The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review.

Objectives: Posttraumatic stress disorder (PTSD) is a potentially debilitating mental health problem. There has been a recent surge of interest regarding the use of cannabinoids in the treatment of PTSD. We therefore sought to systematically review and assess the quality of the clinical evidence of the effectiveness of cannabinoids for the treatment of PTSD. Method: We included all studies published until December 2018 where a patient has had PTSD diagnosed and had been prescribed or were using a cannabinoid for the purpose of reducing PTSD symptoms. Our primary outcome measure was the reduction in PTSD symptoms using a validated instrument. In the absence of randomized controlled trials, we included the next best available levels of evidence including observational and retrospective studies and case reports. We assessed risk of bias and quality using validated tools appropriate for the study design. Results: We included 10 studies in this review, of which only one study was a pilot randomized, double-blind, placebo-controlled, crossover clinical trial. Every identified study had medium to high risk of bias and was of low quality. We found that cannabinoids may decrease PTSD symptomology, in particular sleep disturbances and nightmares. Conclusions: Most studies to date are small and of low quality, with significant limitations to the study designs precluding any clinical recommendations about its use in routine clinical practice. Evidence that cannabinoids may help reduce global PTSD symptoms, sleep disturbances, and nightmares indicates that future well-controlled, randomized, double-blind clinical trials are highly warranted.PROSPERO registration number: 121646.

Base excision repair proteins couple activation-induced cytidine deaminase and endonuclease G during replication stress-induced MLL destabilization.

The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood. We recently proposed that DNA replication stress results in MLLbcr cleavage via endonuclease G (EndoG) and represents the common denominator of genotoxic therapy-induced MLL destabilization. Here we performed a siRNA screen for new factors involved in replication stress-induced MLL rearrangements employing an enhanced green fluorescent protein-based reporter system. We identified 10 factors acting in line with EndoG in MLLbcr breakage or further downstream in the repair of the MLLbcr breaks, including activation-induced cytidine deaminase (AID), previously proposed to initiate MLLbcr rearrangements in an RNA transcription-dependent mechanism. Further analysis connected AID and EndoG in MLLbcr destabilization via base excision repair (BER) components. We show that replication stress-induced recruitment of EndoG to the MLLbcr and cleavage are AID/BER dependent. Notably, inhibition of the core BER factor Apurinic-apyrimidinic endonuclease 1 protects against MLLbcr cleavage in tumour and human cord blood-derived haematopoietic stem/progenitor cells, harbouring the cells of origin of leukaemia. We propose that off-target binding of AID to the MLLbcr initiates BER-mediated single-stranded DNA cleavage, which causes derailed EndoG activity ultimately resulting in leukaemogenic MLLbcr rearrangements.

[What Surgeons Should Know about Risk Management]. / Risikomanagement in der Chirurgie ­ was muss der Chirurg wissen?

Background: The fact that medical treatment is associated with errors has long been recognized. Based on the principle of "first do no harm", numerous efforts have since been made to prevent such errors or limit their impact. However, recent statistics show that these measures do not sufficiently prevent grave mistakes with serious consequences. Preventable mistakes such as wrong patient or wrong site surgery still frequently occur in error statistics. Methods: Based on insight from research on human error, in due consideration of recent legislative regulations in Germany, the authors give an overview of the clinical risk management tools needed to identify risks in surgery, analyse their causes, and determine adequate measures to manage those risks depending on their relevance. The use and limitations of critical incident reporting systems (CIRS), safety checklists and crisis resource management (CRM) are highlighted. Also the rationale for IT systems to support the risk management process is addressed. Results/Conclusion: No single tool of risk management can be effective as a standalone instrument, but unfolds its effect only when embedded in a superordinate risk management system, which integrates tailor-made elements to increase patient safety into the workflows of each organisation. Competence in choosing adequate tools, effective IT systems to support the risk management process as well as leadership and commitment to constructive handling of human error are crucial components to establish a safety culture in surgery.

[Full-scale simulation in German medical schools and anesthesia residency programs : Status quo]. / Full-Scale-Simulation in der anästhesiologischen Lehre und Weiterbildung in Deutschland : Gegenwärtiger Stand.

