Psychological responses to blood donated by men who have sex with men.

BACKGROUND: Restrictions previously limiting the ability of men who have sex with men to donate blood are being eased in a number of nations worldwide. In the context of these changes, it is important to determine public perceptions of receiving a transfusion of blood donated by men who have sex with men. MATERIALS AND METHODS: In online surveys, 510 (Study 1) and 1,062 (Study 2) heterosexual participants reported attitudes, anxiety, disgust, and gratitude towards potentially receiving a transfusion of blood donated by a homosexual male donor and a heterosexual male donor. In Study 2, half of the participants were reminded of the safety testing carried out on donated blood samples. Negative attitudes, anxiety, disgust, and gratitude were compared between the two donors using t-tests and within-participants indirect effects analysis. RESULTS: Stronger negative attitudes, higher anxiety and disgust, and lower gratitude were reported in relation to a potential transfusion of blood donated by the homosexual male donor relative to the heterosexual male donor (|d|=0.26-0.46). This was the case even when participants were reminded of the safety testing completed on donated blood samples in Study 2. In both studies, the effect of donor sexual orientation on attitudes was explained via heightened anxiety and disgust and attenuated gratitude (b=0.05-0.30). DISCUSSION: Considering receiving a transfusion of blood donated by a homosexual male donor elicits more negative attitudes, anxiety and disgust, and less positive emotion, relative to blood donated by a heterosexual male donor. These attitudes and emotional reactions are not shifted by a reminder of the safety testing carried out on donated blood samples. In the context of changing restrictions on blood donation by men who have sex with men, these findings highlight a challenge to shift public perception to embrace this cohort of donors.

Processing speed test: Results from a Japanese normative sample of healthy participants compared with a US normative sample.

BACKGROUND: The Processing Speed Test (PST), a validated iPad®-based cognitive screening test for MS, has been applied to the cognitive assessment of Japanese MS patients using US normative data. METHODS: To develop PST normative data from Japanese healthy volunteers and compare the PST score distribution between Japanese and US healthy volunteers, 254 healthy Japanese-speaking volunteers were enrolled and stratified by age (20-65 years). Potential participants with a Mini-Mental State Examination score < 27 were excluded. PST raw scores (total correct) were from the Japan cohort and compared with age-restricted US normative data and propensity score-matched data created by matching sex, age, and educational level from a published study of 428 healthy participants. PST score distributions and standardized z-scores were compared using t-test and Kolmogorov-Smirnov test statistics. RESULTS: The mean age of the Japan cohort was 44.1 years. The PST scores of Japanese volunteers were significantly different from those of the age-restricted (mean ± SD 61.8 ± 10.1 vs 53.7 ± 10.8; p < 0.001) and the propensity score-matched US cohort (62.1 ± 10.1 vs 53.3 ± 10.6; p < 0.001). CONCLUSION: Regression analyses centered on US normative data could underestimate disease severity in Japanese MS patients, suggesting that separate normative data should be considered for each population sample.

Benefits of early treatment with natalizumab: a real-world study.

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients. METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple Sclerosis Performance Test. Associations were tested using TTNT as a categorical and continuous variable. Linear mixed models addressed within-subject and within-site clustering. RESULTS: TTNT varied from 0.1 to 19.8 years (median [interquartile range] 4.2 [1.8, 9.0] years). A significant association between later natalizumab use and worse outcomes was demonstrated for walking speed (p < 0.001), processing speed (p < 0.001), manual dexterity (p < 0.001), brain atrophy (p = 0.001), and T2 lesion volume (p = 0.02). Covariate-adjusted modelling of a sensitivity population diagnosed with MS in 2006 or later (n = 424) demonstrated significant associations between longer TTNT and worse walking speed (p < 0.05), processing speed (p < 0.001), and manual dexterity (p < 0.001). CONCLUSION: Later initiation of natalizumab was associated with worse clinical and radiologic imaging outcomes. Thus, high-efficacy DMT may have greater benefit when started earlier in MS patients. These results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy.

Multiple Sclerosis Performance Test (MSPT): Normative study of 428 healthy participants ages 18 to 89.

