Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Background: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors. Methods: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02–7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48–0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75–1.34). Conclusions: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.Fil: Mertz, Dominik. Mc Master University; CanadáFil: Lo, Calvin Ka Fung. Mc Master University; CanadáFil: Lytvyn, Lyubov. Mc Master University; CanadáFil: Ortiz, Justin R.. Organizacion Mundial de la Salud; ArgentinaFil: Loeb, Mark. Mc Master University; CanadáFil: Ang, Li Wei. Ministry of Health; SingapurFil: Anlikumar, Mehta Asmita. Amrita Vishwa Vidyapeetham; IndiaFil: Bonmarin, Isabelle. Santé publique; FranciaFil: Borja Aburto, Victor Hugo. Instituto Mexicano del Seguro Social; MéxicoFil: Burgmann, Heinz. Medical University Vienna; AustriaFil: Carratalà, Jordi. Universidad de Barcelona; España. Instituto de Investigación Biomédica de Bellvitge; España. Spanish Network for Research in Infectious Diseases; EspañaFil: Chowell, Gerardo. Georgia State University; Estados Unidos. National Institutes of Health; Estados UnidosFil: Cilloniz, Catia. Universidad de Barcelona; España. Instituto de Investigaciones Biomédicas August Pi i Sunyer; EspañaFil: Cohen, Jessica. Centers for Disease Control and Prevention; Estados UnidosFil: Cutter, Jeffery. Ministry of Health; SingapurFil: Filleul, Laurent. Santé publique; Francia. French National Public Health Agency; FranciaFil: Garg, Shikha. Centers for Disease Control and Prevention; Estados UnidosFil: Geis, Steffen. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Helferty, Melissa. Public Health Agency; CanadáFil: Huang, Wan Ting. Taiwan Centers for Disease Control; ChinaFil: Jain, Seema. Centers for Disease Control and Prevention; Estados UnidosFil: Sevic, Biljana Joves. Institute for Pulmonary Diseases of Vojvodina; SerbiaFil: Kelly, Paul. Australian Capital Territory Health Directorate; Australia. Australian National University Medical School; AustraliaFil: Kusznierz, Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; ArgentinaFil: Lehners, Nicola. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Lenzi, Luana. Universidade Federal do Paraná; BrasilFil: Ling, Ivan T.. Sir Charles Gairdner Hospital; AustraliaFil: Mitchell, Robyn. Public Health Agency; CanadáFil: Mulrennan, Siobhain A.. Sir Charles Gairdner Hospital; Canadá. University of Western Australia; AustraliaFil: Nishioka, Sergio A.. Ministerio de Salud de Brasil; BrasilFil: Norton, Robert. Townsville Hospital; AustraliaFil: Oh, Won Sup. Kangwon National University School of Medicine; Corea del SurFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Management of patients with chronic cough using a clinical protocol: A prospective observational study

Background and aims: Chronic cough is a common symptom the aetiology of which can be challenging to diagnose. Diagnostic protocols for chronic cough have required the use of specialist investigations which are not always easily available. We wanted to determine whether patients with chronic cough can be successfully managed using a clinical algorithm.Methods: 112 consecutive patients with chronic cough were prospectively recruited into this study. They were assessed by history, physical examination, chest radiograph, spirometry and reversibility to nebulised salbutamol. A clinical diagnosis was made and the patient had an 8-week trial of appropriate therapy. Further therapeutic trials were carried out depending on response to treatment and the possible differential diagnoses. Investigations were carried out in cases of failed clinical trials and to exclude specific pathology. The " clinical arm" comprised patients managed on the basis of clinical assessment and without any investigations. The " investigative arm" comprised those who needed further investigations.Results: 81 (72%) were managed in the clinical arm. Of these 74 (66%) were discharged following response to therapy. 31 (28%) patients were converted to the investigative arm after failure of diagnosis in the clinical protocol. The commonest causes of cough were gastroesophageal reflux, asthma and chronic rhinitis. 51 (45.5%) patients responded to therapy based on diagnosis at initial assessment while a further 23 (20.5%) patients responded to sequential clinical trials for the commonest causes of cough. Cough severity score improved by a mean of 3.6 points on a numeric response score (from 0-10, p < 0.0001).Conclusion: It is possible to manage a majority of chronic cough patients successfully using a protocol based on presenting symptoms and therapeutic trials for the common causes of cough. © 2013 Ojoo et al.; licensee BioMed Central Ltd

High usability of a smartphone application for reporting symptoms in adults with cystic fibrosis

© 2017, The Author(s) 2017. Introduction: In cystic fibrosis, exacerbations impair lung function and health-related quality of life, increase healthcare costs and reduce survival. Delayed reporting of worsening symptoms can result in more severe exacerbations and worse clinical outcomes; therefore there is a need for a novel approach to facilitate the early identification and treatment of exacerbations in this population. This study investigated the usability of a smartphone application to report symptoms in adults with cystic fibrosis, and the observer agreement in clinical decision-making between senior clinicians interpreting smartphone application responses. Methods: Adults with cystic fibrosis used the smartphone application weekly for four weeks. The application comprised 10 yes/no questions regarding respiratory symptoms and two regarding emotional well-being. Usability was measured with the System Usability Scale; Observer agreement was tested by providing a cystic fibrosis physician and a nurse practitioner with 45 clinical scenarios. For each scenario the clinicians, who were blinded to each other's responses, were asked to indicate whether or not they would: (i) initiate telephone contact, and/or (ii) request a clinic visit for the individual. Results: Ten participants (five female), aged mean (SD) 33 (11) years, FEV1 49 (27)% predicted completed the study. The mean (SD) System Usability Scale score was 94 (6). There was perfect agreement between clinicians for initiating contact with the participant (? = 1.0, p &lt; 0.001), and near-perfect for requesting a clinic visit (? = 0.86, p &lt; 0.001). Discussion: The use of a smartphone application for reporting symptoms in adults with cystic fibrosis has excellent usability and near-perfect agreement between senior clinicians when interpreting the application responses

Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis

Background: Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases. Methods: In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed. Results: Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo. Conclusions: In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes