Terms Of Study Design Research Articles

Lung ultrasound vs chest radiography in the diagnosis of children pneumonia

Background:The aim of this meta-analysis was to evaluate the diagnostic value of lung ultrasound (LUS) in comparison to chest radiography (CXR) in children with pneumonia.Methods:Computer-based retrieval was performed on PubMed and EMBASE. Quality was evaluated according to the quality assessment of diagnostic accuracy studies-2, and Meta-Disc was adopted to perform meta-analysis. Heterogeneity was assessed using Q and I2 statistics. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs) as the primary outcomes were calculated for each index test.Results:Twenty two studies with a total of 2470 patients met the inclusion criteria. Our results showed that the pooled sensitivity, specificity, and DOR for children with pneumonia diagnosed by LUS were 0.95 (95% CI: 0.94 to 0.96), 0.90 (95% CI: 0.87 to 0.92), and 137.49 (95% CI: 60.21 to 313.98), respectively. The pooled sensitivity, specificity, and DOR for pediatric pneumonia diagnosed by CXR was 0.91 (95% CI: 0.90 to 0.93), 1.00 (95% CI: 0.99 to 1.00), and 369.66 (95% CI: 137.14 to 996.47), respectively. Four clinical signs, including pulmonary consolidation, positive air bronchogram, abnormal pleural line, and pleural effusion were most frequently observed using LUS in the screening of children with pneumonia.Conclusions:The available evidence suggests that LUS is a reliable, valuable, and alternative method to CXR for the diagnosis of pediatric pneumonia.

Feasibility of clinical research studies reported by patients with behavioral variant frontotemporal dementia and their caregivers

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by progressive, profound behavioral changes plus loss of insight and independence, leading to significant burden for affected families both in daily life and clinical research participation. FORWARD study aimed to estimate disease‐related decline in patients with early‐stage bvFTD (NCT03088956) over 1 year (consisting of 6 in‐clinic and at least 4 at home study visits), using a battery of cognitive tests, functional, behavioral, and quality of life assessments. Participants were asked to complete an end‐of‐study questionnaire with the purpose to identify aspects of the study considered as potentially burdensome, challenging and/or positive.MethodThe one‐time end‐of‐study questionnaire consisting of 10 questions was completed by 29 bvFTD subjects and their 29 caregivers at their last study visit (Month 13 or Early Termination).ResultMajority of participants were very satisfied in taking part in the study (66% bvFTD; 72% caregivers). The top motivators to participation included contributing to dementia research (79% bvFTD; 93% caregivers) while the main drivers to complete the study included their commitment to be in the study (83% bvFTD; 86% caregivers) as well as the amount of care and attention received from the study doctor and staff (76% bvFTD; 79% caregivers). In terms of study design, home visits were considered useful (76% bvFTD; 83% caregivers) and not burdensome (79% bvFTD; 86% caregivers) by the majority of participants. Most participants did not find every 3‐months clinic visits (55% bvFTD; 62% caregivers), clinic visit length (62% bvFTD; 76% caregivers), and study duration (59% bvFTD; 72% caregivers) as burdensome. However, bvFTD patients considered burdensome cognitive assessments done either in paper forms (55%) or on iPAD (55%). Use of iPAD was considered useful (48% bvFTD; 64% caregivers) and not burdensome (69% bvFTD; 93% caregivers) mainly by caregivers and less so by patients. Financial travel support was deemed useful (69% bvFTD; 66% caregivers) and 62% of caregivers found the overall study experience not burdensome for bvFTD patients.ConclusionThese insights are useful to minimize the degree of burden for participants with improved clinical trial design in the bvFTD indication with limited drug development precedence.

Clinical Pharmacology in Women's Health: Current Status and Opportunities.

Clinical Pharmacology in Women's Health: Current Status and Opportunities.

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review.

Background: Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.

Opioids in Post-stroke Pain: A Systematic Review and Meta-Analysis.

