Publications by authors named "Arnaud Merglen"

24 Publications

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[Mindfulness based interventions for children and adolescents].

Rev Med Suisse 2020 Nov;16(716):2297-2300

Service du développement et de la croissance, Département de la femme, de l'enfant et de l'adolescent, HUG, 1211 Genève 14.

Mindfulness based interventions (MBI) are widely available to adults. Programs are also offered to children and adolescents. Interventions in school and clinical settings are increasingly being published in scientific literature. In the school context, the effects are promising on psychological health, such as stress, anxiety, depression or externalized behaviours, and on executive functions, attention, and socio-emotional skills. In the clinical context, MBI has a particular effect on stress/anxiety and depression as well as on the key symptoms of Attention Deficit Hyperactivity Disorder. These results are very encouraging, but all meta-analyses and literature reviews nevertheless emphasize the need for studies with robust methodology before proposing MBI on a large scale for this population.
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November 2020

Medical students' knowledge of and attitudes towards LGBT people and their health care needs: Impact of a lecture on LGBT health.

PLoS One 2020 1;15(7):e0234743. Epub 2020 Jul 1.

Interdisciplinary Division for Adolescent Health (DISA), Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Objectives: Lesbian, gay, bisexual, and transgender (LGBT) adolescents have specific health care needs and are susceptible to health care disparities. Lack of skills and knowledge on the part of health care providers have a negative effect on their access to care and health outcomes. This study 1) explores the knowledge and attitudes of medical students regarding LGBT people, and 2) assesses the impact of a one-hour lecture targeting adolescent LGBT health needs.

Methods: Fourth-year medical students attended a compulsory one-hour lecture on sexual orientation and gender identity development in adolescence, highlighting health issues. We created a questionnaire with items to elicit students' knowledge and attitudes about LGBT health issues. Students were invited to complete this questionnaire online anonymously one week before the lecture and one month after the lecture.

Results: Out of a total of 157 students, 107 (68.2%) responded to the pre-intervention questionnaire and 96 (61.1%) to the post-intervention questionnaire. A significant proportion-13.7% of all respondents-identified as LGBT or questioning. Our results show that most medical students already show favorable attitudes towards LGBT people and a certain degree of knowledge of LGBT health needs. They demonstrated a large and significant increase in knowledge of LGBT health issues one month after the lecture.

Discussion: A single one-hour lecture on sexual orientation and LGBT health issues may increase knowledge among medical students. Medical students and professionals should receive such training to increase their knowledge about LGBT patients as it, together with favorable attitudes, has the potential to improve health outcomes among this vulnerable population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234743PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329058PMC
September 2020

[Transgender and non-binary teenagers : management in primary care].

Rev Med Suisse 2020 Apr;16(691):789-793

Unités de pédiatrie hospitalière, Consultation des adolescents, Unité santé jeunes, Service de pédiatrie générale, Département de la femme, de l'enfant et de l'adolescent, HUG, 1211 Genève 14, et Faculté de médecine, Université de Genève, 24 rue du Général-Dufour, 1211 Genève 4.

Transgender, non-binary and questioning teenagers are increasingly visible. However, they face barriers in accessing appropriate care that meet their needs, both specific and regarding their general health. Primary care physicians increasingly see them in consultations but often lack elements of communication and recent knowledge that is needed to accompany them and their close ones in their -individual trajectories. This article aims to answer this need and provides a synthesis about recent evidence and suggested communication approaches for primary care physicians, who play a central role for the health of all patients.
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April 2020

[Adolescence and sexuality: a risky business How best to inform parents ?]

Rev Med Suisse 2018 Apr;14(603):843-848

Unités de pédiatrie hospitalière, Consultation des adolescents et Unité santé jeunes ; Service de pédiatrie générale, Département de l'enfant et de l'adolescent, HUG, 1211 Genève 14 et Département de pédiatrie, Faculté de médecine, Université de Genève, 1211 Genève 4.

Parents are often reluctant to discuss sexuality and romantic relationships with their teenagers. However, these discussions can have a strong impact on their children's health. Care providers can act as a reliable source of information to support parents in this task. Through repeated short interactions with their child over their adolescence, parents can cover most topics related to sexuality, based on teenagers' questions and the situations that they face (e.g. LGBT bullying at school). This article summarizes current best practice on how to facilitate parental dialogue with adolescents about sexuality and offer care providers guidance in transmitting this information to parents.
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April 2018

UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey.

