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The mortality figures related to the coronavirus pandemic has been the topic of debate lately. Several hypothesis are made regarding the expected number of deaths in a region but there are various factors governing the same. In this paper, we have discussed the mortality figures in the Umbria region after analyzing the data from the national Health registry between December 2019 to April 2020; the period of infection and its comparison with the data from previous five years. The factors governing these figures were studied including temperature, standard mortality rates, territorial distribution, death due to all cases as well as the non-COVID deaths. A sharp increase in mortality figures was observed for the month of march and low temperature also had a role to play. However the difference when compared to previous 5 years was not significant as was expected at the start of the study. A single factor cannot be responsible for the total mortality figures in a region as is frequently predicted.

Objectives To describe the characteristics, and estimate the incidence, of trials included in systematic reviews deviating from the intention-to-treat (ITT) principle. Study Design and Setting A 5% random sample of reviews were selected (Medline 2006–2010). Trials from reviews were classified based on the ITT: (1) ITT trials (trials reporting standard ITT analyses); (2) modified ITT (mITT) trials (modified ITT; trials deviating from standard ITT); or (3) no ITT trials. Results Of 222 reviews, 81 (36%) included at least one mITT trial. Reviews with mITT trials were more likely to contain trials that used placebo, that investigated drugs, and that reported favorable results. The incidence of reviews with mITT trial ranged from 29% (17/58) to 48% (23/48). Of the 2,349 trials, 597 (25.4%) were classified as ITT trials, 323 (13.8%) as mITT trials, and 1,429 (60.8%) as no ITT trials. The mITT trials were more likely to have reported exclusions compared to studies classified as ITT trials and to have received funding. Conclusion The reporting of the type of ITT may differ according to the clinical area and the type of intervention. Deviation from ITT in randomized controlled trials is a widespread phenomenon that significantly affects systematic reviews.

Background Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. Methods We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. Results We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90–99), positive predictive value (PPV) 98% (93–100), negative predictive value (NPV) 100% (95–100); intracerebral hemorrhage: SE 100% (97–100), SP 98% (91–100), PPV 98% (94–100), NPV 100% (95–100); other and unspecified intracranial hemorrhage: SE 100% (97–100), SP 96% (90–99), PPV 98% (93–100), NPV 100% (95–100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94–100), SP 66 (57–75), PPV 70% (61–77), NPV 99% (93–100); occlusion of cerebral arteries: SE 100% (97–100), SP 87% (78–93), PPV 91% (84–95), NPV 100% (95–100); acute, but ill-defined, cerebrovascular disease: SE 100% (97–100), SP 78% (69–86), PPV % 83 (75–89), NPV 100% (95–100). Conclusions Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

BackgroundAdministrative healthcare databases are useful and inexpensive tools that can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. However, a crucial issue is the reliability of information gathered. The aim of this study was to validate ICD-9 codes for several major cardiovascular conditions, i.e., acute myocardial infarction (AMI), atrial fibrillation/flutter (AF), and heart failure (HF), in order to use them for epidemiological, outcome, and health services research.MethodsData from the centralised administrative database of the Umbria Region (890,000 residents, located in Central Italy) were considered. Patients with a first hospital discharge for AMI, AF/flutter, and HF, between 2012 and 2014, were identified using ICD-9-CM codes in primary position. A sample of cases and non-cases was randomly selected, and the corresponding medical charts reviewed by specifically trained investigators. For each disease, case ascertainment was based on all clinical, laboratory, and instrumental examinations available in medical charts. Sensitivity, specificity, and predictive values with 95% confidence intervals (CIs), were calculated.ResultsWe reviewed 458 medical charts, 128 for AMI, 127 for AF/flutter, 127 for HF, and 76 of non-cases for each condition. Diagnostic accuracy measures of the original discharge diagnosis were as follows. AMI: sensitivity 98% (95% CI, 94-100%), specificity 91% (95% CI, 83-97%), positive predictive value (PPV) 95% (95% CI, 89-98%), negative predictive value (NPV) 97% (95% CI, 91-100%). AF/flutter: sensitivity 95% (95% CI, 90-98%), specificity 95% (95% CI, 87-99%), PPV 97% (95% CI, 92-99%), NPV 92% (95% CI, 84-97%). HF: sensitivity 96% (95% CI, 91-99%), specificity 90% (95% CI, 81-96%), PPV 94% (95% CI, 88-97%), NPV 93% (95% CI, 85-98%).ConclusionThe case ascertainment for AMI, AF and flutter, and HF, showed a high level of accuracy (≥ 90%). The healthcare administrative database of the Umbria Region can be confidently used for epidemiological, outcome, and health services research.

Objectives:In the past decade, there has been a growing interest in health technology disinvestment. A disinvestment process should involve all relevant stakeholders to identify and deliver the most effective, safe, and cost-effective healthcare interventions. The aim of the present study was to describe the state of the art of health technology disinvestment around the world and to identify parameters that could be associated with the implementation of disinvestment programs.Methods:A systematic review of the literature was performed from database inception to November 2014, together with the collection of original data on socio-economic indicators from forty countries.Results:Overall, 1,456 records (1,199 from electronic databases and 257 from other sources) were initially retrieved. After analyzing 172 full text articles, 38 papers describing fifteen disinvestment programs/experiences in eight countries were included. The majority (12/15) of disinvestment programs began after 2006. As expected, these programs were more common in developed countries, 63 percent of which had a Beveridge model healthcare system. The univariate analysis showed that countries with disinvestment programs had a significantly higher level of Human Development Index, Gross Domestic Product per capita, public expenditure on health and social services, life expectancy at birth and a lower level of infant mortality rate, and of perceived corruption. The existence of HTA agencies in the country was a strong predictor (p= .034) for the development of disinvestment programs.Conclusions:The most significant variables in the univariate analysis were connected by a common factor, potentially related to the overall development stage of the country.

ObjectiveTo define the accuracy of administrative datasets to identify primary diagnoses of breast cancer based on the International Classification of Diseases (ICD) 9th or 10th revision codes.DesignSystematic review.Data sources: MEDLINE, EMBASE, Web of Science and the Cochrane Library (April 2017).Eligibility criteriaThe inclusion criteria were: (a) the presence of a reference standard; (b) the presence of at least one accuracy test measure (eg, sensitivity) and (c) the use of an administrative database.Data extractionEligible studies were selected and data extracted independently by two reviewers; quality was assessed using the Standards for Reporting of Diagnostic accuracy criteria.Data analysisExtracted data were synthesised using a narrative approach.ResultsFrom 2929 records screened 21 studies were included (data collection period between 1977 and 2011). Eighteen studies evaluated ICD-9 codes (11 of which assessed both invasive breast cancer (code 174.x) and carcinoma in situ (ICD-9 233.0)); three studies evaluated invasive breast cancer-related ICD-10 codes. All studies except one considered incident cases.The initial algorithm results were: sensitivity ≥80% in 11 of 17 studies (range 57%–99%); positive predictive value was ≥83% in 14 of 19 studies (range 15%–98%) and specificity ≥98% in 8 studies. The combination of the breast cancer diagnosis with surgical procedures, chemoradiation or radiation therapy, outpatient data or physician claim may enhance the accuracy of the algorithms in some but not all circumstances. Accuracy for breast cancer based on outpatient or physician’s data only or breast cancer diagnosis in secondary position diagnosis resulted low.ConclusionBased on the retrieved evidence, administrative databases can be employed to identify primary breast cancer. The best algorithm suggested is ICD-9 or ICD-10 codes located in primary position.Trial registration numberCRD42015026881.

