Publications by authors named "Antoine Poncet"

50 Publications

Time to Detection of Growth for in a Low Incidence Area.

Front Cell Infect Microbiol 2021 19;11:704169. Epub 2021 Aug 19.

Division of Pulmonary Diseases, Geneva University Hospitals, Geneva, Switzerland.

Background: Diagnosis of (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management.

Objectives: To determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB.

Methods: Retrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500'000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation.

Results: Among 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ AFB- samples, and samples from cavitary non cavitary or extra-thoracic disease.

Conclusions: In Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.
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http://dx.doi.org/10.3389/fcimb.2021.704169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418320PMC
August 2021

Inter- and intraobserver reliability assessment of the 2018 AO/OTA classification for high-energy pelvic ring injuries: A retrospective study.

Orthop Traumatol Surg Res 2021 Jun 30:102999. Epub 2021 Jun 30.

Division of Orthopaedic and Trauma Surgery, Department of Surgery, University Hospitals of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland. Electronic address:

Background: A fracture classification system should be a reliable and reproducible means of communication between different observers. It should be logical, comprehensible, and shouldn't contain an unmanageable number of categories. The aim of this study was to assess the intra- and interobserver agreement and reliability of the revised 2018 AO/OTA classification for high-energy pelvic ring injuries (PRI), at the level of the types, groups, subgroups and qualifications.

Hypothesis: Agreement and reliability of the revised 2018 AO/OTA classification for high-energy PRI are improved when compared to previous versions of the classification.

Patients And Methods: Plain radiographs and computed tomography images of a consecutive series of 86 adult patients admitted at a level I trauma center with a high-energy PRI between 01.01.2014 and 31.12.2016 were retrospectively analyzed. Three orthopedic surgeons independently classified these PRI using the 2018 AO/OTA and the Young and Burgess classifications. The senior surgeon analyzed all injuries twice, at 6 months interval, to determine intraobserver reliability. Classification agreement was assessed using percent agreement and classification reliability was assessed using kappa coefficients.

Results: For the intraobserver analysis, injury classifications with the 2018 AO/OTA classification were concordant in 88% of cases (type), 74% (group), 66% (subgroup) and 49% (qualification). Respective kappa coefficients were 0.79, 0.68, 0.62 and 0.47. Interobserver agreement declined from 77% (type) to 42% (group), 36% (subgroup) and 24% (qualification). Respective kappa coefficients were 0.72, 0.48, 0.48 and 0.37. Intraobserver (respectively interobserver) percent agreement with the Young and Burgess classification was 76% (50%) and kappa coefficient was 0.69 (0.51).

Discussion: The 2018 AO/OTA classification is a reliable tool for daily clinical use and for research purpose at the fracture type level but not at the group, subgroup and qualification levels. These results compare favorably with previously published data for older versions of the classification and may represent an improvement of the AO/OTA classification system in terms of reliability.

Level Of Evidence: III; retrospective diagnostic study.
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http://dx.doi.org/10.1016/j.otsr.2021.102999DOI Listing
June 2021

Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study.

Eur Neurol 2021 24;84(5):375-379. Epub 2021 Jun 24.

Division of Cognitive and Motor Aging, Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA.

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. The TUG was performed at baseline and subsequent evaluations occurred every 3 months. At inclusion, patients were classified as unable to perform the TUG, "slow TUG" (>10.6 s), and "fast TUG" (≤10.6 s). In total, 68 patients with ALS (mean ± SD age: 68.6 ± 11.9 years; 50% female) were included. Baseline TUG was negatively correlated with the total ALSFRS-R score (r = -0.63, p < 0.001). At baseline, ALS patients with bulbar onset performed the TUG faster (9.9 ± 3.7 s) than the non-bulbar ones (17.3 ± 14.9 s, p = 0.008). Thirty of 68 (44%) patients died by the end of the follow-up period. The TUG performance at the first visit did not predict mortality. While we did not find any association with mortality in ALS and gait quantification, the TUG was feasible in a majority of ALS patients, was correlated with functional status, and could be of interest in the follow-up of non-bulbar ALS patients.
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http://dx.doi.org/10.1159/000516772DOI Listing
June 2021

Mortality and high risk of major adverse events in patients with COVID-19 and history of cardiovascular disease.

Open Heart 2021 04;8(1)

Department of Cardiology, University Hospitals of Geneva Department of Medical Specializations, Geneva, Switzerland

Objective: History of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19.

Methods: We included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE.

Results: Median age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), p<0.001). Multivariate analyses showed that history of CVD remained an independent risk factor of in-hospital death or MACE (OR=2.4; (95% CI 1.6 to 3.5)), as did age (OR for a 10-year increase=2.2 (95% CI 1.9 to 2.6)), male gender (OR=1.6 (95% CI 1.1 to 2.3)), chronic obstructive pulmonary disease (OR=2.1 (95% CI 1.0 to 4.2)) and lung infiltration associated with COVID-19 at CT scan (OR=1.9 (95% CI 1.2 to 3.0)). History of CVD (OR=2.9 (95% CI 1.7 to 5)), age (OR=2.5 (95% CI 2.0 to 3.2)), male gender (OR=1.6 (95% CI 0.98 to 2.6)) and elevated C reactive protein (CRP) levels on admission (OR for a 10 mg/L increase=1.1 (95% CI 1.1 to 1.2)) were independent risk factors for mortality.

