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Background: Lymphangiogenic growth factors, such as vascular endothelial growth factor (VEGF)-D, are subjects of interest in studies of targeted therapies in lymphedema treatment. Methods and Results: We conducted a systematic review assessing the use of VEGF-D as a targeted therapy in lymphedema treatment. We hypothesized that VEGF-D was a promising therapy to induce lymphangiogenesis. Our search yielded 90 studies in the literature, but only 4 articles fulfilled our study eligibility criteria, and they were all experimental studies using viral gene transfer. The majority of the studies were conducted on small animals (mice) and investigated the effects of VEGF-D on lymph node transfer. All authors agreed about VEGF-D's lymphangiogenic potential, but they noticed that VEGF-C induced a superior lymphangiogenesis, and one study noticed that VEGF-D induced seroma. Conclusions: The publications assessing the use of VEGF-D as a targeted therapy in lymphedema treatment were able to demonstrate its lymphangiogenic potential. Nonetheless, further studies are still necessary to investigate VEGF-D's efficacy and safety in lymphedema treatment on patients.

Background Entrustable Professional Activities (EPAs) provide a framework to make judgments of trainees’ abilities in several settings including postgraduate medical education. No systematic review of the role of EPAs in pediatrics has yet been performed. Objectives In our systematic review, we sought to determine the use of EPAs in pediatrics to identify research gaps, summarize and discuss evidence relating to the development, implementation, and assessment. Data Sources Medline, Scopus, PsycINFO, MedEdPortal, and Web of Science. Study Eligibility Criteria Two independent reviewers used a structured screening protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Association for Medical Education in Europe’s guide for systematic reviews to include all articles reporting on EPAs in postgraduate medical education and pediatrics in particular. There were no restrictions due to language, study design, or participants. Study Appraisal and Synthesis Methods Data on development, implementation, feasibility, acceptance, and assessment of EPAs were extracted and analyzed by the 2 independent researchers. Results Twenty-eight articles published between 2014 and 2020 were included in the review. We found an increase in publications and a notable shift from descriptions of development processes toward aspects beyond development, ie, implementation, feasibility, acceptance/perception, and assessment. Limitations Studies from non-English–speaking countries are scarce which might lead to an inaccurate representation of actual international practice. Conclusions and Implications of Key Findings We provide a comprehensive overview of EPAs in pediatrics to guide future curriculum developers in collaborative development, implementation and assessment of EPAs in pediatric postgraduate medical education.

Background Primary care providers (PCPs), including pediatricians and general practitioners, are often the first to see children with eczema/atopic dermatitis (AD). Little is known about management of pediatric AD by PCPs and adherence to national guidelines. Objective To review existing literature examining management components of pediatric AD (topical corticosteroids [TCS], topical calcineurin inhibitors [TCIs], antihistamines, bathing, emollients, and diet) by PCPs. Data Sources PubMed/Medline and Embase. Study Eligibility Criteria English-language articles dated 2015 to 2020 reporting outcomes addressing management of pediatric AD by PCPs. Study Appraisal and Synthesis Methods Two authors independently screened titles/abstracts, reviewed full-text articles, extracted relevant data, and evaluated study quality. Disagreements were resolved by a third author. Results Twenty articles were included. Surveys and national database analyses were the most common methodologies (n = 7 each). PCPs commonly prescribed TCS but had a preference for low-potency agents, overprescribed nonsedating antihistamines, and avoided TCIs. PCPs commonly recommended emollients, although this was not universal. Data characterizing nonmedication management were limited. Limitations Most studies did not examine individual patient encounters, but rather relied on providers reporting their general behaviors. Provider behavior may vary based on country of practice. Conclusions and Implications of Key Findings Knowledge and management gaps exist among PCPs in treating pediatric AD in key areas including knowledge of TCS safety profiles and prescribing of TCIs. The current literature is largely limited to small studies that evaluate prescribing behaviors with limited data characterizing nonmedication management, highlighting the need for future research in this area.

Purpose: In adults, correction of such a jaw base relation is done by bilateral sagittal split osteotomy and mandibular advancement which often causes change in the cervicomental angle that might not be within the acceptable and aesthetic range. The objective of this systematic review was to evaluate the changes observed in cervicomental angle after mandibular advancement surgery. Data Sources: Based on the available data, we conducted an electronic database PubMed search, based on the search of published data from 1994 to 2017, six strategies were designed using two keywords, and four articles were shortlisted for systematic review. Study Eligibility Criteria: Studies that provide information on cervicomental angle changes after mandibular advancement surgery, published from 1994 to 2017. Results: The search yielded 168 articles, of which four were included based on the selection criteria. These articles described that the cervicomental angle observed after mandibular advancement surgery falls between 95° and 125°. Conclusion: Cervicomental angle decreases as the mandible is advanced to correct the jaw base Class II relation to Class I. Acceptable range is found to be between 95° and 125°. Implications: An esthetic look is the desire of every patient that reports to the clinics for an orthodontic correction. Surgical correction is an integral part of the treatment. While advancing the mandible, change is observed in the cervicomental angle. Knowing the acceptable range of this angle will help the orthodontist and the oral surgeon to plan the advancement accordingly.

Background Higher enrolment rates of cancer patients into clinical trials are necessary to increase cancer survival. As a prerequisite, an improved semiautomated matching of patient characteristics with clinical trial eligibility criteria is needed. This is based on the computer interpretability, i.e., structurability of eligibility criteria texts. To increase structurability, the common content, phrasing, and structuring problems of oncological eligibility criteria need to be better understood. Objectives We aimed to identify oncological eligibility criteria that were not possible to be structured by our manual approach and categorize them by the underlying structuring problem. Our results shall contribute to improved criteria phrasing in the future as a prerequisite for increased structurability. Methods The inclusion and exclusion criteria of 159 oncological studies from the Clinical Trial Information System of the National Center for Tumor Diseases Heidelberg were manually structured and grouped into content-related subcategories. Criteria identified as not structurable were analyzed further and manually categorized by the underlying structuring problem. Results The structuring of criteria resulted in 4,742 smallest meaningful components (SMCs) distributed across seven main categories (Diagnosis, Therapy, Laboratory, Study, Findings, Demographics, and Lifestyle, Others). A proportion of 645 SMCs (13.60%) was not possible to be structured due to content- and structure-related issues. Of these, a subset of 415 SMCs (64.34%) was considered not remediable, as supplementary medical knowledge would have been needed or the linkage among the sentence components was too complex. The main category “Diagnosis and Study” contained these two subcategories to the largest parts and thus were the least structurable. In the inclusion criteria, reasons for lacking structurability varied, while missing supplementary medical knowledge was the largest factor within the exclusion criteria. Conclusion Our results suggest that further improvement of eligibility criterion phrasing only marginally contributes to increased structurability. Instead, physician-based confirmation of the matching results and the exclusion of factors harming the patient or biasing the study is needed.