ObjectivesTo assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying patients diagnosed with incident carcinoma in situ and invasive breast cancer in three Italian administrative databases.DesignA diagnostic accuracy study comparing ICD-9-CM codes for carcinoma in situ (233.0) and for invasive breast cancer (174.x) with medical chart (as a reference standard). Case definition: (1) presence of a primary nodular lesion in the breast and (2) cytological or histological documentation of cancer from a primary or metastatic site.SettingAdministrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli VeneziaGiulia (FVG) Region.ParticipantsWomen with breast carcinoma in situ (n=246) or invasive breast cancer (n=384) diagnosed (in primary position) between 2012 and 2014.Outcome measuresSensitivity and specificity for codes 233.0 and 174.x.ResultsFor invasive breast cancer the sensitivities were 98% (95% CI 93% to 99%) for Umbria, 96% (95% CI 91% to 99%) for NA and 100% (95% CI 97% to 100%) for FVG. Specificities were 90% (95% CI 82% to 95%) for Umbria, 91% (95% CI 83% to 96%) for NA and 91% (95% CI 84% to 96%) for FVG.For carcinoma in situ the sensitivities were 100% (95% CI 93% to 100%) for Umbria, 100% (95% CI 95% to 100%) for NA and 100% (95% CI 96% to 100%) for FVG. Specificities were 98% (95% CI 93% to 100%) for Umbria, 86% (95% CI 78% to 92%) for NA and 90% (95% CI 82% to 95%) for FVG.ConclusionsAdministrative healthcare databases from Umbria, NA and FVG are accurate in identifying hospitalised news cases of carcinoma of the breast. The proposed case definition is a powerful tool to perform research on large populations of newly diagnosed patients with breast cancer.

ObjectivesTo assess the accuracy ofInternational Classification of Diseases, Ninth Revision – Clinical Modification(ICD-9-CM) codes in identifying subjects with colorectal cancer.DesignA diagnostic accuracy study comparing ICD-9-CM codes (index test) for colorectal cancers with medical chart (as a reference standard). Case ascertainment based on neoplastic lesion(s) within the colon/rectum and histological documentation from a primary or metastatic site positive for colorectal cancer.SettingAdministrative databases from the Umbria region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) region and Friuli Venezia Giulia (FVG) region.ParticipantsWe randomly selected 130 incident patients from each hospital discharge database, admitted between 2012 and 2014, having colorectal cancer ICD-9 codes located in primary position, and 94 non-cases, that is, patients having a diagnosis of cancer (ICD-9 140–239) other than colorectal cancer in primary position.Outcome measuresSensitivity, specificity and predictive values for 153.x code (colon cancer) and for 154.x code (rectal cancer).ResultsThe positive predictive value (PPV) for colon cancer diagnoses was 80% for Umbria (95% CI 73% to 87%), 81% for NA (95% CI 73% to 88%) and 80% for FVG (95% CI 72% to 87%).The sensitivity ranged from 98% to 99%, while the specificity ranged from 78% to 80% in the three units.For rectal cancer, the PPV was 84% for Umbria (95% CI 77% to 90%), 80% for NA (95% CI 72% to 87%) and 81% for FVG (95% CI 73% to 87%). The sensitivities ranged from 98% to 100%, while the specificity estimates from 79% to 82%.ConclusionsAdministrative databases in Italy can be a valuable tool for cancer surveillance as well as monitoring geographical and temporal variation of cancer practice.

Objectives To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying subjects with melanoma. Design A diagnostic accuracy study comparing melanoma ICD-9-CM codes (index test) with medical chart (reference standard). Case ascertainment was based on neoplastic lesion of the skin and a histological diagnosis from a primary or metastatic site positive for melanoma. Setting Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli Venezia Giulia (FVG) Region. Participants 112, 130 and 130 cases (subjects with melanoma) were randomly selected from Umbria, NA and FVG, respectively; 94 non-cases (subjects without melanoma) were randomly selected from each unit. Outcome measures Sensitivity and specificity for ICD-9-CM code 172.x located in primary position. Results The most common melanoma subtype was malignant melanoma of skin of trunk, except scrotum (ICD-9-CM code: 172.5), followed by malignant melanoma of skin of lower limb, including hip (ICD-9-CM code: 172.7). The mean age of the patients ranged from 60 to 61 years. Most of the diagnoses were performed in surgical departments. The sensitivities were 100% (95% CI 96% to 100%) for Umbria, 99% (95% CI 94% to 100%) for NA and 98% (95% CI 93% to 100%) for FVG. The specificities were 88% (95% CI 80% to 93%) for Umbria, 77% (95% CI 69% to 85%) for NA and 79% (95% CI 71% to 86%) for FVG. Conclusions The case definition for melanoma based on clinical or instrumental diagnosis, confirmed by histological examination, showed excellent sensitivities and good specificities in the three operative units. Administrative databases from the three operative units can be used for epidemiological and outcome research of melanoma.