Conclusion: History of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.
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http://dx.doi.org/10.1136/openhrt-2020-001526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039226PMC
April 2021

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

Anesth Analg 2020 Dec 17. Epub 2020 Dec 17.

From the Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.

Background: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine.

Methods: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 μg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively.

Results: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]).

Conclusions: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.
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http://dx.doi.org/10.1213/ANE.0000000000005324DOI Listing
December 2020

Discordant diagnostic assay and treatment practice: a cross-sectional study in a tertiary care hospital, Geneva, Switzerland.

BMJ Open 2020 09 13;10(9):e036342. Epub 2020 Sep 13.

Division of Infectious Diseases, Geneva University Hospitals, Geneve, Switzerland.

Objectives: To determine the proportion of patients who received a treatment for infection (CDI) among those presenting a discordant diagnostic assay and to identify patient characteristics associated with the decision to treat CDI.

Design: Cross-sectional study.

Setting: Monocentric study in a tertiary care hospital, Geneva, Switzerland.

Participants: Among 4562 adult patients tested for between March 2017 and March 2019, 208 patients with discordant tests' results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA-)) were included.

Main Outcome Measures: Treatment for CDI.

Results: CDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95% CI 1.96 to 110.8) was the only factor associated with CDI treatment.

Conclusions: The proportion of NAAT+/EIA- patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.
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http://dx.doi.org/10.1136/bmjopen-2019-036342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488797PMC
September 2020

Walking Speed and Maximal Knee Flexion During Gait After Total Knee Arthroplasty: Minimal Clinically Important Improvement Is Not Determinable; Patient Acceptable Symptom State Is Potentially Useful.

J Arthroplasty 2020 10 26;35(10):2865-2871.e2. Epub 2020 May 26.

Clinical Research Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Clinical Epidemiology, Department of Health and Community Medicine, University Hospitals of Geneva, Geneva, Switzerland.

Background: Total knee arthroplasty (TKA) is the operation of choice in patients with end-stage knee osteoarthritis (OA). Up to 1 in 5 patients still encounter functional limitations after TKA, partly explaining patient dissatisfaction. Which gait ability to target after TKA remains unclear. To determine whether Minimal Clinical Important Improvement (MCII) or Patient Acceptable Symptom State (PASS) values could be derived from gait parameters recorded in patients with TKA. And, if so, to define those values.

Methods: In this ancillary study, we retrospectively analyzed gait parameters of patients scheduled for a unilateral TKA between 2011 and 2013. We investigated MCII and PASS values for walking speed and maximal knee flexion using anchor-based methods: 5 anchoring questions based on perceived body function and patients' satisfaction.

Results: Over the study period, 79 patients performed a clinical gait analysis the week before and 1 year after surgery, and were included in the present study. All clinical and gait parameters improved 1 year after TKA. Nevertheless, changes in gait outcomes were not associated with perceived body function or patients' satisfaction, precluding any MCII estimation in gait parameters. PASS values, however, could be determined as 1.2 m/s for walking speed and 50° for maximal knee flexion.

Conclusion: In this study, we found that MCII and PASS values are not necessarily determinable for gait parameters after TKA in patients with end-stage OA. Using anchor questions based on perceived body function and patient's satisfaction, MCII could not be defined while PASS values were potentially useful.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.arth.2020.05.038DOI Listing
October 2020

Multidisciplinary care in amyotrophic lateral sclerosis: a 4-year longitudinal observational study.

Swiss Med Wkly 2020 Jun 9;150:w20258. Epub 2020 Jun 9.

Division of Pulmonary Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland / Faculty of Medicine, University of Geneva, Switzerland.

Over a four-year period, ALS patients complied with the modalities of the multidisciplinary management follow-up without any drop-outs. The multidisciplinary management structure also contributes to increasing the experience and knowledge of the clinicians involved in managing patients suffering from this rare disease.
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http://dx.doi.org/10.4414/smw.2020.20258DOI Listing
June 2020

Feasibility and safety of high-intensity interval training for the rehabilitation of geriatric inpatients (HIITERGY) a pilot randomized study.

BMC Geriatr 2020 06 5;20(1):197. Epub 2020 Jun 5.

Division of Internal Medicine for the elderly, Trois-Chêne, Department of Rehabilitation and Geriatrics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.

Background: High-intensity interval training (HIIT) has been shown to be more effective than moderate-intensity continuous training (MICT) for the physical rehabilitation. However, data on its suitability for older hospitalized patients is scarce.

