The 2018 ter Brugge Lecture: Problems with the Introduction of Innovations in Neurovascular Care

ABSTRACT:Most endovascular innovations have been introduced into clinical care by showing good outcomes in small enthusiastic case series of selected patients. Randomized clinical trials (RCTs) have rarely been performed, except for acute ischemic stroke, but even then most trial designs were too explanatory to inform clinical decisions. In this article, we review 2 × 2 tables and forest plots that summarize RCT results to examine methodological issues in the design and interpretation of clinical studies. Research results can apply in practice when RCTs are all-inclusive, pragmatic trials. Common problems include the following: (i) using restrictive eligibility criteria in explanatory trials, instead of including the diversity of patients in need of care, which hampers future generalizability of results; (ii) ignoring an entire line of the 2 × 2 table and excluding patients who do not meet the proposed criteria of a diagnostic test in its evaluation (perfusion studies) which renders clinical inferences misleading; (iii) ignoring an entire column of the 2 × 2 table and comparing different patients treated using the same treatment instead of different treatments in the same patients (the “wrong axis” comparisons of prognostic studies and clinical experience) which leads to unjustified treatment decisions and actions; or (iv) combining all aforementioned problems (case series and epidemiological studies). The most efficient and reliable way to improve patient outcomes, after as well as long before research results are available, is to change the way we practice: to use care trials to guide care in the presence of uncertainty.

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Titanium Mesh Exposure After Bone Grafting: Treatment Approaches—A Systematic Review

Craniomaxillofacial Trauma & Reconstruction ◽

10.1177/19433875211046114 ◽

2021 ◽

pp. 194338752110461

Author(s):

Giovanni Cunha ◽

Pedro Henrique de Azambuja Carvalho ◽

Lílian Caldas Quirino ◽

Luiz Henrique Soares Torres ◽

Valfrido Antônio Pereira Filho ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Case Series ◽

Primary Treatment ◽

Mesh Exposure ◽

Titanium Mesh ◽

Mesh Removal ◽

Eligibility Criteria ◽

Oral Hygiene Instructions

Study Design: A systematic review according to PRISMA statement has been designed to answer the preliminary question: “ In titanium mesh exposures, is there a treatment alternative which leads to an increased graft maintenance?” and fill the PICO assessment out. Objective: To review studies published in the past 20 years (1999-2019) in which mesh exposure has occurred, detecting the suitable approaches to treat exposure allowing the graft maintenance. Methods: Initial search on PUBMED, SCOPUS, and COCHRANE databases resulted in 777 articles, and hand-searching identified 6 articles. After removing duplicates and unrelated articles, eligibility criteria were applied, and 31 studies were selected (randomized clinical trials, retrospective/prospective clinical trials, and case series). Results: A total of 677 surgical sites and 225 cases of mesh exposure were identified. Eleven treatments have been identified. Chlorhexidine was the primary approach in 46% of cases, followed by oral hygiene instructions and follow-up with 22.5% of occurrences. In 21% of clinical situations, titanium mesh removal was the treatment of choice, associated with other measures (i.e., antibiotic prescription). There seems to be a consensus in cases of infection. When this complication was associated with tissue dehiscence, the primary treatment was mesh removal. The same does not occur when the site needs to be cleaned for long-term periods. Conclusion: In 2 decades of use of titanium meshes, the available treatments do not seem to have evolved, and there is not enough data to establish a guideline.

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Enhancing the Impact of Genomics Research in Autism through Integration of Research Results into Routine Care Pathways—A Case Series

Journal of Personalized Medicine ◽

10.3390/jpm11080755 ◽

2021 ◽

Vol 11 (8) ◽

pp. 755

Author(s):

Iskra Peltekova ◽

Daniela Buhas ◽

Lara Stern ◽

Emily Kirby ◽

Afiqah Yusuf ◽

...

Keyword(s):

Clinical Care ◽

Genetic Research ◽

Case Series ◽

Routine Care ◽

Autism Spectrum ◽

Care Pathways ◽

Research Results ◽

Individualized Care ◽

The Impact ◽

Genetic Results

The return of genetic results (RoR) to participants, enrolled as children, in autism research remains a complex process. Existing recommendations offer limited guidance on the use of genetic research results for clinical care. We highlight current challenges with RoR and illustrate how the use of a guiding framework drawn from existing literature facilitates RoR and the clinical integration of genetic research results. We report a case series (n = 16) involving the return of genetic results to participants in large genomics studies in Autism Spectrum Disorders (ASD). We outline the framework that guided RoR and facilitated integration into clinical care pathways. We highlight specific cases to illustrate challenges that were, or could have been, resolved through this framework. The case series demonstrates the ethical, clinical and practical difficulties of RoR in ASD genomic studies for participants enrolled as children. Challenges were resolved using pre-established framework to guide RoR and incorporate research genetic results into clinical care. We suggest that optimal use of genetic research results relies on their integration into individualized care pathways for participants. We offer a framework that attempts to bridge the gap between research and healthcare in ASD.

