The association between hope and mortality in homebound elders.

OBJECTIVE: Despite high rates of mortality and depression, there is limited knowledge of how depressive symptoms, especially feeling of hopefulness, affect mortality in the homebound elderly. METHODS: We conducted a secondary analysis of data from a community sample of 1034 adults, age 60 years and older. The Center for Epidemiologic Studies Depression Scale was used to evaluate the mood symptoms and feeling of hopefulness at baseline. The death data were collected within an 8-year follow-up period. Analysis of variance and Chi-square were used to compare the clinical conditions among the groups of individuals who feel hopeful always, sometimes, and rarely. Logistic regression was used to explore the association between the hopefulness about the future and mortality as an outcome. RESULTS: In the 8-year follow-up period, frequency of feeling hopeful, but not other individual depressive symptoms, was associated with mortality rate. The mortality rate among those who always, sometimes, and rarely felt hopeful were 21.6%, 26.4%, and 35.7%, respectively (P = 0.002). Logistic regression also confirmed that individuals who rarely feel hopeful had higher odds of decease within the 8-year follow-up period than those who always felt hopeful (OR = 1.74, CI = 1.14-2.65) after adjusting for age and medical conditions. CONCLUSIONS: Baseline hopefulness predicts mortality outcome among the homebound elderly in the community. Identifying individuals who are depressed with hopelessness in the elderly and providing early intervention may improve the mortality rate. Copyright © 2017 John Wiley & Sons, Ltd.

Amyloid-associated depression and ApoE4 allele: longitudinal follow-up for the development of Alzheimer's disease.

BACKGROUND: Amyloid-associated depression is associated with cognitive impairment cross sectionally. This follow-up study was to determine the relationship between amyloid-associated depression and the development of Alzheimer's disease (AD). METHODS: Two hundred and twenty three subjects who did not have dementia at baseline were given a repeat cognitive evaluation for incident AD. Depression was defined by having a Center for Epidemiological Studies Depression (CES-D) score ≥ 16, and non-amyloid vs. amyloid-associated depression by having a low vs. high plasma amyloid-ß peptide 40 (Aß40)/Aß42 ratio. Apolipoprotein E (ApoE) genotype was determined, and antidepressant usage was documented. RESULTS: Fifteen subjects developed AD (7%) after an average follow-up time of 6.2 years. While none of those with non-amyloid depression developed AD, 9% of those with amyloid-associated depression developed AD. Further, among those with amyloid-associated depression, ApoE4 carriers tended to have a higher risk of AD than ApoE4 non-carriers (40% vs. 4%, p = 0.06). In contrast, 8% of those who did not have depression at baseline developed AD, but ApoE4 carriers and non-carriers did not show a difference in the AD risk. After adjusting for age, the interaction between ApoE4 and amyloid-associated depression (ß = +0.113, SE = 0.047, P = 0.02) and the interaction between ApoE4 and antidepressant use (ß = +0.174, SE = 0.064, P = 0.007) were associated with the AD risk. CONCLUSIONS: Amyloid-associated depression may be prodromal depression of AD especially in the presence of ApoE4. Future studies with a larger cohort and a longer follow-up are warranted to further confirm this conclusion.

Systematic literature review of treatments for management of complications of ischemic central retinal vein occlusion.

BACKGROUND: To understand the clinical and economic outcomes of treatments for managing complications of ischemic central retinal vein occlusion (iCRVO). METHODS: We conducted a systematic literature review by searching multiple databases and ophthalmology conferences from 2004 to 2015. Studies published in English language and populations of age ≥45 years were included. For clinical endpoints, we defined eligibility criteria as randomized controlled trials, prospective before-and-after study designs, and non-randomized studies reporting on treatments in patients with iCRVO. For economic endpoints, all types of study design except cost-of-illness studies were included. We evaluated the definitions of ischemia, clinical and economic endpoints, and rate of development of complications. Risk of bias was assessed for clinical studies using the Cochrane risk-of-bias tool. RESULTS: A total of 20 studies (1338 patients) were included. Treatments included anti-vascular endothelial growth factors (anti-VEGFs), steroids, and procedures primarily targeting macular edema and neovascularization. Ischemia was not defined consistently in the included studies. The level of evidence was mostly low. Most treatments did not improve visual acuity significantly. Development of treatment complications ranged from 11 to 57 %. Incremental cost-effectiveness ratios reported for anti-VEGFs and steroids were below the accepted threshold of GB£30,000, but considering such treatments only ameliorate disease symptoms they seem relatively expensive. CONCLUSIONS: There is a lack of evidence for any intervention being effective in iCRVO, especially in the prevention of neovascularisation. iCRVO poses a significant clinical and economic burden. There is a need to standardize the definition of ischemia, and for innovative treatments which can significantly improve visual outcomes and prevent neovascular complications.

Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.

OBJECTIVE: The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. METHODS: This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. RESULTS: A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. CONCLUSION: The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers.

Positional error and time-activity patterns in near-highway proximity studies: an exposure misclassification analysis.

BACKGROUND: The growing interest in research on the health effects of near-highway air pollutants requires an assessment of potential sources of error in exposure assignment techniques that rely on residential proximity to roadways. METHODS: We compared the amount of positional error in the geocoding process for three different data sources (parcels, TIGER and StreetMap USA) to a "gold standard" residential geocoding process that used ortho-photos, large multi-building parcel layouts or large multi-unit building floor plans. The potential effect of positional error for each geocoding method was assessed as part of a proximity to highway epidemiological study in the Boston area, using all participants with complete address information (N = 703). Hourly time-activity data for the most recent workday/weekday and non-workday/weekend were collected to examine time spent in five different micro-environments (inside of home, outside of home, school/work, travel on highway, and other). Analysis included examination of whether time-activity patterns were differentially distributed either by proximity to highway or across demographic groups. RESULTS: Median positional error was significantly higher in street network geocoding (StreetMap USA = 23 m; TIGER = 22 m) than parcel geocoding (8 m). When restricted to multi-building parcels and large multi-unit building parcels, all three geocoding methods had substantial positional error (parcels = 24 m; StreetMap USA = 28 m; TIGER = 37 m). Street network geocoding also differentially introduced greater amounts of positional error in the proximity to highway study in the 0-50 m proximity category. Time spent inside home on workdays/weekdays differed significantly by demographic variables (age, employment status, educational attainment, income and race). Time-activity patterns were also significantly different when stratified by proximity to highway, with those participants residing in the 0-50 m proximity category reporting significantly more time in the school/work micro-environment on workdays/weekdays than all other distance groups. CONCLUSIONS: These findings indicate the potential for both differential and non-differential exposure misclassification due to geocoding error and time-activity patterns in studies of highway proximity. We also propose a multi-stage manual correction process to minimize positional error. Additional research is needed in other populations and geographic settings.

Highway proximity associated with cardiovascular disease risk: the influence of individual-level confounders and exposure misclassification.

BACKGROUND: Elevated cardiovascular disease risk has been reported with proximity to highways or busy roadways, but proximity measures can be challenging to interpret given potential confounders and exposure error. METHODS: We conducted a cross sectional analysis of plasma levels of C-Reactive Protein (hsCRP), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha receptor II (TNF-RII) and fibrinogen with distance of residence to a highway in and around Boston, Massachusetts. Distance was assigned using ortho-photo corrected parcel matching, as well as less precise approaches such as simple parcel matching and geocoding addresses to street networks. We used a combined random and convenience sample of 260 adults >40 years old. We screened a large number of individual-level variables including some infrequently collected for assessment of highway proximity, and included a subset in our final regression models. We monitored ultrafine particle (UFP) levels in the study areas to help interpret proximity measures. RESULTS: Using the orthophoto corrected geocoding, in a fully adjusted model, hsCRP and IL-6 differed by distance category relative to urban background: 43% (-16%,141%) and 49% (6%,110%) increase for 0-50 m; 7% (-39%,45%) and 41% (6%,86%) for 50-150 m; 54% (-2%,142%) and 18% (-11%,57%) for 150-250 m, and 49% (-4%, 131%) and 42% (6%, 89%) for 250-450 m. There was little evidence for association for TNF-RII or fibrinogen. Ortho-photo corrected geocoding resulted in stronger associations than traditional methods which introduced differential misclassification. Restricted analysis found the effect of proximity on biomarkers was mostly downwind from the highway or upwind where there was considerable local street traffic, consistent with patterns of monitored UFP levels. CONCLUSION: We found associations between highway proximity and both hsCRP and IL-6, with non-monotonic patterns explained partly by individual-level factors and differences between proximity and UFP concentrations. Our analyses emphasize the importance of controlling for the risk of differential exposure misclassification from geocoding error.

