Understanding the experiences of Black Nova Scotians with community pharmacists.

Background: A history of medical abuse and social inequality confounded by persistent racial discrimination in health care has triggered mistrust between Black patients and health care providers. Although the consequences of systemic racism on health outcomes are well understood, little is known about how they manifest in pharmacy practice. The objective of this study was to explore the experiences of Black Nova Scotians with community pharmacists. Methods: This was a qualitative study that used focus groups and one-on-one interviews. Black Nova Scotians 18 years of age and older who have had interactions with community pharmacists were invited to participate. Focus groups and interviews were audio-recorded, transcribed and analyzed thematically. Results: Two focus groups (n = 10) and 6 one-on-one interviews were held between May and June 2021. Three major themes were identified: 1) difficulties navigating a pharmacy as a Black person, 2) lack of inclusivity and cultural competence in the pharmacy and 3) transactional relationships with pharmacists. Discussion: Most participants felt their race negatively affected the quality of care they received from the pharmacist and that pharmacists were not culturally competent. Most participants did not consider pharmacists to be part of their health care team and described feeling unsafe or uncomfortable in the pharmacy. Conclusions: Pharmacists have an important role in closing the health equity gap. This research highlights the need for pharmacy education to include cultural competence and will be used to guide strategies to improve access to culturally safe pharmacy services for Black Nova Scotians.

Optimizing patient education of oncology medications: A quantitative analysis of the patient perspective.

BACKGROUND: With the ever-increasing complexity of cancer treatments, oncology medication patient education is becoming a progressively important component of cancer care. Despite this, cancer patients frequently report that they receive inadequate information and feel that their education needs have not been met. OBJECTIVE: To explore patients' perspectives of optimal oncology medication education across Nova Scotia. METHODS: This was a descriptive survey of adult medical, hematological and gynaecological oncology outpatients receiving intravenous chemotherapy within the Nova Scotia Health Authority between January 26 and April 30, 2018. RESULTS: One hundred forty-two responses were included; 41% and 47% of respondents reported being satisfied or very satisfied with their oncology medication education, respectively; 30% and 43% of respondents would like the opportunity to receive education or follow-up from a hospital pharmacist, respectively. Respondents with post-secondary education were found to have 2.82 higher odds of wanting to make an appointment for education with a hospital pharmacist. CONCLUSIONS: Patients were generally satisfied with their oncology medication education despite the majority not receiving education from a hospital pharmacist. Patients with a higher level of formal education were more likely to want the opportunity to schedule an appointment for education with and/or receive follow-up from a hospital pharmacist. The oncology medication education participants received in the past appeared to align with their education preferences. Findings from this research can be used to optimize the limited time healthcare professionals have to provide meaningful and effective oncology medication patient education and improve patient-centered care.

Increased self-reported pharmacist prescribing during the COVID-19 pandemic: Using the Theoretical Domains Framework to identify barriers and facilitators to prescribing.

BACKGROUND: Community pharmacists are positioned to improve access to medications through their ever-expanding role as prescribers, with this role becoming more pronounced during the COVID-19 pandemic. OBJECTIVES: Our research aimed to determine the extent of self-reported pharmacist prescribing pre-COVID-19 and during the COVID-19 pandemic, to identify barriers and facilitators to pharmacist prescribing, and to explore the relationship between these factors and self-reported prescribing activity. METHODS: A questionnaire based on the Theoretical Domains Framework (TDFv2) assessing self-reported prescribing was electronically distributed to all direct patient care pharmacists in NS (N = 1338) in July 2020. Wilcoxon signed-rank tests were used to examine temporal differences in self-reported prescribing activity. TDFv2 responses were descriptively reported as positive (agree/strongly agree), neutral (uncertain), and negative (strongly disagree/disagree) based on the 5-point Likert scale assessing barriers and facilitators to prescribing from March 2020 onward (i.e., 'during' COVID-19). Simple logistic regression was used to measure the relationship between TDFv2 domain responses and self-reported prescribing activity. RESULTS: A total of 190 pharmacists (14.2%) completed the survey. Over 98% of respondents reported prescribing at least once per month in any of the approved prescribing categories, with renewals being the most common activity reported. Since the pandemic, activity in several categories of prescribing significantly increased, including diagnosis supported by protocol (29.0% vs. 58.9%, p < 0.01), minor and common ailments (25.3% vs 34.7%, p = 0.03), preventative medicine (22.1% vs. 33.2%, p < 0.01). Amongst the TDFv2 domains, Beliefs about Consequences domain had the largest influence on prescribing activity (OR = 3.13, 95% CI 1.41-6.97, p < 0.01), with Social Influences (OR = 2.85, 95% CI 1.42-5.70, p < 0.01) being the next most influential. CONCLUSION: Self-reported prescribing by direct patient care community pharmacists in Nova Scotia increased during the COVID-19 pandemic, particularly for government-funded services. Key barriers to address, and facilitators to support pharmacist prescribing were identified and can be used to inform future interventions.

