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1.
Cephalalgia ; : 333102420921855, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349538

RESUMO

OBJECTIVE: To assess the proportion of individuals who report dizziness and/or vertigo during the prodromal phase or headache phase of migraine. METHODS: The databases of MEDLINE and EMBASE were searched for studies on dizziness and/or vertigo during the prodromal phase or headache phase of migraine. Pooled relative frequencies were estimated using a random-effects meta-analysis. RESULTS: We identified nine articles eligible for inclusion. Of these, one study reported results for the prodromal phase, seven studies for the headache phase and one study for both the prodromal and headache phase. In the prodromal phase, 9.0% of individuals with migraine reported dizziness, while 3.3% reported vertigo. During the headache phase, relative frequency of dizziness ranged from 6.7% to 59.6%, while vertigo ranged from 6.4% to 44.7%. The meta-analysis showed a relative frequency of 35.7% for dizziness (95% CI = 13.7-61.5%, I2 = 99%) and 33.9% for vertigo (95% CI = 26.7-41.5%, I2 = 87%). Study quality was rated 5/9 or below for seven studies and 6/9 or above for two studies. CONCLUSION: We found that there is a scarcity of literature on dizziness and vertigo as prodromal- and headache-associated symptoms in individuals with migraine. Methodological variations confound comparisons of epidemiological patterns, although it appears that dizziness and vertigo are more frequent during the headache phase of migraine, compared with the prodromal phase. Future studies should ensure use of standardized definitions and rigorous methodology to enable accurate measurements of dizziness and vertigo in migraine.

2.
J Alzheimers Dis ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32390624

RESUMO

This study surveys the development of Alzheimer's disease (AD) in the research literature, the scientific community, and the journals containing AD papers over a 35-year period. Research papers on AD published from 1983 to 2017 in journals indexed in the Web of Science were analyzed in seven five-year periods. The number of AD papers increased from 1,095 in 1983-1987 to 50,532 by 2013-2017 and in the same time period, the number of participating countries went from 27 to 152. The US was the most prolific country throughout, followed by several European countries, Canada, Australia, and Japan. Asian countries have emerged and by 2013-2017, China surpassed all but the US in productivity. Countries in Latin America and Africa have also contributed to AD research. Additionally, several new non-governmental institutions (e.g., ADNI, ADI) have emerged and now play a key role in the fight against AD. Likewise the AD scientific publishing universe evolved in various aspects: an increase in number of journals containing AD papers (227 journals in 1983-1987 to 3,257 in 2013-2017); appearance of several AD-focused journals, e.g., Alzheimer's & Dementia, Journal of Alzheimer's Disease; and the development of special issues dedicated to AD. Our paper complements the numerous extant papers on theoretical and clinical aspects of AD and provides a description of the research landscape of the countries and journals contributing papers related to AD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32396611

RESUMO

We aimed to examine the relationship between APOE*4 carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow up duration ranging between 1.2 and 10.7 years. Two-step individual participant data (IPD) meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (i.e., 62 years) and older (i.e., 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

4.
Neurol Sci ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415640

RESUMO

OBJECTIVE: To estimate the relative frequency and relative risk of post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI). DATA SOURCES: PubMed and Embase were searched from database inception until January 26, 2019. STUDY SELECTION: Two independent investigators screened titles, abstracts, and full texts. We selected studies that included subjects presenting with TBI, and where the number of subjects with TBI and PTSD could be extrapolated. There were no restrictions on study design. DATA EXTRACTION AND SYNTHESIS: Data were extracted by two independent investigators and results were pooled using random-effects meta-analysis. RESULTS: In civilian populations, relative frequency of PTSD following TBI was 12.2% after 3 months (CI-95 (7.6 to 16.8%) I2 = 83.1%), 16.3% after 6 months (CI-95 (10.2 to 22.4%), I2 = 88.4%), 18.6% after 12 months (CI-95 (10.2 to 26.9%), I2 = 91.5%), and 11.0% after 24 months (CI-95 (0.0 to 25.8%), I2 = 92.0%). Relative risk was 1.67 after 3 months (CI-95 (1.17 to 2.38), P = 0.011, I2 = 49%), 1.36 after 6 months (CI-95 (0.81 to 2.30), P = 0.189, I2 = 34%), and 1.70 after 12 months (CI-95 (1.16-2.50), P = 0.014, I2 = 89%). In military populations, the relative frequency of associated PTSD was 48.2% (CI-95 (44.3 to 52.1%), I2 = 100%) with a relative risk of 2.33 (CI-95 (2.00 to 2.72), P < 0.0001, I2 = 99.9%). CONCLUSIONS AND RELEVANCE: TBI is a risk factor for PTSD in clinic-based civilian populations. There are insufficient data to assess the relative frequency or relative risk of PTSD in moderate to severe TBI. Due to significant between-study heterogeneity, the findings of our study should be interpreted with caution.

5.
J Alzheimers Dis ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32417772

RESUMO

BACKGROUND: Engaging in mentally challenging activities may protect against dementia in late life. However, little is known whether the association between mentally challenging activities and dementia risk varies with race/ethnicity. OBJECTIVE: The current study investigates whether having jobs with higher mental stimulation is differentially associated with a decreased risk of dementia between African Americans (AAs) and non-Hispanic Whites (nHWs). METHODS: The sample consisted of 1,079 individuals (66% nHWs, 28% AAs; age = 78.6±5.3) from the longitudinal Einstein Aging Study. Occupation information of each participant was collected retrospectively at baseline and was linked to the substantive complexity of work score from the Dictionary of Occupational Titles. Cox proportional hazards models were used to evaluate the associations of occupational complexity with risk of dementia. RESULTS: Individuals whose jobs had moderate-to-high levels of complexity, compared to those with the lowest complexity, were at modestly decreased risk for incident dementia. When stratified by race, moderate-to-high levels of occupational complexity were significantly associated with lower risk of developing dementia for AAs (HR = 0.35). When risk of dementia was evaluated based on the combinations of race×occupational complexity, AAs with lowest occupational complexity showed the highest risk of developing dementia, while other combinations exhibited lower risk of developing dementia (HRs = 0.36 0.43). CONCLUSION: Our results suggest that moderate-to-high levels of complexity at work are associated with a decreased risk of incident dementia in AAs. Understanding the differential effects of mentally challenging occupations across race/ethnicity may suggest important intervention strategies that could mitigate racial disparities in dementia rates.

7.
Mayo Clin Proc ; 95(4): 709-718, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32247344

RESUMO

OBJECTIVE: To characterize self-reported use of acute prescription medication for migraine in a sample representing the US population. PATIENTS AND METHODS: Data were obtained from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study. The CaMEO Study is an Internet-based cross-sectional longitudinal survey administered between September 17, 2012, and November 19, 2013. Demographic characteristics, migraine-related disability, symptom severity, quality of life, and psychiatric comorbidity profiles were evaluated. RESULTS: Data from 13,624 respondents were analyzed, including 3121 (22.9%) self-reported current users of acute prescription medication for migraine, 1719 (12.6%) previous/discontinued users, and 8784 (64.5%) who had never used acute prescription medication for migraine. Mean ± SD monthly headache frequency was 7.3±7.1 days for current users, 5.6±6.6 days for those who discontinued, and 3.9±4.9 days for respondents who never used acute prescription medication for migraine. Current users experienced the highest degree of migraine-related disability based on Migraine Disability Assessment scores and the highest levels of migraine symptom severity based on Migraine Symptom Severity Scale scores. Current users also had the highest scores on the depression and anxiety questionnaires. The most commonly reported prescription medications used or "kept on hand" by current users were triptans (47.2%; 1474 of 3121), opioids (37.3%; 1164 of 3121), nonsteroidal anti-inflammatory drugs (31.9%; 997 of 3121), and barbiturates (12.8%; 399 of 3121), with many people reporting more than 1 medication. CONCLUSION: Despite reporting moderate to severe migraine-related disability and impairment, many people with migraine have never used acute prescription migraine medication. The burden related to migraine is great, especially among individuals currently using acute prescription medication for migraine.