Background People with abdominal aortic aneurysm who receive endovascular aneurysm repair (EVAR) need lifetime surveillance to detect potential endoleaks. Endoleak is defined as persistent blood flow within the aneurysm sac following EVAR. Computed tomography (CT) angiography is considered the reference standard for endoleak surveillance. Colour duplex ultrasound (CDUS) and contrast-enhanced CDUS (CE-CDUS) are less invasive but considered less accurate than CT. Objectives To determine the diagnostic accuracy of colour duplex ultrasound (CDUS) and contrast-enhanced-colour duplex ultrasound (CE-CDUS) in terms of sensitivity and specificity for endoleak detection after endoluminal abdominal aortic aneurysm repair (EVAR). Search methods We searched MEDLINE, Embase, LILACS, ISI Conference Proceedings, Zetoc, and trial registries in June 2016 without language restrictions and without use of filters to maximize sensitivity. Selection criteria Any cross-sectional diagnostic study evaluating participants who received EVAR by both ultrasound (with or without contrast) and CT scan assessed at regular intervals. Data collection and analysis Two pairs of review authors independently extracted data and assessed quality of included studies using the QUADAS 1 tool. A third review author resolved discrepancies. The unit of analysis was number of participants for the primary analysis and number of scans performed for the secondary analysis. We carried out a meta-analysis to estimate sensitivity and specificity of CDUS or CE-CDUS using a bivariate model. We analysed each index test separately. As potential sources of heterogeneity, we explored year of publication, characteristics of included participants (age and gender), direction of the study (retrospective, prospective), country of origin, number of CDUS operators, and ultrasound manufacturer. Main results We identified 42 primary studies with 4220 participants. Twenty studies provided accuracy data based on the number of individual participants (seven of which provided data with and without the use of contrast). Sixteen of these studies evaluated the accuracy of CDUS. These studies were generally of moderate to low quality: only three studies fulfilled all the QUADAS items; in six (40%) of the studies, the delay between the tests was unclear or longer than four weeks; in eight (50%), the blinding of either the index test or the reference standard was not clearly reported or was not performed; and in two studies (12%), the interpretation of the reference standard was not clearly reported. Eleven studies evaluated the accuracy of CE-CDUS. These studies were of better quality than the CDUS studies: five (45%) studies fulfilled all the QUADAS items; four (36%) did not report clearly the blinding interpretation of the reference standard; and two (18%) did not clearly report the delay between the two tests. Based on the bivariate model, the summary estimates for CDUS were 0.82 (95% confidence interval (CI) 0.66 to 0.91) for sensitivity and 0.93 (95% CI 0.87 to 0.96) for specificity whereas for CE-CDUS the estimates were 0.94 (95% CI 0.85 to 0.98) for sensitivity and 0.95 (95% CI 0.90 to 0.98) for specificity. Regression analysis showed that CE-CDUS was superior to CDUS in terms of sensitivity (LR Chi2 = 5.08, 1 degree of freedom (df); P = 0.0242 for model improvement). Seven studies provided estimates before and after administration of contrast. Sensitivity before contrast was 0.67 (95% CI 0.47 to 0.83) and after contrast was 0.97 (95% CI 0.92 to 0.99). The improvement in sensitivity with of contrast use was statistically significant (LR Chi2 = 13.47, 1 df; P = 0.0002 for model improvement). Regression testing showed evidence of statistically significant effect bias related to year of publication and study quality within individual participants based CDUS studies. Sensitivity estimates were higher in the studies published before 2006 than the estimates obtained from studies published in 2006 or later (P < 0.001); and studies judged as low/unclear quality provided higher estimates in sensitivity. When regression testing was applied to the individual based CE-CDUS studies, none of the items, namely direction of the study design, quality, and age, were identified as a source of heterogeneity. Twenty-two studies provided accuracy data based on number of scans performed (of which four provided data with and without the use of contrast). Analysis of the studies that provided scan based data showed similar results. Summary estimates for CDUS (18 studies) showed 0.72 (95% CI 0.55 to 0.85) for sensitivity and 0.95 (95% CI 0.90 to 0.96) for specificity whereas summary estimates for CE-CDUS (eight studies) were 0.91 (95% CI 0.68 to 0.98) for sensitivity and 0.89 (95% CI 0.71 to 0.96) for specificity. Authors' conclusions This review demonstrates that both ultrasound modalities (with or without contrast) showed high specificity. For ruling in endoleaks, CE-CDUS appears superior to CDUS. In an endoleak surveillance programme CE-CDUS can be introduced as a routine diagnostic modality followed by CT scan only when the ultrasound is positive to establish the type of endoleak and the subsequent therapeutic management.

