Assessing the Potential of Multiple Imputation in Sequence Analysis

Sequence analysis and optimal matching are useful heuristic tools for the descriptive analysis of heterogeneous individual pathways such as educational careers, job sequences or patterns of family formation. However, to date it remains unclear how to handle the inevitable problems caused by missing values with regard to such analysis. Multiple Imputation (MI) offers a possible solution for this problem but it has not been tested in the context of sequence analysis. Against this background, we contribute to the literature by assessing the potential of MI in the context of sequence analyses using an empirical example. Methodologically, we draw upon the work of Brendan Halpin and extend it to additional types of missing value patterns. Our empirical case is a sequence analysis of panel data with substantial attrition that examines the typical patterns and the persistence of sex segregation in school-to-work transitions in Switzerland. The preliminary results indicate that MI is a valuable methodology for handling missing values due to panel mortality in the context of sequence analysis. MI is especially useful in facilitating a sound interpretation of the resulting sequence types.

Consensus on the Need for a Hierarchical List of Patient-reported Pain Outcomes for Metaanalyses of Knee Osteoarthritis Trials: An OMERACT Objective.

OBJECTIVE Although protocol registration for systematic reviews is still not mandatory, reviewers should be strongly encouraged to register the protocol to identify the methodological approach, including all outcomes of interest. This will minimize the likelihood of biased decisions in reviews, such as selective outcome reporting. A group of international experts convened to address issues regarding the need to develop hierarchical lists of outcome measurement instruments for a particular outcome for metaanalyses. METHODS Multiple outcome measurement instruments exist to measure the same outcome. Metaanalysis of knee osteoarthritis (OA) trials, and the assessment of pain as an outcome, was used as an exemplar to assess how Outcome Measures in Rheumatology (OMERACT), the Cochrane Collaboration, and other international initiatives might contribute in this area. The meeting began with formal presentations of background topics, empirical evidence from the literature, and a brief introduction to 2 existing hierarchical lists of pain outcome measurement instruments recommended for metaanalyses of knee OA trials. RESULTS After discussions, most participants agreed that there is a need to develop a methodology for generation of hierarchical lists of outcome measurement instruments to guide metaanalyses. Tools that could be used to steer development of such a prioritized list are the COSMIN checklist (Consensus-based Standards for the selection of health status Measurement Instruments) and the OMERACT Filter 2.0. CONCLUSION We list meta-epidemiological research agenda items that address the frequency of reported outcomes in trials, as well as methodologies to assess the best measurement properties (i.e., truth, discrimination, and feasibility).

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (the dorsolateral peritoneal layer (n=100; 73 male, 27 female; median age 68 yrs, range 35-86 yrs) and group B without readapation (n=100; 66 male, 34 female; median age 65 yrs, range 30-86 yrs). Regular postoperative follow-up was performed at our outpatient clinic. Median follow-up was 59 months (range 3-100 months), five patients were lost to follow-up in group A, seven in group B. Bowel function was evaluated using the validated Gastrointestinal Quality of Life Index questionnaire and an institutional questionnaire regarding post-cystectomy outcome. Local recurrences and distal metastases were evaluated using computed tomography and bone scan at the regular follow-up visits. RESULTS There was no significant difference between the two groups in terms of the rate of local (pelvic) recurrence (5/95 [5.3%] in group A; 7/93 [7.5%] in group B; p = 0.53), the rate of distant metastases (21/95 [22.1%] in group A; 23/93 [24.7%] in group B; p = 0.67), cancer-specific survival (p = 0.37), and overall survival (p = 0.59). Group A had significantly better bowel function at 3 (p < 0.001), 6 (p < 0.006), 12 (p <0.006) and 24 months (p = 0.04), and significantly less postoperative abdominal pain and bloating at 3 (p = 0.002) and 6 months (p = 0.01). CONCLUSION Readaptation of the dorsolateral peritoneal layer following PLND and cystectomy has a beneficial long-term impact on bowel function and postoperative pain without compromising oncological radicality. This article is protected by copyright. All rights reserved.

What is the Need for Prostatic Biomarkers in Prostate Cancer Management?

