Jean-François Bussières

Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec.

BACKGROUNDnHepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM 276700) can cause severe hepatic, renal and peripheral nerve damage. In Québec, HT1 is frequent and neonatal HT1 screening is practiced. Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994.nnnMETHODSnWe recorded the clinical course of 78 Québec HT1 patients born between 1984 and 2004. There were three groups: those who never received nitisinone (28 patients), those who were first treated after 1 month of age (26 patients) and those treated before 1 month (24 patients). Retrospective chart review was performed for events before 1994, when nitisinone treatment began, and prospective data collection thereafter.nnnFINDINGSnNo hospitalizations for acute complications of HT1 occurred during 5731 months of nitisinone treatment, versus 184 during 1312 months without treatment (p<0.001). Liver transplantation was performed in 20 non-nitisinone-treated patients (71%) at a median age of 26 months, versus 7 late-treated patients (26%, p<0.001), and no early-treated patient (p<0.001). No early-treated patient has developed detectable liver disease after more than 5 years. Ten deaths occurred in non-nitisinone treated patients versus two in treated patients (p<0.01). Both of the latter deaths were from complications of transplantation unrelated to HT1. One probable nitisinone-related event occurred, transient corneal crystals with photophobia.nnnINTERPRETATIONnNitisinone treatment abolishes the acute complications of HT1. Some patients with established liver disease before nitisinone treatment eventually require hepatic transplantation. Patients who receive nitisinone treatment before 1 month had no detectable liver disease after more than 5 years.

Failure Mode, Effect, and Criticality Analysis of the Parenteral Nutrition Process in a Mother-Child Hospital: The AMELIORE Study

BACKGROUNDnThe parenteral nutrition (PN) process is complex and involves multiple steps and substeps, especially in pediatrics and neonatology, given the particular needs of these patients. The objective of this study was to perform a critical analysis of the PN process at the Centre Hospitalier Universitaire Sainte-Justine to determine which potential pitfalls are related to this process and which should be prioritized when implementing corrective measures.nnnMETHODSnThis is a Failure Mode, Effect, and Criticality Analysis (FMECA) study. A multidisciplinary team assessed each step of the PN process and identified associated failure modes. Adapted rating scales were used to determine severity, frequency, and detectability of the failure modes. Ratings were established through multidisplinary consensus, and a criticality index (CI) was calculated for each failure mode.nnnRESULTSnA total of 265 failure modes were identified in the 5 major steps of the PN process. The failure mode with the highest CI was the inscription of an inaccurate weight at prescription, with a CI of 800. The step with the highest cumulative CIs was administration to patients, with a CI sum of 7691. Various recommendations aimed at minimizing the risks associated with the PN process were made following this FMECA. Additional interventions are expected to emanate from this project because data will be presented throughout the departments involved.nnnCONCLUSIONnThis study is a successful example for other hospitals interested in carrying out the same kind of healthcare improvement initiative.

Closed‐system drug‐transfer devices in addition to safe handling of hazardous drugs versus safe handling alone for reducing healthcare staff exposure to infusional hazardous drugs

and obtaining full texts for references considered relevant based on the full text. Besides, these studies (which do not mention CSTD in the title or abstract) are likely to show no evidence of benefit of CSTD (the probable reason for not mentioning about CSTD in the title or abstract); therefore, the systematic review authors’ conclusions are unlikely to change. The intra-cluster correlation coefficient was not reported in any of the studies. Therefore, the systematic review authors used the intra-cluster correlation coefficient of 0.10 decided a priori based on studies about implementation research. The results were robust in a sensitivity analysis of using 0.05 for intra-cluster correlation coefficient (i.e. half the correlation noted in similar studies) for most analyses; therefore, the systematic review authors’ conclusions are unlikely to change if the studies had reported the intra-cluster correlation. However, the systematic review authors recommend the study authors to report intra-cluster correlation in future to enable accurate estimation of the results. This is the first systematic review on the topic. The systematic review authors disagree with the study authors who concluded that routine CSTD use is beneficial 26, 60-63, 65-68, . Ignoring the design effect by not adjusting the effect estimates for intra-cluster correlation can lead to an underestimation of random errors; therefore, this could lead to erroneous conclusions. Ignoring the design effect by the study authors, the risk of bias in the studies, and the excessive importance given to unvalidated surrogate outcomes by the study authors are the major differences in the conclusions between this systematic review and the primary research studies. The systematic review authors also disagreed with any guidelines or recommendations that CSTD should be used routinely whenever possible 27, . The possible reasons for our disagreement with those guidelines or recommendations that CSTD should be used routinely are the same as the reasons why we disagree with the study authors who concluded that routine CSTD use is beneficial.

Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff

BACKGROUNDnOccupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets (safe handling). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone.nnnOBJECTIVESnTo assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination.nnnSEARCH METHODSnWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017.nnnSELECTION CRITERIAnWe included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE.nnnMAIN RESULTSnWe included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy technicians; in the other two studies, the people who used the intervention and control were nurses, pharmacists, or pharmacy technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5 studies), and not stated (2 studies). The studies descriptions of the control groups were varied. Twenty-one studies provide data on one or more outcomes for this systematic review. All the studies are at serious risk of bias. The quality of evidence is very low for all the outcomes.There is no evidence of differences in the proportion of people with positive urine tests for exposure between the CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52; I² = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control: 91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1 hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1 hospital; 36 participants; 0% in both groups).There is no evidence of a difference in the proportion of surface samples contaminated in the pharmacy areas or patient-care areas for any of the drugs except 5-fluorouracil, which was lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3 studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).The amount of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the control group (MD -49.34 pg/cm², 95% CI -84.11 to -14.56, I² = 0%, 7 studies; 282 hospitals, 1793 surface samples). Additionally, one interrupted time-series study (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD and CSTD (3.9439 pg/cm², 95% CI 1.2303 to 6.6576; P = 0.010), but not between CSTD and post-CSTD withdrawal (-1.9331 pg/cm², 95% CI -5.1260 to 1.2598; P = 0.20). There is no evidence of difference in the amount of the other drugs between CSTD and control groups in the pharmacy areas or patient-care areas.None of the studies report on atmospheric contamination, blood tests, or other measures of exposure to infusional hazardous drugs such as urine mutagenicity, chromosomal aberrations, sister chromatid exchanges, or micronuclei induction.None of the studies report short-term health benefits such as reduction in skin rashes, medium-term reproductive health benefits such as fertility and parity, or long-term health benefits related to the development of any type of cancer or adverse events.Five studies (six hospitals) report the potential cost savings through the use of CSTD. The studies used different methods of calculating the costs, and the results were not reported in a format that could be pooled via meta-analysis. There is significant variability between the studies in terms of whether CSTD resulted in cost savings (the point estimates of the average potential cost savings ranged from (2017) USD -642,656 to (2017) USD 221,818).nnnAUTHORS CONCLUSIONSnThere is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence). None of the studies report health benefits.Well-designed multicentre randomised controlled trials may be feasible depending upon the proportion of people with exposure. The next best study design is interrupted time-series. This design is likely to provide a better estimate than uncontrolled before-after studies or cross-sectional studies. Future studies may involve other alternate ways of reducing exposure in addition to safe handling as one intervention group in a multi-arm parallel design or factorial design trial. Future studies should have designs that decrease the risk of bias and enable measurement of direct health benefits in addition to exposure. Studies using exposure should be tested for a relevant selection of hazardous drugs used in the hospital to provide an estimate of the exposure and health benefits of using CSTD. Steps should be undertaken to ensure that there are no other differences between CSTD and control groups, so that one can obtain a reasonable estimate of the health benefits of using CSTD.

Proof of Concept and Pilot Study on the Development and Implementation of an Electronic Medication Administration Record

Abstract Objective: The main objective is to describe the phases of electronic medication administration record development and implementation. The secondary objective is to compare dose information using medication administration record and electronic medication administration record. Background: Nursing daily work planning is usually done with the use of a medication administration record printed daily based on the information available in the Pharmacy Information System. Results: We identified six guiding principles. A profile compared to medication administration record and electronic medication administration record, revealed 19 parameters related to drug registration doses. Regarding the development phase, a total of 150 pharmacist hours and 150 nursing hours have been carried out on optimization of electronic medication administration record. During the preparatory pilot phase, voluntary nurses have been invited to identify problems associated with the electronic version. During the pilot phase, a training program was set up. We implemented the electronic medication administration record on 26 November 2014. The pilot study demonstrates that electronic medication administration record has been successfully implemented in a university hospital. Conclusion: To our knowledge, this is the first pilot study conducted in Quebec that describes electronic medication administration record development and implementation. Our pilot study shows that we were able to face these challenges through the employment of human, financial and material resources.

