Treatment of lower extremity telangiectasias in women by foam sclerotherapy vs. Nd:YAG laser: a prospective, comparative, randomized, open-label trial.

BACKGROUND Telangiectasias of the lower extremities are very common. There are no blinded, randomized, controlled clinical trials comparing laser modalities with the gold standard sclerotherapy, while the few available studies encompass small patients cohorts. OBJECTIVE This prospective, randomized, open-label trial compares the efficacy of sclerotherapy with polidocanol vs. long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser in the treatment of leg telangiectasias. PATIENTS AND METHODS Fifty-six female patients with primary leg telangiectasias and reticular veins (C1A or S Ep AS 1 PN ) were included in the study. One leg was randomly assigned to get treatment with the multiple synchronized long-pulsed Nd:YAG laser, while the other received foam sclerotherapy with polidocanol 0.5%. The patients were treated in two sessions at intervals of 6 weeks. The patients were evaluated by the handling physician after 6 weeks and 6 months. Two investigators assessed blindly at the end of the study the photographs for clearing of the vessels using a six-point scale from 1 (no change) to 6 (100% cleared). Patients reported about pain sensation and outcome satisfaction. RESULTS According to the handling dermatologist, at the last follow-up, there was an improvement of 30-40% with a median of 3 (IQR 2) and a good improvement of 50-70% with a median of 4 (IQR 2) after laser treatment and sclerotherapy respectively. In contrast, according to the blinded investigators, there was a median of 5 (IQR 1) with a very good improvement of >70% after both therapies. Improvement was achieved more quickly by sclerotherapy, although at the last follow-up visit there was no difference in clearance between the two groups as assessed by the blinded experts (P-value 0.84). The degree of patient's satisfaction was very good and similar with both therapeutic approaches. There was a significant difference (P-value 0.003) regarding pain perception between the types of therapy. Laser was felt more painful than sclerotherapy. CONCLUSION Telangiectasias of the lower extremities can be successfully treated with either synchronized long-pulsed Nd:YAG laser or sclerotherapy. The 1064-nm long-pulsed Nd:YAG laser is associated with more pain and is suitable especially in case of needle phobia, allergy to sclerosants and in presence of small veins with telangiectatic matting, while sclerotherapy can also treat the feeder veins.

Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.

SETTING Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Genetics of upper and lower airway diseases in the horse.

Genetic predispositions for guttural pouch tympany, recurrent laryngeal neuropathy and recurrent airway obstruction (RAO) are well documented. There is also evidence that exercise-induced pulmonary haemorrhage and infectious diseases of the respiratory tract in horses have a genetic component. The clinical expression of equine respiratory diseases with a genetic basis results from complex interactions between the environment and the genetic make-up of each individual horse. The genetic effects are likely to be due to variations in several genes, i.e. they are polygenic. It is therefore unlikely that single gene tests will be diagnostically useful in these disorders. Genetic profiling panels, combining several genetic factors with an assessment of environmental risk factors, may have greater value, but much work is still needed to uncover diagnostically useful genetic markers or even causative variants for equine respiratory diseases. Nonetheless, chromosomal regions associated with guttural pouch tympany, recurrent laryngeal neuropathy and RAO have been identified. The association of RAO with other hypersensitivities and with resistance to intestinal parasites requires further study. This review aims to provide an overview of the available data and current thoughts on the genetics of equine airway diseases.

Which clinical signs predict hypoxaemia in young Senegalese children with acute lower respiratory tract disease?

BACKGROUND Acute lower respiratory tract diseases are an important cause of mortality in children in resource-limited settings. In the absence of pulse oximetry, clinicians rely on clinical signs to detect hypoxaemia. OBJECTIVE To assess the diagnostic value of clinical signs of hypoxaemia in children aged 2 months to 5 years with acute lower respiratory tract disease. METHODS Seventy children with a history of cough and signs of respiratory distress were enrolled. Three experienced physicians recorded clinical signs and oxygen saturation by pulse oximetry. Hypoxaemia was defined as oxygen saturation <90%. Clinical predictors of hypoxaemia were evaluated using adjusted diagnostic odds ratios (aDOR). RESULTS There was a 43% prevalence of hypoxaemia. An initial visual impression of poor general status [aDOR 20·0, 95% CI 3·8-106], severe chest-indrawing (aDOR 9·8, 95% CI 1·5-65), audible grunting (aDOR 6·9, 95% CI 1·4-25) and cyanosis (aDOR 26·5, 95% CI 1·1-677) were significant predictors of hypoxaemia. CONCLUSION In children under 5 years of age, several simple clinical signs are reliable predictors of hypoxaemia. These should be included in diagnostic guidelines.

Shorter time since inflammatory bowel disease diagnosis in children is associated with lower mental health in parents.

