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OBJECTIVE: Utilize machine learning models to identify factors associated with seeking medical care for migraine. BACKGROUND: Migraine is a leading cause of disability worldwide, yet many people with migraine do not seek medical care. METHODS: The web-based survey, ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (US), annually recruited demographically representative samples of the US adult population (2018-2020). Respondents with active migraine were identified via a validated diagnostic questionnaire and/or a self-reported medical diagnosis of migraine, and were then asked if they had consulted a healthcare professional for their headaches in the previous 12 months (i.e., "seeking care"). This included in-person/telephone/or e-visit at Primary Care, Specialty Care, or Emergency/Urgent Care locations. Supervised machine learning (Random Forest) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms identified 13/54 sociodemographic and clinical factors most associated with seeking medical care for migraine. Random Forest models complex relationships (including interactions) between predictor variables and a response. LASSO is also an efficient feature selection algorithm. Linear models were used to determine the multivariable association of those factors with seeking care. RESULTS: Among 61,826 persons with migraine, the mean age was 41.7 years (±14.8) and 31,529/61,826 (51.0%) sought medical care for migraine in the previous 12 months. Of those seeking care for migraine, 23,106/31,529 (73.3%) were female, 21,320/31,529 (67.6%) were White, and 28,030/31,529 (88.9%) had health insurance. Severe interictal burden (assessed via the Migraine Interictal Burden Scale-4, MIBS-4) occurred in 52.8% (16,657/31,529) of those seeking care and in 23.1% (6991/30,297) of those not seeking care; similar patterns were observed for severe migraine-related disability (assessed via the Migraine Disability Assessment Scale, MIDAS) (36.7% [11,561/31,529] vs. 14.6% [4434/30,297]) and severe ictal cutaneous allodynia (assessed via the Allodynia Symptom Checklist, ASC-12) (21.0% [6614/31,529] vs. 7.4% [2230/30,297]). Severe interictal burden (vs. none, OR 2.64, 95% CI [2.5, 2.8]); severe migraine-related disability (vs. little/none, OR 2.2, 95% CI [2.0, 2.3]); and severe ictal allodynia (vs. none, OR 1.7, 95% CI [1.6, 1.8]) were strongly associated with seeking care for migraine. CONCLUSIONS: Seeking medical care for migraine is associated with higher interictal burden, disability, and allodynia. These findings could support interventions to promote care-seeking among people with migraine, encourage assessment of these factors during consultation, and prioritize these domains in selecting treatments and measuring their benefits.
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BACKGROUND: No algorithms exist to identify important osteoarthritis (OA) patient subgroups (i.e., moderate-to-severe disease, inadequate response to pain treatments) in electronic healthcare data, possibly due to the complexity in defining these characteristics as well as the lack of relevant measures in these data sources. We developed and validated algorithms intended for use with claims and/or electronic medical records (EMR) to identify these patient subgroups. METHODS: We obtained claims, EMR, and chart data from two integrated delivery networks. Chart data were used to identify the presence or absence of the three relevant OA-related characteristics (OA of the hip and/or knee, moderate-to-severe disease, inadequate/intolerable response to at least two pain-related medications); the resulting classification served as the benchmark for algorithm validation. We developed two sets of case-identification algorithms: one based on a literature review and clinical input (predefined algorithms), and another using machine learning (ML) methods (logistic regression, classification and regression tree, random forest). Patient classifications based on these algorithms were compared and validated against the chart data. RESULTS: We sampled and analyzed 571 adult patients, of whom 519 had OA of hip and/or knee, 489 had moderate-to-severe OA, and 431 had inadequate response to at least two pain medications. Individual predefined algorithms had high positive predictive values (all PPVs ≥ 0.83) for identifying each of these OA characteristics, but low negative predictive values (all NPVs between 0.16-0.54) and sometimes low sensitivity; their sensitivity and specificity for identifying patients with all three characteristics was 0.95 and 0.26, respectively (NPV 0.65, PPV 0.78, accuracy 0.77). ML-derived algorithms performed better in identifying this patient subgroup (range: sensitivity 0.77-0.86, specificity 0.66-0.75, PPV 0.88-0.92, NPV 0.47-0.62, accuracy 0.75-0.83). CONCLUSIONS: Predefined algorithms adequately identified OA characteristics of interest, but more sophisticated ML-based methods better differentiated between levels of disease severity and identified patients with inadequate response to analgesics. The ML methods performed well, yielding high PPV, NPV, sensitivity, specificity, and accuracy using either claims or EMR data. Use of these algorithms may expand the ability of real-world data to address questions of interest in this underserved patient population.
