[Prescription of split doses in a nursing home: Contribution of an automated dose-dispensing machine]. / Prescription de demi-doses en établissement d'hébergement pour personnes âgées dépendantes : apport d'un automate de préparation de doses à administrer.

OBJECTIVES: The territorial pharmacy of the West of Paris carries out an automated dose dispensing for a nursing home. The machine overpacks dry oral forms in unit doses and dispenses them in named pillboxes. Tablets prescribed in fractions are currently dispensed in whole unit doses, fractioned in advance by a nurse, then administered by a caregiver. These operations present a number of risks, including a break in dose identification right through to administration. The objective was therefore to extend the automated dose dispensing to split tablets by repackaging. METHODS: The development of this new process, its software qualification and its evaluation after six months of routine use are described. RESULTS: This process is composed of three steps, secured by pharmaceutical controls: manual production of fractions in the preparatory area, automated repackaging using a barrel and automated dispensing in pillboxes. In total, 2000 fractions were produced in six months with a non-compliance rate lower than 5% and a negligible financial loss. Following the assumption of this activity by the pharmacy, the care team declares themselves satisfied by the gain in time and safety. CONCLUSIONS: Automated dispensing of unit doses in fractions ensures identification of the dose from prescription to administration, thus limiting administration errors.

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study.

BACKGROUND: Pembrolizumab is approved for patients with metastatic urothelial carcinoma (UC) who progressed under platinum therapy. The aim of this study was to assess the efficacy and safety of pembrolizumab in a cohort of real-life UC patients. METHODS: This retrospective, observational study included advanced UC patients treated with pembrolizumab in a single institution in France. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) at 6 months. Secondary endpoints were objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety. RESULTS: 78 patients were included in the study. The median OS was 7.3 months (3.8-12.2). The estimated OS rate at 6 months was 61.5% (50.5-72.6). The median PFS was 3.1 months (1.4-7.2). The estimated PFS rate at 6 months was 42.3% (31.1-53.5). The best ORR was 35.9%. The mean DOR was 95.5 days. The DCR was 30.8%. The most common treatment-related adverse events (AEs) of any grade were fatigue (46.2%), diarrhea (11.5%), pruritus (10.3%) and nausea (9.0%). There were no grade 3 AEs that occurred with an incidence of 5% or more. CONCLUSION: Our results confirmed those of randomized clinical trials concerning the treatment with pembrolizumab in patients with advanced UC that progressed after platinum-based chemotherapy.

AVK overdose in Covid-19 infected patients.

During the Covid-19 pandemic, four patients were admitted to a healthcare centre. They were treated with vitamin K antagonists (AVK). We observed a substantial increase in their International Normalised Ratio (INR). The mean age of these patients was 90 (± 8 years). All had different usual long-term therapy treatments but had fixed doses of AVK to reach a stable INR. No changes to the background regimen were implemented. One patient presented a cough whereas the three others were asymptomatic. In the context of the pandemic, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was carried out for each patient. The results of the RT-PCR rests were all positive and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 which increased to 5.93 the day after RT-PCR positivity. AVK treatment was stopped but the INR one day after was 7.89. Ms J. presented INR values between 1.96 and 4.58, 10 days later. a PCR test was conducted and AVK treatment was stopped, but the INR still increased to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24 hours after a positive PCR result. Ms F. presented a gradual increase in INR from 1.5 to 3.36, 72 hours after a positive PCR result and three days after discontinuation of AVK. This study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a haemorrhagic risk as the INR increases. There could be a risk of overdose when patients are treated with AVK and are positive for Covid-19. This raises the question of discontinuing AVK and substituting it with another anticoagulant, or performing INR checks more frequently in the context of Covid-19. Moreover, an unexpected increase in INR should indicate the need to conduct a Covid-19 RT-PCR test in the context of this pandemic context.

[VKA overdose in Covid-19 infected patients]. / Cas rapportés de surdosage en anti-vitamines K (AVK) chez des patients infectés par la Covid-19.