Background: Exploration of the efficiency of metal nanoparticles as adjuvants have reported varying results. Objective: The efficacy of metal nanoparticles as adjuvants was investigated Data sources: Database were searched using the terms ‘metal nanoparticles’ and ‘vaccines’. Study eligibility criteria: Studies in animal models utilizing any metal-based vaccines, where the survival rate was described. Study appraisal: The quality of the studies was examined using aspects of the ARRIVE guidelines and assessment of the risk of bias of included studies. Results: Metal nanoparticle-based adjuvants were more effective compared with control (unvaccinated groups) but have not been more successful in competing with common adjuvants or even antigens alone. Limitation: More than 75% of articles have used only gold nanoparticles. Conclusion: Nano-adjuvants do not have a significant effect on reducing mortality.

Background Photodynamic therapy (PDT) is considered as a valid treatment option in various branches of dentistry. This systematic review aims to evaluate the usefulness of PDT for treatment of oral premalignant and malignant lesions. Methods The MeSH terms "Photodynamic therapy" and "PDT", in combination with other terms, have been searched by three search engines (PubMed, ISI Web of Science, and the Cochrane Library), and a systematic review has been performed. The Population, Intervention, Comparison, Outcomes, and Study design (PICOS) has been applied as method to outline our study eligibility criteria. Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) has been performed too. Results Initial results were 1513. Definitely, 27 studies met our selection criteria. Conclusions Topical PDT is an easy to perform technique, well tolerated treatment and it appears to be an effective method with encouraging achievements in the treatment of premalignant and malignant lesions of the soft tissues of the oral cavity; nevertheless more studies are required to integrate the up-to-date experience of this application.

Background The matrix assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI-TOF MS) technology has revolutionized the field of microbiology by facilitating precise and rapid species identification. Recently, machine learning techniques have been leveraged to maximally exploit the information contained in MALDI-TOF MS, with the ultimate goal to refine species identification and streamline antimicrobial resistance determination. Objectives The aim was to systematically review and evaluate studies employing machine learning for the analysis of MALDI-TOF mass spectra. Data sources Using PubMed/Medline, Scopus and Web of Science, we searched the existing literature for machine learning-supported applications of MALDI-TOF mass spectra for microbial species and antimicrobial susceptibility identification. Study eligibility criteria Original research studies using machine learning to exploit MALDI-TOF mass spectra for microbial specie and antimicrobial susceptibility identification were included. Studies focusing on single proteins and peptides, case studies and review articles were excluded. Methods A systematic review according to the PRISMA guidelines was performed and a quality assessment of the machine learning models conducted. Results From the 36 studies that met our inclusion criteria, 27 employed machine learning for species identification and nine for antimicrobial susceptibility testing. Support Vector Machines, Genetic Algorithms, Artificial Neural Networks and Quick Classifiers were the most frequently used machine learning algorithms. The quality of the studies ranged between poor and very good. The majority of the studies reported how to interpret the predictors (88.89%) and suggested possible clinical applications of the developed algorithm (100%), but only four studies (11.11%) validated machine learning algorithms on external datasets. Conclusions A growing number of studies utilize machine learning to optimize the analysis of MALDI-TOF mass spectra. This review, however, demonstrates that there are certain shortcomings of current machine learning-supported approaches that have to be addressed to make them widely available and incorporated them in the clinical routine., Clinical Microbiology and Infection, 26 (10), ISSN:1470-9465, ISSN:1198-743X

Objectives: Clostridioides difficile infection (CDI), its subsequent recurrences (rCDIs), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. In this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI.Methods: PubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. The study eligibility criteria were cohort and caseecontrol studies. Participants were patients >= 18 years old diagnosed with CDI, in which clinical or laboratory factors were analysed to predict sCDI/rCDI. Risk of bias was assessed by using the Quality in Prognostic Research (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool modified for prognostic studies. Study selection was performed by two independent reviewers. Overview tables of prognostic factors were constructed to assess the number of studies and the respective effect direction and statistical significance of an association.Results: 136 studies were included for final analysis. Greater age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were greater age, healthcareassociated CDI, prior hospitalization, proton pump inhibitors (PPIs) started during or after CDI diagnosis, and previous rCDI.Conclusions: Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful metaanalysis of risk factors using data of high-quality trials. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

BACKGROUND Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC). OBJECTIVES The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC. DATA SOURCES PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science. STUDY ELIGIBILITY CRITERIA Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC. RESULTS Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed. CONCLUSIONS Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.

Background & Objective: The aim of this systematic review was to report pregnancy and its outcomes of women who were affected by COVID-19 as pregnancy is known to be adversely affected by most of the viral outbreaks of recent times and it is too early to rule out COVID-19 from the list. Data Sources: Electronic search was made across popular databases such as PubMed and Google Scholar with emphasize on keywords and their combinations keeping “COVID-19 and pregnancy” as a central theme. Study Eligibility Criteria: The major inclusion criteria for articles was that they must have data on pregnant women who were tested positive for COVID-19 and they should have reasonable information on the outcomes of the current pregnancy. Study Appraisal and Synthesis Methods: Median age of the women, gestational age at delivery, Comorbidities, events during current pregnancy, maternal and fetal complications, mode of delivery, birth weight, APGAR scores of the neonate, neonatal outcome and COVID-19 test result of the neonate were the information which were tried to compare from the selected articles. Results: Eight articles were screened and finalized for the systematic review which belonged to China, USA, UK and Singapore which in total had data for 185 pregnant women who were tested positive for COVID-19 and had undergone delivery. Similarly, the median age of the pregnant women was 30 years (29-33) and the median gestational of the women at the time of delivery was 36.75 (34-38) weeks. The caesarean rates was typically higher across the articles, with mean of 77.45%. Fever, cough and shortness of breath were the commonest presentations. The maternal and fetal complications were not significant. The most of the results of neonatal testing for COVID-19 turned out to be negative. The rate of premature births were highly variable. Conclusion: The data thus far showed that the course of a COVID-19 pregnancy is much similar to a noninfected one. However, the rates of premature bir

