Comparison of a generic and a rhinitis-specific quality-of-life (QOL) instrument in patients with house dust mite allergy: Relationship between the SF-36 and rhinitis QOL questionnaire

Background: Generic and disease-specific quality-of-life (QOL) questionnaires are commonly used in subjects with allergic rhinitis (AR). AR, however, is closely associated with other disorders such as bronchial asthma and atopic dermatitis (AD). These co-morbid associations may have an effect on the inter-relation of generic and disease-specific QOL outcomes and the behaviour of this inter-relation in time. Objective: To unravel the inter-relationships between the outcome of a generic instrument (SF-36) and a disease-specific instrument (Rhinitis QOL Questionnaire (RQLQ)). Materials and methods: In the framework of a randomized clinical trial with respect to the efficacy of impermeable bedding covers in house dust mite (HDM) allergy, SF-36 and RQLQ were administered to 224 adults with AR and/or allergic asthma and/or AD at baseline and after 12 months of intervention. Regression analysis and canonical correlation were used to estimate overlap. Results: Overlap between SF-36 and RQLQ domains in terms of explained variance ranged from 6% to 56%. Canonical correlation yielded low coefficients (0.16-0.27). Moreover, both SF-36 and RQLQ s

MLPAinter for MLPA interpretation: An integrated approach for the analysis, visualisation and data management of Multiplex Ligation-dependent Probe Amplification

Background: Multiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.Results: Here, we developed a data management system, MLPAInter for MLPA interpretation, that is windows executable and has a stand-alone database for monitoring and interpreting the MLPA data stream that is generated from the experimental setup to analysis, quality control and visualisation. A statistical approach is applied for the normalisation and analysis of large series of MLPA traces, making use of multiple control samples and internal controls.Conclusions: MLPAinter visualises MLPA data in plots with information about sample replicates, normalisation settings, and sample characteristics. This integrated approach helps in the automated handling of large series of MLPA data and guarantees a quick and streamlined dataflow from the beginning of an experiment to an authorised report

Nij Bosma Zathe: partner met water en natuur

Het integreren van landbouw, waterbeheer en natuur is hierbij een belangrijk onderzoeksthema op het nieuwe praktijkcentrum Nij Bosma Zath

Evaluation of impermeable covers for bedding in patients with allergic rhinitis

BACKGROUND: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease. METHODS: Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention. RESULTS: A total

Immune checkpoint inhibitor-associated myocarditis:Case reports and a review of the literature

Immune checkpoint inhibitors (ICIs) are increasingly recognised to effectuate long-lasting therapeutic responses in solid tumours. However, ICI therapy can also result in various immune-related adverse events, such as ICI-associated myocarditis, a rare but serious complication. The clinical spectrum is wide and includes asymptomatic patients and patients with fulminant heart failure, making it challenging to diagnose this condition. Furthermore, the optimal diagnostic algorithm and treatment of ICI-associated myocarditis is unknown. In this review, we describe two cases on both ends of the spectrum and discuss the challenges in recognising, diagnosing and treating ICI-associated myocarditis

Tissue metabolic changes drive cytokine responses to Mycobacterium tuberculosis

Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis (Mtb). Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms (SNPs) that were trans-acting for in vitro cytokine responses to Mtb stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines. Our findings identify novel therapeutic targets in host metabolism that may shape protective immunity to tuberculosis

A Randomized Ph2 Study of MEDI0680 in Combination With Durvalumab vs. Nivolumab Monotherapy in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

BACKGROUND: MEDI0680 is a humanized anti-programmed cell death-1 (PD-1) antibody and durvalumab is an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase 2 study evaluated antitumor activity and safety of MEDI0680 plus durvalumab versus nivolumab monotherapy in immunotherapy naïve patients with advanced clear cell renal cell carcinoma who received at least one prior line of anti-angiogenic therapy. METHODS: Patients received either MEDI0680 (20 mg/kg) with durvalumab (750 mg) or nivolumab (240 mg), all IV Q2W. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included best overall response, progression-free survival (PFS), safety, overall survival (OS), and immunogenicity. Exploratory endpoints included changes in circulating tumor DNA (ctDNA), baseline tumor mutational burden (TMB), and tumor-infiltrated immune cell profiles. RESULTS: Sixty-three patients were randomized (combination, n = 42; nivolumab, n = 21). ORR was 16.7% (7/42; 95% CI, 7.0-31.4) with combination treatment and 23.8% (5/21; 95% CI, 8.2- 47.2) with nivolumab. Median PFS was 3.6 months in both arms; median OS was not reached in either arm. Due to AEs, 23.8% of patients discontinued MEDI0680 and durvalumab and 14.3% of patients discontinued nivolumab. In the combination arm, reduction in ctDNA fraction was associated with longer PFS. ctDNA mutational analysis did not demonstrate an association with response in either arm. Tumor-infiltrated immune profiles showed an association between immune cell activation and response in the combination arm. CONCLUSIONS: MEDI0680 combined with durvalumab was safe and tolerable; however, it did not improve efficacy versus nivolumab monotherapy

