Development and Validation of a Clinical Scale for the Evaluation of Forearm Skin Photoaging

Background: Despite the focus on facial photoaging ratings, there are few classifications developed for forearm skin aging assessment.Objective: To develop and validate a clinical scale for the evaluation of forearm skin aging.Methods: Three clinical dermatology faculty members selected, discussed, and appraised the main signs of forearm photoaging. The validation of the resulting scale was performed by 5 assessors who were previously trained to classify 102 photographs of forearms with different degrees of aging. Retests were performed in 15 days.Results: There was significant correlation between the selected variables and the subjective global aging scale. The developed scale showed high internal consistency (Cronbach's alpha = 0.87) and high correlation with the global photoaging scale (rho = 0.92). Inter- and intraobserver final scores showed high agreement.Conclusion: A validated clinical photoaging scale for forearms with internal consistency, reliability, and validity was developed.

Outpatient versus inpatient treatment for acute pulmonary embolism

Background: Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people per year. Outpatient treatment instead of traditional inpatient treatment in selected non-high-risk patients with acute PE might provide several advantages, such as reduction of hospitalizations, substantial cost saving and an improvement in health-related quality of life. Objectives: To compare the efficacy and safety of outpatient versus inpatient treatment for acute PE for the outcomes of all-cause and PE-related mortality; bleeding; and adverse events such as hemodynamic instability, recurrence of PE and patients'satisfaction.Search methodsThe Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched October 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 9). The TSC also searched clinical trials databases. The review authors searched LILACS (last searched November 2014). Selection criteria: Randomized controlled trials of outpatient versus inpatient treatment in people diagnosed with acute PE. Data collection and analysis: Two review authors selected relevant trials, assessed methodological quality, and extracted and analyzed data. Main results: We included one study, involving 339 participants. We ranked the quality of the evidence as very low due to not blinding the outcome assessors, the small number of events with imprecision in the confidential interval (CI), the small sample size and it was not possible to verify publication bias. For all outcomes, the CIs were wide and included clinically significant treatment effects in both directions: short-term mortality (30 days) (RR 0.33, 95% CI 0.01 to 7.98, P = 0.49), long-term mortality (90 days) (RR 0.98, 95% CI 0.06 to 15.58, P = 0.99), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57, P = 0.30) and 90 days (RR 6.88, 95% CI 0.36 to 134.14, P = 0.20), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85, P = 0.51) and participant satisfaction (RR 0.97, 95% CI 0.92 to 1.03, P = 0.30). PE-related mortality, minor bleeding, and adverse course such as hemodynamic instability and compliance were not assessed by the single included study. Authors' conclusions: Current very low quality evidence from one published randomized controlled trial did not provide sufficient evidence to assess the efficacy and safety of outpatient versus inpatient treatment for acute PE in overall mortality, bleeding and recurrence of PE adequately. Further well-conducted research is required before informed practice decisions can be made.

Estudo clínico randomizado e duplo cego comparando dois métodos de escleroterapia para veias reticulares e telangiectasias em membros inferiores

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole

Abstract Background:The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. Methods/Design: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. Discussion: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease. Trial registration: ClinicalTrials.gov identifier: NCT01710163

L'Orientamento politico come fattore di differenziazione delle politiche pubbliche locali: I casi di Modena e Verona

La tesi ha per oggetto lo studio delle politiche pubbliche locali ed in particolare delle politiche sociali che dal 2011 sono diventate politiche esclusivamente territoriali. L’obiettivo è quello di verificare se il differente orientamento politico delle amministrazioni genera politiche differenti. Per verificare le ipotesi si sono scelti 2 Comuni simili sul piano delle variabili socio-economiche, ma guidati da giunte con orientamento politico differente: il Comune di Modena a guida Partito Democratico e il Comune di Verona con un sindaco leghista a capo di una giunta di centro-destra. Nella prima parte vengono esposti ed analizzati i principali paradigmi di studio delle politiche (rational choice, paradigma marxista, economia del benessere, corporativismo e pluralismo, neo-istituzionalismo e paradigma relazionale) e viene presentato il paradigma che verrà utilizzato per l’analisi delle politiche (paradigma relazionale). Per la parte empirica si è proceduto attraverso interviste in profondità effettuate ai due Assessori alle Politiche sociali e ai due Dirigenti comunali dei Comuni e a 18 organizzazioni di Terzo settore impegnate nella costruzione delle politiche e selezionate attraverso la metodologia “a palla di neve”. Sono analizzate le disposizioni normative in materia di politica sociale, sia per la legislazione regionale che per quella comunale. L’analisi dei dati ha verificato l’ipotesi di ricerca nel senso che l’orientamento politico produce politiche differenti per quanto riguarda il rapporto tra Pubblica Amministrazione e Terzo settore. Per Modena si può parlare di una scelta di esternalizzazione dei servizi che si accompagna ad un processo di internalizzazione dei servizi tramite le ASP; a Verona almeno per alcuni settori delle politiche (disabilità e anziani) sono stati realizzati processi di sussidiarietà e di governance. Per la fase di programmazione l’orientamento politico ha meno influenza e la programmazione mostra caratteristiche di tipo “top-down”.

