Delayed opportunities for patient-provider communication about medication overuse headache: Mixed methods perspectives from patients and neurologists.

Objectives: Medication overuse headache (MOH) is a common, debilitating condition occurring when migraine patients overuse pain relief medications. We conducted a convergent mixed methods study examining patient-provider communication on MOH. Methods: Migraine patients were identified from one academic health center via electronic health records. Research staff recruited patients and administered a remote survey on MOH awareness, knowledge, and communication; descriptive and bivariate analyses were conducted. Neurologists from the same health center were invited to participate in qualitative interviews; analysis drew from the Rapid Identification of Themes from Audio Recordings procedures. A side-by-side comparison of results followed. Results: Participants included 200 patients and 13 neurologists. More than one third of patients (39.5 %) had never heard of 'medication overuse headache.' Among those who had, 38.4 % learned about MOH ≥ 5 years after their migraine diagnosis. Neurologists similarly reported limited patient awareness of MOH and suggested communication was provider-initiated, reactive to patient-reported symptoms and behaviors. Participants agreed MOH was described as a 'consequence' of frequent medication taking, though specific terminology varied with neurologists suggesting they choose terms they perceive to be easier to understand and less stigmatizing to patients. Neurologists felt they lacked effective patient education resources. Conclusions: Findings reveal delayed opportunities to inform patients about MOH. Standardized education supporting early preventive communication is needed, perhaps in primary care where many patients seek initial care for migraine symptoms.

Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial.

Importance: Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated. Objective: To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO. Design, Setting, and Participants: This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021. Interventions: Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6). Main Outcomes and Measures: Incremental cost-utility ratio. Results: The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health. Conclusions and Relevance: While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

Relationships between headache frequency, disability, and disability-related unemployment among adults with migraine.

BACKGROUND: Migraine is the second most common cause of disability worldwide. Understanding the relationship between migraine and employment status is critical for policymakers, as disability-related unemployment is associated with eligibility for private or governmental disability insurance payments and other associated support for those unable to work because of disability. OBJECTIVE: To assess the association between migraine frequency and selfreported employment status and overall disability in a US representative survey. METHODS: Using data from the 2019 National Health and Wellness Survey (NHWS) (Kantar Health), adults in the United States (aged 18-65 years) reporting at least 1 migraine day in the past 30 days were categorized by headache frequency: low-frequency episodic migraine (LFEM) (≤4 days/month), moderate-frequency EM (MFEM) (5-9 days/month), high-frequency EM (HFEM) (10-14 days/month), or chronic migraine (CM) (≥15 days/month). A control group of adults without migraine with similar baseline characteristics was identified by propensity score matching. Disability-related unemployment was defined as participants responding "short-term disability" or "long-term disability" to occupational status on the NHWS. The frequency of short- or long-term disability was then evaluated across headache frequency groups. In addition, participants were asked to assess migraine-related disability via the Migraine Disability questionnaire (MIDAS). RESULTS: A total of 1,962 respondents with LFEM, 987 with MFEM, 554 with HFEM, and 926 with CM were included in this analysis, along with 4,429 matched controls. Headache frequency was associated both with increased MIDAS score and with employment disability (P < 0.001); 12.3% (n = 114 of 926) of participants with CM reported employment disability, as did 4.4% (n = 86 of 1,962) of the LFEM group and 6.9% (n = 306 of 4,429) of matched controls. There was considerable discordance between the proportion of participants classified as disabled via MIDAS vs those reporting employment-related disability. CONCLUSIONS: More frequent migraine headaches are associated with a higher likelihood of self-reported short- and long-term employment disability and overall migraine-related disability, suggesting that health and economic policymakers must seek ways to maximize the employment opportunities for people living with migraine that may benefit from novel preventive treatments. DISCLOSURES: Robert E Shapiro is a research consultant for Eli Lilly and Lundbeck. Ashley A Martin and Martine C Maculaitis are employees of Cerner Enviza (formerly Kantar Health), which received payment from Lundbeck to conduct the research. Shiven Bhardwaj was an employee of Lundbeck at the time of study and manuscript development. Heather Thomson and Carlton Anderson are employees of Lundbeck. Steven M Kymes is an employee and stockholder of Lundbeck. Financial support for research conducted and manuscript preparation was provided by Lundbeck.

