Impact of Pharmacist-Provided Education Using New Information Sheets on Activation in Patients Treated with Oral Antineoplastic Drugs (IMPACT-OAD Project).

Background: Oral antineoplastic drugs (OADs) play an increasing role in the treatment of cancer. Patients must have a high degree of understanding and autonomy to manage the numerous adverse effects at home. In Quebec, recommendations have been made for oncology pharmacists to systematically counsel all patients who are starting an OAD. Objective: To measure the impact of education provided by oncology pharmacists on patient activation. Methods: In this prospective, single-centre, observational cohort study, patients starting an OAD received education from oncology pharmacists, who used the 2020 updated version of information sheets from the Groupe d'étude en oncologie du Québec (GEOQ, www.geoq.info). The Patient Activation Measure (PAM-13) questionnaire was used to measure patients' activation before and after the intervention. Results: Of the 43 patients recruited in the intention-to-treat analysis, 41 were included in the modified intention-to-treat analysis. The mean difference between PAM-13 scores before and after the intervention was 2.30 (standard deviation [SD] 11.85) (p = 0.22) in the intention-to-treat analysis and 3.63 (SD 10.33) (p = 0.032) in the modified intention-to-treat analysis; these differences were less than the 5 points required for a result to be considered clinically meaningful. None of the effect-modifying variables for which data were collected had a significant impact on the degree of activation; however, a weak negative correlation was observed between the level of health literacy and the change in PAM-13 score. Conclusions: The study did not show a clinically meaningful change in patient activation following pharmacist-provided education, according to the updated GEOQ information sheets. Further studies are needed to evaluate these data in a larger population and to determine whether the impact of education persists beyond the first treatment cycle.

Contexte: Les médicaments antinéoplasiques par voie orale (MAVO) occupent une place grandissante dans le traitement du cancer. Les patients doivent avoir un degré élevé de compréhension et d'autonomie pour gérer les nombreux effets indésirables à domicile. Au Québec, des recommandations ont été émises pour que les pharmaciens en oncologie conseillent systématiquement tous les patients qui débutent des MAVO. Objectif: Mesurer l'impact des enseignements effectués par les pharmaciens en oncologie sur l'activation du patient. Méthodes: Dans cette étude de cohorte prospective, monocentrique et observationnelle, les patients qui commençaient à prendre des MAVO ont reçu un enseignement effectué par un pharmacien en oncologie. Ceux-ci utilisaient les feuillets d'information pour les patients du Groupe d'étude en oncologie du Québec (GEOQ, www.geoq.info) mis à jour en 2020. Le questionnaire de Mesure d'activation du patient (MAP-13) a été utilisé pour mesurer l'activation des participants avant et après l'intervention. Résultats: Sur les 43 participants recrutés dans l'analyse en intention de traiter, 41 ont été inclus dans l'analyse en intention de traiter modifiée (mITT). La différence moyenne entre les scores MAP-13 avant et après était de 2,30 (écart type [SD] 11,85) (p = 0,22) dans l'analyse en intention de traiter et de 3,63 (SD 10,33) (p = 0,032) dans l'analyse mITT; ces différences étaient inférieures aux 5 points requis pour qu'un résultat soit considéré comme cliniquement significatif. Aucune des variables modificatrices d'effet pour lesquelles des données ont été recueillies n'a eu d'effet significatif sur le degré d'activation; cependant, une faible corrélation négative a été observée entre le niveau de littératie en santé et la variation du score MAP-13. Conclusions: L'étude n'a pas démontré de changement cliniquement significatif dans l'activation des patients à la suite de l'enseignement effectué par le pharmacien en oncologie sur la base des feuillets d'information actualisés du GEOQ. D'autres études sont nécessaires pour évaluer ces données chez une plus grande population et pour déterminer si l'impact de l'enseignement perdure au-delà du premier cycle de traitement.

Assessing conservation status with extensive but low-resolution data: Application of frequentist and Bayesian models to endangered Athabasca River rainbow trout.