Development of a nutrient-dense food supplement for HIV-infected women in rural Kenya using qualitative and quantitative research methods.

OBJECTIVE: Formative research to facilitate the development, packaging and delivery of a culturally acceptable nutrition intervention for HIV-infected women in rural Kenya for an intervention trial. DESIGN: Focus group discussion on three areas: (i) ingredients and form of the nutrition intervention, (ii) packaging and delivery and (iii) monitoring of adherence. Two single-blind taste tests with eleven different porridge formulations of various combinations of maize flour, soyabeans, peanuts, sorghum, mung beans, dried fish, raisins and dried whole milk. Follow-up acceptability focus group discussion was also conducted. SETTING: Voi, Kenya, community based. SUBJECTS: Focus group discussion and two taste tests (twenty-one women aged 16-55 years). Follow-up acceptability focus group discussion (four women enrolled in intervention trial). RESULTS: The preferred porridge for taste consisted of maize, soyabeans and peanuts. For animal protein, dried whole milk and dried fish were used. Although the women disliked the taste of dried fish, it was acceptable if added in small undetectable quantities. Sugar over lime was favoured for taste. Women believed they could consume at least two cups of porridge per day without displacing their usual meals. The optimal delivery interval was believed to be every two weeks in individual serving packages. Women who had been consuming porridge for several weeks felt the taste was acceptable for long-term consumption. CONCLUSIONS: This formative research resulted in the development, packaging and delivery of a nutrient-dense food supplement using local ingredients to meet the dietary needs of the population and acceptable for daily consumption by women in Kenya for evaluation in an intervention trial.

A community participatory study of cardiovascular health and exposure to near-highway air pollution: study design and methods.

Current literature is insufficient to make causal inferences or establish dose-response relationships for traffic-related ultrafine particles (UFPs) and cardiovascular (CV) health. The Community Assessment of Freeway Exposure and Health (CAFEH) is a cross-sectional study of the relationship between UFP and biomarkers of CV risk. CAFEH uses a community-based participatory research framework that partners university researchers with community groups and residents. Our central hypothesis is that chronic exposure to UFP is associated with changes in biomarkers. The study enrolled more than 700 residents from three near-highway neighborhoods in the Boston metropolitan area in Massachusetts, USA. All participants completed an in-home questionnaire and a subset (440+) completed an additional supplemental questionnaire and provided biomarkers. Air pollution monitoring was conducted by a mobile laboratory equipped with fast-response instruments, at fixed sites, and inside the homes of selected study participants. We seek to develop improved estimates of UFP exposure by combining spatiotemporal models of ambient UFP with data on participant time-activity and housing characteristics. Exposure estimates will then be compared with biomarker levels to ascertain associations. This article describes our study design and methods and presents preliminary findings from east Somerville, one of the three study communities.

Is there an association between aspirin dosing and cardiac and bleeding events after treatment of acute coronary syndrome? A systematic review of the literature.

BACKGROUND: Current acetylsalicylic acid (ASA) dosing algorithms for the prevention of secondary thrombotic events in acute coronary syndrome (ACS) patients are inconsistent and lack sufficient data support. METHODS: We performed a systematic review of the literature for studies that assessed clinical outcomes in patients with ACS following coronary stent insertion (SI) or medical treatment (MT). Acetylsalicylic acid dosing was stratified into low- (<160 mg) and high- (≥ 160 mg) dose categories. Outcomes were assessed at 1, 6, and 12 months and included major bleeding, myocardial infarction, and all-cause death. A random-effects meta-analysis was used to estimate the value of the mean for each outcome variable. RESULTS: Of 12,472 publications identified, 136 studies with 289,330 patients were analyzed. In the 1-month SI analysis, proportions of patients (95% CI) in the low- and high-dose ASA categories experiencing major bleeding were 2.1% (1.5-2.6) and 1.9% (0.0-3.8); proportions with myocardial infarction were 2.1% (1.3-2.8) and 1.8% (0.9-2.6); and proportions of all-cause death were 2.8% (2.2-3.4) and 2.4% (1.3-3.5), respectively. Results were similar in the MT analysis, except that major bleeding rates for low and high doses were 1.7% (1.3-2.2) and 4.0% (2.2-5.8), respectively. Regression analyses suggested that the proportion of patients reporting each of the outcomes evaluated were not significantly different between the low- and high-dose categories, with the exception of the 1-month major bleeding following MT. CONCLUSIONS: Our results suggest no improved clinical outcomes associated with higher ASA maintenance doses in ACS patients receiving SI or MT. In the MT analysis, there was more major bleeding in the first month after an ACS event with high-dose ASA.

