Surveillance of community genital Chlamydia trachomatis testing in the East of England, 2008-2010.

BACKGROUND: Widespread testing for chlamydia is expected to result in a reduction in prevalence. In 2008, coverage indicators introduced by the Department of Health (DH) required collection and submission of all tests performed outside of genitourinary medicine clinics. No mechanism existed to collect community-based tests conducted outside of the National Chlamydia Screening Programme. The Health Protection Agency Regional Epidemiology Unit in the East of England (EoE) set up a new system to routinely collect and submit these tests on behalf of the regional Primary Care Organizations (PCOs). METHODS: Testing data were requested from all laboratories commissioned to undertake chlamydia testing by EoE PCOs. Data were imported into a bespoke Structured Query Language server database and automated data processing routines were run. Data fulfilling national criteria were submitted for inclusion in the DH indicators. RESULTS: High-quality data were submitted to set deadlines with minimum impact on laboratories. Completeness of data variables varied by laboratory and by variable type. After complex data processing, 96% of laboratory reported tests in the 15-24 year age range were eligible for submission. CONCLUSIONS: This centralized method of data collection provides high-quality data, allowing for further analysis, which can be used to inform improvements in health care. These methods could be transferred to any of the hundreds of organisms for which similar laboratory data exist.

Inequalities in access to knee joint replacements for people in need.

OBJECTIVES: To quantify the effects of socioeconomic deprivation and rurality on evidence of need for total knee joint replacement and the use of health services, after adjusting for age and sex. METHODS: A random stratified sample of 15 000 people aged > or =65 years taken from central age/sex registers for the geographical areas covered by the previous Sheffield and Wiltshire Health Authorities. A self completion validated questionnaire was then mailed directly to subjects to assess need for knee joint replacement surgery and whether general practice and hospital services were being used. Subjects were followed up for 18 months to evaluate access to surgery. RESULTS: The response rate was 78% after three mailings. In those aged 65 years and over (with and without comorbidity), the proportion with no comorbid factors and in need of knee replacement was 5.1%; the rate of need among subjects without comorbidity was 7.9%. There were inequalities in health and access to health related to age, sex, geography, and deprivation but not rurality. People who were more deprived had greater need. Older and deprived people were less likely to access health services. Only 6.4% of eligible people received knee replacement surgery after 18 months of follow up. CONCLUSIONS: There is an important unmet need in older people, with significant age, sex, geographical, and deprivation inequalities in levels of need and access to services. The use of waiting list numbers as a performance indicator is perverse for this procedure. There is urgent need to expand orthopaedic services and training.

Inequalities in accessing hip joint replacement for people in need.

OBJECTIVES: To quantify the effects of rurality and socio-economic disadvantage on prior evidence of need for total hip joint replacement and use of health services after adjusting for age and gender. DESIGN: Self-completion validated questionnaire mailed directly to subjects. SETTINGS: Geographical areas covered by Wiltshire and Sheffield Health Authorities in England. PARTICIPANTS: Random stratified sample of 15,000 aged 65 years and over taken from the central age-sex registers. MAIN OUTCOME MEASURE: Prior need for hip joint replacement surgery and whether general practice and hospital services were being used as assessed by the questionnaire. RESULTS: The response rate was 78% after three mailings. Prevalence of need for total hip replacement in the over 64s was 3.4% (95% confidence interval is 3.0% to 3.8%) and in those without co-morbidity 5.4% (95% confidence interval is 4.8% to 6.0%). There were inequalities demonstrated due to age, geography, and deprivation, but not rurality in accessing general practice and hospital services. People who were poor had more need. Older people in need were less likely to be accessing health services. CONCLUSIONS: There is an important unmet need for hip joint replacement in older people with marked inequalities in levels of need and use of services. The use of numbers of people waiting as a performance indicator is perverse for this procedure. We have urgently to expand orthopaedic services and the training of orthopaedic surgeons in England.

An evaluation of the safety and efficacy of simultaneous bilateral total knee arthroplasty.

