Long-term survival in amyotrophic lateral sclerosis: a population-based study.

OBJECTIVE: To determine the long-term survival in amyotrophic lateral sclerosis (ALS) and identify predictors of prolonged survival in a population-based cohort of newly diagnosed patients. METHODS: An incident cohort from a population-based registry during the years 1998 through 2002 in Lombardy, Italy was followed until death or to February 28, 2013. Age, sex, date of onset of symptoms, site of onset, date of diagnosis, and El Escorial diagnostic category were collected. Survival was assessed using Kaplan-Meier curves. Cox proportional hazards function was used to identify independent prognostic predictors. Standardized mortality ratios (SMRs) were used to assess the 5-year and 10-year excess mortality of ALS patients. RESULTS: Included were 280 men and 203 women aged 18 to 93 years. Spinal onset ALS was present in 312 cases (64.6%). Definite ALS was diagnosed in 213 cases (44.1%), probable ALS in 130 (26.9%), possible ALS in 93 (19.3%), and suspected ALS in 47 (9.7%). The cumulative time-dependent survival at 1, 5, and 10 years from diagnosis was 76.2%, 23.4%, and 11.8%, respectively. Independent predictors included younger age, the diagnosis of possible/suspected ALS, spinal onset, and symptoms having started >12 months previously at diagnosis. SMR was 9.4 at 5 years and 5.4 at 10 years. SMR at 10 years was higher until age 75 year, predominating in women, and became nonsignificant for males thereafter. INTERPRETATION: The outcome in ALS varies with phenotype. Longer survival is predicted by younger age, spinal onset, male gender, and suspected ALS. After age 75 years, 10-year survival in men with ALS is similar to the general population.

Physical activity and amyotrophic lateral sclerosis: a European population-based case-control study.

OBJECTIVE: To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). METHODS: From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities that caused an individual to breath hard at least once per month and was coded as none, job-related, and/or sport-related. Sport-related and work-related physical exercise were quantified using metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma, and job-related physical activity) and expressed as odds ratios (ORs) and adjusted ORs (Adj ORs) with 95% confidence intervals (CIs). RESULTS: Overall physical activity was associated with reduced odds of having ALS (Adj OR=0.65, 95% CI=0.48-0.89) as were work-related physical activity (Adj OR=0.56, 95% CI=0.36-0.87) and organized sports (Adj OR=0.49, 95% CI=0.32-0.75). An inverse correlation was observed between ALS, the duration of physical activity (p=0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR=0.34, 95% CI=0.21-0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. INTERPRETATION: Physical activity is not a risk factor for ALS and may eventually be protective against the disease.

Frequency and time to relapse after discontinuing 6-month therapy with IVIg or pulsed methylprednisolone in CIDP.

BACKGROUND: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. METHODS: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. RESULTS: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). CONCLUSIONS: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP.

In-hospital costs in patients with seizures and epilepsy after stroke.

OBJECTIVES: To verify the net effect of seizures after stroke on the use of in-hospital health care resources. METHODS: Consecutive patients with first-ever stroke were admitted to the stroke unit of a Moscow hospital and followed prospectively until death or discharge. Each patient experiencing seizures was matched for age, sex, stroke type, National Institutes of Health Stroke Scale score at admission, and stroke risk factors to 2+ patients with no seizures, as controls. Resources consumed included length of hospital stay, admission to the intensive care unit (ICU), diagnostic tests, medical consultations and treatments. Cost estimates were based on the Russian National Health Service perspective. RESULTS: The sample comprised 30 patients with in-hospital seizures and 70 matched controls. Patients dying in hospital were 15 of 30 (50%) versus 4 of 70 (5.7%) (p < 0.001). The overall cost of hospital stay was only slightly (nonsignificantly) higher in patients with seizures, but the cost was significantly higher in patients who died than in patients who were discharged alive. Compared to the controls, patients with seizures spent more intensive care unit (ICU) days and required more computed tomography (CT) scans, x-rays, endoscopies, and specialist consultations, causing higher in-hospital costs. SIGNIFICANCE: In patients with first-ever stroke, seizures per se do not increase the overall in-hospital costs. However, the higher than expected mortality in patients with seizures is associated with additional hospital costs.

