[Comparative study of production and control processes of parenteral nutritional admixtures in neonatology]. / Étude comparative des processus de production et de contrôle analytique des préparations magistrales de mélanges nutritifs parentéraux en néonatalogie.

OBJECTIVES: To assess the impact of disparities in production and analytical control processes on the quality of parenteral nutrition (PN) preparations produced in the Auvergne-Rhône-Alpes region. METHODS: This study was carried out in four hospital pharmacies of the Auvergne-Rhône-Alpes region. To assess the impact of production processes, each centre produced ten PN preparations from the same prescription. Analytical controls (sodium, potassium and calcium dosage) were carried out on all the preparations. To assess the impact of the control processes, a batch of ten preparations was produced from the same prescription. Samples were sent to the four hospital pharmacies for analytical control (sodium, potassium and calcium dosage). RESULTS: Measurements of relative production bias show that there is a significant difference between the preparations from the four centres in terms of sodium and potassium content. Each centre had at least one production bias for one of the three electrolytes measured. Concerning analytical controls, there was a significant difference between the four centres in the sodium and potassium levels measured. With the exception of calcium, all the centres reported measurements within the usual specifications of±10% of the target value. The results obtained have no clinically significant impact. CONCLUSION: The diversity of NP practices has a real impact on the quality of the preparations made. A regional collaboration should be envisaged to standardise patient care.

Impact of polypharmacy and comorbidity on survival and systemic parenteral treatment administration in a cohort of hospitalized lung-cancer patients.

BACKGROUND: Although polypharmacy has been described among cancer patients, very few studies have focused on those with lung cancer. We aimed to assess whether polypharmacy and comorbidity have an impact on systemic parenteral treatment administration and survival among lung-cancer patients. METHODS: In this retrospective monocenter cohort study, we included patients hospitalized in thoracic oncology for the first time between 2011 and 2015. The Elixhauser score was used to assess comorbidity and polypharmacy was estimated with a threshold of at least five prescribed medications. The Fine and Gray competitive risk model was used to estimate the impact of polypharmacy and comorbidity on systemic parenteral treatment administration within the first two months of hospitalization. The effect of comorbidity and polypharmacy on overall survival was evaluated by Cox proportional hazards analysis. RESULTS: In total, 633 patients were included (71% men), with a median age of 66 years. The median Elixhauser score was 6 and median overall survival was four months. Among the patients, 24.3% were considered to be receiving polypharmacy, with a median number of medications of 3, and 49.9% received systemic parenteral treatment within two months after hospitalization. Severe comorbidity (Elixhauser score > 11), but not polypharmacy, was independently associated with a lower rate of systemic parenteral treatment prescription (SdHR = 0.4 [0.3;0.6], p < 0.01) and polypharmacy, but not a high comorbidity score, was independently associated with poorer four-month survival (HR = 1.4 [1.1;1.9], p < 0.01) CONCLUSIONS: This first study to evaluate the consequences of comorbidity and polypharmacy on the care of lung-cancer patients shows that a high comorbidity burden can delay systemic parenteral treatment administration, whereas polypharmacy has a negative impact on four-month survival.

Comparison of seven comorbidity scores on four-month survival of lung cancer patients.

BACKGROUND: The comorbidity burden has a negative impact on lung-cancer survival. Several comorbidity scores have been described and are currently used. The current challenge is to select the comorbidity score that best reflects their impact on survival. Here, we compared seven usable comorbidity scores (Charlson Comorbidity Index, Age adjusted Charlson Comorbidity Index, Charlson Comorbidity Index adapted to lung cancer, National Cancer Institute combined index, National Cancer Institute combined index adapted to lung cancer, Elixhauser score, and Elixhauser adapted to lung cancer) with coded administrative data according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems to select the best prognostic index for predicting four-month survival. MATERIALS AND METHODS: This cohort included every patient with a diagnosis of lung cancer hospitalized for the first time in the thoracic oncology unit of our institution between 2011 and 2015. The seven scores were calculated and used in a Cox regression method to model their association with four-month survival. Then, parameters to compare the relative goodness-of-fit among different models (Akaike Information Criteria, Bayesian Information Criteria), and discrimination parameters (the C-statistic and Harrell's c-statistic) were calculated. A sensitivity analysis of these parameters was finally performed using a bootstrap method based on 1,000 samples. RESULTS: In total, 633 patients were included. Male sex, histological type, metastatic status, CCI, CCI-lung, Elixhauser score, and Elixhauser-lung were associated with poorer four-month survival. The Elixhauser score had the lowest AIC and BIC and the highest c-statistic and Harrell's c-statistic. These results were confirmed in the sensitivity analysis, in which these discrimination parameters for the Elixhauser score were significantly different from the other scores. CONCLUSIONS: Based on this cohort, the Elixhauser score is the best prognostic comorbidity score for predicting four-month survival for hospitalized lung cancer patients.

