Use of Anti-Dementia Drugs Reduces the Risk of Potentially Inappropriate Medications: A Secondary Analysis of a Nationwide Survey of Prescribing Pharmacies.

AIMS: As the number of older people with dementia increases, safe pharmacotherapy in this population has attracted attention in recent years. The aims of this study were to clarify the prescribing patterns in older patients who were prescribed anti-dementia drugs and to investigate the association of potentially inappropriate medications (PIMs) with the use of anti-dementia drugs. METHODS: Adults aged ≥65 years, who were prescribed anti-dementia drugs at 585 pharmacies across Japan (N = 7,953), were surveyed. The percentage of prescriptions of anti-dementia drugs and the effect of those prescriptions on PIMs were investigated. RESULTS: Prescriptions of anti-dementia drugs were found in 4.4% of the entire study population. A multiple logistic regression analysis revealed that the use of anti-dementia drugs reduced the risk of prescribing psychotropic drugs, which represented PIMs, and that a combination of anti-dementia drugs (e.g., cholineesterase inhibitor with memantine) may reduce the risk of prescribing PIMs compared with monotherapy. CONCLUSION: The use of anti-dementia drugs was associated with fewer prescriptions of drugs considered as PIMs.

Pharmaceutical Treatment for Alzheimer's Disease and Related Dementias: Utilization and Disparities.

BACKGROUND: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD. OBJECTIVE: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity. METHODS: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities). RESULTS: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis. CONCLUSIONS: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study.

Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer's Disease Treatment Using Real-World Evidence in Thailand.

OBJECTIVES: Decision-analytic models for Alzheimer's disease (AD) have been advanced to a discrete-event simulation (DES), in which individual-level modeling of disease progression across continuous severity spectra become feasible. This study aimed to apply DES to perform cost-effectiveness analysis of AD treatment in Thailand. METHODS: A data set of Thai AD patients, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of 50 000 patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine, or no treatment. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence; mortality; and predictive equations for functional status, costs (Thai baht in 2017), and quality-adjusted life-year (QALY) were derived from country-specific real-world data. RESULTS: From a societal perspective, only the prescription of donepezil to AD patients with all disease-severity levels was found to be cost-effective (incremental cost-effectiveness ratio): 138 524 Thai baht/QALY ($4062/QALY)]. Regardless of whether the treatment-stopping rule when the mini-mental state examination score <10 was introduced, providing early treatment with donepezil to mild AD patients further reduced the incremental cost-effectiveness ratio. Extensive sensitivity analyses indicated robust simulation findings. CONCLUSIONS: Discrete-event simulation greatly enhances the real-world representativeness of decision-analytic models for AD. Donepezil is the most cost-effective treatment option for AD in Thailand and is worth being considered for universal financial coverage. Application of DES in heath technology assessment should be encouraged, especially when the validity of the model is questionable with classical modeling methods.

Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students / Prevalência e fatores associados ao uso de metilfenidato para neuroaprimoramento farmacológico entre estudantes universitários

ABSTRACT Objective To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. Methods Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. Results Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. Conclusion The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

RESUMO Objetivo Estimar a prevalência e os fatores associados ao uso de metilfenidato para neuroaprimoramento entre estudantes universitários. Métodos Amostra aleatória simples de discentes da Universidade Federal de Minas Gerais (n=438), convidados a responder um questionário online sobre o consumo de metilfenidato. A coleta ocorreu de setembro de 2014 a janeiro de 2015. A amostra foi descrita em termos de proporções, médias e desvio padrão. A análise multivariada foi realizada utilizando o algoritmo Classification and Regression Tree para classificação dos casos de uso do metilfenidato para neuroaprimoramento em grupos, com base nas variáveis de exposição. Resultados Dos 378 alunos incluídos, 5,8% (n=22) declararam ter feito uso de metilfenidato para neuroaprimoramento, sendo 41% (9/22) nas 4 semanas anteriores à pesquisa. A situação da moradia foi a variável mais associada ao uso de metilfenidato para neuroaprimoramento. Relataram o uso do metilfenidato para neuroaprimoramento e outros fins nas 4 semanas anteriores à pesquisa 11 estudantes, sendo que 27% não apresentaram prescrição médica para adquiri-lo. Conclusão O uso de metilfenidato para neuroaprimoramento ocorre no meio acadêmico brasileiro e deve ser considerado sério problema de saúde pública, principalmente diante dos riscos de danos e efeitos adversos associados ao seu uso.

Cerebrolysin for vascular dementia.

