Twin studies for the prognosis,prevention and treatment of musculoskeletal conditions

Background

Musculoskeletal conditions are highly prevalent in our ageing society and are therefore incurring substantial increases in population levels of years lived with disability (YLD). An evidence-based approach to the prognosis, prevention, and treatment of those disorders can allow an overall improvement in the quality of life of patients, while also softening the burden on national health care systems.

Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD

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A Cost-Analysis of an Interdisciplinary Pediatric Chronic Pain Clinic

Chronic pain is characterized by high rates of functional impairment, health care utilization, and associated costs. Research supports the use of comprehensive, interdisciplinary treatment approaches. However, many hospitals hesitate to offer this full range of services, especially to Medi-Cal/Medicaid patients whose services are reimbursed at low rates. This cost analysis examines the effect on hospital and insurance costs of patients' enrollment in an interdisciplinary pediatric pain clinic, which includes medication management, psychotherapy, biofeedback, acupuncture, and massage. Retrospective hospital billing data (inpatient/emergency department/outpatient visits, and associated costs/reimbursement) from 191 consecutively enrolled Medi-Cal/Medicaid pediatric patients with chronic pain were used to compare 1-year costs before initiating pain clinic services with costs 1 year after. Pain clinic patients had significantly fewer emergency department visits, fewer inpatient stays, and lower associated billing, compared with the year before without interdisciplinary pain management services. Cost savings to the hospital of $36,228 per patient per year and to insurance of $11,482 per patient per year were found even after pain clinic service billing was included. Analyses of pre-pain clinic costs indicate that these cost reductions were likely because of clinic participation. Findings provide economic support for the use of interdisciplinary care to treat pediatric chronic pain on an outpatient basis from a hospital and insurance perspective.

The clinical evaluation of the CADence device in the acoustic detection of coronary artery disease

The noninvasive detection of turbulent coronary flow may enable diagnosis of significant coronary artery disease (CAD) using novel sensor and analytic technology. Eligible patients (n?=?1013) with chest pain and CAD risk factors undergoing nuclear stress testing were studied using the CADence (AUM Cardiovascular Inc., Northfield MN) acoustic detection (AD) system. The trial was designed to demonstrate non-inferiority of AD for diagnostic accuracy in detecting significant CAD as compared to an objective performance criteria (sensitivity 83% and specificity 80%, with 15% non-inferiority margins) for nuclear stress testing. AD analysis was blinded to clinical, core lab-adjudicated angiographic, and nuclear data. The presence of significant CAD was determined by computed tomographic (CCTA) or invasive angiography. A total of 1013 subjects without prior coronary revascularization or Q-wave myocardial infarction were enrolled. Primary analysis was performed on subjects with complete angiographic and AD data (n?=?763) including 111 subjects (15%) with severe CAD based on CCTA (n?=?34) and invasive angiography (n?=?77). The sensitivity and specificity of AD were 78% (p?=?0.012 for non-inferiority) and 35% (p?<?0.001 for failure to demonstrate non-inferiority), respectively. AD results had a high 91% negative predictive value for the presence of significant CAD. AD testing failed to demonstrate non-inferior diagnostic accuracy as compared to the historical performance of a nuclear stress OPC due to low specificity. AD sensitivity was non-inferior in detecting significant CAD with a high negative predictive value supporting a potential value in excluding CAD.     

The toxicological significance of post-mortem drug concentrations in bile

Context: Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value.

Aim: To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature.

Methods: We made a systematic search of EMBASE 1980–2016 using the search terms (“bile/” OR “exp drug bile level/concentration/”) AND “drug blood level/concentration/”, PubMed 1975–2017 for (“bile[tw]” OR “biliary[tw]”) AND (“concentration[tw]” OR “concentrations[tw]” OR “level[tw]” OR “levels[tw]”) AND “post-mortem[tw]” and also MEDLINE 1990–2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs.

Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058–0.32) for dextromoramide to 520 (range 0.62–43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes.

Limitations: The data were difficult to find. Medline does not explicitly index the term “drug bile concentration”. It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile.

Conclusions: For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection.     

Assessing Organizational Change in Multisector Community Health Alliances

Objective

The purpose of this article was to identify some common organizational features of multisector health care alliances (MHCAs) and the analytic challenges presented by those characteristics in assessing organizational change.

Data Sources

Two rounds of an Internet-based survey of participants in 14 MHCAs.

Study Design

We highlight three analytic challenges that can arise when quantitatively studying the organizational characteristics of MHCAs—assessing change in MHCA organization, assessment of construct reliability, and aggregation of individual responses to reflect organizational characteristics. We illustrate these issues using a leadership effectiveness scale (12 items) validated in previous research and data from 14 MHCAs participating in the Robert Wood Johnson Foundation''s Aligning Forces for Quality (AF4Q) program.

Findings

High levels of instability and turnover in MHCA membership create challenges in using survey data to study changes in key organizational characteristics of MHCAs. We offer several recommendations to diagnose the source and extent of these problems.     

Disparities in Perinatal Quality Outcomes for Very Low Birth Weight Infants in Neonatal Intensive Care

ObjectiveTo determine if hospital-level disparities in very low birth weight (VLBW) infant outcomes are explained by poorer hospital nursing characteristics.ConclusionsPoorer nursing characteristics contribute to disparities in VLBW infant outcomes in two nurse-sensitive perinatal quality standards. Improvements in nursing have potential to improve the quality of care for seven out of ten black VLBW infants who are born in high-black hospitals in this country.