A learning community approach to identifying interventions in health systems to reduce colorectal cancer screening disparities.

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to help two health systems in southeastern Pennsylvania identify evidence-based CRC screening interventions for primary care patients. Initially, this approach involved activating a coordinating team, steering committee (health system leadership and stakeholder organizations), and patient and stakeholder advisory committee to identify candidate CRC screening intervention strategies. The coordinating team guided the steering committee through a scoping review to identify seven randomized trials that identified interventions that addressed CRC screening disparities. Subsequently, the coordinating team and steering committee applied a screening intervention classification typology to select an intervention strategy that involved using an outreach strategy to provide minority patients with access to both stool blood test and colonoscopy screening. Finally, the coordinating team and steering committee engaged the health system patient and stakeholder advisory committee in planning for intervention implementation, thus taking up the challenge of reducing and important health disparity in patient populations served by the two health systems

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Recurrent Cryptococcosis in a Human Immunodeficiency Virus-negative Patient

Introduction Idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder that can predispose otherwise immunocompetent individuals to life-threatening opportunistic infections. We present a case of a human immunodeficiency virus (HIV)-negative patient with ICL who presented with recurrent cryptococcosis. Case Presentation A 39-year-old Caucasian, HIV-negative male with a past medical history of stroke 13 years prior to admission and an episode of cryptococcal meningitis 18 months prior to admission presented to the hospital with generalized weakness for 7 days. The patient had a 10 pack-year smoking history and no significant environmental or occupational exposures. On admission, vital signs were significant for a temperature of 101.1oF, a heart rate of 117 beats per minute, and a blood pressure 93/75 mm Hg. Physical exam was remarkable for an ill-appearing male with dry mucous membranes and tachycardia. Initial laboratory studies were significant for a white blood count of 3.14 cells/μL (normal range = 4.5-11 cells/μL), hemoglobin of 8.7 g/dL (normal range = 13.5-17.5 g/ dL), and creatinine of 5.2 mg/dL (normal range = 0.6-1.2 mg/dL). Blood cultures were positive for Cryptococcus neoformans. Subsequent laboratory studies revealed a serum cryptococcal antigen titer of 1:256 and a CD4+ count of 227 cells/μL (normal range = 410-1590 cells/ μL). The CD4+ count was 98 cells/μL when the patient was diagnosed with cryptococcal meningitis 18 months prior. Enzyme-linked immunosorbent assays for HIV were negative. Anti-nuclear antibody titer was 1:80 and anti-double stranded DNA, anti-Smith, anti-SSA, anti-SSB , and anti-ribonucleoprotein antibodies were negative. Lumbar puncture (LP) showed a normal opening pressure and was negative for cryptococcal infection. Chest X-ray revealed a right pleural mass. Subsequent CT of the thorax revealed a 6.3 x 3.3 cm pleural-based mass in the right upper lobe of the lung (Figure 1). Due to suspicion for a pulmonary malignancy, a Technetium bone scan was performed and found increased uptake in the right femur and left humerus. X-ray of the right femur showed well-circumscribed lytic lesions in the mid-femoral diaphysis (Figure 2). CT-guided biopsy of the pleural mass and the femur lesion revealed narrow-based, budding yeast that stained Gomori methenamine silver (Figure 3a) and a capsule that stained red with mucicarmine (Figure 3b), consistent with a diagnosis of cryptococcosis

Congenital Absence of the Pericardium

Introduction Congenital absence of the pericardium (CAP) is an uncommon finding previously recognized only post-mortem or during surgery. However, its incidence has been on the rise with the use of multiple contemporary imaging techniques. CAP can present with paroxysmal, left-sided chest pain and should be considered in the differential diagnosis of atypical causes of chest pain. We present the case of a 50-year-old male who presented with chest pressure, symptoms of heart failure, and was found to be in atrial fibrillation in whom partial absence of the left pericardium was diagnosed. Case Presentation A 50 year-old African-American male presented to the Emergency Department with a chief complaint of shortness of breath (SOB) and worsening dyspnea on exertion for one week. He described worsening SOB when lying on his left side, as well as palpitations, orthopnea, and non-radiating, left-sided chest pressure. On physical exam, the patient was tachycardic with an irregularly irregular heart rate, crackles in the lower lobes, trace bilateral lower extremity edema, and a non-palpable apical impulse. Laboratory studies were significant for a pro-B-type natriuretic peptide (pro-BNP) level of 2830 pg/mL (normal range = \u3c100 pg/mL) and negative troponins. Electrocardiogram (ECG) showed a ventricular rate of 146 beats per minute, irregularly irregular rhythm, right axis deviation, and poor R-wave progression. Chest x-ray (CXR) (Figure 1) revealed cardiomegaly and a diminished right heart border. Subsequent echocardiogram showed severe mitral regurgitation and moderate tricuspid regurgitation. Of note, it also showed the heart shifted posteriorly in the apical window, suspicious for congenital absence of pericardium. CT scan confirmed the diagnosis of partial absence of the left pericardium

Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Methods and Materials: All patients were irradiated with the same RT technique to ≥66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p ≥ 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted. © 2006 Elsevier Inc. All rights reserved.Link_to_subscribed_fulltex

Next-generation sequencing of AAV.CAP-Mac from Chuapoco et al. (2023) Nature Nanotechnology

Dataset of next-generation sequencing of enrichment of AAV.CAP-Mac in various tissues from the publication: Chuapoco, M.R., Flytzanis, N.C., Goeden, N. et al. Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01419-xThis work was funded by grants from the National Institutes of Health (NIH): NIH Pioneer DP1NS111369 (to V.G.); P51OD011107 (to the California National Primate Research Center), R01HD091325 (to L.T.); U19NS123719 (to L.T.); UG3MH120095 (to J.T.T. and B.P.L.); P51OD010425 (to the Washington National Primate Research Center); U42OD011123 (to the Washington National Primate Research Center); BRAIN Armamentarium UF1MH128336 (to V.G., T.F.S., L.T. and A.S.F.), and in part by Aligning Science Across Parkinson's (ASAP-020495 to V.G., A.S.F. and L.T.) through the Michael J. Fox Foundation for Parkinson's Research (MJFF)