Background: Post-stroke pain is one of the most common sequelae of stroke, which stands among the leading causes of death and adult-acquired disability worldwide. The role and clinical efficacy of opioids in post-stroke pain syndromes is still debated. Objectives: Due to the important gap in knowledge on the management of post-stroke pain, this systematic review aimed at assessing the efficacy of opioids in post-stroke pain syndromes. Methods: A literature search was conducted on databases relevant for medical scientific literature, i.e. PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library databases from databases inception until August 31st, 2020 for clinical trials assessing the effects of opioids and opioid antagonists on pain reduction and pain related symptoms in patients with post-stroke pain syndromes. Studies assessing the effects of other medications (e.g., tricyclic antidepressant, pregabalin) or non - pharmacological management strategies (e.g., neurostimulation techniques) were excluded. The selected studies have been subjected to examination of the risk of bias. Results: The literature search retrieved 83,435 results. After duplicates removal, 34,285 articles were title and abstract screened. 25 full texts were assessed and 8 articles were identified to be eligible for inclusion in the qualitative summary and narrative analysis, of which three were placebo-controlled and two were dose-response. Among placebo-controlled studies, two evaluated the analgesic effect of morphine and one assessed the effects of the opioid antagonist naloxone on patients with central post-stroke pain. With regard to dose-response studies, both were on patients with central post-stroke pain, one assessing the efficacy of levorphanol, and the other on naloxone. Seven out of eight included studies showed an overall slight analgesic effect of opioids, with less consistent effects on other pain-related symptoms (e.g., mood, quality of life). The randomized controlled trials were subjected to meta-analysis and rating of the quality of evidence for the two outcomes considered according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations) system. The overall results are inconclusive because of the small number of studies and of patients. Conclusions: The limited number of the included studies and their heterogeneity in terms of study design do not support the efficacy of opioids in post-stroke pain and in pain-related outcomes. Large double-blind randomized clinical trials with objective assessment of pain and related symptoms are needed to further investigate this topic.

Drivers for Non-Profits’ Success: Volunteer Engagement and Financial Sustainability Practices through the Resource Dependence Theory

The strategies that non-profit organizations choose for volunteer engagement and financial sustainability are of the utmost importance for successful work. The main purpose of this study was to investigate feasible strategies for volunteer engagement and financial sustainability. Interviews were conducted to obtain data on the experience of volunteer managers in dealing with volunteers and financial matters together. Qualitative data analysis methods were used to code and analyze the data. Significant themes emerged from the data gathered through interviews that highlighted the strategies for volunteer engagement and financial sustainability chosen by the managers of non-profit organizations. From the manager’s perspective, the following strategies were considered important for engaging volunteers at non-profit organizations (NPOs): ‘building the skill sets of volunteers’, ‘fulfilling ulterior motives’, and ‘administering a culture of administrative support’. Moreover, ‘local fundraising preference’, ‘transparency’, and ‘building trust’ were regarded as successful strategies for maintaining financial sustainability. The findings of this study showed that, to function smoothly, non-profit organizations need to follow certain strategies to be cautious about volunteers as well as finance. The findings provide fruitful implications for practitioners and policy makers, and these are discussed in the paper. Furthermore, the limitations addressed in the study suggest a future direction for research in terms of study design and more focus on study informants.

