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Objectives: In subsistence populations, high physical activity is typically maintained throughout pregnancy. Market integration shifts activity patterns to resemble industrialized populations, with more time allocated to sedentary behavior. Daasanach semi-nomadic pastoralists living in northern Kenya face lifestyle heterogeneity due to the emergence of a market center. We investigate how Daasanach women manage the energetic demands of pregnancy with subsistence labor tasks and how market integration relates to variation in energetic demands, physical activity, and coping strategies., Methods: We conducted nine focus group discussions with 72 pregnant women. We also deployed wrist-worn fitness trackers with 21 pregnant women in two community types: central or peripheral to the market center to capture variation in market integration. Data from focus group discussions were analyzed using thematic analysis. We used multiple linear regression to examine the relationship between gestational age and physical activity., Results: We identified themes of increased fatigue, diet restrictions, and assistance with labor tasks during pregnancy. Gestational age negatively predicted mean daily steps, with a decrease of 1160 ± 437 steps per day with each consecutive pregnancy month. Stratified by community type, gestational age only negatively predicted mean daily steps for peripheral communities, with a decrease of 1443 ± 629 steps per day with each consecutive pregnancy month., Conclusions: Results suggest that physical activity differs with market integration early, but not late, in pregnancy. Daasanach women cope with the energetic demands of pregnancy by reducing physical activity late in pregnancy and receiving assistance with labor tasks from family and neighbors., (© 2024 Wiley Periodicals LLC.)

Climate change is triggering environmental mobility through chronic water problems and punctuated events. Thinking about moving locations, or "mobility ideation", is the precursor to migration intentionality and actual migration. Drawing on the embodiment construct, this study examines how the worst drought in recent history in the Horn of Africa affected water-related mobility ideation and, in turn, fingernail cortisol concentration (FCC), a chronic stress biomarker, among Daasanach semi-nomadic pastoralists in northern Kenya. To address these questions, we primarily draw on survey, anthropometric, water quality, and biomarker data among 175 adults living in seven communities in 2022. We used mixed-effects ordered logistic regression to test how livestock wealth, water insecurity, food insecurity, and anxiety/depression symptom scores were associated with household mobility ideation. We then used generalized linear models to test the association between mobility ideation on FCC. Thinking about moving at least once due to water problems increased from pre-drought in 2019 (55%) to during the drought in 2022 (92%), while actual mobility declined. Livestock wealth, while associated with actual mobility in the prior year, was protective against increased mobility ideation, while water insecurity, food insecurity, and anxiety/depression symptoms were associated with greater odds of thinking of leaving in 2022. Compared to adults who did not consider moving, those who considered moving rarely, sometimes, and often had FCC levels 18.1% higher (95% CI, 1.01-1.38; p = 0.039), 19.4% higher (1.01-1.41; p = 0.040), and 32.3% higher (1.01-1.73; p = 0.039), respectively, with results consistent in sensitivity analyses. Extreme climatic events in water scarce regions may increase mobility ideation through worsened experiential indicators of well-being and resource insecurity. Mobility ideation may capture measures of adversity suffered by pastoralists and signify climate distress. This research broadens understanding of how droughts get under the skin by leading to resource insecurity and triggering thoughts of moving, which increases chronic stress., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Weather and climate patterns play an intrinsic role in societal health, yet a comprehensive synthesis of specific hazard-mortality causes does not currently exist. Country-level health burdens are thus highly uncertain, but harnessing collective expert knowledge can reduce this uncertainty, and help assess diverse mortality causes beyond what is explicitly quantified. Here, surveying 30 experts, we provide the first structured expert judgement of how weather and climate directly impact mortality, using the UK as an example. Current weather-related mortality is dominated by short-term exposure to hot and cold temperatures leading to cardiovascular and respiratory failure. We find additional underappreciated health outcomes, especially related to long-exposure hazards, including heat-related renal disease, cold-related musculoskeletal health, and infectious diseases from compound hazards. We show potential future worsening of cause-specific mortality, including mental health from flooding or heat, and changes in infectious diseases. Ultimately, this work could serve to develop an expert-based understanding of the climate-related health burden in other countries., Competing Interests: Declaration of interests YTEL was funded by a University of Bristol fellowship in Climate and Health. EB was funded by Policy Bristol. CR is funded by a UKRI Future Leaders Fellowship (MR/V021672). NSF received support of H2020 MSCA IF (grant ID 846824). AG was supported by the Medical Research Council-UK (MR/V034162/1). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Chronic histiocytic intervillositis (CHI) is a recurrent placental lesion where maternal macrophages infiltrate the intervillous space. Its cause is unknown, though due to similarities to rejected allografts one hypothesis is that CHI represents maternal-fetal rejection. Here, virtual crossmatching was applied to healthy pregnancies and those with a history of CHI. Anti-HLA antibodies, measured by Luminex, were present in slightly more controls than CHI (8/17 (47.1%) vs 5/14 (35.7%)), but there was no significant difference in levels of sensitisation or fetal specific antibodies. Quantification of immunohistochemical staining for HLA-Class II was increased in syncytiotrophoblast of placentas with CHI (Grade 0.44 [IQR 0.1-0.7]) compared to healthy controls (0.06 [IQR 0-0.2]) and subsequent pregnancies (0.13 [IQR 0-0.3]) (P = 0.0004). HLA-Class II expression was positively related both to the severity of CHI (r = 0.67) and C4d deposition (r = 0.48). There was no difference in overall C4d and HLA-Class I immunostaining. Though increased anti-HLA antibodies were not evident in CHI, increased expression of HLA-Class II at the maternal-fetal interface suggests that they may be relevant in its pathogenesis. Further investigation of antibodies immediately after diagnosis is warranted in a larger cohort of CHI cases to better understand the role of HLA in its pathophysiology., (© 2024. The Author(s).)