BMJ Open 2017 Nov 16;7(11):e018593. Epub 2017 Nov 16.

Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

Introduction: UpToDate is widely used by clinicians worldwide and includes more than 9400 recommendations that apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. GRADE guidance warns against strong recommendations when certainty of the evidence is low or very low (discordant recommendations) but has identified five paradigmatic situations in which discordant recommendations may be justified.

Objectives: Our objective was to document the strength of recommendations in UpToDate and assess the frequency and appropriateness of discordant recommendations.

Design: Analytical survey of all recommendations in UpToDate.

Methods: We identified all GRADE recommendations in UpToDate and examined their strength (strong or weak) and certainty of the evidence (high, moderate or low certainty). We identified all discordant recommendations as of January 2015, and pairs of reviewers independently classified them either into one of the five appropriate paradigms or into one of three categories inconsistent with GRADE guidance, based on the evidence presented in UpToDate.

Results: UpToDate included 9451 GRADE recommendations, of which 6501 (68.8%) were formulated as weak recommendations and 2950 (31.2%) as strong. Among the strong, 844 (28.6%) were based on high certainty in effect estimates, 1740 (59.0%) on moderate certainty and 366 (12.4%) on low certainty. Of the 349 discordant recommendations 204 (58.5%) were judged appropriately (consistent with one of the five paradigms); we classified 47 (13.5%) as good practice statements; 38 (10.9%) misclassified the evidence as low certainty when it was at least moderate and 60 (17.2%) warranted a weak rather than a strong recommendation.

Conclusion: The proportion of discordant recommendations in UpToDate is small (3.7% of all recommendations) and the proportion that is truly problematic (strong recommendations that would best have been weak) is very small (0.6%). Clinicians should nevertheless be cautious and look for clear explanations-in UpToDate and elsewhere-when guidelines offer strong recommendations based on low certainty evidence.
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http://dx.doi.org/10.1136/bmjopen-2017-018593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701989PMC
November 2017

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

BMJ 2017 Sep 20;358:j3887. Epub 2017 Sep 20.

Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada.

 To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Systematic review and meta-analysis of randomised control trials. Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews. 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. Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee ( 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. 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. 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. PROSPERO CRD42017067808.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605780PMC
http://dx.doi.org/10.1136/bmj.j3887DOI Listing
September 2017

Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis.

BMJ Open 2017 Sep 11;7(9):e019022. Epub 2017 Sep 11.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Objective: To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV).

Design: We performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome.

Data Sources: Embase and Medline to February 2017.

Eligibility Criteria: For maternal outcomes, we considered randomised controlled trials (RCTs) comparing tenofovir-based regimens with those with alternative nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). For child outcomes, we included RCTs and comparative observational studies of tenofovir-based regimens versus alternative NRTIs regimens or, for HBV, placebo.

Results: Ten studies (seven RCTs) met the inclusion criteria for maternal and child outcomes, and an additional 33 studies (12 RCTs) met the inclusion criteria for HBV-specific outcomes. The most common comparison was tenofovir and emtricitabine versus zidovudine and lamivudine. There was no apparent difference between tenofovir-based regimens and alternatives in maternal outcomes, including serious laboratory adverse events (low certainty) and serious clinical adverse events (moderate certainty). There was no difference between NRTIs in vertical transmission of HIV: 1 more per 1000, 8 fewer to 10 more, low certainty; or vertical transmission of HBV: 7 fewer per 1000, 10 fewer to 38 more, moderate certainty. We found moderate certainty evidence that tenofovir/emtricitabine increases the risk of stillbirths and early neonatal mortality (51 more per 1000, 11 more to 150 more) and the risk of early premature delivery at <34 weeks (42 more per 1000, 2 more to 127 more).

Conclusions: Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine, but certainty is low when they are not coprescribed with lopinavir/ritonavir. Other outcomes are likely similar between antiretrovirals.

Trial Registration Number: PROSPERO CRD42017054392.
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http://dx.doi.org/10.1136/bmjopen-2017-019022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027063PMC
September 2017

Adjustment Strategies in Studies of Therapy-Reply.