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The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials

Nutrients ◽

10.3390/nu13114059 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4059

Author(s):

Roser Granero ◽

Alfred Pardo-Garrido ◽

Ivonne Lorena Carpio-Toro ◽

Andrés Alexis Ramírez-Coronel ◽

Pedro Carlos Martínez-Suárez ◽

...

Keyword(s):

Systematic Review ◽

Children And Adolescents ◽

Randomized Clinical Trials ◽

Influencing Factor ◽

Neurodevelopmental Disorder ◽

Developed Countries ◽

Epidemiological Studies ◽

Cellular Respiration ◽

Eligibility Criteria ◽

Iron And Zinc

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder common from childhood to adulthood, affecting 5% to 12% among the general population in developed countries. Potential etiological factors have been identified, including genetic causes, environmental elements and epigenetic components. Nutrition is currently considered an influencing factor, and several studies have explored the contribution of restriction and dietary supplements in ADHD treatments. Iron is an essential cofactor required for a number of functions, such as transport of oxygen, immune function, cellular respiration, neurotransmitter metabolism (dopamine production), and DNA synthesis. Zinc is also an essential trace element, required for cellular functions related to the metabolism of neurotransmitters, melatonin, and prostaglandins. Epidemiological studies have found that iron and zinc deficiencies are common nutritional deficits worldwide, with important roles on neurologic functions (poor memory, inattentiveness, and impulsiveness), finicky appetite, and mood changes (sadness and irritability). Altered levels of iron and zinc have been related with the aggravation and progression of ADHD. Objective: This is a systematic review focused on the contribution of iron and zinc in the progression of ADHD among children and adolescents, and how therapies including these elements are tolerated along with its effectiveness (according to PRISMA guidelines). Method: The scientific literature was screened for randomized controlled trials published between January 2000 to July 2021. The databases consulted were Medline, PsycINFO, Web of Science, and Google Scholar. Two independent reviewers screened studies, extracted data, and assessed quality and risk of bias (CONSORT, NICE, and Cochrane checklists used). Conclusion: Nine studies met the eligibility criteria and were selected. Evidence was obtained regarding the contribution of iron-zinc supplementation in the treatment of ADHD among young individuals. The discussion was focused on how the deficits of these elements contribute to affectation on multiple ADHD correlates, and potential mechanisms explaining the mediational pathways. Evidence also suggested that treating ADHD with diet interventions might be particularly useful for specific subgroups of children and adolescents, but further investigations of the effects of these diet interventions are needed.

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Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

Operative Dentistry ◽

10.2341/19-064-l ◽

2020 ◽

Vol 45 (6) ◽

pp. 589-597

Author(s):

BGS Casado ◽

EP Pellizzer ◽

JR Souto Maior ◽

CAA Lemos ◽

BCE Vasconcelos ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Color Change ◽

Meta Analysis ◽

Present Review ◽

Cochrane Library ◽

Light Sources ◽

Eligibility Criteria ◽

Tooth Color ◽

Significant Difference ◽

Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1.iss1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

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Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors

Indian Journal of Psychological Medicine ◽

10.1177/0253717621992372 ◽

2021 ◽

pp. 025371762199237

Author(s):

Niti Mittal ◽

Rakesh Mittal ◽

M. C. Gupta

Keyword(s):

Adverse Reactions ◽

Case Reports ◽

Case Series ◽

Eligibility Criteria ◽

Study Objective ◽

Spontaneous Reports ◽

Cochrane Database ◽

Sleep Behaviors ◽

Therapeutic Doses ◽

Favorable Side Effect Profile

Background: Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem. Objective: To conduct a systematic review of zolpidem-associated CSBs. Data Sources: An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020. Study Eligibility Criteria: Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem. Results: In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem. Limitations: Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective. Conclusion and Implication of Key Findings: Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

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Scoping review protocol: bladder cancer in Nigeria: what are the gaps in clinical care and research?

BMJ Open ◽

10.1136/bmjopen-2020-041894 ◽

2021 ◽

Vol 11 (1) ◽

pp. e041894

Author(s):

Joyce Kibaru ◽

Pinky Kotecha ◽

Abdulkarim Muhammad Iya ◽

Beth Russell ◽

Muzzammil Abdullahi ◽

...