BACKGROUND: The Multiple Sclerosis Performance Test (MSPT) is a self-administered, iPad®-based, computerized system for quantifying neuroperformance (cognition, upper and lower extremity motor function, and vision) in patients with multiple sclerosis (MS). OBJECTIVE: The goal of the study is to provide regression-based norms for the four MSPT test modules to adjust for the influence of demographic variables (age, education, and sex). METHODS: The MSPT was administered to 428 cognitively intact, healthy adults (ages 18 to 89 years). Participants were recruited to achieve a demographically stratified sample from four geographically diverse United States testing sites. RESULTS: The amount of shared variance in test performance accounted for by demographic variables was 18-23% for an upper extremity motor test, 31% for a walking speed test, 32% for a low contrast visual acuity test, and 48% for a cognitive test. All four test modules were significantly influenced by age (linear and non-linear effects) and education. Additionally, sex influenced performance on the cognitive and walking speed tests. CONCLUSION: This study provides regression-based equations that can enhance the clinical interpretation of MSPT scores by adjusting for the potential influences of age, education, and sex.

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS.

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. METHODS: Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. RESULTS: The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p<0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p<0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p<0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. CONCLUSIONS: The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions.

BACKGROUND: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. METHODS: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. RESULTS: Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. CONCLUSION: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.

B-Doped δ-Layers and Nanowires from Area-Selective Deposition of BCl3 on Si(100).

Atomically precise, δ-doped structures forming electronic devices in Si have been routinely fabricated in recent years by using depassivation lithography in a scanning tunneling microscope (STM). While H-based precursor/monatomic resist chemistries for incorporation of donor atoms have dominated these efforts, the use of halogen-based chemistries offers a promising path toward atomic-scale manufacturing of acceptor-based devices. Here, B-doped δ-layers were fabricated in Si(100) by using BCl3 as an acceptor dopant precursor in ultrahigh vacuum. Additionally, we demonstrate compatibility of BCl3 with both H and Cl monatomic resists to achieve area-selective deposition on Si. In comparison to bare Si, BCl3 adsorption selectivity ratios for H- and Cl-passivated Si were determined by secondary ion mass spectrometry depth profiling (SIMS) to be 310(10):1 and 1529(5):1, respectively. STM imaging revealed that BCl3 adsorbed readily on bare Si at room temperature, with SIMS measurements indicating a peak B concentration greater than 1.2(1) × 1021 cm-3 with a total areal dose of 1.85(1) × 1014 cm-2 resulting from a 30 langmuir BCl3 dose at 150 °C. In addition, SIMS showed a δ-layer thickness of ∼0.5 nm. Hall bar measurements of a similar sample were performed at 3.0 K, revealing a sheet resistance of ρ□ = 1.9099(4) kΩ â–¡-1, a hole carrier concentration of p = 1.90(2) × 1014 cm-2, and a hole mobility of µ = 38.0(4) cm2 V-1 s-1 without performing an incorporation anneal. Finally, 15 nm wide B δ-doped nanowires were fabricated from BCl3 and were found to exhibit ohmic conduction. This validates the use of BCl3 as a dopant precursor for atomic-precision fabrication of acceptor-doped devices in Si and enables development of simultaneous n- and p-type doped bipolar devices.

Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: Results from MS PATHS.

BACKGROUND: Optimizing multiple sclerosis treatment warrants understanding of changes in physical, mental, and social health. OBJECTIVE: To assess the impact of natalizumab on Quality of Life in Neurological Disorders (Neuro-QoL) scores. METHODS: Annualized change in T-scores and likelihood of ≥5-point improvement over baseline were calculated for each Neuro-QoL domain after natalizumab initiation. Comparisons with ocrelizumab-treated patients were conducted after propensity score weighting and adjustment for relevant co-medications, year, and drug-year interaction. RESULTS: Among 164 natalizumab patients analyzed, 8 of 12 Neuro-QoL domains improved significantly, with greater improvement in patients with abnormal baseline Neuro-QoL. In the subgroup comparison of natalizumab-treated (n = 145) and ocrelizumab-treated (n = 520) patients, significant improvement occurred in 9 of 12 and 4 of 12 domains, respectively. The difference between groups was statistically significant for positive affect and well-being (p = 0.02), sleep (p = 0.003), and satisfaction with social roles and activities (SRA) (p = 0.03) in the overall population and for emotional and behavioral dyscontrol (p = 0.01), participation in SRA (p = 0.0001), and satisfaction with SRA (p = 0.02) in patients with abnormal baseline Neuro-QoL. CONCLUSIONS: Natalizumab can produce clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias, as their magnitude exceeded improvements with another high-efficacy therapy, ocrelizumab.

