Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma

Background: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. Conclusion: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials. gov: NCT02231307)

Development and Process Evaluation of a 5-Week Exercise Program to Prevent Falls in People after Stroke: The FALLS Program

Falls are a common complication after stroke, with balance and gait deficits being the most important risk factors. Taking into account the specific needs and capacities of people with stroke, we developed the FALLS program (FALL prevention after Stroke), based on the “Nijmegen falls prevention program” (a proven-effective 5-week exercise program designed for community-dwelling elderly people). The program was tested in twelve community-dwelling persons with stroke, and a process evaluation was conducted with patients, trainers, health care professionals, and managers. The FALLS program was considered suitable and feasible by people with stroke in the study and relevant health care professionals, and recommendations for implementation in clinical practice have been suggested

Smooth HI Low Column Density Outskirts In Nearby Galaxies

This is an author-created, un-copyedited version of an article published in The Astronomical Journal. The Version of Record is available online at https://doi.org/10.3847/1538-3881/aabbaa.The low column density gas at the outskirts of galaxies as traced by the 21 cm hydrogen line emission (H i) represents the interface between galaxies and the intergalactic medium, i.e., where galaxies are believed to get their supply of gas to fuel future episodes of star formation. Photoionization models predict a break in the radial profiles of H i at a column density of ∼5 × 10 19 cm -2 due to the lack of self-shielding against extragalactic ionizing photons. To investigate the prevalence of such breaks in galactic disks and to characterize what determines the potential edge of the H i disks, we study the azimuthally averaged H i column density profiles of 17 nearby galaxies from the H i Nearby Galaxy Survey and supplemented in two cases with published Hydrogen Accretion in LOcal GAlaxieS data. To detect potential faint H i emission that would otherwise be undetected using conventional moment map analysis, we line up individual profiles to the same reference velocity and average them azimuthally to derive stacked radial profiles. To do so, we use model velocity fields created from a simple extrapolation of the rotation curves to align the profiles in velocity at radii beyond the extent probed with the sensitivity of traditional integrated H i maps. With this method, we improve our sensitivity to outer-disk H i emission by up to an order of magnitude. Except for a few disturbed galaxies, none show evidence of a sudden change in the slope of the H i radial profiles: the alleged signature of ionization by the extragalactic background.Peer reviewedFinal Accepted Versio

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo

Disruptive life event or reflexive instrument? On the regulation of hospital mergers from a quality of care perspective

Purpose – Despite the continuation of hospital mergers in many western countries, it is uncertain if and how hospital mergers impact the quality of care. This poses challenges for the regulation of mergers. The purpose of this paper is to understand: how regulators and hospitals frame the impact of merging on the quality and safety of care and how hospital mergers might be regulated, given their uncertain impact on quality and safety of care. Design/methodology/approach –This paper studies the regulation of hospital mergers in The Netherlands. In a qualitative study design, it draws on 30 semi-structured interviews with inspectors from the Dutch Health and Youth Care Inspectorate (Inspectorate) and respondents from three hospitals that merged between 2013 and 2015. This paper draws from literature on process-based regulation to understand how regulators can monitor hospital mergers. Findings – This paper finds that inspectors and hospital respondents frame the process of merging as potentially disruptive to daily care practices. While inspectors emphasise the dangers of merging, hospital respondents report how merging stimulated them to reflect on their care practices and how it afforded learning between hospitals. Although the Inspectorate considers mergers a risk to quality of care, their regulatory practices are hesitant. Originality/value – This qualitative study sheds light on how merging might affect key hospital processes and daily care practices. It offers opportunities for the regulation of hospital mergers that acknowledges rather than aims to dispel the uncertain and potentially ambiguous impact of mergers on quality and safety of car

Conflict in the Indian Kashmir Valley I: exposure to violence

ABSTRACT: BACKGROUND: India and Pakistan have disputed ownership of the Kashmir Valley region for many years, resulting in several conflicts since the end of partition in 1947. Very little is known about the prevalence of violence and insecurity in this population. METHODS: We undertook a two-stage cluster household survey in two districts (30 villages) of the Indian part of Kashmir to assess experiences with violence and mental health status among the conflict-affected Kashmiri population. The article presents our findings for confrontations with violence. Data were collected for recent events (last 3 months) and those occurring since the start of the conflict. Informed consent was obtained for all interviews. RESULTS: 510 interviews were completed. Respondents reported frequent direct confrontations with violence since the start of conflict, including exposure to crossfire (85.7%), round up raids (82.7%), the witnessing of torture (66.9%), rape (13.3%), and self-experience of forced labour (33.7%), arrests/kidnapping (16.9%), torture (12.9%), and sexual violence (11.6%). Males reported more confrontations with violence than females, and had an increased likelihood of having directly experienced physical/mental maltreatment (OR 3.9, CI: 2.7-5.7), violation of their modesty (OR 3.6, CI: 1.9-6.8) and injury (OR 3.5, CI: 1.4-8.7). Males also had high odds of self-being arrested/kidnapped (OR 8.0, CI: 4.1-15.5). CONCLUSION: The civilian population in Kashmir is exposed to high levels of violence, as demonstrated by the high frequency of deliberate events as detention, hostage, and torture. The reported violence may result in substantial health, including mental health problems. Males reported significantly more confrontations with almost all violent events; this can be explained by higher participation in outdoor activities

Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [90Y-DOTA0,Tyr3]octreotide may result in partial remissions in 10–25% of patients. The newer analogue [DOTA0,Tyr3]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0,Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide 177Lu, it has proved very successful in achieving tumour regression in animal models. The effects of 177Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3–6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi 177Lu-octreotate, to a final cumulative dose of 600–800 mCi, with treatment intervals of 6–9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with 177Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression