Publications

OBJECTIVE

Dermatomyositis (DM) and polymyositis (PM) are debilitating inflammatory myopathies associated with significant mortality. We evaluated the relative contribution of infection to hospital mortality in a large population-based study of individuals with PM/DM.

METHODS

Data derive from the 2007 to 2011 Healthcare Cost and Utilization Project National Inpatient Samples and include all hospital discharges that met a validated administrative definition of PM/DM. The primary outcome was hospital mortality. Variables for infections and comorbidities were generated from discharge diagnoses using validated administrative definitions. Logistic regression was used to investigate the relationship between infection and mortality in individuals with PM/DM, adjusting for sociodemographics, utilization variables, and comorbidities. Relative risks (RRs) were calculated to compare the overall prevalence of specific infections and associated mortality in PM/DM hospitalizations with those seen in the general hospitalized population.

RESULTS

A total of 15,407 hospitalizations with PM/DM met inclusion criteria for this study and inpatient mortality was 4.5% (700 deaths). In adjusted logistic regression analyses, infection (odds ratio [OR] 3.4, 95% confidence interval [95% CI] 2.9-4.0) was the strongest predictor of hospital mortality among individuals with PM/DM. Bacterial infection (OR 3.5, 95% CI 3.0-4.1), comprised primarily of pneumonia and bacteremia, and opportunistic fungal infections (OR 2.5, 95% CI 1.5-4.0) were independently associated with hospital mortality. The overall burden of infection in hospitalizations with PM/DM was significantly increased in comparison with the general hospitalized population (RR 1.5, 95% CI 1.4-1.6).

CONCLUSION

Among hospitalized individuals with PM/DM, infection is the leading cause of mortality. Strategies to mitigate infection risk in both the clinic and hospital settings should be evaluated to improve disease outcomes.

BACKGROUND

Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC).

METHODS

Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC).

RESULTS

Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data.

CONCLUSIONS

The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.

IMPORTANCE

For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy.

OBJECTIVE

To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting.

DESIGN, SETTING, AND PARTICIPANTS

This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach.

INTERVENTIONS

Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins.

MAIN OUTCOMES AND MEASURES

Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings.

RESULTS

A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P=.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P=.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were $3.37 per day and $716 per patient.

CONCLUSIONS AND RELEVANCE

This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01415934.

Toll-like receptors (TLRs) recognize common microbial or host-derived macromolecules and have important roles in early activation of the immune system. Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins to the human immune system. Defects in interleukin-1 receptor-associated kinase-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are specific for susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Dampening of TLR responses is seen for TLRs 2 and 4 in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome, and for most TLRs in adenosine deaminase deficiency.