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Background: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. Methods: MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care. Institutional participation required the following: active MS patient census of ≥500, at least one Siemens 3T magnetic resonance imaging scanner, and willingness to standardize patient assessments, share standardized data for research, and offer universal enrolment to capture a representative sample. The eligible participants have diagnosis of MS, including clinically isolated syndrome, and consent for sharing pseudonymized data for research. MS PATHS incorporates a self-administered patient assessment tool, the Multiple Sclerosis Performance Test, to collect a structured history, patient-reported outcomes, and quantitative testing of cognition, vision, dexterity, and walking speed. Brain magnetic resonance imaging is acquired using standardized acquisition sequences on Siemens 3T scanners. Quantitative measures of brain volume and lesion load are obtained. Using a separate consent, the patients contribute DNA, RNA, and serum for future research. The clinicians retain complete autonomy in using MS PATHS data in patient care. A shared governance model ensures transparent data and sample access for research. Results: As of August 5, 2019, MS PATHS enrolment included participants (n = 16,568) with broad ranges of disease subtypes, duration, and severity. Overall, 14,643 (88.4%) participants contributed data at one or more time points. The average patient contributed 15.6 person-months of follow-up (95% CI: 15.5-15.8); overall, 166,158 person-months of follow-up have been accumulated. Those with relapsing-remitting MS demonstrated more demographic heterogeneity than the participants in six randomized phase 3 MS treatment trials. Across sites, a significant variation was observed in the follow-up frequency and the patterns of disease-modifying therapy use. Conclusions: Through digital health technology, it is feasible to collect standardized, quantitative, and interpretable data from each patient in busy MS practices, facilitating the merger of research and patient care. This approach holds promise for data-driven clinical decisions and accelerated systematic learning.

Multiple Sclerosis Performance Test: Technical Development and Usability.

INTRODUCTION: In the clinic, the assessment of patients with multiple sclerosis (MS) is typically qualitative and non-standardized. OBJECTIVES: To describe the MS Performance Test (MSPT), an iPad Air® 2 (Apple, Cupertino, CA, USA)-based neurological assessment platform allowing patients to input relevant information without the aid of a medical technician, creating a longitudinal, clinically meaningful, digital medical record. To report results from human factor (HF) and usability studies, and the initial large-scale implementation in a practice setting. METHODS: The HF study examined use-error patterns in small groups of MS patients and healthy controls (n = 14), the usability study assessed the effectiveness of patient interaction with the tool by patients with a range of MS disability (n = 60) in a clinical setting, and the implementation study deployed the MSPT across a diverse population of patients (n = 1000) in a large MS center for routine clinical care. RESULTS: MSPT assessments were completed by all users in the HF study; minor changes to design were recommended. In the usability study, 73% of patients with MS completed the MSPT, with an average administration time of 32 min; 85% described their experience with the tool as satisfactory. In the initial implementation for routine care, 84% of patients with MS completed the MSPT, with an average administration time of 28 min. CONCLUSION: Patients with MS with varying disability levels completed the MSPT with minimal or no supervision, resulting in comprehensive, efficient, standardized, quantitative, clinically meaningful data collection as part of routine medical care, thus allowing for large-scale, real-world evidence generation. FUNDING: Biogen. TRIAL REGISTRATION: NCT02664324.

The longitudinal impact of depression on disability in Parkinson disease.