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Registros Eletrônicos de Saúde , Osteoartrite do Quadril , Adulto , Humanos , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/tratamento farmacológico , Dor/diagnóstico , Dor/tratamento farmacológico , Algoritmos , Algoritmo Florestas AleatóriasRESUMO
Since the introduction of the propensity score (PS), methods for estimating treatment effects with observational data have received growing attention in the literature. Recent research has added substantially to the number of available statistical approaches for controlling confounding in such analyses. However, researchers need guidance to decide on the optimal analytic strategy for any given scenario. To address this gap, we conducted simulations evaluating both well-established methods (regression, PS weighting, stratification, and matching) and more recently proposed approaches (tree-based methods, local control, entropy balancing, genetic matching, prognostic scoring). The simulation scenarios included tree-based and smooth regression models as true data-generation mechanisms. We evaluated an extensive number of analysis strategies combining different treatment choices and outcome models. Key findings include 1) the lack of a single best strategy across all potential scenarios; 2) the importance of appropriately addressing interactions in the treatment choice model and/or outcome model; and 3) a tree-structured treatment choice model and a polynomial outcome model with second-order interactions performed well. One limitation to this initial assessment is the lack of heterogeneous simulation scenarios allowing treatment effects to vary by patient.
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Modelos Estatísticos , Estudos Observacionais como Assunto , Pontuação de Propensão , Simulação por Computador , Humanos , Prognóstico , Resultado do TratamentoRESUMO
OBJECTIVE: Describe the characteristics, costs, and adherence of patients receiving human regular U-500 insulin (U-500R) compared with those of patients receiving high-dose (≥150 units/day) U-100 insulin. METHODS: Data from Truven Health MarketScan Research Databases, July 1, 2008, through December 31, 2010, were used. The U-100 cohort received ≥150 units/day of U-100 insulin for ≥31 days during the first 60 days after the index date. The U-500R cohort received ≥2 prescriptions of U-500R after the index date. Analyses were performed on propensity-matched cohorts. The changes in annualized costs were compared between the 2 cohorts using paired t tests. Adherence was assessed by the proportion of days covered (PDC) and compared using a 2-sample t test. Glycemic efficacy data were not available in this database. RESULTS: There were 1,044 U-500R-treated patients (19.1% with type 1 diabetes [T1D]) and 11,520 U-100-treated patients (23.8% with T1D) identified, from which 1,039 matched pairs were obtained. The mean decrease of $1,290 in annual pharmacy costs for the U-500R cohort was significantly different from the mean increase of $2,586 for the U-100 cohort (P<.001; 95% confidence interval, -$4,345 to -$3,422). More U-500R patients experienced hypoglycemia (17.3% vs. 11.8%; P<.001), but the hypoglycemia rate per person and related costs were not significantly different between cohorts. Finally, the mean 12-month PDC was 65.0% for U-500R versus 47.6% for U-100 patients (P<.0001). CONCLUSION: Compared with treatment with ≥150 units/day of U-100 insulin, treatment with U-500R was associated with decreases in pharmacy costs, a higher percentage of patients experiencing hypoglycemia, and greater treatment adherence.