Risikomaße in der Finanzmathematik

„Risikomaße in der Finanzmathematik“ Der Value-at -Risk (VaR) ist ein Risikomaß, dessen Verwendung von der Bankenaufsicht gefordert wird. Der Vorteil des VaR liegt – als Quantil der Ertrags- oder Verlustverteilung - vor allem in seiner einfachen Interpretierbarkeit. Nachteilig ist, dass der linke Rand der Wahrscheinlichkeitsverteilung nicht beachtet wird. Darüber hinaus ist die Berechnung des VaR schwierig, da Quantile nicht additiv sind. Der größte Nachteil des VaR ist in der fehlenden Subadditivität zu sehen. Deswegen werden Alternativen wie Expected Shortfall untersucht. In dieser Arbeit werden zunächst finanzielle Risikomaße eingeführt und einige ihre grundlegenden Eigenschaften festgehalten. Wir beschäftigen uns mit verschiedenen parametrischen und nichtparametrischen Methoden zur Ermittlung des VaR, unter anderen mit ihren Vorteilen und Nachteilen. Des Weiteren beschäftigen wir uns mit parametrischen und nichtparametrischen Schätzern vom VaR in diskreter Zeit. Wir stellen Portfoliooptimierungsprobleme im Black Scholes Modell mit beschränktem VaR und mit beschränkter Varianz vor. Der Vorteil des erstens Ansatzes gegenüber dem zweiten wird hier erläutert. Wir lösen Nutzenoptimierungsprobleme in Bezug auf das Endvermögen mit beschränktem VaR und mit beschränkter Varianz. VaR sagt nichts über den darüber hinausgehenden Verlust aus, während dieser von Expected Shortfall berücksichtigt wird. Deswegen verwenden wir hier den Expected Shortfall anstelle des von Emmer, Korn und Klüppelberg (2001) betrachteten Risikomaßes VaR für die Optimierung des Portfolios im Black Scholes Modell.

The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.

Percutaneous closure of patent foramen ovale in cryptogenic embolism

BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy. METHODS We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population. RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56). CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.).

Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.

Drug-related emergency department visits by elderly patients presenting with non-specific complaints

BACKGROUND Since drug-related emergency department (ED) visits are common among older adults, the objectives of our study were to identify the frequency of drug-related problems (DRPs) among patients presenting to the ED with non-specific complaints (NSC), such as generalized weakness and to evaluate responsible drug classes. METHODS Delayed type cross-sectional diagnostic study with a prospective 30 day follow-up in the ED of the University Hospital Basel, Switzerland. From May 2007 until April 2009, all non-trauma patients presenting to the ED with an Emergency Severity Index (ESI) of 2 or 3 were screened and included, if they presented with non-specific complaints. After having obtained complete 30-day follow-up, two outcome assessors reviewed all available information, judged whether the initial presentation was a DRP and compared their judgment with the initial ED diagnosis. Acute morbidity ("serious condition") was allocated to individual cases according to predefined criteria. RESULTS The study population consisted of 633 patients with NSC. Median age was 81 years (IQR 72/87), and the mean Charlson comorbidity index was 2.5 (IQR 1/4). DRPs were identified in 77 of the 633 cases (12.2%). At the initial assessment, only 40% of the DRPs were correctly identified. 64 of the 77 identified DRPs (83%) fulfilled the criteria "serious condition". Polypharmacy and certain drug classes (thiazides, antidepressants, benzodiazepines, anticonvulsants) were associated with DRPs. CONCLUSION Elderly patients with non-specific complaints need to be screened systematically for drug-related problems. TRIAL REGISTRATION ClinicalTrials.gov: NCT00920491.

Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial

BACKGROUND: Arm hemiparesis secondary to stroke is common and disabling. We aimed to assess whether robotic training of an affected arm with ARMin--an exoskeleton robot that allows task-specific training in three dimensions-reduces motor impairment more effectively than does conventional therapy. METHODS: In a prospective, multicentre, parallel-group randomised trial, we enrolled patients who had had motor impairment for more than 6 months and moderate-to-severe arm paresis after a cerebrovascular accident who met our eligibility criteria from four centres in Switzerland. Eligible patients were randomly assigned (1:1) to receive robotic or conventional therapy using a centre-stratified randomisation procedure. For both groups, therapy was given for at least 45 min three times a week for 8 weeks (total 24 sessions). The primary outcome was change in score on the arm (upper extremity) section of the Fugl-Meyer assessment (FMA-UE). Assessors tested patients immediately before therapy, after 4 weeks of therapy, at the end of therapy, and 16 weeks and 34 weeks after start of therapy. Assessors were masked to treatment allocation, but patients, therapists, and data analysts were unmasked. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00719433. FINDINGS: Between May 4, 2009, and Sept 3, 2012, 143 individuals were tested for eligibility, of whom 77 were eligible and agreed to participate. 38 patients assigned to robotic therapy and 35 assigned to conventional therapy were included in analyses. Patients assigned to robotic therapy had significantly greater improvements in motor function in the affected arm over the course of the study as measured by FMA-UE than did those assigned to conventional therapy (F=4.1, p=0.041; mean difference in score 0.78 points, 95% CI 0.03-1.53). No serious adverse events related to the study occurred. INTERPRETATION: Neurorehabilitation therapy including task-oriented training with an exoskeleton robot can enhance improvement of motor function in a chronically impaired paretic arm after stroke more effectively than conventional therapy. However, the absolute difference between effects of robotic and conventional therapy in our study was small and of weak significance, which leaves the clinical relevance in question.

