Correction: Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

[This corrects the article DOI: 10.1371/journal.pone.0158235.].

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 µg) compared to placebo 11 months after initiation of therapy on United Parkinson's Disease Rating Scale (UPDRS) III scores in the « off ¼ condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off ¼ condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01341431.

Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial.

BACKGROUND: No standard chemotherapy regimen exists for primary CNS lymphoma, reflecting an absence of randomised studies. We prospectively tested two promising methotrexate-based regimens, one more intensive and a milder regimen, for primary CNS lymphoma in the elderly population, who account for most patients. METHODS: In this open-label, randomised phase 2 trial, done in 13 French institutions, we enrolled immunocompetent patients who had neuroimaging and histologically confirmed newly diagnosed primary CNS lymphoma, were aged 60 years and older, and had a Karnofsky performance scale score of 40 or more. Participants were stratified by Karnofsky performance scale score (<60 vs ≥60) and treating institution and randomly assigned (1:1) to receive methotrexate (3·5 g/m(2)) with temozolomide (150 mg/m(2)) or methotrexate (3·5 g/m(2)), procarbazine (100 mg/m(2)), vincristine (1·4 mg/m(2)), and cytarabine (3 mg/m(2)). Neither regimen included radiotherapy; both included prophylactic G-CSF and corticosteroids. The primary endpoint was 1-year progression-free survival. Analysis was intent to treat, in a non-comparative phase 2 trial design. This study is registered with ClinicalTrials.gov, number NCT00503594. FINDINGS: Between July 16, 2007, and March 25, 2010, 98 patients were enrolled, of whom 95 were randomly assigned and analysed; 48 to methotrexate with temozolomide and 47 to methotrexate, procarbazine, vincristine, and cytarabine. 1-year progression-free survival was 36% (95% CI 22-50) in the methotrexate, procarbazine, vincristine, and cytarabine group and 36% (22-50) in the methotrexate with temozolomide group; median progression-free survival was 9·5 months (95% CI 5·3-13·8) versus 6·1 months (3·8-11·9), respectively. Objective responses were noted in 82% (95% CI 68-92) of patients in the methotrexate, procarbazine, vincristine, and cytarabine group versus 71% (55-84) of patients in the methotrexate with temozolomide group. Median overall survival was 31 months (95% CI 12·2-35·8) in the methotrexate, procarbazine, vincristine, and cytarabine group and 14 months (8·1-28·4) in the methotrexate with temozolomide group. No differences were noted in toxic effects between the two groups. The most common grades 3 and 4 toxicities in both groups were liver dysfunction (21 [4%] in the the methotrexate and temozolomide group and 18 [38%] in the methotrexate, procarbazine, vincristine, and cytarabine group), lymphopenia (14 [29%] and 14 [30%]), and infection (six [13%] and seven [15%]). To date, 33 (69%) patients in the methotrexate and temozolomide group have died, versus 31 (55%) in the methotrexate, procarbazine, vincristine and cytarabine group. Quality-of-life evaluation (QLQ-C30 and BN20) showed improvements in most domains (p=0·01-0·0001) compared with baseline in both groups. Prospective neuropsychological testing showed no evidence of late neurotoxicity. INTERPRETATION: In this study of two different methotrexate-based combination regimens in elderly patients, the efficacy endpoints tended to favour the methotrexate, procarbazine, vincristine, and cytarabine group. Both regimens were associated with similar, moderate toxicity, but quality of life improved with time, suggesting pursuing treatment in these poor prognosis patients is worthwhile. New alternatives are needed to improve response duration in this population. FUNDING: Schering-Plough/Merck and French Government.

[Depression and dementia]. / Démences et dépression.

Data from the literature devoted to the relationships between dementia and depression are controversial on account of numerous methodological biases (community studies or from neurological or psychiatric departments), categorical versus dimensional approaches and variability of assessment tools for depression, aim of the study (depression versus dementia or versus Alzheimer's disease, AD). The difficulty to discriminate depression from AD is largely overestimated due to the confusion between depression, depressive symptomatology and apathy. The distinction is greatly facilitated by taking into account the qualitative differences of the memory deficits and cerebral imagery. Distinction of depression from frontotemporal or subcortical dementias could be much more difficult. Relationships between depression and AD are controversial. Most reports of depression as a risk factor for AD in the subsequent years, actually describe depressed symptomatology linked to apathy in preclinical AD. However, some studies found a relationship between AD and depression occurring more than 10 years before the onset of AD symptomatology, suggesting some common risk factors. The so-called symptoms of depression in AD are more related to apathy and affective disturbances than to dysphoria. The frequency of major depressive episode (MDE), greatly varies according to studies, but the frequency of suicide is low. Depression in dementia is related to neurobiological factors as well as to psychological mechanisms. Therefore, its treatment should associate antidepressant drugs and psychological support directed to the patient and family.