Transcriptional regulation by Asf1: new mechanistic insights from studies of the DNA damage response to replication stress.

Asf1 is a conserved histone H3/H4 chaperone. We find that Asf1 in budding yeast promotes an essential cellular response to replication stress caused by the ribonucleotide reductase inhibitor hydroxyurea. That is, Asf1 stimulates derepression of DNA damage response (DDR) genes during the S phase. Derepression of DDR genes strongly correlates with Asf1 binding to their promoters. Having identified the C terminus and histone-binding domains of Asf1 as molecular determinants of its constitutive and inducible association with chromatin, we tested whether Asf1 binding to DDR genes is mechanistically important for their derepression. Our results provide little support for this hypothesis. Rather, the contribution of Asf1 to DDR gene derepression depends on its ability to stimulate H3K56 acetylation by lysine acetyltransferase Rtt109. The precise regulation of H3K56 acetylation in the promoters of DDR genes is unexpected: DDR gene promoters are occupied by H3K56-acetylated nucleosomes under repressing conditions, and the steady state level of H3K56 promoter acetylation does not change upon derepression. We propose that replication-coupled deposition of Lys(56)-acetylated H3 poises the DDR genes in newly synthesized daughter duplexes for derepression during the S phase. In this model, the presence of a histone mark that destabilizes nucleosomes is compatible with suppression of transcription because in the uninduced state, DDR gene promoters are constitutively occupied by a potent repressor-corepressor complex.

Opioid Use at End-Of-Life Among Nova Scotia Patients With Cancer.

Purpose: To determine the factors associated with opioid analgesic prescriptions as measured by community pharmacy dispensations to all Nova Scotia (NS) patients with cancer at end-of-life from 2005 to 2009. Methods: The NS Cancer Registry and the NS Prescription Monitoring Program (NSPMP) were used to link Nova Scotians who had a cancer diagnosis and received a prescription for opioids in their last year of life (n = 6,186) from 2005 to 2009. The association of factors with opioid dispensations at end-of-life were determined (e.g., patient demographics, type of prescriber, type of cancer, and opioid type, formulation, and dose). Results: Almost 54% (n = 6,186) of the end-of-life study population with cancer (n = 11,498) was linked to the NSPMP and therefore dispensed opioids. Most prescriptions were written by general practitioners (89%) and were for strong opioids (81%). Immediate-release formulations were more common than modified-release formulations. Although the annual average parenteral morphine equivalents (MEQ) did not change during the study period, the number of opioid prescriptions per patient per year increased from 5.9 in 2006 to 7.0 in 2009 (p < 0.0001). Patients age 80 and over received the fewest prescriptions (mean 3.9/year) and the lowest opioid doses (17.0 MEQ) while patients aged 40-49 received the most prescriptions (mean 14.5/year) and the highest doses of opioid (80.2 MEQ). Conclusion: Our study examined opioid analgesic use at end-of-life in patients with cancer for a large real-world population and determined factors, trends and patterns associated with type and dose of opioid dispensed. We provide information regarding how general practitioners prescribe opioid therapy to patients at end-of-life. Our data suggest that at the time of this study, there may have been under-prescribing of opioids to patients with cancer at end-of-life. This information can be used to increase awareness among general practitioners, and to inform recommendations from professional regulatory bodies, to aid in managing pain for cancer patients at end-of-life. Future work could address how opioid prescribing has changed over time, and whether efforts to reduce opioid prescribing in response to the opioid crisis have affected patients with cancer at end-of-life in Nova Scotia.