Use of extensive but low-resolution abundance data is common in the assessment of species at-risk status based on quantitative decline criteria under International Union for Conservation of Nature (IUCN) and national endangered species legislation. Such data can be problematic for 3 reasons. First, statistical power to reject the null hypothesis of no change is often low because of small sample size and high sampling uncertainty leading to a high frequency of type II errors. Second, range-wide assessments composed of multiple site-specific observations do not effectively weight site-specific trends into global trends. Third, uncertainty in site-specific temporal trends and relative abundance are not propagated at the appropriate spatial scale. A common result is the propensity to underestimate the magnitude of declines and therefore fail to identify the appropriate at-risk status for a species. We used 3 statistical approaches, from simple to more complex, to estimate temporal decline rates for a designatable unit (DU) of rainbow trout in the Athabasca River watershed in western Canada. This DU is considered a native species for purposes of listing because of its genetic composition characterized as >0.95 indigenous origin in the face of continuing introgressive hybridization with introduced populations in the watershed. Analysis of abundance trends from 57 time series with a fixed-effects model identified 33 sites with negative trends, but only 2 were statistically significant. By contrast, a hierarchical linear mixed model weighted by site-specific abundance provided a DU-wide decline estimate of 16.4% per year and a 3-generation decline of 93.2%. A hierarchical Bayesian mixed model yielded a similar 3-generation decline trend of 91.3% and the posterior distribution showed that the estimate had a >99% probability of exceeding thresholds for an endangered listing. We conclude that the Bayesian approach was the most useful because it provided a probabilistic statement of threshold exceedance in support of an at-risk status recommendation.

El uso de datos extensivos, pero de baja resolución, de la abundancia es una práctica común en la evaluación del estado de riesgo de una especie con base en los criterios cuantitativos de declinación establecidos por la Unión Internacional para la Conservación de la Naturaleza (UICN) y la legislación nacional sobre especies en peligro extinción. Dicha información puede ser problemática por tres razones: primero, el poder estadístico para rechazar la hipótesis nula de ningún cambio es frecuentemente bajo debido a un tamaño pequeño de la muestra y a la elevada incertidumbre del muestreo, lo que resulta en una frecuencia elevada de errores de tipo II; segundo, las evaluaciones de amplia variedad compuestas de varias observaciones específicas de sitio no sopesan efectivamente las tendencias específicas de sitio dentro de las tendencias globales; y tercero, la incertidumbre en las tendencias temporales específicas de sitio y en la abundancia relativa no se propagan a la escala espacial apropiada. Un resultado común del uso de esta información es la propensión a subestimar la magnitud de las declinaciones, y por lo tanto equivocarse en la identificación del estado de riesgo apropiado para la especie. Usamos tres estrategias estadísticas, de simples a más complejas, para estimar las tasas de declinación temporal para una unidad designable (UD) de trucha arcoíris en la cuenca del río Athabasca al oeste de Canadá. Esta UD es considerada una especie nativa por razones de listado debido a su composición genética, caracterizada como >0-95 de origen nativo de frente a la continua hibridación introgresiva con poblaciones introducidas a la cuenca. El análisis de las tendencias de abundancia de 57 series de tiempo con un modelo de efectos fijos identificó 33 sitios con tendencias negativas, pero sólo dos fueron estadísticamente significativas. En contraste, un modelo lineal mixto de jerarquías sopesado por abundancia específica de sitio proporcionó una estimación de declinación en toda la UD de 16.4% año−1 y una declinación a tres generaciones de 93.2%. Un modelo bayesiano de jerarquías produjo una tendencia de declinación a tres generaciones de 91.3% y la distribución posterior mostró que el estimado tuvo una probabilidad >99% de exceder los umbrales para la categorización como especie en peligro. Concluimos que la estrategia bayesiana fue la más útil porque proporcionó una afirmación probabilística de la superación del umbral a favor de una recomendación de categorizar el estado como en riesgo.

Anticoagulation management services in community pharmacy: Feasibility of implementing a quality improvement programme through a practice-based research network.

