A systematic review of methods to measure menstrual blood loss

Background Since the publication over 50 years ago of the alkaline hematin method for quantifying menstrual blood loss (MBL) many new approaches have been developed to assess MBL. The aim of this systematic review is to determine for methods of measuring MBL: ability to distinguish between normal and heavy menstrual bleeding (HMB); practicalities and limitations in the research setting; and suitability for diagnosing HMB in routine clinical practice. Methods Embase®™, MEDLINE®, and ClinicalTrials.gov were screened for studies on the development/validation of MBL assessment methods in women with self-perceived HMB, actual HMB or uterine fibroids, or patients undergoing treatment for HMB. Studies using simulated menstrual fluid and those that included women with normal MBL as controls were also eligible for inclusion. Extracted data included study population, results of validation, and advantages/disadvantages of the technique. Results Seventy-one studies fulfilled the inclusion criteria. The sensitivity and/or specificity of diagnosing HMB were calculated in 16 studies of methods involving self-perception of MBL (11 pictorial), and in one analysis of the menstrual-fluid-loss (MFL) method; in 13 of these studies the comparator was the gold standard alkaline hematin technique. Sensitivity and specificity values by method were, respectively: MFL model, 89, 98%; pictorial blood loss assessment chart (PBAC), 58–99%, 7.5–89%; menstrual pictogram, 82–96%, 88–94%; models/questionnaires, 59–87%, 62–86%, and complaint of HMB, 74, 74%. The power of methods to identify HMB was also assessed using other analyses such as comparison of average measurements: statistical significance was reported for the PBAC, MFL, subjective complaint, and six questionnaires. In addition, PBAC scores, menstrual pictogram volumes, MFL, pad/tampon count, iron loss, and output from three questionnaires correlated significantly with values from a reference method in at least one study. In general, pictorial methods have been more comprehensively validated than questionnaires and models. Conclusions Every method to assess MBL has limitations. Pictorial methods strike a good balance between ease of use and validated accuracy of MBL determination, and could complement assessment of HMB using quality of life (QoL) in the clinical and research setting

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

PMCID: PMC4636050.-- et al.Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis.We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.E.B. is a Rosetrees Trust fellow; M.J.H. has a Cancer Research UK fellowship; N.Mu. received funding from the Rosetrees Trust; M.G. is funded by the UK Medical Research Council; I.V. is funded by Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal; R.C.R. and D.M.R. are partly funded by the Cambridge Biomedical Research Centre and Cancer Research UK Cancer Centre; P.V.L. is a postdoctoral researcher of the Research Foundation—Flanders (FWO); S.M.J. is a Wellcome Senior Fellow in Clinical Science; and C.S. is a senior Cancer Research UK clinical research fellow and is funded by Cancer Research UK, the Rosetrees Trust, European Union Framework Programme 7 (projects PREDICT and RESPONSIFY, ID:259303), the Prostate Cancer Foundation, the European Research Council and the Breast Cancer Research Foundation. This research is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.Peer Reviewe

Technologien im Kontext von Behinderung. Bausteine für Teilhabe in Alltag und Beruf

Mit technischen Entwicklungen verbindet sich für Menschen mit Behinderung oft auch die Hoffnung auf eine bessere gesellschaftliche Teilhabe und Integration ins Arbeitsleben. Dieses Technikpotenzial kann umso stärker Wirkung entfalten, je mehr die Bedingungen, normativen Grundlagen und wechselseitigen Verknüpfungen des Arbeitsplatzes mit der umfassenden Ermittlung der jeweiligen individuellen Konditionen sowie den notwendigen Maßnahmen der zuständigen sozialen Institutionen abgestimmt werden. Aus einer solchen Perspektive beschreibt dieses Buch erstmals umfassend, wie mithilfe von neuen Technologien persönliche Fähigkeiten möglichst gut entfaltet und Behinderungen weitgehend vermieden oder kompensiert werden können. Thematisiert wird auch, wie Umweltbedingungen durch den Einsatz von Technologien so gestaltet werden können, dass sie für Menschen mit funktionalen Einschränkungen möglichst niedrige Barrieren für die Lebensführung und soziale Teilhabe darstellen. Die Autoren beschreiben die Zielgruppe dieser behinderungskompensierenden Technologien, analysieren die politischen, rechtlichen und sozioökonomischen Rahmenbedingungen für deren Einsatz am Arbeitsplatz und skizzieren die Potenziale und Trends innovativer bzw. zukünftiger Technologien