OBJECTIVE: Depression in Parkinson disease (PD) is a common problem that worsens quality of life and causes disability. However, little is known about the longitudinal impact of depression on disability in PD. This study examined the association between disability and DSM-IV-TR depression status across six years. METHODS: Longitudinal cohort study with assessments at study entry, year two, four, and six conducted in the Morris K. Udall Parkinson Disease Research Center. Recruitment totaled 137 adult men and women with idiopathic PD in which up to six years of data on demographic, motor, and non-motor variables was collected. Movement disorder specialists used the structured interview for DSM-IV-TR depressive disorders and the Northwestern Disability Scale to assess depression and disability. A generalized linear mixed model was fitted with Northwestern Disability Scale score as the dependent variable to determine the effect of baseline depression status on disability. RESULTS: A total of 43 participants were depressed at baseline compared to 94 without depression. Depressed participants were more likely to be female, were less educated, were less likely to take dopamine agonists, and more likely to have motor fluctuations. Controlling for these variables, symptomatic depression predicted greater disability compared to both never depressed (p = 0.0133) and remitted depression (p = 0.0009). Disability associated with symptomatic depression at baseline was greater over the entire six-year period compared to participants with remitted depressive episodes or who were never depressed. CONCLUSIONS: Persisting depression is associated with a long-term adverse impact on daily functioning in PD. Adequate treatment or spontaneous remission of depression improves ADL function.

A high-mobility electronic system at an electrolyte-gated oxide surface.

Electrolyte gating is a powerful technique for accumulating large carrier densities at a surface. Yet this approach suffers from significant sources of disorder: electrochemical reactions can damage or alter the sample, and the ions of the electrolyte and various dissolved contaminants sit Angstroms from the electron system. Accordingly, electrolyte gating is well suited to studies of superconductivity and other phenomena robust to disorder, but of limited use when reactions or disorder must be avoided. Here we demonstrate that these limitations can be overcome by protecting the sample with a chemically inert, atomically smooth sheet of hexagonal boron nitride. We illustrate our technique with electrolyte-gated strontium titanate, whose mobility when protected with boron nitride improves more than 10-fold while achieving carrier densities nearing 10(14) cm(-2). Our technique is portable to other materials, and should enable future studies where high carrier density modulation is required but electrochemical reactions and surface disorder must be minimized.

Application of depression rating scales in patients with Parkinson's disease with and without co-Occurring anxiety.

BACKGROUND: In patients with Parkinson's disease (PD), depressive symptom rating scales facilitate identification of depressive disorders, which are common and disabling. Anxiety disturbances in PD, which lack valid assessment scales, frequently co-occur with PD-depression, are under-recognized, and require different interventions than depressive disorders. Whether high anxiety rates in PD confound depression scale performance or if any depression scales also predict anxiety disturbances is not known. OBJECTIVE: To test the impact of co-occurring anxiety disorders on psychometric properties of depression rating scales in depressed PD patients and compare disability between PD patients with anxiety, depression, and comorbid anxiety and depressive disorders. METHODS: PD subjects (n = 229) completed self-report and clinician-administered depression scales. Receiver operating characteristic curves were developed to estimate psychometric properties of each scale in those with depression alone, anxiety alone, and comorbid depression and anxiety. Between-group differences on all measures were examined. RESULTS: Comorbid anxiety did not affect the psychometric properties of any scale when identifying depressive disorders, but is associated with greater symptom severity and disability. Depression-scale scores were not significantly different between subjects with anxiety disorders only and those without depressive or anxiety diagnoses. CONCLUSIONS: Co-occurring anxiety disorders do not impact performance of depression rating scales in depressed PD patients. However, depression rating scales do not adequately identify anxiety disturbances alone or in patients with depression.

Improving detection of psychiatric disturbances in Parkinson's disease: the role of informants.

BACKGROUND: Under-recognition of psychiatric disturbances in patients with Parkinson's disease (PD) contributes to greater overall morbidity. Little is known about the value of collateral psychiatric history, obtained using standardized assessments with informants, for increasing recognition of PD-related psychiatric illness. OBJECTIVE: To examine the extent to which informants provide critical information that enabled psychiatrists to establish psychiatric diagnoses in patients with PD. METHODS: Individuals with PD (n = 223) and an informant were interviewed separately regarding the PD patient's psychiatric history and current status. A six-psychiatrist panel rated the extent to which informant data was required to establish the final consensus best-estimate current psychiatric diagnoses. Informants rated as "Crucial" or "Significantly Informative" comprised a "Critical Informant" (CI) subgroup; remaining informants were classified as the "Non-Critical Informant" (NCI) subgroup. RESULTS: Of the informants, 71 (31.4%) were "critical" for determining a psychiatric diagnosis. Without a CI, 81.3% of those with impulse control disorders and 43.8% of those with anxiety disorders would not have been diagnosed. Male PD patients and those with less severe motor deficits were also more likely to require a CI. CONCLUSIONS: Informants aid in the identification of psychiatric diagnoses, especially impulse control and anxiety disorders. This has implications for clinical practice and conduction of clinical trials.

