Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy.

We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH.

MORTALITY AFTER CLINICAL MANAGEMENT OF AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS IN KENYA.

BACKGROUND: Cryptococcal meningitis (CM) is an increasingly prevalent infection among HIV/AIDS patients and is becoming a leading cause of morbidity and mortality in Africa. The short-term prognosis and management of patients with CM may be improved by identifying factors leading to mortality in patients with CM. OBJECTIVE: To assess the clinical management and mortality associated with cryptococcal meningitis (CM) in patients with acquired immunodeficiency syndrome (AIDS) in Kenya. DESIGN: A retrospective study. SETTING: Kenyatta National Hospital and Mbagathi District Hospital, between August 2008 and March 2009. SUBJECTS: Seventy six HIV-infected patients confirmed to be CM positive. RESULTS: Results show that 30 (40%) of 76 patients diagnosed with CM died during hospitalisation after a median hospital stay of ten days (range, 2-73 days). Significant predictors of mortality in the univariate model were Mycobacterium tuberculosis (TB) co-infection (P = 0.04), having been diagnosed with a co-morbid condition such as diabetes mellitus, oral candidiasis and hypertension (P = 0.01), and a low median CD4+ T lymphocyte count (P < 0.001). The multivariable model revealed that male sex, previous or current anti-retroviral therapy (ART) at admission and CD4+ T lymphocyte count less than 50 were significant predictors of mortality. Conversely, a minimum of two weeks of amphotericin B treatment (P < 0.001), initiation of ART (P = 0.007) and monitoring of creatinine and electrolyte levels (P = 0.02) were significantly associated with survival in the univariate model. CONCLUSIONS: CM-associated mortality in Kenya is high; there is an opportunity to improve the management and the short-term outcomes of hospitalised HIV positive patients with CM in Kenya.

Modeling lesion counts in multiple sclerosis when patients have been selected for baseline activity.

The number of new gadolinium-enhancing lesions discovered via magnetic resonance imaging is a well-established outcome for multiple sclerosis studies, especially Phase II Studies. Due to the high cost of magnetic resonance imaging scans, many investigators select participants for the presence of lesions. While this selection procedure is thought to improve the power of inferences, the effect of screening for baseline activity on parameter estimation and interval coverage has not yet been examined. The objective of this study was to investigate the performance of the negative binomial distribution for modeling lesion count data in multiple sclerosis when patients have been selected for activity on a baseline scan. We performed computer simulations to investigate the influence of the screening process on inferences made using a negative binomial model about treatment effects in two independent samples. We also demonstrate how the statistical properties of screening can be incorporated into trial design. We demonstrate that when the negative binomial distribution is used to model lesion counts, while screening for baseline activity improves point estimation, this practice also has the potential to decrease interval coverage and inflate the Type I error rate. For data that is to be modeled using a negative binomial distribution, screening for baseline activity can create a trade-off between cost effectiveness and a higher than desired false positive rate that must be carefully considered in planning Phase II trials.

The prevalence, clinical features, risk factors and outcome associated with cryptococcal meningitis in HIV positive patients in Kenya.

OBJECTIVES: To determine the prevalence, clinical features, risk factors and outcomes associated with cryptococcal meningitis (CM) in human immunodeficiency virus (HIV) positive patients at two referral hospitals in Nairobi, Kenya. DESIGN: Prospective, observational study. SETTING: Kenyatta National Hospital (KNH) and Mbagathi District Hospital (MDH), Nairobi, Kenya. SUBJECTS: Three hundred and forty HIV patients presenting with suspected CM. RESULTS: Of three hundred and forty suspected CM patients, 111 (33%) were diagnosed with CM by CrAg. Among CM patients, in-hospital mortality was 36% (38/106), median age was 35 years (range, 19-60 years) and median CD4 count was 41 cells/microL (n = 89, range 2-720 cells/microL). Common clinical manifestations among CM patients included headache 103 (93%), neck stiffness 76 (69%) and weight loss 53 (48%). Factors independently associated with CM were male sex, headache, blurred vision and previous antifungal drug use. Night sweats and current use of anti-retroviral therapy were associated with reduced risk for CM. CONCLUSIONS: There is a high prevalence of CM and CM-associated mortality in HIV patients at KNH and MDH despite treatment with antifungal and anti-retroviral drugs. This study demonstrates the need to address the existing inadequacies of CM patient outcomes in Kenya.

