Arnaud Merglen

Increased risk of colon cancer after external radiation therapy for prostate cancer

Radiotherapy can induce second cancers. Controversies still exist regarding the risk of second malignancies after irradiation for prostate cancer. We evaluated the risk of developing colon and rectum cancers after prostate cancer in irradiated and nonirradiated patients. Using data from the population‐based Geneva cancer registry, we included in the study all men with prostate cancer diagnosed between 1980 and 1998 who survived at least 5 years after diagnosis. Of the 1,134 patients, 264 were treated with external radiotherapy. Patients were followed for occurrence of colorectal cancer up to 31 December, 2003. We calculated standardized incidence ratios (SIR) using incidence rates for the general population to obtain the expected cancer incidence. The cohort yielded to 3,798 person‐years. At the end of follow‐up 19 patients had developed a colorectal cancer. Among irradiated patients the SIR for colorectal cancer was 3.4 (95% confidence intervals [CI] 1.7–6.0). Compared to the general population, the risk was significantly higher for colon cancer (SIR = 4.0, 95% CI: 1.8–7.6), but not for rectal cancer (SIR = 2.0, 95% CI: 0.2–7.2). The risk of colon cancer was increased in the period of 5–9 years after diagnosis (SIR = 4.7, 95% CI: 2.0–9.2). The overall SIR of secondary cancer in patients treated with radiotherapy was 1.35 (p = 0.056). Nonirradiated patients did not have any increased risk of rectal or colon cancer. This study shows a significant increase of colon but not rectum cancer after radiotherapy for prostate cancer. The risk of second cancer after irradiation, although probably small, needs nevertheless to be carefully monitored.

Clinical disease severity of respiratory viral co-infection versus single viral infection: a systematic review and meta-analysis.

Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). Conclusions No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.

Activity-Based Funding of Hospitals and Its Impact on Mortality, Readmission, Discharge Destination, Severity of Illness, and Volume of Care: A Systematic Review and Meta-Analysis

Background Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care. Methods We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication. Results Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk  = 1.24, 95% CI 1.18–1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences. Conclusions Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes.

Sensitivity and Predictive Value of 15 PubMed Search Strategies to Answer Clinical Questions Rated Against Full Systematic Reviews

Background Clinicians perform searches in PubMed daily, but retrieving relevant studies is challenging due to the rapid expansion of medical knowledge. Little is known about the performance of search strategies when they are applied to answer specific clinical questions. Objective To compare the performance of 15 PubMed search strategies in retrieving relevant clinical trials on therapeutic interventions. Methods We used Cochrane systematic reviews to identify relevant trials for 30 clinical questions. Search terms were extracted from the abstract using a predefined procedure based on the population, interventions, comparison, outcomes (PICO) framework and combined into queries. We tested 15 search strategies that varied in their query (PIC or PICO), use of PubMed’s Clinical Queries therapeutic filters (broad or narrow), search limits, and PubMed links to related articles. We assessed sensitivity (recall) and positive predictive value (precision) of each strategy on the first 2 PubMed pages (40 articles) and on the complete search output. Results The performance of the search strategies varied widely according to the clinical question. Unfiltered searches and those using the broad filter of Clinical Queries produced large outputs and retrieved few relevant articles within the first 2 pages, resulting in a median sensitivity of only 10%–25%. In contrast, all searches using the narrow filter performed significantly better, with a median sensitivity of about 50% (all P < .001 compared with unfiltered queries) and positive predictive values of 20%–30% (P < .001 compared with unfiltered queries). This benefit was consistent for most clinical questions. Searches based on related articles retrieved about a third of the relevant studies. Conclusions The Clinical Queries narrow filter, along with well-formulated queries based on the PICO framework, provided the greatest aid in retrieving relevant clinical trials within the 2 first PubMed pages. These results can help clinicians apply effective strategies to answer their questions at the point of care.

Weekly sport practice and adolescent well-being

Objective Sport practice is widely encouraged, both in guidelines and in clinical practice, because of its broad range of positive effects on health. However, very limited evidence directly supports this statement among adolescents and the sport duration that we should recommend remains unknown. We aimed to determine sport durations that were associated with poor well-being. Methods We conducted a survey including 1245 adolescents (16–20 years) from the general Swiss population. Participants were recruited from various settings (sport centres, peers of sport practicing adolescents, websites) and asked to complete a web-based questionnaire. Weekly sport practice was categorised into four groups: low (0–3.5 h), average (≈ recommended 7 h (3.6–10.5)), high (≈14 h (10.6–17.5)) and very high (>17.5 h). We assessed well-being using the WHO-5 Well-Being Index. Results Compared with adolescents in the average group, those in the very high group had a higher risk of poor well-being (OR 2.29 (95% CI 1.11 to 4.72)), as did those in the low group (OR 2.33 (1.58 to 3.44)). In contrast, those in the high group had a lower risk of poor well-being than those in the average group (OR 0.46 (0.23 to 0.93)). Conclusions We found an inverted, U-shaped relationship between weekly sport practice duration and well-being among adolescents. The peak scores of well-being were around 14 h per week of sport practice, corresponding to twice the recommended 7 h. Practicing higher sport durations was an independent risk factor of poor well-being.