WHAT IS KNOWN AND OBJECTIVE: The literature has reported suboptimal real-world use of oral anticoagulants in patients with atrial fibrillation (AF). Anticoagulation management services (AMSs) in community pharmacy have rarely been evaluated, and no formal process is available to enable pharmacists to evaluate and improve their clinical practices. Our objective was to assess the feasibility of implementing, through a practice-based research network (PBRN), a quality improvement programme on AMSs by community pharmacists for AF patients and explore its impact on the quality of clinical practices and pharmacists' knowledge. METHODS: An uncontrolled pre/post-pilot study was conducted through a PBRN. Pharmacists identified 5-20 AF patients on oral anticoagulants per pharmacy and completed questionnaires at baseline (T0) and after 6 months (T6). Clinical practices were evaluated using a set of quality indicators (QIs). QI scores ranged from 0% (no QI achieved) to 100% (all QIs achieved). The programme included an audit and feedback based on QIs and a personalized training programme (including online videos). Participation rates and satisfaction were documented. Mean changes (T6-T0), with 95% confidence interval (CI), in QIs and knowledge scores were computed. RESULTS AND DISCUSSION: A total of 37 pharmacies (50 pharmacists) identified 222 patients who had received either vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), or both. All pharmacies received their baseline quality report (audit), and facilitators contacted by phone 97% of pharmacies (feedback). Each of the six online videos was completed by at least 48% of pharmacists. Baseline mean global QI scores for VKAs and DOACs were 39.1% (95% CI: 35.7%-42.4%) and 12.3% (7.8%-16.8%), respectively. Over a 6-month period, they increased by 12.5% points (7.5%-17.5%) and 9.9% points (3.8%-16.1%), respectively. Baseline mean global knowledge score was 68.7% (65.4%-72.0%) and increased by 4.3% points (1.2%-7.4%). WHAT IS NEW AND CONCLUSION: Implementing a quality improvement programme for AMS in community pharmacy is relevant and feasible and may improve pharmacists' practices and knowledge.

Habitat availability and ontogenetic shifts alter bottlenecks in size-structured fish populations.

For species that utilize different habitats throughout their life cycle, the habitat limitation at a given stage can act as a bottleneck on population abundance, impacting density-dependent processes such as individual growth and survival. We explore the influence of habitat limitation on population dynamics by developing a multi-stage population model based on lake-dwelling rainbow trout (Oncorhynchus mykiss) populations where adults occupy the lake habitat but use tributaries for spawning and juvenile rearing. The model details density-dependent ecological processes and ontogenetic habitat shifts, harvest mortality, and the impact of climate on growth. We ran model simulations using a range of early life stage habitat availabilities and climatic conditions representative of the native range of rainbow trout in Canada and compared the results to empirical data. The results suggest that (1) increases in early life stage habitat leads to increases in population abundance but, due to density-dependent processes, also results in slower growing stunted populations; (2) population bottlenecks can occur at any life stage, even at the adult stage if spawning and rearing habitats are abundant; (3) when the level of competition for early life stages is increased, inter-cohort competition can lead to population cycles. The model's conclusions are further reinforced by empirical data showing a similar trend in the relationship between fish density and maximum size and providing evidence that limited early life stage habitat leads to lower fish densities and larger fish size. We provide a model that links environmental conditions to population dynamics and is useful for fisheries management and habitat conservation decisions.

Risk Factors for Nephrotoxicity Associated with Cisplatin.

BACKGROUND: Cisplatin-induced nephrotoxicity occurs in about one-third of patients who receive this chemotherapy drug. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure. OBJECTIVE: To evaluate the extent of nephrotoxicity associated with cisplatin and the influence of risk factors for nephrotoxicity. METHODS: This retrospective study involved patients who received a first cycle of cisplatin-based chemotherapy between November 1, 2012, and November 1, 2013. Patients' medical records were reviewed to determine the increase in creatinine level (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events) and the influence of certain prespecified risk factors, such as age, concomitant medications, initial dose of cisplatin, and related medical conditions. RESULTS: Among the 80 patients evaluated, 14 (17%) experienced no increase in the level of serum creatinine (grade 0), 44 (55%) experienced a grade 1 increase, 19 (24%) a grade 2 increase, and 3 (4%) a grade 3 increase; no patients experienced a grade 4 increase. Patients with the greatest risk of a grade 2 or 3 increase were those treated with hydrochlorothiazide (odds ratio [OR] 9.35, 95% confidence interval [CI] 2.49 to 35.14) or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 5.02, 95% CI 1.76 to 14.32). After adjustment, only hydrochlorothiazide was associated with an increased risk of nephrotoxicity (OR 5.39, 95% CI 1.04 to 28.07). Among patients taking hydrochlorothiazide, the average incremental increase in serum creatinine was 59.9 µmol/L (95% CI 34.3 to 85.4 µmol/L). CONCLUSIONS: Taking hydrochlorothiazide was associated with a significant increase in serum creatinine following cisplatin therapy. On the basis of these results, patients should stop taking hydrochlorothiazide before undergoing cisplatin-based chemotherapy.