An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program.

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.

Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP).

The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5-T12 injury, and grade A or B of the ASIA Impairment Scale (AIS), admitted within 8 h, hemodynamically stable, were randomized to MP according to the NASCIS III protocol or EPO iv (500 UI/kg, repeated at 24 and 48 h). Patients were assessed by an investigator blind to treatment assignment at baseline and at day 3, 7, 14, 30, 60 and 90. Primary end point: number of responders (reduction of at least one AIS grade). Secondary end points: treatment safety and the effects of drugs on a number of disability measures. Frequentistic and post hoc Bayesian analyses were performed. Eight patients were randomized to MP and 11 to EPO. Three patients (27.3 %) on EPO and no patients on MP reached the primary end point (p = 0.17). No significant differences were found for the other disability measures. No adverse events or serious adverse events were reported in both groups. The Bayesian analysis detected a 91.8 % chance of achieving higher success rates on the primary end point with EPO in the intention-to-treat population with a 95 % chance the difference between EPO and MP falling in the range (-0.10, 0.51) and a median value of 0.2. The results of Bayesian analysis favored the experimental treatment.

Sensitivity and predictive value of anti-GM1/galactocerebroside IgM antibodies in multifocal motor neuropathy.

BACKGROUND: Increased titres of serum IgM antibodies to GM1 ganglioside are often associated with multifocal motor neuropathy (MMN). Testing for IgM antibodies to other antigens including GM2, the mixture of GM1 and galactocerebroside (GM1/GalC) and the disulfated heparin disaccharide NS6S were reported to increase the sensitivity of antibody testing in MMN even if it is unclear whether the specificity and positive (PPV) or negative predictive value (NPV) for MMN were also affected. METHODS: We measured IgM antibodies to GM1, GM2, galactocerebroside, GM1/GalC and NS6S in 40 consecutive patients with MMN and 142 controls with other neuropathies or related diseases and compared their sensitivity, specificity and PPV for MMN. RESULTS: With the only exception of anti-GM2 and, partially, anti-NS6S antibodies, IgM antibodies to the antigens tested were more frequent in MMN than in controls. Increased titres of anti-GM1 IgM were found in 48% of MMN patients with a specificity of 93% and PPV for MMN of 66%. Anti-GM1/GalC antibodies were present in all anti-GM1 positive MMN patients and in 11 additional patients (28%) with MMN raising the sensitivity of antibody testing to 75%. The specificity (85%) and PPV (59%) for MMN was, however, moderately reduced compared to anti-GM1 IgM, even if they rose with increasing anti-GM1/GalC titres. IgM antibodies to GM2, NS6S and galactocerebroside were found in 8%, 23% and 60% of MMN patients but had a low specificity and PPV for MMN. CONCLUSIONS: Testing for anti-GM1/GalC IgM significantly increased the sensitivity of antibody testing in MMN compared to anti-GM1 alone (p=0.021) and may represent a preferred option for GM1 reactivity testing in MMN.

Comprehensive educational plan for patients with epilepsy and comorbidity (EDU-COM): a pragmatic randomised trial.

BACKGROUND: The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. OBJECTIVE: The EDU-COM study is a randomised, pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity. METHODS: 174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6-month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes. RESULTS: The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups. CONCLUSIONS: A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. Registered at ClinicalTrials.gov, identifier NCT01804322, (http://www.clinicaltrials.gov).

Reliability of clinical diagnosis of dystonia.

BACKGROUND: There is only one small single-center study on the reliability of the diagnosis of focal dystonia. The aim of this study was to assess the inter-rater reliability of dystonia diagnosis among neurologists with different professional experience. METHODS: Twenty-nine adults (18 with dystonia, 9 with other movement disorders, and 2 healthy controls) were videotaped while undergoing neurological examination and during the process of collecting information on the history of their condition. Each case was diagnosed by 35 blind raters (12 general neurologists, 21 neurology residents, and 2 experts in movement disorders) from different hospitals. Sensitivity and specificity were calculated confronting raters with the gold standard (the caring physician). Inter-rater agreement was measured by the Kappa statistic. RESULTS: Specificity and sensitivity were 95.2 and 66.7%, 76.3 and 75.2%, 84.6 and 71.6% for experts, general neurologists, and residents, respectively. Kappa values on dystonia diagnosis ranged from 0.30 to 0.46. The agreement was moderate for experts and residents (0.40-0.60) and fair for general neurologists (0.20-0.40). Kappas were the highest among experts for cranial and laryngeal dystonia (0.61-1), but not for cervical dystonia (0.37). CONCLUSIONS: The diagnosis of dystonia is difficult and only partially mirrors a physician's background.

Prevalence and incidence of epilepsy in a well-defined population of Northern Italy.

OBJECTIVE: To calculate prevalence and incidence of epilepsy using administrative records. METHODS: Claim records from the administrative district of Lecco, Northern Italy (population 311,637; 2001 census), collected during the years 2000-2008, were the data source. Patients of all ages were included. Based on previous findings from our group, the most accurate algorithm to detect epilepsy was the combination of electroencephalography (EEG) (ad hoc code) (at least one during the study period) and antiepileptic drugs (AEDs) (ATC code) (taken in 2008). Using this algorithm, the prevalence of epilepsy for the year 2008 was calculated. The reference population for prevalence was the population residing in the study area during the year 2008. Incident epilepsy cases were a subset of prevalent cases among patients not traced in the years 2000 through 2003. Average annual incidence rates were calculated for 2004 through 2008, taking for reference the person-years of exposure in the resident population. We calculated crude, adjusted (using positive and negative predictive values), and standardized (to the Italian and World population) prevalence and incidence. RESULTS: In 2008, 1,504 patients met the inclusion criteria, giving a prevalence of 4.57 per 1,000 (women 4.26; men 4.89). Prevalence tended to rise slightly with age. There were 864 incident cases, giving an average annual incidence of 53.41 per 100,000 (women 50.98; men 55.95). Incidence rates peaked in the elderly. The adjusted prevalence was 4.42 and the adjusted incidence 47.05. Standardized prevalence and incidence were, respectively, 4.30 per 1,000 and 48.35 per 100,000 (Italian population) and 3.79 per 1,000 and 44.74 per 100,000 (World population). SIGNIFICANCE: The prevalence of epilepsy in the Lecco district was comparable to other studies, whereas the incidence was among the highest. With adjustments, administrative records are a cost-effective instrument to monitor epilepsy frequency.

Knowledge and attitudes towards epilepsy in Zambia: a questionnaire survey.

Misconception and stigma towards epilepsy have a profound impact on this disease in Africa. An unselected sample of Zambian people was interviewed to investigate their knowledge and attitudes towards epilepsy. Proper/improper answers were scored, and a composite score was developed with negative values for unsatisfactory awareness and high stigma levels. The sample comprised 231 people residing in urban (107) or in rural (124) areas. The median and interquartile range of scores for epilepsy awareness and stigma were, respectively, -1 (-3; +1) and +1 (-1; +6). Poor education was the only significant predictor of unsatisfactory awareness (p=0.0131), while education and residency were significantly associated with stigma (p<0.0001 and p=0.0004). Rural people were mostly in the highest stigma level (44.2%) and urban people in the lowest stigma level (60.4%). Misconception and negative attitudes towards epilepsy among Zambian people reflect poor education and rural residency.