A modelling approach to estimate the prevalence of treatment-resistant schizophrenia in the United States.

INTRODUCTION: Schizophrenia is a condition that places a significant burden on individuals with the condition, their family, and society. A large proportion of those treated for schizophrenia do not experience treatment response and are referred to as having "treatment-resistant schizophrenia" (TRS). Expert opinion has long held that the prevalence of TRS among individuals with schizophrenia is 30%, but the basis of this estimate is unclear. This article presents a model developed for estimating the prevalence of TRS in the United States 2014. METHODS: An incidence-prevalence-mortality model was developed to estimate the prevalence of TRS in the United States. The model was populated with data from public health agencies and published literature. Prevalence in 2014 was modelled using a Markov cohort simulation for each birth cohort between 1930 to 2014. RESULTS: Using different scenarios for baseline incidence, relative risks of mortality, it was estimated that approximately 22% of individuals with schizophrenia would be considered treatment-resistant in 2014. DISCUSSION: The results suggests that prevalence of TRS may be somewhat lower than the 30% often reported, however this is highly dependent on the definition of treatment resistance. Methods such as this may help answer epidemiological and health policy questions as well as test the influence of key underlying assumptions.

Real-world droxidopa or midodrine treatment persistence in patients with neurogenic orthostatic hypotension or orthostatic hypotension.

BACKGROUND: Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension (OH) observed in the presence of neuropathy and is associated with increased risk of falling, impaired function, and poor quality of life. Droxidopa and midodrine are approved in the United States to treat symptomatic nOH and OH in adults, respectively. In this study, we compared the treatment persistence of droxidopa and midodrine. METHODS: A retrospective analysis of patients prescribed either droxidopa or midodrine was conducted using the Symphony Health Solutions database (Symphony Health Solutions, Phoenix, AZ, USA). Inclusion criteria were (1) a pharmacy insurance claim in at least 16 consecutive quarters from mid-2014 to 2018 and (2) an active prescription for droxidopa or midodrine of ≥30 days' duration during that period. Treatment persistence was defined as the time to the first break in drug coverage of ≥45 days and was capped at 365 days. RESULTS: Data from 2305 patients who received droxidopa and 117,243 patients who received midodrine were included in this analysis. Median (95% CI) treatment persistence was significantly longer in the droxidopa cohort versus the midodrine cohort (303 [274-325] vs 172 [169-176] days; P < 0.001). After adjustment for confounding factors, patients using droxidopa monotherapy (i.e., without any concomitant midodrine and/or fludrocortisone use) were 16% more likely to be persistent at any time point than patients using midodrine (P < 0.001). CONCLUSIONS: In this real-world data analysis, patients using droxidopa without concomitant medications for OH were more likely to remain on treatment than patients on midodrine.

Six-Month Use of Droxidopa for Neurogenic Orthostatic Hypotension.

BACKGROUND: Droxidopa is approved for adult patients with symptomatic neurogenic orthostatic hypotension (nOH); there is limited information regarding effects on symptoms, outcomes, and quality of life (QOL) beyond two weeks of treatment. OBJECTIVE: Examine the real-world experience of patients taking droxidopa after six months of treatment. METHODS: This non-interventional, US-based, prospective cohort study utilized a pharmacy hub, identifying patients who recently started droxidopa for nOH treatment. Questionnaires for fall frequency and other patient-reported outcomes (PROs) were completed at baseline and one, three, and six months following droxidopa initiation. RESULTS: 179 enrolled patients completed baseline surveys. Droxidopa continuation rates were high at months one, three, and six (87%, 79%, and 75%, respectively). From baseline to month one, there was significant reduction in the proportion of patients reporting falling at least once (54.1% vs. 43.0%; P = 0.0039), with similar observations at month three (52.9% vs. 44.5%; P = 0.0588) and month six (51.4% vs. 40.0%; P = 0.0339). Significant improvements from baseline to month one were observed and maintained at months three and six for most PROs, including the Orthostatic Hypotension Symptom Assessment Item 1, Short Falls Efficacy Scale-International, Sheehan Disability Scale, Physical Component of the 8-item Short-Form Health Survey, and Patient Health Questionnaire-9. CONCLUSIONS: In this non-interventional prospective study, fewer nOH patients reported falling after one, three, and six months of droxidopa treatment. Further, improvements reported in nOH symptoms, physical function, and QOL measures were maintained for six months following treatment initiation. Results from randomized clinical trials are required to validate the findings.