Retrospective study of sacral neuromodulator implantations in a French hospital center: Lifespan and hospital costs assessment.

PURPOSE: Sacral nerve neuromodulation (SNM) is a safe and effective therapy for the management of fecal and/or urinary incontinence. The generators InterStim™ and InterStim™ II (Medtronic™) are non-rechargeable active implantable medical devices with a limited lifespan. The aims of this study were to assess the generators' median lifespan for all indications and the long-term hospital costs of the therapy. METHODS: This was a retrospective monocentric study that included 215 patients aged over 18 years who were treated by SNM for fecal incontinence and/or urinary incontinence. Lifespan was considered as the amount of time between definitive implantation and observed battery depletion by the surgeon and was assessed by the Kaplan-Meier method. Costs were assessed according to the activity-based pricing of the French public health care system. RESULTS: The median observed lifetime of stimulators implanted in our center was 7.29 years and 5.9 years for InterStim™ and InterStim™ II, respectively. The difference observed between the two generations was statistically significant. The modelling of primary implantation and renewal costs allowed us to observe that the decrease in the lifetime of Interstim™ II is associated with an increase in hospital costs over time. The retrospective study design is one limitation and we did not take into consideration stimulation's settings. CONCLUSIONS: The InterStim™ II lifespan is shorter than the first-generation device. This is associated with an increase of the long-term hospital costs. Additional information about the new neuromodulator will be required to choose the most appropriate IPG for the patient while optimizing the costs.

Development of Indirect Health Data Linkage on Health Product Use and Care Trajectories in France: Systematic Review.

BACKGROUND: European national disparities in the integration of data linkage (ie, being able to match patient data between databases) into routine public health activities were recently highlighted. In France, the claims database covers almost the whole population from birth to death, offering a great research potential for data linkage. As the use of a common unique identifier to directly link personal data is often limited, linkage with a set of indirect key identifiers has been developed, which is associated with the linkage quality challenge to minimize errors in linked data. OBJECTIVE: The aim of this systematic review is to analyze the type and quality of research publications on indirect data linkage on health product use and care trajectories in France. METHODS: A comprehensive search for all papers published in PubMed/Medline and Embase databases up to December 31, 2022, involving linked French database focusing on health products use or care trajectories was realized. Only studies based on the use of indirect identifiers were included (ie, without a unique personal identifier available to easily link the databases). A descriptive analysis of data linkage with quality indicators and adherence to the Bohensky framework for evaluating data linkage studies was also realized. RESULTS: In total, 16 papers were selected. Data linkage was performed at the national level in 7 (43.8%) cases or at the local level in 9 (56.2%) studies. The number of patients included in the different databases and resulting from data linkage varied greatly, respectively, from 713 to 75,000 patients and from 210 to 31,000 linked patients. The diseases studied were mainly chronic diseases and infections. The objectives of the data linkage were multiple: to estimate the risk of adverse drug reactions (ADRs; n=6, 37.5%), to reconstruct the patient's care trajectory (n=5, 31.3%), to describe therapeutic uses (n=2, 12.5%), to evaluate the benefits of treatments (n=2, 12.5%), and to evaluate treatment adherence (n=1, 6.3%). Registries are the most frequently linked databases with French claims data. No studies have looked at linking with a hospital data warehouse, a clinical trial database, or patient self-reported databases. The linkage approach was deterministic in 7 (43.8%) studies, probabilistic in 4 (25.0%) studies, and not specified in 5 (31.3%) studies. The linkage rate was mainly from 80% to 90% (reported in 11/15, 73.3%, studies). Adherence to the Bohensky framework for evaluating data linkage studies showed that the description of the source databases for the linkage was always performed but that the completion rate and accuracy of the variables to be linked were not systematically described. CONCLUSIONS: This review highlights the growing interest in health data linkage in France. Nevertheless, regulatory, technical, and human constraints remain major obstacles to their deployment. The volume, variety, and validity of the data represent a real challenge, and advanced expertise and skills in statistical analysis and artificial intelligence are required to treat these big data.