Direct measurement of current-phase relations in superconductor/topological insulator/superconductor junctions.

Proximity to a superconductor is predicted to induce exotic quantum phases in topological insulators. Here, scanning superconducting quantum interference device (SQUID) microscopy reveals that aluminum superconducting rings with topologically insulating Bi2Se3 junctions exhibit a conventional, nearly sinusoidal 2π-periodic current-phase relations. Pearl vortices occur in longer junctions, indicating suppressed superconductivity in aluminum, probably due to a proximity effect. Our observations establish scanning SQUID as a general tool for characterizing proximity effects and for measuring current-phase relations in new materials systems.

Pharmacologic treatment of anxiety disorders in Parkinson disease.

OBJECTIVE: Neither best practices nor an evidence base for the pharmacologic treatment of anxiety in Parkinson disease (PD) has been established. This study investigated pharmacologic treatment of anxiety disorders in idiopathic PD and the associated clinical features. DESIGN: Cross-sectional. SETTING: Three community-based movement disorder neurology practices. PARTICIPANTS: 250 subjects with PD. MEASUREMENTS: Anxiety disorder diagnoses were established by consensus using a panel of six psychiatrists with expertise in geriatric psychiatry and movement disorders. Current medications were provided by the treating neurologists at the time of interview. RESULTS: Among subjects with anxiety disorders only, 53% were untreated with medications. When anxious subjects with comorbid depressive disorders were included, 70.8% were on medications effective for treatment of anxiety. Subjects with anxiety and comorbid depressive disorders were more likely to be treated for their psychiatric disturbances than subjects with anxiety disorders alone (odds ratio: 8.33), as were subjects with comorbid motor fluctuations (odds ratio: 3.65). There were no differences in the types of anti-anxiety medications used in regard to the presence of depression or motor fluctuations. CONCLUSIONS: These findings suggest that over half of nondepressed PD patients with clinically significant anxiety are untreated with medication. A better understanding of the role of clinical features associated with anxiety in PD, such as depression and motor fluctuations, may improve the recognition and treatment of anxiety disorders in this population.

Cardiovascular and mortality risks in Parkinson's disease patients treated with entacapone.

The controlled trial Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) reported an unexpected increase in acute myocardial infarction (AMI) with entacapone use in patients with Parkinson's disease (PD). The authors investigated whether entacapone increased cardiovascular and mortality risk compared with the use of a non-levodopa dopamine agonist (DA) or a selective monoamine oxidase type-B inhibitor (MAOBI). Using national Medicare data, a new-user cohort of elderly patients with PD treated with entacapone was propensity score (PS) matched with new users of either DA or MAOBI. The PS model included variables for sociodemographics, cardiovascular disease, medications, prior PD treatment, and comorbidities. Cox proportional hazards regression was used to compare on-therapy time to event for AMI, stroke, and death with DA-MAOBI as a reference. Study cohorts included 8681 entacapone-treated and 17,362 DA-MAOBI-treated initators who were followed for 2569 and 5385 person-years, respectively. Cohorts were closely balanced for all covariates. During follow-up, there were 106 AMIs, 89 strokes, and 201 deaths. The hazard ratio (HR) and 95% confidence interval (CI) associated with entacapone use was 0.86 (95% CI, 0.57-1.30) for AMI, 0.85 (95% CI, 0.54-1.35) for stroke, and 0.79 (95% CI, 0.58-1.07) for death. The risk was unchanged for treatment of ≤ 6 months' and>6 months' duration and was unaffected by adjustment for time-varying levodopa use during follow-up. The risk of each endpoint was not differentially affected by diabetes, ischemic heart disease, or kidney failure status. However, the risk of stroke was modified by the presence (HR, 2.09; 95% CI, 0.98-4.45) or absence (HR, 0.51; 95% CI, 0.27-0.95) of advanced PD-related morbidities (P value for interaction=0.004). Entacapone was not associated with an increased risk of AMI, stroke, or death in elderly patients with PD.

Screening for DSM-IV-TR cognitive disorder NOS in Parkinson's disease using the Mattis Dementia Rating Scale.

