Cancer outpatients during the COVID-19 pandemic: what Oncoral has to teach us about medical drug use and the perception of telemedicine.

PURPOSE: The COVID-19 pandemic has disrupted healthcare access and telemedicine has been widely deployed. The aim of this study is to assess the impact of this health crisis on treatment consumption and telemedicine development in outpatients treated by oral anti-cancer agents and followed by the Oncoral hospital/community multidisciplinary program where continuity care is maintained by a pharmacist/nurse pair. METHODS: A prospective monocentric study was conducted among cancer patients who received Oncoral telephone follow-up during the 1st lockdown in France using a 56-item questionnaire which covered sociodemographic data, patient medication management, and telehealth. RESULTS: 178 patients received Oncoral follow-up during the 1st lockdown and 67.4% responded to the questionnaire. During lockdown, 9.2% of patients took medication or CAM for fatigue, 6.7% for mood alteration, 10.8% for sleep disorder, 11.7% for stress and anxiety, and 12.5% to get more energy. Homeopathy consumption was triggered by the pandemic. Habits about getting drugs from the pharmacy changed significantly (p < 0.001), while other treatment habits did not. 83% of patients were satisfied by the telephone follow-up established, 69% would be in favor of repeating this in case of a new epidemic wave. Those most in favor of using telemedicine seemed to be the youngest (p < 0.001), with several dependent children (p < 0.007), high school degree or higher education (p = 0.023), and in work (p < 0.001). CONCLUSION: Health system reorganization enables to limit the impact of the crisis on patients' drug use in oncology care. Telemedicine is a promising public health tool.

[Thesaurus of pharmacist interventions associated with inappropriate proton pump inhibitors prescriptions]. / Thésaurus d'interventions pharmaceutiques associées aux prescriptions injustifiées d'inhibiteurs de la pompe à protons.

OBJECTIVES: Proton pump inhibitors (PPI) are the most effective drugs in the treatment of acid-related gastrointestinal disorders. Yet, many studies reported potential adverse drug reactions associated with long-term use. In order to reduce the rates of inappropriate PPI prescriptions and to improve patient safety, a tool aimed at guiding pharmacists to analyze PPI prescriptions was designed. It results in a thesaurus of clinical situations designed to argue about the inappropriateness of some PPI prescriptions and to highlight the risk associated with them. METHODS: Clinical situations in which PPIs are inappropriate were identified by four pharmacists in one gastroenterological, one surgery/liver transplantation, one internal medicine and one oncology units. A scientific literature search was performed for each clinical situation in order to corroborate the pharmacist interventions. RESULTS: The thesaurus comprises two parts, the first one is dedicated to 12 clinical situations in which a PPI is not required (acute pancreatitis, cholecystectomy etc.), while the second one focus on 22 situations in which PPIs are associated with specific adverse drug reactions (Clostridium difficile infection, vitamin deficiency etc.). Eighty-one articles were used to support the pharmacist interventions. CONCLUSION: This thesaurus is an analysis tool aimed at guiding pharmacists identify and argue about the inappropriateness of some PPI prescriptions in order to convince doctors to discontinue or not to initiate PPI prescriptions.

Real-life drug-drug and herb-drug interactions in outpatients taking oral anticancer drugs: comparison with databases.

PURPOSE: Due to polypharmacy and the rising popularity of complementary and alternative medicines (CAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drug. METHOD: All prescribed and non-prescribed medications, including CAM, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis. RESULTS: 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one CAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%). CONCLUSION: Potentially clinically relevant drug interaction were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

Thromboembolic events and thromboprophylaxis associated with immunomodulators in multiple myeloma patients: a real-life study.

PURPOSE: The aim of this study is to assess international guidelines implementation concerning thromboprophylaxis strategy in myeloma patients treated with immunomodulatory drugs. METHODS: This retrospective study includes multiple myeloma patients treated with immunomodulatory drugs between 2014 and 2017 in the Hematology department of a teaching hospital (Hospices Civils de Lyon, France) and followed by the multidisciplinary care plan for cancer outpatients ONCORAL (ONCological care for outpatients with ORAL anticancer drugs). Data from immunomodulatory drugs administration, thromboprophylaxis strategy and thrombotic events were collected from medical files. Adherence to 2010 International Myeloma Working Group (IMWG) guidelines was assessed. RESULTS: 213 patients received at least one immunomodulatory drug: lenalidomide (60.9%), pomalidomide (24.0%) and thalidomide (15.1%). About two third of treatment lines (66.2%) were in accordance with IMWG recommendations. Among the others, 30.5% and 69.5% had thromboprophylaxis, respectively, superior or inferior to IMWG recommendations. 37 venous thrombotic events and 4 arterial thromboembolisms (one patient experienced both a stroke and deep venous thrombosis simultaneously) were reported. CONCLUSION: Thromboprophylaxis was systematically performed in myeloma patients treated with immunomodulatory drugs in this real-life retrospective cohort. However, the choice of anticoagulant or anti-platelet agent remains debatable, as adherence to existing guidelines was variable.

