Publications

BACKGROUND

Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment.

OBJECTIVE

The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations.

METHODS

Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physician-diagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations.

RESULTS

Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P = .580). Pharmacy-based records of metered-dose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score.

CONCLUSIONS

Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations.

We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts"). Autograft MRD was assessed by molecular methods (real-time quantitative PCR [RQ-PCR] for Wilms tumor 1 (WT1) alone or a multigene panel) and by multiparameter flow cytometry (MPFC). WT1 RQ-PCR testing of the autograft had low sensitivity for relapse prediction (14%) and a negative predictive value of 51%. MPFC failed to identify MRD in any of 34 autografts tested. Combinations of molecular MRD assays, however, improved prediction of post-auto-HCT relapse. In multivariate analysis of clinical variables, including age, gender, race, cytogenetic risk category, and CD34 cell dose, only autograft multigene MRD as assessed by RQ-PCR was statistically significantly associated with relapse. One year after transplantation, only 28% patients with detectable autograft MRD were relapse free, compared with 67% in the MRD-negative cohort. Multigene MRD, while an improvement on other methods tested, was however suboptimal for relapse prediction in unselected patients, with specificity of 83% and sensitivity of 46%. In patients with known chromosomal abnormalities or mutations, however, better predictive value was observed with no relapses observed in MRD-negative patients in the first year after auto-HCT compared with 83% incidence of relapse in the MRD-positive patients (hazard ratio, 12.45; P = .0016). In summary, increased personalization of MRD monitoring by use of a multigene panel improved the ability to risk stratify patients for post-auto-HCT relapse. WT1 RQ-PCR and flow cytometric assessment for AML MRD in autograft samples had limited value for predicting relapse after auto-HCT. We demonstrate that cryopreserved autograft material presents unique challenges for AML MRD testing because of the masking effects of previous GCSF exposure on gene expression and flow cytometry signatures. In the absence of information regarding diagnostic characteristics, sources other than GCSF-stimulated PBSC leukapheresis specimens should be considered as alternatives for MRD testing in AML patients undergoing auto-HCT.

BACKGROUND

Postpartum depression is common and adversely affects children of afflicted mothers; postpartum depression recognition and treatment may improve outcomes. Hospitalization represents a potential health encounter for expanding screening and intervention.

OBJECTIVE

We aimed to assess for postpartum depression at infant hospitalization and examine postpartum depression risk factors in this population.

DESIGN, SETTING, AND PARTICIPANTS

We conducted a prospective observational study of 310 English- or Spanish-speaking women with an infant aged 2 weeks to 1 year admitted to a pediatric hospitalist service at a large urban freestanding children's hospital.

MEASUREMENTS

Mothers completed demographic questionnaires, a maternal-infant bonding scale, and the Edinburgh Postpartum Depression Scale (EPDS). Mothers with an EPDS score of 10 or higher (positive screen) received counseling and mental health referrals. Postenrollment calls followed trends in EPDS score and resource utilization. Multivariate logistic regression assessed relationships among risk factors and positive screens.

RESULTS

Eighty-seven mothers (28%) were EPDS+. Only 14.6% reported appropriate prior depression screening. Maternal factors associated with EPDS+ were poor social support (4.40, interquartile range [IQR] = 2.27-8.53) and history of psychiatric diagnoses (5.02, IQR = 2.49-10.15). Having an infant with neurodevelopmental comorbidities was associated with EPDS+ screens (2.78, IQR = 1.03-7.52). Of 21 initially EPDS+ mothers reached by phone, 8 (38%) utilized their doctor or referral resource, resulting in lower EPDS scores (F(1,19) = 5.743, P < 0.05) compared to those not seeking help.

CONCLUSION

Postpartum depression screening during infant hospitalizations captures women previously unscreened. Low social support, past psychiatric diagnoses, or having infants with neurodevelopmental problems may increase postpartum depression risk. Journal of Hospital Medicine 2015;11:840-846. © 2015 Society of Hospital Medicine.

BACKGROUND

Concussion injuries have been highlighted to the American public through media and research. While recent studies have shown increased traumatic brain injuries (TBIs) diagnosed in emergency departments across the United States, no studies have evaluated trends in concussion diagnoses across the general US population in various age groups.

PURPOSE

To evaluate the current incidence and trends in concussions diagnosed across varying age groups and health care settings in a large cross-sectional population.

STUDY DESIGN

Descriptive epidemiological study.

