Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe

Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.

Anesthesia and the developing brain: a way forward for clinical research

It is now well established that many general anesthetics have a variety of effects on the developing brain in animal models. In contrast, human cohort studies show mixed evidence for any association between neurobehavioural outcome and anesthesia exposure in early childhood. In spite of large volumes of research, it remains very unclear if the animal studies have any clinical relevance; or indeed how, or if, clinical practice needs to be altered. Answering these questions is of great importance given the huge numbers of young children exposed to general anesthetics. A recent meeting in Genoa brought together researchers and clinicians to map a path forward for future clinical studies. This paper describes these discussions and conclusions. It was agreed that there is a need for large, detailed, prospective, observational studies, and for carefully designed trials. It may be impossible to design or conduct a single study to completely exclude the possibility that anesthetics can, under certain circumstances, produce long‐term neurobehavioural changes in humans; however , observational studies will improve our understanding of which children are at greatest risk, and may also suggest potential underlying etiologies, and clinical trials will provide the strongest evidence to test the effectiveness of different strategies or anesthetic regimens with respect to better neurobehavioral outcome.     

Successful interferon treatment in a patient chronically infected with hepatitis B virus carrying unusual S- (and P-) mutants in the presence of anti-HBs antibodies.

BACKGROUND: Hepatitis B virus (HBV) immune escape mutants with point mutations within the S gene may arise during the natural course of HBV infection, due to a positive selection pressure exerted by the host immune response. Mutations within the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg) allow the resulting S-mutants to propagate even in the presence of neutralizing anti-HBs antibodies and the HBV-specific T-cell immune response. Aim: To study the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs antibodies. PATIENTS, METHODS AND RESULTS: We report on a 43-year-old male chronically infected with a genotype A HBV strain, with cocirculation of both HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for 24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain reaction and HBsAg were successfully achieved. Improved histology was observed in a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems plausible that the ascribed genotype A could have contributed to the effective response to Peg-IFN, even though the treatment was provided only throughout a 24-week period. CONCLUSION: To our knowledge, this is the first report regarding the successful result obtained by using Peg-IFN as a treatment for a chronically HBV-infected patient carrying HBsAg immune escape mutants.     

Uncontrolled Web-Based Administration of Surveys on Factual Health-Related Knowledge: A Randomized Study of Untimed Versus Timed Quizzing

Background

Health knowledge and literacy are among the main determinants of health. Assessment of these issues via Web-based surveys is growing continuously. Research has suggested that approximately one-fifth of respondents submit cribbed answers, or cheat, on factual knowledge items, which may lead to measurement error. However, little is known about methods of discouraging cheating in Web-based surveys on health knowledge.

Objective

This study aimed at exploring the usefulness of imposing a survey time limit to prevent help-seeking and cheating.

Methods

On the basis of sample size estimation, 94 undergraduate students were randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition knowledge, with or without a time limit of 15 minutes (30 seconds per item); the topic of nutrition was chosen because of its particular relevance to public health. The questionnaire consisted of two parts. The first was the validated consumer-oriented nutrition knowledge scale (CoNKS) consisting of 20 true/false items; the second was an ad hoc questionnaire (AHQ) containing 10 questions that would be very difficult for people without health care qualifications to answer correctly. It therefore aimed at measuring cribbing and not nutrition knowledge. AHQ items were somewhat encyclopedic and amenable to Web searching, while CoNKS items had more complex wording, so that simple copying/pasting of a question in a search string would not produce an immediate correct answer.

Results

A total of 72 of the 94 subjects started the survey. Dropout rates were similar in both groups (11%, 4/35 and 14%, 5/37 in the untimed and timed groups, respectively). Most participants completed the survey from portable devices, such as mobile phones and tablets. To complete the survey, participants in the untimed group took a median 2.3 minutes longer than those in the timed group; the effect size was small (Cohen’s r=.29). Subjects in the untimed group scored significantly higher on CoNKS (mean difference of 1.2 points, P=.008) and the effect size was medium (Cohen’s d=0.67). By contrast, no significant between-group difference in AHQ scores was documented. Unexpectedly high AHQ scores were recorded in 23% (7/31) and 19% (6/32) untimed and timed respondents, respectively, very probably owing to “e-cheating”.

Conclusions

Cribbing answers to health knowledge items in researcher-uncontrolled conditions is likely to lead to overestimation of people’s knowledge; this should be considered during the design and implementation of Web-based surveys. Setting a time limit alone may not completely prevent cheating, as some cheats may be very fast in Web searching. More complex and contextualized wording of items and checking for the “findability” properties of items before implementing a Web-based health knowledge survey may discourage help-seeking, thus reducing measurement error. Studies with larger sample sizes and diverse populations are needed to confirm our results.     

Iliopsoas abscess in adolescents with type 1 diabetes mellitus

Iliopsoas abscesses have been reported in adult diabetic patients, but only one case has been so far reported in the pediatric diabetic literature. We report three cases of iliopsoas abscesses in three adolescents with type 1 diabetes mellitus, suggesting that an increased awareness of this condition is required for its early recognition and prompt treatment.     

The role of postoperative radiotherapy for thymomas: a multicentric retrospective evaluation from three Italian centers and review of the literature

BackgroundThymoma is a rare mediastinal neoplasia. Surgery is the backbone of the treatment, but the role of postoperative radiotherapy (PORT) remains controversial. We aimed to obtain data on survival and safety in patients treated with PORT in three different Italian institutions.MethodsWe retrospectively analyzed 183 consecutive patients who underwent surgery from 1981 to 2015. According to the Masaoka-Koga staging system, 39.3%, 32.7%, 18.6% and 9.8% patients were in stage I, II, III and IV of disease, respectively. PORT was indicated in 114 patients (62.3%), while 69 subjects underwent surgery alone. Complete resection was obtained in 68 patients who underwent PORT. Adverse events (AEs) were graded according to CTCAE v4.0. We analyzed the recent literature to describe the current reports on PORT for resected thymoma.ResultsMean follow-up was 130 months (range, 3–417 months). Overall survival (OS) at 1-, 5- and 10-year from surgery was 98.3%, 90.2% and 69.7% respectively. One-, 5- and 10-year disease specific survival (DSS) was 98.9%, 92.3% and 89.8% respectively. Disease free survival (DFS) at 1, 5 and 10 years from surgery was 96.7%, 88.3% and 82.8% respectively. Univariate analysis showed that complete resection, cell histology A-AB-B1 and stages I–II were significant predictors of better DSS and DFS. Multivariate analysis showed that sex, R0 margins and WHO histology was independent prognostic factors. Among patients treated with PORT, a trend towards better OS was evident with Masaoka stage I–II (P=0.09). Patients with R0 margins treated with PORT showed better OS and DSS (P=0.05). No differences in DSS for performance status (P=0.70), WHO histology (P=0.19), paraneoplastic syndrome (P=0.23) and surgical procedure (P=0.53) were evident. Patients treated with PORT had a higher level of acute AEs compared to surgery alone, but none of these was graded ≥3.ConclusionsOur results confirmed that patients with incompletely resected thymoma had the worst OS and DSS. High grade acute toxicity was not different between PORT and surgery alone. Other trials reported a significant benefit in OS, DSS and DFS in stage IIb–IV thymoma treated with PORT.