Use of benzodiazepines and cognitive performance in primary care patients with first cognitive complaints.

ABSTRACTThe aim of the present study is to investigate the impact of benzodiazepine use on cognitive performance in primary care patients with first cognitive complaints. The association between the exposition to benzodiazepines (short and long half-life) and cognitive performance, evaluated through the Mini Mental State Examination (MMSE), was tested through analysis of the covariance and logistic regression models. Within the 4,249 participants (mean age 77.0 ± 8.2, 66.4% women), 732 (17%) were on benzodiazepines. When compared with non-users, short- and long-acting benzodiazepine users presented overlapping adjusted MMSE mean scores (respectively, mean MMSE score: 25.3, 95%CI 25.2-25.5; 25.4, 95%CI 25.1-25.7, and 25.9, 95%CI 25.3-26.4; p = 0.156). When tested according to the logistical regression model, after adjusting for potential confounders, no association was found between short and long acting benzodiazepine use and a MMSE < 24 (respectively, OR 0.9, 95%CI 0.7-1.2; OR 0.8, 95%CI 0.7-1.3) as compared with non-users. In conclusion, according to the results of our study, benzodiazepine use seems not to impact on cognitive performance- as assessed with the MMSE- of primary care patients referring to GPs for first cognitive complaints.

Role of anticholinergic burden in primary care patients with first cognitive complaints.

BACKGROUND AND PURPOSE: Drugs with anticholinergic properties might have a negative impact on cognition, but findings are still conflicting. The association was evaluated between anticholinergic drugs and cognitive performance in primary care patients with first cognitive complaints. METHODS: From April 2013 to March 2014, 353 general practitioners administered the Mini-Mental State Examination (MMSE) to patients presenting with first cognitive complaints. Drug history was collected and the anticholinergic cognitive burden (ACB) was scored and categorized as ACB 0, ACB 1 and ACB 2+. A mixed effect linear regression model was used to assess the association between ACB and MMSE score. RESULTS: Of 4249 subjects entering the study (mean age 77 ± 8.2 years, 66.4% women and mean years of schooling 8.9 ± 4.5), 25.8% received at least one drug with anticholinergic action. According to multivariate analysis, and after adjustment for several confounders, subjects with ACB 2+ had a statistically significant lower MMSE score compared with those with ACB 0 (ß -0.63; 95% confidence interval -1.19; -0.07). Subjects with ACB 1 had a non-statistically significant lower MMSE score than those with ACB 0 (ß -0.11; 95% confidence interval -0.37; 0.15). CONCLUSIONS: Anticholinergic medication might affect cognitive function in people with first cognitive complaints. Alternatives should be taken into account when possible, balancing the benefits and harms of these medications.

Advanced MRI may complement histological diagnosis of lower grade gliomas and help in predicting survival.

MRI grading of grade II and III gliomas may have an important impact on treatment decisions. Occasionally,both conventional MRI (cMRI) and histology fail to clearly establish the tumour grade. Three cMRI features(no necrosis; no relevant oedema; absent or faint contrast enhancement) previously validated in 196 patients with supratentorial gliomas directed our selection of 68 suspected low-grade gliomas (LGG) that were also investigated by advanced MRI (aMRI), including perfusion weighted imaging (PWI), diffusion weighted imaging(DWI) and spectroscopy. All the gliomas had histopathological diagnoses. Sensitivity and specificity of cMRI preoperative diagnosis were 78.5 and 38.5 %, respectively, and 85.7 and 53.8 % when a MRI was included, respectively. ROC analysis showed that cut-off values of 1.29 for maximum rCBV, 1.69 for minimum rADC, 2.1 for rCho/Cr ratio could differentiate between LGG and HGG with a sensitivity of 61.5, 53.8, and 53.8 % and a specificity of 54.7, 43 and 64.3 %, respectively. A significantly longer OS was observed in patients with a maximum rCBV<1.46 and minimum rADC>1.69 (80 vs 55 months, p = 0.01; 80 vs 51 months, p = 0.002, respectively). This result was also confirmed when cases were stratified according to pathology (LGG vs HGG). The ability of a MRI to differentiate between LGG and HGG and to predict survival improved as the number of a MRI techniques considered increased. In a selected population of suspected LGG,classification by cMRI underestimated the actual fraction of HGG. aMRI slightly increased the diagnostic accuracy compared to histopathology. However, DWI and PWI were prognostic markers independent of histological grade.

