Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta-analysis.

There are 3 methods of interpreting breast strain elastography: the elastographic-to-B-mode length ratio (E/B), a 5-point color scale (5P), and the strain ratio (SR). This meta-analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy-proven or long-term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full-text articles were examined, and 46 were included in the meta-analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.

HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ ß chains.

BackgroundSpecific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.MethodsAfter a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case-control studies and 3 cohort studies). Case-control studies collectively enrolled 740 CD patients and 943 controls.ResultsIn the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/ß2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/ß2 and DQ2/DQ2, as well as between DQ8/ß2 and DQ2/DQ8, and between ß2/DQX and DQ2/X.ConclusionThe HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.

Drug eluting stents are superior to bare metal stents to reduce clinical outcome and stent-related complications in CKD patients, a systematic review, meta-analysis and network meta-analysis.

Aims To compare clinical outcome in Chronic kidney disease (CKD) patients receiving coronary stents according to stent type BMS versus DES and 1st generation versus 2nd generation DES. Methods and Results PubMed, Cinhal, Cochrane, Embase, and Web of Science were searched for studies including CKD patients. CKD was defined as eGFR < 60 mL/min. We selected n = 35 articles leading to 376 169 patients, of which 76 557 CKD patients receiving BMS n = 35,807, 1st generation DES n = 37,650, or 2nd generation DES n = 3100. Patient receiving DES, compared to BMS, had a 18% lower all-cause mortality (RR 0.82, 95%CI 0.71-0.94). The composite of death or myocardial infarction (MI) was lower in DES patients (RR 0.78, 95%CI 0.67-0.91), as was stent thrombosis (ST) (RR 0.57, 95%CI 0.34-0.95), target vessel/lesion revascularization (TVR/TLR) (RR 0.69, 95%CI 0.57-0.84) and death for cardiovascular cause (RR 0.43, 95%CI 0.25-0.74). We also found a gradient between 1st and 2nd generation DES, through BMS. Second, compared to 1st generation DES, were associated with further relative risk (RR) reduction of -18% in of all-cause death, and lower incidence of stent-related clinical events: -39% RR of ST risk; -27 RR of TVR/TLR risk. Conclusions DES in CKD patients undergoing PCI were superior to BMS in reducing major adverse clinical events. This was possibly explained, by a lower risk of stent-related events as ST and TVR or TLR. Second, compared to 1st generation DES may furtherly reduce clinical events.

Endobronchial ultrasound-guided transbronchial needle aspiration for diagnosis of sarcoidosis in clinically unselected study populations.

Literature suggests that ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has excellent performance characteristics for diagnosis of sarcoidosis. However, many authors challenge the external validity of EBUS-TBNA results, as most studies were performed in referral centres by highly experienced investigators, and included populations with very high sarcoidosis prevalence. We performed a systematic review and meta-analysis to estimate the role of EBUS-TBNA for diagnosis of sarcoidosis in studies enrolling consecutive patients with lymphadenopathy detected at imaging studies, regardless of the suspected underlying clinical aetiology. The Pubmed, Embase, Cinahl, Web of Science and Cochrane Library databases were screened to identify the pertinent literature. Quality of eligible studies was assessed by Quality Assessment, Data Abstraction and Synthesis-2 criteria. Pooled diagnostic yield, sensitivity and specificity were calculated, and a summary receiver operating characteristic curve was constructed. Subgroup analysis was planned to identify possible sources of study heterogeneity. Fourteen studies, collectively involving 2097 patients, fulfilled eligibility criteria. The median prevalence of sarcoidosis was 15%. EBUS-TBNA had a pooled diagnostic yield of 0.79 (standard deviation, 0.24), a pooled sensitivity of 0.84 (95% confidence interval (CI), 0.79-0.88) and a pooled specificity of 1.00 (95% CI, 0.99-1.00). Only subgroup analysis exploring the influence of study design seemed to influence the observed inter-study heterogeneity for sensitivity, retrospective studies showing worst sensitivity than prospective ones. The results of EBUS-TBNA for diagnosis of sarcoidosis in clinically unselected populations are excellent and compare favourably with published results from studies conducted in selected populations. High-quality trials would be needed to evaluate factors possibly explaining the observed heterogeneity in sensitivity.

