Kalai and Muller's Possibility Theorem: A Simplified Integer Programming Version

We provide a respecification of an integer programming characterization of Arrovian social welfare functions introduced by Sethuraman et al. (Math Oper Res 28:309–326, 2003). By exploiting this respecification, we give a new and simpler proof of Theorem 2 in Kalai and Muller (J Econ Theory 16:457–469, 1977)

Mapping the characteristics of network meta-analyses on antithrombotic therapies: an overview and critical appraisal

Objectives: A large number of network meta-analyses (NMAs) in the field of cardiac disease are available, yet the scientific literature lacks an updated straightforward synthesis of this evidence to ground the decision-making process. We aimed to map and critically appraise NMAs on antithrombotic therapies used as treatment or prophylaxis of cardiac diseases and cardiac surgical procedures. Methods: A systematic review of systematic reviews with meta-analysis was conducted following Cochrane Collaboration and Joanna Briggs recommendations (PROSPERO-CRD2020166468). Searches to identify NMAs meeting the eligibility criteria of this study were performed in PubMed and Scopus (Jan-2022). NMAs characteristics including metadata, statistical models’ description, and main pooled results were collected. The methodological quality of NMAs was evaluated using the PRISMA-NMA checklist and AMSTAR-2 tools. Descriptive statistical analyses with categorical variables reported as frequencies and continuous variables as the median and interquartile range (IQR) were performed (SPSS-Statistics v.25.0). Results: Overall, n=88 NMAs published between 2007-2022 were identified. The most evaluated clinical condition was atrial fibrillation (n=57; 64.7%); around one-third of the studies (38.6%) assessed cardiac surgical procedures. Only 28.4% NMAs had a registered study protocol. Fifty NMAs (56.8%) were published by authors from one single country China the most frequently. A median of 14 primary studies (IQR 5-20.75) (mostly randomized clinical trials) were included per NMA. A median of 40 (IQR 24-84.25) indirect meta-analyses per study were found. At least one network diagram for a given outcome was provided by 68 (77.2%) studies, yet only 22 (25.6%) performed treatment ranking analyses. Conflict of interest declarations and study funding were informed by 34 (38.6%) and 38 (43.2%) NMAs, respectively. Conclusions: Although there is a widespread of NMA-type studies assessing different antithrombotic agents for different cardiac conditions, the lack of standardized conduction and reporting of NMAs (poor-moderate methodological quality) may limit their comparison and results implementation into clinical practice.info:eu-repo/semantics/publishedVersio

Limitations and perceived delays for diagnosis and staging of lung cancer in Portugal: A nationwide survey analysis

Background We aimed to identify the perception of physicians on the limitations and delays for diagnosing, staging and treatment of lung cancer in Portugal. Methods Portuguese physicians were invited to participate an electronic survey (Feb-Apr-2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR). The association between categorical variables was assessed through Pearson’s chi-square test. Mann-Whitney test was used to compare categorical and continuous variables (Stata v.15.0). Results Sixty-one physicians participated in the study (45 pulmonologists, 16 oncologists), with n = 26 exclusively assisting lung cancer patients. Most experts work in public hospitals (90.16%) in Lisbon (36.07%). During the last semester of 2019, responders performed a median of 85 (IQR 55–140) diagnoses of lung cancer. Factors preventing faster referral to the specialty included poor articulation between services (60.0%) and patients low economic/cultural level (44.26%). Obtaining National Drugs Authority authorization was one of the main reasons (75.41%) for delaying the begin of treatment. The cumulative lag-time from patients’ admission until treatment ranged from 42–61 days. Experts believe that the time to diagnosis could be optimized in around 11.05 days [IQR 9.61–12.50]. Most physicians (88.52%) started treatment before biomarkers results motivated by performance status deterioration (65.57%) or high tumor burden (52.46%). Clinicians exclusively assisting lung cancer cases reported fewer delays for obtaining authorization for biomarkers analysis (p = 0.023). Higher waiting times for surgery (p = 0.001), radiotherapy (p = 0.004), immunotherapy (p = 0.003) were reported by professionals from public hospitals. Conclusions Physicians believe that is possible to reduce delays in all stages of lung cancer diagnosis with further efforts from multidisciplinary teams and hospital administration.This work was supported by AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

A Twistor Formulation of the Non-Heterotic Superstring with Manifest Worldsheet Supersymmetry

