Joan Forns

Purpose: Ascertaining migraine in electronic healthcare data is challenging because of likely diagnosis underrecording and treatment with over‐the‐counter analgesics, which cannot be used as disease proxies. Algorithm‐identified migraine prevalence may depend on algorithm characteristics and target population. Methods: To describe migraine‐identifying algorithms implemented in electronic healthcare data sources and summarize validation results and observed migraine prevalence, we searched PubMed for peer‐reviewed, English‐language, original research articles that identified migraine in adults using electronic algorithms in electronic healthcare data. We summarized algorithms, validation results, and migraine prevalence (PROSPERO: CRD42023491279). Results: Of 360 unique titles and abstracts, 50 articles (14%) were selected for full‐text review; of them, 41 articles (82%) were finally included: 16 were studies conducted in Europe, 13 in North America, and 12 in Asia. Sixteen studies (39%) identified migraine only using diagnosis codes, 5 (12%) only treatments, 9 (22%) diagnosis and/or treatment codes, and 11 (27%) diagnosis codes, treatments, and setting (e.g., primary care, specialist consultation). Reported migraine prevalence in the general population ranged between 4% and 17%. Only two studies reported validation results: one identified prevention‐eligible patients with migraine (positive predictive value [PPV] = 97%), and one identified migraine on the basis of calculated probabilities with PPVs between 74% and 92%. Conclusion: Finding patients with migraine is feasible in various types of data sources; preferred algorithms vary; algorithm performance is mostly unknown. Identifying chronic migraine or other complex types of migraine requires combining diagnosis codes, treatments, and care settings, which is possible in only some data sources.

Introduction Pimavanserin is the only antipsychotic medication approved in the USA to specifically treat hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Objective To compare mortality risk in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics in an overall PDP cohort and in a subcohort of patients residing in long-term care or skilled nursing facilities (LTC/SNFs). Methods This cohort study identified patients aged ≥ 65 years with PDP initiating pimavanserin or a comparator antipsychotic in US Medicare claims (2016–2021). Cox proportional hazards models were used to estimate hazard ratios (HRs) comparing all-cause mortality in the propensity score-matched treatment groups. Cumulative incidence curves, time period-specific relative risk, and risk difference estimates evaluated risk over time. Results In this follow-up analysis, we identified 4384 pimavanserin initiators and 28,042 comparator initiators in the overall PDP cohort, and 921 pimavanserin initiators and 7963 comparator initiators in the LTC/SNF subcohort. After matching, the overall PDP cohort had 4381 patients in each treatment group, and the LTC/SNF subcohort had 905 patients in each group. The matched HR for mortality (pimavanserin versus comparator) was 0.76 (95% CI 0.68–0.85) in the overall PDP cohort and 0.90 (95% CI 0.74–1.10) in the LTC/SNF subcohort. In the overall PDP cohort, time period-specific relative risks and risk differences showed that pimavanserin initiators had a lower risk of mortality throughout the first 365 days of follow-up. Conclusion In the overall PDP cohort, mortality risk was lower among pimavanserin initiators than comparator antipsychotic initiators.

Ascertaining migraine in electronic healthcare data is challenging because of likely diagnosis underrecording and treatment with over-the-counter analgesics, which cannot be used as disease proxies. Algorithm-identified migraine prevalence may depend on algorithm characteristics and target population. To describe migraine-identifying algorithms implemented in electronic healthcare data sources and summarize validation results and observed migraine prevalence, we searched PubMed for peer-reviewed, English-language, original research articles that identified migraine in adults using electronic algorithms in electronic healthcare data. We summarized algorithms, validation results, and migraine prevalence (PROSPERO: CRD42023491279). Of 360 unique titles and abstracts, 50 articles (14%) were selected for full-text review; of them, 41 articles (82%) were finally included: 16 were conducted in Europe, 13 in North America, and 12 in Asia. Sixteen studies (39%) identified migraine only using diagnosis codes, 5 (12%) only treatments, 9 (22%) diagnosis and/or treatment codes, and 11 (27%) diagnosis codes, treatments, and setting (e.g., primary care, specialist consultation). Reported migraine prevalence in the general population ranged between 4% and 17%. Only 2 studies reported validation results: one identified prevention-eligible patients with migraine (positive predictive value [PPV] = 97%), and one identified migraine on the basis of calculated probabilities with PPVs between 74% and 92%. Finding patients with migraine is feasible in various types of data sources; preferred algorithms vary; algorithm performance is mostly unknown. Identifying chronic migraine or other complex types of migraine requires combining diagnosis codes, treatments, and care settings, which is possible in only some data sources.