[Bibliometrics and web use: the birth of altmetrics]. / Bibliometria e uso del web: la nascita degli "Altmetrics".

Counting citations that a research article received by other articles was the traditional bibliometric method for the evaluation of a scientific research. Citations have been used both to evaluate a scientific paper - usually in conjunction with the peer review methods - and to determine the quality of a scientific research output. The development of tools even more Web 2.0 oriented has profoundly changed the scientific communication process. In this context, many web tools have emerged including the so-called "social media" (e-i., Facebook, Twitter). Hence the need for new indicators to measure the influence of these tools on the scientific community and the emergence of alternative metrics. Altmetrics combines the traditional bibliometrics tool with the use of the web. Formulated with the purpose to measure new aspects of scientific production, these new metrics are placed in order to complement and supplement the existing indicators rather than act as their replacements.

Fungal Osteomyelitis: A Systematic Review of Reported Cases.

Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was Aspergillus (26.5%), followed by Candida (20.7%) and Mucor (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.

US-Elastography With Different Techniques for Thyroid Nodule Characterization: Systematic Review and Meta-analysis.

Background: Thyroid nodules are frequent in adult population and thyroid cancer incidence has increased dramatically over the past three decades. The aim of this systematic review and meta-analysis was to evaluate the US-Elastosonography (USE) diagnostic performance in assessing the thyroid nodules malignancy risk. Methods: PubMed and Embase databases were searched from January 2011 to July 2021. We extracted data from selected studies and calculated the overall diagnostic accuracy of qualitative USE, semi-quantitative USE and quantitative USE. Summary receiver operating characteristic (ROC) curve was elaborated to show the results. All statistical tests were performed using Metadisc and Medcal software package. Results: Finally 72 studies with 13,505 patients and 14,015 thyroid nodules (33% malignant) undergoing elastography were included. The pooled sensitivity, specificity and AUC were 84%, 81%, and 0.89 respectively for qualitative USE; 83%, 80%, and 0.93 for semi-quantitative USE and 78%, 81% and 0.87, for quantitative USE. The qualitative and semiquantitative USE present very similar diagnostic accuracy values and both better than the quantitative USE. Conclusions: USE is a useful imaging tool for thyroid nodule characterization. In accordance with recent guidelines and meta-analyses, the USE could be used daily in thyroid nodule malignancy risk stratification. Systematic Review Registration: PROSPERO: CRD42021279257.

A bibliometric analysis of international publications and citation trends of articles in mental health produced by Chinese institutions in mainland China (1990-2019).

