BACKGROUND AND PURPOSE—Endovascular coiling therapy is increasingly popular for obliteration of unruptured intracranial aneurysms, but older patients face higher procedural risks and shorter periods ...during which an untreated aneurysm may rupture causing subarachnoid hemorrhage (SAH). We assessed trends in clipping and coiling of unruptured intracranial aneurysms, outcomes after clipping and coiling of unruptured intracranial aneurysms, and in SAH among Medicare beneficiaries.
METHODS—Using 2000 to 2010 Medicare Provider Analysis and Review data, we identified 2 cohorts of patients admitted electively for clipping or coiling of an unruptured aneurysm(1) utilization cohort (2000–2010)patients ≥65 years enrolled ≥1 month in a given year and (2) outcomes cohort (2001–2010)patients ≥66 years of age enrolled in Medicare for ≥1 year. We calculated rates of clipping, coiling, and SAH per 100 000 Medicare beneficiaries. We tested for trends in the risk of in-hospital mortality and complications, discharge destination, 30-day mortality, 30-day readmissions, and length of hospitalization.
RESULTS—Characteristics of patients undergoing clipping (n=4357) or coiling (n=7942) did not change appreciably. Overall, 30-day mortality, in-hospital complications, and 30-day readmissions decreased, generally reaching their lowest levels in 2008 to 2010 (1.6%, 25.0%, and 14.5% for clipping and 1.5%, 13.8%, and 11.0% for coiling, respectively). Procedural treatment rates per 100 000 beneficiaries increased from 1.4 in 2000 to 6.0 in 2010, driven mainly by increased use of coiling but SAH rates did not decrease.
CONCLUSIONS—Although outcomes tended to improve over time, increased preventative treatment of unruptured intracranial aneurysms among Medicare beneficiaries did not result in a population-level decrease in SAH rates.
Confounding by indication is a serious threat to comparative studies using real world data. We assessed the utility of automated data-adaptive analytic approach for confounding adjustment when both ...claims and clinical registry data are available. We used a comparative study example of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in 2005-2008 when CAS was only indicated for patients with high surgical risk. We included Medicare beneficiaries linked to the Society for Vascular Surgery's Vascular Registry >65 years old undergoing CAS/CEA. We compared hazard ratios (HRs) for death while adjusting for confounding by combining various 1) Propensity score (PS) modeling strategies (investigator-specified IS-PS vs. automated data-adaptive ada-PS); 2) data sources (claims-only, registry-only and claims-plus-registry); and 3) PS adjustment approaches (matching vs. quintiles-adjustment with/without trimming). An HR of 1.0 was used as a benchmark effect estimate based on CREST trial. The cohort included 1,999 CAS and 3,255 CEA patients (mean age 76). CAS patients were more likely symptomatic and at high surgical risk, and experienced higher mortality (crude HR = 1.82 for CAS vs. CEA). HRs from PS-quintile adjustment without trimming were 1.48 and 1.52 for claims-only IS-PS and ada-PS, 1.51 and 1.42 for registry-only IS-PS and ada-PS, and 1.34 and 1.23 for claims-plus-registry IS-PS and ada-PS, respectively. Estimates from other PS adjustment approaches showed similar patterns. In a comparative effectiveness study of CAS vs. CEA with strong confounding by indication, ada-PS performed better than IS-PS in general, but both claims and registry data were needed to adequately control for bias.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The objective of this study was to assess the relationship between factor XI (FXI) deficiency and the risks of bleeding and cardiovascular (CV) events. We conducted a retrospective cohort ...study using data from Maccabi Healthcare Services (MHS). We identified adults with FXI deficiency (severe: <15%, partial: 15 to <50%, any deficiency: <50%) that had been tested for FXI between 2007 and 2018 and matched to patients from the general MHS population. We estimated 10-year risks of outcomes using the Kaplan–Meier approach. Using Cox proportional hazards regression, we compared outcomes among patients with versus without FXI deficiency. Less than 10% of patients tested for FXI activity had activity levels <50% (mean age: 39 years; 72.2% females). Compared with the general population, patients with any FXI deficiency were at higher risk of severe bleeding (adjusted hazard ratio aHR: 2.56, 95% confidence interval CI: 1.13–5.81; 10-year risk: 1.90%, 95% CI: 0.50–3.20% vs. 0.90%, 95% CI: 0.50–1.30%) and clinically relevant nonsevere bleeding (CRNSB) (aHR: 1.45, 95% CI: 1.08–1.97; 10-year risk: 11.60%, 95% CI: 8.30–14.80% vs. 9.20%, 95% CI: 8.00–10.40%). Severe FXI deficiency was associated with a greater risk of CRNSB. While few CV events (
N
= 2) and venous thromboembolisms (VTE) (
N
= 1) were observed in the FXI overall deficient group, there was a nonsignificant negative association between any FXI deficiency and CV events (aHR: 0.55; 95% CI: 0.13–2.36) and VTEs (aHR: 0.45; 95% CI: 0.06–3.47). Overall FXI deficiency was associated with an increased risk of severe bleeding and CRNSB. Further research is warranted to explore the lower risk of CV and VTE among patients with FXI deficiency compared with the general population.
