Search

Purpose: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used.Methods: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men ≥ 65 years at each of two clinical sites. In another study, IVR versions of the SF-36 Vitality Scale (SF-36), Positive and Negative Affect Scale, and Patient Health Questionnaire were evaluated in comparison with previously validated paper versions in 25 men at two clinical sites. Both paper and IVR versions of each instrument were administered in counterbalanced order, and test-retest reliability was evaluated by repeated administration of the test. Bland-Altman plots were used to assess the degree of agreement. Test-retest correlations for each measure were also determined.Results: Satisfactory agreement was observed between IVR and paper versions of each study measure. Specifically, linear and highly positive associations were observed consistently across the study for IVR and paper versions of all study measures. These ranged from r = 0.91-0.99. Test-retest reliability for all measures was acceptable or better (r = 0.70-0.90).Conclusions: The IVR versions of TTrials endpoints in these two studies performed consistently well in comparison with paper versions. [ABSTRACT FROM AUTHOR]

Exploitation of the ever-increasing volume of observational data has become a major challenge for real-world evidence (RWE). Causal inference can be viewed as emulations of clinical trials (ECTs) from real-world data (RWD). This requires in-depth knowledge of data management and modern statistical models, which evolve considerably. We have developed Plug-Stat® to facilitate these analyses. Plug-Stat® is a user-friendly graphical interface of R software implemented with JavaScript and VB.net. The implementation of Plug-Stat® for a specific database consists of two main tasks. The first concerns the automatic importation of data to link the software with the data and to avoid the repetition of data management activities for each study. The second is to define the outcomes and the associated possible confounders. To perform an ECT, we proposed the use of inverse probability weighting, flexible parametric estimation of the propensity score model with B-splines, and robust estimation of the variance. The statistical modeling steps are automatized to direct the user toward the correct methodology without data management. We illustrated the usefulness of Plug-Stat® with several recently published ECTs. In this paper, we presented the outcome comparison of preemptive deceased-donor kidney transplantations versus transplantations after dialysis. The interactive interfaces assist the user in conducting causal research based on ECT, and tutorials are available, offering self-training opportunities. Plug-Stat® reduces the time and, consequently, the cost necessary for different studies from the same cohort. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients. [ABSTRACT FROM AUTHOR]

We introduce this supplemental issue of Prevention Science, which brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect heterogeneity. These studies follow two general paradigms: three papers report findings from single randomized preventive intervention trials, while the remaining papers develop and apply new methods for combining data from multiple studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and SAMHSA also provide commentaries on these studies. They conclude that synthesis of findings from multiple trials holds great promise for advancing the field, and progress will be accelerated if collaborative data sharing becomes the norm rather than the exception. [ABSTRACT FROM AUTHOR]

In the context of the VASelfCare project, we developed an application prototype of an intelligent anthropomorphic virtual assistant. Designed as a relational agent, the virtual assistant has the role of supporting older people with Type 2 Diabetes Mellitus (T2D) in medication adherence and lifestyle changes. Our paper has two goals: describing the essentials of this prototype, and reporting on usability evaluation. We describe the general architecture of the prototype, including the graphical component, and focus on its main feature: the incorporation, in the way the dialogue flows, of Behavior Change Techniques, identified through a theoretical framework, the Behaviour Change Wheel. Usability was experimentally evaluated in field tests in a purposive sample of 20 participants (11 older adults with T2D and 9 experts). The Portuguese version of the System Usability Scale was employed, supplemented with qualitative data from open questions, diaries, digital notes and telephone follow-ups. The aggregated mean SUS score was 73,75 (SD 13,31), which corresponds to a borderline rating of excellent. Textual data were content analyzed and will be prioritized to further improve usability. [ABSTRACT FROM AUTHOR]