How does the dehydration change the host-guest association under homogeneous and heterogeneous conditions?

In this study, the thermodynamic properties of association of some inorganic ions (ClO4(-) and SO4(2-)) with ß-cyclodextrins (ß-CD) in aqueous solution are determined under both free ß-CD and surface confined ß-CD conditions using atomistic simulations. The potential of mean force (PMF) is calculated as a function of the environment and the thermodynamic properties of association are deduced by integrating the free energy profiles. No inclusion complex between SO4(2-) and ß-CD is detected. Nevertheless, the PMF curve obtained for gold-confined CD seems to evidence a small minimum at a larger separation distance that shows specific interactions such as hydrogen bonding outside the cavity. As concerns ClO4(-), our simulations reveal the formation of an inclusion complex with free ß-CD in perfect agreement with the available experimental results. Nevertheless, we do not detect any formation of the host-guest inclusion complex under heterogeneous conditions. Finally, the differences observed as a function of the anions are interpreted through an atomistic description. The general trend of weaker complex stabilities with the increasing free energy of hydration of the anions is found in homogeneous systems.

Communication: Slab thickness dependence of the surface tension: toward a criterion of liquid sheets stability.

Microscopic Monte Carlo simulations of liquid sheets of copper and tin have been performed in order to study the dependence of the surface tension on the thickness of the sheet. It results that the surface tension is constant with the thickness as long as the sheet remains in one piece. When the sheet is getting thinner, holes start to appear, and the calculated surface tension rapidly decreases with thickness until the sheet becomes totally unstable and forms a cylinder. We assume here that this decrease is not due to a confinement effect as proposed by Werth et al. [Physica A 392, 2359 (2013)] on Lennard-Jones systems, but to the appearance of holes that reduces the energy cost of the surface modification. We also show in this work that a link can be established between the stability of the sheet and the local fluctuations of the surface position, which directly depends on the value of the surface tension. Finally, we complete this study by investigating systems interacting through different forms of Lennard-Jones potentials to check if similar conclusions can be drawn.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

EFNS guidelines on diagnosis and treatment of primary dystonias.

OBJECTIVES: to provide a revised version of earlier guidelines published in 2006. BACKGROUND: primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young people. DIAGNOSIS: primary dystonias are classified as pure dystonia, dystonia plus or paroxysmal dystonia syndromes. Assessment should be performed using a validated rating scale for dystonia. Genetic testing may be performed after establishing the clinical diagnosis. DYT1 testing is recommended for patients with primary dystonia with limb onset before age 30, and in those with an affected relative with early-onset dystonia. DYT6 testing is recommended in early-onset or familial cases with cranio-cervical dystonia or after exclusion of DYT1. Individuals with early-onset myoclonus should be tested for mutations in the DYT11 gene. If direct sequencing of the DYT11 gene is negative, additional gene dosage is required to improve the proportion of mutations detected. A levodopa trial is warranted in every patient with early-onset primary dystonia without an alternative diagnosis. In patients with idiopathic dystonia, neurophysiological tests can help with describing the pathophysiological mechanisms underlying the disorder. TREATMENT: botulinum toxin (BoNT) type A is the first-line treatment for primary cranial (excluding oromandibular) or cervical dystonia; it is also effective on writing dystonia. BoNT/B is not inferior to BoNT/A in cervical dystonia. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for primary generalized or cervical dystonia, after medication or BoNT have failed. DBS is less effective in secondary dystonia. This treatment requires a specialized expertise and a multidisciplinary team.

Azathioprine for multiple sclerosis.

BACKGROUND: Azathioprine (AZA) is an immunosuppressive drug widely prescribed for the treatment of multiple sclerosis (MS) until the first half of the 1990s. It could be an alternative to interferon beta because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, have been raised. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in MS. OBJECTIVES: To compare azathioprine with placebo. To assess the effect of azathioprine on major clinical outcomes (ie, disability progression and relapses) in patients with MS, and to evaluate the drug's safety. METHODS: The Cochrane MS Group search strategy was adopted to identify relevant articles. All randomised controlled trials comparing azathioprine treatment of a least 1 year duration with placebo for patients with MS were eligible for the review. Cohorts, case controls, case series and case reports were also considered to assess adverse effects. Regulatory agencies were additional sources of information for adverse effects. More details are available in the full review.

