Cutaneous lymphocyte antigen and α4ß7 T-lymphocyte responses are associated with peanut allergy and tolerance in children.

BACKGROUND: It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy (PA), and tolerance induced by oral exposure. The skin- and gastrointestinal (GI)-homing markers, cutaneous lymphocyte antigen (CLA) and α4ß7 integrin, are used to determine whether the state of PA correlates with peanut-specific CLA responses, with tolerance associated with predominant α4ß7 responses. METHODS: CLA+ and α4ß7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non-allergic (NA) groups, and peanut-specific cytokine production was measured. RESULTS: In peanut allergic patients, peanut-specific proliferation predominates in the skin-homing CLA+ subset, whilst peanut-tolerant groups have a mixed CLA/α4ß7 response (P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI-homing α4ß7+ cells of peanut-tolerant groups and Th2 skewing in the skin-homing CLA+ cells of peanut allergic patients. CONCLUSION: The predominance of the CLA+ response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4ß7+ response in peanut-tolerant groups suggests that allergen exposure through the GI tract induces tolerance.

[The German version of the satisfaction with stroke care questionnaire (SASC) for stroke patients]. / Entwicklung der deutschen Version der Patientenzufriedenheits-Skala (SASC) für den Einsatz bei Patienten nach Schlaganfall.

BACKGROUND AND PURPOSE: Patient satisfaction is an important objective to achieve in all parts of the health-care system. Patient satisfaction probably effects adherence to therapy. Until now, German-speaking countries were lacking a reliable instrument to investigate patient satisfaction. The aim of this study was to translate the English Satisfaction with Stroke Care Questionnaire (SASC), validated and created specifically for patients who had a stroke, and to assess the test-retest reliability of the German version. METHODS: The translation of the satisfaction questionnaire followed the protocol of the Medical Outcome Trust. The validation was carried out with continuously admitted inpatients who had suffered an acute stroke and were able to give written consent. Patients received two questionnaires for self-administration three months after hospital admission. The two questionnaires were compared for test-retest reliability. Reliability was measured using AC 1 values. RESULTS: Out of 202 patients continuously admitted to our hospital with the diagnosis of stroke, 33 could not give written informed consent due to aphasia (N = 29) or foreign-language (N = 4) or refused written consent (N = 8) or died during the following 3 months after the event (N = 14). Recall rate at three months was 71 % with 104 of the remaining 147 patients sending both questionnaires back. (Characteristics of responders: NIHSS = 3 [0 - 26], age = 71.5 [31 - 89] years, 40 % female, 48 % with five or more years of secondary school, 66 % paretic, 17 % with aphasia, 26 % with atrial fibrillation). The test-retest reliability of the German version of the self-administered satisfaction questionnaire was substantial (mean AC 1 = 0.612; range from 0.307 to 0.789). CONCLUSION: The German version of the SASC is a reliable tool to test patient satisfaction in stroke patients in the German language.

Frequency and predictors for the risk of stroke recurrence up to 10 years after stroke: the South London Stroke Register.

BACKGROUND: Data estimating the risk of, and predictors for, long-term stroke recurrence are lacking. METHODS: Data were collected from the population-based South London Stroke Register. Patients were followed up for a maximum of 10 years. Kaplan-Meier estimates and Cox proportional hazards models were used to assess the cumulative risk of and predictors for first stroke recurrence. Variables analysed included sociodemographic factors, stroke subtype (defined as cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage), stroke severity markers and prior-to-stroke risk factors. RESULTS: Between 1995 and 2004, 2874 patients with first-ever stroke were included. The mean follow-up period was 2.9 years. During 8311 person-years of follow-up, 303 recurrent events occurred. The cumulative risk of stroke recurrence at 1 year, 5 years and 10 years was 7.1%, 16.2% and 24.5% respectively. No differences in stroke recurrence were noted between the stroke subtypes. Factors increasing the risk of recurrence at 1 year were previous myocardial infarction (HR 1.73; 95% CI 1.08 to 2.78) and atrial fibrillation (HR 1.61; 95% CI 1.04 to 4.27); at 5 years, hypertension (HR 1.47; 95% CI 1.08 to 1.99) and atrial fibrillation (HR 1.79; 95% CI 1.29 to 2.49); and at 10 years, older age (p = 0.04), and hypertension (HR 1.38, 95% CI 1.04 to 1.82), myocardial infarction (HR 1.50, 95% CI 1.06 to 2.11) and atrial fibrillation (HR 1.51, 95% CI 1.09 to 2.09). CONCLUSIONS: Very-long-term risk of stroke recurrence is substantial. Different predictors for stroke recurrence were identified throughout the follow-up period. Risk factors prior to initial stroke have a significant role in predicting stroke recurrence up to 10 years.