Applying a Constrained Optimization Portfolio Model to Aid Prioritization of Public Health Interventions in Malaysia.

OBJECTIVES: Countries have constrained healthcare budgets and must prioritize new interventions depending on health goals and time frame. This situation is relevant in the sphere of national immunization programs, for which many different vaccines are proposed, budgets are limited, and efficient choices must be made in the order of vaccine introduction. METHODS: A constrained optimization (CO) model for infectious diseases was developed in which different intervention types (prophylaxis and treatment) were combined for consideration in Malaysia. Local experts defined their priority public health issues: pneumococcal disease, dengue, hepatitis B and C, rotavirus, neonatal pertussis, and cholera. Epidemiological, cost, and effectiveness data were informed from local or regionally published literature. The model aimed to maximize quality-adjusted life-year (QALY) gain through the reduction of events in each of the different diseases, under budget and intervention coverage constraints. The QALY impact of the interventions was assessed over 2 periods: lifetime and 20 years. The period of investment was limited to 15 years. RESULTS: The assessment time horizon influenced the prioritization of interventions maximizing QALY gain. The incremental health gains compared with a uninformed prioritization were large for the first 8 years and declined thereafter. Rotaviral and pneumococcal vaccines were identified as key priorities irrespective of time horizon, hepatitis B immune prophylaxis and hepatitis C treatment were priorities with the lifetime horizon, and dengue vaccination replaced these with the 20-year horizon. CONCLUSIONS: CO modeling is a useful tool for making economically efficient decisions within public health programs for the control of infectious diseases by helping prioritize the selection of interventions to maximize health gain under annual budget constraints.

The hydrolysis of epoxides catalyzed by inorganic ammonium salts in water: kinetic evidence for hydrogen bond catalysis.

Naturally-occurring inorganic ammonium ions have been recently reported as efficient catalysts for some organic reactions in water, which contributes to the understanding of the chemistry in some natural environments (soils, seawater, atmospheric aerosols, …) and biological systems, and is also potentially interesting for green chemistry as many of their salts are cheap and non-toxic. In this work, the effect of NH4+ ions on the hydrolysis of small epoxides in water was studied kinetically. The presence of NH4+ increased the hydrolysis rate by a factor of 6 to 25 compared to pure water and these catalytic effects were shown not to result from other ions, counter-ions or from acid or base catalysis, general or specific. The small amounts of amino alcohols produced in the reactions were identified as the actual catalysts by obtaining a strong acceleration of the reactions when adding these compounds directly to the epoxides in water. Replacing the amino alcohols by other strong hydrogen-bond donors, such as trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) gave the same results, demonstrating that the kinetics of these reactions was driven by hydrogen-bond catalysis. Because of the presence of many hydrogen-bond donors in natural environments (for instance amines and hydroxy-containing compounds), hydrogen-bond catalysis is likely to contribute to many reaction rates in these environments.

[Diagnostic issues of lymphogranuloma venereum: A case series of 5 patients]. / Diagnostic de la lymphogranulomatose vénérienne : à propos d'une série de 5 cas.

INTRODUCTION: Lymphogranuloma venereum (LG) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis L serovar. METHODS: These five consecutive cases aim to highlight the risk of LG misdiagnosis, in case of initial presentation with isolated inguinal adenitis. RESULTS: Five men (mean age: 30±7 years) were seen in an internal medicine department, for inguinal adenopathy. One patient had clinical signs of urethritis. None presented an associated rectitis. Three patients had a history of STI, and two had a discovery of related HIV disease. Urinary polymerase chain reaction (PCR) was positive for the symptomatic patient and negative for the others. Lymph node PCR was positive in all patients within a L2b serotype (searched in 4 out of 5 cases). CONCLUSION: LG should be evoked in any patient with inguinal adenomegaly, particularly in case of STI history or risk factors. Negativity of urinary PCR should lead to further investigations, essentially a lymph node cytopuncture to evidence C. trachomatis.