Background: Value of information (VOI) analysis often requires modeling to characterize and propagate uncertainty. In collaboration with a cancer clinical trial group, we integrated a VOI approach to assessing trial proposals.Objective: This paper aims to explore the impact of modeling choices on VOI results and to share lessons learned from the experience.Methods: After selecting two proposals (A: phase III, breast cancer; B: phase II, pancreatic cancer) for in-depth evaluations, we categorized key modeling choices relevant to trial decision makers (characterizing uncertainty of efficacy, evidence thresholds to change clinical practice, and sample size) and modelers (cycle length, survival distribution, simulation runs, and other choices). Using a $150,000 per quality-adjusted life-year (QALY) threshold, we calculated the patient-level expected value of sample information (EVSI) for each proposal and examined whether each modeling choice led to relative change of more than 10% from the averaged base-case estimate. We separately analyzed the impact of the effective time horizon.Results: The base-case EVSI was $118,300 for Proposal A and $22,200 for Proposal B per patient. Characterizing uncertainty of efficacy was the most important choice in both proposals (e.g. Proposal A: $118,300 using historical data vs. $348,300 using expert survey), followed by the sample size and the choice of survival distribution. The assumed effective time horizon also had a substantial impact on the population-level EVSI.Conclusions: Modeling choices can have a substantial impact on VOI. Therefore, it is important for groups working to incorporate VOI into research prioritization to adhere to best practices, be clear in their reporting and justification for modeling choices, and to work closely with the relevant decision makers, with particular attention to modeling choices. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited Teva, the company manufacturing arsenic trioxide (ATO; tradename Trisenox®), to submit evidence for the clinical and cost effectiveness of ATO for untreated and relapsed or refractory acute promyelocytic leukaemia (APL). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG's critical review of the clinical and cost effectiveness evidence in the CS, key methodological considerations and the development of the NICE guidance by the Appraisal Committee (AC). The CS presented three randomized controlled trials (RCTs). Two of these were trials in newly diagnosed APL (APL0406 and AML17) and the third trial was in patients with relapsed APL. Results from APL0406 showed that more people having AATO [ATO plus all-trans retinoic acid (ATRA)] were alive at 50 months compared with people having AIDA (ATRA in combination with idarubicin) (99% vs. 93%; p = 0.007). There was also a statistically significant lower cumulative incidence of relapse with AATO compared with AIDA at 50 months (2% vs. 14%; p = 0.001). At 4 years, results from AML17 showed a significant difference in event-free survival (91% vs. 70%; p = 0.002) favouring AATO but not in overall survival (93% vs. 89%; p = 0.250). The only trial presented for relapsed/refractory patients compared AATO with ATO, which was not a relevant comparison according to the NICE scope. The AC concluded that AATO was effective for untreated APL while for relapsed or refractory APL the effectiveness of ATO was considered uncertain and the long-term safety remains unexplored. In the CS base-case, AATO was less expensive (£31,088 saved) and more effective (2.546 quality-adjusted life-years (QALYs) gained) than AIDA and thus the dominating strategy for newly diagnosed low- to intermediate-risk APL. However, the ERG's critical assessment highlighted a number of concerns, including deviations from the NICE reference case and a lack of detailed description and justification of parameters and assumptions related to (the extrapolation of) treatment effectiveness. However, it was reassuring that AATO for untreated APL remained dominant in the ERG base-case, and that the worst-case scenario produced by the ERG resulted in an incremental cost-effectiveness ratio (ICER) of £21,622. The AC concluded that although there was uncertainty in the model, it could recommend ATO for both untreated and relapsed or refractory APL. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most diagnosable forms of cancer worldwide. The early diagnoses of pulmonary nodules in computed tomography (CT) chest scans are crucial for potential patients. Recent researches have showed that the methods based on deep learning have made a significant progress for the medical diagnoses. However, the achievements on identification of pulmonary nodules are not yet satisfactory enough to be adopted in clinical practice. It is largely caused by either the existence of many false positives or the heavy time of processing. With the development of fully convolutional networks (FCNs), in this study, we proposed a new method of identifying the pulmonary nodules. The method segments the suspected nodules from their environments and then removes the false positives. Especially, it optimizes the network architecture for the identification of nodules rapidly and accurately. In order to remove the false positives, the suspected nodules are reduced using the 2D models. Furthermore, according to the significant differences between nodules and non-nodules in 3D shapes, the false positives are eliminated by integrating into the 3D models and classified via 3D CNNs. The experiments on 1000 patients indicate that our proposed method achieved 97.78% sensitivity rate for segmentation and 90.1% accuracy rate for detection. The maximum response time was less than 30 s and the average time was about 15 s. Graphical Abstract This paper has proposed a new method of identifying the pulmonary nodules. The method segments the suspected nodules from CT images and removes the false positives. As shown in the above, the proposed approach consists of three stages. In stage I, raw data are filtered and normalized. The clean normalized data are then segmented in stage II to extract the suspected nodular lesions through 2D FCNs. Stage III is to remove some false positives generated at stage II via 3D CNNs and outputs the final results. The experiments on 1000 patients indicate that our proposed method has achieved 97.78% sensitivity rate for segmentation and 90.1% accuracy rate for detection. The maximum response time was less than 30 s and the average time was about 15 s. [ABSTRACT FROM AUTHOR]