During the Covid-19 pandemic, four patients were admitted in a healthcare center. They were treated by vitamin K antagonists (VKA). We observed a substantially increased of their International Normalized Ratio (INR) The mean age of patients was 90 (± 8). All had different usual long-term therapy treatments but had fixed doses of VKA to reach a stable INR. No change of background treatment were realized. One patient presented cough whereas the three others were asymptomatic. In the pandemic context, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was realized for each patients. RT-PCR were all positives and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 and it increased to 5.93 the day after RT-PCR positivity. The VKA treatment was stopped but the INR one day after was 7.89. Mrs J. presented INR value from 1.96 to 4.58, 10 days later. PCR have been realized and VKA treatment was stopped: INR still increased up to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24 h after positive PCR results. Mrs F. presented a gradually increase of INR from 1.5 to 3.36, 72 h after PCR results three days after VKA discontinuation. Finally, this study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a hemorrhagic risk with the elevation of the INR. It could have a risk of overdose when patients treated with VKA and positive to Covid-19. This raises the question of discontinuing VKA and substituting them with another anticoagulant, or performing INR controls more frequently in the context of Covid-19. Moreover, an unexpected increase of INR could lead to realize a Covid-19 RT-PCR in this pandemic context.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines.

BACKGROUND: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). METHODS: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. RESULTS: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1-12,589.3) vs. 7268.6, 95% CI (6501.3-8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). CONCLUSIONS: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

De-simplifying single-tablet antiretroviral treatments for cost savings in France: From the patient perspectives to a 6-month follow-up on generics.

In developed countries, most people living with HIV/AIDS are treated with costly brand single-tablet regimens. Given the economic impact, French guidelines recommend using generic antiretroviral therapy when possible to decrease antiretroviral therapy costs. We aimed to study HIV-infected patients' acceptability to switch from a brand single-tablet regimens [abacavir/lamivudine/dolutegravir (Triumeq®) or emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera®)] to a treatment comprising of two pills: one is a fixed-dose generic combination of 2 Nucleoside Analogs and the second tablet is the third antiretroviral. This study was a prospective observational study in a French hospital. During their follow-up, patients on stable single-tablet regimens were made aware of the possible cost-saving. They were questioned about their willingness and barriers accepting the substitution. Participants chose between the two regimens, either to remain on single-tablet regimens or switch to the de-simplified regimen. Six months later, a second survey was given to the patient who chose to de-simplify and HIV viral load was controlled. The study included 98 patients: 60 receiving emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera®) and 38 on abacavir/lamivudine/dolutegravir (Triumeq®). Forty-five patients accepted the de-simplified treatment, 37 refused and 16 were undecided and followed the decision offered by their physician. The main reason for unwillingness to switch is the number of pills (77.3%). In multivariate model analysis, male patients (p = 0.001) who have taken antiretroviral therapy for over 20 years (p = 0.04) and who retrieve their treatment in their community hospital (p = 0.03) are more likely to accept the switch. Fifty-one patients accepted to replace their single-tablet regimens and six months later, the majority was satisfied; only four returned to single-tablet regimens because of suspected side effects. Half of the people living with HIV/AIDS in our cohort accepted to switch from brand single-tablet regimens to a two-tablet regimen containing generic drugs within a process that emphasizes health expenditure savings.

[Implementation of a remote oncology-monitoring program for cancer patients in outpatient care unit: A major challenge for the different actors]. / Mise en place d'un programme de suivi à distance des patients atteints de cancer et traités par chimiothérapie en hôpital de jour : un enjeu de taille pour les différents acteurs.

INTRODUCTION: The development of outpatient departments requires health professionals to reorganize practices for a better patient monitoring and a better patient care pathway. OBJECTIVE: To evaluate, using indicators, the impact of an oncology-monitoring program on activity and organizational fluidity in a Cytotoxic Preparation Unit and clinical departments. Method the clinical and biological data are collected between two injections by calling the patient two days prior chemotherapy is performed by a specialist nurse of an outsourced medical call center. After medical and pharmaceutical validation, early preparations (D-1) for expensive and non-expensive molecules are performed. RESULTS: The program is started in February 2016. After 3 months, 382 patients were included into the program. Twenty-three patients on average are called per day related to 1162 completed clinical questionnaires (87%). Among the files, 47% are complete at D-2 (biological and clinical data). The early preparation rate of expensive drugs, zero before the program for financial reasons, has reached 40% at 3 months. The destroyed preparation rate because of non-administration decreased from 5 to 2%. DISCUSSION: Preliminary results show a significant patient compliance, feasibility of early preparation of expensive and non-expensive chemotherapy. These are preliminary results of a one-year study. They will be completed by an evaluation of patients' and health professionals' satisfaction, evaluation of length of stay, optimization of operations for clinical departments and CPU. The D-2 biological data collection must be improved. A strong doctor/pharmacist collaboration is essential for better patient care pathway.