Azathioprine for multiple sclerosis.

BACKGROUND: Azathioprine is the most widely used immunosuppressive treatment in multiple sclerosis (MS). It is an alternative to interferon beta for treating MS also because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, has limited its use. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in multiple sclerosis. OBJECTIVES: To compare azathioprine versus placebo. To determine the effect of azathioprine on major clinical outcomes, i.e., disability progression and relapses in patients with multiple sclerosis. SEARCH STRATEGY: The Multiple Sclerosis Group's Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL- Issue 4, 2006), Cochrane Database of Systematic Reviews (CDSR - Issue 4, 2006), Database of Abstracts of Reviews of Effectiveness (DARE - searched 28.12.06) MEDLINE (PubMed) (1966 to December 2006), EMBASE (1980 to December 2006). Journals and reference lists were hand searched for relevant articles both to benefit and adverse effects. Regulatory agencies were additional sources of information for adverse effects. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing azathioprine treatment of a least one year duration with placebo for patients with multiple sclerosis. Cohorts, case controls, case series and case reports were also used to assess adverse effects. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data extracted by two independent authors. MAIN RESULTS: The five trials that met our criteria included 698 randomised patients: data from 499 (71.5%) were available for analysis of relapse frequency in patients at one year's, from 488 (70%) at two years' and from 415 (59.5%) at three years' follow-up. Azathioprine reduced the number of patients who had relapses during the first year of treatment (relative risk reduction [RRR] =20%; 95% CI = 5% to 33%), at two years' (RRR =23%; 95% CI = 12% to 33%) and three years' (RRR =18%; 95% CI = 7% to 27%) follow-up. These results were consistent in sensitivity analysis. There was no heterogeneity among the studies. Data from only three small trials with a total of 87 patients were available to calculate the number of patients who progressed during the first two to three years. There was a statistically significant benefit (RRR = 42%; 95% CI = 7% to 64%) of azathioprine therapy at three years' follow-up; this result was robust after sensitivity analyses and there was no heterogeneity among the trials. Gastrointestinal disturbances, bone marrow suppression and hepatic toxicity were greater in the azathioprine group rather than in the placebo group; they were anticipated, and, by monitoring and dosage adjustment, were easily managed. Withdrawals due to adverse effects were few, occurring mostly during the first year of azathioprine treatment and mainly due to gastrointestinal intolerance (5%). Data from the trials and from cohort and case controls studies available in the literature did not show an increase in risk of malignancy from azathioprine. A possible long-term risk of cancer from azathioprine may be related to a treatment duration above ten years and cumulative doses above 600 g. AUTHORS' CONCLUSIONS: Azathioprine is an appropriate maintenance treatment for patients with multiple sclerosis who frequently relapse and require steroids. Cumulative doses of 600 g should not be exceeded in relation to a possible increased risk of malignancy. Considering the trade off between the benefits and harms, azathioprine is a fair alternative to interferon beta for treating multiple sclerosis. A logical next step for future trials would seem the direct comparison of azathioprine and interferon beta. In fact the direct comparison between these two widely used treatments in multiple sclerosis has not been made.

Dietary interventions for multiple sclerosis.