The relationship between underlying type 2 inflammation and immune response to COVID-19 is unclear.
To assess the relationships between allergic conditions and COVID-19 susceptibility and outcomes.
...In the Optum database, adult patients with and without major allergic conditions (asthma, atopic dermatitis AD, allergic rhinitis, food allergy, anaphylaxis, or eosinophilic esophagitis) and patients with and without severe asthma/AD were identified. Adjusted incidence rate ratios for COVID-19 were compared among patients with vs without allergic conditions or severe asthma/AD vs non-severe asthma/AD during April 1, 2020, to December 31, 2020. Among patients with COVID-19, adjusted hazard ratios (aHRs) of 30-day COVID-19–related hospitalization/all-cause mortality were estimated for the same comparisons during April 1, 2020, to March 31, 2022.
Patients with (N = 1,273,231; asthma, 47.2%; AD, 1.5%; allergic rhinitis, 58.6%; food allergy, 5.1%; anaphylaxis, 4.1%; eosinophilic esophagitis, 0.9%) and without allergic conditions (N = 2,278,571) were identified. Allergic conditions (adjusted incidence rate ratios 95% CI, 1.22 1.21-1.24) and asthma severity (1.12 1.09-1.15) were associated with increased incidence of COVID-19. Among patients with COVID-19 (patients with N = 261,076 and without allergic conditions N = 1,098,135 were matched on age, sex, region, index month), having an allergic condition had minimal impact on 30-day COVID-19–related hospitalization/all-cause mortality (aHR 95% CI 0.96 0.95-0.98) but was associated with a lower risk of mortality (0.80 0.78-0.83). Asthma was associated with a higher risk of COVID-19–related hospitalization/all-cause mortality vs non-asthma allergic conditions (aHR 95% CI, 1.27 1.25-1.30), mostly driven by higher hospitalization.
Allergic conditions were associated with an increased risk of receiving COVID-19 diagnosis but reduced mortality after infection.
CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (< 100 children or young adults worldwide) and potentially ...fatal. The study used mixed-methods approaches to assess how pozelimab impacts the signs and symptoms of CHAPLE disease from the patient perspective by combining within-trial interviews and clinical outcome assessments (COAs) (ClinicalTrials.gov, NCT04209634). Interviews conducted with patients/caregivers at screening and week 24 assessed the signs and symptoms of CHAPLE disease, including those which were most bothersome, and evaluated the change. Patients/caregivers and clinicians completed the COAs; interview data contextualized the meaningfulness of change. Ten patients (aged 3-19 years) were enrolled; caregivers contributed to nine interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting are the core signs and symptoms of CHAPLE disease (greater than or equal to 90% patients experienced pre-treatment); the most bothersome signs and symptoms were abdominal pain (n = 9) and facial edema (n = 1). All core signs and symptoms were reported as resolved at week 24 interviews. Severity on global assessments changed from "mild" to "very severe" at baseline to "no signs or symptoms" at week 24. Interview results were generally consistent with sign- or symptom-specific COA scores. Trial registration
ObjectiveTo assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with COVID-19 in the ambulatory setting, ...including patients diagnosed during the Delta-dominant period prior to Omicron emergence.DesignRetrospective cohort study.SettingKomodo Health closed claims database.Participants13 273 128 patients diagnosed with COVID-19 (December 2020 through September 2021) were treated with CAS+IMD or untreated but treatment eligible under the Emergency Use Authorization (EUA). Each treated patient was exact and propensity score matched without replacement to up to five untreated EUA-eligible patients.InterventionsCAS+IMD.Primary and secondary outcome measuresComposite endpoint of 30-day all-cause mortality or COVID-19-related hospitalisation. Kaplan-Meier estimators were used to calculate outcome risks overall and across subgroups: age, COVID-19 vaccination status, immunocompromised status, and timing of diagnosis (December 2020 to June 2021, and July to September 2021). Cox proportional hazards models were used to estimate adjusted HRs (aHRs) and 95% CIs.ResultsAmong 75 159 CAS+IMD-treated and 1 670 338 EUA-eligible untreated patients, 73 759 treated patients were matched to 310 688 untreated patients; matched patients were ~50 years, ~60% were women and generally well balanced across risk factors. The 30-day risk of the composite outcome was 2.1% and 5.2% in the CAS+IMD-treated and CAS+IMD-untreated patients, respectively; equivalent to a 60% lower risk (aHR 0.40; 95% CI, 0.38 to 0.42). The effect of CAS+IMD was consistent across subgroups, including those who received a COVID-19 vaccine (aHR 0.48, 95% CI, 0.41 to 0.56), and those diagnosed during the Delta-dominant period (aHR 0.40, 95% CI, 0.38 to 0.42).ConclusionsThe real-world effectiveness of CAS+IMD is consistent with the efficacy for reducing all-cause mortality or COVID-19-related hospitalisation reported in clinical trials. Effectiveness is maintained across patient subgroups, including those prone to breakthrough infections, and was effective against susceptible variants including Delta.
Introduction
Identifying risk factors for progression to severe COVID-19 requiring urgent medical visits and hospitalizations (UMVs) among patients initially diagnosed in the outpatient setting may ...help inform patient management. The objective of this study was to estimate the incidence of and risk factors for COVID-19-related UMVs after outpatient COVID-19 diagnosis or positive SARS-CoV-2 test.
Methods
Data for this retrospective cohort study were from the Optum
®
de-identified COVID-19 Electronic Health Record database from June 1 to December 9, 2020. Adults with first COVID-19 diagnosis or positive SARS-CoV-2 test in outpatient settings were identified. Cumulative incidence function analysis stratified by risk factors was used to estimate the 30-day incidence of COVID-19-related UMVs. Competing risk regression models were used to derive adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for factors associated with UMVs.
Results
Among 206,741 patients 58.8% female, 77.5% non-Hispanic Caucasian, mean (SD) age: 46.7 (17.8) years, the 30-day incidence was 9.4% (95% CI 9.3–9.6) for COVID-19-related emergency room (ER)/urgent care (UC)/hospitalizations and 3.8% (95% CI 3.7–3.9) for COVID-19-related hospitalizations. Likelihood of hospitalization increased with age and body mass index, with age the strongest risk factor (aHR 5.61; 95% CI 4.90–6.32 for patients ≥ 85 years). Increased likelihood of hospitalization was observed for first presentation in the ER/UC vs. non-ER/UC outpatient settings (aHR 2.35; 95% CI 2.22–2.47) and prior all-cause hospitalization (aHR 1.90; 95% CI 1.79–2.00). Clinical risk factors of hospitalizations included pregnancy, uncontrolled diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and autoimmune disease. A study limitation is that data on COVID-19 severity and symptoms were not captured.
