Environmental scan of current strategies to decrease sedative-hypnotic drug use and promote sleep in hospital patients.

BACKGROUND: Sedative-hypnotic drugs are often initiated in hospital to manage insomnia and anxiety. Guidelines discourage their use, particularly in older adults, due to risks of falls, fractures, and delirium. AIM: To identify publicly available resources to decrease the use of sedative-hypnotic drugs and promote sleep in hospital. METHOD: An advanced Google search with 6 search strategies was conducted. Key websites were also identified and searched. Hospital- or community-based resources using non-pharmacologic measures to reduce sedative-hypnotic drug use and/or to promote sleep were included if they were publicly available in English within the past 5 years. Full text screening and data extraction was performed independently by 2 reviewers; a third reviewer resolved disagreements by consensus. RESULTS: A total of 79 resources met inclusion criteria, with 65 (82.3%) providing education and 31 (39.2%) describing sleep hygiene strategies. Other resources included deprescribing (17, 21.5%), relaxation training (13, 16.5%), cognitive behavioural therapy for insomnia (9, 11.4%), and policies (7, 8.9%). The resources primarily targeted patients (59, 74.7%) followed by healthcare providers (9, 11.4%). There were 9 resources (11.4%) that applied to both community and hospital settings, and another 2 (2.5%) designed specifically for hospital. CONCLUSION: Many resources were available to patients and healthcare providers to reduce inappropriate or ineffective use of sedative-hypnotic drugs and promote better sleep. Specific resources for the hospital setting were infrequent and recommended that clinicians stop hospital-initiated sedatives when patients are discharged. Identified resources can be adapted by healthcare organizations to develop sedative-hypnotic prescribing programs and policies.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Opioid and Sedative Coprescription: Prescribing Patterns after an ICU Admission.

Background: Opioid misuse constitutes a health care crisis in Canada, and coprescription of opioids with sedatives has been associated with adverse events. Opioids and sedatives are frequently administered in the intensive care unit (ICU). The rate of continuation of opioid-sedative combinations after an ICU admission at the study institution was unknown. Objectives: To determine the rates of opioid and sedative coprescriptions following an ICU admission and to identify factors associated with continuation of hospital-initiated opioid-sedative coprescriptions at ICU transfer and hospital discharge. Methods: This retrospective chart review involved patients admitted to ICUs at a tertiary care centre between April 1, 2018, and March 31, 2019. Baseline characteristics were obtained from a clinical database and medication information from medication reconciliation forms. An opioid coprescription was defined as prescription of an opioid in combination with a sedative (benzodiazepine, z-drug, gabapentinoid, tricyclic antidepressant, or antipsychotic), and hospital-initiated coprescriptions encompassed various predefined scenarios of therapy started or modified before ICU transfer. Factors associated with hospital-initiated opioid coprescription were analyzed by multivariable logistic regression. Results: A total of 735 patients met the inclusion criteria. At ICU transfer, 23.0% (169/735) of the patients had an opioid coprescription, and 87.0% (147/169) of these coprescriptions were hospital-initiated. At hospital discharge, 8.6% (44/514) of the patients had an opioid coprescription, and 56.8% (25/44) of these coprescriptions were hospital-initiated. Male sex, home opioid coprescription, surgical patient, prolonged hospital stay, and in-hospital death were significantly associated with hospital-initiated opioid coprescription at the time of ICU transfer. Home opioid coprescription was significantly associated with opioid coprescription at the time of hospital discharge. Conclusions: Hospital-initiated opioid coprescriptions accounted for the majority of opioid coprescriptions at ICU transfer and hospital discharge. Pharmacists should assess all opioid coprescriptions to determine whether discontinuation and/or dose reduction is appropriate.