BACKGROUND: Clinical and experimental data suggest that certain dietary regimens, particularly those including polyunsaturated fatty acids (PUFAs) and vitamins might improve outcomes in people with multiple sclerosis (MS). Diets and dietary supplements are much used by people with MS in the belief that they might improve disease outcomes. OBJECTIVES: We performed a Cochrane review of all randomised trials of dietary regimens for MS with the aim of answering MS consumers' questions regarding the efficacy and safety of these interventions. SEARCH STRATEGY: We searched the Cochrane MS Group trial register (February 2006), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 1, 2006, MEDLINE (PubMed) (1966 to March 2006), EMBASE (1974 to March 2006) and the bibliographies of papers found. SELECTION CRITERIA: All randomised controlled trials comparing a specific dietary intervention, diet plan or dietary supplementation, with no dietary modification or placebo, were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles, assessed trial quality and extracted data. Trial quality was poor, particularly as regards descriptions of randomisation, blinding and adverse event reporting. Some studies had large numbers of drop-outs; dropouts were never included in the analyses. MAIN RESULTS: PUFAs did not have a significant effect on disease progression, measured as worsening of Disability Status Scale. Omega-6 fatty acids (11-23 g/day linoleic acid) had no benefit in 75 relapsing remitting (RR) MS patients (progression at two years: relative risk (RR)=0.78, 95% CI [0.45 to 1.36]) or in 69 chronic progressive (CP) MS patients (RR=1.67, 95% CI [0.75 to 3.72]. Linoleic acid (2.9-3.4 g/day) had no benefit in CPMS (progression at two years: RR=0.78, 95% CI [0.43 to 1.42]). Slight decreases in relapse rate and relapse severity were associated with omega-6 fatty acids in some small studies, however these findings are limited by the limited validity of the endpoints.Omega-3 fatty acids had no benefit on progression at 12 months in 14 RRMS patients or at 24 months in 292 RRMS patients (RR=0.15, 95% CI [0.01 to 3.11], p= 0.22 at 12 months, and 0.82 95% CI [0.65 to 1.03], p=0.08, at 24 months). The low frequency of reported adverse events suggests no major toxicity associated with PUFA administration. No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria. AUTHORS' CONCLUSIONS: PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), and does not substantially affect the risk of clinical relapses over 2 years. However, the data available are insufficient to assess any potential benefit or harm from PUFA supplementation. Evidence bearing on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of diets interventions in MS.

The genetic resistance to gastro-intestinal strongylids in Appenninica sheep: preliminary results.

Heritability parameters of resistance to gastro-intestinal strongylids, measured as FEC (Faecal Egg Count), were evaluated in the Appenninica sheep breed. FEC heritability coefficient was 0.11 +/- 0.061 while FEC repeatability coefficients were 0.58 +/- 0.085 and 0.76 +/- 0.223 in adult females and lambs respectively. Subjects were classified, based on FEC, into three different levels of resistance to strongylids. Ewes belonging to the 'resistant class' should be conveniently exploited in mating schemes, in order to provide a method, alternative to drug administration, for a long-term parasite control; this would result particularly helpful under those production systems, such as organic farming, where the use of drugs is not allowed or limited.

Onset and progression of primary torsion dystonia in sporadic and familial cases.

Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/- 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.

A combination of diagnostic tools for rapid screening of ovine listeriosis.

A combined serological and PCR method for the detection of Listeria monocytogenes infection in symptomatic and asymptomatic ovine flocks was evaluated. Seventy-eight milk samples and 157 serum samples were analysed using a L. monocytogenes PCR detection kit and an anti-listeriolysin O IgG immunoassay kit. The combined use of these commercial kits allowed a rapid and effective detection of L. monocytogenes infection in both the early stage, before seroconversion, and in a later phase, even after antibiotic therapy.

Interobserver agreement in the diagnosis of multiple sclerosis.

Interobserver agreement in the clinical diagnosis of multiple sclerosis (MS) among six neurologists was evaluated. Three of them participated in a study of the clinical diagnosis of MS, the Italian Multicenter Study (IMS). The raters examined the clinical forms of MS of 50 patients randomly selected from among 430 patients recruited from the IMS. For each patient, neurologists were asked to make a diagnosis according to the McDonald-Halliday classification system of MS. The overall agreement on the diagnosis (MS present or absent) was fair, with no difference noted between the two groups of raters. Considering the six diagnostic levels instead, the reliability was higher for the neurologists participating in the IMS program. These neurologists agreed particularly on the Clinically Definite and Progressive Possible classifications. Complete disagreement was observed for the Early Probable or Latent and Progressive Probable classifications. Because of the different level of agreement on diagnosis, we suggest separate consideration of Clinically Definite and Progressive Probable MS cases in clinical trials and epidemiologic studies of this disease.

Clinical and magnetic resonance features of the classic and akinetic-rigid variants of Huntington's disease.

