Causal inference in multi-cohort studies using the target trial framework to identify and minimize sources of bias.

Longitudinal cohort studies, which follow a group of individuals over time, provide the opportunity to examine causal effects of complex exposures on long-term health outcomes. Utilizing data from multiple cohorts has the potential to add further benefit by improving precision of estimates through data pooling and by allowing examination of effect heterogeneity through replication of analyses across cohorts. However, the interpretation of findings can be complicated by biases that may be compounded when pooling data, or, contribute to discrepant findings when analyses are replicated. The "target trial" is a powerful tool for guiding causal inference in single-cohort studies. Here we extend this conceptual framework to address the specific challenges that can arise in the multi-cohort setting. By representing a clear definition of the target estimand, the target trial provides a central point of reference against which biases arising in each cohort and from data pooling can be systematically assessed. Consequently, analyses can be designed to reduce these biases and the resulting findings appropriately interpreted in light of potential remaining biases. We use a case study to demonstrate the framework and its potential to strengthen causal inference in multi-cohort studies through improved analysis design and clarity in the interpretation of findings. Special Collection: N/A.

Cross-vendor multiparametric mapping of the human brain using 3D-QALAS: A multicenter and multivendor study.

PURPOSE: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping. METHODS: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions on each scanner (total scans = 100). To evaluate the feasibility of 3D-QALAS, nine patients with multiple sclerosis (nine women; mean age ± SD, 48.2 ± 11.5 y) underwent imaging examination on two 3T MRI systems from different manufacturers. RESULTS: Quantitative maps obtained with 3D-QALAS showed high linearity (R2 = 0.998 and 0.998 for T1 and T2, respectively) with respect to reference measurements. The mean intra-scanner coefficients of variation for each scanner and structure ranged from 0.4% to 2.6%. The mean structure-wise test-retest repeatabilities were 1.6%, 1.1%, and 0.7% for T1, T2, and PD, respectively. Overall, high inter-vendor reproducibility was observed for all parameter maps and all structure measurements, including white matter lesions in patients with multiple sclerosis. CONCLUSION: The vendor-agnostic multiparametric mapping technique 3D-QALAS provided reproducible measurements of T1, T2, and PD for human tissues within a typical physiological range using 3T scanners from four different MRI manufacturers.

Using natural language processing to facilitate the harmonisation of mental health questionnaires: a validation study using real-world data.

BACKGROUND: Pooling data from different sources will advance mental health research by providing larger sample sizes and allowing cross-study comparisons; however, the heterogeneity in how variables are measured across studies poses a challenge to this process. METHODS: This study explored the potential of using natural language processing (NLP) to harmonise different mental health questionnaires by matching individual questions based on their semantic content. Using the Sentence-BERT model, we calculated the semantic similarity (cosine index) between 741 pairs of questions from five questionnaires. Drawing on data from a representative UK sample of adults (N = 2,058), we calculated a Spearman rank correlation for each of the same pairs of items, and then estimated the correlation between the cosine values and Spearman coefficients. We also used network analysis to explore the model's ability to uncover structures within the data and metadata. RESULTS: We found a moderate overall correlation (r = .48, p < .001) between the two indices. In a holdout sample, the cosine scores predicted the real-world correlations with a small degree of error (MAE = 0.05, MedAE = 0.04, RMSE = 0.064) suggesting the utility of NLP in identifying similar items for cross-study data pooling. Our NLP model could detect more complex patterns in our data, however it required manual rules to decide which edges to include in the network. CONCLUSIONS: This research shows that it is possible to quantify the semantic similarity between pairs of questionnaire items from their meta-data, and these similarity indices correlate with how participants would answer the same two items. This highlights the potential of NLP to facilitate cross-study data pooling in mental health research. Nevertheless, researchers are cautioned to verify the psychometric equivalence of matched items.

A cross-validation based approach for estimating specific gravity in elementary-school aged children using a nonlinear model.

