS: The overall sensitivity and specificity of FNAB in predicting malignancy were 88 and 84%, respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients with serum TSH greater than 0.9 mU/liter, compared with those with lower TSH. Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AORs) for the diagnosis of malignancy in subjects with serum TSH 1.0-1.7 mU/liter, compared with TSH less than 0.4 mU/liter [AOR 2.72, 95% confidence interval (CI) 1.02-7.27, P = 0.046], with further increases evident in those with TSH 1.8-5.5 mU/liter (AOR 3.88, 95% CI 1.48-10.19, P = 0.006, compared with TSH < 0.4 mU/liter) and greater than 5.5 mU/liter (AOR 11.18, 95% CI 3.23-8.63, P < 0.001, compared with TSH < 0.4 mU/liter). Males (AOR 1.8, 95% CI 1.04-3.1, P = 0.04), younger patients (AOR 1.1, 95% CI 1.01-1.15, P = 0.025), and those with clinically solitary nodules (AOR 2.53, 95% CI 1.5-4.28, P = 0.001) were also at increased risk. Based on these findings, a formula to predict the risk of the diagnosis of thyroid malignancy in individual patients, taking into account their gender, age, goiter type determined clinically, and serum TSH, was calculated. CONCLUSIONS: The risk of malignancy in a thyroid nodule increases with serum TSH concentrations within the normal range. In addition to patient's gender, age, and goiter type, the serum TSH concentration at presentation is an independent predictor of the presence of thyroid malignancy. We propose that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy.

Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking.

BACKGROUND: The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility. AIM: To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells. METHODS: Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and non-inflammatory bowel disease control patients. Telomere lengths were measured by quantitative real-time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme-linked immunosorbent serological assay and quantitative real-time polymerase chain reaction, respectively. RESULTS: Age-related telomere loss in peripheral blood lymphocytes was similar in ulcerative colitis, Crohn's disease and control patients. Telomerase activity decreased with age in all groups and correlated positively with telomere length (r = 0.489, P = 0.006). Among Crohn's disease patients, azathioprine was associated with decreased telomerase activity (0.66 vs. 1.54, P = 0.026, P < 0.05) and smoking was associated with decreased human telomerase reverse transcriptase mRNA expression (10.5 vs. 33.3, P = 0.036, P < 0.05). CONCLUSIONS: Telomere shortening is not accelerated and therefore cannot be the cause of the chromosome instability observed in ulcerative colitis peripheral blood lymphocytes. Azathioprine and cigarette smoking modify telomerase expression in these cells.

Outcome of direct restorations placed within the general dental services in England and Wales (Part 3): variation by dentist factors.

AIM: It is the aim of this paper to investigate the survival of direct-placement restorations provided within the General Dental Services in England and Wales, in relation to the dentist factors which may affect this. METHODS: For this work, survival of a restoration was considered to be the time between the date of completion of the course of treatment in which it was placed and the date of acceptance of the course of treatment when the next tooth-specific treatment was carried out on the same tooth. A modified version of Kaplan-Meier statistical methodology was used to plot survival curves for restorations placed by different subgroups of dentists. RESULTS: The age and experience of the dentist who placed the original restoration were found to be related to restoration survival, with older dentists having shorter intervals from placement of restorations to re-intervention (P<0.001). Country of qualification seems not to be relevant within Europe in terms of restoration survival, but dentists who qualified outside Europe achieve different restoration survival times for the restorations that they place. Dentist's gender has no relationship with time from restoration to re-intervention. CONCLUSIONS: Dentist factors such as age, country of qualification, and employment status, but not the gender of the dentist, have been found to influence the survival of directly placed restorations.

Analysis of an administrative database of half a million restorations over 11 years.

AIM: This paper describes the analytical approach used to extract empirical distributions of the interval from the date of placement of a direct restoration to the date when the next intervention took place on the same tooth, that is, an estimate of restoration survival. METHODS: Data, based on the complete attendance and treatment history, over the eleven years from 1991 to 2001, of a statistically representative sample of 82,537 General Dental Services' patients in England and Wales, all of whom received at least one directly placed restoration during the observation period, have been analysed. The patients on the database received a total of 719,009 courses of treatment, and there were 503,965 occasions when a tooth was directly restored. The method of analysis involved, first, the estimation of the probability that the patient will eventually return, given an interval without attending, by analysing the observed patterns of re-attendance. This estimated probability of re-attendance was then used to modify the standard Kaplan-Meier procedure to produce realistic estimates of the hazard of re-intervention. RESULTS: The results demonstrate that the newly developed methodology has produced robust estimates of the distribution of survival intervals to next intervention on the same tooth. Regarding attendance patterns, re-attendance probability varies with length of interval since last attendance. There is also a strong association with patient age. The older the patient, the more likely it is that a gap in attendance is indicative that the patient will never return. The detailed cumulative survival curve over eleven years has been plotted and forty-seven per cent of restorations, overall, survived without re-intervention for at least ten years. The entire analysis was then successfully replicated on a second, independently selected, sample of attendance and treatment records, confirming the ten-year survival estimate. CONCLUSIONS: This newly developed methodology has produced robust estimates of the distribution of survival intervals to next intervention on the same tooth. Patient re-attendance probability varies with length of interval since last attendance and with patient age. The ten-year overall survival rate to next intervention on the same tooth for direct restorations placed within the GDS in England and Wales is circa 47%.

