ABSTRACT Introduction: Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables. Materials and Methods: We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specific data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves. Results: We identified 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P <0.0001) were significantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72. Conclusion: Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.

BACKGROUND: Substance use and psychiatric disorders cause significant burden of disease in low- and middle-income countries. Co-morbid psychopathology and longer duration of untreated psychosis (DUP) can negatively affect treatment outcomes OBJECTIVES: The study assessed substance use amongst adults with severe mental illness receiving services at a regional psychiatric hospital in KwaZulu-Natal (South Africa). We describe the prevalence and correlates of lifetime substance use and examine the association between substance use and DUP. METHODS: A cross-sectional survey recruited adults diagnosed with severe mental illness and assessed lifetime and past 3-month substance use using the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test. Regression analyses were conducted to determine associations between lifetime substance use (other than alcohol and tobacco) and DUP as measured by the World Health Organization Encounter Form. RESULTS: Amongst 87 participants, alcohol (81.6%), tobacco (75.6%) and cannabis (49.4%) were the most common substances reported for lifetime use. Risk of health-related problems (health, social, financial, legal and relationship) of cannabis use was associated with younger age, single marital status and lower education. Adjusted regression analyses indicated that use of amphetamines and methaqualone is associated with longer DUP. CONCLUSIONS: Substance use is prevalent amongst psychiatric patients in KwaZulu-Natal and may contribute to longer DUP. Mental health services in this region should address co-morbid substance use and psychiatric disorders.

The design of malarial vaccine based on the circumsporozoite (CS) protein, a majuor surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inclusion in recombinant or synthetic vaccine candidates. We have investigated the specificity and function of a series of T cell clones, derived from volunteers immunized with Plasmodium falciparum sporozoites in an effort to identify relevant epitopes in the immune response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were obtained wich specifically recognized a repetitive epitope located in the 5'repeat region of the CS protein. This epitope, when conjugated to the 3'repeat region in a synthetic MAPs construct, induced high titers of antisporozoite antibodies in C57B1 mice. A second T cell epitope, which mapped to aa 326-345 of the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL in the volunteers, and the recent studies inthe rodent model (Renia et al., 1991; Tsuji et al., 1990), suggested that CS-specific CD4+ T cells, in addition to their indirect role as helper cells in the induction of antibody and CD8 + effector cells, may also play a direct role in protection against sporozoite challenge by targeting EEF within the liver.