Competing Interests: Declaration of interests CD was supported by the UK Natural Environment Research Council (NE/R010811/1) and the UK Natural Environment Research Council Independent Research Fellowship (NE/N01524X/1) and contributes to the Sustainable and Healthy Food Systems project supported by the Wellcome Trust (205200/Z/16/Z). MD was supported by the Wellcome Trust's Complex Urban Systems for Sustainability and Health (CUSSH) project (209387/Z/17/Z). YL was supported by the US National Aeronautics and Space Administration Applied Sciences Program (80NSSC21K0507). RL was supported by a Royal Society Dorothy Hodgkin Fellowship. MSo was supported by Horizon 2020 project EXHAUSTION (820655) and Academy of Finland HEATCOST (334798). SHG and JKWL were supported by Singapore's National Research Foundation, Singapore's Prime Minister's Office, under its Campus for Research Excellence and Technological Enterprise programme. IH was supported by the UK Research and Innovation (UKRI) Engineering and Physical Sciences Research Council Centre for Research in Energy Demand Solutions (EP/R035288/1) and UKRI APEx (NE/T001887/1). JM was supported by the German Ministry for Education and Research (01LA1826A and 03SFK5J0). ML was supported by the Sloan Foundation. All other authors declare no competing interests.

Exposure to air pollutants is known to exacerbate asthma, with prior studies focused on associations between single pollutant exposure and asthma exacerbations. As air pollutants often exist as a complex mixture, there is a gap in understanding the association between complex air pollutant mixtures and asthma exacerbations. We evaluated the association between the air pollutant mixture (52 pollutants) and pediatric asthma exacerbations., Method: This study focused on children (age ≤ 19 years) who lived in Douglas County, Nebraska, during 2016-2019. A seasonal-scale joint association between the outdoor air pollutant mixture adjusting for potential confounders (temperature, precipitation, wind speed, and wind direction) in relation to pediatric asthma exacerbation-related emergency department (ED) visits was evaluated using the generalized weighted quantile sum (qWQS) regression with repeated holdout validation., Results: We observed associations between air pollutant mixture and pediatric asthma exacerbations during spring (lagged by 5 days), summer (lag 0-5 days), and fall (lag 1-3 days) seasons. The estimate of the joint outdoor air pollutant mixture effect was higher during the summer season (adjusted-β WQS = 1.11, 95% confidence interval [CI]: 0.66, 1.55), followed by spring (adjusted-β WQS = 0.40, 95% CI: 0.16, 0.62) and fall (adjusted-β WQS = 0.20, 95% CI: 0.06, 0.33) seasons. Among the air pollutants, PM 2.5 , pollen, and mold contributed higher weight to the air pollutant mixture., Conclusion: There were associations between outdoor air pollutant mixture and pediatric asthma exacerbations during the spring, summer, and fall seasons. Among the 52 outdoor air pollutant metrics investigated, PM 2.5 , pollen (sycamore, grass, cedar), and mold ( Helminthosporium , Peronospora , and Erysiphe ) contributed the highest weight to the air pollutant mixture., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA VENTURE (VENTURE) study (NCT02528214), dupilumab versus placebo reduced oral corticosteroid (OCS) dose and improved clinical outcomes in patients with OCS-dependent severe asthma. Dupilumab efficacy in patients with varying disease burden (defined by baseline OCS dose) has not been assessed., Objective: This post hoc analysis of VENTURE evaluated dupilumab efficacy across subgroups defined by baseline OCS dose., Methods: The OCS dose, proportion no longer needing OCS at week 24, annualized severe exacerbation rate, and least squares mean change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 second at week 24 were evaluated in VENTURE patients with OCS-dependent severe asthma receiving dupilumab 300 mg every 2 weeks versus placebo, categorized by a baseline OCS dose of less than 10 mg/d or 10 or more mg/d., Results: Dupilumab reduced daily OCS dose from baseline at week 24 in both dose groups. In dupilumab-/placebo-treated patients with a baseline OCS dose of less than 10 mg/d and 10 or more mg/d, 72%/42% and 37%/23% stopped OCS by week 24 (P < .01/P < .05), respectively. Dupilumab significantly reduced the annualized severe exacerbation rate by 71% and 48% (P < .01/P < .05). At week 24, dupilumab improved pre- and post-bronchodilator forced expiratory volume in 1 second in patients in both dose groups., Conclusions: In patients with OCS-dependent severe asthma receiving lower or higher baseline OCS doses, dupilumab significantly reduced the OCS dose and improved the likelihood of no longer requiring OCS while also reducing exacerbations and improving lung function., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical trials have shown treatment benefits of dupilumab in patients with uncontrolled asthma for up to 1 year. This study aimed to evaluate the long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma, as data for extended treatment with dupilumab beyond 1 year are not available., Methods: TRAVERSE was an open-label extension study in 362 hospitals and clinical centres across 27 countries that assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in adults and adolescents (aged 12-84 years) with moderate-to-severe or oral-corticosteroid-dependent severe asthma who had completed a previous dupilumab asthma study (phase 2A EXPEDITION, phase 2B DRI [P2b], phase 3 QUEST, or VENTURE). The primary endpoint was the number and percentage of patients with any treatment-emergent adverse events. Secondary endpoints included annualised exacerbation rate (AER) over the treatment period and change from parent study baseline in pre-bronchodilator FEV 1 , the five-item asthma control questionnaire (ACQ-5), the asthma quality of life questionnaire (AQLQ), type 2 biomarkers (blood eosinophils and serum total IgE), and anti-drug antibodies (ADAs). Statistical analyses were descriptive. We report safety in all enrolled patients, and efficacy in patients with non-oral-corticosteroid-dependent asthma and in subgroups, including patients with a type 2 inflammatory phenotype who received 148 weeks of treatment. This study is registered with ClinicalTrials.gov, NCT02134028., Findings: Between Aug 5, 2014, and Oct 11, 2019, of 2302 patients assessed for eligibility, 2282 adults and adolescents were enrolled (median age 50 years, 62·1% female and 37·9% male). Safety during TRAVERSE was consistent with the known dupilumab safety profile. The proportion of patients reporting treatment-emergent adverse events throughout the study duration was similar to that observed in the parent studies and ranged from 76·3% to 94·7%. The most frequently reported treatment-emergent adverse events were nasopharyngitis (17·5-25·9%), injection-site erythema (2·2-23·4%), and bronchitis (9·3-19·0%). Serious asthma exacerbations (0·5-3·6%) and pneumonia (0·7-2·7%) were the most frequently reported serious adverse events. There were four treatment-emergent adverse events leading to death. Efficacy during TRAVERSE was also consistent with the results of parent studies. In patients who were non-oral-corticosteroid-dependent, AER remained low (0·277-0·327) across parent study and treatment groups, pre-bronchodilator FEV 1 improvements were sustained to the end of treatment at week 96 (mean changes from parent study baseline ranged from 0·22 L [SD 0·44] to 0·33 L [0·44] across parent study and treatment groups), and improvements in ACQ-5 and AQLQ scores were sustained to the