METHODS

Administrative health records of 8,828,248 members of a large private-payer insurance group in the United States were queried. Patients diagnosed with concussion from years 2007 through 2014 were stratified by year of diagnosis, age group, sex, classification of concussion, and health care setting of diagnosis (eg, emergency department vs physician's office). Chi-square testing was used for statistical analysis.

RESULTS

From a cohort of 8,828,248 patients, 43,884 patients were diagnosed with a concussion. Of these patients, 55% were male and over 32% were in the adolescent age group (10-19 years old). The highest incidence of concussion was seen in patients aged 15 to 19 years (16.5/1000 patients), followed by those aged 10 to 14 years (10.5/1000 patients), 20 to 24 years (5.2/1000 patients), and 5 to 9 years (3.5/1000 patients). Overall, there was a 60% increase in concussion incidence from 2007 to 2014. The largest increases were in the 10- to 14-year (143%) and 15- to 19-year (87%) age groups. Based on International Classification of Disease-9th Revision classification, 29% of concussions were associated with some form of loss of consciousness. Finally, 56% of concussions were diagnosed in the emergency department and 29% in a physician's office, with the remainder in urgent care clinics or inpatient settings.

CONCLUSION

The incidence of concussion diagnosed in the general US population is increasing, driven largely by a substantial rise in the adolescent age group. The youth population should be prioritized for ongoing work in concussion education, diagnosis, treatment, and prevention.

CLINICAL RELEVANCE

The rise of concussions in the adolescent age group across the general population is concerning, and clinical efforts to prevent these injuries are needed.

CONTEXT

Concussion legislation has been enacted in all 50 of the United States, aiming to prevent mild traumatic brain injuries and the potential long-term sequelae of these injuries in youth athletics. Sports medicine providers, in addressing this major public health concern, are tasked with adhering to the established standards of medical care while also considering the legal implications.

EVIDENCE ACQUISITION

The PubMed (2011-2016) database was searched using the following search terms: concussion, sports concussion, legislation, and concussion legislation. References from consensus statements, review articles, and book chapters were also utilized.

STUDY DESIGN

Clinical review.

LEVEL OF EVIDENCE

Level 4.

RESULTS

The Lystedt law and its progeny have increased awareness of the signs and symptoms of sports concussion, but adherence to state legislation can pose some challenges.

CONCLUSION

The presence of concussion legislation places a responsibility on the sports medicine provider to have a firm understanding of the legality of concussion management in the state(s) in which they practice.

UNLABELLED

Significant gut microbiota heterogeneity exists among ulcerative colitis (UC) patients, though the clinical implications of this variance are unknown. We hypothesized that ethnically distinct UC patients exhibit discrete gut microbiotas with unique metabolic programming that differentially influence immune activity and clinical status. Using parallel 16S rRNA and internal transcribed spacer 2 sequencing of fecal samples (UC, 30; healthy, 13), we corroborated previous observations of UC-associated bacterial diversity depletion and demonstrated significant Saccharomycetales expansion as characteristic of UC gut dysbiosis. Furthermore, we identified four distinct microbial community states (MCSs) within our cohort, confirmed their existence in an independent UC cohort, and demonstrated their coassociation with both patient ethnicity and disease severity. Each MCS was uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of the metabolic products of these pathways. Using a novel ex vivo human dendritic cell and T-cell coculture assay, we showed that exposure to fecal water from UC patients caused significant Th2 skewing in CD4(+) T-cell populations compared to that of healthy participants. In addition, fecal water from patients in whom their MCS was associated with the highest level of disease severity induced the most dramatic Th2 skewing. Combined with future investigations, these observations could lead to the identification of highly resolved UC subsets based on defined microbial gradients or discrete microbial features that may be exploited for the development of novel, more effective therapies.

IMPORTANCE

Despite years of research, the etiology of UC remains enigmatic. Diagnosis is difficult and the patient population heterogeneous, which represents a significant barrier to the development of more effective, tailored therapy. In this study, we demonstrate the clinical utility of the gut microbiome in stratifying UC patients by identifying the existence of four distinct interkingdom pathogenic microbiotas within the UC patient population that are compositionally and metabolically distinct, covary with clinical markers of disease severity, and drive discrete CD4(+) T-cell expansions ex vivo These findings offer new insight into the potential value of the gut microbiome as a tool for subdividing UC patients, opening avenues to the development of more personalized treatment plans and targeted therapies.