Secondary IgA nephropathy presenting as nephrotic syndrome with glomerular crescentic changes and acute renal failure in a patient with autoimmune hepatitis

Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.     

Testing the level of response to alcohol-based model of heavy drinking and alcohol problems in offspring from the San Diego Prospective Study

OBJECTIVE: The low level of response (LR) to alcohol, an endophenotype related to heavy drinking and alcohol problems, influences the risk for alcoholism in the context of additional life domains. This article evaluates an LR-based model of drinking patterns in 113 drinking offspring, ages 12 to 24 years, from the San Diego Prospective Study. METHOD: Correlations and structural equation models (SEMs) were evaluated using LR as measured from the Self-Report of the Effects of Alcohol questionnaire in the offspring. The expectations of the effects of alcohol (EXPECT), the perception of drinking in peers (PEER), the use of alcohol to cope with stress (COPE), and the drinking quantities and alcohol-related problems (ALCOUT) were evaluated in the SEM. RESULTS: The LR-based model worked well, with good fit characteristics and 78% of the variance of outcome explained. LR related directly to ALCOUT, with additional mediation of that relationship through EXPECT and COPE. CONCLUSIONS: The LR-based model performed well in adolescents from the San Diego Prospective Study. Knowledge of which domains mediate how LR impacts alcohol-related outcomes may be useful in developing more focused and potentially more effective prevention approaches.     

The Relationship Between Substance Use and Sexual Health Among African-American Female Adolescents with a History of Seeking Mental Health Services

BackgroundThis study examined relationships between substance use patterns and problems and sexual health outcomes among low-income, urban, African-American female adolescents with a history of seeking mental health services.MethodsParticipants were recruited from outpatient mental health clinics serving urban, primarily low-income youth and families in Chicago, Illinois, as part of a 2-year, longitudinal investigation of HIV risk behavior during which they completed interviews every 6 months (five time points). Girls who completed at least one follow-up interview were invited to participate in a sixth wave of assessment to assess trauma exposure, substance use problems, and sexual risk. The current study (n = 177) examined the association between sexual risk behavior and substance use problems reported at the most recent interview (ages 14–22) and substance use patterns and sexually transmitted infections (STI) reported at all six times points. Multiple regression examined the combined and unique effects of different patterns of substance use and substance use problems as correlates of sexual risk behavior and STIs.FindingsSubstance use problems were associated with increased sexual risk behavior and increased likelihood of experiencing STIs. Substance use patterns were associated with sexual risk behavior.ConclusionsResults suggest that specific patterns of substance use and substance use problems are important to address in sexual health promotion among low-income, urban, African-American girls with a history of seeking mental health services. Understanding the nuances of these relationships is important in informing how to best serve this vulnerable group of adolescents who experience significant sexual risk and mental health care disparities.     

Reconsidering the role of social disadvantage in physical and mental health: stressful life events, health behaviors, race, and depression

Prevalence of depression is associated inversely with some indicators of socioeconomic position, and the stress of social disadvantage is hypothesized to mediate this relation. Relative to whites, blacks have a higher burden of most physical health conditions but, unexpectedly, a lower burden of depression. This study evaluated an etiologic model that integrates mental and physical health to account for this counterintuitive patterning. The Baltimore Epidemiologic Catchment Area Study (Maryland, 1993-2004) was used to evaluate the interaction between stress and poor health behaviors (smoking, alcohol use, poor diet, and obesity) and risk of depression 12 years later for 341 blacks and 601 whites. At baseline, blacks engaged in more poor health behaviors and had a lower prevalence of depression compared with whites (5.9% vs. 9.2%). The interaction between health behaviors and stress was nonsignificant for whites (odds ratio (OR = 1.04, 95% confidence interval: 0.98, 1.11); for blacks, the interaction term was significant and negative (β: -0.18, P < 0.014). For blacks, the association between median stress and depression was stronger for those who engaged in zero (OR = 1.34) relative to 1 (OR = 1.12) and ≥2 (OR = 0.94) poor health behaviors. Findings are consistent with the proposed model of mental and physical health disparities.     

Extensions to the two‐stage randomized trial design for testing treatment,self‐selection,and treatment preference effects to binary outcomes

While traditional clinical trials seek to determine treatment efficacy within a specified population, they often ignore the role of a patient's treatment preference on his or her treatment response. The two‐stage (doubly) randomized preference trial design provides one approach for researchers seeking to disentangle preference effects from treatment effects. Currently, this two‐stage design is limited to the design and analysis of continuous outcome variables; in this presentation, we extend this current design to include binary variables. We present test statistics for testing preference, selection, and treatment effects in a two‐stage randomized design with a binary outcome measure, with and without stratification. We also derive closed‐form sample size formulas to indicate the number of patients needed to detect each effect. A series of simulation studies explore the properties and efficiency of both the unstratified and stratified two‐stage randomized trial designs. Finally, we demonstrate the applicability of these methods using an example of a trial of Hepatitis C treatment.     

Mood,Dietary Restraint,and Women's Smoking and Eating Urges

Women may have difficulty maintaining smoking cessation efforts due to negative affect and fear of weight gain. Dieting smokers who rely on cigarettes for affect regulation and weight management may be especially prone to weight gain and smoking relapse following initial smoking abstinence. The present study, which included 82 women smokers, assessed the relationship between dieting status, self-efficacy, and temptation to smoke and eat following a depressing or elating mood induction. Women with high levels of dietary restraint (i.e., more dieting behavior) had more confidence in their ability to refrain from smoking when in the elated mood condition, and they were more tempted to smoke when in the depressed condition. At low levels of dietary restraint (i.e., less dieting behavior), depressed or elated mood condition appeared to have little impact on women's confidence to refrain from smoking or their temptation to smoke. Dieting status seems to moderate the impact of positive and negative mood states, especially with respect to women's smoking behavior. These findings may have implications for dieters who are trying to quit smoking and also maintain their weight.     

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy

Objective: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D?+?T; oral) and those initiated on 1?L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous).

Methods: Patients with melanoma initiated on D?+?T or N/P from Q1/2014 to Q2/2016 (defined as 1?L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D?+?T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1?L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates).

Results: Of the 445 patients included, 202 and 243 were initiated on D?+?T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1?L therapy than those initiated on D?+?T (difference?=?18.6 visits PPY [95% CI?=?16.0–21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference?=?8.1 visits PPY [95% CI?=?1.9–13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1?L therapy).

Conclusions: HRU during 1?L therapy was generally similar between patients initiated on D?+?T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.     

Immunosuppression-related fibroproliferative polyps: a substantial subset of acquired pediatric mucocutaneous polyps.

A distinct group of fibroproliferative polyps of the tongue arising in immunosuppressed children and often associated with chromosomal breakpoints at chromosomes 9p34 or 22q11 was recently described. Based on this finding, we reviewed fibroepithelial polyps arising in nonlingual sites in the pediatric population to investigate a possible relationship with immunosuppression. We identified 8 fibroepithelial polyps arising in 6 immunosuppressed patients (4 males and 2 females, median age 17 years) in a wide range of mucocutaneous sites. Histologic features were identical to the common fibroepithelial polyp, or skin tag, with a variably collagenous fibrovascular core covered by unremarkable squamous epithelium. No viral cytopathic changes were identified in any case. Although cytogenetic studies were not performed on any of the biopsy material, 1 patient had a constitutional deletion of chromosome 22q11. We suggest that there may be a relationship between these polyps and the previously described tongue lesions and that immunosuppression may be an important factor in their pathogenesis.