last timepoint assessed at week 48. Rapid improvements were observed in pre-bronchodilator FEV 1 and sustained improvements were seen in all outcome measures for patients given dupilumab who previously received placebo in parent studies; further improvements in AER, asthma control, and health-related quality of life were observed in patients who continued receiving dupilumab. Blood eosinophils and serum total IgE decreased progressively. ADA status had no effect on safety or efficacy. In the subgroup of patients with a type 2 inflammatory phenotype followed-up for 148 weeks, AER decreased progressively, and initial lung function improvements were sustained over 148 weeks., Interpretation: Data show that safety and efficacy of dupilumab in adult and adolescent patients with moderate-to-severe asthma are sustained when treatment is extended up to 148 weeks. These findings therefore support the long-term use of dupilumab in this patient population., Funding: Sanofi and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests MEW reports personal fees from AstraZeneca, Boehringer Ingelheim, Equillium, Gala Therapeutics, Genentech, Genzyme, Mylan, Novartis, Pulmatrix, ResTORbio, Regeneron Pharmaceuticals, Sentien Biotechnologies, and Teva; and grants and personal fees from GSK and Sanofi. LBF reports grant support through the Asthma & Allergy Center, Bellevue, NE, USA, from 3M, Aimmune, AstraZeneca, DBV Technologies, Genentech, Glenmark, GSK, Hoffmann-La Roche, Novartis, Pearl, Sanofi, and Teva; and has served as a national consultant for Sanofi. JFM has served as a consultant for AstraZeneca and Sanofi; received speaker fees from Boehringer Ingelheim, GSK, Menarini, Novartis, and Uriach; and received research grants from Novartis. IDP reports speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva; payments for organisation of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Sanofi, and Teva; consultant fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RespiVert, Sanofi, Schering-Plough, and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, and Teva; and a research grant from Chiesi. AP reports grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and Teva; personal fees and non-financial support from Menarini, Novartis, and Zambon; and grants from Sanofi. AB reports non-financial support during the conduct of the study from GSK; serving as an investigator on clinical trials promoted by Acceleron Pharma, Actelion, Galapagos, MSD, Nuvaira, Pulmonx, United Therapeutic, and Vertex Pharmaceuticals; grants and personal fees from Boehringer Ingelheim; and personal fees from AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals, and Sanofi. HW reports serving as a consultant and receiving travel and speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi, and Takeda. MC reports research support from the American Lung Association, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Patient-Centered Outcomes Research Institute, and Sanofi; serving as a consultant for 4D Pharma, Aviragen Therapeutics, Boston Scientific, Genentech, Nuvaira, Sanofi, Teva, Therabron Therapeutics, Theravance Biopharma, Vectura, and Vida Pharma; speaker fees from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron Pharmaceuticals, Sanofi, and Teva; and royalties from Elsevier. NMN reports speaker fees from ALK, AstraZeneca, Boehringer Ingelheim, Glenmark, MSD, Novartis, Sanofi, Stallergenes Greer, and Teva. YT has served as a consultant for AstraZeneca, Kyorin Pharmaceuticals, and Sanofi. DL has received research funding from Sanofi. CD reports travel and speaker fees from Allergy Therapeutics, ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, HAL Allergy, Inmunotek, Menarini, Novartis, Pfizer, Sanofi-Aventis, Stallergenes Greer, Takeda, and Teva. KRC reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Genentech, Grifols, Kamada, Mereo BioPharma, Novartis, Roche, and Sanofi; grants from Amgen, Baxter, and GSK; and personal fees from the GSK-Canadian Institutes of Health Research chair in Respiratory Health Care Delivery at the University Health Network, and Merck. XM, AHK, PJR, UK, LPM, EL, and MH are Sanofi employees and hold stock or stock options in the company. YZ, YD, FAK, MR, and NA are employees and shareholders at Regeneron Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The phase 3 LIBERTY ASTHMA QUEST study (ClinicalTrials.gov: NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma., Methods: Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) at weeks 12 and 52, and the five-item Asthma Control Questionnaire (ACQ-5) score at weeks 24 and 52 were assessed in patients with ≥1, ≥2 or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL -1 or baseline exhaled nitric oxide fraction ≥25 ppb and baseline inhaled corticosteroid (ICS) dose., Results: Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54-90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV 1 (least squares (LS) mean difference versus placebo: ≥1 exacerbations, 0.15-0.25 L; ≥2 exacerbations, 0.12-0.32 L; ≥3 exacerbations, 0.09-0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbations, -0.30 to -0.57; ≥2 exacerbations, -0.29 to -0.56; ≥3 exacerbations, -0.43 to -0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups., Conclusions: Dupilumab significantly reduced severe exacerbations and improved FEV 1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose., Competing Interests: Conflict of interest: J. Corren reports nonfinancial support for research from Sanofi, outside the submitted work. Conflict of interest: C.H. Katelaris reports nonfinancial support (advisory board member and principal study investigator) from Sanofi, outside the submitted work. Conflict of interest: M. Castro reports nonfinancial support for research from the American Lung Association, Gossamer, NIH, PCORI and Shionogi, personal fees for lectures and nonfinancial support for research from AstraZeneca, personal fees for lectures and consultancy, and nonfinancial support for research from Boehringer Ingelheim and Sanofi, personal fees for consultancy and nonfinancial support for research from Novartis, personal fees for consultancy from Boston Scientific and Vida Pharma, personal fees for lectures and consultancy from Teva, personal fees for lectures from Genentech and Regeneron Pharmaceuticals, Inc., personal fees (royalties) from Elsevier, outside the submitted work. Conflict of interest: J.F. Maspero reports being a speaker for AstraZeneca, GlaxoSmithKline, Menarini, Novartis, Sanofi, Teva and Uriach; and has received research grants from Novartis, outside the submitted work. Conflict of interest: L.B. Ford reports nonfinancial support for research from AstraZeneca, DBV, Genentech, Gossamer, Novartis and Teva, personal fees for consultancy from Sanofi, outside the submitted work. Conflict of interest: D.M.G. Halpin reports personal fees for lectures and advisory board work from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Novartis, Pfizer, Sandoz and Sanofi, outside the submitted work. Conflict of interest: M.S. Rice is an employee of Sanofi and may hold stock and/or stock options in the company. Conflict of interest: A. Radwan is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Conflict of interest: Y. Deniz is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Conflict of interest: P.J. Rowe is an employee of Sanofi and may hold stock and/or stock options in the company. Conflict of interest: A. Teper is a former employee of Sanofi. Conflict of interest: M. Djandji is an employee of Sanofi and may hold stock and/or stock options in the company., (Copyright ©The authors 2021.)