Contexte: L'abus d'opioïdes est une crise sanitaire au Canada, et les opioïdes coprescrits avec des sédatifs ont été associés à des événements indésirables. Les opioïdes et les sédatifs sont fréquemment utilisés en unité de soins intensifs (USI). Sur le lieu de l'étude, on ne connaissait pas le taux de maintien de l'utilisation de la combinaison opioïdes-sédatifs après une admission en USI. Objectifs: Déterminer les taux de coprescription d'opioïdes et de sédatifs suite à une admission en USI et identifier les facteurs associés au maintien de l'utilisation des coprescriptions d'opioïdes et de sédatifs amorcées par l'hôpital au moment du transfert hors de l'USI et du congé hospitalier. Méthodes: Cet examen rétrospectif des dossiers portait sur des patients admis en USI d'un centre de soins tertiaires entre le 1er avril 2018 et le 31 mars 2019. Les caractéristiques de base ont été obtenues à partir d'une base de données clinique et des informations sur les médicaments à partir des formulaires de bilan comparatif des médicaments. Une coprescription d'opioïdes a été définie comme « La prescription d'un opioïde associée à un sédatif (benzodiazépine, médicament z, gabapentinoïde, antidépresseur tricyclique ou antipsychotique) ¼. Les « coprescriptions amorcées par l'hôpital ¼ correspondaient à des coprescriptions initiées ou modifiées avant le transfert hors de l'USI, selon des scénarios préalablement définis. Les facteurs associés à la coprescription d'opioïdes amorcée par l'hôpital ont été analysés par régression logistique multivariée. Résultats: Au total, 735 patients répondaient aux critères d'inclusion. Lors du transfert hors de l'USI, des opioïdes étaient coprescrits à 23,0 % (169/735) d'entre eux; de ces coprescriptions, 87,0 % (147/169) étaient amorcées par l'hôpital. Au moment du congé hospitalier, des opioïdes étaient coprescrits à 8,6 % (44/514) d'entre eux; de ces coprescriptions, 56,8 % (25/44) étaient amorcées par l'hôpital. Le sexe masculin, la coprescription d'opioïdes à domicile, l'admission en chirurgie, le séjour prolongé à l'hôpital et le décès à l'hôpital étaient fortement associés à la coprescription d'opioïdes amorcée par l'hôpital au moment du transfert hors de l'USI. La coprescription d'opioïdes à domicile était fortement associée à la coprescription d'opioïdes au moment du congé de l'hôpital. Conclusions: Les coprescriptions d'opioïdes amorcées par l'hôpital représentaient la majorité des coprescriptions au moment du transfert hors de l'USI et au moment du congé de l'hôpital. Les pharmaciens doivent évaluer toutes les coprescriptions d'opioïdes pour déterminer si l'arrêt et/ou la réduction de la dose est appropriée.

Burnout among Hospital Pharmacists in Canada: A Cross-Sectional Analysis.

Background: Burnout is a growing problem among health care professionals, with consequences for patient safety and personal satisfaction. The prevalence of burnout among hospital pharmacists in Canada is unknown; however, it has been documented at over 60% in other countries. Objectives: To assess the prevalence of burnout and variables associated with burnout among hospital pharmacists in Canada. Methods: This cross-sectional cohort study was based on a survey made available to more than 2600 Canadian hospital pharmacists from February 10 to April 2, 2020, through the Canadian Society of Hospital Pharmacists QID platform. The questionnaire collected data for the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSSMP), demographic data, employment characteristics, and workplace factors; it also included an open-ended question about burnout. Results: A total of 171 respondents provided data suitable for analysis. Of these, only 13 (7.6%) met the criteria for burnout on all 3 subscales of the burnout inventory; however, 105 respondents (61.4%) surpassed the threshold for burnout on the emotional exhaustion subscale. In univariate analyses, not working to one's full scope of practice was associated with meeting the criteria for burnout on all 3 scales. Linear regression highlighted associations between scores on the emotional exhaustion subscale and gender identity, perceived excessive on-call duties, area of practice, and positivity of workplace culture. Content analysis of the open-ended question supported the quantitative findings and pointed to 3 major themes: workload quantity, workload quality, and workplace culture. Conclusions: Results on the emotional exhaustion subscale of the MBI-HSSMP and responses to the open-ended question suggested a relatively high prevalence of burnout among Canadian hospital pharmacists, and indicated potential links between burnout and certain workplace characteristics.