Methods: Randomized controlled trial in a hospital setting. Inclusion of 100 patients, ≥65 years old, hospitalized for rehabilitation after an acute medical condition, in a two-week rehabilitation program of either four HIIT or three MICT sessions per week. Completion was defined as participation in all but two planned sessions accomplishing ≥50% of each session. We assessed: upper-limb muscle strength (handgrip isometric strength test), lower-limb muscle strength (quadriceps and ankle flexion and extension tests); gait speed and spatio-temporal parameters (instrumented walkway), and exercise capacity (6-min walk test). All adverse events were recorded as safety endpoints.

Results: An intention-to-treat analysis showed a 44% completion rate for the HIIT group (95% CI, 30-59) and 77% for MICT (95% CI, 55-82). A modified intention-to-treat analysis restricted to patients who participated in ≥1 session showed an 88% completion rate in the HIIT group (95%CI, 69-97) and an 80% completion rate in MICT (95%CI, 65-90). The exercises most frequently undertaken were the pedal exerciser (54%) and the NuStep (32%). There were no significant differences in the various measures. No serious adverse events occurred.

Conclusion: A HIIT rehabilitation program for this population was feasible, safe and had a high adherence rate.

Trial Registration Number: Clinicatrials.gov ID: NCT02318459. Trial registration date: November 7th, 2014. Retrospectively registered. This study adheres to the CONSORT guidelines.
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http://dx.doi.org/10.1186/s12877-020-01596-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275527PMC
June 2020

Adaptive Servo-Ventilation: A Comprehensive Descriptive Study in the Geneva Lake Area.

Front Med (Lausanne) 2020 3;7:105. Epub 2020 Apr 3.

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Use of adaptive servo-ventilation (ASV) has been questioned in patients with central sleep apnea (CSA) and chronic heart failure (CHF). This study aims to detail the present use of ASV in clinical practice. Descriptive, cross-sectional, multicentric study of patients undergoing long term (≥3 months) ASV in the Cantons of Geneva or Vaud (1,288,378 inhabitants) followed by public or private hospitals, private practitioners and/or home care providers. Patients included (458) were mostly male (392; 85.6%), overweight [BMI (median, IQR): 29 kg/m (26; 33)], comorbid, with a median age of 71 years (59-77); 84% had been treated by CPAP before starting ASV. Indications for ASV were: emergent sleep apnea (ESA; 337; 73.6%), central sleep apnea (CSA; 108; 23.6%), obstructive sleep apnea (7; 1.5%), and overlap syndrome (6; 1.3%). Origin of CSA was cardiac ( = 30), neurological ( = 26), idiopathic ( = 28), or drug-related ( = 22). Among CSA cases, 60 (56%) patients had an echocardiography within the preceding 12 months; median left ventricular ejection fraction (LVEF) was 62.5% (54-65); 11 (18%) had a LVEF ≤45%. Average daily use of ASV was [mean (SD)] 368 (140) min; 13% used their device <3:30 h. Based on ventilator software, apnea-hypopnea index was normalized in 94% of subjects with data available (94% of 428). Use of ASV has evolved from its original indication (CSA in CHF) to a heterogeneous predominantly male, aged, comorbid, and overweight population with mainly ESA or CSA. CSA in CHF represented only 6.5% of this population. Compliance and correction of respiratory events were satisfactory. www.ClinicalTrials.gov, identifier: NCT04054570.
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http://dx.doi.org/10.3389/fmed.2020.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145945PMC
April 2020

GABAergic modulation of secondary hyperalgesia: A randomized controlled 4-way crossover trial with the α2-subunit preferring GABA positive allosteric modulator, N-desmethyl-clobazam in healthy volunteers.

Eur J Pain 2020 07 1;24(6):1094-1106. Epub 2020 Apr 1.

Division of Clinical Pharmacology and Toxicology, Multidisciplinary Pain Center, Geneva University Hospitals, Geneva, Switzerland.

The antihyperalgesic and sedative effects of the α2-subunit preferring GABA positive allosteric modulator (GAM), N-desmethyl-clobazam (NDMC), 20 and 60 mg, were assessed in a randomized, placebo and active-controlled (clonazepam 1,5 mg), 4-way crossover study, in healthy volunteers, using the ultraviolet B-induced experimental pain model. Single (20, 40, 60 mg) and repeated doses (20 mg over 15 days) of NDMC pharmacokinetics were evaluated. Thirty-two subjects participated in the study. Primary outcome parameter was maximal change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH). ASH decreased under all treatments. Mean (SD) relative change was 79 (22)%, 83 (24)%, 77 (30)% and 92 (16)% for placebo, NDMC20, NDMC60 and clonazepam, respectively. Neither absolute change nor relative change in ASH was significantly different between NDMC60 and placebo (mean difference = 2.3 cm [95% CI 4.0-8.5], p = .462 and 0.4% [-11.9 to 12.6], p = .952, respectively). An overall treatment effect was found on level of sedation. Compared to placebo, sedation was higher under clonazepam (mean difference = 39 mm [30-49] on a visual analogue scale, p < .001) while NDMC was free of sedative effect. NDMC pharmacokinetics after single doses showed poor absorption, but was linear. Steady-state plasma concentrations of NDMC20 were attained within 14 days, with low between-subjects variability. Mean steady-state concentration (C , SD) reached 209 (22) ng/ml. NDMC absence of sedative effect and its overall well-characterized safety coming from years of utilization as a metabolite from clobazam, raise the prospect of dose escalating trials in patients to quantify its clinical utility. SIGNIFICANCE: This article, presenting the Phase I data of the new antihyperalgesic compound, α2-subunit GABA positive allosteric modulator, N-desmethyl-clobazam (NDMC) is exploring the modulation of a new target in the treatment of neuropathic pain. Based on these results and on its preclinical properties NDMC would qualify as a good tool compound to seek confirmation of the clinical utility of selective GABA allosteric modulators in neuropathic pain patients.
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http://dx.doi.org/10.1002/ejp.1554DOI Listing
July 2020