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer’s disease by emulating a target trial using the UK CPRD GOLD database (2001-2017). Comparing treatment for 3-6 years vs ≤3 years yielded null results for both types of dementia. Comparing a longer duration of treatment, >6 years vs ≤3 years, yielded a 10-year risk ratio of 0.69 (95% CI, 0.54-0.90) for vascular dementia and 0.91 (95% CI, 0.77-1.10) for Alzheimer’s disease. For illustration, we performed an analysis that failed to emulate a target trial by assigning exposure categories using postbaseline information, obtaining implausible beneficial estimates. Our findings indicate a modest benefit of longer duration of treatment with AC AHT on vascular dementia and highlight the value of the target trial emulation to avoid selection bias in the evaluation of the effect of different durations of treatment. This article is part of a Special Collection on Pharmacoepidemiology.

Introduction Pimavanserin is approved in the USA to treat hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Objectives We evaluated mortality in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics, overall, over time, and across subgroups. Methods A cohort of patients aged ≥65 years in the USA with PDP newly initiating pimavanserin or a comparator atypical antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) was identified in 2016–2019 Medicare claims data. All-cause mortality in the propensity score–matched treatment groups was compared with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated with Cox-proportional hazards models. Cumulative incidence curves and time period–specific models evaluated risk over time. Subgroup and sensitivity analyses were performed, including a sub-cohort of long-term care (LTC) or skilled nursing facility (SNF) residents. Results We identified 2892 pimavanserin initiators and 19,083 comparator initiators (overall 47% female, mean age = 80.9 years, LTC/SNF residents = 30%). Before matching, pimavanserin users had fewer severe comorbidities and more anti-Parkinson medication use than comparators. Matching resulted in 2891 patients in both groups, and all covariates were well balanced. In the matched cohort, the HR for mortality for pimavanserin versus comparator was 0.78 (95% CI 0.67–0.91), with the lowest time period–specific HRs in the first 180 days. Hazard ratios were similar across sensitivity analyses and subgroups. In LTC/SNF residents, the HR was 0.78 (95% CI 0.60–1.01). Conclusion The observed mortality rates were lower among patients treated with pimavanserin compared with those treated with other atypical antipsychotics. Study registration European Union Post-authorization Study (EU PAS) register number 46331.

Background: Little is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis. Given that dementia-related psychosis comprises various dementia types, this study describes the incidence of clinical events and treatment patterns by dementia type after patients with dementia are diagnosed with psychosis. Methods: Adults aged ≥ 65 years with dementia and newly diagnosed with psychosis were identified in US Medicare claims during 2013–2018. Baseline characteristics were evaluated at the time of the psychosis diagnosis. After the initial psychosis diagnosis, incidence rates (IRs) of clinical events (e.g., falls/fractures, infections, healthcare utilization), mortality, and patterns of antipsychotic treatment were described for each dementia type (Alzheimer’s disease [AD], Parkinson’s disease dementia [PDD], dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], vascular dementia [VD], and unspecified dementia). Daily mean cumulative counts were estimated to describe the incidence of recurrent events over time. Mortality was described using Kaplan–Meier survival curves. Results: We identified 484,520 patients with dementia-related psychosis: mean age, 84 years (standard deviation, 7.8); female, 66%. At the time of psychosis diagnosis, the most prevalent type of dementia was unspecified dementia (56%), followed by AD (31%), VD (12%), PDD (10%), DLB (3%), and FTD (< 1%), and most patients had scores indicating severe illness on the Charlson Comorbidity Index (71%) and frailty index (62%). Across all dementia types, IRs (per 100 person-years) were high for emergency department visits, oral anti-infective use, and urinary tract infections after the initial psychosis diagnosis. Patients with DLB had the highest incidence of most clinical outcomes. After 1 year of follow-up, the cumulative probability of death was about 30% for all dementia types, and after 5 years, was about 80% among patients with DLB, VD, AD, or PDD and about 60%-65% among patients with FTD or unspecified dementia. Conclusions: Patients with dementia-related psychosis had a high burden of comorbidities, frailty, emergency department visits, infections, and death. Specifically, after DRP diagnosis, patients with DLB and VD had the highest burden of clinical events of interest.

