Tuberculosis,focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection

Background

The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce.

Aims

To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented.

Methods

Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs.

Results

Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided.

Conclusions

This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost–benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.     

Strategies to enhance physical activity in people with Rheumatoid Arthritis: A Delphi survey

Introduction

Managing symptoms, resisting functional decline and maintaining health and independence are key motivators for people with Rheumatoid Arthritis (RA) who successfully engage with physical activity (PA). To inform PA support for people with RA the aim was to determine whether the broader RA population share similar beliefs and strategies regarding PA to those who report successful engagement.

Methods

A modified two-stage Delphi approach. 200 patients from four National Health Service rheumatology departments received a postal questionnaire containing statements relating to engagement with PA derived from prior interview data from physically active individuals with RA. Statements rated as agree or strongly agree by >50% of respondents were retained and the same respondents asked to rate and prioritize potential PA intervention components. Ethical approval: Oxford C Research Ethics Committee (ref 13/SC/0418).

Results

Questionnaire one received 49 responses (11 males, 37 females, 1 unknown), mean age 65 years (range 29–82). Low levels of PA were reported by 60% of respondents. Questionnaire two responses (n = 36) indicated that a PA intervention should include information about prevention of RA symptoms worsening and benefits of PA for joints; help participants to achieve improved pain management and a feeling of being in control of their RA. For PA maintenance it was important that medication controlled symptoms, and PA instructors understood RA to ensure safety.

Conclusions

A key factor to consider when designing a PA intervention for people with RA is that education from a knowledgeable instructor should underpin programme delivery alongside effective medication. Programmes may need tailoring based on demographics; this should be explored in future studies.     

Additional lesions identified by genomic microarrays are associated with an inferior outcome in low-risk chronic lymphocytic leukaemia patients

We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low-risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%). The concordance rate between FISH and GM was 87.4%. Discordant results between cytogenetic banding analysis (CBA) and GM were observed in 45/119 cases (37.8%) and were mainly due to the intrinsic characteristics of each technique. The presence of additional lesions by GM was associated with age > 65 years (p = 0.047), advanced Binet stage (p = 0.001), CLL-IPI score (p < 0.001), a complex karyotype (p = 0.004) and a worse time-to-first treatment in multivariate analysis (p = 0.009). Additional lesions by GM were also significantly associated with a worse time-to-first treatment in the subset of patients with wild-type TP53 and mutated IGHV (p = 0.025). In CLL patients with low-risk features, the presence of additional lesions identified by GM helps to identify a subset of patients with a worse outcome that could be proposed for a risk-adapted follow-up and for early treatment including targeted agents within clinical trials.     

Antihistamine use during breastfeeding with focus on breast milk transfer and safety in humans: A systematic literature review

Current data on use of antihistamines during breastfeeding and risks to the breastfed infant are insufficient. The aim of this systematic review was to provide an overview of studies measuring the levels of antihistamines in human breast milk, estimating the exposure for breastfed infants and/or reporting possible adverse effects on the breastfed infant. An additional aim was to review the antihistamine product labels available in the European Union (EU) and the United States. We searched seven online databases and identified seven human lactation studies that included 25 mother–infant pairs covering cetirizine, clemastine, ebastine, epinastine, loratadine, terfenadine and triprolidine. In addition, one study investigated the impact of chlorpheniramine or promethazine on prolactin levels among 17 women, and one study investigated possible adverse drug reactions in 85 breastfed infants exposed to various antihistamines. The relative infant dose was below 5% for all antihistamines, ranging from 0.3% for terfenadine to 4.5% for clemastine. Most product labels of the 10 antihistamines with available information in both the EU and the United States reported lack of evidence and recommended to avoid use during breastfeeding. The knowledge gap on antihistamines and lactation is extensive, and further human studies are warranted to ensure optimal treatment of breastfeeding women with allergy.     

The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells

Investigational New Drugs - Our group recently demonstrated that K858, an inhibitor of motor kinesin Eg5, has important antiproliferative and apoptotic effects on breast cancer, prostatic cancer,...     

Safety of Efalizumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: Review of Clinical Data. Part II

Background

The efficacy and safety of efalizumab have been evaluated in multiple clinical trials.

Objective

The purpose of this review is to provide an overview of the safety profile of efalizumab during the clinical trials.

Methods

Twelve-week data from four placebo-controlled trials were pooled and analyzed. Data from patients receiving 13–60 weeks of efalizumab therapy were pooled to evaluate longer-term safety.

Results

The most common adverse events were mild to moderate, self-limiting, flu-like symptoms that were most frequent following the first two efalizumab doses; by the third dose the incidence was comparable to placebo. Serious adverse events were observed in 2.2% and 1.7% of efalizumab- and placebo-treated patients, respectively. Nonserious adverse events leading to withdrawal were infrequent and similar to placebo (2.8% vs 1.8%). There does not appear to be increased risk of end-organ toxicity, infection, or malignancy in efalizumab-treated patients.

Conclusion

Efalizumab was well tolerated, with a favorable safety profile.     

Identification and quantification of fibrotic areas in the human retina using polarization-sensitive OCT

Subretinal fibrosis is one of the most prevalent causes of blindness in the elderly population, but a true gold standard to objectively diagnose fibrosis is still lacking. Since fibrotic tissue is birefringent, it can be detected by polarization-sensitive optical coherence tomography (PS-OCT). We present a new algorithm to automatically detect, segment, and quantify fibrotic lesions within 3D data sets recorded by PS-OCT. The algorithm first compensates for the birefringence of anterior ocular tissues and then uses the uniformity of the birefringent optic axis as an indicator to identify fibrotic tissue, which is then segmented and quantified. The algorithm was applied to 3D volumes recorded in 57 eyes of 57 patients with neovascular age-related macular degeneration using a spectral domain PS-OCT system. The results of fibrosis detection were compared to the clinical diagnosis based on color fundus photography (CFP), and the precision of fibrotic area measurement was assessed by three repeated measurements in a sub-set of 15 eyes. The average standard deviation of the fibrotic area obtained in eyes with a lesion area > 0.7 mm² was 15%. Fibrosis detection by CFP and PS-OCT agreed in 48 cases, discrepancies were only observed in cases of lesion area < 0.7 mm². These remaining discrepancies are discussed, and a new method to treat ambiguous cases is presented.