Implications of managed care for health systems,clinicians, and patients.

The rhetoric and realities of managed care are easily confused. The rapid growth of managed care in the United States has had many implications for patients, doctors, employers, state and federal programmes, the health insurance industry, major medical institutions, medical research, and vulnerable patient populations. It has restricted patients'' choice of doctors and limited access to specialists, reduced the professional autonomy and earnings of doctors, shifted power from the non-profit to the for-profit sectors and from hospitals and doctors to private corporations. It has also raised issues about the future structuring and financing of medical education and research and about practice ethics. However, managed care has also accorded greater prominence to the assessment of patient satisfaction, profiling and monitoring of doctors'' work, the use of clinical guidelines and quality assurance procedures and indicated the potential to improve the integration and outcome of care.     

The necessity of strengthening the cooperation between tissue banks and organ transplant organizations at national, regional, and international levels

The donation of tissues and organs increases significantly when tissue banks and organ transplant organizations work together in the procurement of organs and tissues at donor sources (hospitals, coroners system, organ procurement agencies, and funeral homes, among others). To achieve this important goal, national competent health authorities should considered the establishment of a mechanism that promote the widest possible cooperation between tissue banks and organ transplant organizations with hospitals, research medical institutions, universities, and other medical institutions and facilities. One of the issues that can facilitate this cooperation is the establishment of a coding and traceability system that could identify all tissues and organs used in transplant activities carried out in any country. The promotion of national, regional, and international cooperation between tissue banks and organ transplant organizations would enable the sharing of relevant information that could be important for medical practice and scientific studies carried out by many countries, particularly for those countries with a weak health care system.     

Using aggregate data to estimate the standard error of a treatment–covariate interaction in an individual patient data meta‐analysis

Subgroup analyses are important to medical research because they shed light on the heterogeneity of treatment effectts. A treatment–covariate interaction in an individual patient data (IPD) meta‐analysis is the most reliable means to estimate how a subgroup factor modifies a treatment's effectiveness. However, owing to the challenges in collecting participant data, an approach based on aggregate data might be the only option. In these circumstances, it would be useful to assess the relative efficiency and power loss of a subgroup analysis without patient‐level data. We present methods that use aggregate data to estimate the standard error of an IPD meta‐analysis’ treatment–covariate interaction for regression models of a continuous or dichotomous patient outcome. Numerical studies indicate that the estimators have good accuracy. An application to a previously published meta‐regression illustrates the practical utility of the methodology.     

αCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform

Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.     

Leidraad voor medisch wetenschappelijk onderzoek bij ouderen

This paper describes the development of a guideline on medical research with older subjects. Although our society is aging, evidence on health care for older persons is lacking on many topics, because these subjects are underrepresented in most drug and non-drug trials, while these services are used many older persons, and result in many adverse reactions and unplanned hospitalisation. Part of the reasons for this underrepresentation is the multimorbidity, often leading to exclusion, but also the lack of appropriate research methods plays a major role. Therefore, this paper describes the methods and results of the development of a multidisciplinary, evidence based guideline on how to conduct medical research in older persons. The recent changes in European and Dutch legislation on medical research were another reason to start this guideline project. We conducted two systematic reviews (on informed consent and recruitment) and conducted surveys and focus groups on the other four topics covered by the paper: proportionality, resistance, drop out, and societal relevance. In total we formulated 45 recommendations, all agreed on in consensus meetings, in which older persons’ representatives played a major role. This Guideline on medical research in older persons, will be implemented via the ethical review boards, the medical scientific committees, and the Ministry of Health in the Netherlands, who commissioned the guideline work. We hope the guideline stimulates quality and quantity of research on older adults to answer the increasing number of societal and scientific questions with regard to this populations.     

各种挥发油的药理活性及在医学方面的应用

通过查阅文献对近年来有关挥发油的药理活性及在医学方面应用的研究进行综述。结果表明挥发油具有抗过敏,酶抑制,抗炎,抗突变,抗癌,抗微生物,抗病毒,驱虫,抗氧化和对中枢神经系统的镇静作用等药理活性并在医学方面具有多种用途。本文兹在为今后进一步研究挥发油的药理活性提供依据。     

对新医改医师多点执业试点政策的思考

医师多点执业由于管理、制度和医师因素的原因,政策优势还无法真正显现。结合云南、广东等地试点的展情况,分析现有法律法规体系对政策实施的影响,提出稳步推动医务人员的合理流动,需要正确引导与加强监管并举,把多点执业关注点向提升基层医疗机构的方向倾斜,并积极探索团队多点执业。     

If It’s Not One Thing,It’s Another: An Inverse Relationship of Malignancy and Atherosclerotic Disease