Hormonal therapy for oestrogen receptor-negative breast cancer is associated with higher disease-specific mortality

BACKGROUND Tamoxifen has a remarkable impact on the outcome of oestrogen receptor (ER)-positive breast cancer. Without proven benefits, tamoxifen is occasionally prescribed for women with ER-negative disease. This population-based study aims to estimate the impact of tamoxifen on the outcome of ER-negative disease. METHODS We identified all women (n = 528) diagnosed with ER-negative invasive breast cancer between 1995 and 2005. With Cox regression analysis, we calculated breast cancer mortality risks of patients treated with tamoxifen compared with those treated without tamoxifen. We adjusted these risks for the individual probabilities (propensity scores) of having received tamoxifen. RESULTS Sixty-nine patients (13%) with ER-negative disease were treated with tamoxifen. Five-year disease-specific survival for women treated with versus without tamoxifen were 62% [95% confidence interval (CI) 48% to 76%] and 79% (95% CI 75% to 83%), respectively (P(Log-rank) < 0.001). For ER-negative patients, risk of death from breast cancer was significantly increased in those treated with tamoxifen compared with patients treated without tamoxifen (adjusted hazard ratio = 1.7, 95% CI 1.1-2.9, P = 0.031). CONCLUSION Our results show that patients with ER-negative breast cancer treated with tamoxifen have an increased risk of death from their disease. Tamoxifen use should be avoided for these patients.

Corticosteroids for sore throat: a clinical practice guideline

What is the role of a single dose of oral corticosteroids for those with acute sore throat? Using the GRADE framework according to the BMJ Rapid Recommendation process, an expert panel make a weak recommendation in favour of corticosteroid use. The panel produced these recommendations based on a linked systematic review triggered by a large randomised trial published in April 2017. This trial reported that corticosteroids increased the proportion of patients with complete resolution of pain at 48 hours. Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package. The infographic provides the recommendation together with an overview of the absolute benefits and harms of corticosteroids in the standard GRADE format. Table 2 below shows any evidence that has emerged since the publication of this article. Clinicians and their patients can find consultation decision aids to facilitate shared decision making in MAGICapp (www.magicapp.org/goto/guideline/JjXYAL/section/j79pvn).

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Design Systematic review and meta-analysis of randomised control trials. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews. Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status. Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach. Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval −1.9 to −7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (−0.4 to −21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups. Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat. Systematic review registration PROSPERO CRD42017067808.

A student‐initiated, undergraduate, peer teaching skills programme

biomedical research. These reflect a recognised need to emphasise the scientific basis of medicine throughout medical school. Why the idea was necessary The largely unmet challenge of the Association of American Medical Colleges (AAMC) 2001 Medical School Objectives Project (http://www.aamc.org/meded/msop/) to meaningfully return to basic science after clerkships, and the recent introduction of the Liaison Committee on Medical Education (LCME) requirement to provide instruction in the conduct and evaluation of research (ED-17-A) (http://www.lcme.org/standard. htm#translationalresearch) both require curricular innovation. We suggest here that both challenges can be addressed by the simple expedient of formally engaging students in reading the medical literature. What was done The ‘Medical Literature Curriculum’ (MLC) is a sequence of courses that run in parallel with the standard curriculum at the State University of New York Upstate Medical University, balancing and integrating it. Students progress from studying predominantly published case reports during the pre-clinical years to studying reports of clinical and translational research as they gain experience with patients. We are currently in our sixth year of development of the MLC (http://www.upstate.edu/ mlc/), with established courses running throughout Years 1, 2 and 4. Selected papers are assigned for independent study, after which there is large-group discussion led by faculty experts in the areas of interest. Participation in the process is assured by quizzes prior to class discussion and by written assignments (generation of a ‘pathophysiological hypothesis’ for clinical findings in case reports and preparation of a ‘lay summary’ of research reports suitable for counselling patients). Evaluation of results and impact We have found that case reports provide an accessible means of entry into the literature for beginning students, and that the activity of reading them provides all of the benefits shown for other case methods, namely, it energises students and forces the application of basic science knowledge in a context that is self-evidently relevant to future goals. Reading reports of research studies after clerkships serves as a means of returning students to a scientific approach to questions of importance in medicine. Besides being a substantive response to the challenges posed by the AAMC and LCME relating to medicine as a science, reading the medical literature as formal coursework can represent a central educational experience. The medical literature represents the discourse and culture of medicine in its most refined form, which reflects the conversation that we, as teachers, wish to pass on. If we want to develop students who are familiar and comfortable with the medical literature, who habitually look to it to resolve problems and to remain current, and who can adequately analyse, critique and apply it, then the most direct and authentic means to these ends should include a significant formal immersion in the literature guided by experienced faculty during medical school.

Increased risk of second cancer among patients with ovarian borderline tumors

OBJECTIVES Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. METHODS We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. RESULTS The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. CONCLUSION Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.