BACKGROUND: Although vascular dementia is the second most common cause of dementia globally, evidence-based treatments are still lacking. Cerebrolysin is a porcine brain-derived preparation that is said to have neurotrophic and neuroprotective activity. In many parts of the world Cerebrolysin, given as a series of daily intravenous infusions, is used as a potential intervention for vascular dementia. A previous Cochrane Review on Cerebrolysin in vascular dementia yielded inconsistent results. We wished to update the review to add new studies from the international literature and employ contemporary methods for appraising the strength of the evidence. This is the first update of a review first published in 2013. OBJECTIVES: Primary: to assess the effect of Cerebrolysin on cognitive function, global function, and all-cause mortality in people living with vascular dementia. Secondary: to assess the adverse effects of Cerebrolysin and to assess the effect of Cerebrolysin on quality of life and caregiver burden. SEARCH METHODS: We searched ALOIS, MEDLINE, Embase, PsycINFO, CINAHL, ISI Web of Knowledge, LILACS, the Cochrane Library, ClinicalTrials.gov, and the WHO ICTRP on 16 June 2017, 9 May 2018, and 9 May 2019. We expanded the search by adding four Chinese databases, searched from 1 January 2012 to 19 May 2019. We checked bibliographies of relevant papers identified and contacted pharmaceutical companies, trial authors, and experts in the field to identify any additional published or unpublished data. SELECTION CRITERIA: We included all randomised controlled trials of Cerebrolysin used in people living with vascular dementia. We applied no language restriction. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and evaluated their methodological quality. Data were extracted and analysed using mean differences (MDs) or standardised mean differences (SMDs) with 95% confidence intervals (95% CI) for continuous outcomes. We reported dichotomous outcomes as risk ratio (RR) with 95% CI. We assessed the strength of the available evidence using the GRADE approach. MAIN RESULTS: We identified six randomised controlled trials with a total of 597 participants that were eligible for inclusion in the 2013 review. No new studies were eligible for inclusion in this update. Participants in the included studies, where dementia severity was reported, had mild to moderate severity of vascular dementia (four trials). The included studies tested varying doses and duration of Cerebrolysin treatment. Follow-up ranged from 15 days to three years. Five of included studies were conducted in China (three studies), Russia (one study), and Romania (one study), while relevant information of other study was unclear. Where details of funding were available, all studies were supported by the pharmaceutical industry (three studies). Cognitive function was measured using the Mini-Mental State Examination (MMSE) or Alzheimer's Disease Assessment Scale Cognitive Subpart, extended version (ADAS-cog+). Combining the MMSE and ADAS-cog+ data (three studies, 420 people), there was a beneficial effect of Cerebrolysin (SMD 0.36, 95% CI 0.13 to 0.58; very low-quality evidence). Global function was measured by Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC+) or Investigator's Clinical Global Impression (CGI). We assessed response rates on these measures (the proportion of participants with a CIBIC+ score of < 3; or at least moderate improvement of the CGI rating at the last visit). There was a beneficial effect of Cerebrolysin (two studies, 379 participants, RR 2.69, 95% CI 1.82 to 3.98; very low-quality evidence). Only one trial described mortality and reported no deaths. Four studies reported adverse events; data from two studies (379 people) were in a format that permitted meta-analysis, and there was no difference in rates of adverse effects (RR 0.91, 95% CI 0.29 to 2.85; very low-quality evidence). No studies reported on quality of life or caregiver burden. AUTHORS' CONCLUSIONS: Courses of intravenous Cerebrolysin improved cognition and general function in people living with vascular dementia, with no suggestion of adverse effects. However, these data are not definitive. Our analyses were limited by heterogeneity, and the included papers had high risk of bias. If there are benefits of Cerebrolysin, the effects may be too small to be clinically meaningful. There have been no new studies of Cerebrolysin in vascular dementia since the last Cochrane Review. Cerebrolysin continues to be used and promoted as a treatment for vascular dementia, but the supporting evidence base is weak. Adequately powered, methodologically robust trials are needed to properly assess the effects of Cerebrolysin in vascular dementia.

Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students.

OBJECTIVE: To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. METHODS: Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. RESULTS: Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. CONCLUSION: The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

Effect of drug compliance on health care costs in newly-diagnosed dementia: Analysis of nationwide population-based data.

