Browsing by Author "Broderick, Joseph P."
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Item Heritability of circle of Willis variations in families with intracranial aneurysms(Public Library of Science, 2018-01-29) Sánchez van Kammen, Mayte; Moomaw, Charles J.; Schaaf, Irene C. van der; Brown, Robert D., Jr.; Woo, Daniel; Broderick, Joseph P.; Mackey, Jason S.; Rinkel, Gabriël J. E.; Huston, John, III; Ruigrok, Ynte M.; Neurology, School of MedicineBACKGROUND: Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. METHODS: We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. RESULTS: We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3). No association was found for the other three circle of Willis variations. CONCLUSIONS: In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.Item Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis(MDPI, 2022-08-30) Morel, Sandrine; Hostettler, Isabel C.; Spinner, Georg R.; Bourcier, Romain; Pera, Joanna; Meling, Torstein R.; Alg, Varinder S.; Houlden, Henry; Bakker, Mark K.; van’t Hof, Femke; Rinkel, Gabriel J.E.; Foroud, Tatiana; Lai, Dongbing; Moomaw, Charles J.; Worrall, Bradford B.; Caroff, Jildaz; Constant-dits-Beaufils, Pacôme; Karakachoff, Matilde; Rimbert, Antoine; Rouchaud, Aymeric; Gaal-Paavola, Emilia I.; Kaukovalta, Hanna; Kivisaari, Riku; Laakso, Aki; Jahromi, Behnam Rezai; Tulamo, Riikka; Friedrich, Christoph M.; Dauvillier, Jerome; Hirsch, Sven; Isidor, Nathalie; Kulcsàr, Zolt; Lövblad, Karl O.; Martin, Olivier; Machi, Paolo; Pereira, Vitor Mendes; Rüfenacht, Daniel; Schaller, Karl; Schilling, Sabine; Slowik, Agnieszka; Jaaskelainen, Juha E.; von und zu Fraunberg, Mikael; Jiménez-Conde, Jordi; Cuadrado-Godia, Elisa; Soriano-Tárraga, Carolina; Millwood, Iona Y.; Walters, Robin G.; The @neurIST project; The ICAN Study Group; Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study Investigators; International Stroke Genetics Consortium (ISGC); Kim, Helen; Redon, Richard; Ko, Nerissa U.; Rouleau, Guy A.; Lindgren, Antti; Niemelä, Mika; Desal, Hubert; Woo, Daniel; Broderick, Joseph P.; Werring, David J.; Ruigrok, Ynte M.; Bijlenga, Philippe; Medical and Molecular Genetics, School of MedicineIntracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.Item Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study(Wolters Kluwer, 2017-09-05) Madsen, Tracy E.; Khoury, Jane; Alwell, Kathleen; Moomaw, Charles J.; Rademacher, Eric; Flaherty, Matthew L.; Woo, Daniel; Mackey, Jason; La Rosa, Felipe De Los Rios; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn; Neurology, School of MedicineOBJECTIVE: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. METHODS: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993-June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. RESULTS: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p < 0.001). Incidence of all strokes decreased over time in men (263 [confidence interval 246-281] to 192 [179-205], p < 0.001) but not in women (217 [205-230] to 198 [187-210], p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223-257] to 165 [153-177], p < 0.01; women, 193 [181-205] to 173 [162-184], p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. CONCLUSIONS: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.Item Sleep for Stroke Management and Recovery Trial (Sleep SMART): Rationale and methods(Sage, 2020-10) Brown, Devin L.; Durkalski, Valerie; Durmer, Jeffrey S.; Broderick, Joseph P.; Zahuranec, Darin B.; Levine, Deborah A.; Anderson, Craig S.; Bravata, Dawn M.; Yaggi, H. Klar; Morgenstern, Lewis B.; Moy, Claudia S.; Chervin, Ronald D.; Neurology, School of MedicineRationale: Obstructive sleep apnea is common among patients with acute ischemic stroke and is associated with reduced functional recovery and an increased risk for recurrent vascular events. Aims and/or hypothesis: The Sleep for Stroke Management and Recovery Trial (Sleep SMART) aims to determine whether automatically adjusting continuous positive airway pressure (aCPAP) treatment for obstructive sleep apnea improves clinical outcomes after acute ischemic stroke or high-risk transient ischemic attack. Sample size estimate: A total of 3062 randomized subjects for the prevention of recurrent serious vascular events, and among these, 1362 stroke survivors for the recovery outcome. Methods and design: Sleep SMART is a phase III, multicenter, prospective randomized, open, blinded outcome event assessed controlled trial. Adults with recent acute ischemic stroke/transient ischemic attack and no contraindication to aCPAP are screened for obstructive sleep apnea with a portable sleep apnea test. Subjects with confirmed obstructive sleep apnea but without predominant central sleep apnea proceed to a run-in night of aCPAP. Subjects with use (≥4 h) of aCPAP and without development of significant central apneas are randomized to aCPAP plus usual care or care-as-usual for six months. Telemedicine is used to monitor and facilitate aCPAP adherence remotely. Study outcomes: Two separate primary outcomes: (1) the composite of recurrent acute ischemic stroke, acute coronary syndrome, and all-cause mortality (prevention) and (2) the modified Rankin scale scores (recovery) at six- and three-month post-randomization, respectively. Discussion: Sleep SMART represents the first large trial to test whether aCPAP for obstructive sleep apnea after stroke/transient ischemic attack reduces recurrent vascular events or death, and improves functional recovery.Item Stable incidence but declining case-fatality rates of subarachnoid hemorrhage in a population(American Academy of Neurology, 2016-11-22) Mackey, Jason; Khoury, Jane C.; Alwell, Kathleen; Moomaw, Charles J.; Kissela, Brett M.; Flaherty, Matthew L.; Adeoye, Opeolu; Woo, Daniel; Ferioli, Simona; De Los Rios La Rosa, Felipe; Martini, Sharyl; Khatri, Pooja; Broderick, Joseph P.; Zuccarello, Mario; Kleindorfer, Dawn; Neurology, School of MedicineObjective: To characterize temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes over 5 time periods in a large population-based stroke study in the United States. Methods: All SAHs among residents of the Greater Cincinnati/Northern Kentucky region at least 20 years of age were identified and verified via study physician review in 5 distinct year-long study periods between 1988 and 2010. We abstracted demographics, care patterns, and outcomes, and we compared incidence and case-fatality rates across the study periods. Results: The incidence of SAH in the 5 study periods (age-, race-, and sex-adjusted to the 2000 US population) was 8.8 (95% confidence interval 6.8–10.7), 9.2 (7.2–11.2), 10.0 (8.0–12.0), 9.0 (7.1–10.9), and 7.7 (6.0–9.4) per 100,000, respectively; the trend in incidence rates from 1988 to 2010 was not statistically significant (p = 0.22). Advanced neurovascular imaging, endovascular coiling, and neurologic intensive care unit availability increased significantly over time. All-cause 5-day (32%–18%, p = 0.01; for trend), 30-day (46%–25%, p = 0.001), and 90-day (49%–29%, p = 0.001) case-fatality rates declined from 1988 to 2010. When we included only proven or highly likely aneurysmal SAH, the declines in case-fatality were no longer statistically significant. Conclusions: Although the incidence of SAH remained stable in this population-based region, 5-day, 30-day, and 90-day case-fatality rates declined significantly. Advances in surgical and medical management, along with systems-based changes such as the emergence of neurocritical care units, are potential explanations for the reduced case-fatality.Item Substance Use and Performance of Toxicology Screens in the Greater Cincinnati Northern Kentucky Stroke Study(American Heart Association, 2022-10) Madsen, Tracy E.; Cummings, Olivia W.; De Los Rios La Rosa, Felipe; Khoury, Jane C.; Alwell, Kathleen; Woo, Daniel; Ferioli, Simona; Martini, Sharyl; Adeoye, Opeolu; Khatri, Pooja; Flaherty, Matthew L.; Mackey, Jason; Mistry, Eva A.; Demel, Stacie L.; Coleman, Elisheva; Jasne, Adam S.; Slavin, Sabreena J.; Walsh, Kyle; Star, Michael; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke. Methods Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20–54 years old. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/4–2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed. Results Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0% and 28.8% of cases in 1993/4, 1999, 2005, 2010 and 2015, respectively (ptrend<0.001). Between 1993/4 and 2015, documented substance use increased in all demographic subgroups. Adjusting for gender, comorbidities, and NIHSS, predictors of toxicology screens included Black race (aOR 1.58, 95%CI 1.02–2.45), younger age (aOR 0.70, 95%CI 0.53–0.91, per 10 years), current smoking (aOR 1.62, 95%CI 1.06–2.46) and treatment at an academic hospital (aOR 1.80, 95%CI 1.14–2.84). After adding chart reported substance use to the model, only chart reported substance abuse and age were significant. Conclusions In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.Item Temporal Trends in Stroke Incidence over Time by Sex and Age in the Greater Cincinnati Northern Kentucky Stroke Study(American Heart Association, 2020-04) Madsen, Tracy E.; Khoury, Jane C.; Leppert, Michelle; Alwell, Kathleen; Moomaw, Charles J.; Sucharew, Heidi; Woo, Daniel; Ferioli, Simona; Martini, Sharyl; Adeoye, Opeolu; Khatri, Pooja; Flaherty, Matthew; De Los Rios La Rosa, Felipe; Mackey, Jason; Mistry, Eva; Demel, Stacie L.; Coleman, Elisheva; Jasne, Adam; Slavin, Sabreena J.; Walsh, Kyle; Star, Michael; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 (P<0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 (P<0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.Item Temporal Trends of Sex Differences in Transient Ischemic Attack Incidence Within a Population(Elsevier, 2019-07-01) Madsen, Tracy E.; Khoury, Jane C.; Alwell, Kathleen; Moomaw, Charles J.; Rademacher, Eric; Flaherty, Matthew L.; Woo, Daniel; De Los Rios La Rosa, Felipe; Mackey, Jason; Martini, Sharyl; Ferioli, Simona; Adeoye, Opeolu; Khatri, Pooja; Broderick, Joseph P.; Kissela, Brett M.; Kleindorfer, Dawn; Neurology, School of MedicineObjective: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population. Methods: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient were included in incidence rates. All cases were physician-adjudicated. Incidence rates (during 7/93-6/94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S. population. T-tests with Bonferroni correction were used to compare rates over time. Results: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95%CI 139-167) per 100,000 in 1993/4 to 117 (95%CI 107-128) in 2010 (p<0.05 for trend test) but was similar over time among females (107 (95%CI 97-116) to 102 (95%CI 94-111), p>0.05). Conclusions: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010.Item Trends Over Time in Stroke Incidence by Race in the Greater Cincinnati Northern Kentucky Stroke Study(Wolters Kluwer, 2024) Madsen, Tracy E.; Ding, Lili; Khoury, Jane C.; Haverbusch, Mary; Woo, Daniel; Ferioli, Simona; De Los Rios La Rosa, Felipe; Martini, Sharyl R.; Adeoye, Opeolu; Khatri, Pooja; Flaherty, Matthew L.; Mackey, Jason; Mistry, Eva A.; Demel, Stacie; Coleman, Elisheva; Jasne, Adam; Slavin, Sabreena; Walsh, Kyle B.; Star, Michael; Broderick, Joseph P.; Kissela, Brett; Kleindorfer, Dawn O.; Neurology, School of MedicineBackground and objectives: Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period. Methods: In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported. Results: Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time. Discussion: Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.