8.
Cephalalgia ; : 333102420911209, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32151153

RESUMO

OBJECTIVE: To determine the prevalence of hypnic headache. BACKGROUND: The exact prevalence of hypnic headache is unknown since there are no published population-based prevalence studies. METHODS: This study was a pilot for the SAGA cohort study, a population-based study on life stressors and various indices of health. Of 1398 invited adults, 921 (66%) participated; 402 men (average age 45.6 years, SD 13.2) and 519 women (52.6 years, SD 11.1). Subjects answered a headache questionnaire including a screening question for hypnic headache. "Do you have a headache that occurs only during sleep and causes wakening?". Diagnosis of hypnic headache was made by clinical interview using ICHD-3 criteria. RESULTS: Among 921 participants, six screened positive for hypnic headache, of those two 0.22% (95% CI 0.06-0.79%) had probable hypnic headache and none had definite hypnic headache. CONCLUSION: Confirming that hypnic headache is rare, these data suggest a 0.22% prevalence of probable hypnic headache.

9.
J Headache Pain ; 21(1): 23, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122324

RESUMO

BACKGROUND: Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. METHODS: The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. RESULTS: Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever. CONCLUSIONS: In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.

10.
Diabetes Care ; 43(5): 1111-1117, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32139382

RESUMO

OBJECTIVE: Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos. RESEARCH DESIGN AND METHODS: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes. RESULTS: Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (ßGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models. CONCLUSIONS: Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.

11.
Neurology ; 94(13): e1365-e1377, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32209650

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of chronic migraine (CM). METHODS: The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2 (PROMISE-2) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with CM were randomly assigned to receive IV eptinezumab 100 mg, eptinezumab 300 mg, or placebo administered on day 0 and week 12. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over weeks 1 to 12. RESULTS: Among treated participants (n = 1,072), baseline mean number of MMDs was ≈16.1 across groups. Treatment with eptinezumab 100 and 300 mg was associated with significant reductions in MMDs across weeks 1 to 12 compared with placebo (placebo -5.6, 100 mg -7.7, p < 0.0001 vs placebo; 300 mg -8.2, p < 0.0001 vs placebo). Treatment-emergent adverse events (TEAEs) were reported by 43.5% (100 mg), 52.0% (300 mg), and 46.7% (placebo) of patients. Nasopharyngitis was the only TEAE reported for >2% of eptinezumab-treated patients at an incidence of >2% over placebo; it occurred in the 300 mg eptinezumab arm (eptinezumab 9.4%, placebo 6.0%). CONCLUSION: In patients with CM, eptinezumab 100 and 300 mg was associated with a significant reduction in MMDs from the day after IV administration through week 12, was well tolerated, and demonstrated an acceptable safety profile. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with CM, a single dose of eptinezumab reduces MMDs over 12 weeks of treatment. CLINICALTRIALSGOV IDENTIFIER: NCT02974153.

12.
Cephalalgia ; 40(5): 437-447, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32138526

RESUMO

BACKGROUND: Triptans are the most commonly used acute treatment for migraine. This study evaluated real-world treatment patterns following an initial triptan prescription to understand refill rates and use of non-triptan medications for the acute treatment of migraine. METHODS: Commercially-insured adult patients over 18 years of age with a triptan prescription between 1/1/2013 to 31/12/2013 were identified from the Optum Clinformatics™ Data Mart database, with date of the first triptan fill designated as index date. Inclusion was limited to those with no fills for a triptan in the 12 months prior to index date (i.e. new users or initiators of triptans) and continuous enrollment in the 12 months pre- and 24 months post-index date. Fills for index triptan, non-index triptan, and other acute treatments for migraine were assessed for up to 24 months post-index. RESULTS: Among 10,509 patients, 50.8% did not refill the initial triptan within 12 months and 43.6% did not refill within 24 months. In the 12 months post-index, 90.5% of patients used only one type of triptan, 8.4% used two different triptans, and 1.0% used three or more triptans. Among patients with and without a triptan refill, use of opioids (39% vs. 42%), non-steroidal anti-inflammatory drugs (22% vs. 22%), and butalbital-containing products (9% vs. 10%) were similar. CONCLUSION: More than half of those who newly initiated a triptan did not refill their initial prescription, and less than 1 in 10 used two or more triptans within 12 months. High rates of non-triptan acute medication use were found over 12 and 24 months of follow-up, most commonly opioids.