Due to their impact on premature mortality and long-term disabilities, a better understanding of health risk behavior (HRB) determinants among college students is crucial in order to build the most appropriate prevention tools. Although self-esteem appears to be a relevant candidate, a clear picture summarizing its multiple links with HRB is lacking to guide clinicians and researchers. This study aims to provide a systematic review of the associations between health risk behavior and self-esteem among college students. This search was performed in several databases on 02/02/17. Study eligibility criteria were original articles in peer-reviewed journals, in English; observational quantitative studies; among college students; and investigated the association between self-esteem and HRB. The PRISMA statements were complied with. One hundred fifteen articles were included: 46 on substance use, 35 on sexual behavior, 11 on nutritional habits, 27 on physical activity, and 5 on other HRB. Most studies reported an association between higher self-esteem and healthier behavior. For alcohol consumption and number of sexual partners, both negative and positive associations have been reported. Directionality was investigated in a few studies suggesting potential bidirectional effects. This review points out the need for consensus for the definition of self-esteem and HRB. There was high heterogeneity in (1) the measurement of self-esteem either in the concept measured (global vs. domain) or in the way to implement validated tools; and (2) the definition of HRB. Self-esteem seems to be a relevant target to intervene on HRB, especially alcohol abuse and physical activity. Registration number: PROSPERO (ID = CRD42017056599).

Resilience is increasingly recognized as a factor that improves the functioning and performance of individuals and communities; however, it is underexamined in smaller groups or teams. We performed a comprehensive literature review to examine how resilience is defined, measured and used in small teams. Additionally, we evaluated the effectiveness of trainings or interventions on teams towards increasing unit resilience and performance. Following a literature review, 74 measures across 37 articles were assessed. Study eligibility criteria include English-language publications between 1980 and 2017 that included output from a research trial or survey on military or civilian groups pertaining to their resiliency to adverse events. Resilience of units/teams was assessed across the four phases of resilience defined by NAS: prepare, absorb, recover, adapt. Our review found that while the concept of resilience is not often studied in small groups empirically, the focus of available studies is on recovery with limited attention given to absorption and adaptation. This work reveals a potential mechanism to improve team/unit performance via unit resilience training and improved unit cohesion. Training had small but significant effects on the preparation (r = 0.03, k = 5) and recover (r = 0.05, k = 6) phases of unit resilience. In order to improve resilience in small groups, training programs and other interventions must be appropriately focused on the essential phases of resilience associated with mission execution.

Background: Ultrasound is established as a diagnostic tool in salivary glands for obstructive diseases such as sialolithiasis and tumors. Concerning inflammatory diseases and in non-sialolithiasis-caused obstruction, much fewer data are available. In recent years, technical development has allowed a better assessment of the gland parenchyma, and knowledge about intraductal pathologies has increased considerably, which has provided new insights and a new interpretation of ultrasound findings. Objectives: To provide a comprehensive review of the literature that includes our own experiences and to point out the state of the art in ultrasound in the diagnostics of inflammatory and obstructive salivary gland diseases, taking adequate techniques and recent technical developments into consideration. Data sources and study eligibility criteria: A systematic literature search was performed in Pubmed using various specific key words. Results: According to the literature results, including our own experiences, ultrasound is of value in up to >90% of cases presenting with inflammatory and/or obstructive diseases. Technical developments (e.g., elastography) and the application of modified ultrasound techniques (e.g., transoral ultrasound) have contributed to these results. Today, ultrasound is considered a first-line diagnostic tool in these diseases. However, in some inflammatory diseases, the final diagnosis can be made only after inclusion of the anamnesis, clinical symptoms, serologic blood tests, or histopathologic investigation. Conclusions: Ultrasound can be considered as a first-line diagnostic tool in obstructive and inflammatory salivary gland diseases. In obstructive diseases, it may be sufficient for diagnostics in >90% of cases. In inflammatory diseases, ultrasound is at least an excellent screening method and can be used to establish the diagnosis in cases of an early suspicion. In all diseases ultrasound can contribute to better management and can be used for monitoring during follow-up.

Human bocaviruses (HBoVs) are recently described as human emergent viruses, especially in young children. In this study, we undertook a systematic review and meta-analysis to estimate their prevalence in Europe. PubMed, Web of Science and Scopus databases were systematically screened for clinical studies, up to October 2020. Study eligibility criteria were primary full-text articles from clinical studies, conducted using valid screening test methods and published in peer-reviewed journals, in English or Spanish and from European countries. The overall pooled prevalence, prevalence by country as well as the prevalence of HBoV as a single or co-pathogen were estimated using a random-effects model. Sub-group and meta-regression analyses explored potential sources of heterogeneity in the data. A total of 35 studies involving 32,656 subjects from 16 European countries met the inclusion criteria. Heterogeneity (I2 = 97.0%, p < .01) was seen among studies; HBoV prevalence varied from 2.0 to 45.69% with a pooled estimate of 9.57% (95%CI 7.66-11.91%). The HBoV prevalence both as a single infection (3.99%; 95%CI 2.99-5.31%) or as co-infection with other viruses (5.06%; 95%CI 3.88-6.58%) was also analysed. On a geographic level, prevalence by country did not show statistical differences, ranging from 3.24% (Greece) to 21.05% (Denmark). An odds ratio analysis was also included in order to evaluate the relevance of the variable ‘age’ as a risk factor of HBoV infection in children

Background: Small-sided games (SSGs) are an adjusted form of official games that are often used in training scenarios to introduce a specific tactical issue to team sports players. Besides the acute effects of SSGs on players' performance, it is expectable that the consistent use of these drill-based games induces adaptations in the technical execution and tactical behaviors of youth team sports players.Objective: This systematic review with meta-analysis was conducted to assess the effects of SSG programs on the technical execution and tactical behaviors of young and youth team sports players.Data Sources: The data sources utilized were PubMed, Scopus, SPORTDiscus, and Web of Science.Study Eligibility Criteria: (i) Young and youth team sports players (i.e., < 18 years old) of any sex or skill level, without injury, illness, or other clinical conditions; (ii) SSGs-based programs not restricted to the duration and a minimum of one weekly training session; (iii) passive or active control groups; (iv) pre-post interventions values of technical execution and/or tactical behavior; (v) randomized and non-randomized controlled trials; and (vi) peer-reviewed original full-text studies written in English, Portuguese and/or Spanish.Results: The database search initially yielded 803 titles. From those, six articles were eligible for the systematic review and meta-analysis. None of the included studies presented tactical behavior outcomes. The results showed a small effect of SSGs on technical execution (ES = 0.59; 95% CI = 0.29 to 0.89; p < 0.001; I2 = 0.0%; Egger's test p = 0.590) when compared to controls. Sub-group analysis of the training factor revealed similar (p = 0.433) moderate (ES = 0.68, four study groups) and small (ES = 0.44, three study groups) improvements in technical execution after >17 and Conclusions: This systematic review and meta-analysis revealed a significant beneficial effect of using SSG training programs for enhancing technical execution in young and youth players. The benefits were similar despite the various numbers of training sessions applied. Further studies should add tactical behaviors as one of the outcomes for controlling the effects of SSG training programs.

