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.     

Effects of ondansetron on portal hemodynamics in liver cirrhosis

OBJECTIVE: The double-blind randomized pilot study was undertaken to compare the effects of a 10-day course of ondansetron 8 mg/day and propranolol 80 mg/day perorally in treating portal hypertension. SUBIECTS AND METHODS: 16 patients with liver disease were enrolled in the study. Measurements of portal vein diameter, portal blood flow velocity and portal blood flow volume were done at days 1, 5 and 10 of treatment using duplex Doppler sonography. RESULTS: The propranolol group demonstrated a decrease in portal venous diameter, while patients treated with ondansetron exhibited reduced portal blood flow velocity values. A decreased portal blood flow volume was found in both groups after 10 days of therapy. CONCLUSION: No statistically significant differences were found between the groups with the exception of portal venous diameter which is significantly lower at the end of the treatment in the case of propranolol.     

Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin

The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the adrenal gland. It has been presumed that P-gp, rather than being involved in physiological cortisol secretion, plays a role in protecting the adrenacortical cells from xenobiotics. To explore this a study was performed on perfused bovine adrenal glands. Individual experimental groups were perfused with either a selective P-gp blocker (valspodar) alone, with a xenobiotic (mitotane or doxorubicin) alone or with both valspodar and a xenobiotic. The cumulative amounts of cortisol secreted in each individual group were calculated and the two-sample t-test was used to compare the mean values of cumulative amounts. The mean value of cortisol secreted from the group of adrenals perfused with the P-gp blocker was not significantly different from that of the control group. Treatment with either mitotane or doxorubicin decreased the amount of cortisol secreted but not significantly when compared to the amount of cortisol secreted in basal conditions. However, treatment with the P-gp blocker valspodar in addition to either mitotane or doxorubicin significantly decreased cortisol secreted compared to the amount of cortisol secreted by the glands treated with either mitotane (p=0.009) or doxorubicin (p=0.017) alone. The regressive changes discovered in all experimental groups were most prominent when valspodar was used with either mitotane or doxorubicin. We found that P-gp blockade increases by xenobiotic (mitotane and doxorubicin)-induced damage of adrenocortical cells, which points to a role of P-gp in the protection of adrenal gland from xenobiotics.     

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.