Publications

OBJECTIVE

To understand patient, primary care clinician (PCC), and subspecialist perspectives on potential, unexplored roles for patients in electronic consultation and referral (eCR) systems.

DATA SOURCES

Primary focus group and survey data collected April-November 2015. Zuckerberg San Francisco General Hospital (ZSFG) is part of an integrated public health delivery system. Its mature eCR system was first implemented in 2005.

STUDY DESIGN

This mixed-methods study synthesizes patient, subspecialist, and PCC perspectives through two patient focus groups in English, Spanish, and Cantonese (n = 6); subspecialist focus groups (n = 2); and an electronic survey of all PCCs (n = 222/634, 35 percent response).

DATA COLLECTION/EXTRACTION METHODS

Focus groups were audio-recorded and transcribed. Two researchers coded the transcripts to identify recurrent themes. Survey data were analyzed using summary and bivariate statistics.

PRINCIPAL FINDINGS

Patients expressed minimal desire to directly engage in eCR, instead of emphasizing their PCC's role in advocating, informing, and finding health solutions. Subspecialists requested more consistent communication to patients about the electronic consultation process. Most PCCs (52 percent) supported patient engagement in the eCR process, particularly patient ability to track consult status and securely message with subspecialists.

CONCLUSIONS

Results suggest a continuum of opportunities for patients and their caregivers to engage in eCR systems.

Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

OBJECTIVE

Severe hypoglycemia is a rare but important complication of type 2 diabetes. Few studies have examined the epidemiology of hypoglycemia in a community-based population.

RESEARCH DESIGN AND METHODS

We included 1,206 Atherosclerosis Risk in Communities (ARIC) Study participants with diagnosed diabetes (baseline: 1996-1998). Severe hypoglycemic events were identified through 2013 by ICD-9 codes from claims for hospitalizations, emergency department visits, and ambulance use. We used Cox regression to evaluate risk factors for severe hypoglycemia.

RESULTS

The mean age of participants was 64 years, 32% were black, and 54% were female. During a median follow-up period of 15.2 years, there were 185 severe hypoglycemic events. Important risk factors after multivariable adjustment were as follows: age (per 5 years: hazard ratio [HR] 1.24; 95% CI 1.07-1.43), black race (HR 1.39; 95% CI 1.02-1.88), diabetes medications (any insulin use vs. no medications: HR 3.00; 95% CI 1.71-5.28; oral medications only vs. no medications: HR 2.20; 95% CI 1.28-3.76), glycemic control (moderate vs. good: HR 1.78; 95% CI 1.11-2.83; poor vs. good: HR 2.62; 95% CI 1.67-4.10), macroalbuminuria (HR 1.95; 95% CI 1.23-3.07), and poor cognitive function (Digit Symbol Substitution Test score: HR 1.57; 95% CI 1.33-1.84). In an analysis of nontraditional risk factors, low 1,5-anhydroglucitol, difficulty with activities of daily living, Medicaid insurance, and antidepressant use were positively associated with severe hypoglycemia after multivariate adjustment.

CONCLUSIONS

Poor glycemic control, glycemic variability as captured by 1,5-anhydroglucitol, kidney damage, and measures of cognitive and functional impairments were strongly associated with increased risk of severe hypoglycemia. These factors should be considered in hypoglycemia risk assessments when individualizing diabetes care for older adults.

Two recent studies (Cambier et al., 2017; Madigan et al., 2017) reveal in vivo functions for specific phenolic glycolipids (PGLs) in the mycobacteria that cause tuberculosis or leprosy. M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demyelination characteristic of human leprosy.

Infectious diseases have a profound impact on our health and many studies suggest that host genetics play a major role in the pathogenesis of most of them. We perform 23 genome-wide association studies for common infections and infection-associated procedures, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in over 200,000 individuals of European ancestry. We detect 59 genome-wide significant (P < 5 × 10) associations in genes with key roles in immunity and embryonic development. We apply fine-mapping analysis to dissect associations in the human leukocyte antigen region, which suggests important roles of specific amino acid polymorphisms in the antigen-binding clefts. Our findings provide an important step toward dissecting the host genetic architecture of response to common infections.Susceptibility to infectious diseases is, among others, influenced by the genetic landscape of the host. Here, Tian and colleagues perform genome-wide association studies for 23 common infections and find 59 risk loci for 17 of these, both within the HLA region and non-HLA loci.