JAMA 2017 06;317(21):2238-2239

Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2017.4887DOI Listing
June 2017

Adjusted Analyses in Studies Addressing Therapy and Harm: Users' Guides to the Medical Literature.

JAMA 2017 02;317(7):748-759

Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

Observational studies almost always have bias because prognostic factors are unequally distributed between patients exposed or not exposed to an intervention. The standard approach to dealing with this problem is adjusted or stratified analysis. Its principle is to use measurement of risk factors to create prognostically homogeneous groups and to combine effect estimates across groups.The purpose of this Users' Guide is to introduce readers to fundamental concepts underlying adjustment as a way of dealing with prognostic imbalance and to the basic principles and relative trustworthiness of various adjustment strategies.One alternative to the standard approach is propensity analysis, in which groups are matched according to the likelihood of membership in exposed or unexposed groups. Propensity methods can deal with multiple prognostic factors, even if there are relatively few patients having outcome events. However, propensity methods do not address other limitations of traditional adjustment: investigators may not have measured all relevant prognostic factors (or not accurately), and unknown factors may bias the results.A second approach, instrumental variable analysis, relies on identifying a variable associated with the likelihood of receiving the intervention but not associated with any prognostic factor or with the outcome (other than through the intervention); this could mimic randomization. However, as with assumptions of other adjustment approaches, it is never certain if an instrumental variable analysis eliminates bias.Although all these approaches can reduce the risk of bias in observational studies, none replace the balance of both known and unknown prognostic factors offered by randomization.
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http://dx.doi.org/10.1001/jama.2016.20029DOI Listing
February 2017

The evidence for treating acute pyelonephritis with oral antibiotic therapy and short intravenous treatment is growing for low-risk children.

Evid Based Med 2015 Apr 3;20(2):66. Epub 2015 Mar 3.

Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada; SickKids Research Institute and Institute of Health Policy, Management and Evaluation, University of Toronto, Canada.

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http://dx.doi.org/10.1136/ebmed-2014-110093DOI Listing
April 2015

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.

PLoS One 2014 27;9(10):e109975. Epub 2014 Oct 27.

Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210200PMC
June 2015

Bronchiolitis: the challenge of delivering high value care through restraint.

J Pediatr 2014 Oct;165(4):655-7

Division of Pediatric Medicine, Pediatric Outcomes Research Team (PORT), Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jpeds.2014.07.025DOI Listing
October 2014

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

PLoS One 2014 16;9(6):e99392. Epub 2014 Jun 16.

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Hamilton Health Sciences, Hamilton, Ontario, Canada; Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099392PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059637PMC
October 2015

Weekly sport practice and adolescent well-being.

Arch Dis Child 2014 Mar 20;99(3):208-10. Epub 2013 Nov 20.

Institute of Social and Preventive Medicine, University of Lausanne, , Lausanne, Switzerland.

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.
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http://dx.doi.org/10.1136/archdischild-2013-303729DOI Listing
March 2014

Experiencing regrets in clinical practice.

Lancet 2013 Nov;382(9904):1553-4

Harvard University, Cambridge, MA 02138, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(13)62325-9DOI Listing
November 2013

Sensitivity and predictive value of 15 PubMed search strategies to answer clinical questions rated against full systematic reviews.

J Med Internet Res 2012 Jun 12;14(3):e85. Epub 2012 Jun 12.

Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland.

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.
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http://dx.doi.org/10.2196/jmir.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414859PMC
June 2012

A student-initiated, undergraduate, peer teaching skills programme.

Med Educ 2008 Nov;42(11):1139-40

Department of Medicine, University Hospitals, 1211 Geneva 14, Switzerland.

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http://dx.doi.org/10.1111/j.1365-2923.2008.03206.xDOI Listing
November 2008

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

Int J Cancer 2008 Sep;123(5):1141-5

Geneva Cancer Registry, Institute for Social and Preventive Medicine, University of Geneva, Geneva, Switzerland.

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.
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http://dx.doi.org/10.1002/ijc.23601DOI Listing
September 2008

Increased risk of second cancer among patients with ovarian borderline tumors.

Gynecol Oncol 2008 May 2;109(2):210-4. Epub 2008 Apr 2.

Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva University, Geneva, Switzerland.

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.
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http://dx.doi.org/10.1016/j.ygyno.2008.01.032DOI Listing
May 2008

Short- and long-term mortality with localized prostate cancer.