BACKGROUND: The cost-effectiveness of both cholinesterase inhibitors and memantine by delaying nursing home placement has been supported by numerous studies. The importance of sustained pharmacological treatment in dementia has been relatively less recognized by public health policies compared to early diagnosis. We investigated the effect of the drug (donepezil, rivastigmine, galantamine, and memantine) compliance on the health care costs in newly-diagnosed dementia. METHODS: National Health Insurance Service (NHIS) database which covers the entire population of South Korea was used for analysis. Health care expenditure of patients newly-diagnosed with dementia in between 2012 and 2014 was investigated for 3-5 years. For drug compliance, we used Medication Possession Ratio (MPR) that indicates the percentage of time a patient has access to medication. Multivariate linear regression analysis including generalized estimated equation and gamma distribution was used for statistical analysis. RESULTS: We identified 252,594 patients who were both prescribed with cognitive enhancers and newly diagnosed with dementia. When initial MPR increased 20%, total health care costs decreased 8.4% (RR = 0.916, 95%; CI 0.914 to 0.916). Same relationship was shown with medical costs related to dementia, admission to a general hospital, and emergency room visits. When MPR increased 20% compared to the previous year, the total health care costs, admission to a general hospital, emergency room visits, and admission to a nursing hospital decreased. CONCLUSIONS: This population-based retrospective cohort study provides evidence that patients newly-diagnosed with dementia who showed higher initial drug compliance or maintained antidementia drugs (Cholinesterase inhibitors and memantine) would benefit in total health-care costs.

Drug costs in long-term care facilities under a per diem bundled payment scheme in Japan.

AIM: The present study aimed to evaluate drug costs per resident at Japanese intermediate care facilities for older adults (called Roken) in relation to drug utilization after admission to these facilities. The payment, including coverage of drugs, is mainly determined by the resident's long-term care needs. METHODS: A nationwide drug utilization survey was carried out. The participants were 1324 residents of 350 Roken (up to five individuals per facility) who were admitted in 2015 and agreed to participate in this study. Drug costs per resident per month at admission and 2 months later were calculated for drugs prescribed for regular use. Associations between characteristics of the residents and drug costs were examined. RESULTS: A wide variation in drug costs with a long right tail was observed. Median drug costs were $77 (interquartile range $34-147) at admission, and $46 (interquartile range $19-98) in month 2. There was no apparent association between the level of long-term care needs and drug costs, adjusting for sex, age and main place of residence before admission. Anti-dementia drugs accounted for the largest portion of total drug costs at admission (15.4%) and in month 2 (12.4%). The average drug cost per user was also the highest for anti-dementia drugs ($90.2 per user per month), followed by drugs for Parkinson's disease ($70.3). The proportion of generic drugs across all drug classes examined increased after admission. CONCLUSIONS: These findings might suggest that implementation of the bundled payment scheme would be effective for the reduction of medication costs in institutional long-term care. Geriatr Gerontol Int 2019; 19: 667-672.

Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia.

Importance: Amyloid positron emission tomography (PET) detects amyloid plaques in the brain, a core neuropathological feature of Alzheimer disease. Objective: To determine if amyloid PET is associated with subsequent changes in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology. Design, Setting, and Participants: The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study was a single-group, multisite longitudinal study that assessed the association between amyloid PET and subsequent changes in clinical management for Medicare beneficiaries with MCI or dementia. Participants were required to meet published appropriate use criteria stating that etiology of cognitive impairment was unknown, Alzheimer disease was a diagnostic consideration, and knowledge of PET results was expected to change diagnosis and management. A total of 946 dementia specialists at 595 US sites enrolled 16 008 patients between February 2016 and September 2017. Patients were followed up through January 2018. Dementia specialists documented their diagnosis and management plan before PET and again 90 (±30) days after PET. Exposures: Participants underwent amyloid PET at 343 imaging centers. Main Outcomes and Measures: The primary end point was change in management between the pre- and post-PET visits, as assessed by a composite outcome that included Alzheimer disease drug therapy, other drug therapy, and counseling about safety and future planning. The study was powered to detect a 30% or greater change in the MCI and dementia groups. One of 2 secondary end points is reported: the proportion of changes in diagnosis (from Alzheimer disease to non-Alzheimer disease and vice versa) between pre- and post-PET visits. Results: Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI). Amyloid PET results were positive in 3817 patients with MCI (55.3%) and 3154 patients with dementia (70.1%). The composite end point changed in 4159 of 6905 patients with MCI (60.2% [95% CI, 59.1%-61.4%]) and 2859 of 4504 patients with dementia (63.5% [95% CI, 62.1%-64.9%]), significantly exceeding the 30% threshold in each group (P < .001, 1-sided). The etiologic diagnosis changed from Alzheimer disease to non-Alzheimer disease in 2860 of 11 409 patients (25.1% [95% CI, 24.3%-25.9%]) and from non-Alzheimer disease to Alzheimer disease in 1201 of 11 409 (10.5% [95% CI, 10.0%-11.1%]). Conclusions and Relevance: Among Medicare beneficiaries with MCI or dementia of uncertain etiology evaluated by dementia specialists, the use of amyloid PET was associated with changes in clinical management within 90 days. Further research is needed to determine whether amyloid PET is associated with improved clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02420756.