BACKGROUND: Simulation has been increasingly used in medicine. In 2003 German university departments of anesthesiology were provided with a full-scale patient simulator, designated for use with medical students. Meanwhile simulation courses are also offered to physicians and nurses. Currently, the national model curriculum for residency programs in anesthesiology is being revised, possibly to include mandatory simulation training. OBJECTIVES: To assess the status quo of full-scale simulation training for medical school, residency and continuing medical education in German anesthesiology. METHODS: All 38 German university chairs for anesthesiology as well as five arbitrarily chosen non-university facilities were invited to complete an online questionnaire regarding their centers' infrastructure and courses held between 2010 and 2012. RESULTS: The overall return rate was 86 %. In university simulation centers seven non-student staff members, mainly physicians, were involved, adding up to a full-time equivalent of 1.2. All hours of work were paid by 61 % of the centers. The median center size was 100 m2 (range 20-500 m2), equipped with three patient simulators (1-32). Simulators of high or very high fidelity are available at 80 % of the centers. Scripted scenarios were used by 91 %, video debriefing by 69 %. Of the participating university centers, 97 % offered courses for medical students, 81 % for the department's employees, 43 % for other departments of their hospital, and 61 % for external participants. In 2012 the median center reached 46 % of eligible students (0-100), 39 % of the department's physicians (8-96) and 16 % of its nurses (0-56) once. For physicians and nurses from these departments that equals one simulation-based training every 2.6 and 6 years, respectively. 31 % made simulation training mandatory for their residents, 29 % for their nurses and 24 % for their attending physicians. The overall rates of staff ever exposed to simulation were 45 % of residents (8-90), and 30 % each of nurses (10-80) and attendings (0-100). Including external courses the average center trained 59 (4-271) professionals overall in 2012. No clear trend could be observed over the three years polled. The results for the non-university centers were comparable. CONCLUSIONS: Important first steps have been taken to implement full-scale simulation in Germany. In addition to programs for medical students courses for physicians and nurses are available today. To reach everyone clinically involved in German anesthesiology on a regular basis the current capacities need to be dramatically increased. The basis for that to happen will be new concepts for funding, possibly supported by external requirements such as the national model curriculum for residency in anesthesiology.

[The basis for well-founded simulations]. / Grundlagen für ein fundiertes Simulationskonzept.

In medical education, simulation is gaining increasing importance for teaching a variety of subjects. A well-founded educational approach is necessary for effective use. In addition to material aspects, simulation environment, curriculum, learning environment, and methods of debriefing have to be considered. The role of a competent instructor should be emphasized and the importance of an elaborate change management process to implement a good concept should not be underestimated.

NF-κB-dependent DNA damage-signaling differentially regulates DNA double-strand break repair mechanisms in immature and mature human hematopoietic cells.

Hematopoietic stem and progenitor cells (HSPC), that is, the cell population giving rise not only to all mature hematopoietic lineages but also the presumed target for leukemic transformation, can transmit (adverse) genetic events, such as are acquired from chemotherapy or ionizing radiation. Data on the repair of DNA double-strand-breaks (DSB) and its accuracy in HSPC are scarce, in part contradictory, and mostly obtained in murine models. We explored the activity, quality and molecular components of DSB repair in human HSPC as compared with mature peripheral blood lymphocytes (PBL). To consider chemotherapy/radiation-induced compensatory proliferation, we established cycling HSPC cultures. Comparison of pathway-specific repair activities using reporter systems revealed that HSPC were severely compromised in non-homologous end joining and homologous recombination but not microhomology-mediated end joining. We observed a more pronounced radiation-induced accumulation of nuclear 53BP1 in HSPC relative to PBL, despite evidence for comparable DSB formation from cytogenetic analysis and γH2AX signal quantification, supporting differential pathway usage. Functional screening excluded a major influence of phosphatidylinositol-3-OH-kinase (ATM/ATR/DNA-PK)- and p53-signaling as well as chromatin remodeling. We identified diminished NF-κB signaling as the molecular component underlying the observed differences between HSPC and PBL, limiting the expression of DSB repair genes and bearing the risk of an inaccurate repair.

[Human factors and crisis resource management: improving patient safety]. / "Human factors" und "crisis resource management": Erhöhung der Patientensicherheit.

A continuing high number of patients suffer harm from medical treatment. In 60-70% of the cases the sources of harm can be attributed to the field of human factors (HFs) and teamwork; nevertheless, those topics are still neither part of medical education nor of basic and advanced training even though it has been known for many years and it has meanwhile also been demonstrated for surgical specialties that training in human factors and teamwork considerably reduces surgical mortality.Besides the medical field, the concept of crisis resource management (CRM) has already proven its worth in many other industries by improving teamwork and reducing errors in the domain of human factors. One of the best ways to learn about CRM and HFs is realistic simulation team training with well-trained instructors in CRM and HF. The educational concept of the HOTT (hand over team training) courses for trauma room training offered by the DGU integrates these elements based on the current state of science. It is time to establish such training for all medical teams in emergency medicine and operative care. Accompanying safety measures, such as the development of a positive culture of safety in every department and the use of effective critical incident reporting systems (CIRs) should be pursued.

[Patient safety: data on the topic and ways out of the crisis]. / Patientensicherheit : Daten zum Thema und Wege aus der Krise.