[Translation and adaptation of a tool prescribing errors related to computerized physician order entry coding to the French hospital background]. / Traduction et adaptation au contexte hospitalier français d'un outil de codification des erreurs de prescription liées aux logiciels.

Prescribing errors related to computerized physician order entry are current and may have serious consequences for patients. They can be detected by pharmacists during prescriptions analysis and lead to pharmacist's interventions. In France, few monocentric studies have studied Pharmacist Interventions triggered by prescribing errors identified as System-Related Errors (PISREs) in French hospitals. However, their respective analysis method prevent any comparison between computerized physician order entry systems in order to identify the safest and rule out the most dangerous. A computerized physician prescribing error related to the software is characterized by its causes, consequences and mechanism of occurrence. US researchers have developed and validated a tool to classify and illustrate these three characteristics. The objectives of this article are to present this tool, to propose a French adaptation and to describe the perspectives analyze and understand prescription errors related to computerized physician order entry based on data of Act-IP©. The adaptation was performed using PISREs extracted from the Act-IP© observatory of the French Society of Clinical Pharmacy. Each item of the codification is illustrated with an example of PI. We are considering a training plan in order to allow wide use of this tool. Once adopted this tool, the next step will be to organize a prospective multicenter study including as many computerized prescription order entry systems as possible. The aim of this study will be identifying the safest systems. Consequently, it will then be possible to have arguments to qualify the most dangerous and thus propose their withdrawal from the market.

[Evaluation of the organisational and clinical impacts of supply chain problems in a university hospital]. / Évaluation des impacts organisationnels et cliniques des ruptures de médicaments au sein d'un centre hospitalier universitaire.

Drug supply problems are a real public health concern. Despite the implementation of legal measures, this problem is still relevant, with potential clinical, organizational and financial consequences in hospitals. The objective is to evaluate the organizational and clinical impact of supply problems in a hospital. A retrospective study of the supply problems encountered in our institution made it possible to classify them according to different criteria using an algorithm. A mapping of the organizational impact of the resolution of each supply problem according to the internal organization of the medication circuit was developed. The potential clinical impact of each problem identified was assessed using a 4-level scale. Over an 18-month period, 332 supply problems were recorded, 78 % of which were classified as a stock-outs. Over the entire study, 2415 organizational impact points were identified, with 2019 impacts for the pharmacy department and 396 impacts for the healthcare departments. Approximately 90 % of the drugs with a supply problem were drugs of major therapeutic interest. In 49 % of the situations, they have a lesser clinical impact as soon as shortage management is put in place. The characterization of the different management methods has made it possible to systematically identify and predict the impact on the entire medication circuit. The impact on the patient is thus limited if the management of the supply problem is well anticipated by the pharmacist. The pharmacist plays an important role in managing supply problems, but also in providing support to the care services.

Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus.

AIMS: A new formulation of posaconazole (PCZ), delayed-release tablets (PCZ-tab), increases PCZ bioavailability and plasma trough concentrations (Cmin ) over those achieved with an oral suspension (PCZ-susp). PCZ is an inhibitor of cytochrome P450 3A4 and P-glycoprotein. We therefore investigated the impact of PCZ-tab treatment on blood Cmin and doses of tacrolimus (TAC) and everolimus (EVR). METHODS: Eighteen lung transplant patients receiving TAC (n = 13) or TAC + EVR (n = 5) between June 2015 and March 2016 were retrospectively included. Ten of these patients received both PCZ-tab and PCZ-susp (i.e. switched patients); the other 8 received only PCZ-tab. Plasma Cmin of PCZ (n = 64), blood Cmin of TAC (n = 299) and EVR (n = 80) were determined during routine therapeutic drug monitoring by liquid chromatography-tandem mass spectrometry. RESULTS: PCZ Cmin on PCZ-tab treatment (n = 48) was 2.5 times higher than that on PCZ-susp therapy (n = 16), for both PCZ patients (P < .0001) and for switched patients (P = .003). PCZ initiation, regardless of galenic form, increased TAC and EVR Cmin adjusted for dose (D), 3-fold and 3.5-fold, respectively (P < .0001 for both). PCZ-tab treatment was associated with a higher TAC Cmin /D (PCZ-tab vs PCZ-susp: 0.004 ± 0.004 L-1 vs 0.009 ± 0.006 L-1 , P < .0001) and lower TAC daily dose than PCZ-susp (PCZ-tab vs PCZ-susp: 1.08 ± 0.92 vs 2.32 ± 1.62 mg d-1 , P < .0001). EVR Cmin /D was higher and EVR dose tended to be lower on PCZ-tab than on PCZ-susp. CONCLUSION: The greater PCZ exposure achieved during PCZ-tab treatment increased drug-drug interactions with TAC and EVR, resulting in greater exposure, potentially exposing patients to higher risks of adverse effects.