Environmental research often relies on urinary biomarkers which require dilution correction to accurately measure exposures. Specific gravity (SG) and creatinine (UCr) are commonly measured urinary dilution factors. Epidemiologic studies may assess only one of these measures, making it difficult to pool studies that may otherwise be able to be combined. Participants from the National Health and Nutrition Examination Survey 2007-2008 cycle were used to perform k-fold validation of a nonlinear model estimating SG from UCr. The final estimated model was applied to participants from the School Inner-City Asthma Intervention Study, who submitted urinary samples to the Children's Health Exposure Analysis Resource. Model performance was evaluated using calibration metrics to determine how closely the average estimated SG was to the measured SG. Additional models, with interaction terms for age, sex, body mass index, race/ethnicity, relative time of day when sample was collected, log transformed 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and asthma status were estimated and assessed for improvement. The association between monobenzyl phthalate (MBZP) and asthma symptom days, controlling for measured UCr, measured SG, and each estimated SG were compared to assess validity of the estimated SG. The model estimating SG from UCr alone, resulted in a beta estimate of 1.10 (95% CI: 1.01, 1.19), indicating agreement between model-predicted SG and measured SG. Inclusion of age and sex in the model improved estimation (ß = 1.06, 95% CI: 0.98, 1.15). The full model accounting for all interaction terms with UCr resulted in the best agreement (ß = 1.01, 95% CI: 0.93,1.09). Associations between MBZP and asthma symptoms days, controlling for each estimated SG, were within the range of effect estimates when controlling for measured SG and measured UCr (Rate ratios = 1.28-1.34). Our nonlinear modeling provides opportunities to estimate SG in studies that measure UCr or vice versa, enabling data pooling despite differences in urine dilution factors.

Invited Commentary: Standards, Inputs, and Outputs-Strategies for Improving Data-Sharing and Consortia-Based Epidemiologic Research.

Data-sharing improves epidemiologic research, but the sharing of data frustrates epidemiologic researchers. The inefficiencies of current methods and options for data-sharing are increasingly documented and easily understood by any study group that has shared its data and any researcher who has received shared data. In this issue of the Journal, Temprosa et al. (Am J Epidemiol. 2021;191(1):147-158) describe how the Consortium of Metabolomics Studies (COMETS) developed and deployed a flexible analytical platform to eliminate key pain points in large-scale metabolomics research. COMETS Analytics includes an online tool, but its cloud computing and technology are the supporting rather than the leading actors in this script. The COMETS team identified the need to standardize diverse and inconsistent metabolomics and covariate data and models across its many participating cohort studies, and then developed a flexible tool that gave its member studies choices about how they wanted to meet the consortium's analytical requirements. Different specialties will have different specific research needs and will probably continue to use and develop an array of diverse analytical and technical solutions for their projects. COMETS Analytics shows how important-and enabling-the upstream attention to data standards and data consistency is to producing high-quality metabolomics, consortia-based, and large-scale epidemiology research.

Preserving data privacy when using multi-site data to estimate individualized treatment rules.

Precision medicine is a rapidly expanding area of health research wherein patient level information is used to inform treatment decisions. A statistical framework helps to formalize the individualization of treatment decisions that characterize personalized management plans. Numerous methods have been proposed to estimate individualized treatment rules that optimize expected patient outcomes, many of which have desirable properties such as robustness to model misspecification. However, while individual data are essential in this context, there may be concerns about data confidentiality, particularly in multi-center studies where data are shared externally. To address this issue, we compared two approaches to privacy preservation: (i) data pooling, which is a covariate microaggregation technique and (ii) distributed regression. These approaches were combined with the doubly robust yet user-friendly method of dynamic weighted ordinary least squares to estimate individualized treatment rules. In simulations, we extensively evaluated the performance of the methods in estimating the parameters of the decision rule under different assumptions. The results demonstrate that double robustness is not maintained in data pooling setting and that this can result in bias, whereas the distributed regression provides good performance. We illustrate the methods via an analysis of optimal Warfarin dosing using data from the International Warfarin Consortium.

