African American Renal Transplant Recipients (RTR) Require Higher Tacrolimus Doses to Achieve Target Levels Compared to White RTR: Does Clotrimazole Help?

The number of African Americans (AAs) on the kidney waiting list is increasing in the United States. Several studies showed that AAs are at higher risk for rejection and graft loss. Because of genetic polymorphisms, AAs may metabolize calcineurin inhibitors faster than Caucasian (C) individuals. The goal of this study is to evaluate the tacrolimus (TAC) dose required to reach therapeutic levels and to assess the impact of clotrimazole on TAC metabolism in AAs compared to C patients. One hundred forty-two AA renal transplant recipients (RTRs) were compared to 309 C RTRs. Demographics were similar in both groups. Induction therapy and maintenance immunosuppression were similar in both groups and included TAC, mycophenolate acid (MPA), and steroids. The goal in all RTRs was to maintain a 12-hour trough level of 10 to 15 ng/mL in the first 3 months, 8 to 10 ng/mL for the first year, and 5 to 8 ng/mL thereafter. To achieve these levels, AA RTRs require a significantly higher dosage of TAC compared to C patients (5.9 ± 2.9 vs 3.6 ± 2 mg/d, respectively, P < .0001). By multivariate analysis, TAC dose requirements were not affected by age, gender, MPA or prednisone dose, diabetes, and renal function. Adding clotrimazole (CTM) to the RTR regimen significantly reduced the TAC dose requirements in all RTRs. When CTM was used, the TAC dose requirement was not statistically significantly different between AA and C patients (2.6 ± 1.2 mg/d vs 1.8 ± 1.5 mg/d, P = .07). We conclude that AAs required a higher TAC dose to reach the desired trough level in RTRs compared to C RTRs. The use of CTM eliminates the need for higher doses of TAC in AA RTRs. Thus, CTM may aid AA RTRs in achieving therapeutic TAC levels while reducing drug costs.     

The effect of social support and coping style on depression in patients with continuous ambulatory peritoneal dialysis in southern China

Purpose

To explore the effect of social support and coping style on depression in patients on CAPD in Southern China.

Methods

The patients undergoing CAPD therapy for more than 3 months were recruited from Jan 1 to May 31, 2009. The Beck Depression Inventory–II (BDI-II), Social Support Rating Scale, Medical Coping Modes Questionnaire, and Medical Outcomes Study Short Form (SF-36) were used to evaluate depression, social support, coping style, and quality of life (QoL), respectively.

Results

Of the 191 recruited patients, 65 patients (34.0 %) suffered from depression, with a BDI-II score of 23.8 ± 8.4. The average score of QoL (44.9 ± 13.9 vs. 64.7 ± 14.2, p < 0.001), social support (37.9 ± 7.2 vs. 42.1 ± 7.3, p < 0.001), and “confrontation” coping style (17.2 ± 3.9 vs. 18.8 ± 3.8, p = 0.006) in depressed patients was significantly lower than those in non-depressed patients, respectively. While the depressed patients had significantly higher score of “acceptance–resignation” coping style (12.9 ± 2.5 vs. 10.4 ± 3.5, p < 0.001) compared with those of non-depressed patients. Univariate analysis showed that the BDI-II score was negatively associated with social support (r = ?0.284, p < 0.001) and “confrontation” (r = ?0.180, p = 0.013), but positively associated with “acceptance–resignation” (r = 0.482, p < 0.001). Logistic regression analysis revealed that age (OR = 0.971, p = 0.038), female sex (OR = 2.211, p = 0.039), diabetes mellitus (OR = 3.046, p = 0.015), long PD duration (OR = 1.021, p = 0.020), fatigue (OR = 2.500, p = 0.032), high Pittsburgh Sleep Quality Index (PSQI) score (OR = 1.143, p = 0.001), low social support (OR = 0.945, p = 0.046), and high “acceptance–resignation” (OR = 1.096, p = 0.020) were independently associated with depression.

Conclusion

There was a high prevalence of depression in CAPD patients. Age, female sex, diabetes mellitus, long PD duration, fatigue, sleep disturbance, low social support, and high “acceptance–resignation” coping style were independently associated with depression.     

Chapter 5: Assessing Risk of Bias as a Domain of Quality in Medical Test Studies

Assessing methodological quality is a necessary activity for any systematic review, including those evaluating the evidence for studies of medical test performance. Judging the overall quality of an individual study involves examining the size of the study, the direction and degree of findings, the relevance of the study, and the risk of bias in the form of systematic error, internal validity, and other study limitations. In this chapter of the Methods Guide for Medical Test Reviews, we focus on the evaluation of risk of bias in the form of systematic error in an individual study as a distinctly important component of quality in studies of medical test performance, specifically in the context of estimating test performance (sensitivity and specificity). We make the following recommendations to systematic reviewers: 1) When assessing study limitations that are relevant to the test under evaluation, reviewers should select validated criteria that examine the risk of systematic error, 2) categorizing the risk of bias for individual studies as “low,” “medium,” or “high” is a useful way to proceed, and 3) methods for determining an overall categorization for the study limitations should be established a priori and documented clearly.     

Novel approaches to the diagnosis, prevention, and treatment of medical device-associated infections

The pathogenesis of device-associated infections is related to biofilm bacteria that exhibit distinct characteristics with respect to growth rate, structural features, and protection from host immune mechanisms and antimicrobial agents when compared with planktonic counterparts. Biofilm-associated infections are prevented, diagnosed, and treated differently from infections not associated with biofilms. This article reviews innovative concepts for the prevention of biofilm formation, and novel treatment approaches. Specific approaches for the diagnosis and prevention of catheter-associated urinary tract and bloodstream infections, as well as infections associated with orthopedic implants and cardiovascular implantable electronic devices, are also discussed.     

HIV disclosure patterns, predictors, and psychosocial correlates among HIV positive women in Zimbabwe

Disclosure of positive HIV status in Sub-Saharan Africa has been associated with safer sexual practices and better antiretroviral therapy (ART) adherence, but associations with psychosocial function are unclear. We examined patterns and psychosocial correlates of disclosure in a Zimbabwean community. Two hundred HIV positive women at different stages of initiating ART participated in a cross-sectional study examining actual disclosures, disclosure beliefs, perceived stigma, self-esteem, depression, and quality of life. Ninety-seven percent of the women disclosed to at least one person, 78% disclosed to their current husband/partner, with an average disclosure of four persons per woman. The majority (85-98%) of disclosures occurred in a positive manner and 72-95% of the individuals reacted positively. Factors significantly correlated with HIV disclosure to partners included being married, later age at menses, longer duration of HIV since diagnosis, being on ART, being more symptomatic at baseline, ever having used condoms, and greater number of partners in the last year. In multivariate analysis, being married and age at menses predicted disclosure to partners. Positive disclosure beliefs, but not the total number of disclosures, significantly correlated with lower perceived stigma (ρ = 0.44 for personalized subscale and ρ = 0.51 for public subscale, both p<0.0001), higher self-esteem (ρ = 0.15, p=0.04), and fewer depressive symptoms (ρ = -0.14, p=0.05). In conclusion, disclosure of positive HIV status among Zimbabwean women is common and is frequently met with positive reactions. Moreover, positive disclosure beliefs correlate significantly with psychosocial measures, including lower perceived stigma, higher self-esteem, and lower depression.