BACKGROUND: The recognition of the importance of mental health as a health-target to be pursued at a global level has received additional theoretical legitimacy through its inclusion in the United Nations (UN) 2030 Agenda for Sustainable development. The theoretical axiom - mental health as a development priority - is today expected to drive the focus of research efforts and orient the future policies and funds expenditures, at global and local level. According to these premises, it becomes central to track the international trajectories of mental health research and how the different countries are progressively defining their role in the global mental health effort. In this paper we have focused on China. In light of heavy burden of mental and substance use disorders affecting this country, and considering the impact of this burden at a global level, a basic research was conducted with the main aim of offering a preliminary view on the Chinese scientific activity within the context of global mental health research. This study is not intended to assess the quality of Chinese research, but merely to retrieve and measure a specific output of this research: the articles in mental-health produced by Chinese institutions based in mainland China, published in international journals. Although the publication of articles in internationally indexed journals in not exhaustive of China's scientific activity in global mental health, it is nevertheless informative of the production of new knowledge, it allows an assessment of the impact of this knowledge at the global scientific community level and it could partially reflect the Chinese capacity to benefit from research conducted globally. OBJECTIVE: In consideration of the very limited number of studies assessing the collective evidence of Chinese research in mental health, we developed our analysis with the purpose of providing a preliminary picture of the Chinese contribution, in terms of scientific publications, in this field of knowledge. Our research performs a bibliometric analysis on the articles in mental-health produced by Chinese institutions based in mainland China and published in English-language SCI-E and SSCI journals from 1990 to 2019, providing a measure of the impact of this research at the global scientific community level. METHODS: We performed a search on the Web of Science (WoS) using seven mental and substance use disorders according to their global prevalence, as per estimates of the Global Burden of Disease 2019. A dataset including the overall number of publications for seven diseases was created and exported in InCites. The dataset was analysed on the basis of 11 research areas (WoS categories) to which mental health topic is associated in SCI-E and SSCI journals in WoS. We further extracted publications that originated in mainland China. The citational trends over time are calculated with nonparametric test for trends across ordered groups. An evaluation of the impact of the Chinese scientific production is provided by the number of citations received at the global scientific community level, both as average and percentile. RESULTS: From 1990 to 2020 the overall Chinese scientific production in mental health has been generally increasing, reaching the highest growth in the last decade. A statistically significant increase (p < 0.001) is reported for articles produced by Chinese institutions in mainland China regarding 'depression*', 'bipolar disorders*' and 'schizophrenia*'. Published Chinese research is mostly included in SCI-E journals. There is a substantial overlap regarding the average number of citations for articles in mental-health produced by Chinese institutions and the rest of the world. Despite the increasing trend, the percentage of articles in mental health produced by Chinese institutions in mainland China on the overall scientific production worldwide is below 10%. CONCLUSION: Notwithstanding a substantial increase in the last decade, the volume of Chinese publications appears to be very limited, thus resulting in a relatively low impact at a global level. These results are affecting the potential contribution of Chinese research in the global mental health effort.

Percutaneous Coronary Intervention Techniques for Bifurcation Disease: Network Meta-analysis Reveals Superiority of Double-Kissing Crush.

BACKGROUND: Provisional T-stenting (PS) is generally recommended to treat patients with coronary bifurcation disease (CBD) percutaneously, but PS may not fit all complex bifurcation anatomies. Therefore, several types of up-front 2-stent techniques have been described. We aimed to identify the best percutaneous coronary intervention (PCI) technique to manage patients with CBD. METHODS: We systematically reviewed randomized controlled trials (RCTs) including patients undergoing CBD PCI which included several types of PCI techniques-PS, double-kissing (DK) crush, T-stenting and protrusion, culotte, dedicated bifurcation stents, crushing, and T-stenting-and we compared device-oriented clinical events (DOCEs), a composite of cardiac death, target-vessel myocardial infarction, stent thrombosis, and target-lesion or target-vessel revascularization, in a network meta-analysis. We included 26 RCTs, leading to a pooled population of 10,339 patient-years and a total of 1229 DOCEs. RESULTS: The DK-crush technique was associated with the lowest DOCE rate, with a relative risk of 0.62 (95% CI 0.42-0.92) compared with the PS technique. DK-crush had the highest probability (model likelihood 90.2%, area under the cumulative ranking curve 98.0%) of being the best technique among those explored to reduce DOCEs in patients receiving CBD PCI. CONCLUSIONS: When a 2-stent strategy is considered in a patient with CBD, the DK-crush technique reduces DOCEs compared with other bifurcation techniques based on all available RCTs.

Drug-eluting compared to bare metal stents in patients with end-stage renal disease on dialysis: a meta-analysis.

AIMS: To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce. METHODS: PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis. RESULTS: Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20). CONCLUSIONS: Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

[Genotyping in patients affected by HLA-related diseases. App development for diagnostic support.] / Tipizzazione genetica nelle patologie HLA-correlate. Sviluppo di una app per il supporto diagnostico.