Malaria and cardiovascular disease: a systematic review

Abstract Background Myocardial tissue appears to be a favored site for the malaria parasite, and several studies have suggested that malaria may lead to myocardial dysfunction. Therefore, we conducted a systematic review of clinical studies reporting on malaria and cardiac disease. Methods We searched PubMed and Embase through January 2020. We applied strict inclusion criteria (Figure 1A) and assessed studies reporting on verified cardiac disease by paraclinical tests, ECG, cardiac biomarkers and echocardiographic findings. Two reviewers independently screened articles, extracted data and assessed the PRISMA guidelines. Results Twenty-eight articles were identified (published 1954–2020; n=19 case-reports, n=5 cohort studies, n=4 cross-sectional studies; Figure 1B), of which most were conducted in India (n=11) and Germany (n=4). The studies included a total of 2,221 malaria cases (mean age 42 years; 67% men; 41% complicated infection) and the distribution of species were: Plasmodium falciparum (n=15), vivax (n=12) and knowlesi (n=1). The most commonly reported cardiac diagnoses in case-reports were myocarditis (n=9), pericarditis (n=3) and acute myocardial infarction (n=4). Although the cohort and cross-sectional studies reported on different cardiac parameters (Figure 1C), a majority showed that malaria cases more often had elevated levels of cardiac biomarkers, ECG alterations and reduced left ventricular ejection fraction when compared to controls (P<0.05 for all). Conclusion Studies reporting on malaria and cardiovascular disease display considerable heterogeneity in terms of study design, severity and outcome measurements. Despite this, the included studies demonstrate a potential link between malaria and cardiac disease. This should be explored in future and larger hypothesis generating clinical studies. Figure 1 Funding Acknowledgement Type of funding source: None

To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease

Alzheimer disease (AD) is a global health concern with the majority of pharmacotherapy choices consisting of symptomatic treatment. Recently, ketogenic therapies have been tested in randomized controlled trials (RCTs), focusing on delaying disease progression and ameliorating cognitive function. The present systematic review aimed to aggregate the results of trials examining the effects of ketogenic therapy on patients with AD/mild cognitive impairment (MCI). A systematic search was conducted on PubMed, CENTRAL, clinicaltrials.gov, and gray literature for RCTs performed on adults, published in English until 1 April, 2019, assessing the effects of ketogenic therapy on MCI and/or AD compared against placebo, usual diet, or meals lacking ketogenic agents. Two researchers independently extracted data and assessed risk of bias with the Cochrane tool. A total of 10 RCTs were identified, fulfilling the inclusion criteria. Interventions were heterogeneous, acute or long term (45-180 d), including adherence to a ketogenic diet, intake of ready-to-consume drinks, medium-chain triglyceride (MCT) powder for drinks preparation, yoghurt enriched with MCTs, MCT capsules, and ketogenic formulas/meals. The use of ketoneurotherapeutics proved effective in improving general cognition using the Alzheimer's Disease Assessment Scale-Cognitive, in interventions of either duration. In addition, long-term ketogenic therapy improved episodic and secondary memory. Psychological health, executive ability, and attention were not improved. Increases in blood ketone concentrations were unanimous and correlated to the neurocognitive battery based on various tests. Cerebral ketone uptake and utilization were improved, as indicated by the global brain cerebral metabolic rate for ketones and [11C] acetoacetate. Ketone concentrations and cognitive performance differed between APOE ε4(+) and APOE ε4(-) participants, indicating a delayed response among the former and an improved response among the latter. Although research on the subject is still in the early stages and highly heterogeneous in terms of study design, interventions, and outcome measures, ketogenic therapy appears promising in improving both acute and long-term cognition among patients with AD/MCI. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019128311.

Overview of Mendelian Randomization Analysis

The inference of causality from observational evidence may be problematic, as observational studies frequently include confounding factors or reverse causation for the identification of associations between exposure and outcome. Thus, in observational studies, the association between a risk factor and a disease of interest may not be causal. A randomized controlled trial (RCT) is considered the gold standard, because it has the best possibility to establish a relationship between a risk factor and an outcome. However, RCTs cannot always be performed, because they can be costly, impractical, or even unethical. One of the alternatives is to perform Mendelian randomization (MR) experiments that are similar to RCTs in terms of study design. The MR technique uses genetic variants related to modifiable traits/exposures as tools to detect causal associations with outcomes. MR can provide more credible estimates of the causal effect of a risk factor on an outcome than those obtained in observational studies by overcoming the limitations of observational studies. Therefore, MR can make a substantial contribution to our understanding of complex disease etiology. MR approaches are increasingly being used to evaluate the causality of associations with risk factors, because well-performed MR studies can be a powerful method for exploring causality in complex diseases. However, there are some limitations in MR analyses, and an awareness of these limitations is essential to interpret the results. The validity of results from MR studies depends on three assumptions that should be carefully checked and interpreted in the context of prior biological information. (J Rheum Dis 2020;27:241-246)

Erectile function after focal therapy for localized prostate cancer: a systematic review.