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) affect immunologic homeostasis, leading to immune-related adverse events (irAEs). Early irAE detection and management can prevent significant morbidity and mortality. A retrospective chart review was performed to characterize irAEs associated with nivolumab, ipilimumab, and nivolumab plus ipilimumab in adult medical oncology patients in Nova Scotia Health-Central Zone from 2013-2020, and to describe adherence to toxicity management guidelines. Diarrhea/colitis, hepatitis, pneumonitis, nephrotoxicity, and cardiotoxicity were studied. Of 129 charts reviewed, 67 patients (51.9%) experienced at least one irAE for a total of 98 irAEs and a 1.5% fatality rate. Of these irAEs, 33.7% led to an emergency room visit. Patients were admitted to hospital and steroids were used in 24.5% and 35.7% of cases, respectively. In 17.3% of irAEs, ICIs were permanently discontinued. In 20.4% of irAEs, ICIs were held, and patients were monitored; while in 18.4%, ICIs were held until the irAE was Grade 0-1 (and until steroids were tapered). Almost 47% of irAEs were managed according to guidelines (14.3% were not), and 38.8% had no documented management. Patients receiving immunotherapy frequently experience irAEs with half of irAEs having documented management adhering to guidelines. As immunotherapy indications expand, it is important to ensure irAEs are documented and managed appropriately.

Exploring the perspectives of healthcare professionals in delivering optimal oncology medication education.

BACKGROUND: To optimize patient education, it is important to understand what healthcare professionals perceive to be ideal oncology medication education for patients to receive, and what they feel is their role and the role of others in its delivery. Education provided to patients is an important component of chemotherapy as it has been shown to benefit and positively impact patients who receive it. Educational interventions are often provided by multidisciplinary teams with the goal of improving patient care. However, few studies have explored the roles of healthcare professionals in delivering oncology medication education. OBJECTIVE: To explore the perspectives of healthcare professionals working in medical, gynaecological or hematological oncology to identify what they perceive to be optimal oncology medication education for patients. METHODS: Healthcare professionals (physicians, nurses and pharmacists) working in medical, gynaecological or hematological oncology at the Nova Scotia Health Authority, Central Zone were invited to participate in one-on-one, semi-structured interviews which were audio-recorded, transcribed and analyzed using thematic analysis. FINDINGS: Fifteen interviews, including five physicians, four nurses and six pharmacists were conducted from February to April 2018. Four major themes were identified: Delivery of oncology medication education, Facilitating the patient learning process, Multidisciplinary Approach and Understanding barriers to the healthcare professional in providing education. CONCLUSION: The identified themes uncovered novel ideas about how healthcare professionals felt oncology medication education could ideally be delivered to patients, and supported findings in the literature. Although participants discussed barriers to their ability to deliver optimal education, they also identified ways in which they can facilitate patient learning, for example, through the reinforcement of education. Participants recognized the importance of increasing collaboration and communication with the multidisciplinary team. This research will inform the design of any new models for oncology medication education at the Nova Scotia Health Authority, Central Zone and potentially other sites.

Point Prevalence Survey of Benzodiazepine and Sedative-Hypnotic Drug Use in Hospitalized Adult Patients.

BACKGROUND: Benzodiazepines and sedative-hypnotic drugs (BZD/SHDs), such as zopiclone and the antidepressant trazodone, pose risks such as falls, fractures, and confusion, especially for older adults. Use of these drugs in the acute care setting is poorly understood. OBJECTIVES: To determine the point prevalence and characteristics of use of BZD/SHDs in hospitals in Nova Scotia, Canada. METHODS: A point prevalence survey was conducted for adults admitted to all hospitals with at least 30 acute care beds between May and August 2016. Drugs administered intravenously, patients in long-term care, and patients receiving mental health services, addiction treatment, or critical care were excluded. The proportion of included patients who had received a BZD/SHD within the 24 h before the start of the survey was determined. A descriptive statistical analysis was performed. RESULTS: Overall BZD/SHD prevalence was 34.6% (487/1409) across the 16 eligible hospitals. The average age was 70.3 years, and 150 (30.8%) of the patients were 80 years or older. Among the 585 prescriptions for these patients, commonly used drugs were zopiclone (32.0%), lorazepam (21.9%), and trazodone (21.9%). The most common indications for use were bedtime/daytime sedation (60.0%) and anxiety (12.5%). More than half of the prescriptions (55.7%) had been initiated at home, 37.6% were started in hospital, and the place of initiation was unknown for 6.7%. Benzodiazepines were prescribed more frequently to patients under 65 years than those 80 years or older (41.3% versus 22.2%, p < 0.001) whereas trazodone was more frequently prescribed to the older of these 2 age groups (52.7% versus 14.3%, p < 0.001). CONCLUSIONS: BZD/SHDs were frequently used by hospitalized adult patients in Nova Scotia. Trazodone appears to have been substituted for benzodiazepines in the oldest age group. Pharmacists should direct their efforts toward preventing inappropriate initiation of BZD/SHDs in hospital, particularly for elderly patients.