Background: Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear., Methods: In a phase 2 trial, we randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (at a dose of 300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control, assessed in the itepekimab group and the combination group, as compared with the placebo group. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety., Results: A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, as compared with 41% of those in the placebo group; the corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42 (95% confidence interval [CI], 0.20 to 0.88; P = 0.02); in the combination group, 0.52 (95% CI, 0.26 to 1.06; P = 0.07); and in the dupilumab group, 0.33 (95% CI, 0.15 to 0.70). As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups., Conclusions: Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03387852.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: The effects of food insecurity linked to climate change will be exacerbated in subsistence communities that are dependent upon food systems for their livelihoods and sustenance. Place-and community-based forms of surveillance are important for growing an equitable evidence base that integrates climate, food, and health information as well as informs our understanding of how climate change impacts health through local and Indigenous subsistence food systems., Methods: We present a case-study from southwestern Uganda with Batwa and Bakiga subsistence communities in Kanungu District. We conducted 22 key informant interviews to map what forms of monitoring and knowledge exist about health and subsistence food systems as they relate to seasonal variability. A participatory mapping exercise accompanied key informant interviews to identify who holds knowledge about health and subsistence food systems. Social network theory and analysis methods were used to explore how information flows between knowledge holders as well as the power and agency that is involved in knowledge production and exchange processes., Results: This research maps existing networks of trusted relationships that are already used for integrating diverse knowledges, information, and administrative action. Narratives reveal inventories of ongoing and repeated cycles of observations, interpretations, evaluations, and adjustments that make up existing health and subsistence food monitoring and response. These networks of local health and subsistence food systems were not supported by distinct systems of climate and meteorological information. Our findings demonstrate how integrating surveillance systems is not just about what types of information we monitor, but also who and how knowledges are connected through existing networks of monitoring and response., Conclusion: Applying conventional approaches to surveillance, without deliberate consideration of the broader contextual and relational processes, can lead to the re-marginalization of peoples and the reproduction of inequalities in power between groups of people. We anticipate that our findings can be used to inform the initiation of a place-based integrated climate-food-health surveillance system in Kanungu District as well as other contexts with a rich diversity of knowledges and existing forms of monitoring and response.