Impact of CVS Pharmacy's Discontinuance of Tobacco Sales on Cigarette Purchasing (2012-2014).

OBJECTIVES: To assess the impact of CVS Health's discontinuation of tobacco sales on cigarette purchasing. METHODS: We used households' purchasing data to assess rates at which households stopped cigarette purchasing for at least 6 months during September 2014 to August 2015 among 3 baseline groups: CVS-exclusive cigarette purchasers, CVS+ (CVS and other retailers), and other-exclusive (only non-CVS retailers). In state-level analyses using retailers' point-of-sale purchase data, an interrupted time series compared cigarette purchasing before (January 2012 to August 2014) and after (September 2014 to April 2015) tobacco removal in 13 intervention states with CVS market share of at least 15% versus 3 control states with no CVS stores. RESULTS: Compared with other-exclusive purchasers, CVS-exclusive purchasers were 38% likelier (95% confidence interval = 1.06, 1.81) to stop cigarette purchasing after tobacco removal. Compared with control states, intervention states had a significant mean decrease of 0.14 (95% confidence interval = 0.06, 0.22) in packs per smoker per month. CONCLUSIONS: After CVS's tobacco removal, household- and population-level cigarette purchasing declined significantly. Private retailers can play a meaningful role in restricting access to tobacco. This highlights one approach to reducing tobacco use and improving public health.

Cost and Expected Visual Effect of Interventions to Improve Follow-up After Cataract Surgery: Prospective Review of Early Cataract Outcomes and Grading (PRECOG) Study.

IMPORTANCE: Some experts recommend increasing low rates of follow-up after cataract surgery in low- and middle-income countries using various interventions. However, little is known about the cost and effect of such interventions. OBJECTIVE: To examine whether promoting follow-up after cataract surgery creates economic value. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Review of Early Cataract Outcomes and Grading (PRECOG) is a cohort study with data from patients undergoing cataract surgery from January 19, 2010, to April 18, 2012. Final follow-up was completed on August 10, 2012. Data were collected before surgery, at discharge, and at follow-up at least 40 days after surgery from 27 centers in 8 countries in Asia, Africa, and Latin America. Each center enrolled 40 to 120 consecutive patients undergoing cataract surgery. If patients did not return to the hospital for the follow-up visit, hospitals could use telephone calls or transportation subsidies to increase follow-up rate. Data were analyzed from December 2013 to January 2016. MAIN OUTCOMES AND MEASURES: Cost of interventions (telephone calls and transportation subsidies) to increase follow-up at least 40 days after surgery, visual acuity (VA) in the eye undergoing cataract surgery, presence of complications, patient and facility costs per visit, and willingness to pay for treatment or glasses if needed. The maximum incremental cost of improving VA in 1 patient (incremental cost-effect ratio [ICER]) was calculated for spontaneous follow-up (compared with no follow-up) and follow-up with the telephone and transportation interventions. Expected ICERs were estimated including only those patients willing to pay. RESULTS: Among 2487 patients (1068 men [42.9%]; 1405 women [56.5%]; 14 missing [0.6%]; mean [SD] age, 68.4 [11.3] years), 2316 (93.1%) received follow-up, of whom 369 (16.0%) were seen in an outside facility or home and were in the cost-effectiveness analysis as unable to follow up. A grand mean (a mean of means of the different countries) of 56.3% of patients needed glasses, of whom 56.9% were willing to pay, and 1.6% had treatable complications, of whom 39.4% were willing to pay. Maximum proportions with improved VA (and corresponding ICERs) were 0.08 for no follow-up, 0.45 ($151.56) for spontaneous follow-up, 0.53 ($164.46) for a telephone intervention, and 0.53 ($133.07) for a transportation intervention. These results were most sensitive to the cost of follow-up. Expected proportions (ICERs) were 0.08, 0.27 ($232.69), 0.30 ($456.22), and 0.30 ($206.47), respectively. CONCLUSIONS AND RELEVANCE: Most patients benefiting from follow-up after cataract surgery returned spontaneously when requested at discharge. Use of telephone calls or transportation subsidies to increase follow-up in low- and middle-income countries may not be cost-effective.

Association among change in medical costs, level of comorbidity, and change in adherence behavior.

