Use of re-randomized data in meta-analysis

Background  

Outcomes collected in randomized clinical trials are observations of random variables that should be independent and identically distributed. However, in some trials, the patients are randomized more than once thus violating both of these assumptions. The probability of an event is not always the same when a patient is re-randomized; there is probably a non-zero covariance coming from observations on the same patient. This is of particular importance to the meta-analysts.     

Antioxidants as a Preventive Treatment for Epileptic Process: A Review of the Current Status

Epilepsy is known as one of the most frequent neurological diseases, characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in pathways leading to neurodegeneration, which serves as the most important propagating factor, leading to the epileptic condition and cognitive decline. Moreover, there is also a growing body of evidence showing the disturbance of antioxidant system balance and consequently increased production of reactive species in patients with epilepsy. A meta-analysis, conducted in the present review confirms an association between epilepsy and increased lipid peroxidation. Furthermore, it was also shown that some of the antiepileptic drugs could potentially be responsible for additionally increased lipid peroxidation. Therefore, it is reasonable to propose that during the epileptic process neuroprotective treatment with antioxidants could lead to less sever structural damages, reduced epileptogenesis and milder cognitive deterioration. To evaluate this hypothesis studies investigating the neuroprotective therapeutic potential of various antioxidants in cells, animal seizure models and patients with epilepsy have been reviewed. Numerous beneficial effects of antioxidants on oxidative stress markers and in some cases also neuroprotective effects were observed in animal seizure models. However, despite these encouraging results, till now only a few antioxidants have been further applied to patients with epilepsy as an add-on therapy. Based on the several positive findings in animal models, a strong need for more carefully planned, randomized, double-blind, cross-over, placebo-controlled clinical trials for the evaluation of antioxidants efficacy in patients with epilepsy is warranted.     

Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate

In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.     

Medical considerations in the use of helicopters in mountain rescue

The outcome of patient care can be dramatically improved by bringing rapid rescue and medical care to the mountain rescue scene and by rapid transport to a medical facility. The use of a helicopter for these purposes is common. It is necessary when it has clear advantages for victims in comparison with ground rescue and transport. Helicopters should work within the existing emergency medical system and must be staffed by appropriate mountain rescue and medically trained personnel. Activation time should be as short as possible. Activation of a helicopter for a mountain rescue should primarily include indication and assessment of flight and safety conditions. No other mediators or delaying factors should be permitted. The main safety criteria are appropriate mountain rescue and flight training, competence of air and ground crews, radio communication between the air and ground crews, and mission briefing before the rescue. Criteria for a helicopter used for mountain rescue are proper medical and rescue equipment, load capacity, adequate space, and others. There are two main groups of indications for use of a helicopter for mountain rescue: the patient's condition and the circumstances at the site of the accident. All persons responsible for the activation of the helicopter rescue operation should be aware of specific problems in the mountains or wilderness.     

Use of modified PCR ribotyping for direct detection of Clostridium difficile ribotypes in stool samples

PCR ribotyping was modified to allow direct detection of Clostridium difficile from stool samples. Direct PCR ribotyping was possible in 86 out of 99 C. difficile-positive stool samples, and in 84 cases (84.8%), the ribotype determined directly from the stool sample was identical to the ribotype of the strain isolated from the same stool sample.     

When is it rational to participate in a clinical trial? a game theory approach incorporating trust, regret and guilt

ABSTRACT: BACKGROUND: Randomized controlled trials (RCTs) remain an indispensable form of human experimentation as a vehicle for discovery of new treatments. However, since their inception RCTs have raised ethical concerns. The ethical tension has revolved around "duties to individuals" vs. "societal value" of RCTs. By asking current patients "to sacrifice for the benefit of future patients" we risk subjugating our duties to patients' best interest to the utilitarian goal for the good of others. This tension creates a key dilemma: when is it rational, from the perspective of the trial patients and researchers (as societal representatives of future patients), to enroll in RCTs? METHODS: We employed the trust version of the prisoner's dilemma since interaction between the patient and researcher in the setting of a clinical trial is inherently based on trust. We also took into account that the patient may have regretted his/her decision to participate in the trial, while a researcher may feel guilty because he/she abused the patient's trust. RESULTS: We found that under most typical circumstances of clinical research, most patients can be expected not to trust researchers, and most researchers can be expected to abuse the patients' trust. The most significant factor determining trust was the success of experimental or standard treatments, respectively. The more that a researcher believes the experimental treatment will be successful, the more incentive the researcher has to abuse trust. The analysis was sensitive to the assumptions about the utilities related to success and failure of therapies that are tested in RCTs. By varying all variables in the Monte Carlo analysis we found that, on average, the researcher can be expected to honor a patient's trust 41% of the time, while the patient is inclined to trust the researcher 69% of the time. Under assumptions of our model, enrollment into RCTs represents a rational strategy that can meet both patients' and researchers' interests simultaneously 19% of the time. CONCLUSIONS: There is an inherent ethical dilemma in the conduct of RCTs. The factors that hamper full cooperation between patients and researchers in the conduct of RCTs can be best addressed by: a) having more reliable estimates on the probabilities that new vs. established treatments will be successful, b) improving transparency in the clinical trial system to ensure fulfillment of "the social contract" between patients and researchers.     

Dual processing model of medical decision-making

Background

Interoperable electronic health record (EHR) solutions are currently being implemented in Canada, as in many other countries. Understanding EHR users?? perspectives is key to the success of EHR implementation projects. This Delphi study aimed to assess in the Canadian context the applicability, the importance, and the priority of pre-identified factors from a previous mixed-methods systematic review of international literature.

Methods

A three-round Delphi study was held with representatives of 4 Canadian EHR user groups defined as partners of the implementation process who use or are expected to use EHR in their everyday activity. These groups are: non-physician healthcare professionals, health information professionals, managers, and physicians. Four bilingual online questionnaire versions were developed from factors identified by the systematic review. Participants were asked to rate the applicability and the importance of each factor. The main outcome measures were consensus and priority. Consensus was defined a priori as strong (?? 75%) or moderate (?? 60-74%) according to user groups?? level of agreement on applicability and importance, partial (?? 60%) when participants agreed only on applicability or importance, or as no consensus (< 60%). Priority for decision-making was defined as factors with strong consensus with scores of 4 or 5 on a five-point Likert scale for applicability and importance.

Results

Three Delphi rounds were completed by 64 participants. Levels of consensus of 100%, 64%, 64%, and 44% were attained on factors submitted to non-physician healthcare professionals, health information professionals, managers, and physicians, respectively. While agreement between and within user groups varied, key factors were prioritized if they were classified as strong (?? 75% from questionnaire answers of user groups), for decision-making concerning EHR implementation. The10 factors that were prioritized are perceived usefulness, productivity, motivation, participation of end-users in the implementation strategy, patient and health professional interaction, lack of time and workload, resources availability, management, outcome expectancy, and interoperability.

Conclusions

Amongst all factors influencing EHR implementation identified in a previous systematic review, ten were prioritized through this Delphi study. The varying levels of agreement between and within user groups could mean that users?? perspectives of each factor are complex and that each user group has unique professional priorities and roles in the EHR implementation process. As more EHR implementations in Canada are completed it will be possible to corroborate this preliminary result with a larger population of EHR users.