Purpose: Within psycho-oncology clinical trials, usual care (UC) represents a common and important control condition. Yet recent shifts in oncology, coupled with insufficient description of such conditions, threaten to render UC increasingly difficult to define and interpret. This paper offers evidence of these shifts and recommendations for addressing them.Methods: The broader literature on usual care as a control condition in psychosocial/behavioral intervention trials was assessed, and usual care-controlled trials in psycho-oncology were selectively reviewed, toward to goal of conceptual synthesis.Results: We offer evidence that (1) UC control conditions are often insufficiently defined and assessed; and (2) the context of supportive care in oncology has shifted in a manner that contributes to this problem, with implications for interpreting and comparing findings across clinical trials. Three converging findings support these conclusions. First, the scientific literature increasingly documents the diversity in how "usual care" conditions are defined across psychosocial and behavioral trials, with important considerations for trial interpretation. Second, evidence suggests that the availability of psychosocial oncology care has increased over the past few decades. The increasing availability and variety of psychosocial care introduces potential confounds for UC conditions. Third, mental health care trends in the general population affect the supportive interventions available to oncology patients in UC conditions today versus in the past.Conclusions: Shifts in psychosocial oncology and broader mental health care underscore the importance of carefully defining and assessing UC in psycho-oncology trials. Recommendations are offered for improving the design, evaluation, and interpretation of UC conditions, toward the ultimate goal of improving the quality of the evidence in psycho-oncology. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the manufacturer of pomalidomide (POM; Imnovid®, Celgene) to submit evidence regarding the clinical and cost effectiveness of the drug in combination with dexamethasone (POM + LoDEX) for the treatment of relapsed and refractory multiple myeloma (RRMM) after at least two regimens including lenalidomide (LEN) and bortezomib (BOR). Kleijnen Systematic Reviews Ltd (KSR) and Erasmus University Rotterdam were commissioned as the Evidence Review Group (ERG) for this submission. The ERG reviewed the evidence submitted by the manufacturer, validated the manufacturer's decision analytic model, and conducted exploratory analyses in order to assess the robustness and validity of the presented clinical and cost-effectiveness results. This paper describes the company submission, the ERG assessment, and NICE's subsequent decisions. The company conducted a systematic review to identify studies comparing POM with comparators outlined in the NICE scope: panobinostat with bortezomib and dexamethasone (PANO + BOR + DEX), bendamustine with thalidomide and dexamethasone (BTD) and conventional chemotherapy (CC). The main clinical effectiveness evidence was obtained from MM-003, a randomized controlled trial (RCT) comparing POM + LoDEX with high-dose dexamethasone (HiDEX; used as a proxy for CC). Additional data from other studies were also used as nonrandomized observational data sources for the indirect treatment comparison of POM + LoDEX with BTD and PANO + BOR + DEX. Covariate or treatment switching adjustment methods were used for each comparison. The model developed in Microsoft® Excel 2010 using a semi-Markov partitioned survival structure, submitted in the original submission to NICE for TA338, was adapted for the present assessment of the cost effectiveness of POM + LoDEX. Updated evidence from the clinical-effectiveness part was used for the survival modelling of progression-free survival and overall survival. For POM + LoDEX, the patient access scheme (PAS) discount was applied to the POM price. Three separate comparisons were conducted for each comparator, each comparison using a