We’ve Been Down this Road Before: Evidence on the Health Consequences of Precarious Employment in Industrial Societies, 1840-1920

A large body of international scientific research now indicates that the growth of job insecurity, flexible/temporary work and precarious forms of self-employment have had significant negative consequences for occupational health and safety. What is often overlooked in debates over the ‘changing world of work’ is that today’s widespread use insecure and short term work is not new but represents a return to something more resembling labour markets in Australia, Europe and North America in the 19th and early 20th century. As this paper will seek to show, not only were precarious and exploitive working arrangements common during this period but the adverse effects of these on the health, safety and wellbeing was well documented in government inquiries, medical research, press reports and a variety of other sources. Drawing primarily on Australian and British sources, attention here will focus on casual labourers, sweated garment workers, the self-employed and merchant seamen. The paper highlights the valuable role historical research can play in shedding light on contemporary problems and policy debates.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business

A comparison of weekly versus 3-weekly cisplatin during adjuvant radiotherapy for high-risk head and neck cancer

SummaryObjectivesTo compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC).Materials and methodsConsecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin.ResultsOf 270 high risk patients, 60 received 3-weekly 100mg/m2 and 48 received weekly 50mg/m2 cisplatin during adjuvant radiotherapy (60–66Gy in 30–33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m2 (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m2 (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m2 was given to 67.7% of patients in the 3-weekly cohort and 85.2% (P=0.039) in the weekly cohort. The rate of feeding tube dependency 6months after treatment, osteoradionecrosis, neutropenic fever, and persistent renal function decline were not statistically different.ConclusionsAbout one half of high-risk HNSCC patients are not eligible for cisplatin during postoperative radiotherapy. Patients treated with weekly 50mg/m2 cisplatin received a higher cumulative dose with comparable toxicity as patients who received 3-weekly 100mg/m2 cisplatin. Efficacy and applicability to the frequently used weekly 40mg/m2 schedule remains to be evaluated

Comparison of Carboplatin With 5-Fluorouracil vs. Cisplatin as Concomitant Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Background: Chemoradiotherapy (CRT) including three cycles of cisplatin is considered the standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, around one-third of the patients cannot complete cisplatin because of toxicity. Carboplatin plus 5-fluorouracil (carbo-5FU) is another accepted treatment option with a different toxicity profile. We compared tolerability and efficacy of concomitant carbo-5FU and cisplatin. Patients and Methods: We conducted a retrospective analysis of LA-HNSCC patients treated with CRT in two Dutch cancer centers between 2007 and 2016. All patients received intensity-modulated radiotherapy. One center routinely administered carboplatin 300–350 mg/m2 at day 1, 22, and 43 followed by 5FU 600 mg/m2/day for 96 h. The other center used cisplatin 100 mg/m2 at day 1, 22, and 43. The primary endpoint of this study was chemotherapy completion rate. Secondary endpoints included overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis–free interval (DMFS), toxicity, and unplanned admissions. Results: In the carbo-5FU cohort (n = 211), 60.2% of the patients completed chemotherapy vs. 76.7% (p < 0.001) of the patients in the cisplatin cohort (n = 223). Univariate analysis showed a higher risk of death in the carbo-5FU cohort [hazard ratio (HR) 1.53, 95% CI, 1.09–2.14, p = 0.01] with a 3-year OS of 65.4 vs. 76.5% for cisplatin. OS was independently associated with T and N stage and p16 status, but not with chemotherapy regimen (HR 1.08, 95% CI, 0.76–1.55, p = 0.65). Three-year DFS was 70.0% for carbo-5FU vs. 78.6% for cisplatin (HR 1.37, 95% CI, 0.93–2.01, p = 0.05). A similar outcome was observed for both LRC (HR 1.27, 95% CI, 0.74–2.09, p = 0.4) and DMFS (HR 1.08, 95% CI 0.62–1.90, p = 0.77). The risk of discontinuation for chemotherapy-associated toxicity was higher in the carbo-5FU cohort than in the cisplatin cohort (relative risk = 1.69). Conclusion: LA-HNSCC patients treated with concomitant carbo-5FU completed chemotherapy less frequently than patients treated with cisplatin. Treatment regimen was not an independent prognostic factor for OS