Atherosclerosis and malignancy are pervasive pathological conditions that account for the bulk of morbidity and mortality in developed countries. Our current understanding of the patholobiology of these fundamental disorders suggests that inflammatory processes may differentially affect them; thus, atherosclerosis can be largely driven by inflammation, where as cancer often flourishes as inflammatory responses are modulated. A corollary of this hypothesis is that cancer (or its treatment may significantly attenuate atherosclerotic disease by diminishing host inflammatory response, suggesting potential therapeutic approaches. To evaluate the relationship between cancer and cardiovascular atherosclerotic disease, we assessed 1,024 autopsy reports from Brigham and Women’s Hospital and performed correlative analyses on atherosclerotic severity and cancer prevalence. In gender- and age-matched populations, there is a statistically significant inverse correlation between history of malignancy and autopsy-proven atherosclerotic disease. In a second analysis, we evaluated 147,779 patients through analysis of the Harvard Catalyst SHRINE database and demonstrated a reduced non-coronary atherosclerotic disease rate: control (27.40%), leukemia/lymphoma (12.57%), lung (17.63%), colorectal (18.17%), breast (9.79%), uterus/cervix (11.47%), and prostate (18.40%). We herein report that, based on two separate medical records analysis, an inverse correlation between cancer and atherosclerosis. Furthermore, this correlation is not uniformly associated with anti-neoplastic treatment, suggesting that the inverse relationship may be in part attributable to an individual’s intrinsic inflammatory propensity, and/or to inflammation-modulatory properties of neoplasms.     

Physiological ecology of cheirogaleid primates: variation in hibernation and torpor

Torpor (i.e. the reduction of body temperature and metabolic rate for less than 24 h) and hibernation (i.e. torpor phases longer than 24 h) are among the most extreme adaptations to seasonality in primate habitats. Although widespread among mammals, this form of extreme thermoregulation is rare among primates and is reported only for species of the cheirogaleid family. Understanding their physiological ecology is crucial for many aspects of cheirogaleid socioecology like their social organization and their mating systems. This paper first provides an overview of published information on hibernation and torpor and identifies a patchy distribution for the occurrence of hibernation across genera, species and populations. Based on a review of published studies from the wild and from captivity, we then propose a possible explanation for variation in hibernation behavior among Microcebus species and populations. Accordingly, the amount of energy that can be saved during torpor early in the lean dry season, which is determined by the minimum ambient temperature will be decisive. Only where temperatures are low, early dry season torpor bouts will be long enough to save enough energy to build up fat reserves for longer bouts of hibernation. Finally, we summarize information on the causal factors for the occurrence of hibernation by analyzing sex differences within populations. Further physiological studies on other cheirogaleid species are needed to identify the phylogenetic origin of hibernation in primates.     

A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury

Traumatic brain injuries (TBIs) are potentially lethal medical conditions, with symptoms that can overlap with symptoms of injuries outside the brain. In many cases, current diagnostic methods do not fully distinguish acute brain injury from other organ damage. In the management of stroke patients, the choice of treatment depends on whether the stroke is ischemic or hemorrhagic; however, no quick lab diagnostic tests are available to distinguish between the two types of strokes. As a result, patient triage, disposition, and patient management decisions may be delayed for patients with suspected TBI and stroke. Glial fibrillary acidic protein (GFAP), a brain-specific biomarker that is released into the blood following TBI and stroke, is being explored for potential diagnostic and prognostic value in these indications. We therefore conducted a review of MEDLINE-indexed publications from 2004 to 2011 to evaluate the current status of GFAP as a prognostic and diagnostic tool for TBI and stroke within the context of current published guidelines. Our review suggests that GFAP could provide clinically valuable information for the prognosis of TBI and stroke, but it is still at an early stage of development as a biomarker. Several TBI studies have shown elevated GFAP levels following a TBI event to be associated with greater severity of injury, poorer outcomes, and increased mortality. Clinical studies also indicate that GFAP has potential clinical utility in the differential diagnosis of various types of stroke. However, more clinical research will be required to determine the ability of GFAP levels to diagnose TBI in heterogeneous patient populations, as well as the ability of GFAP to differentiate between ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-stroke conditions in populations of patients with suspected rather than confirmed stroke. Additional clinical studies will also be required to define the temporal patterns of GFAP release in IS, ICH, SAH, and TBI, and their potential use in the differential diagnosis of these conditions. Finally, such research could demonstrate the ability of GFAP test results to provide unique clinical information that informs management decisions for TBI and stroke patients.     

