Publications

BACKGROUND

Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain.

OBJECTIVE

We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children.

METHODS

We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children.

RESULTS

Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores.

CONCLUSION

Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.

BACKGROUND

Patient noncompliance with therapy, treatments, and appointments represents a significant barrier to improving health care delivery and reducing the cost of care. One method to improve therapeutic adherence is to improve feedback loops in getting clinically acute events and issues to the relevant clinical providers as necessary (ranging from detecting hypoglycemic events for patients with diabetes to notifying the provider when patients are out of medications). Patients often don't know which information should prompt a call to their physician and proactive checks by the clinics themselves can be very resource intensive. We hypothesized that a two-way SMS system combined with a platform web service for providers would enable both high patient engagement but also the ability to detect relevant clinical alerts.

OBJECTIVE

The objectives of this study are to develop a feasible two-way automated SMS/phone call + web service platform for patient-provider communication, and then study the feasibility and acceptability of the Epharmix platform. First, we report utilization rates over the course of the first 18 months of operation including total identified clinically significant events, and second, review results of patient user-satisfaction surveys for interventions for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties.

METHODS

To test this question, we developed a web service + SMS/phone infrastructure ("Epharmix"). Utilization results were measured based on the total number of text messages or calls sent and received, with percentage engagement defined as a patient responding to a text message at least once in a given week, including the number of clinically significant alerts generated. User satisfaction surveys were sent once per month over the 18 months to measure satisfaction with the system, frequency and degree of communication. Descriptive statistics were used to describe the above information.

RESULTS

In total, 28,386 text messages and 24,017 calls were sent to 929 patients over 9 months. Patients responded to 80% to 90% of messages allowing the system to detect 1164 clinically significant events. Patients reported increased satisfaction and communication with their provider. Epharmix increased the number of patient-provider interactions to over 10 on average in any given month for patients with diabetes, COPD, congestive heart failure, hypertension, surgical site infections, and breastfeeding difficulties.

CONCLUSIONS

Engaging high-risk patients remains a difficult process that may be improved through novel, digital health interventions. The Epharmix platform enables increased patient engagement with very low risk to improve clinical outcomes. We demonstrated that engagement among high-risk populations is possible when health care comes conveniently to where they are.

Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies. Forty-two patients who had failed 1 to 3 prior treatments received ibrutinib (420 mg) daily until cGVHD progression. The primary efficacy end point was cGVHD response based on 2005 National Institutes of Health criteria. At a median follow-up of 13.9 months, best overall response was 67%; 71% of responders showed a sustained response for ≥20 weeks. Responses were observed across involved organs evaluated. Most patients with multiple cGVHD organ involvement had a multiorgan response. Median corticosteroid dose in responders decreased from 0.29 mg/kg per day at baseline to 0.12 mg/kg per day at week 49; 5 responders discontinued corticosteroids. The most common adverse events were fatigue, diarrhea, muscle spasms, nausea, and bruising. Plasma levels of soluble factors associated with inflammation, fibrosis, and cGVHD significantly decreased over time with ibrutinib. Ibrutinib resulted in clinically meaningful responses with acceptable safety in patients with ≥1 prior treatments for cGVHD. Based on these results, ibrutinib was approved in the United States for treatment of adult patients with cGVHD after failure of 1 or more lines of systemic therapy. This trial was registered at www.clinicaltrials.gov as #NCT02195869.