Prospective Descriptive Study of RFID Tag Detection Rates based on Various Exploratory Scenarios Aimed at Identifying Optimal Conditions of Use

Abstract Objective The main objective is to evaluate RFID tags detection rates using various exploratory scenarios in order to identify optimal conditions of use. The secondary objective is to evaluate RFID tags detection rates based on a real-life scenario involving a cardiorespiratory resuscitation drug tray used within our institution in order to identify optimal conditions of use. Background The traceability of goods has been a subject of interest for more than a century. Traceability makes it possible to locate goods at every step in the chain from production through to disposal. Just as with other Automatic Identification and Data Capture technologies, radio frequency identification (RFID) is used to increase the traceability of objects. Results Seven variables that could influence RFID tags detection rates were evaluated in eight exploratory scenarios. Optimal detection parameters allowing to a 100u2006% detection rate were identified: a 10-second reading time; a reading distance of 10u2006cm; parallel orientation of reader-antenna and at least two back and forth readings for a total of 6 sec were required for optimal reading. Detection rates decreased after 100 RFID tags and it were not affected by the shape of the RFID tags. Reader-antenna and RFID tag interferences resulted from aluminum paper or RFID tags that touched one another. RFID tag detection rates obtained per operator were similar. Regarding real-life scenarios, detection rates increased with reading times and a plateau effect was observed after 10 sec. Undetected elements varied and non-detection was almost always related to the proximity of two RFID tags rather than the nature of the items read. Conclusion To our knowledge, this is the first prospective descriptive study that compares RFID tag detection rates based on various exploratory scenarios in order to identify optimal conditions of use. Such results can be used to develop a software application supporting drug replenishing through RFID in the drug use process.

Le pharmacien en gynécologie-obstétrique : revue de la littérature scientifique, contribution aux soins des patientes et optimisation de la pratique

Objectif. Reviser la documentation scientifique portant sur l’implication du pharmacien en gynecologie-obstetrique, evaluer les activites actuelles et proposer des ajustements pour optimiser la pratique pharmaceutique. Methodes. Etude descriptive comportant trois etapes : revue de la documentation scientifique portant sur l’implication du pharmacien en gynecologie-obstetrique, description des soins et services offerts, optimisation de la pratique pharmaceutique selon la revue documentaire et les suggestions des pharmaciennes œuvrant dans ce secteur. Resultats. Quinze articles ont ete retenus et indiquent que la presence du pharmacien diminue le taux d’erreurs medicamenteuses, augmente les connaissances des patients sur leurs medicaments et est evaluee positivement par les patients. Les resultats de la plupart de ces articles reposent sur des donnees probantes de qualite jugee insuffisante. La majorite des activites decrites sont deja realisees par les pharmaciennes de notre centre. Celles-ci incluent : conciliation medicamenteuse, optimisation de la pharmacotherapie, suivis pharmacocinetiques, conseils aux patientes, formation du personnel soignant et elaboration de protocoles de soins. Les ajustements proposes pour optimiser les activites pharmaceutiques incluent : optimisation des ressources documentaires, evaluation de la satisfaction des patientes, elargissement de l’automedication, etablissement d’une structure de prise en charge des patientes ambulatoires incluant les couples consultant au centre de procreation assistee et participation accrue a la recherche. Conclusion. Le sujet des soins pharmaceutiques en gynecologie-obstetrique est peu explore dans la documentation scientifique. Les pharmaciennes de notre centre realisent de nombreuses activites parmi celles decrites dans la documentation. Cet exercice a neanmoins permis d’identifier des elements a mettre en place afin d’optimiser leur pratique.

Identification des causes de défaillance à l’origine de retraits tardifs du marché et récentes réformes du système de pharmacovigilance au Canada

Les differentes crises sanitaires ont faconne les systemes de pharmacovigilance dans le monde et notamment au Canada. Depuis l’episode dramatique de la thalidomide, d’autres episodes sanitaires ont ete observes rappelant que ces systemes peuvent encore presenter des defaillances.