Focal therapy modalities achieved interest in the management of prostate cancer (PCa) over the last a few years. This systematic review was aimed to investigate erectile function after focal therapy for localized PCa. Twenty-six out of 1287 reports were identified through a database systematic search in MEDLINE, EMBASE, and Web of Science, supplemented with hand search, on June 1st, 2020, according to PRISMA guidelines. Focal therapy modalities investigated were cryotherapy, high-intensity focused ultrasound (HIFU), photodynamic therapy (TOOKAD), irreversible electroporation (IRE), and focal radiotherapy (RT) (i.e. brachytherapy or stereotactic RT). Overall, reported sexual function outcomes after these treatment modalities were generally good, with many studies reporting a complete recovery of EF at 1-year follow-up. However, the quality of current evidence is affected both by the lack of well-conducted comparative studies and by a significant heterogeneity in terms of study design, study population, erectile and sexual function assessment modalities.

Graphical Analyses in the Regulatory Evaluation of Gene Therapy Applications.

The Center for Biologics Evaluation and Research (CBER) at the US Food and Drug Administration (FDA) regulates gene therapies, among other products. The approval of four gene therapy products since 2017 represents a significant milestone for a new class of treatments with the potential to treat or cure diseases, particularly rare diseases, that were previously considered incurable. Several factors have contributed to the recent rapid development of gene therapies including advances in genetics to facilitate target-detection, advances in vectors, and regulatory incentives such as breakthrough therapy designation, priority review and market exclusivity. The patient population affected by a rare disease is typically small, heterogeneous and geographically dispersed. As a result, clinical trials on a rare disease have unique features in terms of study design, subject enrollment, data analyses and interpretation of study results. Given that the patient population affected is small for rare diseases, providing substantial evidence of effectiveness and evidence of safety in trials for rare disease presents challenges. In this paper, we share our experiences in the statistical review of three gene therapy products that have been approved by FDA CBER. Our motivation in writing this paper is to encourage the use of appropriate analysis strategies for other similar small trials, with a focus on data visualization strategies.

The effects of shoe collar height on ankle sprain mechanics in athletes: A review of literature

Background: Our aim was to conduct a review to summarize the existing information regarding the effects of shoe collar height in altering ankle sprain mechanics in athletes. Methods: A systematic literature search of PubMed, Embase, MEDLINE, and SPORTDiscus was conducted in September 2019. Results: There were 10 studies published from 1993 to 2019 that were included. Most studies showed high-top shoes limited ankle sprain kinematics and increased resistance to inversion moment in static but not dynamic testing. High-top shoes were associated with delayed pre-landing ankle evertor muscle activation and smaller electromyography amplitudes. Conclusions: There is currently weak evidence to support that high-top shoes can limit ankle sprain kinematics in dynamic testing. Further studies with more consistent study interventions and outcome variables are needed to definitively establish the effects of shoe collar height on ankle sprain mechanics in athletes. The Translational Potential of this Article: Multiple studies on the effects of shoe collar height and ankle sprain mechanics have been performed but there is a lack of consistency in terms of study design, intervention, and outcome measures. A formal systematic review and meta-analysis were not applicable due to the heterogeneity of studies, and mixed results from these studies can be confusing to interpret, making further research on this topic difficult as a result of lack of future direction. We summarized the existing literature on this topic to provide a clearer picture and guide future research on this controversial matter.