HLA typing requests for association studies of immune-mediated diseases are often redundant and inadequate. We designed a series of meta-analyses to evaluate the accuracy of typing and distribution of HLA alleles predisposing to diseases, aiming at developing an app that can help doctors in choosing the most suitable molecular analysis. The first study was on celiac disease (CD) and HLA-DQ in children. We searched all english articles published in the main bibliographic databases up to May 2016. The search strategy has been developed using controlled terms (e.g. MeSH) and free terms. We identified 1885 articles. 1334 abstracts were examined. 46 manuscripts were evaluated, and 13 studies were included in the meta-analysis (740 CD and 943 controls). The risk of developing CD in children with allelic variants encoding the HLA-DQ2.5 and/or HLA-DQ8 molecules has been confirmed. The greatest CD risk resides in carriers of two DQ2.5 molecules, i.e. subjects homozygous for the DQB1*02:01 and DQA1*05 alleles (OR=5.4, 95 % CI=4.1-6.8) compared to any other DQ genotype. Carriers of two DQB1*02:01 (chain ß2) alleles and one DQA1*05 (chain α5) allele have the same risk (p=0.8089) of DQ2.5 homozygotes (OR=5.3%, 95 CI=4,1 to 6.5). We found no differences between DQ8/ß2 and DQ2.5/DQ8, nor between ß2/DQX and DQ2.5/X. We suggest a two-step process: first typing the DQB1*02:01 allele and, in case of a negative result, full typing of HLA-DQ.

Accuracy of administrative databases in detecting primary breast cancer diagnoses: a systematic review.

OBJECTIVE: To 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. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE, Web of Science and the Cochrane Library (April 2017). ELIGIBILITY CRITERIA: The 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 EXTRACTION: Eligible studies were selected and data extracted independently by two reviewers; quality was assessed using the Standards for Reporting of Diagnostic accuracy criteria. DATA ANALYSIS: Extracted data were synthesised using a narrative approach. RESULTS: From 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. CONCLUSION: Based 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 NUMBER: CRD42015026881.

HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis.

Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis.

Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis.

Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating and pooling crude and adjusted odds ratios (ORs) ±95% confidence intervals (CIs); the data from longitudinal studies were pooled using the adjusted hazard ratios (HRs). Eighteen cohorts with a total of 31,343 participants were meta-analyzed. Using estimates from 10 cross-sectional cohorts, both frailty and pre-frailty were associated with higher odds of CVD than robust participants. Longitudinal data were obtained from 6 prospective cohort studies. After a median follow-up of 4.4 years, we identified an increased risk for faster onset of any-type CVD in the frail (HR=1.70 [95%CI, 1.18-2.45]; I2=66%) and pre-frail (HR=1.23 [95%CI, 1.07-1.36]; I2=67%) vs. robust groups. Similar results were apparent for time to CVD mortality in the frail and pre-frail groups. In conclusion, frailty and pre-frailty constitute addressable and independent risk factors for CVD in older adults.

Does a research group increase impact on the scientific community or general public discussion? Alternative metric-based evaluation.

In this study, we investigated the impact of scientific publications of the Italian SIMPAR (Study In Multidisciplinary PAin Research) group by using altmetrics, defined as nontraditional metrics constituting an alternative to more traditional citation-impact metrics, such as impact factor and H-index. By correlating traditional and alternative metrics, we attempted to verify whether publications by the SIMPAR group collectively had more impact than those performed by its individual members, either in solo publications or in publications coauthored by non-SIMPAR group investigators (which for the purpose of this study we will refer to as "individual publications"). For all the 12 members of the group analyzed (pain therapists, biologists, and pharmacologists), we created Open Researcher and Contributor ID and Impact Story accounts, and synchronized these data. Manually, we calculated the level metrics for each article by dividing the data obtained from the research community by those obtained from the public community. We analyzed 759 articles, 18 of which were published by the SIMPAR group. Altmetrics demonstrated that SIMPAR group publications were more likely to be saved (77.8% vs 45.9%), discussed (61.1% vs 1.1%, P<0.0001), and publicly viewed (11.1% vs 1.3%, P=0.05) than individual publications. These results support the importance of multidisciplinary research groups in the impact of scientific literature; the interaction and synergy among the research participants allowed the obtainment of high impact-literature in the field of personalized pain medicine. Finally, our findings demonstrate the potential of altmetrics in estimating the value of the research products of a group.