different dataset and adjustment methods. The ERG identified and corrected some errors, and the corrected incremental cost-effectiveness ratios (ICERs) for POM + LoDEX versus each comparator were presented: approximately £45,000 per quality-adjusted life-year (QALY) gained versus BTD, savings of approximately £143,000 per QALY lost versus PANO + BOR + DEX, and approximately £49,000 per QALY gained versus CC. The ERG also conducted full incremental analyses, which revealed that CC, POM + LoDEX and PANO + BOR + DEX were on the cost-effectiveness frontier. The committee's decision on the technology under analysis deemed that POM + LoDEX should be recommended as an option for treating multiple myeloma in adults at third or subsequent relapse of treatments including both LEN and BOR, contingent on the company providing POM with the discount agreed in the PAS. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes the international, cross-cultural development of four disease-specific EORTC QoL questionnaires, to supplement the EORTC QLQ-C30, for patients with Hodgkin lymphoma (HL), high- or low-grade non-Hodgkin lymphoma (HG/LG-NHL), and CLL.Methods: Questionnaire development was conducted according to guidelines from the EORTC Quality of Life Group. Phase I comprised generation of QoL issues relevant to patients. Phase II included operationalization and assessment of item relevance. In phase III, items were pretested in a cross-cultural sample.Results: In Phase I, 75 issues were identified through focus groups and systematic literature searches. Interviews with 80 health-care professionals and 245 patients resulted in a provisional module of 38 items (phase II) representing items relevant for all or at least one of the four malignancies. In Phase III, this was tested in 337 patients from five European countries and resulted in a questionnaire with 27 items for HL (EORTC QLQ-HL27), 29 items for HG-NHL (EORTC QLQ-NHL-HG29), 20 items for LG-NHL (EORTC QLQ-NHL-LG20) and 17 items for CLL (EORTC QLQ-CLL17).Conclusions: This study provides four new EORTC modules for use in clinical research and routine practice in conjunction with the EORTC QLQ-C30 for assessing QoL in patients with lymphoma and CLL. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcome measures (PROMs), which are generic or condition-specific, are used for a number of reasons, including clinical care, clinical trials, and in national-level efforts to monitor the quality of health care delivery. Creating PROMs that meet different purposes without overburdening patients, healthcare systems, providers, and data systems is paramount. The objective of this study was to test a generalizable method to incorporate condition-specific issues into generic PROM measures as a first step to producing PROMs that efficiently provide a standardized score. This paper outlines the method and preliminary findings focused on a PROM for osteoarthritis of the knee (OA-K).Methods: We used a mixed-methods approach and PROMIS® measures to test development of a combined generic and OA-K-specific PROM. Qualitative methods included patient focus groups and provider interviews to identify impacts of OA-K important to patients. We then conducted a thematic analysis and an item gap analysis: identified areas covered by existing generic PROMIS measures, identified "gap" areas not covered, compared gap areas to legacy instruments to verify relevance, and developed new items to address gaps. We then performed cognitive testing on new items and drafted an OA-K-specific instrument based on findings.Results: We identified 52 existing PROMIS items and developed 24 new items across 14 domains.Conclusions: We developed a process for creating condition-specific instruments that bridge gaps in existing generic measures. If successful, the methodology will create instruments that efficiently gather the patient's perspective while allowing health systems, researchers, and other interested parties to monitor and compare outcomes over time, conditions, and populations. [ABSTRACT FROM AUTHOR]

Purpose: Wenjing decoction is a well-accepted traditional Chinese medicine for the treatment of primary dysmenorrhea in East Asia, but its clinical effectiveness and risk have not been adequately assessed. In this paper, we conducted a systematic review and meta-analysis to evaluate the efficacy of Wenjing decoction for the treatment of primary dysmenorrhea.Methods: Eight databases were used in our research: the Cochrane Library, the Web of Science, PubMed, EMBASE, the Chinese Biomedical Literature Database (CBM), the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database, and the Wan-fang Database. The following search terms were used: (Wenjing decoction OR Wenjing formula OR Wenjing tang) AND (primary dysmenorrhea OR dysmenorrhea OR painful menstruation) AND (randomized controlled trial). No language limitation was used.Results: A total of 18 studies, including 1736 patients, were included in the meta-analysis. Wenjing decoction was shown to be significantly better than nonsteroidal anti-inflammatory drugs for the improvement of primary dysmenorrhea according to the clinical effective rate (RR 1.41, 95% CI 1.24-1.61), the visual analogue scale (MD -1.77, 95% CI -2.69 to -0.84), and the pain scale for dysmenorrhea (MD -1.81, 95% CI -2.41 to -1.22).Conclusions: The results supported the clinical use of Wenjing decoction for the treatment of primary dysmenorrhea. However, the quality of the evidence for this finding was low due to a high risk of bias in the included studies. Therefore, well-designed randomized controlled trials are still needed to further evaluate the efficacy of Wenjing decoction for the treatment of primary dysmenorrhea. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the uptake of the CONsolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO) statement; determined if use of CONSORT-PRO was associated with more complete reporting of PRO endpoints in randomised controlled trials (RCTs) and identified the extent to which high-impact journals publishing RCTs with PRO endpoints endorse CONSORT-PRO.Methods: CONSORT-PRO citations were identified by systematically searching Medline, EMBASE and Google from 2013 (year CONSORT-PRO released) to 17 December 2015. RCTs that cited CONSORT-PRO (cases) were compared to a comparable control sample of RCTs in terms of adherence to CONSORT-PRO using t tests. General linear models assessed the relationship between CONSORT-PRO score and key, pre-specified variables. The 100 highest-impact journals that published RCTs with PRO endpoints (2014-2015) were identified via a systematic Medline search. Instructions for authors were reviewed to determine whether journals endorsed CONSORT-PRO.Results: Total CONSORT-PRO scores ranged from 47 to 100% for cases and 25-96% for controls. Cases had significantly higher total CONSORT-PRO scores compared to controls: t = 2.64, p = 0.01. 'Citing CONSORT-PRO', 'journal endorsing CONSORT-PRO' and 'dedicated PRO paper' were significant predictors of higher CONSORT-PRO adherence score: R 2 = 0.48, p < 0.001. 11/100 top-ranked journals endorsed CONSORT-PRO in their instructions to authors, seven of these journals published RCTs included as cases in this study.Conclusion: This study demonstrated improved PRO reporting associated with journal endorsement and author use of the CONSORT-PRO extension. Despite growing awareness, more work is needed to promote appropriate use of CONSORT-PRO to improve completeness of reporting; in particular, stronger journal endorsement of CONSORT-PRO. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary metastasectomy for colorectal cancer is a commonly performed and well-established practice of ∼50 years standing. However, there have been no controlled studies, randomised or otherwise. We sought to investigate the evidence base that has been used in establishing its status as a standard of care.Methods: Among 51 papers used in a recent systematic review and quantitative synthesis, a citation network analysis was performed. A total of 344 publications (the 51 index papers and a further 293 cited in them) constitute the citation network.Results: The pattern of citation is that of a citation cascade. Specific analyses show the frequent use of historical or landmark papers, which add authority. Papers expressing an opposing viewpoint are rarely cited.Conclusions: The citation network for this common and well-established practice provides an example of selective citation. This pattern of citation tends to escalate belief in a clinical practice even when it lacks a high-quality evidence base and may create an impression of more authority than is warranted. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this paper was to describe primary care prescribers' perspectives on electronic prescribing drug alerts at the point of prescribing.Design: We used a mixed-method study which included clinician surveys (web-based and paper) and focus groups with prescribers and staff.Participants: Prescribers (n = 157) working in one of 64 practices using 1 of 6 e-prescribing technologies in 6 US states completed the quantitative survey and 276 prescribers and staff participated in focus groups.Measurements: The study measures self-reported frequency of overriding of drug alerts; open-ended responses to: "What do you think of the drug alerts your software generates for you?"Results: More than 40% of prescribers indicated they override drug-drug interactions most of the time or always (range by e-prescribing system, 25% to 50%). Participants indicated that the software and the interaction alerts were beneficial to patient safety and valued seeing drug-drug interactions for medications prescribed by others. However, they noted that alerts are too sensitive and often unnecessary. Participant suggestions included: (1) run drug alerts on an active medication list and (2) allow prescribers to set the threshold for severity of alerts.Conclusions: Primary care prescribers recognize the patient safety value of drug prescribing alerts embedded within electronic prescribing software. Improvements to increase specificity and reduce alert overload are needed. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcome measures (PROMs) are designed to assess patients' perceived health states or health-related quality of life. However, PROMs are susceptible to missing data, which can affect the validity of conclusions from randomised controlled trials (RCTs). This review aims to assess current practice in the handling, analysis and reporting of missing PROMs outcome data in RCTs compared to contemporary methodology and guidance. Methods: This structured review of the literature includes RCTs with a minimum of 50 participants per arm. Studies using the EQ-5D-3L, EORTC QLQ-C30, SF-12 and SF-36 were included if published in 2013; those using the less commonly implemented HUI, OHS, OKS and PDQ were included if published between 2009 and 2013. Results: The review included 237 records (4-76 per relevant PROM). Complete case analysis and single imputation were commonly used in 33 and 15 % of publications, respectively. Multiple imputation was reported for 9 % of the PROMs reviewed. The majority of publications (93 %) failed to describe the assumed missing data mechanism, while low numbers of papers reported methods to minimise missing data (23 %), performed sensitivity analyses (22 %) or discussed the potential influence of missing data on results (16 %). Conclusions: Considerable discrepancy exists between approved methodology and current practice in handling, analysis and reporting of missing PROMs outcome data in RCTs. Greater awareness is needed for the potential biases introduced by inappropriate handling of missing data, as well as the importance of sensitivity analysis and clear reporting to enable appropriate assessments of treatment effects and conclusions from RCTs. [ABSTRACT FROM AUTHOR]