BackgroundWith over 66 million Americans who speak over 350 languages other than English at home, we sought to examine attitudes and behaviors of neurology clinicians and staff when communicating across language differences.MethodsWe conducted an electronic-enabled cross-sectional survey of clinicians and patient services coordinators working at an academic neurology outpatient clinic. Questions focused on professional medical interpreter (PMI) services usage, satisfaction, and perceived barriers to utilization.ResultsA total of 82/235 (35%) neurology clinicians and 24/52 (46%) coordinators met the study eligibility criteria. Most clinicians (96%) reported seeing at least 1 non–English-speaking patient and using PMI services (85%) in the last month. Most commonly self-reported interpretation modalities were face-to-face PMI services (39%) and patients' family members or friends (28%). Perceived barriers to using PMI included time constraints (60%) and lack of available face-to-face PMI (51%). Among patient services coordinators, 33% reported consistently asking patients their preferred language and 50% if they needed a PMI for appointments. Most respondents (77% clinicians and 71% coordinators) were satisfied with PMI services. Recommendations included having more available face-to-face PMI, greater coordinated efforts to preschedule PMI, and more education on the effective use of PMI.ConclusionsMore than 70% of outpatient neurology clinicians and patient services coordinators were satisfied with PMI. However, their perceived barriers and reported practices suggest a need for updated policies and education to improve the use of PMI services.

Purpose The purpose of this paper is to explore how varying definitions of bullying and formats of the definitions affect research study outcomes. Design/methodology/approach A systematic search of empirical studies within the following databases was conducted: PubMed, Scopus, Science Direct, Web of Science and Wiley Online Library. Empirical studies examining laypersons and researcher’s definitions of bullying or how differences in the format of the definition of bullying results in varied outcomes were eligible to be included in this review. As traditional forms of bullying differ from cyber-bullying research on the latter were excluded. Findings Only 17 of the 18,045 screened met the study eligibility criteria. In total, 12 of the screened studies explored how participants define bullying and five explored how the different presentation of the definition may lead to different reported prevalence. The findings showed that laypersons definitions of bullying are not only inconsistent but they rarely meet the criteria used by researchers. The varying presentations of the bullying definition also affected outcomes with the more detailed definitions leading to a better understanding of the behaviour. Research limitations/implications Researchers should always provide a definition of bullying to participants either in a written format or if possible in a more detail like an educational video that clearly highlights the five characteristics researchers used to define the behaviour. Originality/value This is the first paper that reviews empirical studies on the definition of bullying.

Patients with newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS, ≥10% blasts) often receive intensive chemotherapy at diagnosis and relapse. We retrospectively identified 365 patients and categorized the reasons for receiving treatment off study (medical, logistical, or unclear). The pretreatment characteristics of the on and off study groups were similar. Rates of the complete remission (CR) without measurable residual disease were significantly higher for ND patients treated on versus off study (61% versus 35%), but CR rates and survival were low for all RR patients regardless of study assignment. The subset of ND patients treated off study for medical reasons had significantly decreased overall survival and relapse-free survival. Standard, stringent study eligibility criteria may delineate a population of ND, but not RR, patients with improved outcomes with intensive induction chemotherapy.

This systematic review with a meta-analysis was conducted to compare the effects of small-sided games (SSGs)-based interventions with the effects of running-based high-intensity interval training (HIIT) interventions on soccer players’ repeated sprint ability (RSA). The data sources utilized were Web of Science, Scopus, SPORTDiscus, and PubMed. The study eligibility criteria were: (i) parallel studies (SSG-based programs vs. running-based HIIT) conducted in soccer players with no restrictions on age, sex, or competitive level; (ii) isolated intervention programs (i.e., only SSG vs. only running-based HIIT as individual forms) with no restrictions on duration; (iii) a pre–post outcome for RSA; (iv) original, full-text, peer-reviewed articles written in English. An electronic search yielded 513 articles, four of which were included in the present study. There was no significant difference between the effects of SSG-based and HIIT-based training interventions on RSA (effect size (ES) = 0.30; p = 0.181). The within-group analysis revealed no significant effect of SSG-based training interventions (ES = −0.23; p = 0.697) or HIIT-based training interventions (ES = 0.08; p = 0.899) on RSA. The meta-comparison revealed that neither SSGs nor HIIT-based interventions were effective in improving RSA in soccer players, and no differences were found between the two types of training. This suggests that complementary training may be performed to improve the effects of SSGs and HIIT. It also suggests that different forms of HIIT can be used because of the range of opportunities that such training affords.

Background Only clinically validated HPV assays can be accepted in cervical cancer screening. Objectives To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). Data Sources PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014-August 2020. Study eligibility criteria HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer [CIN2+]). Methods Overview tables of relative sensitivity and specificity, including non-inferiority statistics and test reproducibility; random-effect meta-analyses of the relative sensitivity and specificity for CIN2+ on index-vs comparator HPV tests. Participants Women participating in cervical cancer screening. Interventions Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome ( Methods Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility; random effects meta-analyses of the relative sensitivity and specificity of index vs comparator tests. Results Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio’s 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimisation, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review. Conclusions Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.

Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.

Background While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored. Objectives To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19. Data sources PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv. Study eligibility criteria and participants All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations. Interventions PrEP and PEP candidate for COVID-19. Methods Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion. Results We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements. Conclusions The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.

ObjectiveTo examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups.MethodsWe examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed.ResultsNHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data.ConclusionReduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.

Aim: To perform a systematic review on the application of artificial intelligence (AI) based knowledge discovery techniques in pharmacoepidemiology. Study Eligibility Criteria: Clinical trials, meta-analyses, narrative/systematic review, and observational studies using (or mentioning articles using) artificial intelligence techniques were eligible. Articles without a full text available in the English language were excluded. Data Sources: Articles recorded from 1950/01/01 to 2019/05/06 in Ovid MEDLINE were screened. Participants: Studies including humans (real or simulated) exposed to a drug. Results: In total, 72 original articles and 5 reviews were identified via Ovid MEDLINE. Twenty different knowledge discovery methods were identified, mainly from the area of machine learning (66/72; 91.7%). Classification/regression (44/72; 61.1%), classification/regression + model optimization (13/72; 18.0%), and classification/regression + features selection (12/72; 16.7%) were the three most frequent tasks in reviewed literature that machine learning methods has been applied to solve. The top three used techniques were artificial neural networks, random forest, and support vector machines models. Conclusions: The use of knowledge discovery techniques of artificial intelligence techniques has increased exponentially over the years covering numerous sub-topics of pharmacoepidemiology. Systematic Review Registration: Systematic review registration number in PROSPERO: CRD42019136552.