Novel bibliometric scores for evaluating research quality and output: a correlation study with established indexes.

INTRODUCTION: Novel bibliometric indexes (commonly known as altmetrics) are gaining interest within the scientific community and might represent an important alternative measure of research quality and output. AIMS: We evaluate how these new metrics correlate with established bibliometric indexes such as the impact factor (IF), currently used as a measure of scientific production as well as a criterion for scientific research funding, and how they might be helpful in assessing the impact of research. METHODS: We calculated altmetrics scores for all the articles published at our institution during a single year and examined the correlation between altmetrics scores and IFs as a measure of research quality and impact in all departments. RESULTS: For all articles from the various departments published in a single year, the altmetrics score and the sum of all IFs showed a strong and significant correlation (Spearman's rho 0.88). The correlation was significant also when the major components of altmetrics, including Facebook, Twitter and Mendeley, were analyzed. The implementation of altmetrics has been found to be easy and effective at both the researcher and librarian levels. CONCLUSIONS: The novel bibliographic index altmetrics is consistent and reliable and can complement or be considered a valid alternative to standard bibliometric indexes to benchmark output and quality of research for academic and funding purposes.

Effect of telemonitoring of cardiac implantable electronic devices on healthcare utilization: a meta-analysis of randomized controlled trials in patients with heart failure.

AIMS: Implantable device telemonitoring (DTM) is a diagnostic adjunct to traditional face-to-face hospital visits. Remote device follow-up and earlier diagnoses facilitated by DTM should reduce healthcare utilization. We explored whether DTM reduces healthcare utilization over standard of care (SoC), without compromising patient outcomes. METHODS AND RESULTS: This systematic review and meta-analysis of 11 randomized controlled trials on DTM in patients with heart failure consisted of 5702 patients, with a median of 117 [interquartile range (IQR) 76-331] patients per study [age 65 years (IQR 63-67)] and follow-up range of 12-36 months. DTM was associated with a reduction in total number of visits [planned, unplanned, and emergency room (ER)] [relative risk (RR) 0.56; 95% confidence interval (CI) 0.43-0.73, P < 0.001]. Rates of cardiac hospitalizations (RR 0.96; 95% CI 0.82-1.12, P = 0.60) and the composite endpoints of ER, unplanned hospital visits, or hospitalizations (RR 0.99; 95% CI 0.68-1.43, P = 0.96) was similar between the DTM and the SoC groups. An increase in the total number of ER or unscheduled visits (RR 1.37; 95% CI 1.11-1.70, P = 0.004) was observed. This effect was consistent and statistically significant for all studies. Total and cardiac mortality were similar between the groups (DTM RR 0.90; 95% CI 0.69-1.16, P = 0.41; and DTM RR 0.93; 95% CI 0.51-1.69, P = 0.80). Monetary costs favoured DTM (10-55% reduction in five studies). CONCLUSIONS: Compared with SoC, DTM is associated with a marked reduction in planned hospital visits. In addition, DTM was associated with lower monetary costs, despite a modest increase in unplanned hospital and ER visits. DTM did not compromise survival.

Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review.