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Diabetes Mellitus/tratamento farmacológico , Custos de Cuidados de Saúde , Insulina/administração & dosagem , Adesão à Medicação , Adulto , Idoso , Feminino , Humanos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are indicated for migraine prevention in the United States. Limited data comparing real-world treatment patterns for CGRP mAbs are available. Objective: To compare the treatment patterns among patients with migraine initiating galcanezumab, fremanezumab, and erenumab. Methods: This retrospective study included adult patients with one or more claims for a self-injectable CGRP mAb (galcanezumab, fremanezumab, or erenumab), with continuous enrollment in medical and pharmacy benefits for 12 months pre-index and 6 and 12 months post-index using MerativeTM MarketScan® Commercial and Medicare databases from May 2017 through March 2021. Propensity-score matching was used to address confounding by observed covariates. Outcomes analyzed included proportion of days covered (PDC), medication-possession ratio (MPR), persistence (≤60-day gap), treatment discontinuation, and switch to a non-index drug. Descriptive X2 and t-test analyses were conducted. Results: At the 12-month follow-up, matched galcanezumab and fremanezumab cohorts each comprised 2674 patients and the galcanezumab and erenumab cohorts 3503 each. The mean (SD) PDC and MPR were both 0.6 (0.3) across all cohorts. Based on PDC ≥0.80 and MPR ≥0.80, a greater proportion of galcanezumab vs fremanezumab (46.2% vs 43.7%, p=0.053; 46.8% vs 44.3%, p=0.053) and galcanezumab vs erenumab (46.2% vs 44%, p=0.156; 46.7% vs 44.5%, p=0.262), respectively, initiators were adherent. Compared to galcanezumab, fremanezumab (248.0 days vs 236.5 days, p=0.001), and erenumab (247.8 days vs 241.7 days, p=0.061) initiators had lower mean persistence. Galcanezumab initiators were less likely to discontinue treatment than fremanezumab (47.8% vs 51.7%, p=0.005) and erenumab (47.7% vs 50.2%, p=0.040) initiators. Across cohorts, most switchers initiated onabotulinum toxin A as subsequent treatment. Similar results were observed for 6-month follow-up cohorts. Conclusion: Patients with migraine who initiated treatment with galcanezumab showed higher persistence and lower treatment discontinuation rates than those initiating either fremanezumab or erenumab.
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INTRODUCTION: Migraine-related stigma (MiRS) and social burden is increasingly recognized. We assessed perspectives and attitudes toward migraine in people with and without migraine in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, population-based web survey of people with and without migraine (July-September 2020). People with migraine were individuals who met the modified International Classification of Headache Disorders criteria or had self-reported physician-diagnosed migraine. People without migraine were selected per quota sampling to represent the Japanese adult population. People with migraine reported their experiences on stigma and social burden and answered how frequently they experienced stigma using the MiRS questionnaire. Associations between MiRS and disability and MiRS and interictal burden were examined using the migraine disability assessment and Migraine Interictal Burden Scale-4. People without migraine reported their experiences and attitudes toward people with migraine by answering an 11-item attitudinal migraine questionnaire. RESULTS: A total of 17,071 and 2008 people with and without migraine, respectively, completed the survey. Overall, 11,228 (65.8%) respondents with migraine reported that they have never experienced stigma or burden; however, of the 12,383 employed respondents, 5841 (47.2%) reported that their current employers are not "extremely" or "very" understanding about their conditions. Moreover, â¼30%-40% of respondents "sometimes," "often," or "very often" hid their migraine from others. The proportion of respondents who experienced stigma often or very often, as assessed by MiRS, was 16.5%; this increased with the increasing number of monthly migraine headache days. The proportion of respondents with moderate-to-severe disability and interictal burden increased with increasing stigma. Among respondents without migraine, the proportion holding a stigmatizing attitude toward those with migraine was low (<15%); â¼80% had never experienced work- or family-related stigma or burden. CONCLUSION: MiRS and burden exist but may be hidden and underrecognized in Japan. Disease awareness and education may be important to prevent and reduce stigma and burden.
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Efeitos Psicossociais da Doença , Transtornos de Enxaqueca , Estigma Social , Humanos , Transtornos de Enxaqueca/psicologia , Japão , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Adulto Jovem , Inquéritos e Questionários , Idoso , Estereotipagem , Conhecimentos, Atitudes e Prática em Saúde , AdolescenteRESUMO
Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.