To summarize the evidence on the efficacy and safety of neural stem cell therapy (NSCT) for the treatment of spinal cord injury (SCI).A systematic literature review of Medline®, EMBASE® and Cochrane library was performed to identify studies reporting efficacy and safety of NSCT in SCI. Articles were included if they reported efficacy and safety data of SCI patients who received NSCT.Overall, four studies of the 277 records met all the study eligibility criteria. Over the 1-year follow-up period, motor scores were significantly higher among patients who received NSCT compared with those who did not (American Spinal Injury Association [ASIA] motor scores (mean±standard deviation [SD]): 7.9±1.2 versus 3.9±0.6; upper extremity motor score: 7.8±2.1 versus 3.9±0.6, both P0.05). Sensory scores (pinprick score: 4.8±1.3 versus 2.9±0.6; P=0.5; light touch score: 6.9±3.1 versus 2.3±0.5, P=0.3), ASIA impairment scale (26% versus 7%) or pain score (baseline: 2.4±0.6; 1-year: 3.4±0.4) were comparable in both NSCT and non-NSCT cohorts. Over the 1-year follow-up period, the graded redefined assessment of strength, sensibility, and prehension and international standards for neurological classification of SCI scores showed a mean improvement of 14.8 and 17.8 points respectively. Overall, treatment with NSCT showed favorable safety and tolerability profile.Due to the limited and poor-quality evidence, it is too early to make robust conclusions on the efficacy of NSCT in the treatment of SCI. However, based on the included studies, NSCT seems to be a potential option worth exploring among patients with SCI. Nonetheless, prospective, randomized trials in larger cohorts are needed to validate the efficacy and safety of NSCT in the treatment of SCI.

The goal of this systematic review was to evaluate the effects of exercise programs using agility ladders and to assess the quality of available evidence. Search was conducted in October of 2019 using the following databases: Cochrane Library, PEDro, PubMed, Scopus and Web of Science. Study eligibility criteria included randomized trials or randomized controlled trials using agility ladders drills. Participants were healthy humans of any health status. The study appraisal and synthesis methods followed the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and a qualitative synthesis of the main results of each study were applied. Only five studies met our criteria, lasting between 4 and 8 weeks. Only two studies evaluated the effects of ladder drills on more than one dimension. Lack of description of the specific exercises that were used limits reproducibility of current studies. With one exception, the articles had low risk of bias for most domains. Despite the widespread popularity of agility ladder drills, research is scarce and problematic, with poorly described protocols and mostly unidimensional performance measures. Claims that agility ladders improve agility and other physical skills is premature, given the nature and quality of existing research.

Background:Fecal microbiota transplantation (FMT) is an effective therapy in recurrentClostridium difficileinfection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results.Objectives:To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases.Data sources:The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019.Study eligibility criteria:Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster.Methods:A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist.Results:Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole.Conclusions:Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.

It is not infrequent that patients with different cancers are affected by bodily organ dysfunction. Factors such as comorbidities, prior anticancer therapies and tumor-related issues are frequent causes of organ impairment. Since patients with bodily organ dysfunction are not frequently enrolled in conventional clinical trials due to standard study eligibility criteria, such patients are placed at a disadvantage in receiving appropriate anticancer treatment. Renal and hepatic impairment may also have potential detrimental effects on the pharmacokinetic profile of drugs, with subsequent implications for both safety and efficacy.

Lymphoscintigraphy is a well-established radiologic examination to evaluate lymphatic function. We conducted a systematic review of the use of lymphoscintigraphy for evaluation of lymphedema treatment. We hypothesized that this radiologic examination could add relevant findings of treatment outcomes of lymphedema patients. We conducted a systematic review of articles in PubMed, without any time frame or language limitations, about the use of lymphoscintigraphy for the evaluation of lymphedema treatment. Articles were excluded if they investigated other uses of lymphoscintigraphy, such as diagnosis or prevention of lymphedema. Abstracts, presentations, reviews, and meta-analyses were also excluded. Of 101 potential articles found in the literature, 5 fulfilled our study eligibility criteria, and they were all case series. These articles included a total of 327 patients, most of whom had breast cancer-related lymphedema. Interventions included lymph node or vessel transfer (3 of 5 articles), complex decongestive therapy (1 of 5), and adipose-derived stem cell injection (1 of 5). The authors of these studies used lymphoscintigraphy to investigate the treatment functional outcomes, prognostic value, and complications. Lymphoscintigraphy detected lymphangiogenesis in transferred lymph nodes, and it was able to predict patient response to complex decongestive therapy. Studies that used lymphoscintigraphy to evaluate lymphedema treatment demonstrated its flexibility to provide various types of information. We hope this review will support future studies.

OBJECTIVE: The purpose of this study was to examine the literature regarding the natural history and rehabilitative outcomes of sensorineural hearing loss from congenital cytomegalovirus infections. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: A systematic search was performed in PubMed, PsychINFO, CINAHL, and Web of Science to identify peer-reviewed research. Eligible studies were those containing original peer-reviewed research in English addressing either the natural history or rehabilitative outcomes of SNHL in cCMV. STUDY APPRAISAL AND SYNTHESIS METHODS: Two investigators independently reviewed all articles and extracted data. Bias was assessed using the Cochrane Collaboration’s tool and the Newcastle-Ottawa Assessment Scale. RESULTS: Thirty-six articles were reviewed. Universal screening identifies 0.2 – 1% of newborns with cCMV infection. SNHL ranged from 8–32% of infants and was more prevalent in symptomatic vs. asymptomatic cases. 9 – 68% of hearing loss occurs in a late or delayed fashion. In 7–71% of cases hearing loss is progressive. Cochlear implantation is a viable option for patients with cCMV associated hearing loss and leads to improvements in hearing and language. There is limited literature comparing rehabilitation outcomes in cCMV and non-cCMV CI recipients. CONCLUSION: Late onset and progressive hearing loss is seen in children who develop hearing loss from cCMV. Frequent audiologic follow-up is necessary considering the natural history of cCMV hearing loss. Universal screening should be pursued due to the number of asymptomatic children, at birth, who develop late onset/delayed hearing loss. Cochlear implantation is an effective means of improving speech and language in this population.