Purpose: Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a systematic review to investigate whether prophylactic dosages of LMWH accumulate in renal insufficient patients. Methods: A comprehensive search was conducted on 17 February 2015 using Embase, Medline, Web of Science, Scopus, Cochrane, PubMed publisher, and Google scholar. The syntax emphasized for LMWHs, impaired renal function, and pharmacokinetics. The search yielded 674 publications. After exclusion by reading the titles, abstracts, and if necessary the full paper, 11 publications remained. Results: For dalteparin and tinzaparin, no accumulation was observed. Enoxaparin, on the other hand, did lead to accumulation in patients with renal insufficiency, although not in patients undergoing renal replacement therapy. Bemiparin and certoparin also did show accumulation. No data were available for nadroparin. Conclusions: In this systematic review, we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation. However, prophylactic dosages of enoxaparin, bemiparin, and certoparin did show accumulation in patients with a creatinine clearance (CrCl) below 30 ml/min, and therefore, dose reduction is required. The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs. [ABSTRACT FROM AUTHOR]

Combining ASIC and multiple microsensors low-power wireless electronic capsule was developed for the long-term monitoring of the entire human gastro-intestinal (GI) tract. To meet the system requirements, several low-power designs were used in the wireless electronic capsule. The capsule measured 11×22 mm including batteries (45mAh). The capsule system’s lifetime was 233 h, and it could meet the requirements of almost all clinical applications. A wireless electronic capsule, portable data recorder, and workstation comprised the human GI physiological parameters monitoring system. In this paper, this system was used in a clinical trial to compare colon peristaltic pressure between patients with constipation and healthy people. [ABSTRACT FROM AUTHOR]