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Doenças Cardiovasculares , Crotonatos , Diabetes Mellitus Tipo 2 , Hidroxibutiratos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Nitrilas , Insuficiência Renal Crônica , Toluidinas , Adulto , Humanos , Imunossupressores/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Estudos Retrospectivos , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Incidência , Fator 2 Relacionado a NF-E2 , Cloridrato de Fingolimode/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVES: This population-based analysis characterizes the relative frequency of migraine-related stigma and its cross-sectional relationship to migraine outcomes. We hypothesized that migraine-related stigma would be inversely associated with favorable migraine outcomes across headache day categories. METHODS: OVERCOME (US) is a web-based observational study that annually recruited a demographically representative US sample and then identified people with active migraine using a validated migraine diagnostic questionnaire. It also assessed how frequently respondents experienced migraine-related stigma using a novel 12-item questionnaire (Migraine-Related Stigma, MiRS) that contained 2 factors; feeling that others viewed migraine as being used for Secondary Gain (8 items, α = 0.92) and feeling that others were Minimizing disease Burden (4 items, α = 0.86). We defined 5 groups: (1) MiRS-Both (Secondary Gain and Minimizing Burden often/very often; (2) MiRS-SG (Secondary Gain often/very often); (3) MiRS-MB (Minimizing Burden often/very often); (4) MiRS-Rarely/Sometimes; (5) MiRS-Never. Using MiRS group as the independent variable, we modeled its cross-sectional relationship to disability (Migraine Disability Assessment, MIDAS), interictal burden (Migraine Interictal Burden Scale-4), and migraine-specific quality of life (Migraine Specific Quality of Life v2.1 Role Function-Restrictive) while controlling for sociodemographics, clinical features, and monthly headache day categories. RESULTS: Among this population-based sample with active migraine (n = 59,001), mean age was 41.3 years and respondents predominantly identified as female (74.9%) and as White (70.1%). Among respondents, 41.1% reported experiencing, on average, ≥4 monthly headache days and 31.7% experienced migraine-related stigma often/very often; the proportion experiencing migraine-related stigma often/very often increased from 25.5% among those with <4 monthly headache days to 47.5% among those with ≥15 monthly headache days. The risk for increased disability (MIDAS score) was significant for each MiRS group compared with the MiRS-Never group; the risk more than doubled for the MiRS-Both group (rate ratio 2.68, 95% CI 2.56-2.80). For disability, interictal burden, and migraine-specific quality of life, increased migraine-related stigma was associated with increased disease burden across all monthly headache day categories. DISCUSSION: OVERCOME (US) found that 31.7% of people with migraine experienced migraine-related stigma often/very often and was associated with more disability, greater interictal burden, and reduced quality of life.
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Transtornos de Enxaqueca , Qualidade de Vida , Humanos , Feminino , Adulto , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Cefaleia , Efeitos Psicossociais da Doença , Inquéritos e Questionários , Avaliação da DeficiênciaRESUMO
BACKGROUND: Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. OBJECTIVE: To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. METHODS: OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July-September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. RESULTS: The analysis included 9075 survey respondents (OTC only: n = 5791; Rx-NSAIDs/ACE only: n = 751; triptans: n = 2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40-0.54], 0.56 [0.35-0.89], and 0.41 [0.32-0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively). CONCLUSION: People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.
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INTRODUCTION: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) assessed the impact and burden of migraine in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of Japanese people with migraine conducted between July and September 2020. The burden and impact of migraine were assessed using the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), and Work Productivity and Activity Impairment-Migraine scale. Results were stratified by average number of monthly headache days (0-3, 4-7, 8-14, ≥ 15). RESULTS: In total, 17,071 Japanese people with migraine completed the survey. Of these, 14,033 (82.2%) met International Classification of Headache Disorders, 3rd edition criteria for migraine and 9667 (56.6%) reported a physician diagnosis of migraine. Overall, 20.7% of respondents experienced moderate-to-severe disability (MIDAS). Moderate-to-severe interictal burden (MIBS-4) was experienced by 41.5% of respondents. MSQ scores in all domains were lowest in respondents with the most frequent headaches (≥ 15 monthly headache days) and highest in those with the lowest frequency headaches (≤ 3 monthly headache days), indicating poorer quality of life in those with more frequent headaches. Work time missed due to migraine (absenteeism) increased with increasing headache frequency, from 3.8 to 6.2%; presenteeism affected 29.8-49.9% of work time. Although migraine burden was greatest in people with the most frequent headaches, those with the lowest headache frequency still experienced substantial disability, interictal burden, and impacts on productivity and quality of life. There was also substantial unmet need for migraine care: 36.5% of respondents had ever hesitated to seek medical care for their headaches, and 89.8% had never used preventive medication. CONCLUSION: In Japan, the burden of migraine and barriers to migraine care are substantial. Improving patient awareness and healthcare provider vigilance may help improve patient outcomes.