CONTEXTE: Les benzodiazépines et les médicaments sédatifs-hypnotiques (BZD/MSH), comme la zopiclone et l'antidépresseur trazodone, comportent des risques de chute, de fracture et de confusion, particulièrement chez les personnes âgées. Il existe une mauvaise compréhension de l'utilisation de ces médicaments dans un contexte de soins intensifs. OBJECTIFS: Déterminer la prévalence ponctuelle et les caractéristiques de l'utilisation des BZD/MSH dans des hôpitaux en Nouvelle-Écosse, au Canada. MÉTHODES: Une enquête sur la prévalence ponctuelle a été menée entre mai et août 2016 auprès d'adultes admis dans les hôpitaux comptant au moins 30 lits en soins intensifs. Les patients recevant ces médicaments par voie intraveineuse, ceux en établissement de soins de longue durée, ceux recevant des services en santé mentale ou un traitement pour la toxicomanie ou encore ceux des soins intensifs ont été exclus de l'enquête. La détermination de la proportion des patients inclus dans l'étude portait sur ceux qui avaient reçu des BZD/MSH au cours des 24 h précédant le début de l'enquête, et elle a été suivie d'une analyse statistique descriptive. RÉSULTATS: e manière générale, l'usage des BZD/MSH s'élevait à 34,6 % (487/1409) dans les 16 hôpitaux participants. L'âge moyen des patients était de 70,3 ans et 150 (30,8 %) étaient âgés d'au moins 80 ans. Parmi les 585 prescriptions pour ces patients, les médicaments communément utilisés étaient la zopiclone (32,0 %), le lorazepam (21,9 %) et le trazodone (21,9 %). Les indications d'utilisation les plus répandues concernaient la sédation au coucher et en cours de journée (60 %) et l'anxiété (12,5 %). Plus de la moitié des prescriptions (55,7 %) ont commencé à domicile, 37,6 % ont commencé à l'hôpital, et le lieu du début de la prise de ces médicaments était inconnu dans 6,7 % des cas. La prescription des benzodiazépines s'adressait plus souvent aux patients de moins de 65 ans qu'à ceux d'au moins 80 ans (41,3 % par rapport à 22,2 %, p < 0,001), tandis que la prescription de trazodone s'adressait plus souvent aux personnes de la tranche d'âge plus avancée (52,7 % par rapport à 14,3 %, p < 0,001). CONCLUSIONS: Les BZD/MSH étaient fréquemment utilisés par les patients adultes hospitalisés en Nouvelle-Écosse. La trazodone semble avoir remplacé les benzodiazépines dans le groupe plus âgé. Les pharmaciens devraient orienter leurs efforts sur la prévention de la prise inappropriée des BZD/MSH en hôpital, particulièrement par les patients plus âgés.

Identification of the relationship between barriers and facilitators of pharmacist prescribing and self-reported prescribing activity using the theoretical domains framework.