Background: Integral components of behavioral weight-loss treatment include self-monitoring of diet and physical activity along with feedback to participants regarding their behaviors. While providing feedback has been associated with weight loss, no studies have examined the impact of feedback frequency on weight loss or the mediating role of self-monitoring adherence in this relationship. Purpose: This study examined the effect of participant feedback frequency on weight loss and determined if this effect was mediated by adherence to self-monitoring in a behavioral weight-loss trial conducted in the USA. Method: Participants ( N = 210) were randomly assigned to one of three self-monitoring methods with either no-daily feedback messages or daily feedback messages: (1) paper diary (PD), no-daily feedback; (2) personal digital assistant (PDA), no-daily feedback; and (3) PDA, daily tailored feedback messages (PDA + FB). The Sobel test via bootstrapping examined the direct effect of feedback frequency on weight loss and the indirect effect through self-monitoring adherence. Results: Receiving daily feedback messages significantly increased participants' self-monitoring adherence. A significant effect of feedback frequency on weight loss was noted; however, after adjusting for self-monitoring adherence, the effect of feedback frequency on weight loss was no longer significant. Feedback frequency had a significant indirect effect on weight loss through self-monitoring adherence. Conclusion: Self-monitoring adherence mediated the effect of feedback frequency on weight loss. Increasing the frequency with which participants receive feedback could enhance self-monitoring adherence, a critical component of behavioral weight-loss treatment. [ABSTRACT FROM AUTHOR]

This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this paper was to evaluate the relationship between urinary concentrations of Ins P6, bone mass loss and risk fracture in postmenopausal women. Materials and methods: A total of 157 postmenopausal women were included in the study: 70 had low (≤0.76 μM), 42 intermediate (0.76-1.42 μM) and 45 high (≥1.42 μM) urinary phytate concentrations. Densitometry values for neck were measured at enrollment and after 12 months (lumbar spine and femoral neck), and 10-year risk fracture was calculated using the tool FRAX. Results: Individuals with low Ins P6 levels had significantly greater bone mass loss in the lumbar spine (3.08 ± 0.65 % vs. 0.43 ± 0.55 %) than did those with high phytate levels. Moreover, a significantly greater percentage of women with low than with high Ins P6 levels showed more than 2 % of bone mass loss in the lumbar spine (55.6 vs. 20.7 %). The 10-year fracture probability was also significantly higher in the low-phytate group compared to the high-phytate group, both in hip (0.37 ± 0.06 % vs 0.18 ± 0.04 %) and major osteoporotic fracture (2.45 ± 0.24 % vs 1.83 ± 0.11 %). Discussion: It can be concluded that high urinary phytate concentrations are correlated with reduced bone mass loss in lumbar spine over 12 months and with reduced 10-year probability of hip and major osteoporotic fracture, indicating that increased phytate consumption can prevent development of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content. Purpose: This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) programme. Method: A-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group. In two studies, a second intervention arm consisting of low-to-moderate intensity exercise is included. All four A-CaRe trials use similar methods. Results: Outcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model. Measurements will be performed prior to randomization (T0), after completion of the intervention (T1) and at follow-up (T2). The primary outcome measures are cardiorespiratory fitness, muscle strength and fatigue. Secondary outcome measures include health-related quality of life and psychosocial functioning. Furthermore, cost-effectiveness and cost-utility analyses are performed from a societal perspective. Conclusion: We hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group. If so, the programmes will be implemented in the Dutch clinical practice. [ABSTRACT FROM AUTHOR]

Immune tolerance-inducing therapies reprogramme immune cells to eliminate pathogenic immune responses while preserving protective immunity. The Immune Tolerance Network (ITN), sponsored by the US National Institutes of Health, was established in 1999 to evaluate new tolerance-inducing therapies and carry out mechanistic studies using a unique interactive approach in partnership with industry, academia and foundations. Ten years later, the ITN has carried out approximately 36 clinical trials and tolerance studies examining innovative tolerogenic approaches in the settings of allergy, autoimmune diseases and organ transplantation. ITN investigators have published more than 80 original research papers based on this work. This Timeline article summarizes the progress and challenges of clinical research in the ITN. [ABSTRACT FROM AUTHOR]

Optimum treatment of idiopathic membranous nephropathy is both controversial and challenging. The most extensively studied and frequently used immunosuppressive regimens for this disease comprise alkylating agents plus corticosteroids or ciclosporin. All of these treatment options have inherent problems: they are not effective in all patients, partial-rather than complete-remissions are common, adverse effects are worrisome, and relapses after treatment cessation remain problematic. Alternative immunosuppressive agents have been tested in an effort to overcome these unresolved issues. This paper reviews the available evidence regarding both established and new agents for the treatment of patients with idiopathic membranous nephropathy, with an emphasis on the results of the most recent clinical trials. [ABSTRACT FROM AUTHOR]