OBJECTIVES: Interventions to improve medication adherence are effective, but resource intensive. Interventions must be targeted to those who will potentially benefit most. We examined what heterogeneity exists in the value of adherence based on levels of comorbidity, and the changes in spending on medical services that followed changes in adherence behavior. STUDY DESIGN: Retrospective cohort study examining medical spending for 2 years (April 1, 2011, to March 31, 2013) in commercial insurance beneficiaries. METHODS: Multivariable linear modeling was used to adjust for differences in patient characteristics. Analyses were performed at the patient/condition level in 2 cohorts: adherent at baseline and nonadherent at baseline. RESULTS: We evaluated 857,041 patients, representing 1,264,797 patient therapies consisting of 40% high cholesterol, 48% hypertension, and 12% diabetes. Among those with 3 or more conditions, annual savings associated with becoming adherent were $5341, $4423, and $2081 for patients with at least diabetes, hypertension, and high cholesterol, respectively. The increased costs for patients in this group who became nonadherent were $4653, $7946, and $4008, respectively. Depending on the condition and the direction of behavior change, savings were 2 to 7 times greater than the value for individuals with fewer than 3 conditions. In most cases, the value of preventing nonadherence (ie, persistence) was greater than the value of moving people who are nonadherent to an adherent state. CONCLUSIONS: There is important heterogeneity in the impact of medication adherence on medical spending. Clinicians and policy makers should consider this when promoting the change of adherence behavior.

Community pharmacy automatic refill program improves adherence to maintenance therapy and reduces wasted medication.

OBJECTIVES: Automatic prescription refill programs are a popular means of improving medication adherence. A concern is the potential for prescription drug wastage and unnecessary healthcare spending. We evaluated the impact of an automatic refill program on patterns of medication use. STUDY DESIGN: Retrospective propensity score matched cohort study with multivariable generalized linear modeling. METHODS: The setting of the study was a pharmacy benefit manager administering benefits for patients of retail pharmacies. Participants included patients on medication for chronic conditions; those receiving a 30-day supply (n = 153,964) and a 90-day supply (n = 100,394) were analyzed separately. The intervention was the automatic prescription refill program. Measures included medication possession ratio (MPR) and average days excess at the time of refill. The results are reported across 11 therapeutic classes. RESULTS: Overall, patients receiving 30-day supplies of medication in the automatic refill program had an MPR that was 3 points higher than those not in the refill program; among those receiving 90-day fills and in the refill program, the MPR was 1.4 points higher (P < .001 for both 30- and 90-day fills). The MPR was higher for members in the refill program across all therapeutic classes. Limiting our analysis to members receiving more than 365 days of medication, we found that patients who received 30-day fills and enrolled in the automatic refill program had 2.5 fewer days' oversupply than those in the control group, whereas automatic refill patients receiving 90-day supplies had 2.18 fewer days' oversupply than the controls (P < .001 for both 30- and 90-day fills). CONCLUSIONS: For this pharmacy provider, automatic refill programs result in improved adherence without adding to medication oversupply.

The burden of hip osteoarthritis in the United States: epidemiologic and economic considerations.

Osteoarthritis (OA) is a common and disabling disease. Because of improved treatment of chronic diseases and lower mortality from infectious diseases, the US population is aging, and older Americans are living with disabling conditions, including hip OA. The projected number of older adults with arthritis or other chronic musculoskeletal joint symptoms is expected to nearly double, from 21.4 million in 2005 to 41.1 million by 2030. The burden of hip OA is increasing due to the aging population and the obesity crisis; as a result, the need for total hip arthroplasty (THA) is expected to grow 174%, to 572,000 primary THAs per year by 2030 in the United States. Prior projections appear to have underestimated the actual number of primary and revision THAs that are in demand.

High resource utilization does not affect mortality in acute respiratory failure patients managed with tracheostomy.