Discriminating patients with a low risk of progression from those with lethal prostate cancer is one of the main challenges in prostate cancer management. Indeed, such discrimination is essential if we aim to avoid overtreatment in men with indolent disease and to improve survival in those men with lethal disease. We are reporting on the current literature on such prognostic tools that are now available, their clinical role and their limitations in individualizing care. There is an urgent need to incorporate such genomic tools into new platform-based clinical trial structures to further develop and validate prognostic and predictive biomarkers and provide prostate cancer patients with an effective and cost-efficient access to new drugs in the setting of personalized treatment.

Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey

AIMS Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. METHODS AND RESULTS A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. CONCLUSIONS The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

BACKGROUND The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. METHODS We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. FINDINGS Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. INTERPRETATION Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line drugs during the next few years as access to viral load monitoring improves. An urgent need exists to decrease the costs of second-line drugs. FUNDING World Health Organization, Swiss National Science Foundation, National Institutes of Health.

Assessing the Phylogenetic Utility of DNA Barcoding Using the New Zealand Cicada Genus Kikihia

DNA Barcoding (Hebert et al. 2003) has the potential to revolutionize the process of identifying and cataloguing biodiversity; however, significant controversy surrounds some of the proposed applications. In the seven years since DNA barcoding was introduced, the Web of Science records more than 600 studies that have weighed the pros and cons of this procedure. Unfortunately, the scientific community has been unable to come to any consensus on what threshold to use to differentiate species or even whether the barcoding region provides enough information to serve as an accurate species identification tool. The purpose of my thesis is to analyze mitochondrial DNA (mtDNA) barcoding’s potential to identify known species and provide a well-resolved phylogeny for the New Zealand cicada genus Kikihia. In order to do this, I created a phylogenetic tree for species in the genus Kikihia based solely on the barcoding region and compared it to a phylogeny previously created by Marshall et al. (2008) that benefits from information from other mtDNA and nuclear genes as well as species-specific song data. I determined how well the barcoding region delimits species that have been recognized based on morphology and song. In addition, I looked at the effect of sampling on the success of barcoding studies. I analyzed subsets of a larger, more densely sampled dataset for the Kikihia Muta Group to determine which aspects of my sampling strategy led to the most accurate identifications. Since DNA barcoding would by definition have problems in diagnosing hybrid individuals, I studied two species (K. “murihikua” and K. angusta) that are known to hybridize. Individuals that were not obvious hybrids (determined by morphology) were selected for the case study. Phylogenetic analysis of the barcoding region revealed insights into the reasons these two species could not be successfully differentiated using barcoding alone.

Physician coding for mental illness reimbursement and the need for mental health parity

Many patients with anxiety and depression initially seek treatment from their primary care physicians. Changes in insurance coverage and current mental parity laws, make reimbursement for services a problem. This has led to a coding dilemma for physicians seeking payment for their services. This study seeks to determine first the frequency at which primary care physicians use alternative coding, and secondly, if physicians would change their coding practices, provided reimbursement was assured through changes in mental parity laws. A mail survey was sent to 260 randomly selected primary care physicians, who are family practice, internal medicine, and general practice physicians, and members of the Harris County Medical Society. The survey evaluated the physicians' demographics, the number of patients with psychiatric disorders seen by primary care physicians, the frequency with which physicians used alternative coding, and if mental parity laws changed, the rate at which physicians would use a psychiatric illness diagnosis as the primary diagnostic code. The overall response rate was 23%. Only 47 of the 59 physicians, who responded, qualified for the study and of those 45% used a psychiatric disorder to diagnose patients with a primary psychiatric disorder, 47% used a somatic/symptom disorder, and 8% used a medical diagnosis. From the physicians who would not use a psychiatric diagnosis as a primary ICD-9 code, 88% were afraid of not being reimbursed and 12% were worried about stigma or jeopardizing insurability. If payment were assured using a psychiatric diagnostic code, 81% physicians would use a psychiatric diagnosis as the primary diagnostic code. However, 19% would use an alternative diagnostic code in fear of stigmatizing and/or jeopardizing patients' insurability. Although the sample size of the study design was adequate, our survey did not have an ideal response rate, and no significant correlation was observed. However, it is evident that reimbursement for mental illness continues to be a problem for primary care physicians. The reformation of mental parity laws is necessary to ensure that patients receive mental health services and that primary care physicians are reimbursed. Despite the possibility of improved mental parity legislation, some physicians are still hesitant to assign patients with a mental illness diagnosis, due to the associated stigma, which still plays a role in today's society. ^