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A study of the health hazards for workers exposed to styrene in the Dutch glass-reinforced plastics industry was undertaken. The open mould techniques of filament winding, spraying and hand laminating were chosen for study because exposure of workers using them was expected to be high. Occupational hygiene surveys were conducted in four plants. In addition to measurements of exposure, data on health complaints were collected. In 12 smaller plants exposure was estimated in walk-through surveys. The results show that although most of the plants had implemented control measures such as ventilation and extraction, the levels of exposure constituted a health risk. Time-weighted average concentrations for workers involved in filament winding ranged from 134 to 716 mg m, for those who were spraying from 48 to 602 mgm and for those laminating manually from 18 to 538 mgm. The ‘no-adverse-effect level’ based on effects observed in man is considered to be 105 mg m, and the acute subjective health effects experienced by the population studied supported this value. To rduce exposure to below 105 mg m, control measures should combine engineering with codes of practice adapted to the particular process or processes employed. [ABSTRACT FROM PUBLISHER]

Background and Objectives: Cyclophosphamide has been the mainstay of treatment of ANCA-associated vasculitis. However, cyclophosphamide has unfavorable side effects and alternatives are needed. Evidence suggests that mycophenolate mofetil can induce sustained remission in nonlife-threatening disease. The purpose of this study was to compare the efficacy and safety of mycophenolate mofetil versus cyclophosphamide for the induction treatment of nonlife-threatening relapses of proteinase 3-ANCA- and myeloperoxidase-ANCA-associated vasculitis., Design, Setting, Participants, & Measurements: We conducted a multicenter randomized, controlled trial. Participants with a first or second relapse of ANCA-associated vasculitis were randomized to induction treatment with cyclophosphamide or mycophenolate mofetil both in combination with glucocorticoids. Maintenance therapy consisted of azathioprine in both arms. Primary outcome was remission at 6 months, and secondary outcomes included disease-free survival at 2 and 4 years., Results: Eighty-four participants were enrolled, of whom 41 received mycophenolate mofetil and 43 received cyclophosphamide. Eighty-nine percent of participants were proteinase 3-ANCA positive. At 6 months, 27 (66%) mycophenolate mofetil-treated participants versus 35 (81%) cyclophosphamide-treated participants were in remission ( P =0.11). Disease-free survival rates at 2 and 4 years were 61% and 39% for cyclophosphamide, respectively, and 43% and 32% for mycophenolate mofetil, respectively (at 4 years, log rank test, P =0.17)., Conclusions: We did not demonstrate mycophenolate mofetil to be similarly effective as cyclophosphamide in inducing remission of relapsed ANCA-associated vasculitis. However, mycophenolate mofetil might be an alternative to cyclophosphamide for the treatment of selected patients with nonlife-threatening relapses., (Copyright © 2019 by the American Society of Nephrology.)