Different delivery mechanisms have been proposed in the literature for targeted therapies in the treatment of lymphedema. They vary from simple and direct injection to sophisticated induction of gene expression in a targeted tissue. We conducted a systematic review of publications assessing the use of viral vectors for gene transfer in lymphedema treatment. We hypothesized that viral vectors are an effective way to deliver targeted therapy in lymphedema treatment. We conducted a comprehensive systematic review of the published literature on targeted therapies associated with lymphedema surgery using the PubMed database. Eligibility criteria excluded papers that reported use of viral vectors for other medical conditions. Abstracts, presentations, reviews, meta-analyses, and non-English language articles were also excluded. From 21 potential articles found in the literature, fourteen fulfilled study eligibility criteria. Positive outcomes in terms of lymphangiogenesis were seen. The viral vectors used included adenovirus and recombinant adeno-associated virus. Most of the genes expressed were growth factors, but expression of dominant-negative transforming growth factor-β1 receptor-II or Prox1 was also proposed. Five studies targeted genetic expression on lymphedema tissue, five on transplanted lymph nodes, two on skeletal muscle, and one on adipose-derived stem cells. Publications assessing use of viral vectors for gene transfer in lymphedema treatment demonstrated that it is an effective mechanism of delivering targeted therapies. However, to date, all studies were experimental and further studies must be performed before translating these therapies into clinical practice.

Background: Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. Objectives: Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. Data sources: Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. Study eligibility criteria: For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at

Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs ( 20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02–1.37). Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

Aim To compare the educational outcomes using artificial teeth versus extracted teeth for pre-clinical endodontic training. Data sources Literature searches of PubMed, Scopus, Cochrane Library, Trip Database, Web of Science and Open Grey databases were conducted from their inception until November 2018 with no language restriction. Hand searching of most likely relevant journals was performed. The review followed the PRISMA guidelines. Study eligibility criteria, participants and interventions Studies that compared pre-clinical endodontic training using extracted teeth and artificial teeth were included. Study appraisal and synthesis methods The quality of included studies was appraised by Joanna Briggs Institute Critical Appraisal tools. The findings were tabulated and summarized according to their outcomes with distinct narrative syntheses. Results Five studies were included. The component studies included 359 operators in total, mainly consisting of undergraduate students (97%, n = 349) and 10 endodontists (3%). Forty-seven per cent (n = 170) operated on artificial teeth only, whilst 19% (n = 67) worked primarily on extracted teeth, with the final treatment outcome being evaluated by independent observers using objective criteria. Operators in two studies (34%, n = 122) used both artificial teeth and ET and compared their experiences in surveys. Regarding technical outcomes, no significant differences between training with artificial teeth and extracted teeth were found, but the performance tended to be better in artificial teeth than extracted teeth. Operators trained solely on artificial teeth appeared to be adequately educated for subsequent root canal treatment (RCT) in the clinical setting. Limitations Due to the scarcity of research on the topic overall, and the methodological variation between the studies, it was not possible to perform a quantitative analysis (meta-analysis). Conclusions and implications of key findings Based on the available evidence, the use of artificial teeth for pre-clinical endodontic training achieved similar educational outcomes compared to extracted teeth. However, the experiences reported by the operators diverged. Further studies assessing other artificial teeth available in the market testing other RCT procedures are necessary.

Background. Many studies, comparing the health associated risks of electronic cigarettes with conventional cigarettes focus mainly on the common chemical compounds found between them. Aim. Review chemical compounds found exclusively in electronic cigarettes and describe their toxic effects, focusing on electronic-cigarette-only and dual electronic-cigarette and conventional cigarette users. Data Sources. Literature search was carried out using PubMed. Study Eligibility Criteria. Articles related exclusively to conventional and electronic cigarettes’ chemical composition. Articles which reported to be financed from tobacco or electronic cigarettes industries, not reporting source of funding, not related to the chemical composition of electronic and conventional cigarettes and not relevant to tobacco research were excluded. Methods and Results. Chemical compounds reported in the selected studies were tabulated using the Chemical Abstracts Service registry number for chemical substances information. A total of 50 chemical compounds were exclusively reported to be present in electronic cigarettes. Crucial health risks identified were: eye, skin, and respiratory tract irritation, with almost 50% of incidence, an increment of 10% in cytotoxic effects, when compared to compounds in common with conventional cigarettes and around 11% of compounds with unknown effects to human health. Limitations. Articles reporting conflicts of interest. Conclusions and Implications of Key Findings. Despite being considered as less harmful for human health, compounds found in electronic cigarettes are still a matter of research and their effects on health are yet unknown. The use of these devices is not recommended for first time users and it is considered hazardous for dual users.

Made available in DSpace on 2018-12-11T17:02:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-03 Purpose: To assess the efficacy and safety of porous and nonporous implants for management of the anophthalmic socket.Methods: Case series meta-analysis was conducted with no language restriction, including studies from: PUBMED, EMBASE and LILACS. Study eligibility criteria were case series design with more than 20 cases reported, use of porous and/or nonporous orbital implants, anophthalmic socket and, treatment success defined as no implant exposure or extrusion. Complications rates from each included study were quantified. Proportional meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated. Results: A total of 35 case series studies with a total of 3,805 patients were included in the meta-analysis. There are no studies comparing porous and nonporous implants in the anophthalmic socket treatment. There was no statistically significant difference between porous polyethylene (PP) and hydroxyapatite (HA) on implant exposure: 0.026 (0.012-0.045) vs 0.054 (0.041-0.070), respectively and, neither on implant extrusion: 0.0042 (0.0008-0.010) vs. 0.018 (0.004-0.042), respectively. However, there was a significant difference supporting the use of PP when compared to bioceramic implant: 0.026 (0.012-0.045) vs. 0.12 (0.06-0.20), respectively, on implant exposure. Conclusion: PP implants showed lower chance of exposure than bioceramic implant for anophthalmic socket reconstruction, although we cannot rule out the possibility of heterogeneity bias due to the nature and level of evidence of the included studies. Clinical trials are necessary to expand the knowledge of porous and nonporous orbital implants in the anophthalmic socket management. Department of Ophthalmology Faculdade de Medicina de Botucatu/UNESP Campus Universitario Eye and Facial Appearances McMaster Institute of Urology McMaster University-Hamilton Department of Ophthalmology Faculdade de Medicina de Botucatu/UNESP Campus Universitario

Despite the importance of pharmacy practice-based research in generating knowledge that results in better outcomes for patients, health systems and society alike, common challenges to PPBR persist. Herein, we authors describe PPBR challenges our research teams have encountered, and our experiences using technology-driven solutions to overcome such challenges. Notably, limited financial resources reduce the time available for clinicians and researchers to participate in study activities, therefore, resource allocation must be optimized. We authors have also encountered primary data collection challenges due to unique data needs and data access/ownership issues. Moreover, we have experienced a wide geographic dispersion of study practices and collaborating researchers, a lack of trained, on-site research personnel, and the identification and enrollment of participants meeting study eligibility criteria. To address these PPBR challenges, we authors have begun to turn to technology-driven solutions, as described here.

