Phase III randomized, double-blind study of maintenance CAI or placebo in patients with advanced non-small cell lung cancer (NSCLC) after completion of initial therapy (NCCTG 97-24-51)

PURPOSE: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen. METHODS: After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). RESULTS: Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p<0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and UNISCALE (72% versus 51%, p=0.04). CONCLUSION: The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC.     

Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93.

PURPOSE: To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma. PATIENTS AND METHODS: A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m(2) (or 1.2 mg/m(2) for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks. RESULTS: A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m(2) or 0.8 mg/m(2) for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months. CONCLUSION: Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved.     

Evaluation of nutritive value and functional qualities of sorghum subjected to different traditional processing methods

Sorghum (Sorghum bicolar L. Moench), a staple food in many parts of the world, is underutilised compared to its potential due to inherent problems. A study was conducted to evaluate the effect of different traditional processing methods on the nutritional and functional qualities of sorghum. The review of literature established the main causes of the low level of sorghum utilisation to be low nutritional and inferior organoleptic qualities. It was further established that traditional processing methods, such as germination and fermentation, can promote its utilisation. Three processing methods, namely germination (G), fermentation (F), and germination combined with fermentation (GF), were used to prepare feeds from two sorghum varieties, Tegemeo and Udo. Evaluation of the feed qualities in terms of acceptability, retention, feed efficiency ratio (FER) and protein efficiency ratio (PER), using weanling rats was carried out and compared to the untreated one which served as control. An element of functional properties was assessed in terms of diastatic power (DP). Regarding feed intake, there was no significant difference between the feeds. Body retention for Tegemeo variety was higher than that for Udo. FER ranged from 0.019 +/- 0.015 to 0.095 +/- 0.015, PER ranged from 0.113 +/- 0.089 to 0.703 +/- 0.111 and diastatic power from 15.99 +/- 1.20 to 114.58 +/- 0.95. In all the three cases, germinated feeds had the highest values and were therefore considered of higher nutritional value. It was therefore concluded that germination was superior to the other processing methods in improving the nutritional and functional qualities of sorghum.     

Clinical usefulness of the framingham cardiovascular risk profile beyond its statistical performance: the tehran lipid and glucose study

The utility of a risk function in clinical practice is an important concept that has received insufficient attention. The authors evaluated the clinical usefulness of the Framingham risk function (FRF) for cardiovascular disease in a Middle Eastern population (2,640 men and 3,584 women aged 30-74 years) free of cardiovascular disease at baseline in 1999. They calculated the net benefit fraction for treatment of subjects with an estimated 10-year risk of ≥10% and also ≥20%, where the net benefit fraction is a weighted sum of true-positive and false-positive rates divided by incidence, as estimated by Kaplan-Meier analysis. The authors drew a decision curve by plotting the net benefit fraction against a wide range of risk thresholds for treatment. The cumulative incidence of cardiovascular disease was 7.6% and 12.3% in women and men, respectively. The FRF had a C index of 0.832 in women and 0.785 in men with a reasonable calibration. On the basis of the net benefit fraction, about 50% of the incidence in men and women could be appropriately treated by using the 10% threshold; however, the FRF was not useful at the 20% threshold, especially in women. In both genders, usefulness of the FRF was as good as the function derived directly from Tehrani data with the same variables; however, it could be useful in low thresholds for treatment.     

Diagnosis,clinical manifestations and management of rare bleeding disorders in Iran

Background: Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs.

Objective: In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs.

Methods: For this study, all relevant publications were searched in Medlin until 2015.

Results and discussion: Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ～3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients.

Conclusion: Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.     

Associations between age of menarche,early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls: A cross-sectional study

Objectives

This cross-sectional survey aimed to explore associations between age of menarche, early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls.

Methods

Secondary schoolgirls aged 17–18 years from Mwanza, Tanzania, participated in structured face-to-face questionnaire-based interviews, conducted by nurses and clinicians. Age of menarche was evaluated in categories of 11–12, 13–14, 15–16 or ≥17 years. Primary outcome measures were self-reported early sexual debut (first vaginal sex at <16 years) and high-risk sexual behaviour, including non-use of condoms, having sex for gifts/money, having older sexual partners and/or other risky behaviours.

Results

Of 401 girls enrolled, 174 (43.4%) reported prior vaginal sex. Prevalence of early sexual debut was 14.2% but pressured/forced sex and risky sexual behaviours were common. Adjusted for potential confounding, younger age at menarche was associated with early sexual debut (adjusted odds ratio for linear trend: 1.88 per category, 95% confidence interval: 1.21–2.92, p = 0.005). This association remained after excluding girls with first sex at <8 years or experiencing pressure or force at first sex. Further, adjusted for potential confounding (including ever experiencing forced sex), early sexual debut was associated with high-risk sexual behaviour (adjusted odds ratio: 2.85, 95% confidence interval: 1.38–5.88, p = 0.004).

Conclusions

Among urban Tanzanian school girls, younger age of menarche was associated with early sexual debut, and early sexual debut was associated with high-risk sexual behaviour. Researchers and public health professionals developing and delivering interventions aimed at preventing adverse sexual health outcomes should consider the impact of these early biological and sexual exposures.