13.
J Headache Pain ; 21(1): 20, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093628

RESUMO

BACKGROUND: Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT1F receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study. METHODS: Completers of two single-attack parent studies were offered participation in the 1 year GLADIATOR study, that randomized participants to treatment with lasmiditan 100 mg or 200 mg taken as needed for migraine attacks of at least moderate severity. Changes in MIDAS were modeled using a mixed model repeated measures analysis. RESULTS: The sample included 1978 patients who received ≥1 lasmiditan dose and were followed for a median of 288 days. Baseline mean MIDAS scores for the lasmiditan 100-mg and 200-mg groups were 29.4 and 28.9, respectively, indicating severe migraine-related disability. Relative to baseline, MIDAS total scores were significantly lower at 3, 6, 9, and 12 months for both dose groups. At 12 months, changes in MIDAS scores were - 12.5 and - 12.2 for lasmiditan 100 mg and 200 mg, respectively, with 49% and 53% of patients, respectively, achieving at least a 50% decrease in MIDAS total score. Statistically significant improvements were also seen for work and/or school absenteeism and presenteeism, monthly headache days, and mean headache pain intensity at all time points up to 1 year. Findings for patients who completed all visits versus those dropping out early were similar. Responses were generally similar for the lasmiditan 100 mg or 200 mg doses, between subgroups defined based on the number of baseline monthly migraine attacks (≤5 vs. >5), and also between subgroups defined by pain-free response (yes/no) during initial attacks. CONCLUSIONS: Long-term treatment with lasmiditan was associated with significant reductions in migraine-related disability, including both work or school absenteeism and presenteeism. The similarity of responses in completers and those who dropped out suggests that selective attrition does not account for the improvements. Benefits were significant at 3 months and maintained through 12 months. TRIAL REGISTRATION: clinicaltrials.govNCT02565186; first posted October 1, 2015.

14.
Headache ; 60(4): 686-700, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32073660

RESUMO

OBJECTIVE: To evaluate the efficacy of ubrogepant on patient-reported functional disability, satisfaction with study medication, and global impression of change. BACKGROUND: Ubrogepant is a small-molecule, oral calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine. In 2 phase 3 trials (ACHIEVE I and II), ubrogepant demonstrated efficacy vs placebo on the 2 co-primary endpoints of headache pain freedom and absence of the most bothersome migraine-associated symptom at 2 hours post dose for the 50 and 100 mg doses. Patient-reported outcomes, such as functional disability, satisfaction, and patient global impression of change, can provide additional evidence of the efficacy of an acute treatment for migraine on clinically meaningful and patient-relevant outcomes. METHODS: ACHIEVE I and ACHIEVE II were multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack trials in adults (18-75 years) with migraine. In ACHIEVE I, participants were randomized 1:1:1 to placebo or ubrogepant 50 or 100 mg; in ACHIEVE II, participants were randomized 1:1:1 to placebo or ubrogepant 25 or 50 mg to treat a migraine attack with moderate or severe headache pain. Participants rated ability to perform daily activities on the Functional Disability Scale, before dosing and at 1, 2, 4, and 8 hours after the initial dose; satisfaction with study medication at 2 and 24 hours; and impression of overall change in migraine on the Patient Global Impression of Change scale at 2 hours. In prespecified analyses for each trial, each outcome was compared between each ubrogepant dose group and the relevant placebo group. Data were pooled from the ubrogepant 50 mg and placebo groups of the 2 trials in a post hoc analysis. RESULTS: In ACHIEVE I, 559 participants were randomized to placebo, 556 to ubrogepant 50 mg, and 557 to ubrogepant 100 mg; in ACHIEVE II, 563 were randomized to placebo, 561 to ubrogepant 25 mg, and 562 to ubrogepant 50 mg. At 2 hours post dose, significantly higher proportions of ubrogepant-treated participants vs placebo-treated participants reported being able to function normally (ACHIEVE I: ubrogepant 50 mg, 40.6% [171/421], P = .0012 vs placebo; ubrogepant 100 mg, 42.9% [192/448], P < .0001 vs placebo; placebo, 29.8% [136/456]; ACHIEVE II: ubrogepant 25 mg, 42.6% [185/434], P = .0015 vs placebo; ubrogepant 50 mg, 40.5% [188/464], P = .0118 vs placebo; placebo, 34.2% [156/456]; pooled 50 mg, 40.6% [359/885], vs pooled placebo, 32.0% [292/912]; P < .0001), were satisfied/extremely satisfied with study medication (ACHIEVE I: 50 mg, 36.3% [147/405], P < .0001 vs placebo; 100 mg, 35.8% [149/416], P = .0002 vs placebo; placebo, 24.1% [104/432]; ACHIEVE II: 25 mg, 35.1% [141/402], P = .0018 vs placebo; 50 mg, 37.8% [163/431], P < .0001 vs placebo; placebo, 24.8% [106/427]; pooled ubrogepant 50 mg, 37.1% [310/836], vs pooled placebo, 24.5% [210/859]; P < .0001), and indicated that their migraine was much/very much better on the Patient Global Impression of Change scale (ACHIEVE I: 50 mg, 34.4% [103/299], P = .0006 vs placebo; 100 mg, 34.3% [102/297], P = .0009 vs placebo; placebo, 22.0% [69/313]; ACHIEVE II: 25 mg, 34.1% [124/364], P < .0001 vs placebo; 50 mg, 33.4% [131/392], P = .0002 vs placebo; placebo, 20.7% [78/376]; pooled 50 mg, 33.9% [234/691], vs pooled placebo, 21.3% [147/689]; P < .0001). CONCLUSIONS: A significantly higher proportion of participants treated with ubrogepant were able to function normally, were satisfied with the study medication, and reported clinically meaningful improvement compared with those receiving placebo. The results reinforce the potential benefits of ubrogepant on patient-centered outcomes in the acute treatment of migraine.

