Patterns of self-management practices undertaken by cancer survivors: variations in demographic factors.

The study purpose was to examine self-management (SM) use among cancer survivors; and to explore variations in uptake of SM in survivorship and whether these differed in relation to age, income, gender, ethnicity, cancer type and treatment type. This is an important area for exploration as SM utilisation has the potential to impact on the health status, health behaviours and quality of life (QoL) of cancer survivors. A postal survey was conducted among 445 cancer survivors identified from a hospital in the West Midlands, UK. Demographic data were collected and respondents were asked to identify which practices across six SM categories - diet, exercise, complementary and alternative medicine (CAM), psychological therapies, support groups and spirituality/religion - they had used (if any). The findings indicate that the large majority (91%) had used some form of SM after their cancer treatment. Exercise (84%) and diet (56%) were the most popular SM interventions for cancer survivors and socio-demographic and cancer-related factors were associated with SM uptake. These findings can form the basis for designing and implementing appropriate SM interventions aimed at improving the health, well-being and QoL of cancer survivors.

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.

Short term effects of cocoa consumption on blood pressure.

Hypertension, defined as diastolic pressure ≥ 90 mmHg and systolic pressure ≥ 140 mmHg, is a major cause of morbidity and mortality among black populations globally. Several studies have shown that prolonged consumption of cocoa or cocoa containing products leads to decreased blood pressure (BP) in hypertensives. In this study, we investigated the flavonoid content of the top selling cocoa/cocoa based products in Trinidad and Tobago and attempted to determine if consumption of cocoa had any immediate impact on blood pressure levels. The flavonoid content of three 100% cocoa powder products and four cocoa based formulas was measured using a modified Folin-Ciocalteu procedure. The brand with the highest flavonoid content, 372 gallic acid equivalents, was selected to evaluate the short-term impact of cocoa consumption on blood pressure. Thirty-six participants comprising nineteen hypertensives and seventeen persons with normal blood pressure had their blood pressure recorded on three separate days using ambulatory blood pressure monitors; the blood pressure was recorded every half hour for eight hours. On the first day, the participants received no intervention but on the second and third days, they received either the intervention (5 g cocoa in 125 ml water) or a placebo, in any order. Statistical analysis conducted using t-test statistic and a 95% confidence interval revealed that whether participants regularly took antihypertensive medication or not, a single intervention of cocoa induced decreases in both the diastolic and systolic BPs that were significant (p = 0.0001). Mean decreases of between 8 mmHg and 18 mmHg were observed.

Assessing the value of matrix metalloproteinase 9 (MMP9) in improving the appropriateness of referrals for colorectal cancer.

BACKGROUND: A blood test may be an effective means of improving the appropriateness of referrals for symptomatic patients referred to specialist colorectal clinics. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test in indicating colorectal cancer or its precursor conditions in a symptomatic population. METHODS: Patients aged over 18, referred urgently or routinely to secondary care following primary care presentation with colorectal symptoms completed a questionnaire and provided a blood sample for serum MMP9 estimation. Univariate analysis and logistic regression modelling investigated the association between presenting symptoms, MMP9 measurements and the diagnostic outcome of patient investigations, in order to derive the combination of factors which best predicted a high risk of malignancy. RESULTS: Data were analysed for 1002 patients. Forty-seven cases of neoplasia were identified. Age, male gender, absence of anal pain, diabetes, blood in stools, urgent referral, previous bowel polyps and previous bowel cancer were significantly associated with neoplasia. Matrix metalloproteinase 9 measurements were not found to be associated with significant colorectal pathology. CONCLUSION: This study, despite robust sampling protocols, showed no clear association between MMP9 and colorectal neoplasia. Matrix metalloproteinase 9 therefore appears to have little value as a tool to aid referral decisions in the symptomatic population.

Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test.

BACKGROUND: A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population. METHODS: A cohort, aged 50-69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity. RESULTS: Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%. CONCLUSION: We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.

Maternal plasma and amniotic fluid angiogenic factors and their receptors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome.