Studies have shown for many years that the cause of errors or patient injury is in a high proportion of cases to be found under human factors. Human factors include all those factors which determine the safety and capabilities of humans especially in complex situations or systems. Up to now this topic has barely been systematically dealt with in training and there is a large deficit. Modern simulation team training with systematic use of established principles of adult education and the implementation of crisis resource management (CRM) for teams can have enormous positive effects for patient safety. The concept of CRM for increasing human reliability is, however, barely used systematically for training. Simulation team training for critical events (not for emergency cases) is barely used. Professional performance at the highest level can only be expected from teams which regularly participate in team training for critical situations. In addition to simulation training with human factors, other aspects of patient safety are also essential. The concept of high reliability organizations (HRO) could make an important contribution in the sense of a safe hospital concept and includes the collection and analysis of critical incidents (critical incident reporting system CIRS) as well as the focus on the system of patient safety instead of individual persons and errors.

The role of patient simulation and incident reporting in the development and evaluation of medical devices and the training of their users.

We describe how simulation and incident reporting can be used in combination to make the interaction between people, (medical) technology and organisation safer for patients and users. We provide the background rationale for our conceptual ideas and apply the concepts to the analysis of an actual incident report. Simulation can serve as a laboratory to analyse such cases and to create relevant and effective training scenarios based on such analyses. We will describe a methodological framework for analysing simulation scenarios in a way that allows discovering and discussing mismatches between conceptual models of the device design and mental models users hold about the device and its use. We further describe how incident reporting systems can be used as one source of data to conduct the necessary needs analyses - both for training and further needs for closer analysis of specific devices or some of their special features or modes during usability analyses.

The role of the registered nurse in the marketing of primary healthcare services, as part of health promotion.

Existing literature on the marketing of primary healthcare services was reviewed to determine the role of registered nurses in this regard. The systematic review included five searches and ensured wide coverage of the results of available primary research studies on the topic. The results were summarised and the role of registered nurses in the marketing of primary healthcare services was identified. Primary research sources on the topic included textbooks on marketing by experts in the field and relevant journal articles by authorities on healthcare marketing. The data were analysed and four main categories identified. To ensure the trustworthiness of the research, Lincoln and Guba's (1981: 215-216) criteria, as explained by Krefting (1991: 217), were applied. Because the population consisted of only literature, ethical considerations concerning human subjects were irrelevant. Results indicated that the basic commercial marketing principles (the so-called 4Ps--product, price, place, and promotion) could be adapted for the health sector. The conclusion was that registered nurses could contribute to the marketing of primary healthcare services by communicating with the community (promotion) and by ensuring effective service (product) delivery at the right price and place. Registered nurses could influence the community's perceptions of health care and facilitate behaviour changes, thereby promote health. The implementation of the findings and recommendations of this research could create a new awareness among registered nurses of their role in the marketing of primary healthcare services in South Africa and improve their skills in this regard.

Prospective memory failures as an unexplored threat to patient safety: results from a pilot study using patient simulators to investigate the missed execution of intentions.

This study investigated failures of prospective memory (PM) as a relevant but neglected error type in medicine. A patient simulator was used to investigate PM failures. The influence of subjective importance (high, low) and type of intention (educational, internal, external) on the (missed) execution of intention was investigated in a 2 x 2 design. The effects on missed executions by importance (high < low) and type of intention (educational < external < internal) were hypothesized. Of 73 valid intentions in 40 prepared simulator scenarios 19 (26%) were missed overall. A total of 64% of unimportant and 80% of important intentions were executed 79% of educational 67% of external and 72% of internal intentions were executed. Neither difference was statistically significant using chi(2) tests. Interaction was significant for missed executions (p = 0.025; n = 19; df = 2; chi(2) = 7.41) and for executions (p = 0.002; n = 54; df = 2; chi(2) = 12.50). Despite low statistical support and some methodological limitations, it was possible to show that PM failures are relevant to patient safety and that patient simulators are a suitable but so far unused tool for their investigation.

[Innovative training for enhancing patient safety. Safety culture and integrated concepts]. / Neue Trainingsformen und Erhöhung der Patientensicherheit. Sicherheitskultur und integrierte Konzepte.

INTRODUCTION: Patient safety is determined by the performance safety of the medical team. Errors in medicine are amongst the leading causes of death of hospitalized patients. These numbers call for action. Backgrounds, methods and new forms of training are introduced in this article. METHOD: Concepts from safety research are transformed to the field of emergency medical treatment. Strategies from realistic patient simulator training sessions and innovative training concepts are discussed. RESULTS: The reasons for the high numbers of errors in medicine are not due to a lack of medical knowledge, but due to human factors and organisational circumstances. A first step towards an improved patient safety is to accept this. We always need to be prepared that errors will occur. A next step would be to separate "error" from guilt (culture of blame) allowing for a real analysis of accidents and establishment of meaningful incident reporting systems. Concepts with a good success record from aviation like "crew resource management" (CRM) training have been adapted my medicine and are ready to use. These concepts require theoretical education as well as practical training. Innovative team training sessions using realistic patient simulator systems with video taping (for self reflexion) and interactive debriefing following the sessions are very promising. CONCLUSION: As the need to reduce error rates in medicine is very high and the reasons, methods and training concepts are known, we are urged to implement these new training concepts widely and consequently. To err is human - not to counteract it is not.