Systematic review and meta-analysis of the efficacy of cardioversion by vernakalant and comparators in patients with atrial fibrillation.

PURPOSE: Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted. METHODS AND RESULTS: A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8-24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension. CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

Multi-Criteria Decision Analysis Model for Assessing the Risk from Multi-Ingredient Dietary Supplements (MIDS).

Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk.Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions.We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.

Patient experience with non-invasive vagus nerve stimulator: gammaCore patient registry.

gammaCore is cleared by the FDA for acute and preventive treatment of cluster headache and the acute treatment of migraine in adults. Previously, only 2 treatments were approved for acute treatment of cluster headache while none were approved for preventive treatment. Following the initial FDA clearance, based on the ACT-1 and ACT-2 studies, a gammaCore Patient Registry (GPR) was designed to provide insights on the use of gammaCore and prescription patterns in the real-world setting and to characterize respective benefits and challenges during the acute treatment of episodic cluster headache. GPR was a prospective observational registry in which patients with episodic cluster headache (3rd edition of the International Classification of Headache Disorders criteria) who were prescribed gammaCore were invited to voluntarily enroll and provide information on their experiences between July 2017 and June 2018. Participants provided baseline information and were trained to self-administer treatment with gammaCore for cluster pain. Participants were also requested to record information for each cluster attack. Of the 182 patients who provided baseline demographic and cluster headache characteristics, 152 provided health index baseline data using EuroQol Health Index tool, 5-level format (EQ5D-5L) and 17 patients provided attack data on a total of 192 cluster headache attacks. The mean age was 49 years; 65% were male and 82% were white; the mean number of months of known diagnosis of cluster headache was 57; the mean number of attacks per cluster headache 4-week period was 14; and the mean pain score was 3.7 (0-4 scale) with a mean attack duration of 74 minutes. Sixty-seven percent of patients had used preventive treatments and 83% had used abortive treatments for cluster headaches; 25% of participants reported at least 1 comorbidity. The mean EQ5D-5L score (scale 0-1) was 0.83. Of the 192 cluster headache attacks reported, gammaCore was used in 116 (60%) attacks. Within this group, the mean pain score at the start of the attacks was 2.7, the mean number of stimulations used was 3.6, and the pain score after 30 minutes was 1.3. At 30 minutes, the pain of 81 (70%) attacks was reduced to none (27%) or mild (43%) (a pain score of 0 or 1) and in 94 (81%) attacks, patients experienced a reduction of at least 1 point in the pain score. This real-world observational evidence suggests that gammaCore adds clinically meaningful value to patients with episodic cluster headache by providing rapid pain relief and confirms that there is significant interest among prescribers in providing this new treatment and technology. This evidence further supports the need to redefine gammaCore as no longer investigational or experimental during considerations for reimbursement.

Real-world assessment of concomitant opioid utilization and associated trends in patients with migraine.