How well Informed are Cancer Patients Prior to a Life Cycle of Injectable Chemotherapy Drug Treatment?

Cancer patient dissatisfaction, due to a long waiting time for chemotherapy treatment, is a common complaint. To improve patient satisfaction, our pharmaceutical team was prompted to design a series of information tools for injectable chemotherapy drug treatment (ICDT) patients. This study was based on French Health Authorities recommendations. All three stages were monitored: the preparation stage using a 204 patient survey, the design stage, and the assessment stage with a 12 point questionnaire patient evaluation. An information brochure and a 10-min film were designed which chronologically described key stages in the life cycle of ICDT. Both tools were assessed by 29 and 84 patients respectively. The questionnaire confirmed that this approach met the needs of more than 90 % of patients. The brochure and the film also accurately met the objectives and improved the understanding of the chemotherapy long waiting time which resulted in higher patient satisfaction. The designed tools will continue to evolve with changes in oncology practices based on various indicators defined in the study. Our study proposes an original method to assist health professionals to better inform cancer patients regarding the preparation of ICDT. It is also a part of a continuous quality program to assure quality outpatient healthcare.

Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

OBJECTIVES: The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. STUDY DESIGN AND SETTING: A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. RESULTS: Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. CONCLUSION: To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices.

Use of a risk assessment method to improve the safety of negative pressure wound therapy.

To conduct a risk analysis of the negative pressure wound therapy (NPWT) care process and to improve the safety of NPWT, a working group of nurses, hospital pharmacists, physicians and hospital managers performed a risk analysis for the process of NPWT care. The failure modes, effects and criticality analysis (FMECA) method was used for this analysis. Failure modes and their consequences were defined and classified as a function of their criticality to identify priority actions for improvement. By contrast to classical FMECA, the criticality index (CI) of each consequence was calculated by multiplying occurrence, severity and detection scores. We identified 13 failure modes, leading to 20 different consequences. The CI of consequences was initially 712, falling to 357 after corrective measures were implemented. The major improvements proposed included the establishment of 6-monthly training cycles for nurses, physicians and surgeons and the introduction of computerised prescription for NPWT. The FMECA method also made it possible to prioritise actions as a function of the criticality ranking of consequences and was easily understood and used by the working group. This study is, to our knowledge, the first to use the FMECA method to improve the safety of NPWT.

A practical approach to improve safety and management in chemotherapy units based on the PROCHE - programme for optimisation of the chemotherapy network monitoring program.

The PROCHE (PRogramme d'Optimisation du circuit CHimiothErapie [Programme for optimisation of the chemotherapy network]) initiative is an innovative oncology-monitoring program designed to reduce patient waiting time and chemotherapy wastage, ultimately improving patient care. Laboratory test results and side effects data were collected for patients in the PROCHE monitoring program group 2d prior to scheduled chemotherapy visits, allowing oncologists to confirm or delay each patient's chemotherapy. Data from 1037 patients entered in the PROCHE program were compared with 513 control patients, who had been treated according to previous typical hospital procedures. Results demonstrated significant reductions in mean hospital stay i.e. decreased it by 66 min and drug wastage decreased from 6% to 2% (95% CI (confidence interval) 0.21-0.59, P<0.0001), and a significant increase in bed occupancy rates with the PROCHE initiative (all P<0.0001 vs. controls). The incidence of pain and severity of fatigue were also reduced. In conclusion, the PROCHE initiative resulted in improved patient quality of care and reduced chemotherapy toxicities, and improved hospital and pharmacy productivity. These encouraging preliminary results warrant further study.

Evaluating single-incision slings in female stress urinary incontinence: the usefulness of the CONSORT statement criteria.