Contexte: L'épuisement professionnel est un problème croissant chez les professionnels de la santé qui entraîne des conséquences sur la sécurité des patients et la satisfaction personnelle des professionnels. La prévalence de l'épuisement professionnel chez les pharmaciens d'hôpitaux au Canada est inconnue; cependant, il a été documenté à plus de 60 % dans d'autres pays. Objectifs: Évaluer la prévalence de l'épuisement professionnel et les variables associées à celui-ci chez les pharmaciens d'hôpitaux au Canada. Méthodes: Cette étude de cohorte transversale se basait sur un sondage distribué à plus de 2600 pharmaciens d'hôpitaux canadiens entre le 10 février et le 2 avril 2020 via la plateforme QID de la Société canadienne des pharmaciens d'hôpitaux. Le questionnaire a permis de recueillir des données pour le Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSSMP; un inventaire de l'épuisement professionnel chez les professionnels de la santé), des données démographiques, des caractéristiques professionnelles et des facteurs liés au lieu de travail; il comprenait également une question ouverte sur l'épuisement professionnel. Résultats: Au total, 171 répondants ont fourni des données se prêtant à l'analyse. Parmi ceux-ci, seuls 13 (7,6 %) répondaient aux critères de l'épuisement professionnel des 3 sous-échelles de l'inventaire de l'épuisement professionnel; cependant, 105 répondants (61,4 %) ont dépassé le seuil d'épuisement professionnel de la sous-échelle d'épuisement émotionnel. Dans les analyses univariées, le fait de ne pas travailler dans l'ensemble de son champ d'exercice était associé au respect des critères d'épuisement professionnel sur les 3 sous-échelles. La régression linéaire a mis en évidence des associations entre les scores sur la sous-échelle d'épuisement émotionnel et l'identité de genre, les tâches de garde excessives perçues, le domaine de pratique et la positivité de la culture sur le lieu de travail. L'analyse du contenu de la question ouverte étayait les résultats quantitatifs et a souligné 3 thèmes principaux : la quantité et la qualité de la charge de travail, ainsi que la culture sur le lieu de travail. Conclusions: Les résultats relatifs à la sous-échelle d'épuisement émotionnel du MBI-HSSMP et les réponses à la question ouverte suggèrent une prévalence relativement élevée d'épuisement professionnel chez les pharmaciens d'hôpitaux canadiens et indiquent des liens potentiels entre l'épuisement professionnel et certaines caractéristiques du milieu de travail.

Q94 is not a selective modulator of proteinase-activated receptor 1 (PAR1) in platelets.

Thrombin is a potent platelet activator, acting through proteinase-activated receptors -1 and -4 (PAR1 and PAR4). Of these, PAR-1 is activated more rapidly and by lower thrombin concentrations. Consequently, PAR-1 has been extensively investigated as a target for anti-platelet drugs to prevent myocardial infarction. Q94 has been reported to act as an allosteric modulator of PAR1, potently and selectively inhibiting PAR1-Gαq coupling in multiple cell lines, but its effects on human platelet activation have not been previously studied. Platelet Ca2+ signaling, integrin αIIbß3 activation and α-granule secretion were monitored following stimulation by a PAR1-activating peptide (PAR1-AP). Although Q94 inhibited these responses, its potency was low compared to other PAR1 antagonists. In addition, αIIbß3 activation and α-granule secretion in response to other platelet activators were also inhibited with similar potency. Finally, in endothelial cells, Q94 did not inhibit PAR1-dependent Ca2+ signaling. Our data suggest that Q94 may have PAR1-independent off-target effects in platelets, precluding its use as a selective PAR1 allosteric modulator.

Health Care Professionals' Perceptions of the Role of the Clinical Pharmacist and Expanded Pharmacist Coverage in Critical Care.

BACKGROUND: During the first wave of the COVID-19 pandemic, coverage by critical care pharmacists (CCPs) was expanded in 2 medical-surgical intensive care units at the Queen Elizabeth II Health Sciences Centre, in Halifax, Nova Scotia, from 8 hours per day, 5 days per week, excluding holidays, to 8 hours per day, 7 days per week, including holidays. OBJECTIVES: To describe health care professionals' opinions about and perceived impacts of the expanded CCP coverage on patient care, as well as their opinions about the role of the CCP as a member of the critical care team. METHODS: An electronic 22-item survey was distributed to critical care health care professionals to capture opinions and perceived impacts of expanded CCP coverage. The perceived importance of 25 evidence-informed CCP activities was assessed using a 5-point Likert scale. RESULTS: Thirty-eight complete responses were included (15% response rate, based on distribution of the survey to 249 health care professionals). Most respondents agreed or strongly agreed with the following statements: CCPs are integral members of the critical care team (34/38 [89%]), CCPs play an important role in improving patient outcomes (34/38 [89%]), the presence of CCPs on the unit and on patient care rounds allows other health care professionals to concentrate on their own professional responsibilities (33/38 [87%]), and the expanded CCP coverage improved patient care (29/35 [83%]). Respondents most frequently categorized 23 of the 25 CCP activities as very important. CONCLUSIONS: Expanded CCP coverage was perceived to have a positive effect on both patient care and members of the critical care team. Most CCP activities were perceived as very important. Given the findings of this quality project, novel staffing models are being explored to optimize CCP coverage.