This study directly compared the clinical and radiographic results and patient satisfaction of a group of simultaneous, bilateral total knee arthroplasties (92) with a year of surgery matched unilateral total knee arthroplasties (92). Death within 1 month of surgery occurred in 1 bilateral patient and no unilateral patients. Significant cardiorespiratory complications were recorded in 6 bilateral patients and 2 unilateral patients. Patients with pre-existing cardiorespiratory conditions were particularly at risk. Analysis revealed a 98% 7-year survivorship for unilateral procedures and 97% for bilateral. In this study, 95% of bilateral patients stated they would choose the same option again.

Tumour necrosis factor alpha stimulated rheumatoid synovial microvascular endothelial cells exhibit increased shear rate dependent leucocyte adhesion in vitro.

OBJECTIVE: To investigate endothelial cell adhesion molecule expression and leucocyte adhesion to endothelial cells isolated from the microvasculature of rheumatoid arthritic synovial tissue (SMEC) in comparison with similar cells isolated from healthy subcutaneous adipose tissue (ADMEC) or from umbilical veins (HUVEC). METHODS: Cultured endothelial cells were treated with tumour necrosis factor alpha (TNFalpha) for 2-24 hours before the assessment of cell surface E-selectin, vascular (VCAM-1) or intercellular cell adhesion molecule-I (ICAM-1) expression. Neutrophil and T lymphocyte adhesion to TNFalpha treated endothelial cells was assessed using static and shear dependent assay systems. RESULTS: VCAM-1 expression by SMEC was significantly less sensitive to TNFalpha stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared to be more sensitive to TNFalpha stimulation and maximal expression was about 30% greater in comparison with HUVEC or ADMEC. Sensitivity to TNFalpha induction and maximal ICAM-1 expression was similar in all three endothelial cell types. Static neutrophil adhesion to TNFalpha stimulated SMEC was significantly increased in comparison with HUVEC, however this phenomenon was dependent on the presence of neutralising antibodies to ICAM-1. At shear rates in excess of 2.4 dynes/cm(2) significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNFalpha stimulated SMEC than HUVEC. CONCLUSION: Rheumatoid synovial endothelial cells differentially regulate E-selectin and VCAM-1. The increased ability of TNFalpha stimulated synovial endothelial cells to support leucocyte adhesion may help to explain the leucocyte, in particular CD45RO+ T-lymphocyte, recruitment observed in the rheumatoid synovium.

Estimating the sample size for a t-test using an internal pilot.

If the sample size for a t-test is calculated on the basis of a prior estimate of the variance then the power of the test at the treatment difference of interest is not robust to misspecification of the variance. We propose a t-test for a two-treatment comparison based on Stein's two-stage test which involves the use of an internal pilot to estimate variance and thus the final sample size required. We evaluate our procedure's performance and show that it controls the type I and II error rates more closely than existing methods for the same problem. We also propose a rule for choosing the size of the internal pilot, and show that this is reasonable in terms of the efficiency of the procedure.

Symmetric tests and confidence intervals for survival probabilities and quantiles of censored survival data.

We describe existing tests and introduce two new tests concerning the value of a survival function. These tests may be used to construct a confidence interval for the survival probability at a given time or for a quantile of the survival distribution. Simulation studies show that error rates can differ substantially from their nominal values, particularly at survival probabilities close to zero or one. We recommend our new constrained bootstrap test for its good overall performance.

A prevalence study of age-associated memory impairment.

BACKGROUND: Age-associated memory impairment (AAMI) describes a non-disease ageing-related decline in memory. Pharmacological treatment trials have been reported and DSM-IV has introduced a term for the disorder. No prevalence study with the original criteria has previously been published. METHOD: An age-stratified sample was taken of 50-95-year-olds registered with a local health centre. Diagnosis of AAMI was made by questionnaire, cognitive testing, and medical and psychiatric assessment. RESULTS: Prevalence rates for the total population and for the over-50s were estimated to be 5.8% and 18.5%, respectively. These rates are dramatically affected by minor alterations to individual criteria. CONCLUSIONS: It appears AAMI is less common than previous estimates suggested, although the diagnostic criteria do not satisfactorily define people with an age-related decline in memory. Complaint of memory decline is more strongly correlated with measures of affect and personality than with measures of current memory test performance or estimates of memory decline.