An educational campaign toward epilepsy among Italian primary school teachers: 1. Survey on knowledge and attitudes.

A questionnaire survey was undertaken to assess the impact of a nationwide educational campaign about epilepsy on the knowledge and attitudes toward the disease among Italian primary school teachers. Five hundred and eighty-two teachers participated. All interviewees were aware of the existence of epilepsy, and most of them had direct experience with the disease. Answers about frequency, causes, outcome, and response to treatments were variable and not correlated with age, residency, and years of experience. Teachers had positive attitudes toward epilepsy, except for the idea that driving and sports can be safe for people with epilepsy. Epilepsy and its treatment were considered a source of learning disability and social disadvantages. Several teachers declared themselves being unable to help a child having seizures. Calling an ambulance was a frequent action. Knowledge and attitudes toward epilepsy are improved compared with those reported in our previous studies. Although this may be a positive reflection of the increasing knowledge and the greater availability of information on epilepsy, there are still areas of uncertainty and incorrect behaviors.

Treatment patterns and healthcare resource utilization among patients with alopecia areata: A real-world chart review in South Korea.

Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September-November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22-68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0-20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies.

Acceptance of epilepsy surgery in the pediatric age - what the parents think and what the doctors can do.

Epilepsy surgery (ES) in pediatrics is safe and effective but can be underutilized. Possible barriers could be parental resistance and doctor inertia. We surveyed 138 parents of pediatric patients with epilepsy and found that 25.2% were opposed to this treatment. However, upon completing the questionnaire that contained factual information about ES, 50.4% of the responders stated that they had become more favorable vs. 3.3% more contrary and 46.3% unchanged. Parents of prepubescent patients were most receptive (p=0.0343) and more likely to shift to a more favorable attitude. Thus, pediatric neurologists should not hesitate to discuss ES as soon as indicated, providing all necessary information to increase acceptance. However, among 60 child neurologists surveyed, 60% did not fully comply with guidelines or follow accepted standards of practice, indicating that they may not be apt to provide proper parental guidance. We conclude that education of both practicing neurologists and parents is needed to facilitate the process.

Migraine and pregnancy: an internet survey.

Data in the literature show that migraine tends to improve during pregnancy in most migrainous women. The aim of this Internet survey was to obtain the most likely cross section of the situation in the general population with respect to the presence and course of migraine in pregnancy. All women who participated were asked to answer questions pertaining to their history of pregnancy and headache. One thousand and eighteen women participated in the survey; only 775 met the eligibility criteria for inclusion. One hundred and ninety-five women (25.2 %) reported having had a headache only before pregnancy, 425 (54.8 %) before and during pregnancy, and 155 (20.0 %) only during pregnancy. Women suffering from headache before and/or during pregnancy were much more likely to have headaches with more migrainous features at the ID Migraine Screener test when compared to women whose headache began during pregnancy. "Definite migraines" were 277/620 (44.7 %) and 26/155 (16.8 %), respectively, in the two groups (p < 0.0001). Among the 620 females that suffered from headache before pregnancy, 375 (60.5 %) improved, 195 (31.5 %) showed complete resolution of the disorder, and 180 (29.0 %) had a reduction in headache frequency. Moreover, the multinomial logistic model (with headache pattern as dependent variable) proved fetal presentation as significant (p = 0.0042). Women with "new headache" (No/Yes pattern) had an OR (95 % CI) of 1.9 (1.2-3.0) of breech presentation at delivery versus those with a stable pattern of headache (Yes/Yes). Finally, women with not recent pregnancy stated they suffered from headache less than the women with recent pregnancy.

Barriers toward epilepsy surgery. A survey among practicing neurologists.