CONTEXTE: Au cours de la première vague de la pandémie de COVID-19, la couverture par les pharmaciens de soins intensifs (PSI) a été étendue dans 2 unités de soins intensifs médico-chirurgicaux du Queen Elizabeth II Health Sciences Centre, à Halifax (Nouvelle-Écosse) : de 8 heures par jour, 5 jours par semaine, hors jours fériés, la couverture est passée à 8 heures par jour, 7 jours par semaine, y compris les jours fériés. OBJECTIFS: Décrire les opinions des professionnels de la santé sur la couverture élargie des PSI et leurs perceptions des incidences de celle-ci sur les soins aux patients, ainsi que le rôle des PSI en tant que membres de l'équipe de soins intensifs. MÉTHODES: Un sondage électronique comportant 22 questions a été distribué aux professionnels de la santé en soins intensifs pour recueillir les opinions et les impacts perçus de l>élargissement de la couverture des PSI. L'importance perçue des 25 activités des PSI fondées sur des données probantes a été évaluée à l'aide d'une échelle de Likert à 5 points. RÉSULTATS: Trente-huit réponses complètes ont été incluses (taux de réponse de 15 %, basé sur une distribution de l'enquête à 249 professionnels de la santé). La plupart des répondants étaient d'accord ou fortement d'accord avec les affirmations suivantes : « les PSI font partie intégrante de l'équipe de soins intensifs ¼ (34/38, 89 %); « les PSI jouent un rôle important dans l'amélioration des résultats pour les patients ¼ (34/38, 89 %); « la présence des PSI dans l'unité et lors des tournées de soins aux patients permet à d'autres professionnels de la santé de se concentrer sur leurs propres responsabilités professionnelles ¼ (33/38, 87 %); et « la couverture élargie des PSI a amélioré les soins aux patients ¼ (29/35, 83 %). Les répondants ont le plus souvent classé 23 des 25 activités du PSI comme « très importantes ¼. CONCLUSIONS: L'élargissement de la couverture des PSI était perçu comme ayant un effet positif à la fois sur les soins aux patients et sur les membres de l'équipe de soins intensifs. La plupart des activités des PSI étaient perçues comme très importantes. Compte tenu des résultats de ce projet de qualité, de nouveaux modèles de dotation en personnel sont à l'étude pour optimiser la couverture des PSI.

Maintaining flippase activity in procoagulant platelets is a novel approach to reducing thrombin generation.

BACKGROUND: During thrombosis, procoagulant platelets expose phosphatidylserine (PS), which enhances local thrombin generation. Reducing platelet PS exposure could be a novel anti-thrombotic approach. PS is confined to the inner leaflet of the plasma membrane in unstimulated platelets by ATP-dependent "flippase" activity. Ca2+ ionophores trigger all platelets to expose a high level of PS by activating a scramblase protein and inactivating the flippase. Although R5421 was previously shown to reduce Ca2+ ionophore-induced PS exposure, its mechanism of action is unknown. OBJECTIVES: To determine the mechanism by which R5421 reduces platelet PS exposure. METHODS: Washed human platelets were stimulated with the Ca2+ ionophore, A23187, to induce procoagulant platelet formation while bypassing proximal receptor signalling. Platelets PS exposure was detected using annexin V or lactadherin in flow cytometry. NBD (7-nitro-2-1,3-benzoxadiazol-4-yl)-PS was used to assess scramblase and flippase activity. Thrombin generation was monitored using a fluorogenic substrate. RESULTS AND CONCLUSIONS: R5421 reduced the extent of A23187-stimulated platelet PS exposure, as demonstrated with annexin V or lactadherin binding. R5421 also maintained flippase activity in procoagulant platelets. Although R5421 appeared to inhibit scramblase activity in procoagulant platelets, it did not once the flippase had been inhibited, demonstrating that scramblase activity is not directly inhibited. Furthermore, R5421 inhibited the contribution of A23187-stimulated platelets to thrombin generation. Together these data demonstrate that R5421 reduces the extent of PS exposure in procoagulant platelets by maintaining flippase activity. Maintaining flippase activity in procoagulant platelets is a novel and effective approach to reducing thrombin generation.

Aspiring to establish a family: Reproductive health among young unmarried women in Abidjan, Côte d'Ivoire.