Background : Administrative healthcare databases are widely present in Italy. Our aim was to describe the current state of healthcare databases validity in terms of discharge diagnoses (according to the International Classification of Diseases, ICD-9 code) and their output in terms of research. Methods : A systematic search of electronic databases including Medline and Embase (1995-2013) and of local sources was performed. Inclusion criteria were: healthcare databases in any Italian territory routinely and passively collecting data; medical investigations or procedures at patient level data; the use of a validation process. The quality of studies was evaluated using the STARD criteria. Citations of the included studies were explored using Scopus and Google Scholar. Results : The search strategy allowed the identification of 16 studies of which 3 were in Italian. Thirteen studies used regional administrative databases from Lombardia, Piemonte, Lazio, Friuli-Venezia Giulia and Veneto. The ICD-9 codes of the following diseases were successfully validated: amyotrophic lateral sclerosis (3 studies in four different regional administrative databases), stroke (3 studies), gastrointestinal bleeding (1 study), thrombocytopenia (1 study), epilepsy (1 study), infection (1 study), chronic obstructive pulmonary disease (1 study), Guillain-Barre syndrome (1 study), and cancer diseases (4 studies). The quality of reporting was variable among the studies. Only 6 administrative databases produced further research related to the validated ICD-9 codes. Conclusion : Administrative healthcare databases in Italy need an extensive process of validation for multiple diagnostic codes to perform high quality epidemiological and health services research.

Introduction Healthcare databases are useful sources to investigate the epidemiology of chronic obstructive pulmonary disease (COPD), to assess longitudinal outcomes in patients with COPD, and to develop disease management strategies. However, in order to constitute a reliable source for research, healthcare databases need to be validated. The aim of this protocol is to perform the first systematic review of studies reporting the validation of codes related to COPD diagnoses in healthcare databases. Methods and analysis MEDLINE, EMBASE, Web of Science and the Cochrane Library databases will be searched using appropriate search strategies. Studies that evaluated the validity of COPD codes (such as the International Classification of Diseases 9th Revision and 10th Revision system; the Real codes system or the International Classification of Primary Care) in healthcare databases will be included. Inclusion criteria will be: (1) the presence of a reference standard case definition for COPD; (2) the presence of at least one test measure (eg, sensitivity, positive predictive values, etc); and (3) the use of a healthcare database (including administrative claims databases, electronic healthcare databases or COPD registries) as a data source. Pairs of reviewers will independently abstract data using standardised forms and will assess quality using a checklist based on the Standards for Reporting of Diagnostic accuracy (STARD) criteria. This systematic review protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement. Ethics and dissemination Ethics approval is not required. Results of this study will be submitted to a peer-reviewed journal for publication. The results from this systematic review will be used for outcome research on COPD and will serve as a guide to identify appropriate case definitions of COPD, and reference standards, for researchers involved in validating healthcare databases. Trial registration number CRD42015029204.

Objectives To assess the accuracy of International Classification of Diseases 9th Revision–Clinical Modification (ICD-9-CM) codes in identifying subjects with lung cancer. Design A cross-sectional diagnostic accuracy study comparing ICD-9-CM 162.x code (index test) in primary position with medical chart (reference standard). Case ascertainment was based on the presence of a primary nodular lesion in the lung and cytological or histological documentation of cancer from a primary or metastatic site. Setting Three operative units: administrative databases from Umbria Region (890 000 residents), ASL Napoli 3 Sud (NA) (1 170 000 residents) and Friuli Venezia Giulia (FVG) Region (1 227 000 residents). Participants Incident subjects with lung cancer (n=386) diagnosed in primary position between 2012 and 2014 and a population of non-cases (n=280). Outcome measures Sensitivity, specificity and positive predictive value (PPV) for 162.x code. Results 130 cases and 94 non-cases were randomly selected from each database and the corresponding medical charts were reviewed. Most of the diagnoses for lung cancer were performed in medical departments. True positive rates were high for all the three units. Sensitivity was 99% (95% CI 95% to 100%) for Umbria, 97% (95% CI 91% to 100%) for NA, and 99% (95% CI 95% to 100%) for FVG. The false positive rates were 24%, 37% and 23% for Umbria, NA and FVG, respectively. PPVs were 79% (73% to 83%)%) for Umbria, 58% (53% to 63%)%) for NA and 79% (73% to 84%)%) for FVG. Conclusions Case ascertainment for lung cancer based on imaging or endoscopy associated with histological examination yielded an excellent sensitivity in all the three administrative databases. PPV was moderate for Umbria and FVG but lower for NA.

