Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Periodic lateralized epileptiform discharges: etiology, clinical aspects, seizures, and evolution in 130 patients.

The purpose of this study was to analyze the clinical aspects in 130 patients presenting periodic lateralized epileptiform discharges (PLEDs) in their EEG and to compare these results with those found in the literature. Etiology, neurologic deficit, seizure occurrence, and evolution were studied in each patient by historical review. The recordings were obtained on 8- or 16-channel EEGs with electrode placement according to the International 10-20 System. Recordings containing PLEDs were selected. PLEDs were defined as repetitive periodic, focal, or hemispheric epileptiform discharges (spikes, spike and waves, polyspikes, sharp waves) usually recurring every 1 to 2 seconds. The statistical study was carried out via the chi(2) test using the computer program SPSS. The main etiology found in this group of patients was stroke (61 of 130 patients). Other processes found were brain infections, tumors, hematomas, and several other entities grouped together as miscellaneous (anoxic encephalopathy, subarachnoid hemorrhage, craniocerebral trauma, Creutzfeldt-Jacob disease, migraine, multiple sclerosis, and aminophylline intoxication). Half of these patients (65 of 130) developed seizures, mostly partial motor seizures. No significant relation between etiology and seizures was found (chi(2) = 2.81, P = 0.4222). Seizures recurred in 14 of 130 patients during a follow-up of 14.5 months. PLEDs were not recorded in any EEG at the time of seizure recurrence. PLEDs constitute a distinctive but uncommon EEG phenomenon of repetitive, periodic, and stereotyped lateralized complexes. In agreement with the literature, PLEDs were associated with an acute process and occurred early during the course of the illness in all patients studied and were usually associated with structural lesions, with stroke being the main etiology. Traditionally, seizures occur with PLEDs but it is also accepted that they can exist in patients who never develop epileptic activity, either clinically or electrically, as demonstrated in 50% of the patients studied. No significant association between seizures and any etiology could be found. It was not demonstrated that the occurrence of seizures may influence the outcome in any way.     

What methods do stakeholders prefer for feeding back performance data: a qualitative study in palliative care.

OBJECTIVE: To investigate the opinions of stakeholders (service commissioners and providers) on how performance data should be presented, in order to develop effective feedback methods to facilitate the use of these data in decision making. DESIGN: A qualitative analysis of semi-structured face-to-face and telephone interviews. League tables and fictional box plots were presented as an illustrative guide. The themes covered in the interviews were the effectiveness of these two feedback formats, their positive and negative characteristics, and ideas for new and improved feedback mechanisms. PARTICIPANTS: Thirty-six stakeholders representing a range of clinical and non-clinical roles within palliative care and the wider health care system across a variety of statutory and non-statutory organizations from London and the West Midlands. RESULTS: Box plots were received more positively than league tables, and qualitative information was considered more appropriate than pictorial feedback. Conventional methods such as league tables and box plots were judged to lack essential information on which important decisions could be based, such as additional contextual information and the methodological assumptions of the instrument. Both feedback methods were considered useful as an impetus to further discussion. There was a consensus that feedback should be constructive and able to be adapted to the organizational realities in which UK health services function. CONCLUSION: Qualitative research was viewed as the right evidence for gaining an understanding of the quality of end of life care. Stakeholders highlighted the importance of the lay perspective, which requires approaches that illuminate the subjective meanings of patient experience.     

缺血性卒中或短暂性脑缺血发作患者的卒中预防指南

这份新声明旨在为缺血性卒中或短暂性脑缺血发作存活者的缺血性卒中预防提供全面和及时的循证推荐，循证推荐包括对危险因素的控制，动脉粥样硬化性疾病的干预措施，心源性栓塞的抗栓治疗以及非心源性卒中抗血小板药的应用。另外，还为其他多种特殊情况下复发性卒中的预防提供了推荐、包括动脉夹层分离、卵圆孔未闭、高同型半胱氨酸血症、高凝状态、镰状细胞病、脑静脉窦血栓形成、女性卒中（特别是与妊娠和绝经后激素替代治疗相关卒中），脑出血后肮凝药的应用，以及该指南在高危人群中执行和应用的特殊措施。     

Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Repetitive, negligible force reaching in rats induces pathological overloading of upper extremity bones.

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption. INTRODUCTION: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. MATERIALS AND METHODS: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA. RESULTS: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4-6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks. CONCLUSIONS: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.     

Comorbidities of migraine: a user-friendly overview

Comorbidity of migraine is important from a number of different perspectives. Co-occurrence of different diseases may complicate diagnosis as a high degree of symptomatic overlap may occur among conditions associated with migraine. Furthermore, comorbidity has also important implications for treatment. The commonest comorbidities of migraine are represented by psychiatric disorders, epilepsy, tremor, stroke, and cardiovascular abnormalities.