Arch Intern Med 2007 Oct;167(18):1944-50

Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva University, 55 Boulevard de la Cluse, 1205 Geneva, Switzerland.

Background: No clear guidelines exist for managing localized prostate cancer because clinical studies have not yet established which treatment provides the best long-term outcome. We assessed the effect of treatment on prostate cancer-specific mortality considering the determinants of treatment and prognosis.

Methods: The population-based cohort included all 844 patients having a diagnosis of localized prostate cancer between January 1, 1989, and December 31, 1998, in Geneva, Switzerland. Treatments included prostatectomy (n = 158), radiotherapy (n = 205), watchful waiting (n = 378), hormone therapy (n = 72), and other types of therapy (n = 31). We compared survival curves using the log-rank test. With multivariate Cox proportional hazards analysis and propensity score methods, we evaluated the independent effect of treatments on prostate cancer-specific mortality.

Results: Treatment options only slightly influenced 5-year prostate cancer-specific mortality but had an important effect on long-term mortality. Ten-year specific survival was 83% (95% confidence interval [CI], 73%-93%), 75% (95% CI, 67%-83%), and 72% (95% CI, 66%-80%) for patients who underwent surgery, radiotherapy, and watchful waiting, respectively (P < .001). At 10 years, patients treated with radiotherapy or watchful waiting had a significantly increased risk of death from prostate cancer compared with patients who underwent prostatectomy (multiadjusted hazard ratio, 2.3 [95% CI, 1.2-4.3] and 2.0 [95% CI, 1.1-3.8], respectively). The increased mortality associated with radiotherapy and watchful waiting was primarily observed in patients younger than 70 years and in patients with poorly differentiated tumors (Gleason score > or = 7; reference, 1 [best]-10 [worst]). Patients who received hormone therapy alone already had an increased risk of prostate cancer-specific mortality at 5 years (hazard ratio, 3.5 [95% CI, 1.4-8.7]).

Conclusions: Our study results suggest that surgery offers the best chance of long-term prostate cancer-specific survival, in particular for younger patients and patients with poorly differentiated tumors. Until clinical trials provide conclusive evidence, physicians and patients should be informed of these results and their limitations.
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http://dx.doi.org/10.1001/archinte.167.18.1944DOI Listing
October 2007

Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells.

Endocrinology 2004 Feb 30;145(2):667-78. Epub 2003 Oct 30.

Division of Clinical Biochemistry, Department of Internal Medicine, DBC-9100, University Medical Center, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.

Rat insulinoma-derived INS-1 cells constitute a widely used beta-cell surrogate. However, due to their nonclonal nature, INS-1 cells are heterogeneous and are not stable over extended culture periods. We have isolated clonal INS-1E cells from parental INS-1 based on both their insulin content and their secretory responses to glucose. Here we describe the stable differentiated INS-1E beta-cell phenotype over 116 passages (no. 27-142) representing a 2.2-yr continuous follow-up. INS-1E cells can be safely cultured and used within passages 40-100 with average insulin contents of 2.30 +/- 0.11 microg/million cells. Glucose-induced insulin secretion was dose-related and similar to rat islet responses. Secretion saturated with a 6.2-fold increase at 15 mm glucose, showing a 50% effective concentration of 10.4 mm. Secretory responses to amino acids and sulfonylurea were similar to those of islets. Moreover, INS-1E cells retained the amplifying pathway, as judged by glucose-evoked augmentation of insulin release in a depolarized state. Regarding metabolic parameters, INS-1E cells exhibited glucose dose-dependent elevations of NAD(P)H, cytosolic Ca(2+), and mitochondrial Ca(2+) levels. In contrast, mitochondrial membrane potential, ATP levels, and cell membrane potential were all fully activated by 7.5 mm glucose. Using the perforated patch clamp technique, 7.5 and 15 mm glucose elicited electrical activity to a similar degree. A K(ATP) current was identified in whole cell voltage clamp using diazoxide and tolbutamide. As in native beta-cells, tolbutamide induced electrical activity, indicating that the K(ATP)conductance is important in setting the resting potential. Therefore, INS-1E cells represent a stable and valuable beta-cell model.
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http://dx.doi.org/10.1210/en.2003-1099DOI Listing
February 2004