BACKGROUND: The scope of pharmacist practice has expanded in many jurisdictions, including Nova Scotia, Canada, to include prescribing of medications. OBJECTIVE: To identify the relationship between barriers and facilitators to pharmacist prescribing and self-reported prescribing activity using the Theoretical Domains Framework version 2 (TDF(v2)). METHODS: The study was a self-administered electronic survey of all registered pharmacists (approximately 1300) in Nova Scotia, Canada. The questionnaire was developed using a consensus process that mapped facilitators and barriers to prescribing with the 14 domains of the TDF(v2). The questionnaire captured information about the type and rate of pharmacists' prescribing activities, pharmacists' perceptions of their prescribing role at the patient, pharmacist, pharmacy organization and health system level, and pharmacist demographics and practice settings. A 5-point Likert scale was used for most TDF(v2) domains. Cronbach's alpha was used to study the internal consistency of responses within each of the TDF(v2) domains and simple logistic regression was used to measure the relationship between TDF(v2) domain responses and self-reported prescribing activity. Open-ended questions were analyzed separately. RESULTS: Eighty-seven pharmacists completed the questionnaire. The majority of respondents were female (70 %), staff pharmacists (52 %) practicing pharmacy for a mean of 18 years. The three domains that respondents most positively associated with prescribing were Knowledge (84 %), Reinforcement (81 %) and Intentions (78 %). The largest effect on prescribing activity was the Skills domain (OR 4.41, 95% CI, 1.34-14.47). CONCLUSIONS: We determined the TDF(v2) domains associated with pharmacist self-reported prescribing behaviours. This understanding can assist the development of policy and program interventions at the pharmacist, pharmacy, and health system levels, to increase the uptake of pharmacist prescribing. Further work is needed to develop and implement interventions based on the domains identified, and to test these in pilot settings and then in large-scale interventions.

Domain organization of the yeast histone chaperone FACT: the conserved N-terminal domain of FACT subunit Spt16 mediates recovery from replication stress.

The abundant nuclear complex termed FACT affects several DNA transactions in a chromatin context, including transcription, replication, and repair. Earlier studies of yeast FACT, which indicated the apparent dispensability of conserved sequences at the N terminus of the FACT subunit Cdc68/Spt16, prompted genetic and biochemical studies reported here that suggest the domain organization for Spt16 and the other FACT subunit Pob3, the yeast homolog of the metazoan SSRP1 protein. Our findings suggest that each FACT subunit is a multidomain protein, and that FACT integrity depends on Pob3 interactions with the Spt16 Mid domain. The conserved Spt16 N-terminal domain (NTD) is shown to be without essential function during normal growth, but becomes important under conditions of replication stress. Genetic interactions suggest that some functions carried out by the Spt16 NTD may be partially redundant within FACT.

Trends in Statin Use in Seniors 1999 to 2013: Time Series Analysis.

PURPOSE: To examine HMG-CoA reductase inhibitor (statin) drug dispensing patterns to Nova Scotia Seniors' Pharmacare program (NSSPP) beneficiaries over a 14-year period in response to: 1) rosuvastatin market entry in 2003, 2) JUPITER trial publication in 2008, and 3) generic atorvastatin availability in 2010. METHODS: All NSSPP beneficiaries who redeemed at least one prescription for a statin from April 1, 1999 to March 31, 2013 were included. Aggregated, anonymous monthly prescription counts were extracted by the Nova Scotia Department of Health and Wellness (Nova Scotia, Canada) and changes in dispensing patterns of statins were measured. Data were analyzed using descriptive analyses and interrupted time series methods. RESULTS: The percentage of NSSPP beneficiaries dispensed any statin increased from 5.3% in April 1999 to 20.7% in March 2013. In 1999, most NSSPP beneficiaries were dispensed either simvastatin (29.5%) or atorvastatin (28.7%). When rosuvastatin was added to the NSSPP Formulary in August 2003, prescriptions dispensed for simvastatin, lovastatin, pravastatin, and fluvastatin declined significantly (slope change, -0.0027; 95% confidence interval (CI), (-0.0046, -0.0009)). This significant decline continued following the publication of JUPITER (level change, -0.1974; 95% CI, (-0.2991, -0.0957)) and the availability of generic atorvastatin (level change, -0.2436; 95% CI, (-0.3314, -0.1558)). Atorvastatin was not significantly affected by any of the three interventions, although it maintained an overall decreasing trend. Only upon the availability of generic atorvastatin did the upward trend in rosuvastatin use decrease significantly (slope change, -0.0010, 95% CI, (-0.0015, -0.0005)). CONCLUSIONS: The type and rate of statins dispensed to NSSPP beneficiaries changed from 1999 to 2013 in response to the availability of new agents and publication of the JUPITER trial. The overall proportion of NSSPP beneficiaries dispensed a statin increased approximately 4-fold during the study period. In 2013, rosuvastatin was the most commonly dispensed statin (44.1%) followed by atorvastatin (39.1%).