Introduction This study aimed to estimate risks of cardiovascular and cerebrovascular events in patients treated with lisdexamfetamine dimesylate (LDX) compared with patients previously treated with other attention-deficit/hyperactivity disorder (ADHD) medications (amphetamine, dexamphetamine, methylphenidate or atomoxetine). Methods This population-based cohort study used data from Danish and Swedish medical and administrative national registers. The LDX cohort included adult patients initiating LDX with at least 12 months’ data preceding first LDX dispensing (index date). A random sample of patients treated with at least one non-LDX ADHD medication in the 6–24 months (but not less than 6 months) before index date (previous-users cohort) were matched to LDX users on age, sex, region and calendar year. The primary outcome, a composite of major adverse cardiovascular and cerebrovascular events (MACE), included first hospitalisation for acute myocardial infarction or stroke and out-of-hospital coronary heart disease or cerebrovascular disease death. Incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) of MACE were estimated using Poisson regression. Results From Denmark/Sweden, 5516/40,163 LDX users and 27,494/200,389 previous users were included. In Denmark, IRs of MACE/1000 person-years (95% CI) were similar for LDX (1.63 [0.85–3.14]) and previous users (1.61 [1.28–2.01]). In Sweden, IRs (95% CI) were 1.40 (1.09–1.79) in LDX users and 1.17 (1.00–1.38) in previous users. Adjusted MACE IRRs (95% CI) for LDX versus previous use were 1.01 (0.48–2.13) in Denmark, 1.13 (0.75–1.71) in Sweden, and 1.10 (0.77–1.58) in the pooled analysis. Conclusion Our findings suggest little to no increased risk of cardiovascular and cerebrovascular events in patients treated with LDX compared with patients previously treated with other ADHD medications.

Background Little is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis (DRP). Given that DRP is composed of various dementia types, this current study describes the similarities and differences across the dementia types in the incidence of clinical events and treatment patterns after patients with dementia are diagnosed with psychosis. Methods Adults aged ≥ 65 years and newly diagnosed with DRP were identified in US Medicare claims during 2013–2018. Baseline characteristics were evaluated at the time of the initial DRP diagnosis. After DRP diagnosis, for each dementia type (Alzheimer’s disease [AD], Parkinson’s disease dementia [PDD], dementia with Lewy bodies [DLB], frontotemporal dementia [FTD], vascular dementia [VD], and dementia, unspecified), incidence rates (IRs) of clinical events (e.g., falls/fractures, infections, healthcare utilization), mortality, and patterns of antipsychotic treatment were described. Daily mean cumulative counts were estimated to describe the potentially varying incidence of recurrent events over time. Mortality by time since DRP diagnosis was described using Kaplan-Meier survival curves. Results We identified 484,520 patients with DRP: mean age, 84 years; female, 66%. The most prevalent type of dementia at the index date was unspecified dementia (56%), followed by AD (31%), VD (12%), PDD (10%), DLB (3%), and FTD (< 1%). At the time of DRP diagnosis, most patients had scores on the Charlson Comorbidity Index (71%) and frailty index (62%) indicating severe illness. After DRP diagnosis, IRs (per 100 person-years) were high for emergency department visits, oral anti-infective use, and urinary tract infections for all dementia types. Overall, DLB was the dementia type with the highest incidence of clinical outcomes. After 1 year of follow-up, the cumulative probability of death was about 30% for all types of dementia. After 5 years of follow-up, the cumulative probability of death was about 80% among DRP patients with DLB, VD, AD, or PDD and about 60%-65% among patients with FTD or unspecified dementia Conclusions Patients with DRP had a high burden of comorbidities, frailty, emergency department visits, infections, and death. Specifically, after DRP diagnosis, patients with DLB and VD had the highest burden of clinical events of interest.

Background Parkinson’s disease-related psychosis increases patients’ risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson’s disease-related psychosis. Objective We aimed to compare the risk of falls/fractures among patients with Parkinson’s disease-related psychosis treated with pimavanserin vs other atypical antipsychotics. Patients and Methods We identified a cohort of patients with Parkinson’s disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015–2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Results We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson’s disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7–35.0) for pimavanserin and 40.8 (35.0–47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators—all characteristics were well balanced after matching—with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27–1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34–0.86). Conclusions The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson’s disease-related psychosis. Sensitivity analyses suggest a decreased risk.