CONTEXTE: La néphrotoxicité associée au cisplatine se produit chez environ le tiers des patients qui reçoivent ce médicament de chimiothérapie. À la fin de 2012, l'établissement de santé des auteurs a commencé à mesurer la créatinine sérique au jour 7 après l'administration de cisplatine afin de repérer les patients atteints d'insuffisance rénale aiguë. OBJECTIF: Évaluer le degré de la néphrotoxicité associée au cisplatine et déterminer si des facteurs de risque favorisent cette néphrotoxicité. MÉTHODES: Cette étude rétrospective a été menée auprès de patients ayant subi un premier cycle de chimiothérapie à base de cisplatine entre le premier novembre 2012 et le premier novembre 2013. Les dossiers médicaux des patients ont été examinés afin de détecter les cas d'augmentation de créatinine sérique (qui ont été classés selon les critères pour une terminologie commune des événements indésirables du National Cancer Institute) et l'influence de facteurs de risque préétablis (âge, médicaments concomitants, dose initiale de cisplatine et pathologies associées). RÉSULTATS: Parmi les 80 patients analysés, 14 (17 %) n'affichaient aucune augmentation du taux de créatinine sérique (degré 0), 44 (55 %) présentaient une augmentation de degré 1, 19 (24 %) affichaient une augmentation de degré 2 et 3 (4 %) présentaient une augmentation de degré 3; aucun ne présentait une augmentation de degré 4. Les patients qui couraient le plus grand risque de connaître une augmentation de degré 2 ou 3 étaient ceux traités avec l'hydrochlorothiazide (risque relatif approché [RRA] de 9,35, intervalle de confiance [IC] à 95 % de 2,49 à 35,14) ou d'un inhibiteur de l'enzyme de conversion de l'angiotensine ou d'un bloqueur des récepteurs de l'angiotensine II (RRA de 5,02, IC à 95 % de 1,76 à 14,32). Après ajustement, seul l'hydrochlorothiazide était associé à une augmentation du risque de néphrotoxicité (RRA de 5,39, IC à 95 % de 1,04 à 28,07). Parmi les patients qui prenaient de l'hydrochlorothiazide, l'augmentation différentielle moyenne de créatinine sérique était de 59,9 µmol/L (IC à 95 % de 34,3 à 85,4 µmol/L). CONCLUSIONS: La prise concomitante d'hydrochlorothiazide a été associée à une augmentation significative de la créatinine sérique après un traitement de cisplatine. Considérant ces résultats, les patients devraient cesser de prendre de l'hydrochlorothiazide avant de recevoir une chimiothérapie à base de cisplatine.

Evaluation of a continuous quality improvement program in anticoagulant therapy: Feasibility, satisfaction and perception.

BACKGROUND: The ACO Program (Programme ACO), a continuous quality improvement program (CQIP) in anticoagulation therapy, was offered in community pharmacies as a pilot project. OBJECTIVE: To evaluate the participants' appreciation for the various activities of the program. METHODS: Participants had access to training activities, including an audit with feedback, online training activities (OTA), clinical tools and support from facilitators. Cognitive behavioural learning determinants were evaluated before and 5 months after the beginning of the program. Participants' satisfaction and perception were documented via online questionnaires and a semistructured interview. RESULTS: Of the 52 pharmacists in the ACO Program, 47 participated in this evaluation. Seventy-seven percent of the participants completed at least 1 OTA and 6% published on the forum. The feeling of personal effectiveness rose from 8.01 (7.67-8.35) to 8.62 (8.24-8.99). The audit and feedback, as well as the high-quality OTA and their lecturers, were the most appreciated elements. DISCUSSION: There was a high OTA participation rate. The facilitators seemed to play a key role in the CQIP. The low level of participation in the forum reflects the known phenomenon of social loafing. Technical difficulties affecting the platform and data collection for the audit with feedback constituted limitations. CONCLUSION: The CQIP in anticoagulation therapy is appreciated by community pharmacists and is associated with an improved feeling of personal effectiveness.

Interaction of ecological and angler processes: experimental stocking in an open access, spatially structured fishery.