OBJECTIVE: To evaluate the usefulness and applicability of the Consolidated Standards of Reporting Trials (CONSORT) for journal articles reporting randomized, controlled trials evaluating single-incision slings in the treatment of female stress urinary incontinence. METHODS: Original articles reporting randomized, controlled trials assessing single-incision slings in the treatment of female stress urinary incontinence were searched for in the PubMed and Embase databases in 2011. Reporting quality was studied by 2 hospital pharmacists and 2 urologic surgeons. Primary outcome was the score out of 20 in the abstract CONSORT checklist. Secondary outcomes were the scores in the standard CONSORT checklist and the extension CONSORT additional items for trials assessing nonpharmacologic treatments. RESULTS: Among 135 articles retrieved, 8 met the inclusion criteria and were assessed. Abstract scores ranged from 4.7-14.1. Standard scores were >10.0 out of 20 for most articles; the extension scores did not exceed 5.0 out of 10. Four reported trials were not identified as randomized in the title. The interventions were incompletely reported. Four articles reported whether blinding was achieved but lack of blinding was never discussed as a potential source of bias. Few articles reported the operators and centers characteristics and their impact on statistical analysis. The combination of the 3 checklists was considered a useful guideline to enhance and assess the reporting quality of a surgical trial. CONCLUSION: Our results support the further use of CONSORT criteria as a basic standardized tool in all stages of clinical evaluation for any prosthetic device in female pelvic surgery.

Interest of the preliminary risk analysis method in a central sterile supply department.

OBJECTIVES: In order to improve its quality-assurance programme based on ISO 9001, the Central Sterile Supply Department of a public university hospital has performed a prospective risk analysis using the Preliminary Risk Analysis method (PRA). The objectives were the achievement of a global risk mapping related to the whole process of sterilising medical devices, and second, the implementation of corrective measures to reduce identified risks. METHODS: A multidisciplinary team, formed in January 2008, validated results at each step of the study. During the analysis, 416 hazardous situations were identified, among which 81 were quoted first in priority and led to the description of 141 risk scenarios. The PRA team assessed 42 scenarios with risk ranking assessed as 'acceptable under control' or 'unacceptable.' They adopted 23 follow-up actions measures and 13 safety parameters. RESULTS AND DISCUSSION: The PRA constitutes an appropriate tool for assessing quality-improvement policy and safety in healthcare facilities that can be easily integrated into standard quality-management systems.

FabAct®: a decision-making tool for the anticipation of the preparation of anticancer drugs.

RATIONALE: Due to the increase of new cancer cases, our chemotherapy compounding unit must face with ever-growing production needs. To support this increasing workload, we decided to anticipate the preparation of several anti-cancer drugs. AIMS AND OBJECTIVES: To help us in the decision making, we needed a modern tool able to combine several criteria for selecting appropriate medications for an anticipated preparation. The aim of this study was to assess the decision-making software, FabAct(®) (Version 1.0). METHODS: FabAct(®) ranked all of the anti-cancer drugs used in our chemotherapy compounding unit according to price, chemical stability, compounding difficulties, dosage and production per year. Then, we started to anticipate currently the preparation of four medications and conducted a follow-up of destroyed preparations between January and May 2007. We tried to identify the destruction causes and calculated the time saved for the patients and for the pharmacy technicians. RESULTS: According to the decision-making software, the first four drugs for an anticipated preparation were: fluorouracil, cisplatin, carboplatin and paclitaxel. A total of 3913 (50.2%) anticipated preparations were performed and among those, 470 (12%) were destroyed. The main cause of destruction was due to the preparation expiration. Finally, the mean waiting time per patient was reduced from 118 minutes to 68 minutes after the application of the anticipated model. CONCLUSION: According to this 5-month follow-up, FabAct(®) helped us to select appropriate anti-cancer drugs to anticipate the compounding. Most of the anticipated preparations were administrated to patients and the patient waiting time was significantly reduced.

Stability of antineoplastic agents in use for home-based intravenous chemotherapy.