Clinical, economic and organizational impact of pharmacist interventions on injectable antineoplastic prescriptions: a prospective observational study.

BACKGROUND: Pharmacists play a key role in ensuring the safe use of injectable antineoplastics, which are considered as high-alert medications. Pharmaceutical analysis of injectable antineoplastic prescriptions aims to detect and prevent drug related problems by proposing pharmacist interventions (PI). The impact of this activity for patients, healthcare facilities and other health professionals is not completely known. This study aimed at describing the clinical, economic, and organizational impacts of PIs performed by pharmacists in a chemotherapy preparation unit. METHODS: A prospective 10-week study was conducted on PIs involving injectable antineoplastic prescriptions. Each PI was assessed by one of the four multidisciplinary expert committees using a multidimensional tool with three independent dimensions: clinical, economic and organizational. An ancillary quantitative evaluation of drug cost savings was conducted. RESULTS: Overall, 185 patients were included (mean age: 63.5 ± 13.7 years; 54.1% were male) and 237 PIs concerning 10.1% prescriptions were recorded. Twenty one PIs (8.9%) had major clinical impact (ie: prevented hospitalization or permanent disability), 49 PIs (20.7%) had moderate clinical impact (ie: prevented harm that would have required further monitoring/treatment), 62 PIs (26.2%) had minor clinical impact, 95 PIs (40.0%) had no clinical impact, and 9 PIs (3.8%) had a negative clinical impact. For one PI (0.4%) the clinical impact was not determined due to insufficient information. Regarding organizational impact, 67.5% PIs had a positive impact on patient management from the healthcare providers' perspective. A positive economic impact was observed for 105 PIs (44.3%), leading to a saving in direct drug costs of 15,096 €; 38 PIs (16.0%) had a negative economic impact, increasing the direct drug cost by 11,878 €. Overall cost saving was 3218€. CONCLUSIONS: PIs are associated with positive clinical, economic and organizational impacts. This study confirms the benefit of pharmacist analysis of injectable antineoplastic prescriptions for patient safety with an overall benefit to the healthcare system.

Integrating anatomo-physiological changes and pharmacogenomics in anti-infective therapy management: is it a major concern?

Success of anti-infective therapy is a major challenge in some patients given anatomo-physiological changes and genetic variations. In this case anecdote, we report the management strategy of a patient suffering from chronic pulmonary aspergillosis in a context of anorexia nervosa and genetic polymorphism.

Multimorbidity medications and poor asthma prognosis.

Multimedication related to multimorbidity is common in the elderly with asthma. We aimed at comprehensively characterising medications used by elderly women and assessing how multimedication impacts on asthma prognosis.We performed network-based analyses on drug administrative databases to visualise the prevalence of drug classes and their interconnections among 17 458 elderly women from the Asthma-E3N study, including 4328 women with asthma. Asthma groups sharing similar medication profiles were identified by a clustering method relying on all medications and were studied in association with adverse asthma events (uncontrolled asthma, attacks/exacerbations and poor asthma-related quality of life).The network-based analysis showed more multimedication in women with asthma than in those without asthma. The clustering method identified three multimedication profiles in asthma: "Few multimorbidity-related medications" (43.5%), "Predominantly allergic multimorbidity-related medications" (32.8%) and "Predominantly metabolic multimorbidity-related medications" (23.7%). Compared with women belonging to the "Few multimorbidity-related medications" profile, women belonging to the two other profiles had an increased risk of uncontrolled asthma and asthma attacks/exacerbations, and had lower asthma-related quality of life.The integrative data-driven approach on drug administrative databases identified specific multimorbidity-related medication profiles that were associated with poor asthma prognosis. These findings support the importance of multimorbidity in the unmet needs in asthma management.