Pharmacists' Perceptions of the Barriers and Facilitators to the Implementation of Clinical Pharmacy Key Performance Indicators.

BACKGROUND: In hospitals around the world, there has been no consensus regarding which clinical activities a pharmacist should focus on until recently. In 2011, a Canadian clinical pharmacy key performance indicator (cpKPI) collaborative was formed. The goal of the collaborative was to advance pharmacy practice in order to improve patient outcomes and enhance the quality of care provided to patients by hospital pharmacists. Following a literature review, which indicated that pharmacists can improve patient outcomes by carrying out specific activities, and an evidence-informed consensus process, a final set of eight cpKPIs were established. Canadian hospitals leading the cpKPI initiative are currently in the early stages of implementing these indicators. OBJECTIVE: To explore pharmacists' perceptions of the barriers and facilitators to the implementation of cpKPIs. METHODS: Clinical pharmacists employed by the Nova Scotia Health Authority were invited to participate in focus groups. Focus group discussions were audio-recorded and transcribed, and data was analyzed using thematic analysis. FINDINGS: Three focus groups, including 26 pharmacists, were conducted in February 2015. Three major themes were identified. Resisting the change was comprised of documentation challenges, increased workload, practice environment constraints, and competing priorities. Embracing cpKPIs was composed of seeing the benefit, demonstrating value, and existing supports. Navigating the unknown was made up of quality versus quantity battle, and insights into the future. CONCLUSIONS: Although pharmacists were challenged by documentation and other changes associated with the implementation of cpKPIs, they demonstrated significant support for cpKPIs and were able to see benefits of the implementation. Pharmacists came up with suggestions for overcoming resistance associated with the implementation of cpKPIs and provided insights into the future of pharmacy practice. The identification of barriers and facilitators to cpKPI implementation will be used to inform the implementation process on a local and national level.

SWI/SNF and Asf1 independently promote derepression of the DNA damage response genes under conditions of replication stress.

The histone chaperone Asf1 and the chromatin remodeler SWI/SNF have been separately implicated in derepression of the DNA damage response (DDR) genes in yeast cells treated with genotoxins that cause replication interference. Using genetic and biochemical approaches, we have tested if derepression of the DDR genes in budding yeast involves functional interplay between Asf1 and SWI/SNF. We find that Asf1 and SWI/SNF are both recruited to DDR genes under replication stress triggered by hydroxyurea, and have detected a soluble complex that contains Asf1 and the Snf2 subunit of SWI/SNF. SWI/SNF recruitment to DDR genes however does not require Asf1, and deletion of Snf2 does not affect Asf1 occupancy of DDR gene promoters. A checkpoint engagement defect is sufficient to explain the synthetic effect of deletion of ASF1 and SNF2 on derepression of the DDR genes in hydroxyurea-treated cells. Collectively, our results show that the DDR genes fall into a class in which Asf1 and SWI/SNF independently control transcriptional induction.

Asf1 can promote trimethylation of H3 K36 by Set2.

Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble nucleosomes and promote histone acetylation. Set2 is an H3 K36 methyltransferase. The functions of these proteins intersect in the context of transcription elongation by RNA polymerase II: both contribute to the establishment of repressive chromatin structures that inhibit spurious intragenic transcription. Here we characterize further interactions between budding yeast (Saccharomyces cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4 posttranslational modification, coding region cross-linking of Asf1 and Set2, and cooccurrence of Asf1 and Set2 in protein complexes. We find that at some genes Asf1 and Set2 control chromatin metabolism as components of separate pathways. However, the existence of a low-abundance complex containing both proteins suggests that Asf1 and Set2 can more directly collaborate in chromatin regulation. Consistent with this possibility, we show that Asf1 stimulates Set2 occupancy of the coding region of a highly transcribed gene by a mechanism that depends on Asf1 binding to H3/H4. This function of Asf1 promotes the switch from di- to trimethylation of H3 K36 at that gene. These results support the view that Set2 function in chromatin metabolism can intimately involve histone chaperone Asf1.