Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.
Neurocysticercosis is an infection of the central nervous system caused by the larval form of the pork tapeworm Taenia solium. In the brain it occurs in two forms: parenchymal and extraparenchymal or racemose cysts. The clinical presentation of racemose cysts is pleomorphic, and is quite different from parenchymal cysticercosis. The clinical diagnosis of racemose cysts is quite challenging, with neuroimaging being the mainstay. However, the advent of newer brain imaging modalities has made a more accurate diagnosis possible. The primary focus of this article is racemose neurocysticercosis and its multitude manifestations, and includes a discussion of the newer diagnostic modalities and treatment options.
Objectives To determine whether preoperative dexamethasone reduces postoperative vomiting in patients undergoing elective bowel surgery and whether it is associated with other measurable benefits during recovery from surgery, including quicker return to oral diet and reduced length of stay. Design Pragmatic two arm parallel group randomised trial with blinded postoperative care and outcome assessment. Setting 45 UK hospitals. Participants 1350 patients aged 18 or over undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology. Interventions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia compared with standard care. Main outcome measures Primary outcome: reported vomiting within 24 hours reported by patient or clinician. Secondary outcomes: vomiting with 72 and 120 hours reported by patient or clinician; use of antiemetics and postoperative nausea and vomiting at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120 hours or discharge and at 30 days; time to return to fluid and food intake; length of hospital stay; adverse events. Results 1350 participants were recruited and randomly allocated to additional dexamethasone (n=674) or standard care (n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22; P=0.003). Additional postoperative antiemetics were given (on demand) to 265 (39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to 72 hours. There was no increase in complications. Conclusions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly reduces both the incidence of postoperative nausea and vomiting at 24 hours and the need for rescue antiemetics for up to 72 hours in patients undergoing large and small bowel surgery, with no increase in adverse events. Trial registration EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).
Background:Hashimoto encephalopathy (HE) is a poorly understood and often misdiagnosed entity with variable clinical spectrum. There are many uncertainties that still remain about this condition and the pathological significance of thyroid peroxidase (TPO) antibody.Objective:To characterize the clinical, laboratory and radiologic findings in patients with HE.Design:Retrospective analysis of clinical features and diagnostic test data.Main Outcome Measures:Clinical features, laboratory, radiologic, electroencephalography (EEG) findings associated with HE and therapeutic outcome.Results:Thirteen consecutive patients were identified as having HE. The median age at onset was 48.5 years (range, 19–62 years). There was a female preponderance (76.9%). Clinical manifestations were cognitive impairment and behavioral changes in 10 (76.9%), sleep disturbance in 9 (69.2%), seizures in 6 (46.1%), headache in 4 (30.8%), psychosis or paranoia in 5 (38.5%), transient symptoms in 6 (46.1%), myoclonus in 4 (30.8%), ataxia or gait disorder in 4 (30.8%). The most frequent laboratory abnormalities were increased TPO (n = 13) in all cases, increased thyroid stimulating hormone levels (n = 6), and increased erythrocyte sedimentation rate (n = 5). The cerebrospinal fluid protein level was elevated in 8 of 9 patients (88.8%). Magnetic resonance imaging abnormalities were present in 2 patients (15.4%). EEG changes were seen in 7 patients (53.8%). All but two patients showed significant therapeutic benefit with steroids.Conclusions:HE has a wide range of clinical, laboratory, and radiologic findings. All patients with an unexplained encephalopathy should be screened for this condition as treatment response is excellent. To the best of our knowledge, this is the largest single center clinical series of HE from the Indian subcontinent.
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