Predicting respiratory failure in amyotrophic lateral sclerosis: still a long way to go.

Eur Respir J 2019 Aug 1;54(2). Epub 2019 Aug 1.

Division of Pulmonary Diseases, Dept of Medicine, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.1183/13993003.01065-2019DOI Listing
August 2019

Patient-adjusted deep-brain stimulation programming is time saving in dystonia patients.

J Neurol 2019 Oct 13;266(10):2423-2429. Epub 2019 Jun 13.

Division of Neurology, Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, UHN, University of Toronto, 399 Bathurst St, 7McL412, Toronto, ON, M5T 2S8, Canada.

Background: Deep-brain stimulation (DBS) programming for dystonia patients is a complex and time-consuming task.

Objective: To analyze whether programming a programming paradigm based on patient's self-adjustment is practical, effective and time saving in dystonia.

Methods: We retrospectively compared dystonia rating scales as well as the time necessary to optimize programming and the number of in-hospital visits in all patients (n = 102) operated at our center who used simple mode (SM) or advanced mode (AM) programming; the latter uses groups of different stimulation parameters and allows the patient and their caregiver to change stimulation groups at home, using the patient remote control.

Results: Both AM- and SM-allocated patients improved clinically to the same extent after DBS, as assessed by the Burke-Fahn-Marsden (BFM) and the Toronto Western Spasmodic Torticollis (TWSTRS) dystonia rating scales. All subscores improved after DBS without statistically significant differences in improvement between AM and SM (BFM: - 43% vs. - 53%, p = 0.569; TWSTRS: - 63% vs. - 72%, p = 0.781). AM and SM patients reached optimization within a similar median time [5.5 months (95% CI 4.6-6.3) for AM vs. 6.2 months (4.2-7.6) for SM, p = 0.674) but patients on advanced programming needed fewer in-hospital visits to achieve the same improvement [median of 5 visits (95% CI 4-7) for AM vs. 8 visits (7-9) for SM, p = 0.008].

Conclusions: Advanced DBS programming based on patient's self-adjustment under the supervision of the treating physician is feasible, practical and significantly reduces consultation time in dystonia patients.
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http://dx.doi.org/10.1007/s00415-019-09423-9DOI Listing
October 2019

Assessing Inspiratory Muscle Strength for Early Detection of Respiratory Failure in Motor Neuron Disease: Should We Use MIP, SNIP, or Both?

Respiration 2019;98(2):114-124. Epub 2019 Apr 24.

Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.

Background: Motor neuron disease (MND) invariably impacts on inspiratory muscle strength leading to respiratory failure. Regular assessment of sniff nasal inspiratory pressure (SNIP) and/or maximal mouth inspiratory pressure (MIP) contributes to early detection of a requirement for ventilatory support.

Objectives: The aim of this study was to compare the feasibility, agreement, and performance of both tests in MND.

Methods: Patients with MND followed by a multidisciplinary consultation were prospectively included. Pulmonary follow-up included forced expiratory volumes, vital capacity (VC) seated and supine, MIP, SNIP, pulse oximetry, and daytime arterial blood gases.

Results: A total of 61 patients were included. SNIP and MIP could not be performed in 14 (21%) subjects; 74% of the subjects showed a decrease in MIP or SNIP at inclusion versus 31% for VC. Correlation between MIP and SNIP (Pearson's rho: 0.68, p < 0.001) was moderate, with a non-significant bias in favor of SNIP (3.6 cm H2O) and wide limits of agreement (-34 to 41 cm H2O). Results were similar in "bulbar" versus "non-bulbar" patients. At different proposed cut-off values for identifying patients at risk of respiratory failure, the agreement between MIP and SNIP (64-79%) and kappa values (0.29-0.53) was moderate.