16.
17.
Pain ; 161(5): 880-888, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31977938

RESUMO

Neck pain and headache are 2 of the most common complications of whiplash injury. Therefore, we performed a systematic literature search on PubMed and Embase for publications reporting on the prevalence of neck pain and headache after whiplash injury. The literature search identified 2709 citations of which 44 contained relevant original data. Of these, 27 studies provided data for the quantitative analysis. For non-population-based studies, the present meta-analysis showed that a pooled relative frequency of neck pain was 84% confidence interval (68%-95%) and a pooled relative frequency of headache was 60% (46%-73%), within 7 days after whiplash injury. At 12 months after injury, 38% (32%-45%) of patients with whiplash still experienced neck pain, while 38% (18%-60%) of whiplash patients reported headache at the same time interval after injury. However, we also found considerable heterogeneity among studies with I-values ranging from 89% to 98% for the aforementioned meta-analyses. We believe that the considerable heterogeneity among studies underscores the need for clear-cut definitions of whiplash injury and standardized reporting guidelines for postwhiplash sequelae such as neck pain and headache. Future studies should seek to optimize these aspects paving the way for a better understanding of the clinical characteristics and natural course of whiplash-associated sequelae.

18.
J Alzheimers Dis ; 74(1): 55-63, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31985462

RESUMO

BACKGROUND: The ideal participants for Alzheimer's disease (AD) clinical trials would show cognitive decline in the absence of treatment (i.e., placebo arm) and also would be responsive to the therapeutic intervention being studied (i.e., drug arm). One strategy to boost the power of trials is to enroll individuals who are more likely to progress targeted using data-driven predictive models. OBJECTIVE: To investigate if machine learning (ML) models can effectively predict clinical disease progression (cognitive decline) in mild-to-moderate AD patients during the timeframe of a phase III clinical trial. METHODS: Data from 202 participants with a diagnosis of AD at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to train ML classifiers that can differentiate between individuals who had declining cognitive function (DC) and individuals with stable cognitive function (SC). DC was defined as any downward change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score over 12 months of follow-up. SC was defined by the absence of decline in ADAS-cog. Trained models were applied to data from 77 participants from the placebo arm of the phase III trial of Semagacestat (LFAN study) to identify subgroups of SC versus DC. RESULTS: Only 74.8% of ADNI participants and 63.6% of LFAN participants had cognitive decline after one year of follow up. K-nearest neighbors (kNN) classifier had an accuracy of 68.3%, sensitivity of 80.1%, and specificity of 33.3% for identifying decliners in ADNI (training sample). In LFAN (validation sample), the model showed an overall accuracy of 61.3%, sensitivity of 65.5%, and specificity of 47.0% in identifying decliners at the 12 months of follow-up. The model had a positive predictive value of 80.8%, which was 17.2% more than the base prevalence of decliners. CONCLUSIONS: Machine learning predictive models can be effectively used to boost the power of clinical trials by reducing the sample size.