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INTRODUCTION: Using data from the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]), we describe the current status of the acute treatment of migraine in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of people with migraine in Japan (met modified International Classification of Headache Disorders criteria or had a physician diagnosis of migraine) conducted between July and September 2020. Respondents reported current acute medication use and effectiveness (assessed using the Migraine Treatment Optimization Questionnaire [mTOQ-4]). Cardiovascular history and risk factors of the respondents were also recorded. Potential unmet acute treatment needs were defined as insufficient effect of current acute treatments (mTOQ-4 score ≤ 5), a history of oral triptan use (and not currently taking any triptan), potential contraindications to triptans due to cardiovascular comorbidities, and/or cardiovascular risk factors. RESULTS: In total, 17,071 people with migraine in Japan completed the survey; 14,869 (87.1%) of these were currently using acute treatments. Poor effectiveness of current acute treatment was reported by 7170 respondents (42.0%), 900 respondents (5.3%) were former triptan users, 1759 (10.3%) had contraindications to triptans, and 9026 (52.9%) reported at least one cardiovascular risk factor. Overall, 12,649 (74.1%) of OVERCOME (Japan) respondents were categorized into one or more of these groups and were considered to have potential unmet acute treatment needs. CONCLUSION: Almost three-quarters of people with migraine in Japan may have potential unmet needs for acute treatment of migraine. There are substantial opportunities for improving care for people with migraine in Japan, including prescription of novel acute medications.
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Transtornos de Enxaqueca , Triptaminas , Estudos Transversais , Humanos , Japão/epidemiologia , Estudos Longitudinais , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Triptaminas/uso terapêuticoRESUMO
OBJECTIVE: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) aimed to provide an up-to-date assessment of migraine epidemiology in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, population-based web survey of Japanese adults recruited from consumer panels. People with active migraine (met modified International Classification of Headache Disorders, 3rd edition [ICHD-3] criteria or had a self-reported physician diagnosis of migraine) answered questions about headache features, physician consultation patterns, and migraine medication use. The burden and impact of migraine were assessed using Migraine Disability Assessment (MIDAS) and Work Productivity and Activity Impairment scales. RESULTS: In total, 231,747 respondents accessed the screener, provided consent, and were eligible for the survey. The migraine group included 17,071 respondents (mean ± SD age 40.7 ± 13.0 years; 66.5% female). ICHD-3 migraine criteria were met by 14,033 (82.2%) respondents; 9667 (56.6%) self-reported a physician diagnosis of migraine. The mean number of monthly headache days was 4.5 ± 5.7 and pain severity (0-10 scale) was 5.1 ± 2.2. In the migraine group, 20.7% experienced moderate to severe migraine-related disability (MIDAS score ≥ 11). Work productivity loss was 36.2% of work time missed, including 34.3% presenteeism. Only 57.4% of respondents had ever sought medical care for migraine/severe headache. Most respondents (75.2%) were currently using over-the-counter medications for migraine; 36.7% were using prescription nonsteroidal anti-inflammatory drugs, and only 14.8% were using triptans. Very few (9.2%) used preventive medications. CONCLUSIONS: Unmet needs for migraine health care among people with migraine in Japan include low rates of seeking care and suboptimal treatment.