Objectives: We aimed to investigate whether five potential functional haplotypes of the glucocorticoid receptor (GR) gene and a single-nucleotide polymorphism of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) are associated with clinical outcome in ANCA-associated vasculitis., Methods: Patients diagnosed with ANCA-associated vasculitis (n = 241) were genotyped for five polymorphisms of the GR gene and one polymorphism of the HSD11B1 gene. GR gene haplotypes were predicted based on genotyping results. Relapse-free survival, mortality, renal survival, metabolic adverse events and infections were compared between carriers and non-carriers of GR haplotypes and the HSD11B1 genotype., Results: Carriers of haplotype 4 (ER22/23EK + 9β+TthIII1) of GR had a significantly higher 5-year mortality risk [hazard ratio (HR) 4.5 (95% CI 1.6, 12.8)] and had a higher risk of developing end-stage renal disease [HR 7.4 (95% CI 1.9, 28.7)]. Carriers of a minor variant of HSD11B1 more frequently experienced relapse [HR 2.5 (95% CI 1.5, 4.1)] except if they also carried haplotype 1 (BclI) of GR. Homozygous carriers of haplotype 1 had a higher risk of developing dyslipidaemia [HR 4.1 (95% CI 1.8, 9.6)]. The occurrence of infections did not differ between GR haplotypes and HSD11B1 genotypes., Conclusion: Haplotypes 1 and 4 of GR and a polymorphism of the HSD11B1 gene were associated with clinically relevant inflammatory and metabolic outcomes in ANCA-associated vasculitis., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To assess the level of comprehensiveness of health technology assessment (HTA) practices around the globe and to formulate recommendations for enhancing legitimacy and fairness of related decision-making processes., Methods: To identify best practices, we developed an evaluation framework consisting of 13 criteria on the basis of the INTEGRATE-HTA model (integrative perspective on assessing health technologies) and the Accountability for Reasonableness framework (deliberative appraisal process). We examined different HTA systems in middle-income countries (Argentina, Brazil, and Thailand) and high-income countries (Australia, Canada, England, France, Germany, Scotland, and South Korea). For this purpose, desk research and structured interviews with relevant key stakeholders (N = 32) in the selected countries were conducted., Results: HTA systems in Canada, England, and Scotland appear relatively well aligned with our framework, followed by Australia, Germany, and France. Argentina and South Korea are at an early stage, whereas Brazil and Thailand are at an intermediate level. Both desk research and interviews revealed that scoping is often not part of the HTA process. In contrast, providing evidence reports for assessment is well established. Indirect and unintended outcomes are increasingly considered, but there is room for improvement. Monitoring and evaluation of the HTA process is not well established across countries. Finally, adopting transparent and robust processes, including stakeholder consultation, takes time., Conclusions: This study presents a framework for assessing the level of comprehensiveness of the HTA process in a country. On the basis of applying the framework, we formulate recommendations on how the HTA community can move toward a more integrated decision-making process using HTA., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially after treatment with orally administered cyclophosphamide., Methods: We retrospectively studied the onset of menopause and the influence of cyclophosphamide in women diagnosed as having AAV in our center between 1970 and 2012., Results: Ninety-four premenopausal women diagnosed as having AAV were included. Sixty-seven patients received cyclophosphamide, and 27 received other, mostly immunosuppressive, medication. Forty-six cyclophosphamide-treated women developed menopause, 22 of whom were considered to have primary ovarian insufficiency. None of the patients who were not treated with cyclophosphamide developed primary ovarian insufficiency. There was a significant association between a cumulative cyclophosphamide dose of >16.6 gm, versus a cumulative dose of <16.6 gm, and menopause (χ(2)  = 8.72, P = 0.003; odds ratio [OR] 2.60 [95% confidence interval 1.38-4.90]). In addition, there was a significant association between a cumulative cyclophosphamide dose of <16.6 gm, versus no cyclophosphamide exposure, and menopause (χ(2)  = 16.37, P < 0.001; OR 7.32 [95% confidence interval 2.79-19.20]). Both women who received cyclophosphamide and those who did not experienced involuntary childlessness., Conclusion: Earlier menopause and primary ovarian insufficiency frequently develop after oral cyclophosphamide therapy in premenopausal women with AAV. Involuntary childlessness is common after the development of primary ovarian insufficiency, but it also occurs in women not treated with cyclophosphamide. These findings emphasize the importance of the use of drugs that are not toxic to gonadal function in women of childbearing age., (© 2016, American College of Rheumatology.)

Goldenhar syndrome is characterized by the typical features of craniofacial microsomia (CFM) with the addition of epibulbar dermoids and vertebral anomalies. The aim of this study is to examine the objective differences between patients carrying a diagnosis of Goldenhar syndrome to those diagnosed with CFM. Thus, we performed an Institutional Review Board-approved retrospective chart review on all patients who presented with a diagnosis of CFM or Goldenhar syndrome from January 1990 to December 2012. Demographic, diagnosis, OMENS+ classification, accompanying diagnoses, and radiographic data were collected. For subjective analysis, subgroups were designed based on the diagnosis Goldenhar syndrome or CFM per history. For objective analysis, subgroups were designed based on the presence of epibulbar dermoids and/or vertebral anomalies. The cohorts were compared with respect to associated medical abnormalities and severity of CFM features. One hundred thirty eight patients met inclusion criteria. Epibulbar dermoids and vertebral anomalies were seen in 17% and 34% of the patients, respectively. Only 10 patients (7.2%) had both epibulbar dermoids and vertebral anomalies. The subjective "Goldenhar" group (N = 44, 32%) was found to have a higher percentage of bilaterally affected patients (P = 0.001), a more severe mandibular deformity (P = <0.001), a more severe soft tissue deformity (P = 0.01), and a higher incidence of macrostomia (P = 0.003). In the objective subgroup analysis, the only significant difference was found in the degree of soft tissue deficiency (P = 0.049). The diagnostic criteria of Goldenhar syndrome remain unclear, thereby making clinical use of the term "Goldenhar" inconsequential. Goldenhar syndrome is over diagnosed subjectively in patients who show more severe CFM features.