Background: Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial (NCT02414854), dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV 1 ) in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline (blood eosinophils and fractional exhaled nitric oxide)., Objective: To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR., Methods: Severe asthma exacerbation rates, FEV 1 , asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed., Results: A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and ≥1 perennial aeroallergen specific immunoglobulin E (IgE) level ≥0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P < .05 for both) and improved FEV 1 at week 12 by 0.14 L and 0.18 L (P < .01 for both); greater efficacy was observed in patients with elevated baseline blood eosinophil counts (≥300 cells/μL) and fractional exhaled nitric oxide. Dupilumab treatment also numerically improved the 5-item Asthma Control Questionnaire and Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores and suppressed type 2 inflammatory biomarkers., Conclusion: Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitis-specific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV 1 ) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype., Objective: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS)., Methods: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV 1 , patient-reported outcomes, type 2 biomarkers, and safety were assessed., Results: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup., Conclusion: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Dupilumab, a fully human anti-IL-4Rα monoclonal antibody, inhibits signaling of both interleukin (IL)-4 and IL-13, which are key drivers of type 2-mediated inflammation. Dupilumab is approved in the EU, USA, and other countries for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. Following positive phase 2 results in asthma, the phase 3 Liberty Asthma QUEST trial was initiated to provide further evidence for dupilumab efficacy and safety in patients with uncontrolled, moderate-to-severe asthma., Methods: Liberty Asthma QUEST is a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (NCT02414854) in patients with persistent asthma who are receiving continuous treatment with inhaled corticosteroids (ICS) plus one or two other asthma controller medicines. A total of 1902 patients (aged ≥ 12 years) were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on therapy with subcutaneously administered dupilumab 200 or 300 mg every 2 weeks or matched placebo. The study consisted of a 4 ± 1-week screening period, 52-week randomized treatment period, and 12-week post-treatment follow-up period. All patients continued to receive their prescribed ICS plus up to two additional controller medications. The primary efficacy endpoints were annualized rate of severe exacerbation events during the 52-week treatment period and absolute change from baseline in pre-bronchodilator FEV 1 at week 12., Conclusion: Uncontrolled asthma patients with persistent symptoms represent a population of significant unmet need, for whom new treatments are required. Patients with severe asthma are at high risk of asthma exacerbations, and face an accelerated decline in lung function and impaired quality of life. QUEST examines the efficacy of dupilumab in this at-risk patient population; it is the largest placebo-controlled study in uncontrolled, moderate-to-severe asthma with a biologic agent to date, and the only phase 3 study of a biologic therapy of asthma that enrolled patients irrespective of baseline type 2 inflammatory biomarker levels., Funding: Sanofi and Regeneron Pharmaceuticals, Inc. CLINICAL TRIALS., Gov Identifier: NCT02414854.

