Publications

Objective

To evaluate hypogammaglobulinaemia and risk of serious infectious adverse events in active lupus nephritis.

Methods

The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared abatacept with placebo in participants with lupus nephritis undergoing treatment with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were assessed prior to initiation of treatment and throughout the trial. Hypogammaglobulinaemia was defined as IgG <450 mg/dL.

Results

Hypogammaglobulinaemia was observed in 16/102 (15.7%) participants prior to initiation of induction therapy for active lupus nephritis. Participants with nephrotic range proteinuria were more likely to have hypogammaglobulinaemia, and serum IgG levels were inversely correlated with urine protein to creatinine ratio (r=-0.42, p<0.0001). Following initiation of treatment for active lupus nephritis, additional participants developed hypogammaglobulinaemia by weeks 2-4. Serum IgG levels then increased, and all but one participant had serum IgG ≥450 mg/dL at 24 weeks. Hypogammaglobulinaemia was not associated with an increased risk of serious infectious adverse events.

Conclusions

In active lupus nephritis in ACCESS, hypogammaglobulinaemia was common and inversely correlated with proteinuria. Serum IgG levels were lowest in the weeks immediately following initiation of induction therapy, and subsequently improved by 24 weeks. Hypogammaglobulinaemia was not associated with serious infectious adverse events.

Trial registration

In active lupus nephritis in ACCESS, hypogammaglobulinaemia was common and inversely correlated with proteinuria. Serum IgG levels were lowest in the weeks immediately following initiation of induction therapy, and subsequently improved by 24 weeks. Hypogammaglobulinaemia was not associated with serious infectious adverse events.

CONTEXT

Patients with breast cancer who undergo chemotherapy (CTX) experience between 10 and 32 concurrent symptoms. An evaluation of how these symptoms cluster together and how these symptom clusters change over time may provide insights into how to treat these multiple co-occurring symptoms.

OBJECTIVES

The purposes of this study were to determine the occurrence rates and severity ratings for 38 common symptoms, evaluate for differences in the number and types of symptom clusters, and evaluate for changes over time in these symptom clusters (i.e., before CTX, the week after CTX, and two weeks after CTX).

METHODS

At each of the assessments, a modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence and severity of the 38 symptoms. Exploratory factor analyses were used to extract the symptom clusters.

RESULTS

Although across the two symptom dimensions (i.e., occurrence and severity) and the three assessments, eight distinct symptom clusters were identified, only five were relatively stable across both dimensions and across time (i.e., psychological, hormonal, nutritional, gastrointestinal, and epithelial). Two of the additional clusters varied by time but not by symptom dimension (i.e., sickness behavior and weight change). The CTX neuropathy cluster was identified only at the assessment performed in the week after CTX.

CONCLUSION

These findings provide insights into the most common symptom clusters in patients undergoing CTX for breast cancer. In addition, the most common symptoms within each cluster appear to be relatively stable across the two dimensions, as well as across time.

BACKGROUND

The cost of treating and managing cases of active tuberculosis (TB) disease-from diagnosis to treatment completion-is needed by agencies working on public health budgets, resource allocation and cost-effectiveness analysis. Although components of TB costs have been published in the United States (US), no recent study has assessed overall costs for TB care and potential gaps. To systematically review the US literature for costs of treating and managing cases of active TB disease, adjust these costs to current (2015) values, and assess gaps. We quantified total direct costs-from the perspective of the health care payer-of the treatment and case management of active TB disease. Estimates were based on published figures in the US, and operational data of the California Department of Public Health.

RESULT

The average direct cost of treating and managing a TB case was $34,600 in 2015. The average cost of a multidrug-resistant TB case was $110,900. Health care spending for treating and case managing TB patients in California amounted to approximately $75.6 million for the 2133 new cases reported in 2015. Most published cost estimates were based on data from the 1990s.

CONCLUSION

TB is resource-intensive to treat and manage. Our synthesis provides inputs for budgets and economic analyses. New studies to provide original cost data are needed to better reflect current clinical and public health practices.

The host immune response is critical for homeostasis; however, when chronic low level activation of the immune response with or without the driver continues, a cascade of events can trigger immunological dysfunction. Monocytes are key peripheral sensors of the immune response and their activation is instrumental in the development of cognitive impairment. Here, we show that monocytes activated by interferon alpha, lipopolysaccharide or a combination of both generate exosomes carrying significantly altered microRNA profiles compared to non-activated monocytes. These exosomes alone can activate human brain microvascular endothelial cells to stimulate adhesion molecules, CCL2, ICAM1, VCAM1 and cytokines, IL1β and IL6. This activation is through the toll like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) pathway that activates nuclear factor-κB and increases monocyte chemotaxis. Inhibition of monocyte exosome release reverses endothelial cell activation and monocyte chemotaxis. Our study suggests that activated monocytes have an impact on brain vascular function through intercellular exosome signaling.

Wilson's disease is a well-characterized disorder known to cause liver and brain disease due to abnormal copper deposition. Data regarding copper infiltration of the heart is conflicting, and the risk of heart disease has not been well described. We aimed to determine whether Wilson's disease is associated with cardiac myopathy, clinically evident in the atria as atrial fibrillation (AF) and in the ventricles as heart failure (HF). We longitudinally assessed 14.3 million patients in the California Healthcare Cost and Utilization Project database from 2005 through 2009 for diagnoses of Wilson's disease, AF, HF, and covariates using International Classification of Diseases-9th Edition codes. Cirrhosis and appendicitis diagnoses were assessed for positive and negative validation, respectively. We identified 463 patients with Wilson's disease. As expected in validation analyses, patients with Wilson's disease had a threefold greater risk of cirrhosis (hazard ratio [HR] 2.85, 95% confidence interval [CI] 2.81 to 2.90, p <0.0001) and no increased risk of appendicitis (HR 0.24, 95% CI 0.04 to 1.71, p = 0.16). Patients with Wilson's disease exhibited a 29% higher risk of AF after adjusting for age, gender, race, income, hypertension, diabetes, renal disease, hyperlipidemia, obesity, coronary disease, and obstructive sleep apnea (HR 1.29, 95% CI 1.15 to 1.45, p <0.0001). After adjusting for the same covariates, patients with Wilson's disease had a 55% higher risk of incident HF (HR 1.55, 95% CI 1.41 to 1.71, p <0.0001). Patients with Wilson's disease have an increased risk of AF and HF, supporting the need for careful surveillance for heart disease. These findings also suggest that the role of copper metabolism in heart disease should be more broadly investigated.