In Abidjan, Côte d'Ivoire, young women navigate a complicated transition from adolescence to adult life. In an evolving context, young women are expected to succeed in education and the economy, while negotiating the social pressure to start families and prove womanhood by becoming mothers. In this project, we closely followed twenty young adult unmarried women who desire to find a life partner or have a child soon. The study sought to understand women's experiences and reproductive health needs using a variety of methods, including daily diary keeping, in-depth interviews, focus groups and interactive exercises. Research indicated that young adult women who aspire to establish a family must navigate conflicting pressures, making it challenging for them to identify and act on their own fertility needs. Women who use family planning prioritise their future fertility and navigate complex social dynamics while selecting a method. The study builds on existing literature and contributes additional insight into the nuanced family planning needs and experiences of single women who aspire to establish a family, particularly around fertility desires, the use of calendar methods, and economic and social empowerment.

Using the behavior change wheel to link published deprescribing strategies to identified local primary healthcare needs.

BACKGROUND: Polypharmacy is a major global problem. Evidence in primary care shows deprescribing can be beneficial. Behaviour change theories such as the Theoretical Domains Framework (TDF) and the Behaviour Change Wheel (BCW) can help develop successful implementation of deprescribing initiatives. OBJECTIVES: To link locally identified deprescribing influencers with components of successfully trialed deprescribing strategies, with the aim of informing the development of local deprescribing initiatives. METHODS: Two background studies were completed. A qualitative study of interviews and focus groups identified influencers of deprescribing from local primary care physicians, nurse practitioners, and pharmacists. Transcripts were coded using the TDF and mapped to the Intervention Functions of the BCW. A scoping review identified studies that investigated primary care deprescribing strategies, which were mapped to the BCW Intervention Functions and the Behaviour Change Techniques (BCTs). For this analysis, six main TDF domains from the qualitative study were linked to the BCTs identified in the scoping review through the Intervention Functions of the BCW. RESULTS: Within the BCW component Capability, one TDF domain identified in the qualitative study, Memory, Attention and Decision Process, was linked to strategies like academic detailing from the scoping review. For the Opportunity component, two TDF domains, Social Influences and Environmental Context and Resources, were linked to strategies such as pharmacist medication reviews, providing patient information leaflets, and evidence-based deprescribing tools. For the Motivation component, three TDF domains, Social/Professional Role and Identity, Intentions, and Beliefs about Consequences, were linked to strategies such as sending deprescribing information to prescribers, using tools to identify eligible patients, and having patients report adverse events of medications. CONCLUSIONS: This analysis identified deprescribing strategies that can be used to address influencers related to behaviour change from the perspective of primary care providers, and to assist with future deprescribing initiative development and implementation in the local context.

Rhabdomyolysis: An evidence-based approach.

A 76-year-old lady was found on the floor following a fall at home. She was uninjured, but unable to get up, and had been lying on the floor for roughly 18 hours before her son arrived. She had been unwell for the past 3 days with a cough and shortness of breath. She had a past medical history of diabetes, hypertension, hypercholesterolaemia and atrial fibrillation (AF). On examination, she was alert but distressed, clinically dehydrated, febrile and tachycardic. She was treated for community acquired pneumonia with co-amoxiclav and was fluid resuscitated with Hartmann's solution. Her hyperkalaemia was treated with 50 mL of 50% glucose containing 10 units of rapid-acting insulin. Her creatinine kinase (CK) on admission was 200,000, and she had an acute kidney injury (AKI). Urine dipstick was positive for blood. However, her renal function continued to deteriorate over the succeeding 48 h, when she required renal replacement therapy (RRT) due to fluid overload and anuria.

Measuring Family Planning Provider Bias: A Discrete Choice Experiment among Burkinabé, Pakistani, and Tanzanian Providers.

The unmet need for modern contraception remains high around the world, particularly for youth. While some of this unmet need is driven by limited health infrastructure and method mix availability, many adolescents who visit family planning providers still do not receive methods that fit their needs. This suggests that providers may be biased against youth and that interventions to change provider behavior could help close this gap. However, it is unclear if this bias is a result of age or other characteristics common among young women such as not being married and not having children. We use a discrete choice experiment in Burkina Faso, Pakistan, and Tanzania to disentangle the effects of age on providers' decisions to provide contraception from the effects of other potential confounding factors. We find that, although young women may experience the most bias, age is not the main driver. Rather, marital status and parity seem to influence provider decisions to offer services or counsel on modern methods. These findings suggest that interventions to reduce provider bias should focus on changing behavior towards unmarried and nulliparous women, regardless of their age.