Hospitalización a domicilio del anciano con enfermedad aguda

The aging of population uses to evolve suffering from chronic diseases, many times in pluripathological shaped, which may engender frailty, disability and, as a last term, dependence. The aggravation of those and/or the appearance of others acute processes become the old people into a regular patient of our hospitals. The hospital at home (HaH) has showed that it may play an important role in the provision of range hospital cares to these patients, unimpaired of efficacy and security; but with indubitable benefits within the scope of their comfort (physical, psychical) and in the field of their functional condition. Available technical means at the present day and the staff's professionalism from these units make easier that any serious illness, medical or surgical, will be subsidiary in this type of attention sometime during their hospital care process. The HaH permits a more efficient rationalization of sanitary resources and should play an important role in the longed for interconnection between primary attention and specialized one.     

OxMaR: Open Source Free Software for Online Minimization and Randomization for Clinical Trials

Minimization is a valuable method for allocating participants between the control and experimental arms of clinical studies. The use of minimization reduces differences that might arise by chance between the study arms in the distribution of patient characteristics such as gender, ethnicity and age. However, unlike randomization, minimization requires real time assessment of each new participant with respect to the preceding distribution of relevant participant characteristics within the different arms of the study. For multi-site studies, this necessitates centralized computational analysis that is shared between all study locations. Unfortunately, there is no suitable freely available open source or free software that can be used for this purpose. OxMaR was developed to enable researchers in any location to use minimization for patient allocation and to access the minimization algorithm using any device that can connect to the internet such as a desktop computer, tablet or mobile phone. The software is complete in itself and requires no special packages or libraries to be installed. It is simple to set up and run over the internet using online facilities which are very low cost or even free to the user. Importantly, it provides real time information on allocation to the study lead or administrator and generates real time distributed backups with each allocation. OxMaR can readily be modified and customised and can also be used for standard randomization. It has been extensively tested and has been used successfully in a low budget multi-centre study. Hitherto, the logistical difficulties involved in minimization have precluded its use in many small studies and this software should allow more widespread use of minimization which should lead to studies with better matched control and experimental arms. OxMaR should be particularly valuable in low resource settings.     

Creating outbred and inbred populations in haplodiploids to measure adaptive responses in the laboratory

Laboratory studies are often criticized for not being representative of processes occurring in natural populations. One reason for this is the fact that laboratory populations generally do not capture enough of the genetic variation of natural populations. This can be mitigated by mixing the genetic background of several field populations when creating laboratory populations. From these outbred populations, it is possible to generate inbred lines, thereby freezing and partitioning part of their variability, allowing each genotype to be characterized independently. Many studies addressing adaptation of organisms to their environment, such as those involving quantitative genetics or experimental evolution, rely on inbred or outbred populations, but the methodology underlying the generation of such biological resources is usually not explicitly documented. Here, we developed different procedures to circumvent common pitfalls of laboratory studies, and illustrate their application using two haplodiploid species, the spider mites Tetranychus urticae and Tetranychus evansi. First, we present a method that increases the chance of capturing high amounts of variability when creating outbred populations, by performing controlled crosses between individuals from different field‐collected populations. Second, we depict the creation of inbred lines derived from such outbred populations, by performing several generations of sib‐mating. Third, we outline an experimental evolution protocol that allows the maintenance of a constant population size at the beginning of each generation, thereby preventing bottlenecks and diminishing extinction risks. Finally, we discuss the advantages of these procedures and emphasize that sharing such biological resources and combining them with available genetic tools will allow consistent and comparable studies that greatly contribute to our understanding of ecological and evolutionary processes.     

Estimating Genetic Effects and Quantifying Missing Heritability Explained by Identified Rare-Variant Associations

Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner’s curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study where the association is identified. This is because there can be substantial heterogeneity of RV sites and frequencies even among closely related populations. In order to obtain an unbiased estimate for aggregated RV analysis, we developed bootstrap-sample-split algorithms to reduce the bias of the winner’s curse. The unbiased estimates are greatly important for understanding the population-specific contribution of RVs to the heritability of complex traits. We also demonstrate both theoretically and via simulations that for aggregate RV analysis the genetic variance for a gene or region will always be underestimated, sometimes substantially, because of the presence of noncausal variants or because of the presence of causal variants with effects of different magnitudes or directions. Therefore, even if RVs play a major role in the complex-trait etiologies, a portion of the heritability will remain missing, and the contribution of RVs to the complex-trait etiologies will be underestimated.     

Patient Preferences and Shared Decision Making in the Treatment of Substance Use Disorders: A Systematic Review of the Literature

Background

Shared Decision Making (SDM) as means to the involvement of patients in medical decision making is increasingly demanded by treatment guidelines and legislation. Also, matching of patients’ preferences to treatments has been shown to be effective regarding symptom reduction. Despite promising results for patients with substance use disorders (SUD) no systematic evaluation of the literature has been provided. The aim is therefore to give a systematic overview of the literature of patient preferences and SDM in the treatment of patients with SUD.

