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.     

Indicators of choking risk in adults with learning disabilities: a questionnaire survey and interview study

Purpose. Feeding and swallowing impairments are key predictors of increased morbidity and mortality in adults with learning disabilities. This postal survey and interview study sought to identify risk factors in adults with learning disabilities who have histories of choking. Method. A total of 2000 questionnaires were sent to carers of all adults with learning disabilities registered as service users by three local health authorities. (A 'service user' may be using any specialist learning disability health or social care facility with day, residential or therapeutic services). Of the 674 service users for whom surveys were returned, 47 were living in hospital, 396 were living in residential or group homes and 208 were living with relatives, or in their own homes. Eighteen subjects who had reported serious or repeated episodes of choking were interviewed in depth in their residences or workplaces. Responses were subjected to frequency analyses. Personal characteristics were analysed. Choking patterns were differentiated by food texture. Results. A total of 34% of questionnaires on 674 service users were returned; 42% of respondents reported one or more choking episodes. There was a significantly greater occurrence of choking among people with more severe learning disability, with Down syndrome, people who had an incomplete dentition or were taking a greater number of psychotropic drugs. Antisocial eating habits learnt in institutional settings presented an additional choking hazard for some individuals. Conclusion. Choking is a serious hazard for many adults with learning disabilities. This study establishes many of the characteristics associated with swallowing problems in this population. Clinicians and carers should benefit from awareness of these predictors, leading to better management of eating behaviours and habits. A choking and swallowing risk assessment should be included in routine health assessments of adults with learning disability, paying especial attention to the condition of a person's teeth; possible side effects from prescribed medication, and abnormal eating behaviour.     

Diagnostic and treatment concordance between a physiotherapist and an orthopedic surgeon--a pilot study

Musculoskeletal impairments affect one-third of the adult population, are one of the major contributors to lost time from work, and account for one-third of a general practitioner's caseload. These injuries respond well to physiotherapy, but access can be limited in a publicly funded health care system. Improved access to physiotherapy occurs in a collaborative model of care in orthopedic clinics however the extent to which the patient receives similar diagnoses and treatment recommendations has not been reported. The purpose of this study was to determine diagnostic concordance and accuracy, and treatment concordance between a physiotherapist and orthopedic surgeons. Twenty-five subjects in an orthopedic clinic were assessed by a physiotherapist and an orthopedic surgeon. Diagnosis and treatment recommendations were made by each separately. These were compared for concordance between professionals and diagnostic accuracy. The physiotherapist and the orthopedic surgeon had 90% concordance in diagnoses of knee and shoulder impairments, and 75% accuracy when compared to definitive diagnostic methods. They had 87% agreement in treatment recommendations, however, the physiotherapist gave three treatment recommendations per patient where the surgeon gave two. In a collaborative care context therefore, this study suggests, that physiotherapists have similar diagnostic capabilities to orthopedic surgeons, and they will enhance the conservative treatment options offered to orthopedic patients.     

Living with chronic heart failure: a review of qualitative studies of older people

Title. Living with chronic heart failure: a review of qualitative studies of older people Aim. This paper is a report of a systematic review of qualitative studies of how older people live with chronic heart failure. Background. Chronic heart failure is a global epidemic mainly affecting an ageing population. Understanding how older people live with this disease is important to help promote their adjustment to the distressing illness experience. Data sources. Eligible studies published in 1997–2007 were identified from several databases (Medline, CINAHL, PsycINFO and Sociological Abstracts). A manual search was conducted of bibliographies of the identified studies and relevant journals. Review methods. Two researchers independently reviewed the studies and extracted the data. Key concepts from the papers were compared for similarities and differences. The transactional model of stress was used to guide data synthesis. Findings. Fourteen qualitative studies were identified. Most described the illness experiences of older people with chronic heart failure and associated coping strategies. There was some emerging work exploring the adjustment process. The findings indicated that living with chronic heart failure was characterized by distressing symptoms, compromised physical functioning, feelings of powerlessness and hopelessness, and social and role dysfunction. There were gender differences in the way the disease was conceived. Adjustment required patients to make sense of the illness experience, accept the prognosis, and get on with living with the condition. Conclusion. Empowering older people to manage chronic heart failure, instilling hope and bolstering support system are means of promoting successful adjustment to the disease. Further research needs to explore the cultural differences in the adjustment process.