Objective To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Design Meta-epidemiological study. Data sources Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. Eligibility criteria for selecting studies From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value

Introduction Administrative healthcare databases can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions and use of healthcare resources, thus providing answers to a wide spectrum of research questions. However, a crucial issue is the reliability of information gathered. Aim of this protocol is to validate International Classification of Diseases, 9th Revision—Clinical Modification (ICD-9-CM) codes for major cardiovascular diseases, including acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and stroke. Methods and analysis Data from the centralised administrative database of the entire Umbria Region (910 000 residents, located in Central Italy) will be considered. Patients with a first hospital discharge for AMI, HF, AF or stroke, between 2012 and 2014, will be identified in the administrative database using the following groups of ICD-9-CM codes located in primary position: (1) 410.x for AMI; (2) 427.31 for AF; (3) 428 for HF; (4) 433.x1, 434 (excluding 434.x0), 436 for ischaemic stroke, 430 and 431 for haemorrhagic stroke (subarachnoid haemorrhage and intracerebral haemorrhage). A random sample of cases, and of non-cases, will be selected, and the corresponding medical charts retrieved and reviewed for validation by pairs of trained, independent reviewers. For each condition considered, case adjudication of disease will be based on symptoms, laboratory and diagnostic tests, as available in medical charts. Divergences will be resolved by consensus. Sensitivity and specificity with 95% CIs will be calculated. Ethics and dissemination Research protocol has been granted approval by the Regional Ethics Committee. Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences.

Section Editor: Graeme J. Hankey MD, FRCP Glycoprotein (GP) IIb-IIIa inhibitors block the final common pathway to platelet aggregation antagonizing with receptors that bind fibrinogen molecules forming bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favor endogenous thrombolysis by reducing thrombus growth and prevent thrombus reformation by competitive inhibition with fibrinogen. Currently used in clinical practice for acute coronary syndromes and percutaneous coronary interventions, they could be useful also for patients with acute ischemic stroke. To perform a systematic review of controlled clinical trials in order to assemble all the available data to evaluate the potential efficacy and safety of GP IIb-IIIa inhibitors in patients with acute ischemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched May 31, 2005). In addition we …