Black and minority ethnic men who have sex with men: a London genitourinary medicine clinic experience.

The aim was to examine sexual behaviour and rates of sexually transmitted infections (STIs) in black and minority ethnic (BME) men who have sex with men (MSM) attending a London genitourinary medicine clinic. A case-note review of BME MSM (n = 203) attending our service between 1 April 2005 and 31 March 2006 was carried out. BME MSM were those who self-identified as being of Black (Caribbean, African or Other), South Asian (Indian, Pakistani, Bangladeshi or Sri Lankan) and Chinese/South-East Asian (Malaysian, Thai, Filipino, Japanese) ethnicities. Consecutively attending self-identified white British (WB) MSM (n = 203) were used as a comparative group. BME MSM were significantly more likely to report unprotected anal intercourse with casual male partners in the preceding three months (P = 0.0016) and were more likely to report female sexual partners (P = 0.0018). Rectal gonorrhoea was more common in WB MSM (P = 0.02). Numbers of other bacterial STIs and HIV infection were similar in both groups. The higher reported rates of risk behaviour in BME MSM are of concern and support the need for focussed sexual health promotion.

The association of post-stroke neurological improvement with risk of subsequent deterioration due to stroke events.

We sought to simultaneously confirm that substantial recovery at day 1 and day 7 after acute ischaemic stroke onset is associated with subsequent neurological deterioration in patients of the Acute Stroke Therapy by Inhibition of Neutrophils randomized clinical trial. Substantial recovery was assessed by improvement in the National Institutes of Health Stroke Score (NIHSS). Neurological deterioration was defined as any stroke event or NIHSS worsening from recovery assessment to day 90. After adjusting for age, t-PA and day 1 NIHSS, there was a non-significant tendency of substantial (pre-specified as 75%) recovery at day 1 to be associated with later deterioration [odds ratio (OR) 2.47; 95% CI, 0.95-6.50]. The corresponding OR for substantial (pre-defined as 65%) recovery at day 7 was 1.84 (0.85-3.96). Other thresholds for recovery were significantly associated with later deterioration: >50%, 80%, 90% and 100% for day 1 and >50%, 60%, 70%, 90% and 100% for day 7. The effect of recovery at day 1 was more important than that of later recovery. This study confirms the association between recovery and subsequent neurological deterioration and is the first to indicate the greater importance of acute recovery at day 1 in comparison with later recovery.

Bayesian approach to bioequivalence assessment: an example.

The statistical methods required for a Bayesian analysis of bioequivalence are outlined and numerically illustrated. The analysis consists of the calculation of the posterior probability, given the experimental results, that the ratio of true means of a new and a standard formulation of a drug with respect to some biological response lies in a given interval. Nomograms helpful for the calculation of these probabilities are provided.

Bayesian analyses of two-treatment crossover studies.

This review covers Bayesian analyses of two-treatment crossover studies. The main emphasis is placed on the analysis of continuous data although we also consider dichotomous responses. Studies discussed include (1) the simple two-period, two-treatment crossover, (2) the two-period crossover with one baseline measurement, (3) the two-period crossover with two baselines and (4) the extra-period design with two treatment sequences.

Seasonal variation of temperatures in rabbits.

Determinations of rectal temperatures were performed in a series of measurements in male and female drug-naive SPF rabbits of the Chinchilla type maintained under standard environmental conditions (temperature 19 degrees C, relative humidity 60%, light 14 h/day) in weekly tests collected over 3 1/2 years. The results indicated a seasonal variation in rectal temperature. The temperature was affected by restraint, and female animals showed significantly higher temperatures than males. Bodyweight had no effect on temperature.

Effects of pressure on whole blood glucose measurements using the Bayer Glucometer 4 blood glucose meter.