Outcome of direct restorations placed within the general dental services in England and Wales (Part 2): variation by patients' characteristics.

AIM: It is the purpose of this paper to investigate the outcome of direct-placement restorations provided within the General Dental Services in England and Wales, and to identify the patient factors which may affect this using a database derived from patient treatment data at the Dental Practice Board. METHODS: For this work, survival of a restoration was considered to be the time between the date of completion of the course of treatment in which it was placed and the date of acceptance of the course of treatment when the next tooth-specific treatment was carried out on the same tooth. A modified version of Kaplan-Meier statistical methodology was used to plot survival curves for restorations in different subgroups of patients within the population of patients for whom data were available. RESULTS: The results indicated that patients' gender was of little significance in the long-term survival of restorations, but patient age had a significant effect, with the restorations of older patients surviving less well than those of younger patients (P<0.001). The charge-paying status of the patient had a statistically significant but small effect (P<0.001), with survival for charge-payers being slightly higher throughout the observation period. There was a strong relationship between attendance frequency and survival time, with restorations of more frequent attenders performing less well than those of less frequent attenders (P<0.001). CONCLUSIONS: Patient factors such as age, charge-paying status, interval between courses of treatment, continuity of care by one dentist, and annual gross fees incurred, have all been found to influence the survival of directly placed restorations.

Outcome of direct restorations placed within the general dental services in England and Wales (Part 1): variation by type of restoration and re-intervention.

AIM: It is the aim of this paper to consider the dental factors associated with the need for re-intervention on a restoration, such as the tooth position, size of cavity, and restoration material. METHODS: Patients whose data were included in this study were those whose birthdays were included within a set of randomly selected dates, one of which was chosen in each possible year of birth. The restoration records consisted of all those records containing directly placed restorations which related to courses of treatment of patients 18 years or older with last date on the claim form after 31st December 1990, and with date of acceptance after September 1990 and before January 2002. For each tooth treated with a direct restoration the subsequent history of intervention on that tooth was consulted, and the next date of intervention, if any could be found in the extended data set, was obtained. Thus a data set was created of direct restorations with their dates of placement and their dates, if any, of re-intervention. RESULTS: Data for over 80,000 different adult patients were analyzed, of whom 46% were male and 54% female. A total of 503,965 tooth restoration occasions were obtained from the data over a period of eleven years. Single surface amalgam restorations were found to have the longest survival --58% at 10 years, and glass ionomer the shortest 38% at 10 years. Factors which were found to reduce restoration outcome included involvement of the incisal angle in composite restorations--this resulted in a reduction in median survival of around two years--and the placement of pins in a restoration. The presence of a root filling was also found to reduce the survival of restorations in the crown of the root filled tooth. CONCLUSIONS: Small amalgam restorations have longer survival times before re-intervention than large amalgam restorations such as MOD. Composite and glass ionomer restorations perform less well than amalgam restorations. Pin placement and root filling reduce the survival time of restorations.

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.

Age and gender predict the outcome of treatment for Graves' hyperthyroidism.

The response to treatment in Graves' hyperthyroidism is unpredictable, and factors postulated to predict outcome have not generally proved clinically useful or been widely adopted in clinical practice. We audited outcome in 536 patients with Graves' hyperthyroidism presenting consecutively to determine whether simple clinical features predict disease presentation and response to treatment. At presentation males had slightly more severe biochemical hyperthyroidism [free T4: males, 64.3 +/- 3.0 pmol/L (mean +/- SE); females, 61.3 +/- 1.7 (P = 0.45); free T3: males, 24.3 +/- 1.5 pmol/L; females, 21.0 +/- 0.6, (P = 0.04)]. Patients less than 40 yr at diagnosis had more severe hyperthyroidism than patients more than 40 yr old [free T4: <40 yr, 64.3 +/- 2.0; >40 yr, 56.7 +/- 2.3 (P = 0.02); free T3: <40 yr, 22.8 +/- 0.8; >40 yr, 19.0 +/- 0.9 (P = 0.003)]. Males had a lower remission rate than females after a course of antithyroid medication [19.6% vs. 40%; odds ratio, 0.37; 95% confidence interval (CI), 0.17-0.79; P < 0.01]. Similarly, patients aged less than 40 yr had a lower remission rate than older patients (32.6% vs. 47.8%; odds ratio, 0.53; 95% CI, 0.32-0.87; P = 0.01). One dose of radioiodine cured hyperthyroidism in fewer males than females (47% vs. 74%; P < 0.0001). Logistic regression analysis demonstrated male sex (odds ratio, 2.80; 95% CI, 1.31-5.98; P = 0.008), serum free T4 concentration at diagnosis (odds ratio, 1.02; 95% CI, 1.0-1.04; P = 0.01), and dose of radioiodine administered (odds ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) were contributing factors associated with failure to respond to a single dose of radioiodine. As males and younger patients are more likely to fail to respond to medical treatment, and male patients are likewise less likely to respond to a single dose of radioiodine, we suggest that those groups with low remission rates should be offered definitive treatment with radioiodine or surgery soon after presentation and that the value of higher initial doses of radioiodine in males be evaluated.

Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer.

Differentiated thyroid cancers are the most common endocrine cancers, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumor initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor (FGF)-2. Increased expression of PTTG has been demonstrated in follicular thyroid lesions, and expression of this oncogene has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We assessed the expression of PTTG and FGF-2 and its receptor FGF-R-1 in 27 differentiated thyroid cancers, and we compared this with expression in 11 normal thyroids, 25 multinodular goiters, and 13 Graves' disease specimens. We also examined the relationship between gene expression and clinical markers of tumor behavior. PTTG and FGF-2 were overexpressed in thyroid carcinomas (9.5-fold increase, P = 0.003, and 5.0-fold increase, P < 0.001, respectively) compared with normal thyroid. Increased FGF-2 mRNA expression was independently associated with the findings of lymph node invasion (R(2) = 0.71; P < 0.001) and distant metastasis (R(2) = 0.55; P = 0.009) at tumor presentation, after taking into account known prognostic factors such as age and gender of the patient and size and type of the tumor. High PTTG expression was independently associated with tumor recurrence (R(2) = 0.64; P = 0.003). We conclude that PTTG and FGF-2 expression are potential prognostic markers (and perhaps therapeutic targets) for differentiated thyroid cancer.

The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.

Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.

Modeling elite male athletes' peripheral bone mass, assessed using regional dual x-ray absorptiometry.

There is still considerable debate as to whether bone mineral content (BMC) increases in proportion to the projected bone area, A(p), or an estimate of the skeletal bone volume, (A(p))(3/2), being assessed. The results from this study suggest that the bone mass acquisition of elite athletes' arms and legs increases in proportion to the projected bone area, A(p), having simultaneously controlled/removed the effect of the confounding variables of body mass and body fat. Although this supports the use of the traditional bone mineral density ratio (BMD=BMC/A(p)), it also highlights the dangers of overlooking the effect of known confounding variables. Ignoring the effect of such confounding variables, athletic groups whose activities involve upper body strength (rugby, rock climbing, kayaking, weight lifting) had the highest arm BMD, while runners were observed to have the lowest arm BMD (lower than that of the controls). Similarly, leg BMD was highest in rugby players, whose activities included both running and strength training. However, the rugby players were also observed to have the greatest body mass. When the important determinants of body mass, body fat, as well as projected bone area, A(p), were incorporated as covariates into a proportional allometric ANCOVA model for BMC, different conclusions were obtained. The introduction of these covariates had the effect of reducing the sporting differences on adjusted arm BMC, although the "sport" by "side" interaction still identified racket players as the only group with a greater dominant arm BMC (P < 0.05). In contrast, sporting differences in adjusted leg BMC remained highly significant, but with a rearranged hierarchy. The runners replaced the rugby players as having the greatest adjusted leg BMC. The results confirm the benefits of activity on peripheral bone mass as being site-specific but reinforce the dangers of making generalizations about the relative benefits of different exercises ignoring the effects of known confounding variables, such as body size, body composition, and age.

Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men.

There is an increasing interest in low density lipoprotein (LDL) subfractions since some of them are associated with a higher risk for coronary artery disease (CAD). Small LDL particles are particularly atherogenic and more of those are produced in hypertriglyceridaemia. However, high triglyceride concentrations are not the only explanation for the predominance of small LDL particles and other influences, including genetic factors, are also responsible for LDL particle size. We investigated LDL subfraction profiles in two groups: 46 men with and 21 men without CAD proven angiographically. For the separation of LDL subfractions, we used continuous disc polyacrylamide gel electrophoresis (PAGE) that is rapid and easier to perform than the other methods usually used which, although more precise in terms of measuring particle diameter, are much more demanding of time and equipment. The described method is suitable for routine use in assessing large numbers of patients. All studied men had triglyceride concentrations below 2.3 mmol/l. LDL scores were calculated on the basis of all LDL subfractions present in a particular profile; the higher the score, the greater the proportion of small LDL particles. LDL cholesterol (P < 0.05) and LDL score (P < 0.001) were the only significant discriminators between two groups. LDL score was significantly correlated with CAD, even after adjusting for triglyceride and HDL cholesterol concentrations and it was the best discriminant factor for the presence of CAD.