The impact of health literacy environment on patient stress: a systematic review

BackgroundThere exists little literature on situational health literacy - that is, how an individual’s health literacy varies across different health literacy environments. However, one can consider the role of stress when examining the relationship between health situations and decision-making ability, and by proxy health literacy. The aim of this study was to assess the strength of the evidence on the relationship between health situations and patient stress, considered in the context of health professional perception, and determine what health situations act to influence patient stress.MethodsA systematic review of English articles using PubMed, PsycINFO, CINAHL and Embase databases was conducted. Search terms focused on ‘patient’, ‘stress’, and ‘health care situations’. Only peer-reviewed original research with data on patient stress in the context of a health facility environment was included. Studies were screened and critically appraised by both authors. Study elements for extraction were defined by RO and extracted by JY.ResultsTwenty-four studies were included for narrative synthesis. Patients in Intensive Care Units were more stressed about factors relating to their physical discomfort, with some agreement from health care professionals. Parents of children in Intensive Care Units were more concerned with stressors relating to their child’s appearance and behaviour, and alteration in their parental role. Few studies examined health settings other than Intensive Care Units, and those that did varied greatly in terms of study design and population characteristics, lacking generalisability.ConclusionsOverall, the findings of what patients find most stressful in Intensive Care Units can guide health care professionals practicing best practice care. However, the evidence on how patient stress is influenced by non-Intensive Care Unit health care settings is weak. Further research is needed to enhance current understanding of the interaction between patient stress and health care environments in both hospital and primary care settings.

Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma

Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5–7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.

Surgical treatments for women with stress urinary incontinence: a systematic review of economic evidence

BackgroundSurgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women.MethodsThe following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity.ResultsTwenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options.ConclusionsThe review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines.Systematic review registrationRegistered in PROSPERO in 2016, CRD42016049339

A scoping review of community paramedicine: evidence and implications for interprofessional practice

ABSTRACT Community paramedicine (CP) is an evolving method of providing community-based health care in which paramedics function outside of their traditional emergency response roles in order to improve access to primary and preventive health care and to basic social services. Early evidence indicates that CP programs have contributed to reducing health care utilization and improving patient outcomes leading some to call for a transformation of EMS into value-based mobile healthcare fully integrated within an interprofessional care team. The purpose of this scoping review was to understand the evidence base of CP in order to inform the further evolution of this model of care. Following the PRISMA extension for Scoping Reviews, 1,163 titles were screened by our research team. Eligibility criteria were publication in English after January 1, 2000; description of a CP program located in a Western nation; and inclusion of a discussion of outcomes. Twenty-nine publications met the criteria for inclusion. The literature was varied in terms of study design, program purpose, and target audience. The lack of rigorous, longitudinal studies with control groups makes rendering conclusions as to the value and effectiveness of CP programs difficult. Further, the extent to which community paramedics operate within interprofessional teams remains unclear. However, some programs demonstrated improvement in both health services and patient outcomes. As stakeholders continue to explore the potential of CP, results of this review highlight the importance of further investigation of outcomes, the professional identity of the community paramedic, and the role of the community paramedic on interprofessional teams.

The Prognostic Value of DNA Methylation Markers in Renal Cell Cancer: A Systematic Review

Introduction: DNA methylation is an epigenetic event that occurs in normal tissues but changes in both the early and late stages of multiple tumor entities, including renal cell cancer (RCC). Many studies have shown that DNA methylation markers are relevant to RCC prognosis, but none of these markers have entered into clinical routine. Furthermore, because of its potential reversibility, DNA methylation might provide a new target for RCC therapy strategies. Materials and methods: Following PRISMA guidelines, we performed a systematic literature search up to February 2019. After selection for eligibility, a total of 56 studies were identified for analysis. Each study was categorized and the level of evidence assessed. Only articles reporting on DNA methylation markers and their association with survival were included. Descriptive statistical analyses were conducted with R statistical software. Results: We identified promoter methylation of SFRP1, GATA5, NEFH, GREM1, and BCN1 as associated with survival in RCC. Moreover, we found evidence that methylation signatures, i.e., grouping of different potential gene markers, might be of better prognostic value than single gene marker investigations. Nevertheless, because of the heterogeneous features of the studies in terms of design, methodology, patient cohorts, and statistics, the true clinical impact of these methylation markers for prognosis in RCC patients remains uncertain. Conclusion: This systematic review elucidates the potential impact of DNA methylation on survival of patients with RCC. Several promising prognostic markers, especially methylation signatures, were identified, which is encouraging, but prospective validations are necessary to establish their true clinical value.