OBJECTIVE: Angiogenic factors play a role in human placentation and may be aberrant in severe twin-to-twin transfusion syndrome (TTTS). The aim of this study was to investigate the maternal plasma and amniotic fluid angiogenic factor and receptor concentrations in twin pregnancies complicated by TTTS and to evaluate the effects of fetoscopic laser ablation. METHODS: A prospective cohort of monochorionic (MC) twins complicated by severe TTTS (n = 23) was studied between October 2006 and December 2007. A cohort of uncomplicated dichorionic (DC) (n = 12) and MC (n = 7) pregnancies were studied for comparison. Circulating angiogenic factors and their receptors were measured in the maternal plasma and the recipient twin's amniotic fluid by enzyme-linked immunosorbent assay and/or FAST Quant human angiogenesis array. RESULTS: Plasma vascular endothelial growth factor (VEGF)-C concentrations were significantly lower in TTTS than in uncomplicated twin pregnancies (P < 0.0001). In contrast, plasma angiopoietin (Ang)-2 levels and the ratio of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) to placental growth factor (PlGF) levels were significantly increased in TTTS (P < 0.01). Plasma VEGF-D was significantly increased in advanced stage TTTS (Stage III/IV cohort; P < 0.01). This was independent of fetal size, amniotic fluid volumes or the number of apparent placental arteriovenous anastomoses. In TTTS pregnancies, amniotic fluid VEGF-C, VEGF-A, Ang-1 and the sVEGFR-1/PlGF ratio were increased compared to paired maternal plasma concentrations (P < 0.0001) while amniotic fluid concentrations of PlGF, Ang-2 and soluble tyrosine kinase with immunoglobulin-like/epidermal growth factor-like domains 2 (sTie-2) were significantly lower than plasma concentrations (P < 0.0001). No significant association between maternal plasma and amniotic fluid concentrations of angiogenic factors was noted. Plasma PlGF was transiently decreased after fetoscopic laser ablation, returning to baseline by 1 week (P = 0.0314). Fetoscopic laser ablation also affected plasma sVEGFR-1/PlGF ratio with a transient increase after therapy, followed by a significant reduction to below basal concentrations by 1 week (P = 0.0102). Only VEGF-D was significantly different (+8.3%; P = 0.0155) in amniotic fluid immediately after the completion of fetoscopic laser ablation. CONCLUSION: Maternal angiogenic activity is decreased in severe TTTS, with an increased sVEGFR-1/PlGF ratio and concentrations of Ang-2 and VEGF-D in the maternal plasma compared to uncomplicated MC twin pregnancies. Maternal circulating PlGF concentrations decrease and the sVEGFR-1/PlGF ratio increases transiently in response to fetoscopic laser ablation, but in general the angiogenic factor and receptor concentrations studied are altered little by this therapy.

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.

General practitioners' attitudes to assessment of genetic risk of common disorders in routine primary care.

In 2003, the UK Department of Health set out the genetics white paper, a plan for action and investment with particular emphasis on integration of genetic health care into primary care. Since the delivery of the genetics white paper, there has been little exploration of UK primary care doctors' attitudes towards extending their role to include provision of routine genetics services. We explored explore general practitioners' (GPs) attitudes towards provision of genetic health care including routine family history screening and familial risk assessment for common disorders in primary care using a quantitative, evaluative postal survey. Only 25% (797 of 3160) of the GPs returned a completed questionnaire. Although 32% of GPs supported collection of family history information and 41.5% familial risk assessment, 18% were not willing to offer these services even if training is provided. Of the GPs, 50% stated they recognized when referral to genetics services is appropriate, although 43% felt unprepared to collect family history or assess familial risk. Lack of training within the last 3 years was a significant predictor of feeling unprepared to undertake these activities (OR = 2.53,p = 0.012). A substantial group of GPs remain unprepared or unwilling to provide genetic health care. GPs' attitudes to delivery of genetic health care are significantly influenced by factors such as a lack of evidence of the direct benefits to patients, local guidelines and specialist services. These factors need addressing if delivery of genetic health care is to be incorporated into routine primary care.

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.

Ethnicity and other risk factors for acute lower limb cellulitis: a U.K.-based prospective case-control study.

BACKGROUND: Acute lower limb cellulitis is a common yet potentially serious condition. Previous studies have identified risk factors in the non-U.K. population. Ethnicity has been postulated as a possible risk factor but has not previously been investigated. OBJECTIVES: To identify risk factors for acute lower limb cellulitis in the U.K. population. METHODS: One hundred and fifty consecutive patients with cellulitis requiring hospital admission and 300 controls were recruited to this prospective case-control study. Controls were matched for age and sex. RESULTS: Strongly predictive risk factors for acute lower limb cellulitis in the U.K. include being of white ethnicity and preceding episodes of injury to the affected leg. No systemic illnesses were identified as increasing an individual's risk of presenting with cellulitis. CONCLUSIONS: This study has identified that patients of white ethnicity are at higher risk of developing acute lower limb cellulitis compared with other ethnic groups. The importance of local risk factors has also been shown in the U.K. population.

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.

The effect of the apolipoprotein E gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. METHODS: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. RESULTS: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. CONCLUSIONS: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.

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%.