Background Non-responsiveness to treatment occurs in approximately one third of patients. Randomized clinical trials of psychotherapy options for these patients are scarce and systematic knowledge about whether psychotherapy is a viable option is lacking. Objectives This meta-analysis aimed to 1) determine the amount of evidence available for treatment non-response using psychotherapy relative to pharmacological procedures; 2) systematically review randomized controlled psychotherapy trials (RCTs) used to treat non-responders; and 3) examine whether some psychotherapies are more efficacious than others. Data sources Online databases were systematically examined and references of relevant systematic reviews were hand-searched. Study eligibility criteria RCTs that administered a psychotherapy new to non-responders were considered. All Mood and Anxiety Disorders were considered. No limitations were made with respect to type of treatment. Review method A meta-analytic review of the psychotherapy RCTs for treatment non-responders. Results Results showed that psychotherapy was successful in treating treatment non-responders with a medium to large effect size. Between-group comparisons did not reveal significant differences in treatment effects for any of the assessed disorder or treatment types. Effects were maintained at follow-up. Conclusions Psychotherapy is a viable treatment option for treatment non-responders. More attention to this group of patients is needed and more research with better quality studies is warranted. Recommendations are discussed.

The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2-3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.

Prior research has focused primarily on the educational benefits of high socioeconomic status (SES). Little is known about educationally successful youth from low-SES backgrounds, and no published review has systematically evaluated the methodological characteristics of research in this area. The primary aim of this report was to systematically review methodological characteristics of research identifying parenting factors conducive to the educational success of low-SES youth. A secondary aim was to briefly summarize the substantive findings of research in this area. A bibliographic search of 11 electronic databases, a manual search of two journals, and reference harvesting yielded 30 English-language studies published between 1994 and 2014 employing quantitative, qualitative, and mixed-method designs that met a-priori study eligibility criteria. Studies of parent–school involvement, parental expectations for current and long-term academic performance, and warm, responsive, and consistent parenting styles...

Objective To determine the risk of recurrent spontaneous preterm birth (sPTB) following sPTB in singleton pregnancies. Design Systematic review and meta-analysis using random effects models. Data sources An electronic literature search was conducted in OVID Medline (1948–2017), Embase (1980–2017) and ClinicalTrials.gov (completed studies effective 2017), supplemented by hand-searching bibliographies of included studies, to find all studies with original data concerning recurrent sPTB. Study eligibility criteria Studies had to include women with at least one spontaneous preterm singleton live birth (

Background: The introduction of optical coherence tomography (OCT) in dentistry enabled the integration of already existing clinical and laboratory investigations in the study of the oral cavity. This systematic review presents an overview of the literature, to evaluate the usefulness of in vivo OCT for diagnosing oral soft tissues lesions, to compare the OCT results with traditional histology, and to identify limitations in prior studies so as to improve OCT applications. Methods: We performed a review of the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library) employing MeSH terms such as “optical coherence tomography” and “OCT” in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. Results: Initial results were 3155. In conclusion, there were only 27 studies which met our selection criteria. We decided to allocate the 27 selected items into three groups: healthy mucosa; benign, premalignant, and malignant lesions; and oral manifestations of systemic therapies or pathological conditions. Conclusions: Although the OCT is an easy-to-perform test and it offers an attractive diagnostic and monitoring prospect for soft tissues of the oral cavity, further studies are needed to complete the current knowledge of this imaging technique. Background: The introduction of optical coherence tomography (OCT) in dentistry enabled the integration of already existing clinical and laboratory investigations in the study of the oral cavity. This systematic review presents an overview of the literature, to evaluate the usefulness of in vivo OCT for diagnosing oral soft tissues lesions, to compare the OCT results with traditional histology, and to identify limitations in prior studies so as to improve OCT applications. Methods: We performed a review of the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library) employing MeSH terms such as “optical coherence tomography” and “OCT” in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. Results: Initial results were 3155. In conclusion, there were only 27 studies which met our selection criteria. We decided to allocate the 27 selected items into three groups: healthy mucosa; benign, premalignant, and malignant lesions; and oral manifestations of systemic therapies or pathological conditions. Conclusions: Although the OCT is an easy-to-perform test and it offers an attractive diagnostic and monitoring prospect for soft tissues of the oral cavity, further studies are needed to complete the current knowledge of this imaging technique.

Purpose: The goal of this study was to examine preference for collaborative decision-making in Japanese patients with rheumatoid arthritis (RA). Patients and methods: A national online survey identified five hundred Japanese patients with RA who met study eligibility criteria. Subjects were queried regarding their preference for shared decision-making (SDM), using a questionnaire developed by Baars et al. to evaluate preference for SDM among Dutch patients. Participants in this study were asked to identify a number of clinical and socioeconomic characteristics, medical history, and treatment details. Multivariable regression analyses were applied to determine factors that were related to patient preference for SDM. Results: The study showed that 52% of patients surveyed considered shared medical decision-making “Very important” on a 4-item Likert scale. Females and patients with RA in Japan who are treated with biologic agents are more likely to have a preference for SDM. On the other hand, patients with a comorbidity of depression are less likely to prefer SDM. Conclusion: A majority of Japanese patients with RA prefer a collaborative role in medical decision-making. Treatment with biologic agents is associated with a higher likelihood of preference for SDM.