Effective management of socioecological systems requires an understanding of the complex interactions between people and the environment. In recreational fisheries, which are prime examples of socioecological systems, anglers are analogous to mobile predators in natural predator-prey systems, and individual fisheries in lakes across a region are analogous to a spatially structured landscape of prey patches. Hence, effective management of recreational fisheries across large spatial scales requires an understanding of the dynamic interactions among ecological density dependent processes, landscape-level characteristics, and angler behaviors. We focused on the stocked component of the open access rainbow trout (Oncorhynchus mykiss) fishery in British Columbia (BC), and we used an experimental approach wherein we manipulated stocking densities in a subset of 34 lakes in which we monitored angler effort, fish abundance, and fish size for up to seven consecutive years. We used an empirically derived relationship between fish abundance and fish size across rainbow trout populations in BC to provide a measure of catch-based fishing quality that accounts for the size-abundance trade off in this system. We replicated our experimental manipulation in two regions known to have different angler populations and broad-scale access costs. We hypothesized that angler effort would respond to variation in stocking density, resulting in spatial heterogeneity in angler effort but homogeneity in catch-based fishing quality within regions. We found that there is an intermediate stocking density for a given lake or region at which angler effort is maximized (i.e., an optimal stocking density), and that this stocking density depends on latent effort and lake accessibility. Furthermore, we found no clear effect of stocking density on our measure of catch-based fishing quality, suggesting that angler effort homogenizes catch-related attributes leading to an eroded relationship between stocking density and catch-based fishing quality at the timescale of annual surveys. We conclude that declines in fishing quality resulting from understocking (due to declines in catch rate with low fish abundance) and overstocking (due to suppressed growth and limited recruitment at high density) give an optimal stocking rate that depends on accessibility and latent effort.

Supply-demand equilibria and the size-number trade-off in spatially structured recreational fisheries.

Recreational fishing effort varies across complex inland landscapes (e.g., lake-districts) and appears influenced by both angler preferences and qualities of the fishery resource, like fish size and abundance. However, fish size and abundance have an ecological trade-off within a population, thereby structuring equal-quality isopleths expressing this trade-off across the fishing landscape. Since expressed preferences of recreational anglers (i.e., site-selection of high-quality fishing opportunities among many lakes) can be analogous to optimal foraging strategies of natural predators, adopting such concepts can aid in understanding scale-dependence in fish-angler interactions and impacts of fishing across broad landscapes. Here, we assumed a fish supply-angler demand equilibria and adapted a novel bivariate measure of fishing quality based on fish size and catch rates to assess how recreational anglers influence fishing quality among a complex inland landscape. We then applied this metric to evaluate (1) angler preferences for caught and released fish compared to harvested fish, (2) the nonlinear size-numbers trade-off with uncertainty in both traits, and (3) the spatial-scale of the equilibria across 62 lakes and four independent management regions in British Columbia's (BC) rainbow trout Oncorhynchus mykiss fishery. We found anglers had low preference for caught and released fish (~10% of the value compared to harvested fish), which modified anglers' perception of fishing quality. Hence, fishing quality and angler effort was not influenced simply by total fish caught, but largely by harvested fish catch rates. Fishing quality varied from BC's northern regions (larger fish and more abundant) compared to southern regions (smaller fish and less abundant) directly associated with a 2.5 times increase in annual fishing effort in southern regions, suggesting that latent fishing pressure can structure the size-numbers trade-off in rainbow trout populations. The presence of two different equal-quality isopleths suggests at least two effective landscapes support co-occurring ideal free distributions of recreational fishing effort in BC's rainbow fishery. Anglers' expressed preferences among lakes interacted with density dependent growth and survival within lakes to structure a size-numbers trade-off influencing how anglers perceive fishing quality and, ultimately, distribute across complex inland landscapes.

Development and validation of a high-throughput screening assay for the hepatitis C virus p7 viroporin.

The HCV p7 protein is not involved in viral RNA replication but is essential for production of infectious virus. Based on its putative ion channel activity, p7 belongs to a family of viral proteins known as viroporins that oligomerize after insertion into a lipid membrane. To screen for compounds capable of interfering with p7 channel function, a low-throughput liposome-based fluorescent dye permeability assay was modified and converted to a robust high-throughput screening assay. Escherichia coli expressing recombinant p7 were grown in high-density fed-batch fermentation followed by a detergent-free purification using a combination of affinity and reversed-phase chromatography. The phospholipid composition of the liposomes was optimized for both p7 recognition and long-term stability. A counterscreen was developed using the melittin channel-forming peptide to eliminate nonspecific screening hits. The p7 liposome-based assay displayed robust statistics (Z' > 0.75), and sensitivity to inhibition was confirmed using known inhibitors.