Association of Antidementia Therapies With Time to Skilled Nursing Facility Admission and Cardiovascular Events Among Elderly Adults With Alzheimer Disease.

Importance: To date, no study has compared time to skilled nursing facility (SNF) admission and cardiovascular events across medications available to treat Alzheimer disease. Objective: To compare time to SNF admission and cardiovascular events between acetylcholinesterase inhibitor (AChEI) monotherapy, memantine hydrochloride monotherapy, and combination therapy with an AChEI and memantine in treating elderly adults with Alzheimer disease. Design, Setting, and Participants: This retrospective cohort study uses January 1, 2006, to December 31, 2014, claims data from a 5% random sample of Medicare beneficiaries who had received a new diagnosis of Alzheimer disease between January 1, 2007, and December 31, 2013, and who initiated AChEI monotherapy, memantine monotherapy, or combination therapy with an AChEI and memantine (N = 73 475). Patients were followed up until discontinuation of treatment, switch of treatment, death, or the end of the study period. Statistical analysis was conducted from February 15, 2018, to June 15, 2018. Exposures: Acetylcholinesterase inhibitor monotherapy (n = 44 424), memantine monotherapy (n = 11 809), and combination therapy with an AChEI and memantine (n = 17 242). Main Outcomes and Measures: Primary outcomes were time to SNF admission and the composite of the following cardiovascular events: acute myocardial infarction, bradycardia, syncope, atrioventricular block, QT interval prolongation, and ventricular tachycardia. Cox proportional hazards regression models were constructed to compare outcomes between each pair of treatment groups, controlling for a comprehensive list of patient characteristics. Results: The study population included 73 475 participants (53 068 women and 20 407 men; mean [SD] age, 81.8 [8.3] years); 25.5% of the participants initiating AChEI monotherapy, 25.6% of participants initiating memantine monotherapy, and 29.7% of participants initiating combination therapy with an AChEI and memantine were admitted to an SNF. Similarly, 22.2% of the participants initiating AChEI monotherapy, 20.0% of those initiating memantine monotherapy, and 24.5% of those initiating combination therapy experienced at least 1 cardiovascular event. No difference in time to SNF admission was found across the 3 treatment groups. The risk of the composite measure of any cardiovascular event did not differ between the combination therapy and AChEI monotherapy groups (adjusted hazard ratio [aHR], 0.99; 95% CI, 0.96-1.03); however, it was higher for both AChEI monotherapy (aHR, 1.07; 95% CI, 1.02-1.12) and combination therapy (aHR, 1.07; 95% CI, 1.01-1.12), relative to memantine monotherapy. This result was mainly driven by the lower risk of bradycardia and syncope observed for the memantine monotherapy group relative to both AChEI monotherapy (bradycardia: aHR, 0.88; 95% CI, 0.82-0.95; and syncope: aHR, 0.92; 95% CI, 0.86-0.97) and combination therapy (bradycardia: aHR, 0.89; 95% CI, 0.82-0.97; and syncope: aHR, 0.87; 95% CI, 0.83-0.94). Conclusions and Relevance: Time to SNF admission did not differ across treatment groups, but memantine monotherapy was associated with a lower risk of cardiovascular events compared with both AChEI monotherapy and combination therapy with an AChEI and memantine.

Predictions of Alzheimer's disease treatment and care costs in European countries.

BACKGROUND: Given the increasing lifespan of the elderly and the higher proportion of older people in the global population, the incidence rate of neurodegenerative diseases is increasing. The aim of this study is to evaluate, by means of computer simulations, developments in the costs of treating and caring for people suffering from Alzheimer's disease (AD) in the EU 28 by 2080, while assuming the introduction of drug administrations at various disease stages. METHODS: Impact analysis leverages a mathematical model that compares five different population development scenarios when introducing different types of drugs to the scenarios but without changing the treatment. Changes in the economic burden are considered as of 2023, when new drugs are expected to enter the market. FINDINGS: The results of the simulations show that by prolonging the length of a person's 'stay' in the Mild, Moderate, or Severe stage, the total cost of care for all persons with AD will increase by 2080. For individual scenarios, the percentage of patients and costs increased as follows: Mild by one year, by 10.61%; Mild by two years, by 17.73%; Moderate by one year, by 16.79%; Moderate by two years, by 34.88%; and Severe by one year, by 23.79%. The change in cost development when prolonging the stay in the Mild cognitive impairment stage (by lowering the incidence by 10%, 30%, or 50%) reduced the cost (by 4.88%, 16.78% and 32.48%, respectively). INTERPRETATION: The results unambiguously show that any intervention prolonging a patient's stay in any stage will incur additional care costs and an increase in the number of persons with AD. Therefore, extending lifespan is important in terms of improving the quality of life of patients, and the introduction of new drugs must consider the additional costs imposed upon society.

Long-term medical costs of Alzheimer's disease: matched cohort analysis.

OBJECTIVES: Medical costs associated with Alzheimer's disease (AD) are characterised by uncertainty and are often presented in a format unsuitable for decision modelling. We set out to estimate long-term medical costs attributable to AD compared to the general population for use in decision modelling. METHODS: We used multiple logistic regressions to generate propensity scores to match 26,951 incident cases of AD with 26,951 people without AD, identified from Danish hospital and medication registries. Costs were available for up to 11 years for each individual, representing costs for 10 years before and 5 years after diagnosis. Generalised estimating equations were employed to investigate the effect of having AD on primary care, medication, hospital and total costs in the matched cohort. We also explored the impact of other socio-economic and demographic factors on healthcare costs. RESULTS: We report costs by year to diagnosis, from 10 years before to 5 after. AD was associated with significantly higher costs, driven by medication and hospital costs, especially around the time of diagnosis. Mean total medical cost was €4996 higher for AD than for the control group in year of diagnosis, after which primary and hospital costs decreased to pre-diagnostic levels. AD had higher attributable primary care costs in years preceding diagnosis. CONCLUSIONS: Reporting AD-attributable costs by year to diagnosis can be useful for use in decision modelling. Medical costs attributed to AD are driven by diagnostic procedures and medication, and the impact of AD on medical costs may not be as high or prolonged as previously suggested.

Predicting Diagnosis of Alzheimer's Disease and Related Dementias Using Administrative Claims.

BACKGROUND: Predictive models for earlier diagnosis of Alzheimer's disease and related dementias (ADRD) that rely on variables requiring assessment during an office visit, such as cognitive function, body mass index, or lifestyle factors, may not be broadly applicable, since that level of data may be inaccessible or inefficient. OBJECTIVE: To build a predictive model for earlier diagnosis of ADRD using only administrative claims data to enhance applicability at the health care-system level. Building on the strength of this approach and knowledge that health care utilization (HCU) is increased before dementia diagnosis, it was hypothesized that previous HCU history would improve predictive ability of the model. METHODS: We conducted a case-control study using data from the OptumLabs Data Warehouse. ADRD was defined using ICD-9-CM codes and prescription fills for antidementia medications. We included individuals with mild cognitive impairment. Cases aged ≥ 18 years with a diagnosis between 2011-2014 were matched to controls without ADRD. HCU variables were incorporated into regression models along with comorbidities and symptoms. RESULTS: The derivation cohort comprised 24,521 cases and 95,464 controls. Final adjusted models were stratified by age. We obtained moderate accuracy (c-statistic = 0.76) for the model among younger (aged < 65 years) adults and poor discriminatory ability (c-statistic = 0.63) for the model among older adults (aged ≥ 65 years). Neurological and psychological disorders had the largest effect estimates. CONCLUSIONS: We created age-stratified predictive models for earlier diagnosis of dementia using information available in administrative claims. These models could be used in decision support systems to promote targeted cognitive screening and earlier dementia recognition for individuals aged < 65 years. These models should be validated in other cohorts. DISCLOSURES: This research was supported by AstraZeneca, Global CEO Initiative, Janssen, OptumLabs, and Roche. Albrecht was supported by Agency for Healthcare Quality and Research grant K01HS024560. Perfetto is employed by the National Health Council, which accepts membership dues and sponsorships from a variety of organizations and companies. The authors declare no other potential conflicts of interest.

Effect of Medicare Part D on Ethnoracial Disparities in Antidementia Medication Use.

OBJECTIVES: To examine ethnoracial disparities in antidementia medication use, accounting for implementation of Part D, and to evaluate the role of prescription drug coverage as a cause of antidementia medication disparities. DESIGN: Rotating panel of Medicare beneficiaries who participated in the Medicare Current Beneficiary Survey from 2003 to 2013. SETTING: Nationally representative sample of Medicare fee-for-service (FFS) beneficiaries with dementia. PARTICIPANTS: Community-dwelling FFS Medicare beneficiaries with dementia (N=4,304). MEASUREMENTS: Antidementia medication use, defined as at least one prescription fill in a given year. RESULTS: Unadjusted antidementia medication use was 10-percentage points lower for ethnoracial minority beneficiaries before Part D was implemented in 2006 (p=.01). This difference was attenuated after adjusting for demographic and socioeconomic factors (6-percentage points; p=.10). Part D was associated with a 6-percentage point increase in use (p<.01). The increase in use associated with Part D was higher although not statistically significantly so in ethnoracial minority beneficiaries (8-percentage points, p=.08). Analyses of each ethnoracial group found a significant effect of Part D only in Hispanic/Latino beneficiaries (18-percentage points; p<.01, adjusted). CONCLUSION: Antidementia medication disparities were reduced with expanded prescription drug coverage through Medicare Part D. Increases in antidementia medication use for minority beneficiaries started after Part D was implemented, with the largest increases in use observed in Hispanic/Latino beneficiaries.

Diagnosing and treating dementia in German primary and specialized care between 2011 and 2015
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BACKGROUND: Whilst there was no upturn in detection rate of persons with dementia (PwD) in German general practitioner (GP) practices before 2012, dementia diagnoses markedly increased in 2013 and 2014. OBJECTIVE: (1) Verify the increase of dementia diagnoses in GP practices and neurologist/psychiatrist (NP) practices; (2) examine the subsequent prescription of antidementia drugs. MATERIALS AND METHODS: We performed a retrospective, longitudinal analysis of 874 GP and 141 NP practices collecting clinical data about 220,213 patients who received a dementia diagnosis (ICD-10: G30, F01, F03) between 2011 and 2015. RESULTS: In GP practices, documented dementia diagnoses increased by 73% between 2012 and 2014 (mean 6.4 - 11.1 PwD/practice) and decreased by 26% in 2015 (8.3 PwD/practice). This trend was mostly due to the subgroup of nonspecific (+63%) and vascular dementia (+170%). The upturn has been accompanied by a downturn of the proportion of PwD receiving antidementia drugs (2012: 13.9% vs. 2014: 7.8%). Neither of these trends was found in NP practices. CONCLUSION: The upturn parallels the introduction of monetary incentives for both patients and GPs. It should be examined if these monetary incentives will also lead to an improvement in treatment and care of PwD in the long run.
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Levetiracetam para o tratamento da epilepsia / Levetiracetam for the treatment of epilepsy

CONTEXTO: A epilepsia é uma desordem crônica neurológica prevalente, caracterizada por sinais e sintomas característicos (crises convulsivas) associados a descargas elétricas cerebrais anormais. O tratamento da epilepsia geralmente inclui o uso contínuo em longo prazo de medicamentos com efeito anticonvulsivante. No eixo topográfico, as epilepsias são separadas em generalizadas e focais. Este relatório foi elaborado como parte da conduta de revisão do PCDT de epilepsia e tem por objetivo avaliar as evidências de eficácia e segurança do levetiracetam no tratamento de epilepsia focal e generalizada, a fim de embasar a avaliação da CONITEC a respeito de sua incorporação na versão atualizada do PCDT. TECNOLOGIA: levetiracetam (Keppra®). INDICAÇÃO: Tratamento da epilepsia focal e generalizada. PERGUNTA: O uso do levetiracetam em monoterapia ou e em terapia de adição no tratamento de crianças ou adultos com epilepsia, crises focais (parciais) ou generalizadas, é eficaz, seguro e custo-efetivo, comparativamente ao tratamento ativo (antiepilépticos de primeira ou segunda linha previstos no PCDT de epilepsia) ou placebo? EVIDÊNCIAS CIENTÍFICAS: há evidências de superioridade do levetiracetam em comparação ao placebo, em terapia de adição, para o tratamento de crises focais e primariamente generalizada em crianças e adultos que não responderam à monoterapia, com magnitude de efeito pequena a moderada, com taxas de resposta maiores entre crianças. Não foram estudados efeitos adversos em longo prazo. Não foi possível estabelecer a relação de eficácia comparativa em relação a outros agentes potencialmente úteis após falha de agentes de segunda linha no tratamento de adição da epilepsia refratária. Mais estudos são necessários para estabelecer sua eficácia em monoterapia. O nível de evidência é muito baixo, pois se trata de ensaios clínicos abertos, com pequeno número de pacientes. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário da incorporação do levetiracetam será superior à R$ 29 milhões de reais no primeiro ano, considerando um cenário base onde a assumiu-se que a dose média por paciente seria de 2000mg por dia. CONSIDERAÇÕES FINAIS: Há evidências de eficácia e segurança para a utilização do levetiracetam em terapia de adição para tratamento de pacientes com epilepsia focal e epilepsia primariamente generalizada em adultos e crianças com mais de 6 anos (12 anos para crises tônico-clônico generalizadas) que não responderam à monoterapia com anticonvulsivante de primeira linha conforme previsto no PCDT de epilepsia. RECOMENDAÇÃO FINAL: Os membros da CONITEC presentes na 57ª reunião ordinária do plenário realizada nos dias 05 e 06 de julho de 2017, recomendaram por unanimidade a ampliação de uso do levetiracetam para o tratamento da epilepsia conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 272/2017. DECISÃO: Incorporado levetiracetam para o tratamento da epilepsia segundo Portaria SCTIE/MS nº 56, DE 1º DE DEZEMBRO DE 2017.(AU)

Levetiracetam para o tratamento de convulsões em pacientes com microcefalia / Levetiracetam for the treatment of seizures in patients with microcephaly

CONTEXTO: A infecção decorrente do Zika vírus vem apresentando possíveis complicações nos pacientes acometidos pela doença desde sua chegada ao Brasil. O Zika possui sintomas semelhantes aos outros flavivírus prevalentes no país, sendo transmitido pelo mesmo mosquito (Aedes aegypti). A doença tem sido associada ao desenvolvimento de microcefalia e alterações neurológicas em filhos de mulheres que tiveram contato com o vírus durante a gravidez, destacando-se relatos de episódios convulsivos. O SUS fornece medicamentos anticonvulsivantes para outras doenças com sintomas de convulsão, como a epilepsia. TECNOLOGIA: LEVETIRACETAM (KEPPRA®). INDICAÇÃO: CONVULSÕES EM PACIENTES PEDIÁTRICOS. PERGUNTA 1: O levetiracetam, em comparação aos tratamentos anticonvulsivantes disponíveis no SUS, é eficaz, efetivo e seguro no controle de convulsões em pacientes com microcefalia? PERGUNTA 2: O Levetiracetam, em comparação aos tratamentos anticonvulsivantes disponibilizados pelo SUS, é eficaz, efetivo e seguro no tratamento de convulsões em pacientes pediátricos com epilepsia? EVIDÊNCIAS CIENTÍFICAS: Foi elaborado um Parecer Técnico-Científico seguindo as Diretrizes do Ministério da Saúde. Após duas buscas contemplando os desfechos em questão, foram incluídos três estudos, sendo que dois deles comparavam o levetiracetam com carbamazepina e o último com o ácido valpróico. A análise do risco de viés evidenciou estudos com qualidade moderada. A avaliação conjunta dos estudos não demonstrou eficácia ou efetividade superior do levetiracetam em comparação aos anticonvulsivantes já padronizados pelo SUS. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O custo incremental total estimado para o tratamento com levetiracetam na população pediátrica, com peso médio de 10 kg, foi de R$1.682.535,63 em cinco anos. EXPERIÊNCIA INTERNACIONAL: O levetiracetam foi incorporado como terapia adjuvante pela agência Inglesa e Escocesa. Pela agência do Canadá, existe o uso em primeira linha em algumas províncias ou em situações especiais. CONSIDERAÇÕES FINAIS: Foram realizadas duas buscas para atender ao demandante, a Secretaria Estadual de Saúde de Pernambuco. Na primeira, não foi recuperado nenhum estudo e na segunda busca foram recuperados três estudos. Em nenhuma das publicações analisadas foram encontradas evidências da superioridade do Levetiracetam em comparação com a carbamazepina ou o ácido valpróico. DELIBERAÇÃO FINAL: Os membros da CONITEC, presentes na 57ª reunião ordinária, realizada nos dias 5 e 6 de julho de 2017, deliberaram por unanimidade recomendar a ampliação de uso do medicamento levetiracetam para o tratamento de convulsões em pacientes com microcefalia decorrente de infecção pelo vírus zika. Foi assinado o Registro de Deliberação nº nº 271/2017. DECISÃO: Incorporado levetiracetam para o tratamento de convulsões em pacientes com microcefalia segundo Portaria SCTIE/MS nº 38, DE 31 DE AGOSTO DE 2017.(AU)

Levetiracetam como terapia adjuvante em pacientes com epilepsia mioclônica juvenil resistentes à monoterapia / Levetiracetam as adjuvant therapy in patients with juvenile myoclonic epilepsy resistant to monotherapy

CONTEXTO: A epilepsia é uma doença cerebral crônica caracterizada pela recorrência de crises epilépticas não provocadas. Conforme Protocolo Clínico e Diretrizes Terapêuticas (PCDT) vigente do Ministério da Saúde (MS), o tratamento disponível no Sistema Único de Saúde (SUS) inclui os agentes antiepilépticos fenobarbital, fenitoína, primidona, topiramato, lamotrigina, carbamazepina e valproato de sódio. As epilepsias idiopáticas generalizadas são classificadas como síndromes epilépticas. A EMJ é a mais comum dentre as síndromes da adolescência e uma das mais frequentemente diagnosticadas. A maioria dos pacientes com EMJ apresentam bom controle do quadro clínico com a utilização do valproato de sódio em monoterapia, mas na falha ou impossibilidade de seu uso, fármacos como a lamotrigina e o levetiracetam podem ser utilizados. TECNOLOGIA: levetiracetam (Keppra®). INDICAÇÃO: Terapia adjuvante, ou seja em associação com o valproato de sódio, em pacientes com epilepsia mioclônica juvenil (EMJ) resistentes à monoterapia. PERGUNTA: O uso do levetiracetam em regime de terapia adjuvante, é eficaz, seguro e custoefetivo em relação à continuação da monoterapia em pacientes com epilepsia mioclônica juvenil, resistentes a outros agentess antiepilépticos na perspectiva do SUS? EVIDÊNCIAS CIENTÍFICAS: A evidência da utilização do levetiracetam associado à tratamento prévio com um agente antiepiléptico para o tratamento da EMJ é baseada em um ensaio clínico duplo-cego que apresentou redução significante de 50% no número de dias por semana com crises convulsivas s (OR = 4,77; IC 95% 2,12 ­ 10,77; p<0,0001 e um maior número de pacientes, que receberam levetiracetam, apresentaram ausência total de crises durante o tratamento (16,7% dos pacientes, p = 0,03, vs 3,3 % do grupo que recebeu placebo). AVALIAÇÃO ECONÔMICA: Foi apresentado um modelo de custo-efetividade comparando a monoterapia com ácido valpróico ao tratamento adjuvante do levetiracetam (associado) ao ácido valpróico. Foi elaborado um modelo baseado primeiramente em uma árvore de decisão, seguido por um modelo de Markov. No caso-base a razão de custo-utilidade incremental (RCUI) foi de R$ 58.294 por ano de vida ajustada pela qualidade, que na análise de sensibilidade univariada variou entre R$ 22.119 e R$ 80.359. Avaliação de Impacto Orçamentário: Conforme as estimativas feitas pelo demandante o impacto orçamentário será de aproximadamente R$ 1,58 milhão no primeiro ano e de R$ 43,6 milhões nos primeiros 5 anos após a incorporação. Na análise de sensibilidade realizada o impacto orçamentário para os próximos 5 anos variou entre R$ 14,5 e R$ 87,3 milhões. EXPERIÊNCIA INTERNACIONAL: o levetiracetam é utilizado em terapia adjuvante para o tratamento de crises mioclônicas em agências como o National Institute for Health and Clinical Excellence (NICE) e Canadian Agency for Drugs and Technologies in Health (CADTH), de acordo com condições estabelecidas Discussão: A evidência do tratamento com levetiracetam em pacientes resistentes à monoterapia padrão, associado ao medicamento já utilizado, ocasionou em redução significante de pelo menos 50% no número de dias por semana com crises convulsivas e um maior número de pacientes apresentaram ausência total de crises convulsivas durante seu período de seguimento. Porém trata-se de evidência indireta e de baixa qualidade. Os estudos para essa indicação da tecnologia são escassos e há baixa probabilidade de novos estudos serem realizados. A avaliação econômica foi custo-efetiva na adição do levetiracetam ao medicamento previamente utilizado em monoterapia, em pacientes resistentes, com um impacto orçamentário de até R$ 87,3 milhões em 5 anos, de acordo com a análise de sensibilidade. A secretaria executiva da CONITEC estimou o número de pacientes, que considera mais adequada para o cálculo, que foi 7,8% maior que a população considerada na análise do demandante, o que levaria a um impacto orçamentário ainda maior. RECOMENDAÇÃO DA CONITEC: A CONITEC em sua 54ª reunião no dia 06 de abril de 2017, recomendou preliminarmente a incorporação no SUS do levetiracetam como terapia adjuvante em pacientes com epilepsia mioclônica juvenil resistentes à monoterapia, condicionada à redução de preço e consonância com a atualização do PCDT de Epilepsia. Consulta pública: Foi realizada a Consulta Pública nº 22/2017, entre os dias 25/04/2017 e 16/05/2017 e recebeu 105 contribuições, sendo 88 sobre experiência ou opinião e 17 técnicocientíficas. Todas as contribuições foram avaliadas quantitativamente e qualitativamente. Seu conteúdo não trouxe novas evidências e informações que pudessem modificar a recomendação inicial da CONITEC. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 56ª reunião ordinária do plenário do dia 07/06/2017 deliberaram, por unanimidade, por recomendar a incorporação do levetiracetam para pacientes com epilepsia mioclônica juvenil (EMJ) resistentes à monoterapia, associando-o ao medicamento já utilizado, condicionado à negociação de preço e conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 264/2017.(AU)