Conclusions: MIP and SNIP were equally feasible. There was no significant bias in favor of either test, but a considerable disparity in results between tests, suggesting that use of both tests is warranted to screen for early detection of patients at risk of respiratory failure and avoid over diagnoses. SNIP, MIP, and VC all follow a relatively linear downhill course with a steeper slope for "bulbar" versus "non-bulbar" patients.
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http://dx.doi.org/10.1159/000498972DOI Listing
September 2020

Comparison of the contributions of female and male authors to medical research in 2000 and 2015: a cross-sectional study.

BMJ Open 2019 02 13;9(2):e024436. Epub 2019 Feb 13.

Medical Directorate / Division of Clinical Epidemiology, Hopitaux Universitaires de Geneve, Geneva, GE, Switzerland.

Objectives: The proportion of women engaged in clinical research has increased over time. However, it is unclear if women and men contribute to the same extent during the conduct of research and, if so, if they are equally rewarded by a strategic first or last author position. We aim to describe the prevalence of women authors of original articles published 15 years apart and to compare the research contributions and author positions according to gender.

Design: Repeated cross-sectional study.

Setting: Published original articles.

Participants: 1910 authors of 223 original articles published in the in 2000 and 2015.

Primary And Secondary Outcomes Measures: Self-reported contributions to 10 aspects of the article (primary) and author position on the byline.

Results: The proportion of women authors increased from 32% (n=243) to 41% (n=469) between 2000 and 2015 (p<0.0001). In 2000, women authors were less frequently involved than men in the conception and design (134 (55%) vs 323 (61%); p=0.0256), critical revision (171 (70%) vs 426 (81%); p=0.0009), final approval (196 (81%) vs 453 (86%); p=0.0381) and obtaining of funding (39 (16%) vs 114 (22%); p=0.0245). Women were more frequently involved than men in administration and logistics (85 (35%) vs 137 (26%); p=0.0188) and data collection (121 (50%) vs 242 (46%); p=0.0532), but they were similarly involved in the analysis and interpretation of data, drafting of the manuscript, provision of materials/patients and statistical expertise. Women were less often last authors than men (22 (9%) vs 82 (16%); p=0.0102). These gender differences persisted in 2015.

Conclusions: The representation of women among authors of medical articles increased notably between 2000 and 2015, but still remained below 50%. Women's roles differed from those of men with no change over time.
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http://dx.doi.org/10.1136/bmjopen-2018-024436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398775PMC
February 2019

Cost-effectiveness evaluation of HPV self-testing offered to non-attendees in cervical cancer screening in Switzerland.

Gynecol Oncol 2019 04 1;153(1):92-99. Epub 2019 Feb 1.

Division of Clinical Epidemiology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.

Objective: About 30% of women who are eligible for cervical cancer (CC) screening remain un-screened or under-screened in Switzerland. HPV testing on self-collected vaginal samples (Self-HPV) has shown to be more sensitive than cytology while also reaching non-attendees. The objective of this study was to explore the cost-effectiveness of offering Self-HPV to non-attendees in Switzerland.

Methods: A recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: Self-HPV and triage with colposcopy (Self-HPV/colpo), Self-HPV and triage with Pap cytology (Self-HPV/PAP), cytological screening and triage with HPV (PAP/HPV). Sensitivity analyses for the key parameters of the model were conducted to check the robustness of findings.

Results: Offering a Self-HPV screening to non-attendees could prevent 90% of CC and 94% of CC-related deaths in the study population. The current cytology-based program could reduce by 83% the number of CC cases and by 88% the number of CC-related deaths over the population's lifetime. Compared to the absence of screening, incremental cost-effectiveness ratios (ICER) were estimated to be, per saved Quality Adjusted Life Year (QALY), 12413US$ for the strategy Self-HPV/colpo, 11138US$ for the strategy Self-HPV/Pap and 22488US$ for the strategy PAP/HPV.

Conclusions: Offering Self-HPV as a CC screening strategy to non-attendees in Switzerland is a cost-effective solution that is associated with a reduction of CC cases and related deaths. Self-HPV is more cost-effective than the currently used cytology-based screening.
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http://dx.doi.org/10.1016/j.ygyno.2019.01.021DOI Listing
April 2019

Factors Influencing the Filing of Complaints, Their Investigation, and Subsequent Legal Judgment in Cases of Sexual Assault.

J Forensic Sci 2019 Jul 17;64(4):1119-1124. Epub 2018 Dec 17.

University Center of Legal Medicine, Geneva and Lausanne, Geneva site de Genève, 1 rue Michel Servet, 1211, Genève 4, Switzerland.

In Geneva, examination of victims of sexual assault is performed by a gynecologist and a medical examiner. 48% of the victims file a complaint and we wanted to investigate the factors leading to file a complaint, those leading the Prosecutor to go to trial, and those influencing a conviction. Between 2006 and 2012, 676 victims of sexual assault were investigated (averaged age 26 year, mean 22). Information on injuries, perpetrators, and circumstances of the assault was collected and analyzed. The attacker being the ex-spouse or a friend and the presence of semen were factors leading to file a complaint. The assailant being a family member or ex-spouse and the presence of genital/anal lesions were factors influencing the Prosecutor. The presence of nongenital lesions, the assailant being known by the victim, influenced conviction. This study shows that the medical examiner plays a vital role in the investigation of cases of sexual assault.
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http://dx.doi.org/10.1111/1556-4029.13971DOI Listing
July 2019

Accuracy of whole-body HDP SPECT/CT, FDG PET/CT, and their combination for detecting bone metastases in breast cancer: an intra-personal comparison.

