Looking for opportunities to co-enroll: The DISCOVERY study experience.

BACKGROUND: Conducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment. METHODS: This analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll. RESULTS: 59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment. CONCLUSION: A large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.

Brain Connectivity Measures Improve Modeling of Functional Outcome After Acute Ischemic Stroke.

Background and Purpose- The ability to model long-term functional outcomes after acute ischemic stroke represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brain's connectivity as a graph, whose topological properties have helped uncover underlying mechanisms of brain function in health and disease. Specifically, we assessed the impact of stroke lesions on rich club organization, a high capacity backbone system of brain function. Methods- In a hospital-based cohort of 41 acute ischemic stroke patients, we investigated the effect of acute infarcts on the brain's prestroke rich club backbone and poststroke functional connectomes with respect to poststroke outcome. Functional connectomes were created using 3 anatomic atlases, and characteristic path-length (L) was calculated for each connectome. The number of rich club regions affected were manually determined using each patient's diffusion weighted image. We investigated differences in L with respect to outcome (modified Rankin Scale score; 90 days) and the National Institutes of Health Stroke Scale (NIHSS; early: 2-5 days; late: 90-day follow-up). Furthermore, we assessed the effect of including number of rich club regions and L in outcome models, using linear regression and assessing the explained variance (R2). Results- Of 41 patients (mean age [range]: 70 [45-89] years), 61% were male. Lower L was generally associated with better outcome. Including number of rich club regions in the backward selection models of outcome, R2 increased between 1.3- and 2.6-fold beyond that of traditional markers (age and acute lesion volume) for NIHSS and modified Rankin Scale score. Conclusions- In this proof-of-concept study, we showed that information on network topology can be leveraged to improve modeling of poststroke functional outcome. Future studies are warranted to validate this approach in larger prospective studies of outcome prediction in stroke.

Isolated Upper Limb Weakness From Ischemic Stroke: Mechanisms and Outcome.

OBJECTIVE: To characterize isolated upper extremity (UE) weakness from stroke. METHODS: In our Get with the Guidelines-Stroke dataset (n = 7643), 87 patients (1.14%) had isolated UE weakness and underwent thorough stroke evaluation with diffusion-weighted magnetic resonance imaging and good-quality arterial imaging. We analyzed clinical-imaging features, etiology, management, and outcome. Since isolated UE weakness is typically associated with contralateral hand-knob area infarcts, patients were classified into Group-A (motor strip infarct) or Group-B (non-motor strip infarct). RESULTS: The mean age was 68 years; 66% were male, 72% had hypertension, 22% diabetes, 53% hyperlipidemia, and 16% were smokers. In Group-A (n = 71), 18 patients had single and 53 had multiple infarcts involving the contralateral motor strip. In Group-B (n = 16), 6 patients had contralateral subcortical white matter infarcts, 9 had bihemispheric infarcts and 1 had a brainstem infarct. Compared to Group-B, patients in Group-A more often had carotid artery stenosis or irregular plaque (84.5% versus 50%, P = .006) and large-artery atherosclerosis mechanism (46% versus 19%, P = .05), and less often cardioembolic mechanism (13% versus 44%, P = .008). Among 36 patients with large-artery mechanism, 27 had less than 70% stenosis including 19 with plaque ulceration/thrombus. Recurrent strokes occurred in 10 patients (11.5%), including 5 with mild-moderate carotid stenosis and plaque ulceration/thrombosis, over 1515 days follow-up. CONCLUSION: Stroke mechanism in acute isolated UE weakness is variable. Contralateral motor-strip infarcts are associated with carotid stenosis, often with plaque ulceration ("vulnerable carotid plaque"), and infarcts in other locations with cardioembolism. Recurrent stroke risk is high especially with mild-moderate carotid artery stenosis and plaque ulceration/thrombus.

High-flow oxygen therapy for treatment of acute migraine: A randomized crossover trial.

Background Impaired oxygen utilization and cerebrovascular dysfunction are implicated in migraine. High-flow oxygen is effective in cluster headache and has shown promise in animal models of migraine, but has not been adequately studied in patients with migraine. Methods In this randomized, crossover-design, placebo-controlled trial, adult migraineurs self-administered high-flow oxygen or medical air at 10-15 l/min via face mask in blinded fashion starting soon after symptom onset for 30 minutes, for a total of four migraine attacks. Participants recorded the severity of headache, nausea, and visual symptoms on visual analog scales periodically up to 60 minutes. Results We enrolled 22 individuals (mean age 36 years, 20 women) who self-treated 64 migraine attacks (33 oxygen, 31 air). The pre-specified primary endpoint (mean decrease in pain score from baseline to 30 minutes) was 1.38 ± 1.42 in oxygen-treated and 1.22 ± 1.61 in air-treated attacks ( p = 0.674). Oxygen therapy resulted in relief (severity score 0-1) of pain (24% versus 6%, p = 0.05), nausea (42% versus 23%, p = 0.08) and visual symptoms (36% versus 7%, p = 0.004) at 60 minutes. Exploratory analysis showed that in moderately severe attacks (baseline pain score <6), pain relief was achieved in six of 13 (46%) oxygen versus one of 15 (7%) air ( p = 0.02). Gas therapy was used per protocol in 91% of attacks. There were no significant adverse events. Conclusion High-flow oxygen may be a feasible and safe strategy to treat acute migraine. Further studies are required to determine if this relatively inexpensive, widely available treatment can be used as an adjunct or alternative migraine therapy.

