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BackgroundThe analysis aimed to examine the impact of pulmonary exacerbations (PEs) and lung function on generic measures of HRQL in patients with cystic fibrosis (CF) using trial-based data.MethodsIn a 48-week randomized, placebo-controlled study of ivacaftor in patients ≥12 years with CF and a G551D-CFTR mutation the relationship between PEs, PE-related hospitalizations and percent predicted forced expiratory volume in one second (ppFEV1) with EQ-5D measures (index and visual analog scale [VAS]) was examined in post-hoc analyses. Multivariate mixed-effects models were employed to describe the association of PEs, PE-related hospitalizations, and ppFEV1 on EQ-5D measures.ResultsOne hundred sixty one patients (age: mean 25.5 [SD 9.5] years; baseline ppFEV1: 63.6 [16.4]) contributed 1,214 observations (ppFEV1: no lung dysfunction [n = 157], mild [n = 419], moderate [n = 572], severe [n = 66]). Problems were most frequently reported on pain/discomfort, anxiety/depression, and usual activities EQ-5D items. The mean (SE) EQ-5D index nominally decreased (worsened) with worsening severity of lung dysfunction (P = 0.070): 0.931 (0.023); mild: 0.923 (0.021); moderate: 0.904 (0.018); severe: 0.870 (0.020). 146 PEs were experienced by 72 patients, including 52 PEs (35.6 %) that required hospitalization. Mean EQ-5D index and VAS scores were lowest (worst) within 1 week (before or after PE start) for PEs requiring hospitalization. Pulmonary exacerbations, PE-related hospitalizations, and ppFEV1 were significant predictors of EQ-5D index and VAS.ConclusionsIn a clinical study of patients with CF (≥12 years of age and a G551D-CFTR mutation), PEs, primarily those requiring hospitalization, were associated with low EQ-5D index and VAS scores. The impact of ppFEV1 was relatively smaller. Reducing PEs, in particular those requiring hospitalization, would likely improve HRQL among these patients.Trial registrationClinicalTrials.gov, NCT00909532; URL: clinicaltrials.gov, May 26, 2009Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0465-z) contains supplementary material, which is available to authorized users.

ObjectiveThis study used a decision-analytic framework to assess the cost-effectiveness of brexpiprazole vs comparator branded therapies for reducing relapses and hospitalizations among adults with schizophrenia from a US payer perspective.MethodsAn economic model was developed to assess patients with stable schizophrenia initiating treatment with brexpiprazole (1–4 mg), cariprazine (1–6 mg), or lurasidone (40–80 mg) over a 1-year period. After 6 months, patients remained on treatment or discontinued due to relapse, adverse events, or other reasons. Patients who discontinued due to relapse or adverse events were assumed to have switched to other therapy, and those who discontinued due to other reasons were assumed to have received no therapy. Primary outcomes were incremental cost per relapse avoided and hospitalization avoided, and the secondary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity and scenario analyses were also conducted.ResultsBrexpiprazole was associated with the highest per-patient clinical effectiveness (avoided relapses 0.637, avoided hospitalizations 0.719, QALYs 0.707) among comparators, followed by cariprazine (avoided relapses 0.590, avoided hospitalizations 0.683, QALYs 0.683) and lurasidone (avoided relapses 0.400, avoided hospitalizations 0.536, QALYs 0.623). Annual per-patient health-care costs were lowest for brexpiprazole ($20,510), followed by cariprazine ($22,282) and lurasidone ($25,510). Brexpiprazole was the least costly and most effective treatment strategy for all outcomes. Results were sensitive to relapse rates and daily cost of brexpiprazole. Limitations include data principally obtained from drug-specific randomized withdrawal studies and lack of direct-comparison trials.ConclusionThis analysis evaluated brexpiprazole treatment for the reduction of schizophrenia relapses and hospitalizations over a 1-year period compared to other recently available branded antipsychotics, and excluded generic antipsychotic treatments. Brexpiprazole treatment may lead to clinical benefits and medical cost savings, and provides a cost-effective treatment option for patients relatively to other branded second-generation antipsychotics.

Intravenous rt-PA was associated with lower patients' disabilities, fewer in-hospital days, and comparable total costs compared to conservative therapy for the management of AIS.

Heterotopic ossification (HO) is the formation of abnormal mature lamellar bone in extra-skeletal sites, including soft tissues and joints, which result in high rates of disability. The understanding of the mechanism of HO is insufficient. The aim of this study was to explore biomarkers and pathological processes in HO+ samples. The gene expression profile GSE94683 was downloaded from the Gene Expression Omnibus database. Sixteen samples from nine HO- and seven HO+ subjects were analyzed. After data preprocessing, 3,529 genes were obtained for weighted gene co-expression network analysis. Highly correlated genes were divided into 13 modules. Finally, the cyan and purple modules were selected for further study. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the cyan module was enriched in a variety of components, including protein binding, membrane, nucleoplasm, cytosol, poly(A) RNA binding, biosynthesis of antibiotics, carbon metabolism, endocytosis, citrate cycle, and metabolic pathways. In addition, the purple module was enriched in cytosol, mitochondrion, protein binding, structural constituent of ribosome, rRNA processing, oxidative phosphorylation, ribosome, and non-alcoholic fatty liver disease. Finally, 10 hub genes in the cyan module [actin related protein 3 (ACTR3), ADP ribosylation factor 4 (ARF4), progesterone receptor membrane component 1 (PGRMC1), ribosomal protein S23 (RPS23), mannose-6-phosphate receptor (M6PR), WD repeat domain 12 (WDR12), synaptosome associated protein 23 (SNAP23), actin related protein 2 (ACTR2), siah E3 ubiquitin protein ligase 1 (SIAH1), and glomulin (GLMN)] and 2 hub genes in the purple module [proteasome 20S subunit alpha 3 (PSMA3) and ribosomal protein S27 like (RPS27L)] were identified. Hub genes were validated through quantitative real-time polymerase chain reaction. In summary, 12 hub genes were identified in two modules that were associated with HO. These hub genes could provide new biomarkers, therapeutic ideas, and targets in HO.