Migraine is a debilitating condition that affects approximately 16% of adults and is the fifth leading cause of emergency department visits in the United States. There are several treatment options for migraines; opioids are frequently prescribed. Results from a recent study showed that more than half of the patients with chronic migraine and a third of the patients with episodic migraine received an opioid prescription in the past year. The American Headache Society recognizes the magnitude of this issue and is working to educate providers on the danger of prescribing opioids in the migraine population The objective of this article is to assess the utilization trends of prescription opioid products and evaluate the impact of opioid utilization on healthcare costs in this patient population. This retrospective claims database analysis used real-world medical claims from multiple health plans. The study period was from January 1, 2009, to September 30, 2017. Patients were included if they were 18 years or older and continuously enrolled in the study period for at least 3 years. Patients were included in the migraine cohort if they had any diagnosis of migraine headache during the study period, while patients without a headache related diagnosis were included in the control cohort. Control patients were propensity matched 1:1 to migraine patients. Discrete (count) data are represented by frequencies and percentages. Continuous results are presented as means, medians, and standard deviations. In the study, 107,216 patients met the inclusion criteria, with 53,608 assigned to each cohort. In the migraine and control cohorts, respectively, 28% and 11% were prescribed opioids. In both cohorts, a majority of the patients were female (81.8%). In both cohorts, opioid use was associated with higher total costs compared with patients who were not prescribed opioids: $82,007 for 200 morphine milligram equivalents (MME)/day or more versus $19,792 for no opioid in patients with migraine; and $54,200 for 200 MME/day or more versus $12,060 for no opioid use in control patients; P <.0001. Patients with more than 2 comorbidities who were prescribed opioids had higher costs than patients with more than 2 comorbidities who were not prescribed opioids and patients with less than 2 comorbidities who were prescribed opioids ($65,980, $32,152, and $35,964, respectively, for patients with migraine, and $52,883, $24,641, and $35,748, respectively, for control patients; P <.0001). Patients with migraine have more than twice the healthcare costs as patients without migraines. The additional increase in healthcare costs in patients with migraine who use opioids for treatment and/or have 2 or more comorbidities is significant. Control of the pain associated with migraine, specifically among those with multiple comorbid conditions, may contribute to substantial reductions in healthcare costs.

Concomitant medical conditions and total cost of care in patients with migraine: a real-world claims analysis.

This study evaluates the impact of concomitant medical conditions on patients with and without migraine, assessing healthcare utilization, and total cost of care. Medical and pharmacy claims from multiple health plans, both nationally and internationally, were examined to evaluate overall real-world trends in commercially insured patients diagnosed with migraine. A total of 53,608 patients with diagnosis codes for migraine met the study criteria and were matched 1:1 with controls (81.8% female; mean age, 42 years; mean Charlson Comorbidity Index score, 0.34). During the 3-year measurement period, mean medical costs per patient in the migraine cohort were about 1.7 times that of the control group ($22,429 vs $13,166). Unique encounters and cost per patient by medical service type for the migraine cohort compared with the control group were as follows: emergency department, 4.13 ($4000) versus 2.94 ($2639); hospital inpatient, 3.15 ($17,748) versus 2.67 ($16,010); hospital outpatient, 5.14 ($365) versus 4.85 ($396); physician office, 36.78 ($6803) versus 21.39 ($4069); laboratory, 10.12 ($1433) versus 7.71 ($1057); radiology, 7.64 ($2609) versus 5.94 ($1733). Mean pharmacy costs per patient were approximately 1.8 times higher in the migraine cohort compared with the control cohort ($8441 vs $4588, respectively; P <.0001). These results suggest that patients with migraine have more comorbidities compared with those without migraine. These patients also utilize healthcare resources at a significantly higher rate compared with similar patients without a migraine diagnosis. An unmet need exists for new treatment modalities in this patient population. More effective interventions and proper management may lead to improved patient outcomes and healthcare costs for patients with migraine.

Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes.

BACKGROUND: Atherosclerotic cardiovascular disease remains a major cause of death and disability, especially for high-risk familial hypercholesterolemia individuals. PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitors) reduce low-density lipoprotein cholesterol levels and cardiovascular event rates. However, PCSK9i prescriptions are rejected at high rates by payers, and use is often delayed or eventually abandoned as a treatment option. We tested the hypothesis that acute coronary syndromes, coronary interventions, stroke, and cardiac arrest are more prevalent in patients with rejected or abandoned PCSK9i prescriptions than for those with paid PCSK9i prescriptions. METHODS AND RESULTS: We identified 139 036 individuals aged ≥18 years who met the following 3 criteria: prescribed PCSK9i between August 2015 and December 2017, had claims history, and had an established date of exposure for paid, rejected, or abandoned status. To compare the effects of rejected versus paid and abandoned versus paid status, propensity score matching was performed to minimize confounding because of baseline differences in patient groups. Cox regression analyses and incidence density rates for cardiovascular events were estimated on the propensity score-matched cohorts. Patients who received 168 or more days of paid PCSK9i medication within a 12-month period were defined as paid. The hazard ratios for composite cardiovascular events outcome in propensity score-matched analyses were 1.10 (95% CI, 1.01-1.19; P=0.02) for rejected versus paid and 1.12 (95% CI, 1.01-1.24; P=0.03) for abandoned versus paid. In a stricter analysis where paid patients were defined by receiving 338 or more days of therapy within 12-months, hazard ratio was 1.16 (95% CI, 1.02-1.30; P=0.04) for rejected versus paid and 1.21 (95% CI, 1.04-1.38; P=0.03) for the abandoned versus paid status. Higher PCSK9i rejection rates were observed with women, racial minorities, and lower-income groups. CONCLUSIONS: Individuals in the rejected and abandoned cohorts had significantly increased risk of cardiovascular events compared with those in the paid cohort. Rejection, abandonment, and disparities related to PCSK9i prescriptions are related to higher cardiovascular outcome rates.