Am J Nucl Med Mol Imaging 2018 5;8(3):159-168. Epub 2018 Jun 5.

Department of Nuclear Medicine, Geneva University and University Hospitals of Geneva Rue Gabrielle-Perret-Gentil, 4, CH-1211 Geneva, Switzerland.

New generation SPECT/CT scanners allow rapid whole-body imaging, and potentially facilitate significantly improved diagnostic accuracy. Thus, the aim of this study was to compare the diagnostic accuracy of whole-body Tc-99m-HDP SPECT/CT, F-18-FDG PET/CT, and their combination for detecting bone metastases in breast cancer. Women with biopsy-proven breast cancer that were referred for whole-body SPECT/CT and FDG PET/CT were consecutively included in this retrospective study. Two blinded readers independently interpreted all scans. In a per-patient analysis, the diagnostic performances of whole-body SPECT/CT, FDG PET/CT, and their combination were compared using (ROC) analysis. In a per-lesion analysis, the performances were compared using figures of merit (FoM) differences in ROC analysis, which considers the location information. Follow-up served as reference standard. Overall, 25 consecutive women (median age: 55; range 38-82) with 117 lesions were included. The median follow-up was 21 months (2-46 months). The per-patient analysis revealed no significant differences in diagnostic performance (P = 0.16), while the per-lesion analysis revealed a diagnostic superiority of whole-body SPECT/CT over FDG PET/CT (P = 0.004). Specifically, the PET/CT FoM was significantly lower than the SPECT/CT FoM (FoM difference = -0.11, 95% CI [-0.21; -0.02], P = 0.021). No significant difference was observed between SPECT/CT and the combination of SPECT/CT and PET/CT. The per-lesion analysis suggest that SPECT/CT has a higher diagnostic accuracy than FDG PET/CT for the detection of bone metastases. Thus, SPECT/CT may be a useful adjunct to FDG PET/CT for staging of breast cancer patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056244PMC
June 2018

Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine.

Pharmacogenomics J 2019 04 3;19(2):211-218. Epub 2018 Jan 3.

Division of Nephrology, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.

Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA. A semi-Markovian model was developed to simulate the progress of a cohort of adult men and women who received clozapine as a third-line antipsychotic medication. We compared current practices using two genotype-guided strategies: (1) HLA genotyping followed by clozapine, with ANCM only for patients who tested positive for one or both alleles (genotype-guided blood sampling); (2) HLA genotyping followed by clozapine for low-risk patients and alternative antipsychotics for patients who tested positive (clozapine substitution scheme). Up to a decision threshold of $3.9 million per quality-adjusted life-year (90-fold the US gross domestic product per capita), the base-case results indicate that compared with current ANCM, genotype-guided blood sampling prior to clozapine initiation appeared cost-effective for targeted blood monitoring only in patients with HLA susceptibility alleles. Sensitivity analysis demonstrated that at a cost of genotype testing of up to USD700, HLA genotype-guided blood monitoring remained a cost-effective strategy compared with either current ANCM or clozapine substitution.
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http://dx.doi.org/10.1038/s41397-017-0004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462824PMC
April 2019

Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test.

Clin Neurophysiol 2018 01 28;129(1):51-58. Epub 2017 Oct 28.

Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

Objective: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders.

Methods: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle.

Results: Responses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, -0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested.

Conclusions: Maximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle.

Significance: These findings may provide clues to understand the changes observed in neuromuscular disorders.
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http://dx.doi.org/10.1016/j.clinph.2017.10.013DOI Listing
January 2018

Thinker, Soldier, Scribe: cross-sectional study of researchers' roles and author order in the .

BMJ Open 2017 06 24;7(6):e013898. Epub 2017 Jun 24.

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

Objective: How researchers' contributions relate to author order on the byline remains unclear. We sought to identify researchers' contributions associated with author order, and to explore the existence of author profiles.

Design: Observational study.

Setting: Published record.

Participants: 1139 authors of 119 research articles published in 2015 in the .

Primary Outcomes: Presence or absence of 10 contributions, reported by each author, published in the journal.

Results: On average, first authors reported 7.1 contributions, second authors 5.2, middle authors 4.0, penultimate authors 4.5 and last authors 6.4 (p<0.001). The first author made the greatest contributions to drafting the article, designing the study, analysing and interpreting the data, and providing study materials or patients. The second author contributed to data analysis as well and to drafting the article. The last author was most involved in obtaining the funding, critically revising the article, designing the study and providing support. Factor analysis yielded three author profiles- (study design, revision of article, obtaining funding), (providing material or patients, providing administrative and logistical support, collecting data) and (analysis and interpretation of data, drafting the article, statistical expertise). These profiles do not strictly correspond to byline position.