Experiences from the harmonization of Finnish national population-based health survey data.

Aims: There are several advantages to pooling survey data from individual studies over time or across different countries. Our aim is to share our experiences on harmonizing data from 13 Finnish health examination surveys covering the years 1972-2017 and to describe the challenges related to harmonizing different variable types using two questionnaire variables - blood pressure measurement and total cholesterol assessment - as examples. Methods: Data from Finnish national population-based health surveys were harmonized as part of the research project 'Projections of the Burden of Disease and Disability in Finland - Health Policy Prospects', including variables from questionnaires, objective health measurements and results from the laboratory analysis of biological samples. The process presented in the Maelstrom Research guidelines for data harmonization was followed with minor adjustments. Results: The harmonization of data from objective measurements and biomarkers was reasonably straightforward, but questionnaire items proved more challenging. Some questions and response options had changed during the covered time period. This concerned, for example, questionnaire items on the availability and use of medication and diet. Conclusions: The long time period - 45 years - made harmonization more complicated. The survey questions or response options had changed for some topics due to changes in society. However, common core variables for topics that were especially relevant for the project, such as lifestyle factors and certain diseases or conditions, could be harmonized with sufficient comparability. For future surveys, the use of standardized survey methods and the proper documentation of data collection are recommended to facilitate harmonization.

How to translate and locally adapt a PROM. Assessment of cross-cultural differential item functioning.

Translating patient-reported outcome measures (PROMs) can alter the meaning of items and undermine the PROM's psychometric properties (quantified as cross-cultural differential item functioning [DIF]). The aim of this paper was to present the theoretical background for PROM translation, adaptation, and cross-cultural validation, and assess how PROMs used in sports medicine research have been translated and adapted. We also assessed DIF for the Knee Injury and Osteoarthritis Outcome Score (KOOS) across Danish, Norwegian, and Swedish versions. We conducted a search in PubMed and Scopus to identify the method of translation, adaptation, and validation of PROMs relevant to musculoskeletal research. Additionally, 150 preoperative KOOS questionnaires were obtained from the Scandinavian knee ligament reconstruction registries, and cross-cultural DIF was evaluated using confirmatory factor analysis and Rasch analysis. There were 392 studies identified, describing the translation of 61 PROMs. Ninety-four percent were performed with forward-backward technique. Forty-nine percent used cognitive interviews to ensure appropriate wording, understandability, and adaptation to the target culture. Only two percent were validated according to modern test theory. No study assessed cross-cultural DIF. One KOOS subscale showed no cross-cultural DIF, two had DIF with respect to some (but not all) items, and thus conversion tables could be constructed, and two KOOS subscales could not be pooled. Most PROM translations are of undocumented quality, despite the common conclusion that they are valid and reliable. Scores from three of five KOOS subscales can be pooled across the Danish, Norwegian, and Swedish versions, but two of these must be adjusted for DIF.

Harmonizing altered measures in integrative data analysis: A methods analogue study.

In the current study, we used an analogue integrative data analysis (IDA) design to test optimal scoring strategies for harmonizing alcohol- and drug-use consequence measures with varying degrees of alteration across four study conditions. We evaluated performance of mean, confirmatory factor analysis (CFA), and moderated nonlinear factor analysis (MNLFA) scores based on traditional indices of reliability (test-retest, internal, and score recovery or parallel forms) and validity. Participants in the analogue study included 854 college students (46% male; 21% African American, 5% Hispanic/Latino, 56% European American) who completed two versions of the altered measures at two sessions, separated by 2 weeks. As expected, mean, CFA, and MNLFA scores all resulted in scales with lower reliability given increasing scale alteration (with less fidelity to formerly developed scales) and shorter scale length. MNLFA and CFA scores, however, showed greater validity than mean scores, demonstrating stronger relationships with external correlates. Implications for measurement harmonization in the context of IDA are discussed.