The chronotropic response of the sinus node to exercise: a new method of analysis and a study of pacemaker patients.

In this study, the intercepts and slopes of the regression lines of sinus heart rate response to exercise were examined as a possible means of assessing normal and abnormal chronotropic responses. The regressions were plotted for 223 normal subjects and 93 pacemaker patients during progressive bicycle exercise. The 93 pacemaker patients consisted of two groups, (a) 46 with symptomatic sick sinus syndrome (daytime sinus or nodal bradycardia of < 45.min-1 or atrial asystole > 1.5 s together with other features of the syndrome) and (b) 47 with second- or third-degree AV block (in whom a one-to-one AV relationship was either restored by dual chamber pacing or in whom normal AV conduction was present at the time of exercise). Examination of the regression lines showed them to be sufficiently linear in both normal subjects and pacemaker patients to allow calculation of the intercept and slope values. Multiple regression analysis of these values showed that the AV block group did not differ significantly from the normal individuals. However, in the patients with sick sinus syndrome, the intercept but not the slope values were significantly lower than in the normal subjects (P < 0.01). The patients with sick sinus syndrome appeared to have an abnormality of sinus node function, where the basic rate setting is too low at all levels of exercise, although the acceleration with exercise is normal. Among the sick sinus syndrome patients, only four (9%) had intercept values lying more than 2 standard deviations below that of the normal control group and were deemed to be chronotropically incompetent. Finally, the problems with the various methods used to investigate chronotropic incompetence are reviewed.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal and weather factors in parasuicide.

BACKGROUND: Seasonal variation in suicide and parasuicide has previously been reported. Few investigations have examined whether meteorological factors could influence suicidal behaviour, and the inconclusive results produced may be due to a variety of methodological problems. The present study overcomes some previous difficulties and tested whether parasuicide admission rate is related to weather variables. METHOD: Over 12,000 admissions for parasuicide were analysed by month, season, and in relation to meteorological data, which were measured close to the admitting hospital. RESULTS: Marked seasonal (P < 0.001) and monthly (P < 0.001) variations in mean daily parasuicide numbers were seen in women but not men. Small but highly significant correlations were demonstrated between parasuicide rate and weather parameters (P < 0.01), which were more marked in women (P < 0.01). These effects were additional to the monthly variation (P < 0.05). CONCLUSIONS: Weather has a small influence on parasuicide. Gender differences in body temperature regulation might account for the sex difference seen.

Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety endpoints.

We describe group sequential tests for a bivariate response. The tests are defined in terms of the two response components jointly, rather than through a single summary statistic. Such methods are appropriate when the two responses concern different aspects of a treatment; for example, one might wish to show that a new treatment is both as effective and as safe as the current standard. We present a formulation of the bivariate testing problem, introduce group sequential tests that satisfy Type I error conditions, and show how to find the sample size guaranteeing a specified power. We describe how properties of group sequential tests for bivariate normal observations can be computed by numerical integration.

Sequential equivalence testing and repeated confidence intervals, with applications to normal and binary responses.

We propose group sequential tests of the equivalence of two treatments based on ideas related to repeated confidence intervals. These tests adapt readily to unpredictable group sizes, to the possibility of continuing even though a boundary has been crossed, and to nonnormal observations. In comparing two binomial distributions, the required sample size depends strongly on the average success probability and an adaptive choice of group size is needed to produce an efficient test meeting specified error probability constraints. A special case is the experiment where interim analyses are performed, not for the purpose of early termination but simply to adjust the sample size so that nominal error rates will be guaranteed, despite the presence of a nuisance parameter.

Repeated confidence intervals for group sequential clinical trials.

We describe methods for the construction of valid confidence intervals for parameters of interest at repeated times during the course of a clinical trial with two treatments. This approach gives the investigator a way to monitor the trial and allows greater flexibility than methods that have rigid statistical stopping rules. Two situations are considered. In the first, responses are available immediately and normally distributed, the parameter of interest being the difference in means. In the second, observations are survival times and a proportional hazards model is assumed. Here the parameter of interest is the hazard ratio. Group sequential tests can be based on repeated confidence interval methods and these are compared to other multiple testing procedures that have been proposed.