19.
Neurology ; 94(20): e2121-e2125, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31932515

RESUMO

OBJECTIVE: To provide the first clinical report that 2 calcitonin gene-related peptide (CGRP) therapies, a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody, can be used concomitantly to treat refractory migraine. METHODS: Case reports are presented of 2 patients participating in a long-term safety study of rimegepant 75 mg oral tablets for acute treatment (NCT03266588). After Food and Drug Administration approval of erenumab, both patients started subcutaneous erenumab monthly as allowed per protocol. RESULTS: Patients were women 44 and 36 years of age with ≥2 decades of self-reported suboptimal response to multiple migraine medications. Patient 1 used rimegepant for 6 months and then started erenumab 70 mg subcutaneous monthly. Despite a response to preventive treatment with erenumab, she experienced substantial relief treating 7 of 7 acute attacks with rimegepant and eliminated regular, frequent use of ibuprofen and a caffeinated analgesic. Patient 2 used rimegepant for 60 days before starting erenumab 140 mg subcutaneously monthly. While on erenumab, 9 of 9 attacks treated with rimegepant responded. She stopped near-daily use of injectable ketorolac and diphenhydramine. While using rimegepant alone or together with erenumab, patients reported no related adverse events. CONCLUSIONS: Rimegepant 75 mg may be effective for acute treatment during concomitant erenumab preventive administration. The mechanism underlying the benefits of concomitant use of a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody is unknown and requires further study. CLINICALTRIALSGOV IDENTIFIER: NCT03266588. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with migraine using erenumab, rimegepant is effective for acute treatment.

20.
Headache ; 60(1): 141-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31913519

RESUMO

OBJECTIVE: To evaluate the long-term safety and tolerability of ubrogepant for the acute treatment of migraine. BACKGROUND: Ubrogepant is an oral, calcitonin gene-related receptor antagonist in development for the acute treatment of migraine. The efficacy of ubrogepant was demonstrated in 2 phase 3 trials in which a significant improvement was observed in migraine headache pain, migraine-associated symptoms, and ability to function. METHODS: This was a phase 3, multicenter, randomized, open-label, 52-week extension trial. Adults with migraine with or without aura entered the trial after completing one of 2 phase 3 lead-in trials and were re-randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg. Randomization to ubrogepant dose was blinded. Those randomized to usual care continued to treat migraine attacks with their own medication. The usual care arm was included in this trial to capture background rates of hepatic laboratory parameters and contextualize hepatic safety assessments. Safety and tolerability were the primary outcome measures. The safety population for the ubrogepant arms included all randomized participants who received at least 1 dose of treatment. All cases of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations of ≥3 times the upper limit of normal were adjudicated by an independent panel of liver experts who were blinded to dose. RESULTS: The safety population included 1230 participants (404 in the ubrogepant 50-mg group, 409 in the ubrogepant 100-mg group, and 417 in the usual care group). Participants were on average 42 years of age, 90% (1106/1230) female and 85% (1043/1230) white, with an average BMI of 30 kg/m2 . Throughout the trial, 21,454 migraine attacks were treated with 31,968 doses of ubrogepant. Treatment-emergent adverse events (TEAEs) were reported by 268/404 (66%) participants receiving ubrogepant 50 mg and 297/409 (73%) receiving ubrogepant 100 mg. The most commonly reported TEAE was upper respiratory tract infection (<12%); findings were similar across dose groups. Treatment-related TEAEs were reported by 42/404 (10%) participants in the ubrogepant 50-mg group and 43/409 (11%) in the ubrogepant 100-mg group. Serious adverse events (SAEs) were reported by 9/404 (2%) participants in the ubrogepant 50-mg group and 12/409 (3%) participants in the ubrogepant 100-mg group. Twenty cases of ALT/AST levels of ≥3 times the upper limit of normal were reported and reviewed by an independent clinical adjudication committee of liver experts. There were no cases of Hy's Law. CONCLUSIONS: Long-term intermittent use of ubrogepant 50 and 100 mg given as 1 or 2 doses per attack for the acute treatment of migraine was safe and well tolerated, as indicated by a low incidence of treatment-related TEAEs and SAEs and discontinuations due to adverse events in this 1-year trial.

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