Methods

An electronic literature search of the databases Medline, Embase, Psyndex and Clinical Trials Register was performed. Variations of the search terms substance use disorders, patient preferences and SDM were used. For data synthesis the populations, interventions and outcomes were summarized and described according to the PRISMA statement. Methodological quality of the included articles was assessed with the Mixed Methods Appraisal Tool.

Results

N = 25 trials were included in this review. These were conducted between 1986 and 2014 with altogether n = 8.729 patients. Two studies found that patients with SUD preferred to be actively involved in treatment decisions. Treatment preferences were assessed in n = 18 studies, where the majority of patients preferred outpatient compared with inpatient treatment. Matching patients to preferences resulted in a reduction on substance use (n = 3 studies), but the majority of studies found no significant effect. Interventions for SDM differed across patient populations and optional therapeutic techniques.

Discussion

Patients with substance use disorders should be involved in medical treatment decisions, as patients with other health conditions. A suitable approach is Shared Decision Making, emphasizing the patients’ preferences. However, due to the heterogeneity of the included studies, results should be interpreted with caution. Further research is needed regarding SDM interventions in patient populations with substance use disorders.     

Viral transformation for production of personalized type I interferons

Type I interferons (IFN) are cytokines with many functions and have been widely used to treat many human diseases such as hepatitis C virus infection. Using the viral transformation and priming properties of Epstein-Barr virus, we have developed a system that can produce high levels of “personalized” IFNs, which are produced from the cells of the patient to whom the IFNs are to be administrated. We demonstrate the feasibility of the system. This seems to be the first report for the establishment of a personalized IFN-production system. The personalized IFNs could have a longer circulation time, fewer side effects but higher efficacy. We anticipate that the system can provide an improved form of IFN for medical uses.     

Field studies to determine mancozeb based spray programmes with minimal impact on predatory mites in European vine cultivation

Mancozeb is an ethylene bisdithiocarbamate (EBDC) fungicide with contact activity against a wide range of economically important fungal diseases. Its multi-site mode of action means that to date there have been no recorded incidences of resistance developing despite many years of use on high risk diseases. One such disease, Grape downy mildew (Plasmopara viticola) has developed resistance to a number of important oomycete specific fungicides following their introduction onto the market. The role of Mancozeb either as a mixing or alternation partner in helping to manage these resistance situations remains critically important. Historical use patterns for mancozeb in tree and vine crops involved many applications of product at high use rates. Although this gave excellent disease control, a negative impact on predatory mites has been reported by researchers. This has lead to the development of mancozeb spray programmes in vines and other crops with a much reduced impact on predatory mites. A range of field studies was conducted in France, Germany, Italy, Portugal and Spain where either 2 or 4 applications of mancozeb containing products were made per season at different spray timings. These trials covered the representative range of uses, agronomic practices, mite species and geographical locations in Europe. In this paper findings from ten field studies in five different vine growing regions in Europe indicated that two to four applications of mancozeb at 1.6 kg a.i./ha as part of a spray programme caused minimal impact on naturally occurring populations of predatory mites which in turn was compatible with Integrated Pest Management programmes and the conservation of predatory mites.     

From Research to Practice: Which Research Strategy Contributes More to Clinical Excellence? Comparing High-Volume versus High-Quality Biomedical Research

The question when and to what extent academic research can benefit society is of great interest to policy-makers and the academic community. Physicians in university hospitals represent a highly relevant test-group for studying the link between research and practice because they engage in biomedical academic research while also providing medical care of measurable quality. Physicians’ research contribution to medical practice can be driven by either high-volume or high-quality research productivity, as often pursuing one productivity strategy excludes the other. To empirically examine the differential contribution to medical practice of the two strategies, we collected secondary data on departments across three specializations (Cardiology, Oncology and Orthopedics) in 50 U.S.-based university hospitals served by 4,330 physicians. Data on volume and quality of biomedical research at each department was correlated with publicly available ratings of departments’ quality of care, demonstrating that high-quality research has significantly greater contribution to quality of care than high-volume research.     

RESPECTING AUTONOMY WITHOUT DISCLOSING INFORMATION

There is widespread agreement that it would be both morally and legally wrong to treat a competent patient, or to carry out research with a competent participant, without the voluntary consent of that patient or research participant. Furthermore, in medical ethics it is generally taken that that consent must be informed. The most widely given reason for this has been that informed consent is needed to respect the patient's or research participant's autonomy. In this article I set out to challenge this claim by considering in detail each of the three most prominent ways in which ‘autonomy’ has been conceptualized in the medical ethics literature. I will argue that whilst these accounts support the claim that consent is needed if the treatment of competent patients, or research on competent individuals, is to respect their autonomy, they do not support the claim that informed consent is needed for this purpose.