Anti-TNF-alpha therapy in patients with chronic non-infectious uveitis: the experience of Jules Gonin Eye Hospital.

BACKGROUND: The purpose of this study is to describe the experience of Jules Gonin Eye Hospital on the long-term outcome of anti-TNF-alpha therapy in chronic non-infectious uveitis. PATIENTS AND METHODS: We identified and followed those patients with chronic non-infectious uveitis who received systemic anti-TNF-alpha therapy. Anti-TNF-alpha therapy was administered when no response had been obtained with classical immunosuppressive therapies or in the presence of severe rheumatoid disease. RESULTS: Fifteen patients (28 eyes), 7 male and 8 female (mean age, 43 years; range: 7 to 70 years) were identified. Diagnoses included HLA-B27-associated anterior uveitis (n = 4), sarcoidosis (n = 2), juvenile idiopathic arthritis (n = 2), idiopathic retinal vasculitis with uveitis (n = 2), pars planitis (n = 2), Adamantiades-Behçet disease (n = 1), birdshot retinochoroidopathy (n = 1), and Crohn's disease (n = 1). Mean duration of ocular disease was 8 years (range: 1 to 29 years). Treatment with infliximab (n = 11), etanercept (n = 2), or adalimumab (n = 2) was initiated. One patient with etanercept was switched to infliximab due to lack of clinical response. Clinical and angiographic regression of uveitis was observed within the first two months of therapy in all patients, and was maintained throughout the entire follow-up period (mean 18 months; range: 3 - 72 months). Recurrence was observed in 3 patients, and resolved after adjustment of therapy. Adverse events were recorded in only one patient (arterial hypotension). CONCLUSIONS: In this series of patients with chronic non-infectious uveitis, anti-TNF-alpha therapy was effective and safe. Further clinical studies are needed to determine an adequate duration of therapy.

A randomized trial of spiritual assessment of outpatients with schizophrenia: Patients' and clinicians' experience

Objective: Recovery-oriented care for patients with schizophrenia involves consideration of cultural issues, such as religion and spirituality. However, there is evidence that psychiatrists rarely address such topics. This study examined acceptance of a spiritual assessment by patients and clinicians, suggestions for treatment that arose from the assessment, and patient outcomes-in terms of treatment compliance and satisfaction with care (as measured by treatment alliance). Methods: Outpatients with psychosis were randomly assigned to two groups: an intervention group that received traditional treatment and a religious and spiritual assessment (N=40) and a control group that received only traditional treatment (N=38). Eight psychiatrists were trained to administer the assessment to their established and stable patients. After each administration, the psychiatrist attended a supervision session with a psychiatrist and a psychologist of religion. Baseline and three-month data were collected. Results: The spiritual assessment was well accepted by patients. During supervision, psychiatrists reported potential clinical uses for the assessment information for 67% of patients. No between-group differences in medication adherence and satisfaction with care were found at three months, although patients in the in- tervention group had significantly better appointment attendance dur- ing the follow-up period. Their interest in discussing religion and spirituality with their psychiatrists remained high. The process was not as well accepted by psychiatrists. Conclusions: Spiritual assessment can raise important clinical issues in the treatment of patients with chronic schizophrenia. Cultural factors, such as religion and spirituality, should be considered early in clinical training, because many clinicians are not at ease addressing such topics with patients.

Assessing alpine plant vulnerability to climate change: A modeling perspective

The potential ecological impact of ongoing climate change has been much discussed. High mountain ecosystems were identified early on as potentially very sensitive areas. Scenarios of upward species movement and vegetation shift are commonly discussed in the literature. Mountains being characteristically conic in shape, impact scenarios usually assume that a smaller surface area will be available as species move up. However, as the frequency distribution of additional physiographic factors (e.g., slope angle) changes with increasing elevation (e.g., with few gentle slopes available at higher elevation), species migrating upslope may encounter increasingly unsuitable conditions. As a result, many species could suffer severe reduction of their habitat surface, which could in turn affect patterns of biodiversity. In this paper, results from static plant distribution modeling are used to derive climate change impact scenarios in a high mountain environment. Models are adjusted with presence/absence of species. Environmental predictors used are: annual mean air temperature, slope, indices of topographic position, geology, rock cover, modeled permafrost and several indices of solar radiation and snow cover duration. Potential Habitat Distribution maps were drawn for 62 higher plant species, from which three separate climate change impact scenarios were derived. These scenarios show a great range of response, depending on the species and the degree of warming. Alpine species would be at greatest risk of local extinction, whereas species with a large elevation range would run the lowest risk. Limitations of the models and scenarios are further discussed.