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Transtornos de Enxaqueca , Adulto , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Inquéritos e Questionários , TriptaminasRESUMO
OBJECTIVE: The effects of GH replacement on glucose metabolism in GH-deficient (GHD) adults in clinical practice are not well defined. Therefore, we assessed GH treatment effects on fasting plasma glucose (FPG) and haemoglobin A1c (A1c) concentrations in GHD adults in a clinical setting. DESIGN: Post-hoc analysis of the observational Hypopituitary Control and Complications Study conducted at 157 US centres (1997-2002). PATIENTS: GH-deficient adults who were GH-naïve at study entry and had at least two FPG measurements. MEASUREMENTS: Effect of GH treatment on the frequency and time course of abnormal FPG (> or =5.6 mmol/l) development, FPG normalization, progression of increased FPG and abnormal follow-up A1c (>6%) values in GHD patients treated with GH (n = 403) or untreated (n = 169) at their physician's discretion. RESULTS: In subjects without pre-existing diabetes mellitus, development of an abnormal FPG tended to occur in a greater percentage of GH-treated than untreated subjects (35.3% versus 24.5, P = 0.06). Additionally, GH treatment was associated with a mild, transient increase in FPG and shorter time to development of an abnormal FPG in these subjects (P < 0.01). Most ( approximately 80%) abnormal FPG values were below 7 mmol/l and normalized in 69% of GH-treated subjects without diabetes. Treatment with GH had no effect on the rate of FPG normalization, progression of increased FPG or abnormal follow-up A1c values. CONCLUSIONS: Initiation of GH replacement in GHD adults was associated with a mild increase in FPG that often normalized spontaneously. Nevertheless, clinicians should monitor FPG in patients receiving GH treatment.
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Intolerância à Glucose/epidemiologia , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/epidemiologia , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Algoritmos , Glicemia/metabolismo , Complicações do Diabetes/sangue , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Jejum/sangue , Jejum/metabolismo , Seguimentos , Hemoglobinas Glicadas/análise , Transtornos do Crescimento/sangue , Transtornos do Crescimento/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de TempoRESUMO
CONTEXT: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth. OBJECTIVE: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort. DESIGN: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003). SETTING: The study was conducted at 11 U.S. pediatric endocrine centers. SUBJECTS: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled. INTERVENTIONS: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr. MAIN OUTCOME MEASURE: The main outcome measure was baseline-to-2-yr change in height SDS. RESULTS: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected. CONCLUSION: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.
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Transtornos do Crescimento/complicações , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Determinação da Idade pelo Esqueleto , Desenvolvimento Ósseo/efeitos dos fármacos , Pré-Escolar , Feminino , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Lactente , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Síndrome de Turner/sangueRESUMO
CONTEXT: Little information exists regarding FSH values in very young girls with Turner syndrome (TS). OBJECTIVES: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS. STUDY DESIGN: FSH was measured at study entry and annually for 2 yr. SETTING: The Toddler Turner study was conducted at 11 U.S. pediatric endocrine centers. STUDY PARTICIPANTS: Eighty-eight girls with karyotype-proven TS aged 9 months to 4 yr participated in the study. MAIN OUTCOME MEASURES: By-karyotype differences in FSH concentration and age-related changes in FSH were measured. RESULTS: Mean (+/- SD) FSH was markedly elevated in the 45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P < 0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (-13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell within normal range for age at any time during the 2-yr study. FSH decline was similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no significant decrease in FSH with age was observed in the 45,X/46,XX group. CONCLUSIONS: In contrast to the original report of FSH concentrations in individuals with TS, this study demonstrates distinct differences in patterns of FSH secretion between young girls with monosomy TS, who have persistent elevation of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest retained ovarian function in the majority. These findings have implications for patient management and family counseling.
Assuntos
Hormônio Foliculoestimulante/metabolismo , Mosaicismo , Síndrome de Turner/sangue , Envelhecimento/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Aberrações Cromossômicas , Feminino , Hormônio do Crescimento/uso terapêutico , Cardiopatias Congênitas/genética , Humanos , Lactente , Padrões de Herança , Rim/anormalidades , Síndrome de Turner/tratamento farmacológicoRESUMO
OBJECTIVE: The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus (DM). METHODS: This single-center, randomized, double-blind, 3-way crossover study was conducted at the Diabetes and Glandular Disease Research Center, San Antonio, Texas. We measured serum glucose responses after a standardized breakfast test meal (500 kcal; 50% carbohydrate, 34% fat, 16% protein) in patients with type 2 DM receiving a single preprandial dose of human insulin 70/30, insulin lispro 75/25, or insulin lispro 50/50 by SC injection. All patients previously used insulin for at least 1 month prior to the study. The glucose responses were compared with those of healthy, untreated subjects administered the identical meal. RESULTS: A total of 33 patients were enrolled (23 with type 2 DM and 10 healthy controls). The baseline characteristics of the patients were as follows: sex ratio (M:F), 17:6; mean (SD) age, 61.3 (10.0) years; mean (SD) body weight, 98.5 (13.2) kg; mean (SD) body mass index, 33.0 (3.8) kg/m(2); mean (SD) glycosylated hemoglobin, 8.1% (1.6%); mean (SD) fasting serum glucose (FSG), 158.7 (27.6) mg/dL; and 56.5% white, 8.7% black, and 34.8% Hispanic. The mean (SD) doses (U/d) of the fixed-mixture preparations were similar: human insulin 70/30, 44.1 (18.2); insulin lispro 75/25, 44.1 (18.2); and insulin lispro 50/50, 43.8 (17.8). FSG levels obtained before the test meal were not significantly different between treatments. Compared with those in healthy subjects, incremental glucose AUC values for the 4 hours after the meal (AUCglucose 0-4) for patients with type 2 DM were 6.4-fold higher with human insulin 70/30, 4.6-fold higher with insulin lispro 75/25, and 3.0-fold higher with insulin lispro 50/50. Each insulin regimen produced AUC(glucose) 0-4 and 2-hour PPG values significantly different from all other regimens (all, P < 0.05). Mean (SD) 2-hour PPG values (mg/dL) were lower with mixtures containing insulin lispro than with human insulin 70/30 and decreased as the proportion of insulin lispro within the fixed mixtures increased: human insulin 70/30, 212.6 (47.0); insulin lispro 75/25, 198.0 (67.5); and insulin lispro 50/50, 158.8 (52.3). CONCLUSIONS: In this small study in patients with type 2 DM and healthy controls, preprandial administration of a fixed mixture containing rapid-acting or regular insulin and intermediate-acting components was associated with attenuation of the rise in PPG in patients with type 2 DM administered a test meal. Mixtures containing insulin lispro were associated with greater decreases in PPG concentrations compared with human insulin 70/30. Furthermore, greater amounts of rapid-acting insulin contained within the mixture were associated with better PPG control.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Insulina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Período Pós-PrandialRESUMO
OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/sangue , Lipídeos/sangue , Tiazolidinedionas/uso terapêutico , Idoso , Apolipoproteínas B/sangue , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pioglitazona , Placebos , Rosiglitazona , Triglicerídeos/sangueRESUMO
OBJECTIVES: This study assessed whether the choice of vascular access site influenced outcomes among non-ST-segment elevation myocardial infarction (NSTEMI) patients enrolled in the ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction NCT01015287). BACKGROUND: Transfemoral access (TFA) has been associated with the risk of bleeding and increased mortality that is elevated compared to transradial access (TRA) in acute coronary syndromes, although less consistently in NSTE acute coronary syndrome (NSTE-ACS) than in STE-ACS. METHODS: The ACCOAST study evaluated a prasugrel loading dose of 60 mg given at the start of percutaneous coronary intervention (PCI) versus a split loading dose of 30 mg given at the time of diagnosis of NSTE-ACS (prior to coronary angiography), followed by 30 mg given at the start of PCI. In the study, choice of access site was at the investigator's discretion. We compared ischemic and bleeding outcomes with TFA versus those with TRA, using propensity score correction. RESULTS: Of 4,033 patients, 1,711 (42%) underwent TRA. Use of TRA varied widely by country. TFA was not associated with significant increases in noncoronary bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) (hazard ratio [HR] for TFA = 1.46; 95% confidence interval [CI]: 0.59 to 3.62; p = 0.42), nor in GUSTO (Global Utilization Of Streptokinase and Tpa for Occluded arteries) or STEEPLE (Safety and Efficacy of Enoxaparin in PCI) major bleeding after propensity score correction. TFA, however, increased combined non-CABG TIMI major or minor bleeding (HR for TFA = 2.34; 95% CI: 1.17 to 4.69; p = 0.017). Primary ischemic outcomes did not differ by access site, albeit individual endpoint analysis suggested an association between TFA with an increase in urgent revascularizations and reduced risk of procedure-related stroke. CONCLUSIONS: In the ACCOAST trial, TFA did not significantly increase TIMI major bleeding, although TRA was associated with a reduction in TIMI major or minor bleeding. Further study is needed to determine whether wider application of radial approach to NSTE-ACS patients at high risk for bleeding improves overall outcomes. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287).