Keyword(s):

Bladder Cancer ◽

Scoping Review ◽

Low Income ◽

Clinical Care ◽

Grey Literature ◽

Case Series ◽

Cochrane Library ◽

Future Research ◽

Scoping Reviews ◽

Local Risk

IntroductionBladder cancer (BC) is the 10th common cancer worldwide and ranks seventh in Nigeria. This scoping review aims to identify the gaps in clinical care and research of BC in Nigeria as part of the development of a larger national research programme aiming to improve outcomes and care of BC.Methods and analysisThis review will be conducted according to Arksey and O’Malley scoping review methodology framework. The following electronic databases will be searched: Medline (using the PubMed interface), Ovid Gateway (Embase and Ovid), Cochrane library and Open Grey literature. Two independent reviewers will screen titles and abstracts and subsequently screen full-text studies for inclusion, any lack of consensus will be discussed with a third reviewer. Any study providing insight into the epidemiology or treatment pathway of BC (RCTs, observations, case series, policy paper) will be included. A data chart will be used to extract relevant data from the included studies. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. A consultation process will be carried out with a multidisciplinary team of Nigerian healthcare professionals, patients and scientists.Ethics and disseminationThe results will be disseminated through peer-reviewed publications. By highlighting the key gaps in the literature, this review can provide direction for future research and clinical guidelines in Nigeria (and other low-income and middle-income countries), where BC is more prevalent due to local risk factors and healthcare settings.

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Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling

BMC Neurology ◽

10.1186/s12883-021-02233-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Christopher Dardis ◽

David Donner ◽

Nader Sanai ◽

Joanne Xiu ◽

Sandeep Mittal ◽

...

Keyword(s):

Copy Number ◽

Epithelial To Mesenchymal Transition ◽

Clinical Care ◽

Case Series ◽

Molecular Profiling ◽

Retrospective Case ◽

Who Grade ◽

Exact Test ◽

Mesenchymal Transition ◽

Dna And Rna

Abstract Background Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. Methods Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. Results Potentially meaningful associations (p<0.1, Fisher’s exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. Conclusions GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

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Epidemiologic Study of the Discoid Meniscus: Investigating Demographic-Based Predictors in Large-Scale Claims Database

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967121s00086 ◽

2021 ◽

Vol 9 (7_suppl3) ◽

pp. 2325967121S0008

Author(s):

Sahej S Randhawa ◽

Emily P Tran ◽

Nicole A Segovia ◽

Theodore J Ganley ◽

Marc Tompkins ◽

...

Keyword(s):

Logistic Regression ◽

Total Population ◽

Clinical Care ◽

Epidemiologic Study ◽

Case Series ◽

Incidence Rates ◽

National Database ◽

Discoid Meniscus ◽

Racial Categories ◽

Claims Database

Background: Discoid meniscus epidemiology remains poorly defined for race and sex, in part, due to limitations of retrospective studies and small case series. A better understanding of epidemiology may improve clinical care and diagnostic precision. Purpose: Our purpose is to better define the epidemiology of discoid meniscus by analyzing a large, national database for incidence rates by sex and race. Methods: Analysis was conducted on the national-scale Clinformatics Data Mart Database by Optum. Proportions of the database’s racial categories (Asian, Black, Hispanic, White, and Unknown) in the total population of diagnosed discoid meniscus cases (n = 1,006) were calculated and compared via chi-squared tests to the total database population (n = 65,759,970). This analysis was repeated for the population of patients who received knee arthroscopies (81,205). Incidence rates were calculated from these populations as well. Finally, a multivariable logistic regression analysis based on the population of arthroscopy-receiving patients was performed to control for age, reported gender, and income. Results: Proportions of Asian, Black, Hispanic, and White racial categories in the discoid meniscus group were 5.7%, 7.3%, 20.6%, 66.4%, respectively; the proportions of each racial category in the total population were 5.2%, 10.3%, 13.5%, 71.0%, respectively. Incidence rates (per 10,000) for these groups in the arthroscopy population were 72.9, 25.6, 49.2, 25.6, respectively. Our logistic regression model indicated that race was not a statistically significant predictor for our dataset after income adjusting. Adjusting for other covariates, the odds of a discoid meniscus diagnosis decreased by 6% for each increase in age (p < 0.001) and were 41% lower for males compared to females (p < 0.001). Conclusion: Prior studies have suggested that race (Asian and Hispanic, is a predictor of higher incidence of discoid meniscus – this study did not show a difference in incidence based upon race. Patient sex and age was identified as significant predictors for discoid meniscus, and increasing age showed a decreasing incidence of this condition. This study’s analysis of a large, national claims database allows for a comprehensive epidemiological study on this topic, offering proportions and incidence rates by race appropriate for application to the US population. Its conclusions promote patient sex and age as significant predictors and question the beliefs on race-associated incidence often based on comparing results from the corpus of single-site cohort studies. Tables/Figures: [Table: see text]

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