Background Congenital left ventricular outpouchings (LVOs) are reported under five overlapping and poorly defined terms including left ventricular accessory chamber, left ventricular aneurysm (LVA), left ventricular diverticulum (LVD), double-chambered LV, and accessory left ventricle. Diagnostic criteria are frequently mixed and not mutually exclusive. They convey no information regarding treatment strategy and prognosis. Objectives The aim of this systematic review is to provide a clear and inclusive classification, with therapeutic and prognostic implications, for congenital LVOs. Data sources We performed three separate sets of search on three subjects including “congenital left ventricular outpouchings,” “important and simply measurable markers of left ventricular function,” and “relationship of mechanics of intraventricular blood flow and optimal vortex formation in left ventricle and elliptical geometry of LV.” Study eligibility criteria We enrolled case series, review articles, and case reports with literature review. All types of acquired LVO's were excluded. Study appraisal and synthesis methods We studied the abstracts of all searched articles. We focused on diagnostic criteria and patients' outcome. To examine the validity and reliability of the novel classification, fifteen previous studies were revisited using the novel classification. Results A total of 20 papers from 11 countries fulfilled our inclusion criteria. The age of patients ranged from prenatal age to geriatric age range. Diagnostic criteria were clearly stated only for two of the above five terms (i.e., congenital LVA and congenital LVD). Cases with mixed diagnostic criteria were frequent.Elliptical geometry of left ventricle was found to have significant impact on effective blood flow mechanics in LV. A simple inclusive classification for congenital LVOs, with therapeutic and prognostic implications, was introduced. Conclusion The cornerstone of this classification is elliptical LV geometry. Large-type IIc LVO have dismal prognosis, if left untreated. LVO type I and small LVO type IIa have the best prognosis.

Background The lack of systematic review on reference values of elements in human hair with the consideration of methodological approach. The absence of worldwide accepted and implemented universal reference ranges causes that hair mineral analysis has not become yet a reliable and useful method of assessment of nutritional status and exposure of individuals. Objectives Systematic review of reference values of elements in human hair. Data sources PubMed, ISI Web of Knowledge, Scopus. Study eligibility criteria Humans, hair mineral analysis, elements or minerals, reference values, original studies. Results The number of studies screened and assessed for eligibility was 52. Eventually, included in the review were 5 papers. The studies report reference ranges for the content of elements in hair: macroelements, microelements, toxic elements and other elements. Reference ranges were elaborated for different populations in the years 2000–2012. The analytical methodology differed, in particular sample preparation, digestion and analysis (ICP-AES, ICP-MS). Consequently, the levels of hair minerals reported as reference values varied. Conclusions It is necessary to elaborate the standard procedures and furtherly validate hair mineral analysis and deliver detailed methodology. Only then it would be possible to provide meaningful reference ranges and take advantage of the potential that lies in Hair Mineral Analysis as a medical diagnostic technique.

Objective The purpose of the present systematic review is to identify whether an association between gallbladder polyps and colorectal adenoma or neoplasia exists. Data sources We conducted a systematic review searching the Medline (1966–2016), Scopus (2004–2016), ClinicalTrials.gov (2008–2016) and Cochrane Central Register of Controlled Trials CENTRAL (1999–2016) databases together with reference lists from included studies. Study eligibility criteria All prospective and retrospective observational cohort studies were included. Results Four studies were finally included which included 17,437 patients. The association between gallbladder polyps and colorectal adenoma or even neoplasia is not unanimously supported. However, a possible association is clearly depicted. According to one study it seems that this correlation seems to become significant only when the gallbladder polyps exceed the size of 5 mm. However, the impact of size of gallbladder polyps was not investigated in the remaining studies. Conclusion According to the results of our systematic review there is some evidence to support the hypothesis that gallbladder polyps might adequately predict future risk of colorectal neoplasia. At present, however, current knowledge is very limited and the available data scarce. In this context further studies are necessary to be carried out, before the presence of gallbladder polyps on ultrasound can be recommended as an indication to perform a screening colonoscopy on the same patient.

This study attempted to systematically assess the experiences of Medicare and Medicaid "dual-eligible" psychiatric patients, including evaluating patients' access to medications and the administrative functioning of the program, during the first 4 months of the Medicare Part D prescription drug benefit.Psychiatrists (N=5,833) were randomly selected from the American Medical Association's Physicians Masterfile. After exclusion of those not practicing and with undeliverable addresses, 64% responded; 35% met study eligibility criteria of treating at least one dual-eligible patient during their last typical workweek and reported clinically detailed information on one systematically selected patient.A total of 53.4% had at least one medication access problem to report between Jan. 1 and April 30, 2006. Although 9.7% experienced improved medication access, 22.3% discontinued or temporarily stopped taking medication because of prescription drug coverage or management issues, and 18.3% were previously stable but were required to switch medications. Among those with medication access problems, 27.3% experienced a significant adverse clinical event; 19.8% had an emergency room visit. Most drug plan features studied, including preferred drug/formulary lists, prior authorization, medication dosing/number limits, "fail-first" protocols, and requirements to switch to generics, were associated with significantly higher rates of medication access problems.The findings indicate consequential medication access problems for psychiatric patients during the implementation of Medicare Part D. Although Centers for Medicare and Medicaid Services policies were enacted to ensure access to protected classes of psychopharmacologic medications, the high rates of medication access problems observed indicate further refinement of these policies is needed.

To describe visual acuity (VA) testing and scoring methods used in multicenter randomized clinical trials in ophthalmology in the United States (USA) sponsored by the National Eye Institute (NEI).A survey was conducted among multicenter studies in the US that included one or more randomized clinical trials and were sponsored by the NEI, National Institutes of Health. To be included in the survey, a study had to have VA reported in one or more publications or patient eligibility based on VA, a majority of study subjects 13 years of age or older, and a patient population primarily or exclusively from the US. A standard survey form was completed for each study based on information presented in the study manual of procedures and publications. Findings were summarized and displayed with frequency distributions.The survey included 24 studies, each with enrollment initiated in the period 1972 to 1999. VA was one of the study eligibility criteria for 19 (79%) studies, and VA or change in VA was the primary outcome in 12 (50%) studies. ETDRS charts have been employed in 16 of 19 studies initiated after the charts were published in 1982. All studies but one specified in the documents reviewed that VA testing was performed at multiple VA test distances. For studies that used ETDRS charts, methods of converting VA scores obtained at different test distances to a common scale fell into two categories: 11 studies used a method similar in nature to that first reported in the Macular Photocoagulation Study, and 7 studies used a method similar in nature to that first reported in the Krypton-Argon Regression of Neovascularization Study. conclusion The development of the ETDRS charts and a custom light box has led to more uniformity in VA test charts and chart illumination. However, details of VA measurement protocols vary widely from study to study. To assure comparable data across studies and ocular conditions, it would be useful to have a standard VA testing and scoring protocol with provisions for testing different levels of visual acuity that recommends a single method for converting scores from different test distances to a common scale and standard conversion of "off the chart" VA levels for calculation of means and changes in VA.