Background: Intranasal corticosteroids are generally considered the most effective medication class for controlling allergic rhinitis. Previous comparative studies with oral antihistamines have been only partially informative due to a variety of variables encountered during their execution., Objective: To compare fluticasone propionate nasal spray (FPNS) with the second-generation antihistamine cetirizine (oral tablet) and with placebo in a head-to-head study in a 2-week treatment study during fall ragweed season., Methods: A total of 978 subjects were screened for this study. Six hundred and eighty-two subjects were randomized into the study (170 subjects, FPNS 200 mcg once daily; 170, cetirizine 10 mg once daily; 171, FPNS placebo; 171, cetirizine placebo) and comprised the intent-to-treat population. A 1-week placebo run-in was followed by a 2-week active treatment period during which time a total nasal symptom score (TNSS), total ocular symptom score, and the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire were collected., Results: The primary efficacy end point was the mean change from baseline over the entire treatment period in A.M. reflective TNSS. The TNSS was the sum of the four individual nasal congestion, nasal itching, rhinorrhea, and sneezing scores, in which each symptom was scored on a scale of 0 to 3. Both FPNS and cetirizine improved the primary end point when compared with placebo during the active treatment period. Although there was a trend that favored FPNS with regard to the primary and secondary end points, there was not a statistical difference between the two treatments., Conclusion: FPNS and cetirizine were equally effective in treating fall seasonal allergic rhinitis during a 2-week head-to-head treatment investigation. Clinical trial NCT01916226, www.clinicaltrials.gov.

Chemokine-directed leukocyte migration is crucial for effective immune and inflammatory responses. Conventional chemokine receptors (cCKRs) directly control cell movement; atypical chemokine receptors (ACKRs) regulate coexpressed cCKRs; and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo, a process referred to as scavenging. A leukocyte's migratory and chemokine-scavenging potential is determined by which cCKRs and ACKRs it expresses, and by the ligand specificity, signaling properties, and chemokine internalization capacity of these receptors. Most chemokines can bind at least one cCKR and one ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). In this study, by using fluorescent CCL2 uptake to label cells bearing functional CCL2 receptors, we have defined the expression profile, scavenging activity, and ligand specificity of CCL2 receptors on mouse leukocytes. We show that qualitative and quantitative differences in the expression of CCR2 and ACKR2 endow individual leukocyte subsets with distinctive CCL2 receptor profiles and CCL2-scavenging capacities. We reveal that some cells, including plasmacytoid dendritic cells, can express both CCR2 and ACKR2; that Ly6C(high) monocytes have particularly strong CCL2-scavenging potential in vitro and in vivo; and that CCR2 is a much more effective CCL2 scavenger than ACKR2. We confirm the unique, overlapping, ligand specificities of CCR2 and ACKR2 and, unexpectedly, find that cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent chemokine uptake assays were instrumental in providing these novel insights into CCL2 receptor biology, and the sensitivity, specificity, and versatility of these assays are discussed., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Some patients with allergic rhinitis (AR) may prefer a "dry" intranasal corticosteroid aerosol to avoid certain sensory perceptions such as the "wet feeling in the nose" and the "dripping down the throat" associated with aqueous nasal sprays. A nonaqueous hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol with an established efficacy and safety profile was approved to treat the nasal symptoms associated with AR in adult and adolescent patients. This study was designed to evaluate ease of use and patient satisfaction with the BDP nasal aerosol device in patients with perennial AR (PAR). In this phase 3, randomized, double-blind, parallel-group, placebo-controlled study, eligible patients (≥12 years of age) with PAR were randomly assigned to receive BDP nasal aerosol at 320 micrograms/day or placebo for 6 weeks. At the end of the treatment period, patients assessed device ease of use and satisfaction with the device using a questionnaire with a 5-point representative scale (not at all, not very, neither nor, somewhat, very [certain/easy/satisfactory]). Nearly all patients (89.7%) reported that the BDP nasal aerosol device with integrated dose counter was "very easy" or "somewhat easy" to use. The majority of patients (87.5%) also indicated that it was "very easy" or "somewhat easy" to tell when the device was empty, compared with only 42.3% who were "very certain" or "somewhat certain" of being able to tell when previously used aqueous nasal spray devices were empty. Overall, patient satisfaction with the BDP nasal aerosol device was high: 65.7% responded that they were "very satisfied" or "somewhat satisfied" and only 3.6% were "not satisfied at all" or "not very satisfied." These results indicate that the majority of patients considered the BDP nasal aerosol device easy to use and reported a high degree of satisfaction with the device compared with other nasal sprays they had used in the past.