Pediatric tracheotomy: a 30-year experience.

BACKGROUND/PURPOSE: The aim of this study was to investigate changes of pediatric tracheotomy practice over time. METHODS: A retrospective analysis of all tracheotomies at the University Children's Hospital Zurich from January 1990 to December 2009 was performed. Data analyzed included the indication for tracheotomy, patient comorbidities, age, duration of cannulation, and complications. The second part of the study consisted of comparing our results with data from an earlier study done at the same institution by Simma et al. (Eur J Pediatr 1994;153:291-296) reviewing the patients with tracheotomies treated from 1979 to 1989. RESULTS: Between 1990 and 2009, 119 patients were included. The indication for tracheotomy was airway obstruction in 70% and prolonged ventilation in 30%. 70% of the patients were operated on before 1 year of age. Serious postoperative complications occurred in 25 patients (23%). There was one death related to tracheotomy. Successful decannulation was achieved in 60%, on average 28 months after tracheotomy. The decannulation rate in patients with airway obstruction was 74% compared to 52% for the patients in prolonged ventilation group; a statistically significant difference was observed (p < 0.05). The longitudinal analysis showed an increase of indications for prolonged ventilation and a trend toward decreased tracheotomy complications. CONCLUSION: Over 30 years, a shift in the indications of pediatric tracheotomy, with an increasing number of procedures performed for prolonged ventilation, was found. The tracheotomy-related mortality was under 1%. Tracheotomy remains a valid and safe option for pediatric patients. Level of evidence 2c.

External beam radiotherapy ± chemotherapy in the treatment of anal canal cancer: a single-institute long-term experience on 100 patients.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1-4N0-3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3-G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

Renal arteries: navigator-gated balanced fast field-echo projection MR angiography with aortic spin labeling: initial experience.

A cardiac-triggered free-breathing three-dimensional balanced fast field-echo projection magnetic resonance (MR) angiographic sequence with a two-dimensional pencil-beam aortic labeling pulse was developed for the renal arteries. For data acquisition during free breathing in eight healthy adults and seven consecutive patients with renal artery disease, real-time navigator technology was implemented. This technique allows high-spatial-resolution and high-contrast renal MR angiography and visualization of renal artery stenosis without exogenous contrast agent or breath hold. Initial promising results warrant larger clinical studies.

The experience of transplantation for patients and their significant ones: A difficult encounter of two worlds

Objectives This paper reports on a longitudinal qualitative study exploring concerns of 60 patients before and after transplantation. Methods Semi-structured interviews were conducted without time constraints in a protected space out of the hospital. Qualitative analysis was performed. Results Prior to transplantation, all patients talked freely about negative feelings, stigmatisation, being misunderstood by others, loneliness and culpability caused by increasing physical dependency or abandoned roles. They mentioned alternative ways to cope (magic, spirituality), and even expressed their right to let go. In a subset of 13 patients, significant ones allowed themselves in the interview, or were integrated on the request of the patients. In this modified setting, two illness-worlds were confronted. If common themes were mentioned (e.g., modified life plans, restricted space, physical and psychological barriers), they were experienced differently. Fear of transplantation or guilt towards the donors was overtly expressed, often for the first time. Mutual hiding of anxiety in order to protect loved ones or to prevent loss of control was disclosed. The significant ones talked about accumulated stress and exhaustion related to the physical degradation of the patient, fear of the unpredictable evolution of illness and financial problems, and stressed their difficulty to adapt adequately to the fluctuating state of the patient. After transplantation, other themes emerged, where difficulty in disclosure was observed: intensive care and near death experiences, being a transplanted person, debt to the donor and his/her family, fear of rejection. Conclusions With the self-imposed strategy of hiding concerns to protect one another, a discrepancy between two illness-worlds was created. When concerns were confronted during the interviews, a new mutual understanding emerged. Patients and their families stated the need for sharing concerns in the course of illness.

Cost-effective experimental design to support modeling of concentration-response functions

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments

Video-assisted thoracoscopic resection of a small pulmonary nodule after computed tomography-guided localization with a hook-wire system. Experience in 45 consecutive patients.