Conclusions: First, second and last authors of research articles made distinct contributions to published research. Three authorship profiles can be used to summarise author contributions. These findings shed light on the organisation of clinical research teams and may help researchers discuss, plan and report authorship in a more transparent way.
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http://dx.doi.org/10.1136/bmjopen-2016-013898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577892PMC
June 2017

Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: Evidence from a randomised controlled trial in Nepal.

PLoS Negl Trop Dis 2017 May 16;11(5):e0005612. Epub 2017 May 16.

Division of Tropical and Humanitarian Medicine, University Hospitals of Geneva, Geneva, Switzerland.

Background: Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming.

Methodology/ Principal Findings: This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom.

Conclusions: This first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients' outcomes.

Trial Registration: The study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1).
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http://dx.doi.org/10.1371/journal.pntd.0005612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446183PMC
May 2017

Determinants of the calibration of SAPS II and SAPS 3 mortality scores in intensive care: a European multicenter study.

Crit Care 2017 04 4;21(1):85. Epub 2017 Apr 4.

Clinical Research Center, Faculty of Medicine, University of Geneva, Geneva 4, 1211, Geneva, Switzerland.

Background: The aim of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 is to predict the mortality of patients admitted to intensive care units (ICUs). Previous studies have suggested that the calibration of these scores may vary across countries, centers, and/or characteristics of patients. In the present study, we aimed to assess determinants of the calibration of these scores.

Methods: We assessed the calibration of the SAPS II and SAPS 3 scores among 5266 patients admitted to ICUs during a 4-week period at 120 centers in 17 European countries. We obtained calibration curves, Brier scores, and standardized mortality ratios. Points attributed to SAPS items were reevaluated and compared with those of the original scores. Finally, we tested associations between the calibration and center characteristics.

Results: The mortality was overestimated by both scores: The standardized mortality ratios were 0.75 (95% CI 0.71-0.79) for the SAPS II score and 0.91 (95% CI 0.86-0.96) for the SAPS 3 score. This overestimation was partially explained by changes in associations between some items of the scores and mortality, especially the heart rate, Glasgow Coma Scale score, and diagnosis of AIDS for SAPS II. The calibration of both scores was better in countries with low health expenditures. The between-center variability in calibration curves was much greater than expected by chance.

Conclusions: Both scores overestimate current mortality among European ICU patients. The magnitude of the miscalibration of SAPS II and SAPS 3 scores depends not only on patient characteristics but also on center characteristics. Furthermore, much between-center variability in calibration remains unexplained by these factors.

Trial Registration: ClinicalTrials.gov identifier: NCT01422070 . Registered 19 August 2011.
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http://dx.doi.org/10.1186/s13054-017-1673-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379500PMC
April 2017

Respiratory weakness after mechanical ventilation is associated with one-year mortality - a prospective study.

Crit Care 2016 07 31;20(1):231. Epub 2016 Jul 31.

University of Applied Sciences and Arts Western Switzerland (HES-SO), Lausanne, Switzerland.

Background: Diaphragm dysfunction in mechanically ventilated patients is associated with poor outcome. Maximal inspiratory pressure (MIP) can be used to evaluate inspiratory muscle function. However, it is unclear whether respiratory weakness is independently associated with long-term mortality. The aim of this study was to determine if low MIP is independently associated with one-year mortality.

Methods: We conducted a prospective observational cohort study in an 18-bed ICU. Adults requiring at least 24 hours of mechanical ventilation with scheduled extubation and no evidence of pre-existing muscle weakness underwent MIP evaluation just before extubation. Patients were divided into two groups: low MIP (MIP ≤30 cmH2O) and high MIP (MIP >30 cmH2O). Mortality was recorded for one year after extubation. For the survival analysis, the effect of low MIP was assessed using the log-rank test. The independent effect of low MIP on post mechanical ventilation mortality was analyzed using a multivariable Cox regression model.

Results: One hundred and twenty-four patients underwent MIP evaluation (median age 66 years (25(th)-75(th) percentile 56-74), Simplified Acute Physiology Score (SAPS) 2 = 45 (33-57), duration of mechanical ventilation 7 days (4-10)). Fifty-four percent of patients had low MIP. One-year mortality was 31 % (95 % CI 0.21, 0.43) in the low MIP group and 7 % (95 % CI 0.02, 0.16) in the high MIP group. After adjustment for SAPS 2 score, body mass index and duration of mechanical ventilation, low MIP was independently associated with one-year mortality (hazard ratio 4.41, 95 % CI 1.5, 12.9, p = 0.007). Extubation failure was also associated with low MIP (relative risk 3.0, 95 % CI 1, -9.6; p = 0.03) but tracheostomy and ICU length of stay were not.