[Medico-economic evaluation of therapeutic strategies at hospital: A systematic review of French studies]. / L'évaluation médico-économique des stratégies thérapeutiques en milieu hospitalier : une revue systématique des travaux français.

INTRODUCTION: Therapeutic innovation contributes to the increase of health care expenditures in France. Medico-economic evaluation has still a minor role in the decision-making for the registration of drugs and medical devices in hospitals. This study aimed to systematically review published works on medico-economic studies conducted within French hospitals. METHODS: A literature review was carried out to search for medico-economic studies conducted by hospital teams on therapeutic or diagnostic strategies employed within French hospitals and published from 2010 to 2014. Quality assessment of selected studies was performed according to Drummond et al.'s checklist, which is also used within French guidelines. RESULTS: Of the 44 analyzed articles, methods for identification and measure of costs and results complied with guidelines in 95 % of cases. For results interpretation, compliance was 91 %. Costs discounting (29 %) and the use of sensitivity analysis to account for results uncertainty (70 %) were the parameters with the lowest compliance to guidelines. CONCLUSION: A good training of health professionals in using economic and statistic tools, and the transferability of results of medico-economic studies are essential and should be optimized to enable a broader use of medico-economic evaluation within the scope of decision-making in French hospitals.

[Care pathway for high urinary tract infection: an update in an emergency department of a French military hospital]. / Parcours de prise en charge des infections urinaires hautes: état des lieux aux urgencies d'un établissement militaire français.

Objectives Assessing the impact of professional practices on a patient's course is an interesting way to optimize health care pathway. The aim of our study is to update and evaluate the compliance to the recommendations of the Societe de Pathologie Infectieuse de Langue Francaise with regards to professional practices and the route of patients admitted to the emergency department of a French military hospital for high urinary tract infection. Patients and methods A retrospective study was carried out on patients admitted to the emergency department and treated for high urinary tract infection from January 1st, 2015 to April 30th, 2015. Clinical and administrative data, medical exams, and antibiotic prescriptions were extracted from computerized patient medical files and from emergency medical files. Results Out of 91 medical cares, 57% were compliant with the recommendations. For 60% of the patients, blood cultures were not argued and in 70% of cases, imaging wasn't justified. Antibiotic prescriptions were not compliant in 31% of cases, mostly due to long prescription durations. Two third of patients received outpatient care. All hospitalizations were argued. Conclusions Drawing up a caring protocol, regularly raising awareness to the good use of antibiotics, as well as reinforcing a cross disciplinary approach will allow optimizing health care pathways for patients coming to the emergency department with high urinary tract infection.

[Advantages and special features of hospital preparations of parenteral nutrition in neonatalogy]. / Avantages et spécificités des préparations hospitalières de nutrition parentérale en néonatalogie.

INTRODUCTION: The care of premature infants requires specific, suitable parenteral nutrition, in which the dosage must be frequently adjusted. METHOD: A comparative analysis of four industrial standard parenteral nutrition formulations NP 100®, Pediaven AP-HP Nouveau-né 1®, Pediaven AP-HP Nouveau-né 2® and Numetah G13% E® and of two hospital preparations made specifically in hospital pharmacies produced by two separate university hospitals (Nutrine® HCL and Formule standardisée début de nutrition) was conducted. The comparison between the formulations focused on electrolytic compositions and protein/energy ratio. RESULTS: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are free from (i) sodium and potassium, (ii) potassium respectively. Almost equivalent sodium concentration (19-27 mM) and more variable potassium concentration (∼9-26 mM) characterize the other formulations. Protein/energy ratio of Numetah G13% E®, Nutrine® HCL and Formule standardisée début de nutrition is 58% higher than that of NP 100®, Pediaven AP-HP Nouveau-né 1® and Pediaven AP-HP Nouveau-né 2®. DISCUSSION: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are in accordance with the recommendations about hydro-electrolytic supplies during transition phase. Nutrine® HCL complies best to the recommendations about hydro-electrolytic account during stabilization phase. CONCLUSION: Hydro-electrolytic composition and protein/energy ratio of standard hospital parenteral nutrition formulations comply best to nutritional needs of premature infants.

Budget constraint and vaccine dosing: a mathematical modelling exercise.

BACKGROUND: Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective. METHODS: An optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example. RESULTS: With a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ≥5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development. CONCLUSIONS: Under budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.