BACKGROUND: This study is a single-institution validation of video-assisted thoracoscopic (VATS) resection of a small solitary pulmonary nodule (SPN) previously localized by a CT-guided hook-wire system in a consecutive series of 45 patients. METHODS: The records of all patients undergoing VATS resection for SPN preoperatively localized by CT-guided a hook-wire system from January 2002 to December 2004 were assessed with respect to failure to localize the lesion by the hook-wire system, conversion thoracotomy rate, duration of operation, postoperative complications, and histology of SPN. RESULTS: Forty-five patients underwent 49 VATS resections, with simultaneous bilateral SPN resection performed in 4. Preoperative CT-guided hook-wire localization failed in two patients (4%). Conversion thoracotomy was necessary in two patients (4%) because it was not possible to resect the lesion by a VATS approach. The average operative time was 50 min. Postoperative complications occurred in 3 patients (6%), one hemothorax and two pneumonia. The mean hospital stay was 5 days (range: 2-18 days). Histological assessment revealed inflammatory disease in 17 patients (38%), metastasis in 17 (38%), non-small-cell lung cancer (NSCLC) in 4 (9%), lymphoma in 3 (6%), interstitial fibrosis in 2 (4%), histiocytoma in one (2%), and hamartoma in one (2%). CONCLUSIONS: Histological analysis of resected SPN revealed unexpected malignant disease in more than 50% of the patients indicating that histological clarification of SPN seems warranted. Video-assisted thoracoscopic resection of SPN previously localized by a CT-guided hook-wire system is related to a low conversion thoracotomy rate, a short operation time, and few postoperative complications, and it is well suited for the clarification of SPN.

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Eight years experience from a skeletal dysplasia referral center in a tertiary hospital in Southern India: A model for the diagnosis and treatment of rare diseases in a developing country.

We report on a series of 514 consecutive diagnoses of skeletal dysplasia made over an 8-year period at a tertiary hospital in Kerala, India. The most common diagnostic groups were dysostosis multiplex group (n = 73) followed by FGFR3 (n = 49) and osteogenesis imperfecta and decreased bone density group (n = 41). Molecular confirmation was obtained in 109 cases. Clinical and radiographic evaluation was obtained in close diagnostic collaboration with expert groups abroad through Internet communication for difficult cases. This has allowed for targeted biochemical and molecular studies leading to the correct identification of rare or novel conditions, which has not only helped affected families by allowing for improved genetic counseling and prenatal diagnosis but also resulted in several scientific contributions. We conclude that (1) the spectrum of genetic bone disease in Kerala, India, is similar to that of other parts of the world, but recessive entities may be more frequent because of widespread consanguinity; (2) prenatal detection of skeletal dysplasias remains relatively rare because of limited access to expert prenatal ultrasound facilities; (3) because of the low accessibility to molecular tests, precise clinical-radiographic phenotyping remains the mainstay of diagnosis and counseling and of gatekeeping to efficient laboratory testing; (4) good phenotyping allows, a significant contribution to the recognition and characterization of novel entities. We suggest that the tight collaboration between a local reference center with dedicated personnel and expert diagnostic networks may be a proficient model to bring current diagnostics to developing countries. © 2014 Wiley Periodicals, Inc.

Estimating dormant and active hematopoietic stem cell kinetics through extensive modeling of bromodeoxyuridine label-retaining cell dynamics.

Bone marrow hematopoietic stem cells (HSCs) are responsible for both lifelong daily maintenance of all blood cells and for repair after cell loss. Until recently the cellular mechanisms by which HSCs accomplish these two very different tasks remained an open question. Biological evidence has now been found for the existence of two related mouse HSC populations. First, a dormant HSC (d-HSC) population which harbors the highest self-renewal potential of all blood cells but is only induced into active self-renewal in response to hematopoietic stress. And second, an active HSC (a-HSC) subset that by and large produces the progenitors and mature cells required for maintenance of day-to-day hematopoiesis. Here we present computational analyses further supporting the d-HSC concept through extensive modeling of experimental DNA label-retaining cell (LRC) data. Our conclusion that the presence of a slowly dividing subpopulation of HSCs is the most likely explanation (amongst the various possible causes including stochastic cellular variation) of the observed long term Bromodeoxyuridine (BrdU) retention, is confirmed by the deterministic and stochastic models presented here. Moreover, modeling both HSC BrdU uptake and dilution in three stages and careful treatment of the BrdU detection sensitivity permitted improved estimates of HSC turnover rates. This analysis predicts that d-HSCs cycle about once every 149-193 days and a-HSCs about once every 28-36 days. We further predict that, using LRC assays, a 75%-92.5% purification of d-HSCs can be achieved after 59-130 days of chase. Interestingly, the d-HSC proportion is now estimated to be around 30-45% of total HSCs - more than twice that of our previous estimate.