Citations

AbstractBackgroundAn analysis of the ethnoracial and educational composition of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, and the relationship between ethnoracial/education and screening, enrollment, dropout, and biomarkers is needed to assess the generalizability of ADNI data to diverse populations, and to inform efforts to increase diversity.MethodData from all 4 ADNI phases were used to determine ethnoracial and educational breakdown and differences of the following ADNI participation metrics: screening, screen fails, enrollment, as well as drop‐out within and between ADNI phases. Multivariable logistic regression was used to analyze the association between ethnoracial and educational group and either amyloid positivity or ApoE e4 status, adjusting for age, gender, and diagnostic group.ResultAcross the 4 ADNI phases (screened: n=3,739; enrolled: n=2,286), 11% of screened and enrolled participants identified as Latinx, non‐Latinx Black, or non‐Latinx‐Asian and 16% of the screened and 15% of the enrolled participants reported having =<12 years of education. In contrast, the 2019 US Census American Community Survey for adults 60+ reports 25% non‐White, and 44 % =< 12 years of education. There were no observed differences between participants from historically underrepresented ethnoracial groups and NLW participants in screen fail and dropout rates. We found that individuals with =<12 years of education failed screening at a significantly higher rate (p=.01) and rolled‐over significantly less to subsequent ADNI phases (p<.001) compared to individuals with an education >12 years. Identifying as non‐Latinx Asian was associated with lower odds of being amyloid positive (OR=0.36; p=.014) and an ApoE4 carrier (OR=0.36; p=.008) compared to NLW. Identifying as Latinx was associated with being less likely to be amyloid positive than NLW participants (OR=0.54; p=.031).ConclusionCompared to the US Census, ADNI underrepresents enrollment of Latinx, non‐Latinx Black, and non‐Latinx Asian participants and those with low educational attainment. Hence, ADNI reflects the on‐going challenges with recruiting and enrolling underrepresented populations into most AD research. Our findings highlight the need for ADNI to increase enrollment and engagement of underrepresented ethnoracial and educational populations. ADNI is actively undertaking steps to implement improved recruitment approaches aimed at increasing ethnoracial and socioeconomical representation in multi‐center cohort studies.

ObjectiveTo determine the independent risk factors for diastolic dysfunction (DD) in patients with systemic sclerosis (SSc) and to evaluate the impact of DD on mortality.MethodsSSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort between November 1, 2006 and November 1, 2017 with ≥1 analyzable 2‐dimensional (2‐D) echocardiogram in our system were included (n = 806). DD risk factors and SSc disease characteristics were prospectively obtained, and the presence or absence of DD was determined using the most recent 2‐D echocardiogram. Logistic regression models examined associations between clinical risk factors and DD, and Cox proportional hazards models were used to assess survival.ResultsDD was present in 18.6% of participants. The majority of participants were female (84%) with a median age of 58.4 years (interquartile range 48.8–68.1). Older age (odds ratio [OR] 1.12 [95% confidence interval (95% CI) 1.09–1.15], P < 0.001), coronary artery disease (OR 3.69 [95% CI 1.52–8.97], P = 0.004), obesity (OR 4.74 [95% CI 2.57–8.74], P < 0.001), longer SSc disease duration (OR 1.04 [95% CI 1.01–1.06], P = 0.004), diffusing capacity for carbon monoxide ≤60% of predicted (OR 2.41 [95% CI 1.40–4.16], P = 0.002), and history of scleroderma renal crisis (OR 3.18 [95% CI 1.12–9.07], P = 0.031) were all independently associated with an increased risk of DD. Anti–Scl‐70 positivity (OR 0.49 [95% CI 0.26–0.93], P = 0.03) and severe gastrointestinal disease (OR 0.48 [95% CI 0.30–0.79], P = 0.004) were associated with a reduced risk of DD. The presence of DD was independently associated with an increase in the risk of mortality (hazard ratio 1.69 [95% CI 1.07–2.68], P = 0.027).ConclusionDD is independently associated with an increased risk of mortality in patients with SSc. Potentially modifiable risk factors, including coronary artery disease and obesity, should be addressed in patients with SSc to reduce mortality risk.

Abstract This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

AbstractObjectiveComputed tomography (CT) imaging is frequently obtained for recurrent abdominal pain after a prior emergency department (ED) evaluation. We evaluate the utility of repeat CT imaging following an indeterminate index CT in low‐risk abdominal pain adult ED patients.MethodsAn electronic search was designed for the patient‐intervention‐control‐outcome‐timing (PICOT) question: (P) adult patients with low‐risk, recurrent, and previously undifferentiated atraumatic abdominal pain presenting to the ED after an index‐negative CT within 12 months; (I) repeat CT versus (C) no repeat CT; for (O) abdominal surgery or other invasive procedure, mortality, identification of potentially life‐threatening diagnosis, and hospital and intensive care unit admission rates; and return ED visit (T), all within 30 days. Four reviewers independently selected evidence for inclusion and then synthesized the results around the most prevalent themes of repeat CT timing, diagnostic yield, ionizing radiation exposure, and predictors of repetitive imaging.ResultsAlthough 637 articles and abstracts were identified, no direct evidence was found. Thirteen documents were synthesized as indirect evidence. None of the indirect evidence defined a low‐risk subset of abdominal pain nor did investigators describe whether reimaging occurred for complaints similar to the initial ED evaluation. Included studies did not describe the index CT findings and some reported explanatory findings noted on the original CT for which repeat CTs might have been indicated. The time frame for a repeat CT ranged from hours to 1 year. The frequency of repeat CTs (2%–47%) varied across studies as did the yield of imaging to alter downstream clinical decision making (range = 5%–67%).ConclusionDue to the absence of direct evidence our scoping review is unable to provide high‐quality evidence‐based recommendations upon which to confidently base an imaging practice guideline. There is no evidence to support or refute performing a CT for low‐risk recurrent abdominal pain.

Background: The modern scalp block consists of local anesthesia injections that target the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, and greater and lesser occipital nerves. Limited data exist on the local anesthetic spread that occurs with this technique. This study examines the extent of the spread of a scalp block using methylene blue in a cadaveric model. Methods: A traditional landmark-based scalp block was performed on 6 unembalmed human cadavers using 25-G, 1.5-inch needles to inject 1 to 2 mL of methylene blue 0.1% at each nerve bilaterally; a total volume of 20 mL was injected. The cadavers were then dissected, and the spread of injectate was measured and recorded. Results: All the nerves required for analgesic coverage were appropriately stained by the injections, except for in 2 specimens where the lesser occipital nerve could not be identified. The zygomatic (stained in 2 of 8 specimens) and temporal (stained in 5 of 8 specimens) branches of the facial nerve were stained as a result of the zygomaticotemporal and/or auriculotemporal injections. Tracking from the zygomatic injection site was noted as far inferior as the temporalis muscle attachments on the mandible. Conclusions: This cadaveric study confirms that the landmark-based technique for scalp blocks consistently stained all 6 nerves involved in scalp innervation. There was significant unintentional spread to the branches of the facial nerve when using the landmark technique.