Economics of vaccines revisited.

Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model; (1) appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment; (2) the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries; (3) and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison. (4.)

Rotavirus vaccine series completion and adherence to vaccination schedules among infants in managed care in the United States.

BACKGROUND: Two rotavirus vaccines are currently approved in the United States: 3-dose RotaTeq (RV5; Merck & Co., Inc., Whitehouse Station, NJ, USA) is administered at ages 2, 4, and 6 months; and 2-dose Rotarix (RV1; GlaxoSmithKline, Research Triangle Park, NC, USA) is administered at ages 2 and 4 months. Our objective was to compare rotavirus vaccine series completion and dosing schedule compliance between cohorts of infants who received these vaccines. METHODS: Infants aged less than 1 year who initiated a rotavirus vaccine series between 01 January 2009 and 30 June 2009 were identified in US health insurance claims data. Cohorts were formed based on vaccine brand use. Series completion and compliance with the FDA-approved and ACIP-recommended harmonized schedules were analyzed descriptively and a log binomial model was used to estimate the difference in series completion by vaccine brand while adjusting for demographic variables. RESULTS: Among infants in the RV1 and RV5 cohorts (N=55,584), 84.3% completed a full series. A greater proportion of the RV1 cohort than the RV5 cohort completed their series (91.0% vs. 83.4%; P<0.001; multivariate-adjusted relative risk 1.07; 95% CI 1.06-1.08). In the RV1 and RV5 cohorts, respectively, 75.0% and 59.5% of infants were fully compliant with the FDA-approved administration schedule for their vaccine (P<0.001); 83.3% and 76.4% of infants were fully compliant with the harmonized schedule (P<0.001). CONCLUSIONS: The proportion of infants that completed the series was greater and compliance with respective FDA-approved and harmonized dosing schedules was higher among infants vaccinated with RV1 than among infants who received RV5.

Non-oxidative coupling of methane catalysed by supported tungsten hydride onto alumina and silica-alumina in classical and H2 permeable membrane fixed-bed reactors.

Non-oxidative coupling of methane with high selectivity into ethane (>99% among hydrocarbon) in a classical fixed-bed reactor catalysed by SiO(2)-Al(2)O(3) or gamma-Al(2)O(3) supported tungsten hydride is presented. Continuous hydrogen separation, using a Pd-Ag membrane in a fixed-bed reactor, led to methane coupling far beyond the thermodynamic equilibrium conversion.

Dinitrogen dissociation on an isolated surface tantalum atom.

Both industrial and biochemical ammonia syntheses are thought to rely on the cooperation of multiple metals in breaking the strong triple bond of dinitrogen. Such multimetallic cooperation for dinitrogen cleavage is also the general rule for dinitrogen reductive cleavage with molecular systems and surfaces. We have observed cleavage of dinitrogen at 250 degrees C and atmospheric pressure by dihydrogen on isolated silica surface-supported tantalum(III) and tantalum(V) hydride centers [(identical with Si-O)2Ta(III)-H] and [(identical with Si-O)2Ta(V)H3], leading to the Ta(V) amido imido product [(identical with SiO)2Ta(=NH)(NH2)]: We assigned the product structure based on extensive characterization by infrared and solid-state nuclear magnetic resonance spectroscopy, isotopic labeling studies, and supporting data from x-ray absorption and theoretical simulations. Reaction intermediates revealed by in situ monitoring of the reaction with infrared spectroscopy support a mechanism highly distinct from those previously observed in enzymatic, organometallic, and heterogeneous N2 activating systems.

A biomechanical review of factors affecting rowing performance.

This review analyses rowing by linking the biological and mechanical systems that comprise the rowing system. Blade force was found to be the only propulsive force to counter the drag forces, consisting of both air drag and hydrodynamic drag, acting on the system. Vertical oscillations of the shell are shown to have minimal impact on system dynamics. The oar acts as the link between the force generated by the rower and the blade force and transmits this force to the rowing shell through the oarlock. Blade dynamics consist of both lift and drag mechanisms. The force on the oar handle is the result of a phased muscular activation of the rower. Oar handle force and movement are affected by the joint strength and torque-velocity characteristics of the rower. Maximising sustainable power requires a matching of the rigging setup and blade design to the rower's joint torque-velocity characteristics. Coordination and synchrony between rowers in a multiple rower shell affects overall system velocity. Force-time profiles should be better understood to identify specific components of a rower's biomechanics that can be modified to achieve greater force generation.