Conclusion: Low MIP is frequent in patients on mechanical ventilation and is an independent risk factor for long-term mortality in ICU patients requiring mechanical ventilation. MIP is easily evaluated at the patient's bedside.

Trial Registration: This study was retrospectively registered in www.clinicaltrials.gov (NCT02363231) in February 2015.
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http://dx.doi.org/10.1186/s13054-016-1418-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967510PMC
July 2016

Snapshot of the prescribing practice for the clopidogrel and esomeprazole coprescription and cost evaluation of the application guidelines.

Pharmacol Res Perspect 2016 06 21;4(3):e00234. Epub 2016 Apr 21.

Division of Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland; School of Pharmaceutical Sciences University of Geneva University of Lausanne Geneva University Hospitals Geneva Switzerland.

The antiplatelet clopidogrel and the proton pump inhibitor esomeprazole demonstrate a pharmacokinetic interaction through CYP2C19 that could translate into clinical inefficacy of clopidogrel. No medical consensus as to their coprescription has been reached, and different guidelines are available. We evaluated the prescribing practices at the Geneva University Hospitals (HUG) by measuring whether the coprescription was staggered as suggested by experts. We estimated the financial impact of different implementation guidelines. We used the HUG electronic patient records to follow the physicians' prescriptions and the administration by nurses from January 2013 to April 2014. We performed a time series analysis to assess 15 years of proton pump inhibitors (PPIs) and antiplatelet drug use. "Extra costs" were calculated assuming that clopidogrel or esomeprazole would replace prasugrel or ticagrelor and pantoprazole or ranitidine, respectively. Only 10.8% of the patient medical orders for the clopidogrel and esomeprazole coprescription specified to stagger the administration, 12.6% specified a concomitant coprescription, and 76.6% had no clear information. A high rate of 49.6% of the nurses staggered the clopidogrel and esomeprazole coprescription when no clear information was given. We found a statistically significant decrease in clopidogrel use after the publication of the OCLA (Omeprazole-CLopidogrel-Aspirin) study and a significant increase in the trend of esomeprazole. Alternative treatments to avoid this interaction are cost ineffective or offer therapeutic options of lesser quality. We observed a high rate of 56.2% of the clopidogrel and esomeprazole coprescription in our hospital and can therefore not ignore the PK/PD interaction. The most common prescription practice was to not specify the time frame of administration, which was translated by nurses in 49.6% of the cases to a scheduled staggered coprescription of clopidogrel and esomeprazole. As long as no consensus has been reached, the medical orders time frame information should be mandatory to allow a clear and harmonious staggering strategy.
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http://dx.doi.org/10.1002/prp2.234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876144PMC
June 2016

Establishing On-Site Reference Values for (123)I-FP-CIT SPECT (DaTSCAN®) Using a Cohort of Individuals with Non-Degenerative Conditions.

Mol Imaging Biol 2016 Apr;18(2):302-12

Department of Neurology, Geneva University Hospitals, 4, rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.

Purpose: To overcome the issue of reference values for DaTSCAN® requiring healthy controls, we propose an original approach using scans from individuals with non-degenerative conditions performed at one single center following the same acquisition protocol.

Procedures: From a cohort of 970 consecutive patients, we identified 182 patients with a clinical diagnosis of non-degenerative parkinsonism or tremor and a visually normal DATSCAN®. Caudate nucleus (C), putamen (P), and striatum (S) uptake values, C/P ratios, and asymmetry indexes (AI) were calculated using semi-quantitative methods. Outcomes were assessed according to age and gender, and reference limits were established using the percentile approach.

Results: A significant negative linear effect of age was found upon striatal nuclei uptake of 0.21-0.22 per decade (6.8%/decade for striatum), whereas a potential gender influence proved unclear. Inferior reference limits were established at the 5th percentile. C/P ratios and AIs were not influenced by age or gender, and superior reference limits were set at the 95th percentile.

Conclusions: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects.
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http://dx.doi.org/10.1007/s11307-015-0889-6DOI Listing
April 2016

Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis.

PLoS One 2015 12;10(6):e0127213. Epub 2015 Jun 12.

Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals and University of Geneva, rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; Medical Directorate, University Hospitals and University of Geneva, rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; Centre for Health Economics, University of York, Heslington,York, United Kingdom.

Importance: Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality.

Objective: To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients.

Design, Setting, And Participants: We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER).

Main Outcomes And Measures: Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY).

Results: In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT.

Conclusion And Relevance: In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127213PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466505PMC
April 2016

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases--a longitudinal study.

Arthritis Res Ther 2015 Jun 6;17:151. Epub 2015 Jun 6.

Division of Clinical Immunology and Allergy, Department of Medical Specialties, University Hospital and Faculty of Medicine, Geneva, Switzerland.

Introduction: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects.

Methods: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients.

Results: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30%) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81% of patients, and 87% became seropositive. After 1 year, 67% of vaccinated compared with 90% of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections.

Conclusions: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections.
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http://dx.doi.org/10.1186/s13075-015-0663-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481118PMC
June 2015
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