Postoperative Delirium in Older Patients: A Systematic Review of Assessment and Incidence of Postoperative Delirium.

BACKGROUND: Postoperative delirium is the most common complication of surgery particularly in older patients. AIMS: The current study aimed to summarize the commonly used delirium assessment tools in assessing postoperative delirium (POD) and to estimate the incidence rates of POD. METHODS: A systematic review that included empirical cohort studies reporting the use of delirium assessment tools in assessing POD between 2000 and 2019. Five core databases were searched for eligible studies. The methodological quality assessment of the included studies was undertaken using the Joanna Briggs Institute (JBI) critical appraisal checklist to examine the risk of bias. Pooled incidence estimates were calculated using a random effects model. RESULTS: Nineteen studies with a total of 3,533 postsurgery older patients were included in this review. The confusion assessment method (CAM) and CAM-ICU were the most commonly used tools to assess POD among older postoperative patients. The pooled incidence rate of POD was 24% (95% CI [0.20, 0.29]). The pooled incidence estimates for mixed (noncardiac) surgery, orthopedic surgery, and tumor surgery were 23% (95% CI [0.15, 0.31]), 27% (95% CI [0.20, 0.33]), and 19% (95% CI [0.15, 0.22]), respectively. More than 50% of included studies used CAM to assess POD in different types of postoperative patients. Using CAM to assess delirium is less time-consuming and it was suggested as the most efficient tool for POD detection. LINKING EVIDENCE TO ACTION: We identified that CAM could be implemented in different settings for assessing POD. The incidence and risk factors for POD introduced can be used for future research to target these potential indicators. The incidence rate, risk factors, and predictors of POD explored can provide robust evidence for clinical practitioners in their daily practice.

Twelve weeks of ledipasvir/sofosbuvir all-oral regimen for patients with chronic hepatitis C genotype 2 infection: Integrated analysis of three clinical trials.

AIM: The combination of ledipasvir and sofosbuvir (LDV/SOF) has been approved for the treatment of various hepatitis C virus (HCV) genotypes across many countries. This article presents an integrated analysis of three prospective phase II/III trials in the Asia-Pacific region to evaluate the efficacy and safety of 12 weeks of LDV/SOF in HCV genotype 2 patients without cirrhosis or with compensated cirrhosis. METHODS: A total of 200 patients were included in the integrated analysis. The primary end-point was the rate of sustained virologic response for 12 weeks after the end of therapy (SVR12), analyzed by fibrosis stage, treatment history, HCV genotype subtype, and presence of baseline resistance-associated substitutions (RAS). Safety was evaluated by adverse events and laboratory abnormalities. RESULTS: Twelve weeks of treatment with LDV/SOF was associated with high SVR12 rates (overall 98%) in patients with genotype 2 HCV, irrespective of fibrosis stage, treatment history, genotype 2 subtype, and presence of baseline non-structural protein 5A resistance-associated substitution (NS5A RAS), and LDV/SOF was well tolerated. CONCLUSIONS: Twelve weeks of treatment with LDV/SOF provides a highly effective and safe treatment for patients with genotype 2 HCV, including those with advanced fibrosis. As a ribavirin-free and protease inhibitor-free regimen with minimal on-treatment monitoring requirements, LDV/SOF can potentially play a crucial role in achieving the WHO's goal of HCV elimination.

Quality Assessment of Systematic Reviews on Platform-Switching vs Platform-Matched Implants: An Overview.