Assuntos
Síndrome Coronariana Aguda/terapia , Cateterismo Periférico/métodos , Artéria Femoral , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Artéria Radial , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Cateterismo Periférico/efeitos adversos , Angiografia Coronária , Bases de Dados Factuais , Feminino , Hemorragia/induzido quimicamente , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Punções , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Many patients with childhood-onset growth hormone (GH) deficiency do not fulfill diagnostic criteria for GH deficiency (GHD) after attainment of adult height and may not require long-term GH treatment. Patients with history of idiopathic GHD (IGHD) pose the greatest management dilemma, as data regarding factors predictive of persistent GHD in this group are lacking. OBJECTIVES: The objective of this study was to assess potential predictors of persistent GHD in a US patient cohort during transition from childhood to adulthood, particularly in patients with history of IGHD. METHODS: We studied 73 US patients with history of childhood-onset GHD screened at 21 US pediatric endocrine centers for a randomized clinical trial of GH replacement after attainment of adult height. The cohort comprised 42 boys/men and 31 girls/women aged14-22 years, who had received ≥1 year of GH treatment and had completed linear growth. The main outcome measures were sensitivity, specificity, positive and negative predictive values (PPV, NPV) of clinical and hormonal factors for persistent GHD (defined a priori in this study as peak GH < 5 µg/L). RESULTS: For the cohort as a whole, the best predictors of persistent GHD (100% PPV) were history of organic hypothalamic-pituitary disorder or ≥2 additional pituitary hormone deficiencies (PHD). Best predictors of persistent GHD in patients with childhood history of IGHD were standard deviation scores (SDS) for serum insulin-like growth factor binding protein-3 (IGFBP-3) below -2.0, and for insulin-like growth factor-I (IGF-I) below -5.3 (measured ≥6 weeks after completion of GH treatment; PPV 100% for both), and age <4 years at original diagnosis (PPV 89%). IGF-I above -1.6 SDS had 100% NPV. CONCLUSIONS: US patients with an organic cause of childhood-onset GHD or ≥2 additional PHDs may not require GH stimulation testing to reconfirm GHD after completion of childhood treatment. In contrast, patients with idiopathic childhood-onset GHD almost invariably require retesting, as GHD persists in only a minority (those who were very young at initial diagnosis and those who have subnormal IGFBP-3 or extremely low IGF-I after completion of childhood treatment). Subnormal posttreatment IGF-I (<-2.0 SDS) lacked predictive power for persistent GHD, whereas IGF-I > -1.6 SDS was 100% predictive of GH sufficiency.
RESUMO
OBJECTIVES: To compare adherence between once-daily (QD) and twice-daily (BID) dosing with chronic-use prescription medications used by patients with cardiovascular disease. STUDY DESIGN: Retrospective cohort database analysis. METHODS: Analysis consisted of 1,077,474 patients aged >18 years with a prescription index date from January 1 to December 31, 2007, for an antidiabetic, antihyperlipidemic, antiplatelet, or cardiac agent with QD or BID dosing. Adherence (medication possession ratio [MPR]) was the number of days of medication supplied between the first prescription fill date and the subsequent 365 days divided by 365 days. Overall mean MPR and comparisons between dosing frequency groups were assessed with a generalized estimating equation. Covariates included age at index date, gender, Charlson comorbidity index, therapeutic class, dosing frequency, and the interaction between therapeutic class and dosing frequency group. RESULTS: Overall, the adjusted mean MPR ± standard error (SE) value for QD agents was 13.6% greater than BID agents (0.66 ± 0.0006 vs 0.57 ± 0.0016; P <.01). The adjusted mean MPR value for QD agents was 2.9%, 17.5%, and 29.4% greater than BID agents in the antidiabetic, antihyperlipidemic, and antiplatelet therapeutic classes, respectively. For cardiac agents, the adjusted mean MPR value was similar between QD and BID agents. Carvedilol represented approximately 80% of the cardiac agents in the BID group. The adjusted mean MPR ± SE for carvedilol phosphate QD was 0.73 ± 0.0024 and 0.65 ± 0.0027 for carvedilol BID (11% difference; P <.01). CONCLUSIONS: In this large analysis, the QD dosing regimen was related to greater adherence versus a BID regimen.