BACKGROUND: Tracheostomy practice in patients with acute respiratory failure (ARF) varies greatly among institutions. This variability has the potential to be reflected in the resources expended providing care. In various healthcare environments, increased resource expenditure has been associated with a favorable effect on outcome. OBJECTIVE: To examine the association between institutional resource expenditure and mortality in ARF patients managed with tracheostomy. METHODS: We developed analytic models employing the University Health Systems Consortium (Oakbrook, Illinois) database. Administrative coding data were used to identify patients with the principal diagnosis of ARF, procedures, complications, post-discharge destination, and survival. Mean resource intensity of participating academic medical centers was determined using risk-adjusted estimates of costs. Mortality risk was determined using a multivariable approach that incorporated patient-level demographic and clinical variables and institution-level resource intensity. RESULTS: We analyzed data from 44,124 ARF subjects, 4,776 (10.8%) of whom underwent tracheostomy. Compared to low-resource-intensity settings, treatment in high-resource-intensity academic medical centers was associated with increased risk of mortality (odds ratio 1.11, 95% CI 1.05-1.76), including those managed with tracheostomy (odds ratio high-resource-intensity academic medical center with tracheostomy 1.10, 95% CI 1.04-1.17). We examined the relationship between complication development and outcome. While neither the profile nor number of complications accumulated differed comparing treatment environments (P > .05 for both), mortality for tracheostomy patients experiencing complications was greater in high-resource-intensity (95/313, 30.3%) versus low-resource-intensity (552/2,587, 21.3%) academic medical centers (P < .001). CONCLUSIONS: We were unable to demonstrate a positive relationship between resource expenditure and outcome in ARF patients managed with tracheostomy.

Accounting for costs, QALYs, and capacity constraints: using discrete-event simulation to evaluate alternative service delivery and organizational scenarios for hospital-based glaucoma services.

BACKGROUND: Decision-analytic models are routinely used as a framework for cost-effectiveness analyses of health care services and technologies; however, these models mostly ignore resource constraints. In this study, we use a discrete-event simulation model to inform a cost-effectiveness analysis of alternative options for the organization and delivery of clinical services in the ophthalmology department of a public hospital. The model is novel, given that it represents both disease outcomes and resource constraints in a routine clinical setting. METHODS: A 5-year discrete-event simulation model representing glaucoma patient services at the Royal Adelaide Hospital (RAH) was implemented and calibrated to patient-level data. The data were sourced from routinely collected waiting and appointment lists, patient record data, and the published literature. Patient-level costs and quality-adjusted life years were estimated for a range of alternative scenarios, including combinations of alternate follow-up times, booking cycles, and treatment pathways. RESULTS: The model shows that a) extending booking cycle length from 4 to 6 months, b) extending follow-up visit times by 2 to 3 months, and c) using laser in preference to medication are more cost-effective than current practice at the RAH eye clinic. CONCLUSIONS: The current simulation model provides a useful tool for informing improvements in the organization and delivery of glaucoma services at a local level (e.g., within a hospital), on the basis of expected effects on costs and health outcomes while accounting for current capacity constraints. Our model may be adapted to represent glaucoma services at other hospitals, whereas the general modeling approach could be applied to many other clinical service areas.

Asymmetry in keratoconus and vision-related quality of life.

PURPOSE: To examine the relationship of increased ocular asymmetry over time to vision-related quality of life in keratoconus. METHODS: The subjects were from the Collaborative Longitudinal Evaluation of Keratoconus Study and had complete data on a least 1 scale of the National Eye Institute Visual Function Questionnaire and examination data at baseline and at least 1 follow-up visit. Three measures of disease asymmetry [visual acuity (VA), corneal curvature, and refractive error] and better eye status were assessed. Multilevel models were fit to the data. RESULTS: The analyses were completed using the data from 961 subjects. Six scales on the National Eye Institute Visual Function Questionnaire had adequate variability to the model (distance activity, driving, mental health, near activity, ocular pain, and role difficulties). Refractive error changes were not associated with statistically significant quality-of-life differences. Except for ocular pain, statistically significant, but not clinically meaningful, differences were found for VA changes and corneal curvature changes. For a 0.1-unit logarithm of the minimum angle of resolution of VA change, the quality-of-life scales decreased between 0.20 and 0.99 units. For a 1.00-diopter steepening of corneal curvature, these decreases were on the order of 0.20 to 0.59 units. Changes related to asymmetry were small as well; decreases were on the order of 0.20 to 0.38 units. CONCLUSIONS: Increasing ocular asymmetry and decreases in VA and corneal steepening in the better eye were associated with decreasing vision-related quality of life, although the magnitudes of the changes were not clinically meaningful. Of these 2 disease status indicators, the vision in the better eye had greater effect on the vision-related quality of life.