We studied 32 patients with confirmed Huntington's disease (HD); six (mean age, 31.7 years) had the akinetic-rigid form and 26 (mean age, 46.1 years) had the classic hyperkinetic form. Clinical examination included a count of abnormal involuntary movements, motor self-sufficiency evaluation by the Physical Disability Rating Scale, cognitive function assessment by the Mini-Mental State examination, and a verbal fluency test. Magnetic resonance imaging permitted measurement of bicaudate diameter, a sensitive indicator of caudate atrophy in HD. Patients with the akinetic-rigid form of HD were younger and had earlier disease onset than those with the classic form of HD. All patients with akinetic-rigid HD (group 1) had striatal hyperintensity on T2-weighted magnetic resonance images; seven patients with classic HD (group 2) had a similar abnormality. Groups 1 and 2 were in fact similar in all other respects, except that the number of abnormal involuntary movements was greater in group 2. Groups 1 and 2 together had significantly younger age at onset, lower Mini-Mental State Examination score, more severe motor disability, worse verbal fluency test result, and greater bicaudate diameter than the 19 patients with classic HD without magnetic resonance signal abnormality (group 3) and appear to be a uniform population, distinct from group 3. The abnormalities on magnetic resonance images indicated greater striatal damage in groups 1 and 2, which could be the neuroanatomic substrate of their greater motor and cognitive compromise.

The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A controlled study.

In a double-blind study versus placebo, the serotonergic agent m-chlorophenylpiperazine (mCPP) was administered to 20 healthy control subjects and 19 migraineurs to investigate the ability of mCPP (0.5 mg/kg) to induce typical migraine attacks. In the following 24 hours there were more migraines after mCPP than after placebo in both groups. These findings are consistent with involvement of 5HT2B,2C,1A receptor subtypes in the pathophysiology of migraine.

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.

BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Synthesis and CLOGP correlation of imidooxy anticonvulsants.

Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss structure activity and the Craig plot analytical approaches as well as a semiempirical method. CLOG P analysis was also applied to this series after experimentally determining the NOR fragment. All compounds were minimized and these physicochemical parameters correlated to anticonvulsant activity. Several interesting substituted benzyloxy compounds emerged from this study: the 2',4'-dichloro (2b), 4'-(trifluoromethyl) (2c), 2'-bromo (2d), 3'-chloro (2o), 2'-chloro (2r), 2'-fluoro (2p), and 3'-fluoro (2w) analogs, all of which had comparable, or better activity than the parent unsubstituted analog (2a). X-ray crystal analysis of the active 2a versus inactive N-benzyl-2-azaspiro[4.4]nonane-1,3-dione (10) is discussed.

Results from an international case-control study of childhood brain tumors: the role of prenatal vitamin supplementation.

An international case-control study of primary pediatric brain tumors included interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of population controls. Data are available on maternal vitamin use during pregnancy for 1051 cases and 1919 controls from eight geographic areas in North America, Europe, and Israel. Although risk estimates varied by study center, combined results suggest that maternal supplementation for two trimesters may decrease risk of brain tumor (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5-0.9), with a trend of less risk with longer duration of use (p trend = 0.0007). The greatest risk reduction was among children diagnosed under 5 years of age whose mothers used supplements during all three trimesters (OR 0.5, CI 0.3-0.8). This effect did not vary by histology and was seen for supplementation during pregnancy rather than during the month before pregnancy or while breast feeding. These findings are largely driven by data from the United States, where most mothers took vitamins. The proportion of control mothers who took vitamins during pregnancy varied tremendously: from 3% in Israel and France, 21% in Italy, 33% in Canada, 52% in Spain and 86 to 92% at the three U.S. centers. The composition of the various multivitamin compounds taken also varied: the daily dose of vitamin C ranged from 0 to 600 mg, vitamin E ranged from 0 to 70 mg, vitamin A ranged from 0 to 30,000 IU, and folate ranged from 0 to 2000 micrograms. Mothers also took individual micronutrient supplements (e.g., vitamin C tablets), but most mothers who took these also took multivitamins, making it impossible to determine potential independent effects of these micronutrients.

Survival in multiple system atrophy: a study of prognostic factors in 59 cases.

The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.