We propose a new formulation of the $D=3$ type II superstring which is manifestly invariant under both target-space $N=2$ supersymmetry and worldsheet $N=(1,1)$ super reparametrizations. This gives rise to a set of twistor (commuting spinor) variables, which provide a solution to the two Virasoro constraints. The worldsheet supergravity fields are shown to play the r\^ole of auxiliary fields.Comment: 21p., LaTe

Reports of substandard medicines: a lexicographic analysis of the Brazilian Health Surveillance Report System

Regulatory agencies are responsible for collecting and evaluating spontaneous reports of suspected problems related to medications, including those from substandard medicines (SM). Objectives: The aim was to evaluate the profile of SM reports submitted to the Brazilian Health Surveillance Notification System (Notivisa) and classify these reports objectively by means of lexicographic analysis. Methods: Was extracted all SM reports available in Notivisa during the period 1 January 2007 to 31 December 2017. Descriptive statistics were performed and the reasons for SM reporting were standardized (using OpenRefine and Microsoft Excel). The following analyses were performed using IRAMuTeQ 0.7 alpha2: lexicographic analysis to obtain the frequency of active words; descending hierarchical classification (DHC) to categorize the active words into lexical classes; factorial correspondence analysis (FCA) to obtain graphs of the classes. Approved by the Ethics Committee of the Hospital do Trabalhador/SES/PR CAAE 81873417.3.0000.5225 (protocol number: 2.506.594). Results: A total of 61,775 reports were analyzed, most of them reported by hospitals (46%). The DHC of the reasons for SM produced four classes visualized in the FCA: (i) packaging problems (16%) mainly leakages/opening issues; (ii) inadequate drug identification (22%), such as illegible label information; (iii) stability and contamination issues (11%) such as presence of particles; (iv) damaged tablets/blisters (23%) mainly broken tablets. Most SM (52%) were solutions for parenteral use; sodium chloride (9%), glucose and dipyrone (3%) were the products with most complaints. Conclusions: The reasons for SM reporting can be objectively classified into classes that represent the main problems submitted to Notivisa. This classification could guide the standardization of SM reporting and contribute to improving surveillance reporting systems worldwide

Publication speed in pharmacy practice journals: A comparative analysis

Background Scholarly publishing system relies on external peer review. However, the duration of publication process is a major concern for authors and funding bodies. Objective To evaluate the duration of the publication process in pharmacy practice journals compared with other biomedical journals indexed in PubMed. Methods All the articles published from 2009 to 2018 by the 33 pharmacy practice journals identified in Mendes et al. study and indexed in PubMed were gathered as study group. A comparison group was created through a random selection of 3000 PubMed PMIDs for each year of study period. Articles with publication dates outside the study period were excluded. Metadata of both groups of articles were imported from PubMed. The duration of editorial process was calculated with three periods: acceptance lag (days between 'submission date' and 'acceptance date'), lead lag (days between 'acceptance date' and 'online publication date'), and indexing lag (days between 'online publication date' and 'Entry date'). Null hypothesis significance tests and effect size measures were used to compare these periods between both groups. Results The 33 pharmacy practice journals published 26,256 articles between 2009 and 2018. Comparison group random selection process resulted in a pool of 23,803 articles published in 5,622 different journals. Acceptance lag was 105 days (IQR 57-173) for pharmacy practice journals and 97 days (IQR 56-155) for the comparison group with a null effect difference (Cohen's d 0.081). Lead lag was 13 (IQR 6-35) and 23 days (IQR 9-45) for pharmacy practice and comparison journals, respectively, which resulted in a small effect. Indexing lag was 5 days (IQR 2-46) and 4 days (IQR 2-12) for pharmacy practice and control journals, which also resulted in a small effect. Slight positive time trend was found in pharmacy practice acceptance lag, while slight negative trends were found for lead and indexing lags for both groups. Conclusions Publication process duration of pharmacy practice journals is similar to a general random sample of articles from all disciplines

Principles of pharmacoeconomic analysis: the case of pharmacist-led interventions