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner. [ABSTRACT FROM AUTHOR]

Background: Rising public and private expenditure on antipsychotic medications is concentrated on the cost of second generation or 'atypical' medications, which are more expensive than first generation medications and make up a rapidly growing share of all antipsychotic prescriptions. Previous studies have examined whether the higher acquisition costs of atypicals are offset by other cost and/or utilisation benefits. This paper extends this literature by examining possible effects of atypicals on earnings and related measures of labour supply in a large naturalistic study with a long-term follow-up period.Methods: We analysed data on earnings and other characteristics from the Schizophrenia Care and Assessment Program (SCAP), a 3-year longitudinal study (with data collection during the years 1997-2003) of 2327 adults with schizophrenia (including schizoaffective and schizophreniform disorders) recruited from behavioural healthcare provider systems in six areas of the US. We used empirical criteria and data from the SCAP database to identify 336 patients aged < 50 years who were in the stable or 'maintenance' phase of their antipsychotic treatment during the 6 months prior to baseline. Effects of atypicals compared with typicals were estimated from Tobit regression models that included additional covariates and the baseline-dependent variable values. Regression-dependent variables were reported earnings per month, hours worked per month, days worked per month and a binary indicator of employment. To control for the effect of selection bias in choice of type of atypical, we employed an instrumental variables (IV) estimation procedure.Results: For all dependent variables, our IV Tobit regressions yielded consistently positive coefficient estimates for atypical use that were either marginally significant (p < 0.1) or significant (p < 0.05) for earnings, significant for hours and days of work and not as consistently significant for employment status. Results from these regressions imply a positive effect of atypical use on monthly earnings in the range of Dollars US 107-122. In regressions that did not control for selection bias by using IVs, coefficients for atypical use were often negative and never statistically significant.Conclusions: Our results indicate that higher drug costs of atypicals for maintenance-phase treatment are at least partially offset by higher earnings among patients. These effects represent benefits to consumers as well as savings to taxpayer-supported income transfer programmes. Future studies should seek to determine if treatment with atypicals increases patients' earnings via better control over negative symptoms and/or improved patient cognition. Both appear to be connected with employment and labour supply in patients with schizophrenia, and both may be improved through use of atypicals. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire.Methods: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure.Results: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status.Conclusions: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers. [ABSTRACT FROM AUTHOR]

In 1990, the Fast Track Project was initiated to evaluate the feasibility and effectiveness of a comprehensive, multicomponent prevention program targeting children at risk for conduct disorders in four demographically diverse American communities (Conduct Problems Prevention Research Group [CPPRG], 1992). Representing a prevention science approach toward community-based preventive intervention, the Fast Track intervention design was based upon the available data base elucidating the epidemiology of risk for conduct disorder and suggesting key causal developmental influences (R. P. Weissberg & M. T. Greenberg, 1998). Critical questions about this approach to prevention center around the extent to which such a science-based program can be effective at (1) engaging community members and stakeholders, (2) maintaining intervention fidelity while responding appropriately to the local norms and needs of communities that vary widely in their demographic and cultural/ethnic composition, and (3) maintaining community engagement in the long-term to support effective and sustainable intervention dissemination. This paper discusses these issues, providing examples from the Fast Track project to illustrate the process of program implementation and the evidence available regarding the success of this science-based program at engaging communities in sustainable and effective ways as partners in prevention programming. [ABSTRACT FROM AUTHOR]

This paper reviews evidence that behavioral family interventions are effective at improving child-rearing in distressed families and families with children exhibiting disruptive behavior. Essential therapeutic strategies offered within a collaborative therapeutic process are identified. Exemplary materials for parents and clinicians are identified. Differences between behavioral family interventions and two popular press parenting approaches are highlighted, including the lack of empirical support for these widely used programs and the advice they offer which runs counter to behavioral approaches. Recommendations are offered for combining behavioral family interventions with other empirically supported approaches, promoting more widespread use of empirically supported treatments, such as behavioral family interventions, and the need for a public health perspective on family functioning, involving collaboration among clinicians, policy makers, and researchers. [ABSTRACT FROM AUTHOR]