Review of evidence on noninvasive vagus nerve stimulation for treatment of migraine: efficacy, safety, and implications.

GammaCore was cleared by the FDA for the acute treatment of episodic migraine and episodic cluster headache and has 5 Conformité Européenne marks. Data indicate that gammaCore treatment is both safe and effective as an acute treatment for migraine. Current reimbursement policies need to be updated based on the growing body of evidence to reflect the established status of gammaCore that is no longer experimental. GammaCore provides substantial value to patients and to payers for consideration for pay-for-performance health coverage strategies and policies.

Cost-effectiveness of noninvasive vagus nerve stimulation for acute treatment of episodic migraine and role in treatment sequence strategies.

Migraine affects 15% of the population in the United States and is associated with comorbidities, with an estimated economic burden of $78 billion annually. GammaCore is used adjunctively with current standard of care and abortive medications and has shown to be superior in acute treatment of episodic migraine compared to sham. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analyses for 2 hypothetical scenarios: a primary model for treatment options gammaCore plus standard of care compared to standard of care alone for acute treatment of migraine; and a secondary model for treatment sequence strategies where acute treatment with gammaCore or standard of care each prior to erenumab prevention compared to initiating erenumab prevention with no prerequisite. The time horizon for the model is 1 year, using a payer perspective. GammaCore plus standard of care arm was dominant over standard of care alone in the primary model. The mean costs for gammaCore plus standard of care arm and standard of care individually were $9678 and $10,010, respectively. The mean quality of life-years for gammaCore plus standard of care arm and standard of care alone were 0.67, and 0.63, respectively. For the secondary model, the mean costs for gammaCore followed by erenumab, standard of care followed by erenumab and initiating with erenumab with no prior gammaCore or standard of care treatment were $10,678, $11,583, and $13,766. The corresponding mean for quality of life-years were 0.70, 0.67, and 0.65, respectively. For gammaCore dominance, ie, in this scenario, patients were more satisfied on gammaCore, to not need erenumab for preventative therapy lower mean costs and represents savings for payers. This was driven by efficacy, improvement in quality of life, and reduction in costs of care associated with successful treatment of migraine attacks. These findings provide new economic evidence to support value forcoverage for gammaCore.

Noninvasive vagus nerve stimulation in a primary care setting: effects on quality of life and utilization measures in multimorbidity patients with or without primary headache.

A patient audit was conducted in the UK to evaluate the impact of gammaCore use in multimorbidity patients on quality of life and healthcare resources utilization measures. A total of 233 patients were enrolled and their data was examined over a 1-year period after their gammaCore prescription. Of these patients, 132 (56%) had primary headache disorders while 101 (44%) were patients without a headache disorder (nonheadache patients). The mean age was 49 years, 169 (72%) were female, the mean number of comorbid conditions was 3.1, and the mean baseline EQ-5D score was 0.581. The mean paired difference in EQ-5D index for persistent gammaCore users (ie patients who used gammaCore for at least 40 weeks) was +0.156 at week 40. The mean percentage reductions in number of general practice consults (doctor's office appointments) was -28.5% from baseline mean of 7.31 and, 40.0% from baseline mean of 3.52 for medical codes used. This evidence demonstrates that a significant proportion of these multimorbidity patients on gammaCore remained compliant with the prescribed treatment regimen for an extended period. GammaCore use in multimorbidity patients may be associated with lower costs of care and provide opportunities for pay-for-performance coverage policies.

Review of non-invasive vagus nerve stimulation (gammaCore): efficacy, safety, potential impact on comorbidities, and economic burden for episodic and chronic cluster headache.