Background: Craniofacial microsomia encompasses a spectrum of diagnoses associated with variable degrees of mandibular hypoplasia, facial asymmetry, chin deviation, occlusal abnormalities, and potential airway compromise. This study presents one surgeon's experience with costochondral rib grafting for mandibular reconstruction in children with Pruzansky/Kaban type 2B and type 3 mandibular hypoplasia., Methods: An institutional review board-approved retrospective chart review was performed of all patients with craniofacial microsomia who underwent costochondral rib grafting for mandibular reconstruction performed by the senior author (S.P.B.) at The Children's Hospital of Philadelphia from January of 1998 to September of 2013. Demographic information, surgical history, operative details, postoperative complications, and outcomes were recorded. Plain radiographs and preoperative and postoperative three-dimensional computed tomographic scans were reviewed., Results: Two hundred fifty-five patients were diagnosed with craniofacial microsomia, and 22 patients met inclusion criteria. Twelve boys and 10 girls underwent grafting at an average age of 7.2 years. Thirty-three costochondral rib grafts were performed, 11 unilateral reconstructions and 11 bilateral reconstructions. Twelve hemimandibles were type 2B and 21 were type 3. No intraoperative complications were reported, and no incidence of graft resorption was noted. No additional procedures were required in 27 reconstructed hemimandibles (81.8 percent), whereas six (18.2 percent) required secondary distraction osteogenesis. Only one patient developed postoperative ankylosis. No malunion or nonunion was noted., Conclusion: The approach described in this article allowed the authors to obtain reliably good results with costochondral rib grafting for type 2B and type 3 mandibular hypoplasia associated with craniofacial microsomia., Clinical Question/level of Evidence: Therapeutic, IV.

Introduction: Low testosterone levels in men are associated with fatigue, limited physical performance and reduced health-related quality of life (HRQOL); however, this relationship has never been assessed in patients with anti-neutrophil cytoplasmic antibodies (ANCA) -associated vasculitides (AAV). The aim of this study was to assess the prevalence of androgen deficiency and to investigate the role of testosterone in fatigue, limited physical condition and reduced HRQOL in men with AAV., Methods: Male patients with AAV in remission were included in this study. Fatigue and HRQOL were assessed by the multi-dimensional fatigue inventory (MFI)-20 and RAND-36 questionnaires., Results: Seventy male patients with a mean age of 59 years (SD 12) were included. Scores of almost all subscales of both questionnaires were significantly worse in patients compared to controls. Mean total testosterone and free testosterone levels were 13.8 nmol/L (SD 5.6) and 256 pmol/L (SD 102), respectively. Androgen deficiency (defined according to Endocrine Society Clinical Practice Guidelines) was present in 47% of patients. Scores in the subscales of general health perception, physical functioning and reduced activity were significantly worse in patients with androgen deficiency compared to patients with normal androgen levels. Testosterone and age were predictors for the RAND-36 physical component summary in multiple linear regression analysis. Testosterone, age, vasculitis damage index (VDI) and C-reactive protein (CRP) were associated with the MFI-20 subscale of general fatigue., Conclusions: This study showed that androgen deficiency was present in a substantial number of patients with AAV. Testosterone was one of the predictors for physical functioning and fatigue. Testosterone may play a role in fatigue, reduced physical performance and HRQOL in male patients with AAV.