The effect of pressure was investigated on the readings of whole blood glucose obtained from the Bayer Glucometer 4 blood glucose meter which uses the hexokinase enzymatic reaction. Sixteen subjects (eight normal and eight insulin-dependent diabetics) were exercised in a hyperbaric chamber at a depth of 3.7 atm abs. Venous blood samples were monitored at regular intervals for whole blood glucose concentration as measured by a Glucometer 4 inside the chamber. The blood samples were immediately placed in an airlock and taken to 1 atm abs, where whole blood glucose concentrations were measured using an identical instrument. The remaining blood was then analyzed in duplicate for serum glucose concentration using standard laboratory methods. The results show a significant difference between whole blood glucose concentrations measured at pressure and those measured at atmospheric pressure. Significant differences are also observed between whole blood glucose concentrations measured under pressure and serum blood glucose concentrations measured at atmospheric pressure.

Control of blood glucose in a group of diabetic scuba divers.

A preliminary study to examine the hypothesis that the ability of well-controlled (defined as no hypoglycemic episodes within the last 12 mo., HbAlc < 9.0%, and none of the long-term complications of diabetes type I) diabetic scuba divers to control their serum glucose and dive without becoming hypoglycemic during a simulated dive to 27 meters of seawater in controlled environment is impaired. An open, controlled, crossover study compared blood glucose levels, hematocrits, and hematologic cell counts in a group of eight type I diabetic scuba divers to those from eight age- and sex-matched, normoglycemic control scuba divers. Each diver did one simulated dive and one control exercise on the surface on 2 consecutive days. The simulated dive was done to depth of 375 kPa in a hyperbaric chamber, the control exercise was done at ambient pressure. The order of the dive and the control exercise was randomized. No statistically significant differences were observed between serum glucose levels in the diabetic divers measured during the simulated dive to 375 kPa vs. the serum glucose levels in the diabetic divers measured during the control exercise at the same time points. All divers with type I diabetes remained free of symptoms and signs of hypoglycemia throughout the course of the trial, and no diabetic subject had a serum glucose less than 4 mmol/liter before the end of the trial. As the sample size was small, larger studies including subject with type II diabetes will be necessary to extend these results to the diabetic diving population at large. The authors conclude that, contrary to advice issued by most diving agencies to scuba divers, it may be safe to allow well-controlled subjects with type I diabetes with no long-term complications to undertake scuba diving, and that high partial pressures of oxygen do not seem to lower serum glucose levels significantly in the diabetic diver during the dive.

Visible iris sign as a predictor of problems during and following anterior approach ptosis surgery.

OBJECTIVE: To describe the pre- and postoperative features of the visible iris sign (VIS), which is the apparent visibility of iris colour through a closed upper eyelid, in patients undergoing anterior approach surgery for severe involutional aponeurotic ptosis, and to assess its effect on postoperative outcome. DESIGN: Prospective, comparative interventional case series. METHODS: Prospective series of all patients undergoing surgery for severe involutional aponeurotic ptosis during a 16-month period at a single centre. INCLUSION CRITERIA: Severe involutional ptosis (upper eyelid margin reflex distance (MRD) ≤1 mm) treated by anterior-approach surgery. MAIN OUTCOME MEASURES: Presence of VIS, type of ptosis (primary or recurrent), preoperative MRD, levator function and skin crease height, documented unusual intra-operative findings, postoperative complications, and follow-up time. RESULTS: Of 133 procedures for involutional aponeurotic ptosis, 96 procedures (56 patients) were included in the study. In total, 12 patients (21%, 12/56, 2 males, and 10 females) had been identified as having VIS preoperatively. In order to avoid any selection bias, only patients with severe degree of ptosis were included in the two groups with the two groups being alike in the preoperative lid height, levator function or the skin crease. In the VIS group, 55% (12/22) had a thinned, significantly retracted levator aponeurosis and a thin tarsus prone to full-thickness suture passes (36.3%, 8/22) during aponeurosis reattachment. Immediate persistent overcorrection during surgery was seen in three procedures, with one patient having an under corrected outcome when treated with a hang-back suture. In the non-VIS group, no patients were documented intra-operatively, as having significant retraction of the levator aponeurosis. However, 14% (10/74) of the eyelids were recorded as having a very attenuated levator and one patient (3%, 1/44) was noted to have a floppy tarsus that was difficult to suture. The total incidence of intra-operative difficulties during surgery were 78% in the VIS group and 22% in the non-VIS group. Mean postoperative follow-up was 22 weeks. (median 18, range 12-64). The overall success rates were 63.6% (14/22) in the VIS group, compared with 77.0% (57/74) in the non-VIS group (P = 0.260). After excluding cases undergoing concurrent blepharoplasty and non-Caucasians, success rates were 57.1% (4/7) and 69.2% (9/13) in the VIS and non-VIS groups, respectively (P = 0.598). All failures were because of under-correction. CONCLUSION: The VIS is a clinical sign of severe involutional ptosis. Patients with VIS have one or more features, including a retracted levator aponeurosis, a thinned tarsus prone to full-thickness suture passes, and a tendency for immediate persistent overcorrection following levator advancement. Preoperative identification of VIS may help in appropriate patient counselling, procedure selection, anticipation of intraoperative difficulties, and possibly further standardisation of future cohorts when evaluating the results of involutional ptosis surgery. PRÉCIS: The authors describe the pre-, intra- and postoperative features of visible iris sign. They discuss the success rates of anterior approach surgery in VIS patients and discuss the contributing factors for a poorer outcome.

Predictive probability in clinical trials.

In a recent paper, Choi and Pepple (1989, Biometrics 45, 317-323) consider the use of predictive probabilities in the monitoring of clinical trials. In particular, they characterise the predictive probability as a "useful conservative measure" for monitoring purposes. In this note the nature and source of this "conservatism" are investigated.

Extending a Bayesian analysis of the two-period crossover to allow for baseline measurements.

In the context of a two-period crossover study with baseline measurements a graphical method is developed for displaying the dependence of posterior inferences concerning the treatment effect on unavoidable prior beliefs about the 'correct' model. The method is a generalization of the approach developed by Grieve for the corresponding case without baselines.

A Bayesian analysis of the two-period crossover design for clinical trials.

Statisticians have been critical of the use of the two-period crossover designs for clinical trials because the estimate of the treatment difference is biased when the carryover effects of the two treatments are not equal. In the standard approach, if the null hypothesis of equal carryover effects is not rejected, data from both periods are used to estimate and test for treatment differences; if the null hypothesis is rejected, data from the first period alone are used. A Bayesian analysis based on the Bayes factor against unequal carryover effects is given. Although this Bayesian approach avoids the "all-or-nothing" decision inherent in the standard approach, it recognizes that with small trials it is difficult to provide unequivocal evidence that the carryover effects of the two treatments are equal, and thus that the interpretation of the difference between treatment effects is highly dependent on a subjective assessment of the reality or not of equal carryover effects.

On the construction of shortest confidence intervals and Bayesian highest posterior density intervals.

In this note it is argued that the principal characteristic of the confidence intervals proposed by Bartoszynski & Powers (1990) is not primarily the fact that they are of minimum length but that they are Bayesian highest posterior density intervals. A simple iterative process for determining the ends of the interval is presented.

Confidence intervals and sample sizes.

In a recent paper, Beal (1989, Biometrics 45, 969-977) considers the problem of determining the appropriate sample size when inference about a parameter theta is to be made on the basis of a confidence interval (CI). He suggests that the sample size should be chosen so that the probability that the length of the CI is less than a given value, conditional on the interval including the true theta, is greater than a specified level. In this note, in which we concentrate on two-sided intervals, this suggestion is examined, as is the effect of uncertainty in our knowledge of the population variance sigma 2 on estimates of sample size.

Joint equivalence of means and variances of two populations.

Clinical equivalence has almost exclusively been treated from the view of average equivalence. However, as in bioequivalence, there has been recent interest in more general definitions of clinical equivalence. In particular, Bauer and Bauer (1) have investigated the possibility of the use of a pair of tests for the equality of means and variances taking account of the multiplicity issues involved. In bioequivalence, a number of authors have considered a Bayesian approach; in this article we generalize these previous Bayesian approaches to this more general problem. We investigate the operating characteristics of a decision procedure based on the posterior probability that the parameters lie within a prespecified region of equivalence.

Issues for statisticians in pharmaco-economic evaluations.

Economic evaluations of new pharmaceutical products are of increasing importance to pharmaceutical companies. In this paper we investigate a number of topics of greater or lesser importance to statisticians who need to involve themselves in pharmaco-economic evaluations. These range from the need to consider whether traditional randomized clinical trials provide the most appropriate setting for an economic evaluation, to the more technical question of how to handle cost-effectiveness ratio data, including the issue of the most appropriate inferential apparatus-hypothesis testing, confidence intervals or Bayesian methods.

A comment on interim analyses in crossover trials.

In a recent issue of Biometrics, Cook (1995, Biometrics, 51, 932-945) considered the possibility of applying sequential analysis to 2 x 2 crossover trials and made a comparison with more conventional approaches. We believe this comparison to be misleading in a number of respects.