The objective of this study was to perform a quality analysis of systematic reviews with meta-analyses that focused on the comparison of platform-switching (implant-abutment mismatching) and platform-matched (PM) implants. The assessment of multiple systematic reviews (AMSTAR) and Glenny (Checklist) Scales were used to qualify the studies. PubMed, Scientific Electronic Library Online (SciELO), Web of Science (formerly ISI Web of Knowledge), and Cochrane databases were searched, by topic, for systematic reviews on dental implants with switching platforms. A total of 8 systematic reviews, including 7 studies with meta-analyses, were selected. The AMSTAR scale indicated a high (n = 6) to moderate (n = 2) score for the included studies. The quantitative analysis indicated that platform-switching implants preserved more bone tissue when compared with platform-matched implants (6 meta-analyses; P < .001, smaller mean difference: -0.29 mm, 95% CI: -0.38, -0.19 and greater mean difference: -0.49 mm, 95% CI: -0.73, -0.26). Quantitative analysis based on 7 systematic reviews with meta-analysis indicated positive peri-implant bone preservation for implants restored with an implant-abutment mismatching (PSW). Further, there is evidence to improve the design of current systematic reviews. Future systematic reviews in this thematic area should consider searches in gray literature and different databases and include only randomized controlled clinical studies.

Diagnostic Performance of Delirium Assessment Tools in Critically Ill Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Critical care nurses are in the best position to detect and monitor delirium in critically ill patients. Therefore, an optimum delirium assessment tool with strong evidence should be identified with critical care nurses to perform in the daily assessment. AIM: To evaluate and compare the diagnostic performance of delirium assessment tools in diagnosing delirium in critically ill patients. METHODS: We searched five electronic databases including the Cochrane Library, PubMed, Embase, CINAHL, and a Chinese database for eligible diagnostic studies published in English or Mandarin up to December 2018. This diagnostic test accuracy meta-analysis was limited to studies in intensive care unit (ICU) settings, using the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a standard reference to test the accuracy of delirium assessment tools. Eligible studies were critically appraised by two investigators independently. The summary of evidence was conducted for pooling and comparing diagnostic accuracy by a bivariate random effects meta-analysis model. The pooled sensitivities and specificities, summary receiver operating characteristic curve (sROC), the area under the curve (AUC), and diagnostic odds ratio (DOR) were calculated and plotted. The possibility of publication bias was assessed by Deeks' funnel plot. DATA SYNTHESIS: We identified and evaluated 23 and 8 articles focused on CAM-ICU and ICDSC, respectively. The summary sensitivities of 0.85 and 0.87, and summary specificities of 0.95 and 0.91 were found for CAM-ICU and ICDSC, respectively. The AUC of the CAM-ICU was 0.96 (95% CI, 0.94-0.98), with DOR at 99 (95% CI, 55-177). The AUC of the ICDSC was 0.95 (95% CI, 0.92-0.96), and the DOR was 65 (95% CI, 27-153). LINKING EVIDENCE TO ACTION: CAM-ICU demonstrated higher diagnostic test accuracy and is recommended as the optimal delirium assessment tool. However, the results should be interpreted with caution due to the between-study heterogeneity of this diagnostic test accuracy meta-analysis.

Comparison of physical behavior estimates from three different thigh-worn accelerometers brands: a proof-of-concept for the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS).

BACKGROUND: Pooling data from thigh-worn accelerometers across multiple studies has great potential to advance evidence on the health benefits of physical activity. This requires harmonization of information on body postures, physical activity types, volumes and time patterns across different brands of devices. The aim of this study is to compare the physical behavior estimates provided by three different brands of thigh-worn accelerometers. METHODS: Twenty participants volunteered for a 7-day free-living measurement. Three accelerometers - ActiGraph GT3X+, Axivity AX3 and ActivPAL Micro4 - were randomly placed in a vertical line on the midsection of the right thigh. Raw data from each accelerometer was processed and classified into 8 physical activities and postures using the Acti4 software. Absolute differences between estimates and the respective coefficient of variation (CV) were calculated. RESULTS: We observed very minor differences between physical behavior estimates from three different accelerometer brands. When averaged over 24 h (1,440 min), the absolute difference (CV) between accelerometers were: 1.2 mins (0.001) for lying/sitting, 3.4 mins (0.02) for standing, 3.5 mins (0.06) for moving, 1.9 mins (0.03) for walking, 0.1 mins (0.19) for running, 1.2 mins (0.19) for stair climbing, 1.9 mins (0.07) for cycling. Moreover, there was an average absolute difference of 282 steps (0.03) per 24 h. CONCLUSIONS: Physical behaviors were classified with negligible difference between the accelerometer brands. These results support harmonization of data from different thigh-worn accelerometers across multiple cohorts when analyzed in an identical manner.

Harmonising data on the correlates of physical activity and sedentary behaviour in young people: Methods and lessons learnt from the international Children's Accelerometry database (ICAD).

BACKGROUND: Large, heterogeneous datasets are required to enhance understanding of the multi-level influences on children's physical activity and sedentary behaviour. One route to achieving this is through the pooling and co-analysis of data from multiple studies. Where this approach is used, transparency of the methodology for data collation and harmonisation is essential to enable appropriate analysis and interpretation of the derived data. In this paper, we describe the acquisition, management and harmonisation of non-accelerometer data in a project to expand the International Children's Accelerometry Database (ICAD). METHOD: Following a consultation process, ICAD partners were requested to share accelerometer data and information on selected behavioural, social, environmental and health-related constructs. All data were collated into a single repository for cataloguing and harmonisation. Harmonised variables were derived iteratively, with input from the ICAD investigators and a panel of invited experts. Extensive documentation, describing the source data and harmonisation procedure, was prepared and made available through the ICAD website. RESULTS: Work to expand ICAD has increased the number of studies with longitudinal accelerometer data, and expanded the breadth of behavioural, social and environmental characteristics that can be used as exposure variables. A set of core harmonised variables, including parent education, ethnicity, school travel mode/duration and car ownership, were derived for use by the research community. Guidance documents and facilities to enable the creation of new harmonised variables were also devised and made available to ICAD users. An expanded ICAD database was made available in May 2017. CONCLUSION: The project to expand ICAD further demonstrates the feasibility of pooling data on physical activity, sedentary behaviour and potential determinants from multiple studies. Key to this process is the rigorous conduct and reporting of retrospective data harmonisation, which is essential to the appropriate analysis and interpretation of derived data. These documents, made available through the ICAD website, may also serve as a guide to others undertaking similar projects.

Feasibility of Combining Common Data Elements Across Studies to Test a Hypothesis.

PURPOSE: The purpose of this article is to describe the outcomes of a collaborative initiative to share data across five schools of nursing in order to evaluate the feasibility of collecting common data elements (CDEs) and developing a common data repository to test hypotheses of interest to nursing scientists. This initiative extended work already completed by the National Institute of Nursing Research CDE Working Group that successfully identified CDEs related to symptoms and self-management, with the goal of supporting more complex, reproducible, and patient-focused research. DESIGN: Two exemplars describing the group's efforts are presented. The first highlights a pilot study wherein data sets from various studies by the represented schools were collected retrospectively, and merging of the CDEs was attempted. The second exemplar describes the methods and results of an initiative at one school that utilized a prospective design for the collection and merging of CDEs. METHODS: Methods for identifying a common symptom to be studied across schools and for collecting the data dictionaries for the related data elements are presented for the first exemplar. The processes for defining and comparing the concepts and acceptable values, and for evaluating the potential to combine and compare the data elements are also described. Presented next are the steps undertaken in the second exemplar to prospectively identify CDEs and establish the data dictionaries. Methods for common measurement and analysis strategies are included. FINDINGS: Findings from the first exemplar indicated that without plans in place a priori to ensure the ability to combine and compare data from disparate sources, doing so retrospectively may not be possible, and as a result hypothesis testing across studies may be prohibited. Findings from the second exemplar, however, indicated that a plan developed prospectively to combine and compare data sets is feasible and conducive to merged hypothesis testing. CONCLUSIONS: Although challenges exist in combining CDEs across studies into a common data repository, a prospective, well-designed protocol for identifying, coding, and comparing CDEs is feasible and supports the development of a common data repository and the testing of important hypotheses to advance nursing science. CLINICAL RELEVANCE: Incorporating CDEs across studies will increase sample size and improve data validity, reliability, transparency, and reproducibility, all of which will increase the scientific rigor of the study and the likelihood of impacting clinical practice and patient care.

Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

INTRODUCTION: Various factors play a role in the development of erectile dysfunction (ED). AIM: To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. METHODS: In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. MAIN OUTCOME MEASURES: The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. RESULTS: Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. CONCLUSION: Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other.

Effectiveness of Pressure Ulcer Prevention Strategies for Adult Patients in Intensive Care Units: A Systematic Review.

BACKGROUND: Pressure ulcers are associated with substantial health burden, but could be preventable. Hospital-acquired pressure ulcers (HAPUs) prevention has become a priority for all healthcare settings, as it is considered a sign of quality of care providing. Intensive care unit (ICU) patients are at higher risk for HAPUs development. Despite the availability of published prevention strategies, there is a little evidence about which strategies can be safely integrated into routine standard care and have an impact on HAPUs prevention. AIMS: The aim was to synthesize the best available evidence regarding the effectiveness of single strategies designed to reduce the incidence and prevalence of HAPUs development in ICUs. METHODS: The search strategy was designed to retrieve studies published in English across CINAHL, Medline, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Mednar between 2000 and 2015. All adult ICU participants were aged 18 years or over. This review included randomized controlled trials, quasi-experimental and comparative studies. The studies that were selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical-appraisal instruments. RESULTS: The review included 25 studies, and the meta-analysis revealed a statistically significant effect of a silicon foam dressing strategy in reducing HAPUs incidence (effect size = 4.62; 95% CI: 0.05-0.29; p < .00001, effect size = 4.50; 95% CI: 0.05-0.31; p = .00001, respectively) in critically ill patients. Evidence of the effectiveness of nutrition, skin-care regimen, positioning and repositioning schedule, support surfaces, and the role of education in prevention of HAPUs development in the ICU was limited, which precludes strong conclusions. LINKING EVIDENCE TO ACTION: The review provides an evidence-based guide to future priorities for clinical practice. In particular, a silicone foam dressing has positive impact in reducing sacrum and heel HAPUs incidence in the ICU.

An Evidence-Based Approach to Scoping Reviews.

OBJECTIVE: Scoping reviews are used to assess the extent of a body of literature on a particular topic, and often to ensure that further research in that area is a beneficial addition to world knowledge. The aim of this paper reports upon the development of a methodology for scoping reviews based upon the Arksey and O'Malley framework, the Levac, Colquhoun, and O'Brien, and the Joanna Briggs Institute methods of evidence synthesis. METHODS: A working group consisting of members of the Joanna Briggs collaborating organizations met to discuss the proposed framework for the methodology and develop a draft for the scoping review methodology based on the Arksey and O'Malley framework and the work of Levac et al. This was followed by a workshop attended by other members of the organizations consisting of 30 international researchers to discuss the proposed methodology. Further refinement of the methodology was undertaken as a result of the feedback received from the workshop. RESULTS: The development of the methodology focused on five stages of the protocol and review development. These were identifying the research question by clarifying and linking the purpose and research question, identifying the relevant studies using a three-step literature search in order to balance feasibility with breadth and comprehensiveness, careful selection of the studies to using a team approach, charting the data and collating the results to identify the implications of the study findings for policy, practice, or research. LINKING EVIDENCE TO ACTION: The current methodology recommends including both quantitative and qualitative research, as well as evidence from economic and expert opinion sources to answer questions of effectiveness, appropriateness, meaningfulness and feasibility of health practices and delivery methods. The proposed framework has the potential to provide options when faced with complex concepts or broad research questions.