OBJECTIVE: This study explores the utility of the Mattis Dementia Rating Scale (MDRS) as a screening tool for the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV-TR) diagnosis cognitive disorder not otherwise specified (NOS) in Parkinson's disease (PD). METHODS: A total of 125 individuals with PD were diagnosed using DSM-IV-TR criteria for cognitive disorder NOS and dementia. Receiver operating characteristics (ROC) tested the discriminant validity of the MDRS, with the clinician's diagnosis serving as the gold standard. RESULTS: The MDRS ROC curve to discriminate subjects with cognitive disorder NOS from non-demented subjects had an area under the curve of 0.59 (standard error = 0.08, 95% CI: 0.43-0.74). CONCLUSIONS: The MDRS is not effective for identifying PD patients with cognitive disorder NOS without dementia.

Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System.

AIM: To determine the rate ratio of neuropsychiatric hospitalizations in new users of varenicline compared to new users of nicotine replacement therapy (NRT) patch in the Military Health System (MHS). DESIGN, SETTING AND PARTICIPANTS: Varenicline (n = 19,933) and NRT patch (n = 15,867) users who initiated therapy from 1 August 2006 to 31 August 2007 within the MHS were included in this retrospective cohort study. After matching according to propensity scores, 10,814 users remained in each cohort. The study population included those with and without a history of neuropsychiatric disease. MEASUREMENTS: Patients were followed for neuropsychiatric hospitalizations defined by primary neuropsychiatric discharge diagnosis using ICD-9 codes from in-patient administrative claims. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated after propensity score matching on exposure for socio-demographic factors, health-care utilization, comorbidities, medication history and neuropsychiatric history. FINDINGS: There was no increase in the rate of neuropsychiatric hospitalizations in patients treated with varenicline compared to NRT patch when followed for 30 days (propensity-score matched HR = 1.14, 95% CI: 0.56-2.34). Results were similar after 60 days of follow-up. CONCLUSIONS: There does not appear to be an increase in neuropsychiatric hospitalizations with varenicline compared with nicotine replacement therapy patch over 30 or 60 days after drug initiation.

Diagnosis pathway for patients with amyotrophic lateral sclerosis: retrospective analysis of the US Medicare longitudinal claims database.

BACKGROUND: Initial symptoms of amyotrophic lateral sclerosis (ALS) are often subtle and can delay diagnosis. This exploratory analysis was conducted to better characterize the pre-diagnosis pathway undertaken by patients with ALS in the US Centers for Medicare & Medicaid Services Medicare longitudinal claims database. METHODS: Quarterly Medicare claims data were analyzed to determine the pre-diagnosis pathway for an ALS patient cohort that included patients aged ≥ 65 years with ≥ 2 ALS claims (International Classification of Diseases, Ninth Revision, Clinical Modification code 335.20) between the first quarter of 2007 and the fourth quarter of 2009, and were enrolled in Medicare ≥ 2 years before the first ALS claim (diagnosis). A cohort of Medicare patients without claims for motor neuron diseases were identified for comparison. A subset of these patients with ≥ 3 years of claims data was included in a time to diagnosis analysis. Data extraction included the most common initial symptoms of ALS, the time from first ALS symptom to diagnosis, and the diagnostic procedures performed before the diagnosis of ALS. RESULTS: A total of 399 patients met the inclusion criteria and were included in the ALS cohort; 272 patients were included in the time to diagnosis cohort. Before the quarter of diagnosis, symptoms that were more frequently seen in the ALS cohort than the general Medicare cohort included muscle weakness, lack of coordination and speech/swallowing difficulties. Limb-onset ALS (74%) was more common than bulbar-onset ALS (17%). Median time to diagnosis for limb- and bulbar-onset patients was 2.5 years and 1.25 years, respectively. The most common tests conducted before the quarter of diagnosis included sensory and motor nerve conduction tests, imaging studies, and electromyography; however, a substantial number of patients did not receive any nerve conduction testing. Motor nerve conduction testing in patients with bulbar-onset ALS had the largest impact on time to diagnosis. CONCLUSIONS: This analysis describes a diagnostic delay for patients with ALS in the US Medicare population, similar to previous reports. The development of tools and ongoing education that can help to identify patients with ALS earlier in their disease course is needed.