AIM OF THE REVIEW: The aim of this work was first to define which antineoplastic agents with sufficiently long stability could be eligible in the circuit of home-based therapy (centralised preparation, transport to the patient's home and administration by nurses) and, second, to propose a standardisation of the stability data of anticancer drugs in use for home hospitalisation. METHOD: A survey carried out in six hospital pharmacies of the Assistance Publique-Hôpitaux de Paris (AP-HP) hospitals, with important activity in oncology, listed the stability data used locally by each site. The final goal is to reach a consensus for the stability of cytotoxic drugs, which was the result of an original collaboration between the pharmacists of the compounding unit and the quality control unit. These results were compared to marketing authorisation data. RESULTS: The survey showed that eight antineoplastic agents of 34 were prepared under identical conditions (infusion diluent, concentration range, protection from light, temperature) by all hospitals (3 < or = n < or = 6): the stability was identical between each site for only two cytotoxic drug preparations (fotemustine and gemcitabine) and varied by up to 168 h or 7 days for the preparations of dacarbazine, epirubicine and cisplatin. Stability validated by pharmacists and those provided by marketing authorisation ranged respectively from "extemporaneously prepared" at 1,344 h (median = 168 h) to "extemporaneously prepared" at 720 h (median = 4 h). For 11 antineoplastic drugs, no information about the stability after compounding was specified in the marketing authorisation. Of all cytotoxic drugs used in the Hospital at Home of AP-HP, stability after compounding validated by pharmacists was less than 30 h for six of them, between 30 and 78 h for four and exceeding 78 h for the remaining 24. CONCLUSION: Considering the lack of data about cytotoxic drugs stability provided by the pharmaceutical companies and the difficulties in retrieving and interpreting the literature data, a consensus on the stability of cytotoxic drug preparations is essential for the current practice. With this approach, initiated for home hospitalisation, we propose in this study an initiative of the standardisation of stability data which offers a decision support for other centres.

The application of hazard analysis and critical control points and risk management in the preparation of anti-cancer drugs.

OBJECTIVE: To apply the Hazard analysis and Critical Control Points method to the preparation of anti-cancer drugs. To identify critical control points in our cancer chemotherapy process and to propose control measures and corrective actions to manage these processes. SETTING: The Hazard Analysis and Critical Control Points application began in January 2004 in our centralized chemotherapy compounding unit. From October 2004 to August 2005, monitoring of the process nonconformities was performed to assess the method. METHODS: According to the Hazard Analysis and Critical Control Points method, a multidisciplinary team was formed to describe and assess the cancer chemotherapy process. This team listed all of the critical points and calculated their risk indexes according to their frequency of occurrence, their severity and their detectability. The team defined monitoring, control measures and corrective actions for each identified risk. Finally, over a 10-month period, pharmacists reported each non-conformity of the process in a follow-up document. RESULTS: Our team described 11 steps in the cancer chemotherapy process. The team identified 39 critical control points, including 11 of higher importance with a high-risk index. Over 10 months, 16,647 preparations were performed; 1225 nonconformities were reported during this same period. CONCLUSIONS: The Hazard Analysis and Critical Control Points method is relevant when it is used to target a specific process such as the preparation of anti-cancer drugs. This method helped us to focus on the production steps, which can have a critical influence on product quality, and led us to improve our process.

Therapeutic strategy for treatment of metastatic non-small cell lung cancer.

OBJECTIVE: To review the current practices for metastatic non-small cell lung cancer (NSCLC) management and highlight the latest progress. DATA SOURCES: A literature review using HighWire Press (1960-May 2008) was conducted using the following key words: non-small cell lung cancer, chemotherapy, supportive care, therapeutic strategy, quality of life (QOL), and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: Review articles, clinical trials, and case reports, as well as the references of those articles, were reviewed. Statistical significance and number of patients included in the studies were some of the aspects that were considered seriously. Response rates, overall survival, and progression-free survival were the major data considered. DATA SYNTHESIS: The therapeutic management of metastatic NSCLC has undergone a profound evolution over the past 10 years. The positive impact of chemotherapy on survival compared with supportive care alone has been demonstrated by several meta-analyses. The development of third-generation agents with better efficacy/toxicity ratios, such as vinorelbine, paclitaxel, docetaxel, gemcitabine, and pemetrexed, has led to improved therapeutic management of NSCLC, especially when tailored to patients' comorbidities and performance status. First-line platinum-based combinations remain the standard of care, with median survival 8 months and 1-year survival 35%, but no particular combination has yet shown superiority. First-line platinum regimens in combination with bevacizumab, a targeted inhibitor of vascular endothelial growth factor, have further improved NSCLC median survival. Moreover, second- and third-line treatments have evolved. The addition of small-molecule epidermal growth factor inhibitors and other targeted therapies has modified the pattern of NSCLC treatment. Specific management of the elderly and patients with poor performance status should be applied. CONCLUSIONS: Although there has been progress in the treatment of NSCLC, the gain in terms of clinical response and survival is still modest. Maintaining QOL and tailoring therapy for patients based on age, performance status, comorbidities, and toxicities, remain the first priority for clinicians.