AIM This study assessed the mental health of parents of children with inflammatory bowel disease (IBD), compared their mental health with age-matched and gender-matched references and examined parental and child predictors for mental health problems. METHODS A total of 125 mothers and 106 fathers of 125 children with active and inactive IBD from the Swiss IBD multicentre cohort study were included. Parental mental health was assessed by the Symptom Checklist 27 and child behaviour problems by the Strengths and Difficulties Questionnaire. Child medical data were extracted from hospital records. RESULTS While the mothers reported lower mental health, the fathers' mental health was similar, or even better, than in age-matched and gender-matched community controls. In both parents, shorter time since the child's diagnosis was associated with poorer mental health. In addition, the presence of their own IBD diagnosis and child behaviour problems predicted maternal mental health problems. CONCLUSIONS Parents of children with IBD may need professional support when their child is diagnosed, to mitigate distress. This, in turn, may help the child to adjust better to IBD. Particular attention should be paid to mothers who have their own IBD diagnosis and whose children display behaviour problems.

A Swiss paradox? Higher income inequality of municipalities is associated with lower mortality in Switzerland.

It has long been surmised that income inequality within a society negatively affects public health. However, more recent studies suggest there is no association, especially when analyzing small areas. This study aimed to evaluate the effect of income inequality on mortality in Switzerland using the Gini index on municipality level. The study population included all individuals >30 years at the 2000 Swiss census (N = 4,689,545) living in 2,740 municipalities with 35.5 million person-years of follow-up and 456,211 deaths over follow-up. Cox proportional hazard regression models were adjusted for age, gender, marital status, nationality, urbanization, and language region. Results were reported as hazard ratios (HR) with 95 % confidence intervals. The mean Gini index across all municipalities was 0.377 (standard deviation 0.062, range 0.202-0.785). Larger cities, high-income municipalities and tourist areas had higher Gini indices. Higher income inequality was consistently associated with lower mortality risk, except for death from external causes. Adjusting for sex, marital status, nationality, urbanization and language region only slightly attenuated effects. In fully adjusted models, hazards of all-cause mortality by increasing Gini index quintile were HR = 0.99 (0.98-1.00), HR = 0.98 (0.97-0.99), HR = 0.95 (0.94-0.96), HR = 0.91 (0.90-0.92) compared to the lowest quintile. The relationship of income inequality with mortality in Switzerland is contradictory to what has been found in other developed high-income countries. Our results challenge current beliefs about the effect of income inequality on mortality on small area level. Further investigation is required to expose the underlying relationship between income inequality and population health.

The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry.

BACKGROUND Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

BACKGROUND Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. DISCUSSION It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction. TRIAL REGISTRATION TRIAL REGISTRATION NUMBER http://www.clinicaltrials.gov; Identifier: NCT02165774.

PCSK9 inhibitors: emerging treatment to lower cholesterol?

The achievement rate of recommended low-density lipoprotein cholesterol (LDL-C) targets of < 1.8 mmol/l for secondary prevention in very high risk patients is difficult. Observational studies reported that loss of function mutation of the PCS9 was associated with LDL-C decrease level and reduction of cardiovascular events. Monoclonal antibodies to PCSK9 (REGN727 and AMG 145, PSCK9 inhibitors) have been tested in clinical studies of phase I and II and showed LDL-C level reduction of 60-70% compared to placebo. This approach appears safe and well-tolerated. The PCSK9 inhibitors are now tested in large phase III clinical studies to assess the long-term safety and efficacy of this new promising approach.

The trouble with quality filtering based on relative Cramér-Rao lower bounds.

Cramér Rao Lower Bounds (CRLB) have become the standard for expression of uncertainties in quantitative MR spectroscopy. If properly interpreted as a lower threshold of the error associated with model fitting, and if the limits of its estimation are respected, CRLB are certainly a very valuable tool to give an idea of minimal uncertainties in magnetic resonance spectroscopy (MRS), although other sources of error may be larger. Unfortunately, it has also become standard practice to use relative CRLB expressed as a percentage of the presently estimated area or concentration value as unsupervised exclusion criterion for bad quality spectra. It is shown that such quality filtering with widely used threshold levels of 20% to 50% CRLB readily causes bias in the estimated mean concentrations of cohort data, leading to wrong or missed statistical findings-and if applied rigorously-to the failure of using MRS as a clinical instrument to diagnose disease characterized by low levels of metabolites. Instead, absolute CRLB in comparison to those of the normal group or CRLB in relation to normal metabolite levels may be more useful as quality criteria. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Blind Deconvolution via Lower-Bounded Logarithmic Image Priors

In this work we devise two novel algorithms for blind deconvolution based on a family of logarithmic image priors. In contrast to recent approaches, we consider a minimalistic formulation of the blind deconvolution problem where there are only two energy terms: a least-squares term for the data fidelity and an image prior based on a lower-bounded logarithm of the norm of the image gradients. We show that this energy formulation is sufficient to achieve the state of the art in blind deconvolution with a good margin over previous methods. Much of the performance is due to the chosen prior. On the one hand, this prior is very effective in favoring sparsity of the image gradients. On the other hand, this prior is non convex. Therefore, solutions that can deal effectively with local minima of the energy become necessary. We devise two iterative minimization algorithms that at each iteration solve convex problems: one obtained via the primal-dual approach and one via majorization-minimization. While the former is computationally efficient, the latter achieves state-of-the-art performance on a public dataset.