PURPOSE: Guidelines for refractory epilepsy recommend timely referral of potential surgical candidates to an epilepsy center for evaluation. However, this approach is seldom a priority for treating neurologists, possibly because of inertia of previous practice and personal attitudes, leading to a buildup of psychosocial disabilities and increased risk of morbidity and mortality. The aim of this study was to assess knowledge and attitudes toward epilepsy surgery among practicing neurologists and identify the barriers that delay the treatment. METHODS: We surveyed 183 Italian adult and child neurologists with an ad hoc questionnaire exploring physicians' willingness to refer patients for epilepsy surgery when such treatment may be indicated. Thirteen of 14 questions had graded answers ranging from 1 (unfavorable to surgery) to 10 (favorable). We compared the overall scores and per-question scores of the neurologists versus a group of academic and clinical leaders in the field. KEY FINDINGS: The neurologists gave responses characterized by extreme variability (i.e., wide response interquartile range) around intermediate scores. Experts had higher and less variable scores favoring surgery. The two groups differed significantly on issues such as how long to pursue pharmacologic treatment and information about indications and outcome of surgery. Multivariate analysis indicated that neurologists' attitudes correlated with the number of patients referred for surgery (p < 0.01) and the geographical region where specialty was attained (p < 0.01). Other variables such as years in practice, number of patients treated for epilepsy, or type of specialty had no predictive value on physicians' behavior. SIGNIFICANCE: The majority of Italian neurologists have highly variable attitudes toward epilepsy surgery, reflecting ambivalence and uncertainty toward this type of treatment. About two thirds of responders are nonaligned with the opinion leaders, mainly due to differences in handling pharmacologic treatment and information regarding epilepsy surgery, which affect their attitudes and ultimately patient management. Strategies that may solve the lack of agreement include reinforcing the concept of pharmacoresistance and associated risks, as opposed to the safety and potential benefits of surgery, the use of epilepsy quality measures during follow-up, and the adoption of structured referral sheets and greater involvement of patients in decision making. These measures should facilitate the referral of potential candidates for surgical evaluation and improve overall quality of care.

Acceptance of epilepsy surgery among adults with epilepsy--what do patients think?

Physician inertia is usually blamed for the underutilization of epilepsy surgery (ES) at the cost of increased patient disability and risk of mortality. Investigations on selected groups of patients with intractable TLE and minorities suggested that patient beliefs may also limit access to ES. To assess acceptance of ES among "mainstream" patients, we distributed an ad hoc questionnaire to 228 adults attending epilepsy clinics and found widespread fears and misconceptions leading to unfavorable perception of ES, irrespective of diagnosis, seizure type, and degree of intractability. Moreover, while a group firmly rejected ES, the majority became more favorable when given further information about modality, rationale, and expected outcome of ES. Attitude changes correlated with patient's social profile. Neurologists are responsible for providing all pertinent information to potential surgical candidates as soon as indicated. Therefore, an untimely or inadequate intervention of the treating physician constitutes an additional barrier to optimal utilization of ES.

Coffee and amyotrophic lateral sclerosis: a possible preventive role.

The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007-2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk.

Low noise, low heat dissipation, high gain AC-DC front end amplification for scanning probe microscopy.

We report here on the design, construction and testing of a vacuum compatible AC-DC amplification system for low signal measurements with scanning probes. The most important feature of this new amplification system is incorporated within the head of a scanning tunneling microscope (STM). This is achieved with a very low thermal dissipation radio frequency amplifier at the STM head. The amplifier gain is higher than 40 dB and has a 50 dB maximum. Further, the AC noise figure is 0.7 dB between 100 and 1000 MHz. The noise induced in the DC amplifier is less than 2 pA RMS (root mean square), which enables the microscope to scan over soft insulating molecular layers. Thermal drift at the STM tip-sample interface is below 0.1 nm min(-1) both in air and in vacuum operation. Atomic resolution on highly oriented pyrolytic graphite surfaces is reliably achieved. Spin noise measurements are provided as an example of an application.

Voluptuary Habits and Risk of Frontotemporal Dementia: A Case Control Retrospective Study.

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.