In the past years, several factors such as evidence-based healthcare culture, quality-linked incentives, and patient-centered actions, associated with an important increase of financial constraints and pressures on healthcare budgets, resulted in a growing interest by policy-makers in enlarging pharmacists' roles in care. Numerous studies have demonstrated positive therapeutic outcomes associated with pharmaceutical services in a wide array of diseases. Yet, the evidence of the economic impact of the pharmacist in decreasing total health expenditures, unnecessary care, and societal costs relies on well-performed, reliable, and transparent economic evaluations, which are scarce. Pharmacoeconomics is a branch of health economics that usually focuses on balancing the costs and benefits of an intervention towards the use of limited resources, aiming at maximizing value to patients, healthcare payers and society through data driven decision making. These decisions can be guide by a health technology assessment (HTA) process that inform governmental players about medical, social, and economic implications of development, diffusion, and use of health technologies including clinical pharmacy interventions. This paper aims to provide an overview of the important concepts in costing in healthcare, including studies classification according to the type of analysis method (e.g. budget-impact analysis, cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis), types of costs (e.g. direct, indirect and intangible costs) and outcomes (e.g. events prevented, quality adjusted life year - QALY, disability adjusted life year - DALY). Other key components of an economic evaluation such as the models' perspective, time horizon, modelling approaches (e.g. decision trees or simulation models as the Markov model) and sensitivity analysis are also briefly covered. Finally, we discuss the methodological issues for the identification, measurement and valuation of costs and benefits of pharmacy services, and suggest some recommendations for future studies, including the use of Value of Assessment Frameworks

Efficacy and safety of pharmacological interventions for managing sickle cell disease in children and adolescents: protocol for a systematic review with network meta-analysis

IntroductionSickle cell disease (SCD), an inherited haemoglobinopathy, has important impact on morbidity and mortality, especially in paediatrics. Previous systematic reviews are limited to adult patients or focused only on few therapies. We aim to synthesise the evidence on efficacy and safety of pharmacological interventions for managing SCD in children and adolescents.Methods and analysisThis systematic review protocol is available at Open Science Framework (doi:10.17605/OSF.IO/CWAE9). We will follow international recommendations on conduction and report of systematic reviews and meta-analyses. Searches will be conducted in PubMed, Scopus and Web of Science (no language nor time restrictions) (first pilot searches performed in May 2022). We will include randomised controlled trials comparing the effects of disease-modifying agents in patients with SCD under 18 years old. Outcomes of interest will include: vaso-occlusive crisis, haemoglobin levels, chest syndrome, stroke, overall survival and adverse events. We will provide a narrative synthesis of the findings, and whenever possible, results will be pooled by means of pairwise or Bayesian network meta-analyses with surface under the cumulative ranking curve analyses. Different statistical methods and models will be tested. Dichotomous outcomes will be reported as OR, risk ratio or HR, while continuous data will be reported as standard mean differences, both with 95% CI/credibility interval. The methodological quality of the trials will be evaluated using the Risk of Bias 2.0 tool, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationThis study refers to a systematic review, so no ethics approval is necessary. We intent to publish our findings in international, peer-reviewed journal. Data will also be presented to peers in scientific events. Additionally, the results obtained in this study may contribute towards the update of therapeutic guidelines and for the development of health policies for SCD.PROSPERO registration numberCRD42022328471.</jats:sec

Description of network meta-analysis geometry: A metrics design study

© 2019 Tonin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background The conduction and report of network meta-analysis (NMA), including the presentation of the network-plot, should be transparent. We aimed to propose metrics adapted from graph theory and social network-analysis literature to numerically describe NMA geometry. Methods A previous systematic review of NMAs of pharmacological interventions was performed. Data on the graph’s presentation were collected. Network-plots were reproduced using Gephi 0.9.1. Eleven geometric metrics were tested. The Spearman test for non-parametric correlation analyses and the Bland-Altman and Lin’s Concordance tests were performed (IBM SPSS Statistics 24.0). Results From the 477 identified NMAs only 167 graphs could be reproduced because they provided enough information on the plot characteristics. The median nodes and edges were 8 (IQR 6–11) and 10 (IQR 6–16), respectively, with 22 included studies (IQR 13–35). Metrics such as density (median 0.39, ranged 0.07–1.00), median thickness (2.0, IQR 1.0–3.0), percentages of common comparators (median 68%), and strong edges (median 53%) were found to contribute to the description of NMA geometry. Mean thickness, average weighted degree and average path length produced similar results than other metrics, but they can lead to misleading conclusions. Conclusions We suggest the incorporation of seven simple metrics to report NMA geometry. Editors and peer-reviews should ensure that guidelines for NMA report are strictly followed before publication