Background: Adrenomodulin (ADM) is a peptide hormone secreted in response to cellular strain such as ischemia and is believed to have a beneficial effect on the cardiovascular system. However, the epidemiological relationships between ADM and measurements of haemodynamics, arteriosclerosis and atherosclerosis are not well established. The aim of this study was to investigate the association between the mid-regional part of pro-ADM (MR-proADM) and brachial pulse pressure (PP), carotid intima-media thickness (cIMT) and carotid atherosclerosis., Method: This study has a cross-sectional design and includes 4924 individuals (mean age 58 years, 40% men) from Malmö, Sweden, examined between 1991 and 1994. Participants underwent physical examination, measurement of MR-proADM and ultrasound of the carotid arteries., Results: There was a positive association between MR-proADM and brachial PP, cIMT as well as a carotid plaque score. The associations were significant after adjustment for age, sex, BMI, hypertension, diabetes, low-density lipoprotein cholesterol and smoking., Conclusion: ADM is positively associated with brachial PP and both carotid IMT and plaques, suggesting a role for ADM in early haemodynamic pathophysiology related to arteriosclerosis and the atherosclerotic plaque development.

Fluorescent activated cell sorting (FACS) is a powerful technique that allows rapid quantitative cell-by-cell analysis of the expression of multiple distinct proteins and the isolation of specific cell types from complex cellular mixtures. FACS-based detection of chemokine receptors is typically achieved using chemokine receptor-specific antibodies. However, this approach has some limitations, and, in our experience, many anti-chemokine receptor antibodies have poor signal-to-noise ratios and thus low sensitivity and reliability in FACS. Moreover, antibodies against some chemokine receptors are not commercially available, particularly in nonhuman species, and generating good antibodies against chemokine receptors is challenging and expensive. Here, we describe a simple alternative method of detecting chemokine receptors by FACS that relies on cellular internalization of fluorescently labelled chemokines. This approach detects chemokine receptors with high sensitivity, specificity, and reliability, and consistently outperforms antibody-based detection methods when applied to the analysis of mouse cells in our experience. It can also be used to study receptor specificity on primary cells and, since chemokines from one species often bind to receptors from other species, a single fluorescently labelled chemokine should allow reliable chemokine receptor detection and analysis across a range of species.

Background: Climate change is among the major challenges for health this century, and adaptation to manage adverse health outcomes will be unavoidable. The risks in Ontario - Canada's most populous province - include increasing temperatures, more frequent and intense extreme weather events, and alterations to precipitation regimes. Socio-economic-demographic patterns could magnify the implications climate change has for Ontario, including the presence of rapidly growing vulnerable populations, exacerbation of warming trends by heat-islands in large urban areas, and connectedness to global transportation networks. This study examines climate change adaptation in the public health sector in Ontario using information from interviews with government officials., Methods: Fifty-three semi-structured interviews were conducted, four with provincial and federal health officials and 49 with actors in public health and health relevant sectors at the municipal level. We identify adaptation efforts, barriers and opportunities for current and future intervention., Results: Results indicate recognition that climate change will affect the health of Ontarians. Health officials are concerned about how a changing climate could exacerbate existing health issues or create new health burdens, specifically extreme heat (71%), severe weather (68%) and poor air-quality (57%). Adaptation is currently taking the form of mainstreaming climate change into existing public health programs. While adaptive progress has relied on local leadership, federal support, political will, and inter-agency efforts, a lack of resources constrains the sustainability of long-term adaptation programs and the acquisition of data necessary to support effective policies., Conclusions: This study provides a snapshot of climate change adaptation and needs in the public health sector in Ontario. Public health departments will need to capitalize on opportunities to integrate climate change into policies and programs, while higher levels of government must improve efforts to support local adaptation and provide the capacity through which local adaptation can succeed.

A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above ~44°N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.

Background: The contribution made by fish ponds (pisciculture) to malaria transmission in the Peruvian Amazon remains to be confirmed. Recent entomological evidence indicates that Anopheles darlingi, the main malaria vector in the region, is frequently found in fish ponds along the Iquitos-Nauta road (Loreto, Peru). The aim of this study was to quantify the effect of fish pond density on malaria occurrence., Methods: A retrospective 30-month cohort study was conducted in eight communities along the Iquitos-Nauta road. Malaria incidence was ascertained from malaria registries of the local health post, which consist of data from both active and passive surveillance (247 cases). Fish pond density was measured using an interpreted satellite image and information on potential confounders was collected through interviewer-administered questionnaires., Results: A total of 1018 individuals from 234 eligible households (90% of the 259 total number of households in the study area) provided complete information on exposures and outcome. Fish pond density was found to be a significant predictor of malaria occurrence (aOR=1.23; 95% CI: 1.09-1.38)., Conclusion: The association between fish pond density and malaria suggests that fish ponds contribute to malaria transmission in the region. These results have important implications for the prevention and control of malaria and the development of pisciculture as an important economic activity in Amazonia and beyond., (2010. Published by Elsevier B.V.)

Background: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously., Objective: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS)., Methods: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning., Results: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001)., Conclusions: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.