The FDA has cleared gammaCore (non-invasive vagus nerve stimulator [nVNS]) for the treatment of episodic cluster headache (eCH). With the exception of subcutaneous sumatriptan, all other treatments are used off label and have many limitations. The FDA approval process for devices differs from that of drugs. We performed a review of the literature to evaluate new evidence on various aspects of gammaCore treatment and impact. The ACute Treatment of Cluster Headache Studies (ACT1 and ACT2), both double-blind sham-controlled randomized trials, did not meet the primary endpoints of the trials but each demonstrated significant superiority of gammaCore among patients with eCH. In ACT1, gammaCore resulted in a higher response rate (RR) (RR, 3.2; 95% CI, 1.6-8.2; P = .014), higher pain-free rate for >50% of attacks (RR, 2.3; 95% CI, 1.1-5.2; P = .045), and shorter duration of attacks (mean difference [MD], -30 minutes; P <.01) compared with the sham group. In ACT2, gammaCore resulted in higher odds of achieving pain-free attacks in 15 minutes (OR, 9.8; 95% CI, 2.2-44.1; P = .01), lower pain intensity in 15 minutes (MD, -1.1; P <.01), and higher rate of achieving responder status at 15 minutes for ≥50% of treated attacks (RR, 2.8; 95% CI, 1.0-8.1; P = .058) compared with the sham group. The PREVention and Acute Treatment of Chronic Cluster Headache (PREVA) study also demonstrated that gammaCore plus standard of care (SOC) was superior to SOC alone in patients with chronic cluster headache (CH). Medical costs, pharmacy refills, and pharmacy costs were higher in patients coded for CH in claims data compared with controls with nonheadache codes. gammaCore is easy to use, practical, and safe; delivery cannot be wasted; and patients prefer using gammaCore compared with SOC. The treatment improves symptoms and reduces the need for CH rescue medications. Current US reimbursement policies, which predate nVNS and are based on expensive, surgically implanted, and permanent implanted vagus nerve stimulation (iVNS), need to be modified to distinguish nVNS from iVNS. gammaCore, cleared by the FDA in April 2017, provides substantial value to patients and also to payers. There is sufficient evidence to support the need to modify current reimbursement policies to include coverage for gammaCore (nVNS) for eCH.

Cost-effectiveness of gammaCore (non-invasive vagus nerve stimulation) for acute treatment of episodic cluster headache.

Cluster headache is a debilitating disease characterized by excruciatingly painful attacks that affects 0.15% to 0.4% of the US population. Episodic cluster headache manifests as circadian and circannual seasonal bouts of attacks, each lasting 15 to 180 minutes, with periods of remission. In chronic cluster headache, the attacks occur throughout the year with no periods of remission. While existing treatments are effective for some patients, many patients continue to suffer. There are only 2 FDA-approved medications for episodic cluster headache in the United States, while others, such as high-flow oxygen, are used off-label. Episodic cluster headache is associated with comorbidities and affects work, productivity, and daily functioning. The economic burden of episodic cluster headache is considerable, costing more than twice that of nonheadache patients. gammaCore adjunct to standard of care (SoC) was found to have superior efficacy in treatment of acute episodic cluster headaches compared with sham-gammaCore used with SoC in ACT1 and ACT2 trials. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analysis of gammaCore adjunct to SoC compared with SoC alone for the treatment of acute pain associated with episodic cluster headache attacks. The model structure was based on treatment of acute attacks with 3 outcomes: failures, nonresponders, and responders. The time horizon of the model is 1 year using a payer perspective with uncertainty incorporated. Parameter inputs were derived from primary data from the randomized controlled trials for gammaCore. The mean annual costs associated with the gammaCore-plus-SoC arm was $9510, and mean costs for the SoC-alone arm was $10,040. The mean quality-adjusted life years for gammaCore-plus-SoC arm were 0.83, and for the SoC-alone arm, they were 0.74. The gammaCore-plus-SoC arm was dominant over SoC alone. All 1-way and multiway sensitivity analyses were cost-effective using a threshold of $20,000. gammaCore dominance, representing savings, was driven by superior efficacy, improvement in quality of life (QoL), and reduction in costs associated with successful and consistent abortion of episodic attacks. These findings serve as additional economic evidence to support coverage for gammaCore. Additional real-world data are needed to characterize the long-term impact of gammaCore on comorbidities, utilization, QoL, daily functioning, productivity, and social engagement of these patients, and for other indications.