[Patient safety and errors in medicine: development, prevention and analyses of incidents]. / Patientensicherheit und Fehler in der Medizin. Entstehung, Prävention und Analyse von Zwischenfällen.

"Patient safety" and "errors in medicine" are issues gaining more and more prominence in the eyes of the public. According to newer studies, errors in medicine are among the ten major causes of death in association with the whole area of health care. A new era has begun incorporating attention to a "systems" approach to deal with errors and their causes in the health system. In other high-risk domains with a high demand for safety (such as the nuclear power industry and aviation) many strategies to enhance safety have been established. It is time to study these strategies, to adapt them if necessary and apply them to the field of medicine. These strategies include: to teach people how errors evolve in complex working domains and how types of errors are classified; the introduction of critical incident reporting systems that are free of negative consequences for the reporters; the promotion of continuous medical education; and the development of generic problem-solving skills incorporating the extensive use of realistic simulators wherever possible. Interestingly, the field of anesthesiology--within which realistic simulators were developed--is referred to as a model for the new patient safety movement. Despite this proud track record in recent times though, there is still much to be done even in the field of anesthesiology. Overall though, the most important strategy towards a long-term improvement in patient safety will be a change of "culture" throughout the entire health care system. The "culture of blame" focused on individuals should be replaced by a "safety culture", that sees errors and critical incidents as a problem of the whole organization. The acceptance of human fallability and an open-minded non-punitive analysis of errors in the sense of a "preventive and proactive safety culture" should lead to solutions at the systemic level. This change in culture can only be achieved with a strong commitment from the highest levels of an organization. Patient safety must have the highest priority in the goals of the institution: "Primum nihil nocere"--"First, do not harm".

The residual anthelmintic efficacy of moxidectin against selected nematodes affecting sheep.

Determination of the residual anthelmintic efficacy in sheep of an oral formulation of moxidectin at a dosage rate of 0.2 mg kg-1 was evaluated 27-29 (mean: 28) d after dosing and that of the injectable formulation of moxidectin at a dosage rate of 0.2 mg kg-1 at 27-29 (mean: 28) and 34-36 (mean: 35) d post-treatment. The injectable formulation was more than 80% effective in more than 80% of treated sheep against a third larval stage challenge of Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Gaigeria pachyscelis and Oesophagostomum columbianum at both 28 and 35 d post-treatment. The oral formulation on the other hand was equally effective against a third larval stage challenge of G. pachysce1is at 28 d post-treatment and more than 60% effective in more than 60% of treated sheep against a third larval stage challenge at 28 d post-treatment of H. contortus, T. circumcincta and O. columbianum.

[The value of a new IRMA for determining thyroglobulin]. / Wertigkeit eines neuen IRMA zur Thyreoglobulinbestimmung.

A total of 277 patients suffering from differentiated thyroid carcinoma with individual follow-up periods of up to five years had been investigated. More than 1,000 sera were collected. The present paper reports on the results of the parallel serum Tg determinations by means of a recently introduced Tg-IRMA system in comparison with the previously used, well established Tg-RIA method. The intra- and the interassay variation of the IRMA were found at 37% and 46%, respectively, for 4 ng Tg/ml, and 3% and 6%, respectively, for Tg values above 40 ng/ml. Several effects that could interfere with the serum Tg determination (freezing or repeated freezing and thawing of sera, hemolysis or lipemia or dilution of sera, preanalytical use of serum separating tubes) were examined. Although statistically significant in some instances, at least, all of the above mentioned effects were without any practical relevance for the clinical routine use of the IRMA. In patients being in complete remission and on complete TSH suppressive thyroid hormone treatment but having no residual thyroid tissue (n = 70), the level of clinical significance was 1 ng Tg/ml for the IRMA system, resulting in a sensitivity of 99% and a specificity of 90%, respectively. For the RIA system, however, the level of clinical significance was found to be 10 ng Tg/ml with a sensitivity of 89% and a specificity of 95%. We could additionally define the grey-zone for the practical use of the IRMA (1-3 ng Tg/ml). The IRMA system is significantly more sensitive and detects more sera correctly positive than the Tg-RIA.(ABSTRACT TRUNCATED AT 250 WORDS)