Best practice for analysis of shared clinical trial data

BACKGROUND: Greater transparency, including sharing of patient-level data for further research, is an increasingly important topic for organisations who sponsor, fund and conduct clinical trials. This is a major paradigm shift with the aim of maximising the value of patient-level data from clinical trials for the benefit of future patients and society. We consider the analysis of shared clinical trial data in three broad categories: (1) reanalysis - further investigation of the efficacy and safety of the randomized 3 intervention, (2) meta-analysis, and (3) supplemental analysis for a research question that is not directly assessing the randomized intervention. DISCUSSION: In order to support appropriate interpretation and limit the risk of misleading findings, analysis of shared clinical trial data should have a pre-specified analysis plan. However, it is not generally possible to limit bias and control multiplicity to the extent that is possible in the original trial design, conduct and analysis, and this should be acknowledged and taken into account when interpreting results. We highlight a number of areas where specific considerations arise in planning, conducting, interpreting and reporting analyses of shared clinical trial data. A key issue is that that these analyses essentially share many of the limitations of any post hoc analyses beyond the original specified analyses. The use of individual patient data in meta-analysis can provide increased precision and reduce bias. Supplemental analyses are subject to many of the same issues that arise in broader epidemiological analyses. Specific discussion topics are addressed within each of these areas. SUMMARY: Increased provision of patient-level data from industry and academic-led clinical trials for secondary research can benefit future patients and society. Responsible data sharing, including transparency of the research objectives, analysis plans and of the results will support appropriate interpretation and help to address the risk of misleading results and avoid unfounded health scares

Evaluating the Relationship Between Visual Acuity and Utilities in Patients With Diabetic Macular Edema Enrolled in Intravitreal Aflibercept Studies

PURPOSE. The purpose of this study was to explore the relationship between visual acuity and utility (health-related quality of life) in diabetic macular edema (DME) using intravitreal aflibercept data. METHODS. The relationship between visual acuity in the best-seeing eye (BSE) and worseseeing eye (WSE) and utility was explored using ordinary least squares (OLS) and randomeffects models adjusted for different covariates (age, age2 , sex, body mass index, smoking status, glycated hemoglobin, diabetes severity, comorbidities, and geographic region). Utility was measured using the EuroQoL-five dimensions questionnaire (EQ-5D) and Visual Functioning Questionnaire-Utility Index (VFQ-UI). For each model, coefficients (R2 ) were reported, and WSE/BSE was expressed as the ratio of coefficients (OLS models). Models were independent of treatment effects, and outcomes from all time points (up to week 100) were included where available. RESULTS. Data from 1320 patients with DME were analyzed. In all models, the association between visual acuity (BSE > WSE) was stronger with VFQ-UI– than EQ-5D–derived utilities. The estimated relationship between VFQ-UI and visual acuity in the BSE and WSE was robust, even with an increasing number of covariates. WSE/BSE coefficient ratios were similar across VFQ-UI OLS models (32%) compared with EQ-5D models (41%–48%). Actual (unadjusted) versus predicted data plots also showed a better fit with VFQ-UI– than EQ-5D–derived utilities. CONCLUSIONS. These analyses show that VFQ-UI was more sensitive than EQ-5D–derived utilities for measuring the impact of visual acuity in the BSE and WSE. Visual acuity in the BSE was a major contributor to utility, but WSE is also important though to a lesser degree as shown by the coefficient ratios. These new data will be useful for health technology assessments in DME, where utilities data are lacking. Keywords: diabetic macular edema, intravitreal aflibercept, utilit

Teaching breast ultrasound skills including core-needle biopsies on a phantom enhances undergraduate student's knowledge and learning satisfaction

Purpose To investigate whether a training program on breast ultrasound skills including core-needle biopsies to undergraduate students can improve medical knowledge and learning satisfaction. Methods Medical students attending mandatory classes at the Medical School of the University of Saarland received a supplemental theoretical and hands-on training program on ultrasound (US) breast screening and on US-guided core-needle biopsy using an agar–agar phantom. Experienced breast specialists and ultrasound examiners served as trainers applying Peyton’s 4-step training approach. The students’ theoretical knowledge and hands-on skills were tested before and after the training program, using a multiple-choice questionnaire (MCQ), the Objective Structured Clinical Examination (OSCE) and a student curriculum evaluation. Results The MCQ results showed a significant increase of the student’s theoretical knowledge (50.2–75.2%, p < 0.001). After the course, the OSCE showed a mean total of 17.3/20 points (86.5%), confirming the practical implementation of the new skills. The student curriculum evaluation in general was very positive. A total of 16/20 questions were rated between 1.2 and 1.7 (very good) and 3 questions were rated as 2.1 (good). Conclusion Undergraduate student’s medical education can be enhanced by teaching breast US skills

Characterization of the “frequent exacerbator phenotype” in bronchiectasis

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. Objectives: To establish if there is a \u201cfrequent exacerbator phenotype\u201d in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype.The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P, 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P, 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P, 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during followup. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up