OBJECTIVE: To evaluate whether rituximab at a low dose of 250 mg/m(2) × 2 may be as effective as at higher dosages, most commonly 375 mg/m(2)×4, used in previous studies on the treatment of patients with refractory mixed cryoglobulinemia (MC) vasculitis associated with hepatitis C virus (HCV) infection. METHODS: We conducted a phase 2, single-arm two-stage trial (EUDRACT n. 2008-000086-38) of low-dose rituximab in 52 patients with HCV-associated MC who were ineligible/intolerant or non-responder to antiviral therapy. The primary outcomes were response of vasculitis evaluated by the Birmingham Vasculitis Activity Score (BVAS) at months 3, 6 and 12, rate of relapses and time to relapse, and rate of adverse events. Our data were compared with those reported in 19 published studies selected among 291 reviewed in a literature search. RESULTS: The cumulative response rate (complete and partial) at month 3 was 81% in our patients, and 86% in 208 patients from studies using high-dose rituximab. The relapse rate and median time to relapse were, respectively, 41% and 6 months in our study, and 32% and 7 months in high-dose studies. Treatment-related adverse events were 11.5% in our study and 19.9% in high-dose studies. None of these differences was statistically significant. CONCLUSION: Rituximab at a low dosage of 250 mg/m(2) × 2 is as effective as at higher dosages for treating MC vasculitis. This low-dose regimen may improve the cost/benefit profile of rituximab therapy for MC.

Use of IVUS guided coronary stenting with drug eluting stent: a systematic review and meta-analysis of randomized controlled clinical trials and high quality observational studies.

BACKGROUND/OBJECTIVES: Long term safety of DES, particularly regarding thrombosis is of concern. The hypothesized underlying mechanisms (stent under expansion, malapposition) could be prevented by IVUS guidance. Aim of this meta-analysis of randomized controlled clinical trials (RCT) and high quality observational cohort studies (HQ-OBS) is to quantify the potential clinical benefit of intravascular ultrasound (IVUS) guidance in drug-eluting stents (DES) implantation. METHODS: We performed an extensive literature search for full-text articles published in 2003­2013. The primary outcome was the rate of major adverse cardiac events (MACE) in RCT and HQ-OBS; secondary outcomes were death, myocardial infarction (MI), revascularization, thrombosis and post-procedural minimum lumen diameter (MLD). Fixed/random effect relative risks (RRs) or standardized mean difference (SMD) and 95% confidence interval (95% CI) were computed for the meta-analysis. RESULTS: Thirty-four articles were retrieved from 268 found; of these 3 were RCT and 9 were HQ-OBS; 18,707 patients were enrolled, 1037 in RCT and 17,670 in OBS. Median follow-up was 20 months. IVUS guidance was associated with a significantly lower rate of MACE (RR=0.80, 95% CI 0.71­0.89, p b 0.001), death (RR=0.60, 95% CI 0.48­0.74, p b 0.001), MI (RR=0.59, 95% CI 0.44­0.80, p=0.001) and thrombosis (RR=0.50, 95% CI 0.32­0.80, p=0.007) and larger MLD (SMD=0.15, 95% CI 0.03 to 0.27, p=0.014), but not of revascularization (RR=0.95, 95% CI 0.82­1.09, p=0.75). CONCLUSIONS: In this meta-analysis, IVUS guidance in DES implantation appears to reduce MACE, mortality and MI, possibly by reducing thrombosis rather than restenosis rate. Patients at high risk for thrombosis might be identified as the best candidate for IVUS guidance.

N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design.

OBJECTIVE: To investigate the use of a novel study design in analysis of bilateral elbow pain. DESIGN: N of 1, two contemporary arm, open label, randomised controlled clinical trial. SETTING: A clinical epidemiologist at a university hospital in Pavia, Italy. PARTICIPANTS: Two elbows with epicondylitis. INTERVENTIONS: Autologous platelet lysate versus "wait and see" strategy. MAIN OUTCOME MEASURES: Visual analogue scale for pain on elbow extension and resisted wrist extension. RESULTS: Over six months' follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points). CONCLUSIONS: Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs.