Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis.

OBJECTIVE: To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). METHODS: ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age ≥18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as ≥40% improvement from baseline (≥20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and ≥40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. RESULTS: In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. CONCLUSION: Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases.

Surveillance of insecticide resistance in head lice using biochemical and molecular methods.

Treatment of head louse infection is primarily through topical insecticides. However, there is growing evidence of resistance. A representative population sample was tested using biochemical and molecular methods; it was shown that, in Wales, treatments containing pyrethroids are likely to be less effective in controlling head louse infection than those containing organophosphates.

Outcomes of permanent pacemaker implantation for carotid sinus hypersensitivity in a district general hospital with a Falls Fits Faints and Funny Turns Clinic.

UNLABELLED: Permanent pacemaker implantation is considered for carotid sinus hypersensitivity with asystolic pause of > 3 seconds during carotid sinus massage, with or without associated systolic blood pressure drop of > 50 mmHg. AIMS: To assess the outcome of treatment with dual chamber permanent pacemaker implantation for carotid sinus hypersensitivity in a district general hospital and to compare our practice with available national data. METHODS: Patients presenting with syncope, dizziness or unexplained falls were initially assessed as outpatient and investigations, commonly cardiovascular were performed including tilt table test with carotid sinus massage to look for carotid sinus hypersensitivity, vasovagal syncope and postural hypotension. A retrospective analysis was performed on patients who had pacemaker implantations for carotid sinus hypersensitivity. RESULTS: Fifty pacemaker implantations were performed, 14 (28%) were for carotid sinus hypersensitivity. Mean follow-up period was 10 months. Age range was 56-88 (mean = 71.9) years. In the eighteen months prior to pacemaker implantation, 71.4% of patients had syncope, 64% dizziness and 50% had unexplained falls. Following pacemaker implantations, only 2 (14.3%) had symptoms. Scottish national figures show 13.6% of all new pacemaker implants were for carotid sinus hypersensitivity, and in district general hospitals this was 16%. CONCLUSIONS: Health benefits for patients presenting with syncope dizziness and falls can be achieved by cardiovascular investigations including tilt table testing. We have shown carotid sinus hypersensitivity is successfully treated with pacemaker implantation in a district general hospital setting and this type of clinic has an impact on the rate and type of new pacemaker implantation.

Analysis of six months' referrals to a "one-stop" neurovascular clinic in a district general hospital: implications for purchasers of a stroke service.

OBJECTIVE: To determine the effectiveness of a "one-stop" neurovascular clinic (NVC) in guiding the diagnosis and investigation of patients suffering a mild stroke or transient ischaemic attack (TIA). DESIGN: Six months' survey of the activity of a new neurovascular clinic (NVC). SETTING: Borders region of Scotland. SUBJECTS: Patients referred with a suspected diagnosis of stroke or TIA. RESULTS: The clinic served 23 general practices and a population of 106,000. Over a 6 month period 128 patients were referred; 93% of patients were referred by general practitioners, 5% by consultant physicians and 2% from wards in the Borders General Hospital. Most patients were independent prior to the presenting event and had minimal disability on presentation to the clinic. Patients were seen within 48 hours of referral in the majority of cases and all within five working days. However, only 52% were seen within two weeks of the onset of their symptoms. Only 50% of patients were shown to have sustained a stroke or TIA. A variety of other diagnoses mimicked vascular events including epilepsy, migraine, cranial nerve palsies and cerebral tumour. The stroke-related group differed significantly in age (P = 0.003) and in the number of patients already on aspirin (P = 0.010) but not in any other risk factor. CT scan and carotid doppler examination were considered necessary in only 47% and 24% respectively of referred patients. Only five stroke-related patients and one non-stroke-related patient needed further input from physiotherapy, occupational therapy or speech therapy. Over 90% of patients were discharged home. Patient and general practitioner satisfaction with the service received were rated at 9 (0 = very poor; 10 = excellent). CONCLUSION: Applying evidence-based medicine to patients attending a "one-stop" neurovascular clinic with minor stroke and/or transient ischaemic attack resulted in an efficient delivery of appropriate investigations and therapy to this group of patients. The NVC prevented unnecessary requests for both CT scanning and carotid doppler examination, which are valuable resources, and may have prevented admissions to hospital. Patients were anxious about their symptoms and appreciated being seen quickly and a diagnosis made. We would recommend that these clinics be set up as part of the stroke service in all district general hospitals.

Analysis of Swedish male breast cancer family data: a simple way to incorporate a common sibling effect.

Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.

A multivariate logistic model (MLM) for analyzing binary family data.

We consider modeling the familial correlation between 2 related individuals using a multiple logistic regressive model. It is shown that there is a discrepancy in the marginal probability of the second individual. We investigate the conditions under which this discrepancy can be minimized and show how it can have a direct effect on handling missing values and ascertainment. We derive a functional relationship between the parameters in the model that eliminates this discrepancy, hence solving the problems that can arise in the handling of missing values and ascertainment. Because this methodology fails when there are more than 2 related individuals, we present a new model based on a multivariate logistic distribution. Residual familial correlations can be directly related to the parameters of this model. The likelihood for family data under this model is independent of the order in which the family members enter the calculation. The marginal probabilities can be easily computed.

Modeling age of onset and residual familial correlations for the linkage analysis of bipolar disorder.

We applied regressive modeling to the data described by Stine et al. [1995] and further explored the possible linkage of bipolar disorder to marker D18S41 on chromosome 18. We performed analyses to determine age-dependent penetrance functions that best fit the data and that allow for residual familial correlations. Specifically, we introduce here a simple method to allow for a sibling correlations. that is not due to segregation at the linked locus, and then extend the results of Stine et al. [1995] by using the best fitting "regressive" model of this kind as input into a lod score linkage analysis. Although a formal segregation analysis was not attempted, a surprising finding was that, except for doubtful linkage to D18S41, there is little evidence for genetic transmission of bipolar disorder in these families.