Background Glycoprotein (GP) IIb-IIIa inhibitors are antiplatelet agents that act by antagonising GP IIb-IIIa receptors on the platelet surface and block the final common pathway to platelet aggregation by preventing the binding of fibrinogen molecules that form bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favour endogenous thrombolysis by reducing thrombus growth and preventing thrombus re-formation through competitive inhibition with fibrinogen and, due to their mechanism of action, are likely to have a more profound antiplatelet effect with more rapid onset than conventional antiplatelet agents, such as aspirin or clopidogrel. Currently used in clinical practice for the treatment of individuals with acute coronary syndromes and during coronary angioplasty, GP IIb-IIIa inhibitors could also be useful for the treatment of people with acute ischaemic stroke. Objectives To assess the use of GP IIb-IIIa inhibitors in people with acute ischaemic stroke to evaluate whether such treatments (1) reduce the proportion of patients who die or remain dependent, and (2) are sufficiently safe for general use. We wished to examine the effects GP IIb-IIIa inhibitors alone or in combination with thrombolytic agents. Search methods We searched the Cochrane Stroke Group trials register (last searched 10 June 2013), MEDLINE (1966 to June 2013), EMBASE (1980 to June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 5, 2013), and major ongoing clinical trials registers (June 2013). We also searched reference lists and contacted trial authors and pharmaceutical companies. Selection criteria We aimed to analyse unconfounded randomised controlled trials (RCTs) of GP IIb-IIIa inhibitors in the treatment of people with acute ischaemic stroke. Only individuals who started treatment within six hours of stroke onset were included. Data collection and analysis We independently selected trials for inclusion, assessed trial quality and extracted the data. Main results We included four trials involving 1365 participants. Three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo (1215 participants) and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin (150 participants). Treatment with either of these GP IIb-IIIa inhibitors did not significantly reduce long-term death or dependency (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.77 to 1.22, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.52 to 1.92, for the comparison between Tirofiban and aspirin) and had no effect on deaths from all causes (OR 1.08, 95% CI 0.77 to 1.53, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.35 to 2.82, for the comparison between Tirofiban and aspirin). Abciximab was associated with a significant increase in symptomatic intracranial haemorrhage (OR 4.6, 95% CI 2.01 to 10.54) and with a non-significant increase in major extracranial haemorrhage (OR 1.81, 95% CI 0.96 to 3.41), whereas the only small trial comparing Tirofiban with aspirin showed no increased risk of bleeding complications with Tirofiban (OR 0.32, 95% CI 0.03 to 3.19, for symptomatic intracranial haemorrhage; OR 3.04, 95% CI 0.12 to 75.83, for major extracranial haemorrhages). There was no significant inconsistency across the studies. Authors' conclusions The available trial evidence showed that, for individuals with acute ischaemic stroke, GP IIb-IIIa inhibitors are associated with a significant risk of intracranial haemorrhage with no evidence of any reduction in death or disability in survivors. These data do not support their routine use in clinical practice. The conclusion is driven by trials of Abciximab, which contributed 89% of the total number of study participants considered.

The purpose of this study was to evaluate the medium-term clinical and radiological outcomes of two metal-backed acetabular cups with metal-on-metal and metal-on-polyethylene joint couples, in patients unselected for age. Seventy-five metal-on-polyethylene CLS expansion cups were implanted in 70 patients and 66 metal-on-metal Fitek cups were implanted in 65 patients. The average age at surgery in the two groups was 63 years (range, 25 to 72 years) and 58 years (range, 32 to 68 years), respectively. Data regarding 64 of 75 CLS cups (85%) and 58 of 66 Fitek cups (88%) were collected at a minimum 36-month and maximum 144-month follow-up. The Harris hip score showed excellent results in 86% of the CLS cups, good results in 7%, and fair results in 7%. No poor results were recorded. For metal-on-metal acetabular components, excellent results were recorded in 84% of the cups, good results in 8%, fair results in 5%, and poor results in 3%. Fifty-five patients with 57 of 64 CLS cups (89%) and 50 patients with 51 of 58 Fitek cups (88%) were fully satisfied with their prosthesis. No acetabular reconstructions were revised for aseptic loosening. No radiolucent lines greater than 2 mm were observed, either about CLS or Fitek cups, and low incidence of osteolysis and polyethylene wear was noted in metal-on-polyethylene articulations. Post-operative three-phase bone scanning was obtained in 51 patients and this examination did not show increased uptake in blood pool or bone phase indicating aseptic loosening of CLS and Fitek cups. In conclusion, we found similar rates of excellent and good results using two acetabular components with different bearing surfaces, in patients of unselected age. Therefore, the less expensive implant should be selected for total hip arthroplasty in elderly or low-demand patients.

