A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis.

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

Genetic Link Between Gender Dysphoria and Sex Hormone Signaling.

Context: There is a likely genetic component to gender dysphoria, but association study data have been equivocal. Objective: We explored the specific hypothesis that gender dysphoria in transgender women is associated with variants in sex hormone-signaling genes responsible for undermasculinization and/or feminization. Design: Subject-control analysis included 380 transgender women and 344 control male subjects. Associations and interactions were investigated between functional variants in 12 sex hormone-signaling genes and gender dysphoria in transgender women. Setting: Patients were recruited from the Monash Gender Clinic, Monash Health, Melbourne, Australia, and the University of California, Los Angeles. Patients: Caucasian (non-Latino) transgender women were recruited who received a diagnosis of transsexualism [Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV) or gender dysphoria (DSM-V)] pre- or postoperatively. Most were receiving hormone treatment at the time of recruitment. Main Outcome Measured: Genomic DNA was genotyped for repeat length polymorphisms or single nucleotide polymorphisms. Results: A significant association was identified between gender dysphoria and ERα, SRD5A2, and STS alleles, as well as ERα and SULT2A1 genotypes. Several allele combinations were also overrepresented in transgender women, most involving AR (namely, AR-ERß, AR-PGR, AR-COMT, CYP17-SRD5A2). Overrepresented alleles and genotypes are proposed to undermasculinize/feminize on the basis of their reported effects in other disease contexts. Conclusion: Gender dysphoria may have an oligogenic component, with several genes involved in sex hormone-signaling contributing.

Factors affecting community participation in the CDTI program in Morogoro, Tanzania.

BACKGROUND: Up to 4 million people in Tanzania are at risk for the parasitic disease onchocerciasis. A treatment program, Community-Directed Treatment with Ivermectin (CDTI), has made significant gains in prevention and treatment. Understanding factors affecting participation could help boost treatment coverage and sustain gains made in controlling onchocerciasis in endemic areas. PURPOSE: To explore community-perceived factors related to participation in and sustainability of the CDTI program in southwest Tanzania. METHODS: Multilevel triangulation design using surveys, focus group discussions (FGDs), and semistructured interviews to collect data in two villages in the Morogoro Rural District of Tanzania. In total, 456 villagers participated in the survey and 42 in FDGs. Five community-directed distributors (CDDs) and three community health workers were interviewed. FINDINGS: High levels of awareness of onchocerciasis (90%) and methods of prevention and treatment (95%) were reported. Over 75% of participants knew how ivermectin was distributed and 74% have taken the drug. Over 90% of villagers knew that distribution of the drug was for treatment and prevention. Only 43% knew the cause of onchocerciasis. Through FGDs, villagers reported barriers to participation, including lack of comprehensive understanding of the disease, fears of medication, distrust of the method determining dose, lack of health education materials, insufficient CDD-resident communication, and inflexible drug distribution mechanisms. CONCLUSIONS: Sustaining programs without supporting growth of CDDs and reinforcing education of communities could lead to a decrease in treatment and an increase in the public health threat. This research uncovered a need for more effective community education and sensitization. CLINICAL RELEVANCE: Understanding barriers to participation in community-based programs can assist public health and community health nurses and key stakeholders including Ministries of Health and local and regional health systems in the development of education and support materials to enhance health literacy and encourage program participation.

Depression and religiosity and/or spirituality in college: a longitudinal survey of students in the USA.

The aim of this study was to conduct a longitudinal test of an explanatory model of depression, where religiosity and/or spirituality (R/S) represents a potentially protective factor in college students in the USA. A Web-based survey was administered monthly to 214 students from religious and public colleges. At 1 month and 6 months, the measures of R/S, depression, stress, and cognitive vulnerability were administered. Between 2 and 5 months, only the measures of stress and depression were administered. The data were analyzed to test the hypothesis that R/S buffers the effect of stress on depression over time in the context of cognitive vulnerability. The results supported a direct and protective effect over time between R/S and depression, but a buffering effect on the relationship between stress and depression was not found. Although all aspects of R/S were demonstrated to protect the participants from depression, it did not appear that the relationship between R/S and stress or R/S and cognitive vulnerability explains this relationship. Nurses who are working with college students should take holistic approaches to their emotional difficulties, realizing the potentially beneficial effects of students' religiousness or spirituality.