The impact of clinical heterogeneity on conducting network meta-analyses in transthyretin amyloidosis with polyneuropathy

Objective: The comparative safety and efficacy of tafamidis, patisiran and inotersen treatments for transthyretin amyloidosis with polyneuropathy (ATTR-PN) has not been evaluated in clinical trials. In the absence of head-to-head evidence, indirect treatment comparisons such as network meta-analyses (NMAs) can be performed to evaluate relative effects of treatments. This study aims to assess the feasibility of conducting an NMA of available therapies for ATTR-PN patients.Methods: Pivotal trials for three approved ATTR-PN treatments, tafamidis (Fx-005), patisiran (APOLLO) and inotersen (NEURO-TTR), were compared in terms of study design, baseline population characteristics, outcome definitions and baseline risk. These assessments of heterogeneity informed the decision to perform Bayesian NMAs.Results: Despite similar study designs, clear differences in eligibility criteria between trials were accompanied by imbalances in baseline population characteristics considered to be plausible effect modifiers, such as disease stage and previous treatment. Of the outcomes assessed, only quality of life and adverse events were similarly reported in all trials. Neuropathy outcomes were not evaluated consistently between trials.Conclusions: An NMA of ATTR-PN treatments was not feasible, given the observed cross-trial heterogeneity. This decision highlights the importance of careful consideration for clinical heterogeneity that may threaten the validity of indirect comparisons.

Quantitative bias analysis for study and grant planning

PurposeEpidemiologists often think about the balance between study error and cost-efficiency in terms of study design and strategies to reduce random error. We less often consider cost-efficiencies in terms of dealing with systematic errors that arise within a study, such as in deciding how to measure study variables and misclassification implications. MethodsGiven the information used to inform a study size calculation, the expected study data can be simulated during study planning, and the impact of anticipated biases can be estimated using quantitative bias analysis. This would allow investigators and stakeholders to identify areas where better data collection through more valid instruments is critical and where additional investment will not yield strong validity benefits. This could promote better use of study resources and help increase investigators’ chances of funding by demonstrating they have thought through biases and have a plan for mitigating the impact. ResultsWe demonstrate how this would work with a practical example using the relationship between smoking during pregnancy as measured on birth certificates and incident breast cancer. ConclusionsWe show that although exposure sensitivity would likely be poor, spending more money to get a better smoking measure is unlikely to yield more valid estimates.

Beyond Oncology: Question Prompt Lists in Healthcare-A Scoping Review Protocol.

Question prompt lists (QPL) are an instrument to promote patient participation in medical encounters by providing a set of questions patients can use during consultations. QPL have predominantly been examined in oncology. Less is known about their use in other contexts. Therefore, we plan to conduct a scoping review to provide an overview of the fields of healthcare in which QPL have been developed and evaluated. MEDLINE/PUBMED, PSYCINFO, PSYNDEX, WEB OF SCIENCE, and CINAHL will be systematically searched. Primary studies from different healthcare contexts that address the following participants/target groups will be included: persons with an acute, chronic, or recurring health condition other than cancer; healthy persons in non-oncological primary preventive measures. There will be no restrictions in terms of study design, sample size, or outcomes. However, only published studies will be included. Studies that were published in English and German between 1990 and 2019 will be examined. Two independent reviewers will apply defined inclusion/exclusion criteria and determine study eligibility in the review process guided by the PRISMA statement.