A new method to facilitate valid and consistent grading cardiac events in childhood cancer survivors using medical records

BACKGROUND Cardiac events (CEs) are among the most serious late effects following childhood cancer treatment. To establish accurate risk estimates for the occurrence of CEs it is essential that they are graded in a valid and consistent manner, especially for international studies. We therefore developed a data-extraction form and a set of flowcharts to grade CEs and tested the validity and consistency of this approach in a series of patients. METHODS The Common Terminology Criteria for Adverse Events version 3.0 and 4.0 were used to define the CEs. Forty patients were randomly selected from a cohort of 72 subjects with known CEs that had been graded by a physician for an earlier study. To establish whether the new method was valid for appropriate grading, a non-physician graded the CEs by using the new method. To evaluate consistency of the grading, the same charts were graded again by two other non-physicians, one with receiving brief introduction and one with receiving extensive training on the new method. We calculated weighted Kappa statistics to quantify inter-observer agreement. RESULTS The inter-observer agreement was 0.92 (95% CI 0.80-1.00) for validity, and 0.88 (0.79-0.98) and 0.99 (0.96-1.00) for consistency with the outcome assessors who had the brief introduction and the extensive training, respectively. CONCLUSIONS The newly developed standardized method to grade CEs using data from medical records has shown excellent validity and consistency. The study showed that the method can be correctly applied by researchers without a medical background, provided that they receive adequate training.

Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial

BACKGROUND Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. METHODS We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. FINDINGS Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014). INTERPRETATION In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. FUNDING Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

High Incorrect Use of the Standard Error of the Mean (SEM) in Original Articles in Three Cardiovascular Journals Evaluated for 2012.

RATIONALE In biomedical journals authors sometimes use the standard error of the mean (SEM) for data description, which has been called inappropriate or incorrect. OBJECTIVE To assess the frequency of incorrect use of SEM in articles in three selected cardiovascular journals. METHODS AND RESULTS All original journal articles published in 2012 in Cardiovascular Research, Circulation: Heart Failure and Circulation Research were assessed by two assessors for inappropriate use of SEM when providing descriptive information of empirical data. We also assessed whether the authors state in the methods section that the SEM will be used for data description. Of 441 articles included in this survey, 64% (282 articles) contained at least one instance of incorrect use of the SEM, with two journals having a prevalence above 70% and "Circulation: Heart Failure" having the lowest value (27%). In 81% of articles with incorrect use of SEM, the authors had explicitly stated that they use the SEM for data description and in 89% SEM bars were also used instead of 95% confidence intervals. Basic science studies had a 7.4-fold higher level of inappropriate SEM use (74%) than clinical studies (10%). LIMITATIONS The selection of the three cardiovascular journals was based on a subjective initial impression of observing inappropriate SEM use. The observed results are not representative for all cardiovascular journals. CONCLUSION In three selected cardiovascular journals we found a high level of inappropriate SEM use and explicit methods statements to use it for data description, especially in basic science studies. To improve on this situation, these and other journals should provide clear instructions to authors on how to report descriptive information of empirical data.

The timing of significant arch dimensional changes with fixed orthodontic appliances: data from a multicenter randomised controlled trial.

OBJECTIVES To identify the timing of significant arch dimensional increases during orthodontic alignment involving round and rectangular nickel-titanium (NiTi) wires and rectangular stainless steel (SS). A secondary aim was to compare the timing of changes occurring with conventional and self-ligating fixed appliance systems. METHODS In this non-primary publication, additional data from a multicenter randomised trial initially involving 96 patients, aged 16 years and above, were analysed. The main pre-specified outcome measures were the magnitude and timing of maxillary intercanine, interpremolar, and intermolar dimensions. Each participant underwent alignment with a standard Damon (Ormco, Orange, CA) wire sequence for a minimum of 34 weeks. Blinding of clinicians and patients was not possible; however, outcome assessors and data analysts were kept blind to the appliance type during data analysis. RESULTS Complete data were obtained from 71 subjects. Significant arch dimensional changes were observed relatively early in treatment. In particular, changes in maxillary inter-first and second premolar dimensions occurred after alignment with an 0.014in. NiTi wire (P<0.05). No statistical differences in transverse dimensions were found between rectangular NiTi and working SS wires for each transverse dimension (P>0.05). Bracket type had no significant effect on the timing of the transverse dimensional changes. CONCLUSIONS Arch dimensional changes were found to occur relatively early in treatment, irrespective of the appliance type. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed. CLINICAL SIGNIFICANCE On the basis of this research orthodontic expansion may occur relatively early in treatment. Nickel-titanium wires may have a more profound effect on transverse dimensions than previously believed.