Long-term outcomes after reversible cerebral vasoconstriction syndrome.

BACKGROUND: Long-term outcomes of reversible cerebral vasoconstriction syndrome (RCVS) have not been systematically investigated. METHODS: The following validated questionnaires were mailed to patients recruited from the RCVS registries of two academic hospitals: headache screening form, Headache Impact Test, Migraine Disability Assessment Test, Barthel Index (BI), EuroQoL (EQ-5D-5L) and Patient Health Questionnaire (PHQ-9). RESULTS: Of the 191 patients in the registries, 109 could be contacted and 45 responded. Median follow-up time after symptom onset was 78 months. After RCVS resolution, 24 (53%) patients continued to have headache, but the majority (88%) reported improvement in its severity. Thirteen of the 24 patients with persistent headache had a history of migraine prior to RCVS diagnosis. The majority (97.5%) of respondents were functionally independent based on BI scores. EQ-5D-5L showed better scores in the domains of mobility, self-care and usual activities, as compared to pain and anxiety/depression. Patients with persistent headache had significantly higher levels of EQ-5D-5L pain scores. PHQ-9 scores revealed only one patient (3%) with severe depression. CONCLUSION: More than half of RCVS patients will continue to have chronic headaches of mild to moderate intensity that are distinct from the "thunderclap" headaches at RCVS onset. The vast majority regain complete functional ability. However, pain and anxiety/depression are frequent, often aggravated by concomitant chronic headaches, and may be associated with lower quality of life.

Cumulative environmental quality is associated with breast cancer incidence differentially by summary stage and urbanicity.

Individual environmental contaminants have been associated with breast cancer; however, evaluations of multiple exposures simultaneously are limited. Herein, we evaluated associations between breast cancer summary stages and the Environmental Quality Index (EQI), which includes a range of environmental factors across five domains. The EQI (2000-2005) was linked to county-level age-standardized incidence rates (SIRs) obtained from the North Carolina Central Cancer Registry (2010-2014). Incidence rates and SIRs of total, in situ, localized, regional, and distant breast cancers were evaluated stratified by rural-urban status. In counties with poor environmental quality compared to those with good environmental quality, total breast cancer incidence was higher by 10.82 cases per 100,000 persons (95% CI 2.04, 19.60, p = 0.02). This association was most pronounced for localized breast cancer (ß = 5.59, 95% CI 0.59, 10.58, p = 0.03). Higher incidence of early-stage disease (carcinoma in situ ß = 5.25, 95% CI 2.34, 8.16, p = 0.00 and localized breast cancer ß = 6.98, 95% CI 2.24, 11.73, p = 0.00) and total breast cancer (ß = 11.44, 95% CI 3.01, 19.87, p = 0.01) occurred in counties with poor land quality, especially urban counties. Our analyses indicate significant associations between environmental quality and breast cancer incidence, which differ by breast cancer stage and urbanicity, identifying a critical need to assess cumulative environmental exposures in the context of cancer stage.

Evaluation of Medication Therapy Issues, Resolutions, and Adherence Among Persons With HIV in the Pharmacist-Led Patient-Centered HIV Care Model.

OBJECTIVE: To identify medication therapy issues and resolutions and assess their relationship to antiretroviral therapy (ART) adherence among participants of the Patient-Centered HIV Care Model demonstration project. METHODS: Adult persons with HIV (PWH) in the United States were enrolled in the Patient-Centered HIV Care Model from August 2014 to September 2016. Pharmacists conducted regular medication therapy reviews and documented ART and non-ART issues and suggested resolutions. Adherence to ART was calculated using proportion of days covered (PDC), and the mean PDC by the number of ART issues was compared using a generalized linear model with linear trend estimation. RESULTS: The most common ART issue was adherence (57%). Adherence ART issues were resolved by adherence management (48%) or patient education (36%). Participants had a mean of 4.2 ART issues and 6.4 non-ART issues. PDC was 89% for those with 0 ART issues and 73% for those with ≥3 ART issues. Persons with 0 ART issues had an increase in adherence (+8%) in the postperiod, whereas those with ≥3 ART issues had a decrease in adherence (-6%) (P = 0.02) in the postperiod. CONCLUSIONS: Identifying therapy issues could help pharmacists improve care for PWH. Because PWH are an aging population with an increased risk of comorbidities and polypharmacy, pharmacists and providers should collaborate to provide holistic, primary care solutions to address both the number and nature of therapy issues.

Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate.

BACKGROUND: In human immunodeficiency virus (HIV) treatment, tenofovir alafenamide (TAF) is associated with greater increases in all fasting cholesterol subgroups compared with tenofovir disoproxil fumarate (TDF). Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naive adults living with HIV treated with TAF or TDF. METHODS: Participants (N = 1744) were randomized (1:1) to initiate TAF or TDF, each coformulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40-79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on American College of Cardiology/American Heart Association Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF versus TDF were calculated. RESULTS: Participants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at W96, including total cholesterol (191 vs 177 mg/dL; P < .001), low-density lipoprotein ([LDL] 119 vs 112 mg/dL; P < .001), and high-density lipoprotein ([HDL] 51 vs 48 mg/dL; P < .001), respectively. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF versus TDF at baseline (4.9% vs 5.4%; P = .35) and W96 (6.1% vs 6.2%; P = .04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total cholesterol (TC) and HDL cholesterol. At W96, TC/HDL ratios (median) were 3.7 for both groups (P = .69). There was no difference between shifts in categorical risk for TAF versus TDF (9% vs 5%; P = .19). Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%; P = .47). CONCLUSIONS: Lipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared with TDF.

White Matter Integrity and Early Outcomes After Acute Ischemic Stroke.

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3-5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3-5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10-3, mm2/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (ß = - 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8-221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

Time of day that Aedes sierrensis females enter oviposition sites prior to laying eggs.

An ovitrap with a time-segregated entrance was used to separate eggs laid by Aedes sierrensis females according to the time of day that females entered the ovitrap. During a 37-day period in Lake County, CA, females that entered the ovitrap between sunrise and sunset laid 82% of the total number of eggs collected. A daily peak in oviposition (eggs per hour) was produced by females that entered during the 2-h period ending at sunset. Overall, females that oviposited had entered the ovitrap throughout the diel cycle except for a 2-h period ending at sunrise. Those eggs laid by females that entered the ovitrap between 2 h after sunset and 2 h before sunrise provided the 1st evidence that Ae. sierrensis females are capable of locating oviposition sites during the night.

Pharmacist-led Tdap vaccination of close contacts of neonates in a women's hospital.

BACKGROUND: Pertussis can cause severe illness and death in infants. Immunization of family members with the tetanus toxoid, reduced diphtheria toxoids, and acellular pertussis (Tdap) vaccine can decrease risk of pertussis infection among infants. A community pharmacy on a women's hospital campus implemented a Tdap vaccination pilot program. OBJECTIVE: To investigate the rate of Tdap vaccination among close contacts of neonates in a women's hospital pharmacy and to assess the impact of a coordinated pharmacy and hospital Tdap vaccination program. METHODS: The intervention entailed education from hospital staff who explained the risks of pertussis, advocated the benefits of vaccination, and encouraged family members to be vaccinated. In the on-site clinic or in the pharmacy, pharmacists administered vaccine to eligible patients. Rates of Tdap vaccinations in the intervention pharmacy with in-hospital vaccination were compared to comparison pharmacies without Tdap interventions. RESULTS: In the pre-study period (December 2008-November 2010), there were 31 Tdap vaccinations administered at the intervention pharmacy (mean=1.3/month); during the study period (December 2010-November 2012), 2045 Tdap vaccinations were administered (mean=85.2/month). In four comparison hospital-campus pharmacies, there were 77 vaccinations (mean=0.8/month) during the pre-study period and 817 vaccinations (mean=8.5/month) during the study period. There were 155 vaccinations administered in 44 area-community pharmacies (mean=0.1/month) during the pre-study period and 2930 (mean=2.8/month) during the study period. The intervention pharmacy had the highest average monthly rate of change in Tdap volume from pre-study to study period (83.9), compared to comparison hospital-campus pharmacies (7.7, p<.001) and area-community pharmacies (2.7, p<.001). During the study period, the estimated Tdap vaccination coverage per live births was 8.1% in the intervention pharmacy versus 5.5% in the comparison hospital-campus pharmacies (p<.001). CONCLUSIONS: Tdap vaccination rates increased after implementation of the intervention program. This project illustrates how health systems and community pharmacists can collaborate to improve patient care.