Electronic Medication Regimen Complexity Index at admission and complications during hospitalization in medical wards: a tool to improve quality of care?

OBJECTIVE: Adverse events during hospitalization are a major worry considering their frequency and their burden. Many could be avoided by immediate identification of at-risk patients at admission and adapted prevention. The complexity of a patient's medication regimen immediately available at admission is a good indicator of the complexity of the patient's condition. This study aims to determine whether the electronic Medication Regimen Complexity Index (MRCI) at admission is associated with complications during hospitalization. DESIGN: We performed a multilevel logistic regression model, adjusted for age and sex. SETTING: Premier Perspective™ database, a clinical and financial information system from 417 US hospitals. PARTICIPANTS: Adults hospitalized for more than 3 days in a medical ward and included in Premier's Perspective™ database for 2006. INTERVENTION(S): Multilevel logistic regression. MAIN OUTCOME MEASURE: Association of the MRCI and complications during hospitalization, defined as in-hospital death, hospital-acquired infection, pressure ulcers; and need for highly technical healthcare, identified as the secondary introduction of catecholamines. RESULTS: In total, 1 592 383 admissions were included. The median MRCI at admission was 13 [interquartile range: 9-19]. The higher the MRCI, the higher the adjusted odds ratio of the following: in-hospital mortality, hospital-acquired infections, pressure ulcers and the secondary introduction of catecholamines. CONCLUSIONS: Our results suggested that the MRCI at admission was correlated with patient complexity, independent of age. Considering that patients with complex conditions pose a heavier workload for staff, measuring MRCI at admission could be used to allocate resources in medical wards at an institutional level. The MRCI might be a useful tool to assess the management of care.

Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension.

BACKGROUND: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation. OBJECTIVES: We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications. METHODS: We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors). RESULTS: Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized. CONCLUSIONS: About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication.

Automated drug dispensing systems in the intensive care unit: a financial analysis.

INTRODUCTION: To evaluate the economic impact of automated-drug dispensing systems (ADS) in surgical intensive care units (ICUs). A financial analysis was conducted in three adult ICUs of one university hospital, where ADS were implemented, one in each unit, to replace the traditional floor stock system. METHOD: Costs were estimated before and after implementation of the ADS on the basis of floor stock inventories, expired drugs, and time spent by nurses and pharmacy technicians on medication-related work activities. A financial analysis was conducted that included operating cash flows, investment cash flows, global cash flow and net present value. RESULTS: After ADS implementation, nurses spent less time on medication-related activities with an average of 14.7 hours saved per day/33 beds. Pharmacy technicians spent more time on floor-stock activities with an average of 3.5 additional hours per day across the three ICUs. The cost of drug storage was reduced by €44,298 and the cost of expired drugs was reduced by €14,772 per year across the three ICUs. Five years after the initial investment, the global cash flow was €148,229 and the net present value of the project was positive by €510,404. CONCLUSION: The financial modeling of the ADS implementation in three ICUs showed a high return on investment for the hospital. Medication-related costs and nursing time dedicated to medications are reduced with ADS.

Long-term benefits of inhaled corticosteroids in asthma: the propensity score method.

PURPOSE: The aim of this study was to apply a propensity score approach to assess the long-term benefits of inhaled corticosteroids (ICS) on respiratory health in asthma. METHODS: This analysis was conducted on adults with persistent asthma from the Epidemiological study on the Genetics and Environment of Asthma, a 12-year follow-up study. ICS exposure was assessed by questionnaire. Change in lung function over the follow-up period, asthma control, and health-related quality of life (asthma quality of life questionnaire) were assessed by standardized and validated methods. RESULTS: Among 245 adults with persistent asthma, 78 (31.8%) were regularly/continuously exposed to ICS (≥6 months/year, ICS++ ) and 167 never/irregularly exposed to ICS (<6 months/year, ICS+/- ) over the follow-up period. Compared with ICS+/- subjects, a nonsignificant trend for a slower lung function decline (mL/year) was observed in ICS++ subjects (ß [95%CI] = -11.4 [-24.9; 2.0]). The ICS++ subjects did not have better controlled asthma and higher health-related quality of life as compared with ICS+/- subjects. CONCLUSIONS: Applying a propensity score method did not offer evidence of a statistical significant long-term benefit of ICS on respiratory health in adults with persistent asthma regularly or continuously exposed to ICS over a long period.