Conclusion
Predictors of COVID-19-related UMVs include older age, obesity, and several comorbidities. These findings may inform patient management and resource allocation following outpatient COVID-19 diagnosis.
IMPORTANCE: Despite increased carotid artery stenting (CAS) dissemination following the 2005 National Coverage Determination, to our knowledge, periprocedural and long-term outcomes have not been ...described among Medicare beneficiaries. OBJECTIVE: To describe the incidence of outcomes during and after the periprocedural period among Medicare beneficiaries undergoing CAS. DESIGN, SETTING, AND PARTICIPANTS: Observational study with a mean follow-up time of approximately 2 years among 22 516 fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for Medicare & Medicaid Services’ CAS database. Database procedure dates were required to fall during a Medicare hospitalization for CAS. MAIN OUTCOMES AND MEASURES: Periprocedural (30-day) and long-term risks of mortality and stroke or transient ischemic attack, as well as periprocedural myocardial infarction. Subgroups were based on sociodemographic, clinical, and center-level factors, as well as the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) enrollment criteria. RESULTS: The mean patient age was 76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least 70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial infarction risks were 1.7% (95% CI, 1.5%-1.8%), 3.3% (95% CI, 3.0%-3.5%), and 2.5% (95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of 2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3% (95% CI, 35.8%-38.7%) among symptomatic patients and 27.7% (95% CI, 26.4%-28.9%) among asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective hospital admission were associated with increased adjusted hazards of mortality and stroke or transient ischemic attack during and after the periprocedural period. The presence of a stroke center, government ownership, and a hospital bed capacity of 500 or more were associated with increased adjusted hazards of periprocedural mortality and stroke or transient ischemic attack. Few patients met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians did not meet proficiency requirements either due to exceeding periprocedural complication trial thresholds or not meeting minimum CAS volume requirements. CONCLUSIONS AND RELEVANCE: Competing risks may limit the benefits of CAS in certain Medicare beneficiaries, particularly among older and symptomatic patients who have higher periprocedural and long-term mortality risks. The generalizability of trials like the SAPPHIRE or CREST to the Medicare population may be limited, underscoring the need to evaluate real-world effectiveness of carotid stenosis treatments.
The dominant allergen in cat dander, Felis domesticus allergen 1 (Fel d 1), is a persistent trigger for allergic rhinitis and asthma symptoms.
We evaluated the efficacy of Fel d 1 monoclonal ...antibodies (REGN1908/1909) in preventing cat allergen–induced early asthmatic responses (EARs) in cat-allergic patients with mild asthma.
Patients were randomized to single-dose REGN1908/1909 600 mg (n = 29) or placebo (n = 27). The FEV1 was measured for up to 4 hours in a cat allergen environmental exposure unit up to 85 days after dosing. Assessments included between-group differences in change from baseline in FEV1 area under the curve (AUC; 0-2 hours) and incidence of EAR (FEV1 reduction ≥20%). Trial registration: NCT03838731.
Single-dose REGN1908/1909 significantly prevented reductions in FEV1 on days 8, 29, 57, and 85. Most REGN1908/1909 patients did not have an EAR by 4 hours (the last time point tested). In contrast, placebo-treated patients experienced a ≥20% mean FEV1 reduction on days 8, 29, 57, and 85 after dosing, with most experiencing an EAR within 1 hour. REGN1908/1909-treated patients tolerated 3-fold higher allergen quantities (P < .05 at all time points) versus placebo. REGN1908/1909 substantially reduced skin test reactivity to cat allergen versus placebo at all time points tested (nominal P < .001). REGN1908/1909 was generally well tolerated; no serious adverse events or deaths were reported.
Single-dose REGN1908/1909 significantly prevented reductions in FEV1 in cat-allergic patients with mild asthma on cat allergen environmental exposure unit exposure at 8 days and up to 85 days after dose.
The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown.
To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy.
This ...retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period.
A total of 1963 adults were identified who initiated dupilumab (mean SD age 42.1 15.7 years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months.
Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.
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