Background: We have noted several patients who had rhinitis and/or asthma symptoms when exposed to Cannabis plants in the summer months. Cannabis plants are common in the Midwest., Objectives: To examine whether Cannabis might be a clinically important allergen, we determined Cannabis pollination patterns in the Omaha area for 5 years, the prevalence of skin test positivity, and the association with respiratory symptoms., Methods: Airborne Cannabis (and other weed) pollens were collected using a Rotorod air impactor, and pollen counts were done using a standardized protocol., Results: Measurable Cannabis pollen count was not recorded until the last 2 weeks of July. Peak pollination typically occurred during mid- to late-August, and comprised up to 36% of the total pollen counts. Cannabis pollen was not observed after mid-September. To determine the prevalence of skin test positivity, we added Cannabis to the multi-test routine skin test battery. Seventy-eight of 127 patients tested (61%) were skin test positive. Thirty of the 78 patients were randomly selected to determine if they had allergic rhinitis and/or asthma symptoms during the Cannabis pollination period. By history, 22 (73%) claimed respiratory symptoms in the July through September period. All 22 of these subjects were also skin test positive to weeds pollinating during the same period as Cannabis (ragweed, pigweed, cocklebur, Russian thistle, marsh elder, or kochia)., Conclusions: The strong association between skin test reactivity, respiratory symptoms, and pollination period suggests that Cannabis could be a clinically important aeroallergen for certain patients and should be further studied.

Background: Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking., Objective: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy., Methods: Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals., Results: Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment., Conclusion: Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.

Background: Attempts to delineate efficacy and safety differences among inhaled corticosteroids have been difficult because of the lack of well-controlled, comparative studies reported in the medical literature., Methods: A randomized, double-blind, double-dummy study was conducted in 24 outpatient centers. A total of 291 male and female patients at least 12 years of age with asthma (FEV1 between 50% and 80% of predicted value), who had previously received maintenance therapy with beclomethasone dipropionate or triamcinolone acetonide, were switched to treatment with fluticasone propionate powder (250 microg twice daily), triamcinolone acetonide aerosol (200 microg four times daily), or placebo for 24 weeks., Results: Mean increase in FEV1 from baseline to end point was significantly (p = 0.009) greater in patients switched to treatment with fluticasone compared with patients switched to treatment with triamcinolone (0.27 L and 0.07 L, respectively). At end point, mean increase in morning peak expiratory flow from baseline was 21 L/min with fluticasone compared with mean decreases of 6 L/min and 28 L/min with triamcinolone and placebo, respectively (p < 0.001 vs triamcinolone and placebo). Supplemental rescue albuterol use decreased by 30% from baseline with fluticasone (p < 0.05 vs triamcinolone and placebo) compared with triamcinolone (6%) or placebo (increased by 50%). The percentage of patients withdrawn from the study because they met predefined lack-of-efficacy criteria was higher with placebo (60%) and triamcinolone (27%) than with fluticasone (17%). Incidence of adverse events and low morning plasma cortisol concentrations were similar across treatment groups except for oral candidiasis (p = 0.035, fluticasone vs placebo)., Conclusion: Fluticasone propionate powder twice daily (500 microg/day) was superior in efficacy to triamcinolone acetonide aerosol four times daily (800 microg/day) in patients with persistent asthma.

Objective: To more closely approximate the use of a nonsteroidal inhaled anti-inflammatory medication for asthma, nedocromil sodium, under actual ambulatory practice conditions., Design: Large, open-label trial., Patients: One thousand two hundred one patients from 286 primary care and specialty centers., Intervention: Four weeks of treatment with nedocromil sodium (4 mg delivered from the valve and 3.5 mg delivered from the mouthpiece of a metered inhalor [2 puffs, four times daily])., Main Outcome Measures: Asthma symptom scores, peak expiratory flow rate, a lifestyle assessment measures questionnaire, and mean number of days missed per month from work or school., Results: Statistically significant improvements were seen after 1 and 4 weeks of treatment for cough, daytime and nighttime asthma, morning tightness, peak expiratory flow rate, and all four measured lifestyle assessment factors (P < .001). An additional clinically relevant outcome measure, mean number of days missed per month from work or school, was reduced by 75% (P < .001). No serious adverse reactions were reported., Conclusion: This study reproduces the high level of efficacy and safety of nedocromil that was previously reported in placebo-controlled clinical studies.

The purpose of this article is to present a review of several of the basic bunionectomy criteria as they apply to the so-called soft-tissue bunionectomy. A variation of the McBride bunionectomy is presented using a minimal traumatic technique, and a retrospective study of 80 cases is presented. It can be concluded from this study that the soft-tissue bunionectomy is a viable procedure when the appropriate criteria are present. It does appear, however, that this procedure will be successful in only the mildest cases of deformity.

The deformity of the hallux that is described in this article is most probably more common than we realize and is often seen in patients with mycotic nails and subungual exostosis. This pathology is easily corrected with a tenotomy-capsulotomy at the level of the distal interphalangeal joint. This procedure, when accomplished as described, does not affect the function of the hallux at the level of the metatarsophalangeal joint.