Background Randomized controlled trials (RCTs) that use the modified intention-to-treat (mITT) approach are increasingly being published. Such trials have a preponderance of post-randomization exclusions, industry sponsorship, and favourable findings, and little is known whether in terms of these items mITT trials are different with respect to trials that report a standard intention-to-treat. Methods To determine differences in the methodological quality, sponsorship, authors' conflicts of interest, and findings among trials with different "types" of intention-to-treat, we undertook a cross-sectional study of RCTs published in 2006 in three general medical journals (the Journal of the American Medical Association, the New England Journal of Medicine and the Lancet) and three specialty journals (Antimicrobial Agents and Chemotherapy, the American Heart Journal and the Journal of Clinical Oncology). Trials were categorized based on the "type" of intention-to-treat reporting as follows: ITT, trials reporting the use of standard ITT approach; mITT, trials reporting the use of a "modified intention-to-treat" approach; and "no ITT", trials not reporting the use of any intention-to-treat approach. Two pairs of reviewers independently extracted the data in duplicate. The strength of the associations between the "type" of intention-to-treat reporting and the quality of reporting (sample size calculation, flow-chart, lost to follow-up), the methodological quality of the trials (sequence generation, allocation concealment, and blinding), the funding source, and the findings was determined. Odds ratios (OR) were calculated with 95% confidence intervals (CI). Results Of the 367 RCTs included, 197 were classified as ITT, 56 as mITT, and 114 as "no ITT" trials. The quality of reporting and the methodological quality of the mITT trials were similar to those of the ITT trials; however, the mITT trials were more likely to report post-randomization exclusions (adjusted OR 3.43 [95%CI, 1.70 to 6.95]; P < 0.001). We found a strong association between trials classified as mITT and for-profit agency sponsorship (adjusted OR 7.41 [95%CI, 3.14 to 17.48]; P < .001) as well as the presence of authors' conflicts of interest (adjusted OR 5.14 [95%CI, 2.12 to 12.48]; P < .001). There was no association between mITT reporting and favourable results; in general, however, trials with for-profit agency sponsorship were significantly associated with favourable results (adjusted OR 2.30; [95%CI, 1.28 to 4.16]; P = 0.006). Conclusion We found that the mITT trials were significantly more likely to perform post-randomization exclusions and were strongly associated with industry funding and authors' conflicts of interest.

Objective The aim of the present study was to evaluate the use of previously frozen, thawed platelet gel supplementation to accelerate the healing of long bone nonunions treated by external fixation. Design Prospective case series with historical controls. Setting University Hospital. Patients Twenty patients affected by tibial, humeral, or forearm atrophic nonunions were treated by percutaneous stabilization with unilateral external fixators and injection of autologous platelet gel. The healing time was compared to the result obtained in a historical control group treated without platelet gel supplementation. Main outcome measurements Consolidation rate and radiographic healing time of nonunions in the 2 groups were assessed by independent blinded observers. The nonunion was judged to be healed when bridging callus formation on both radiographic views was observed on at least 3 of 4 cortices. Results The healing rate of nonunion was 90% (18/20) in platelet gel cases and 85% (17/20) in controls, respectively (P = 0.633). The mean time until radiographic consolidation in nonunions supplemented with platelet gel (147 +/- 63 days) was not different to the result in the control group (153 +/- 61 days; P = 0.784). Analyzing the mean healing time for separate segments, no differences were noted between study and control group-that is, tibia: 112 +/- 43 and 130 +/- 5 days, respectively (P = 0.382); humerus, 225 +/- 36 and 202 +/- 70 days, respectively (P = 0.530). Conclusion The present study failed to show the clinical usefulness of isolated percutaneous platelet gel supplementation in long bone nonunions treated by external fixation; however, caution should be exercised in interpreting this result because the actual numbers are small and the statistical power is limited.

Background Congenital hearing loss is one of the most frequent birth defects, and Early Detection and Intervention has been found to improve language outcomes. The American Academy of Pediatrics (AAP) and the Joint Committee on Infant Hearing (JCIH) established quality of care process indicators and benchmarks for Universal Newborn Hearing Screening (UNHS). We have aggregated some of these indicators/benchmarks according to the three pillars of universality, timely detection and overreferral. When dealing with inter-comparison, relying on complete and standardised literature data becomes crucial. The purpose of this paper is to verify whether literature data on UNHS programmes have included sufficient information to allow inter-programme comparisons according to the indicators considered. Methods We performed a systematic search identifying UNHS studies and assessing the quality of programmes. Results The identified 12 studies demonstrated heterogeneity in criteria for referring to further examinations during the screening phase and in identifying high-risk neonates, protocols, tests, staff, and testing environments. Our systematic review also highlighted substantial variability in reported performance data. In order to optimise the reporting of screening protocols and process performance, we propose a checklist. Another result is the difficulty in guaranteeing full respect for the criteria of universality, timely detection and overreferral. Conclusions Standardisation in reporting UNHS experiences may also have a positive impact on inter-program comparisons, hence favouring the emergence of recognised best practices. Electronic supplementary material The online version of this article (doi:10.1186/s12887-015-0404-x) contains supplementary material, which is available to authorized users.