Risk behaviours in HIV-positive men who have sex with men participating in an intervention in a primary care setting.

Men who have sex with men receiving HIV care reported their sexual behaviours and their intentions, classified according to the Transtheoretical Model of Change, to modify the following behaviours: (1) condom use by partner type and activity type; (2) reduction of partner number; and (3) disclosure of HIV serostatus to partners. Most participants were white (68.8%) or black (29.5%) and were more likely to report unprotected sex with HIV-positive than with serodiscordant partners for most activities. Whites reported more partners than black patients (mean 4.1 versus 2; P < 0.0001) and black participants reported fewer HIV-negative (P = 0.0084) and -unknown status partners (P = 0.00095) than whites. Cocaine/crack use was associated with more sexual partners (P = 0.001) and more frequent unprotected sex with HIV-negative or -unknown status partners (P = 0.036). Readiness to change risk behaviour varied by partner status and type of sexual activity. Understanding patients' risks and their readiness to change behaviours may help providers to promote sexual health.

A process evaluation of the implementation of a computer-based, health provider-delivered HIV-prevention intervention for HIV-positive men who have sex with men in the primary care setting.

There is increasing interest in using healthcare providers to deliver HIV-prevention services to their patients. Unfortunately, lack of counselling skills and time constraints within busy clinics serve as barriers to such efforts. The Providers Advocating for Sexual Health Initiative (PASHIN) study used state-of-the-art computer technology to assess each participant's risk behaviours and to determine the patient's readiness for changing each behaviour. The computer synthesized the participant-entered data, determined the targeted risk behaviour and printed a behavioural theory-based provider advice sheet and a 3-point patient prescription for the targeted risk behaviour. Since the intervention does not require providers to spend time performing a detailed sexual-risk assessment and it does not require providers to have received extensive counselling training, it has the potential to minimize some of the barriers associated with provider-delivered interventions. Thus, the purpose of this process evaluation was to assess how the PASHIN intervention was implemented in the field, including issues such as the fidelity of implementation and health providers' views on and experience with implementing the intervention. Overall, the results demonstrated that the computer-based, provider-delivered intervention was successfully delivered by providers within the context of regularly scheduled treatment sessions with HIV-positive men who have sex with men (MSM) patients. The majority of providers (79.4%) and patients (83.5%) reported that the quality of HIV-prevention services delivered during these sessions was 'good'. The majority of the providers also reported that they had received adequate training, felt more confident in communicating HIV-prevention issues with their patients and provided more HIV-prevention counselling to their patients, due to the project. However, the experience of delivering HIV-prevention counselling during an 18-month period did not appear to change providers' attitudes toward a provider-delivered HIV-prevention intervention nor their belief in the effectiveness of HIV prevention in general. Future studies should focus on how to enhance providers' acceptance and commitment to delivering HIV-prevention counselling to their patients during the clinic visit.

Experimental avoidance and high-risk sexual behavior in survivors of child sexual abuse.

While many long-term correlates of child sexual abuse (CSA) have been identified, theories to explain the development of these correlates have received little empirical validation. The process of experiential avoidance is one theory that has been proposed to account for many of the correlates of CSA. The purpose of the current study was twofold: (1) To attempt to develop a more complex measure of experiential avoidance in women with and without a CSA history, and (2) to explore variables related to two of the long-term correlates of CSA, general psychological distress and high risk sexual behavior. Levels of current distress, high-risk sex, and experiential avoidance were examined in 257 undergraduate females (mean age 20.0) using self-report questionnaires. The results of the current study indicate that CSA survivors report higher levels of experiential avoidance and high-risk sexual behavior with persons other than their primary partners. Implications of these findings for theory development, therapy with CSA survivors, and HIV prevention programs are discussed.