Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.     

Transparency and credibility of industry-sponsored clinical trial publications: a survey of journal editors

Objective: To examine how medical journal editors perceive changes in transparency and credibility of industry-sponsored clinical trial publications over a 5 year period (2010 to 2015).

Methods: From July to September 2015, a survey link was emailed to journal editors identified from the Thomson Reuters registry. Editors ranked their perception of: a) change in transparency and credibility of industry-sponsored clinical trial publications; b) 8 “Publication Best Practices” and the impact of each on transparency; and c) the importance and adoption of the previously published “10 Recommendations for Closing the Credibility Gap in Reporting Industry-Sponsored Clinical Research”.

Results: Of 510 editors who opened the survey, the analysis pool comprised a total of 293 editors. The majority of respondents reported their location as the US (46%) or EU (45%) and most commonly reported editorial titles were deputy/assistant editor (36%), editor-in-chief (35%) and section editor (24%). More editors reported improved versus worsened transparency (63.5% vs. 6.1%) and credibility (53.2% vs. 10.4%). Best practices that contributed most to improved transparency were “disclosure of the study sponsor” and “registration and posting of trial results”. Respondents ranked the importance of nine recommendations as moderate or extremely important, and adoption of all recommendations was ranked minimal to moderate.

Conclusions: The 293 editors who responded perceived an improvement in the transparency and credibility of industry-sponsored publications from 2010 to 2015. Confirmation of the importance of 9/10 recommendations by the respondents was encouraging. Yet, low adoption rates suggest that additional work is required by all stakeholders to improve best practices, transparency and credibility.     

“Children are Sexually Innocent”: Iranian Parents’ Understanding of Children’s Sexuality

Sexuality education (SE) is hotly contested in the West and there is much abstinence-only education; however, it remains controversial in a variety of contexts, including in Iran. The lack of consensus about children’s SE in Muslim societies obliges us to explore different aspects of this topic systematically. The qualitative research presented here was about how Iranian parents perceived children’s sexuality. Data from parents of 26 children were collected during four focus group sessions. Informants were selected from Area 5 in West Tehran. This area included 72 primary schools for girls and 82 for boys. The sessions were facilitated by using a semi-structured focus group guide. Content analysis was adopted using combined free and analytical coding to reduce data, to extract meanings, and to categorize domains. One of the three main domains identified, family management of child sexuality, is comprised of the following: (1) understanding of child sexuality, (2) family rules, (3) parent–child interactions, and (4) opposite sex interactions. Parental misinformation, accumulated myths, and ignorance about children’s sexual development were evident. Strict family rules and a lack of consistent policy and instruction for SE were also identified. Parents said they were neither well-prepared nor competent to educate their children about sexuality. In fact, a majority of mothers raised “incompetence” as an important determinant in their own parent–child interactions. Societal changes as well as children’s socialization patterns have forced parents to accept their children’s opposite sex friendships as a reality. Results suggest a community need for developing comprehensive and culturally sensitive SE for schools and parental use.     

Amphotericin B-induced depression in the phagocytic function of the isolated rat liver and its prevention by nifedipine

We investigated the effects of the antimycotic agent amphotericin B (AmB) on the phagocytic activity of the isolated perfused rat liver. At a concentration of 5 microM, the drug markedly reduced the clearance of latex beads by the liver as compared to control preparations. Scanning electron microscopy observations showed that latex beads were attached only to Kupffer cells. A liver scan performed infusing 99Tc-colloidal albumin showed that AmB depressed the uptake of the colloid in all hepatic lobes, with no focal defects. Both in control and AmB experiments no trypan blue uptake occurred. The pretreatment of the perfused liver with the calcium antagonist nifedipine prevented the decrease in phagocytosis induced by AmB. In addition, AmB had no effect on livers perfused with a Ca2(+)-free medium. A decrease in the phagocytic capacity of the perfused liver was also observed after the administration of the Ca2(+)-ionophore A23187. The observations suggest that AmB may exert an intrinsic toxicity on the Kupffer cells, which is, at least in part, responsible for the decrease in phagocytosis induced by the drug. This effect may be of relevance to clinical situations and deserves careful consideration.     

Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis

BACKGROUND AND AIMS: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. METHODS: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. RESULTS: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy". CONCLUSIONS: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.