Epigallocatechin gallate inhibits release of extracellular vesicles from platelets without inhibiting phosphatidylserine exposure.

Arterial thrombosis triggers myocardial infarction and is a leading cause of death worldwide. Procoagulant platelets, a subpopulation of activated platelets that expose phosphatidylserine (PS), promote coagulation and occlusive thrombosis. Procoagulant platelets may therefore be a therapeutic target. PS exposure in procoagulant platelets requires TMEM16F, a phospholipid scramblase. Epigallocatechin gallate (EGCG) has been reported to inhibit TMEM16F but this has been challenged. We investigated whether EGCG inhibits PS exposure in procoagulant platelets. PS exposure is often measured using fluorophore-conjugated annexin V. EGCG quenched annexin V-FITC fluorescence, which gives the appearance of inhibition of PS exposure. However, EGCG did not quench annexin V-APC fluorescence. Using this fluorophore, we show that EGCG does not inhibit annexin V binding to procoagulant platelets. We confirmed this by using NBD-labelled PS to monitor PS scrambling. EGCG did not quench NBD fluorescence and did not inhibit PS scrambling. Procoagulant platelets also release PS-exposing extracellular vesicles (EVs) that further propagate coagulation. Surprisingly, EGCG inhibited EV release. This inhibition required the gallate group of EGCG. In conclusion, EGCG does not inhibit PS exposure in procoagulant platelets but does inhibit the EV release. Future investigation of this inhibition may help us further understand how EVs are released by procoagulant platelets.

Cytosolic and mitochondrial Ca2+ signaling in procoagulant platelets.

SummaryPlatelets are the major cellular contributor to arterial thrombosis. However, activated platelets form two distinct subpopulations during thrombosis. Pro-aggregatory platelets aggregate to form the main body of the thrombus. In contrast, procoagulant platelets expose phosphatidylserine on their outer surface and promote thrombin generation. This apparently all-or-nothing segregation into subpopulations indicates that, during activation, platelets commit to becoming procoagulant or pro-aggregatory. Although the signaling pathways that control this commitment are not understood, distinct cytosolic and mitochondrial Ca2+ signals in different subpopulations are likely to be central. In this review, we discuss how these Ca2+ signals control procoagulant platelet formation and whether this process can be targeted pharmacologically to prevent arterial thrombosis.

Pathways to Modern Family Planning: A Longitudinal Study on Social Influence among Men and Women in Benin.

Despite improvements in family planning (FP) knowledge and services in West Africa, unmet need for FP continues to grow. Many programs apply a demographically and biologically driven definition of unmet need, overlooking the complex social environment in which fertility and FP decisions are made. This longitudinal, qualitative cohort study captures the changing nature of FP need, attitudes and behaviors, taking into account life context to inform understanding of the complex behavior change process. Purposively sampled, 25 women and 25 men participated in three rounds of in-depth interviews over 18 months. Analyses used a social network influence lens. Findings suggest alignment of six foundational building blocks operating at individual, couple, services, and social levels is essential to meet FP need. If one block is weak, a person may not achieve met need. Women and men commonly follow five pathways as they seek to fulfill their FP need. Some pathways achieve met need (determined users, quick converters), some do not (side effect avoiders), and some do not lead to consistent FP outcomes (male-priority decision makers, gender-egalitarian decision makers). Findings clarify the role of social determinants of FP and offer insight into program approaches informed by user typologies and return on program investments.

Deprescribing interventions in primary health care mapped to the Behaviour Change Wheel: A scoping review.

BACKGROUND: Polypharmacy and inappropriate medication use are an increasing concern. Deprescribing may improve medication use through planned and supervised dose reduction or stopping of medications. As most medication management occurs in primary health care, which is generally described as the first point of access for day-to-day care, deprescribing in primary health care is the focus on this review. OBJECTIVE: This scoping review aimed to identify and characterize strategies for deprescribing in primary health care and map the strategies to the Behaviour Change Wheel (BCW). METHODS: A scoping review was conducted that involved searches of six databases (2002-2018) and reference lists of relevant systematic reviews and included studies. Studies that described and evaluated deprescribing strategies in primary health care were eligible. Two independent reviewers screened articles and completed data charting with charting verified by a third. Deprescribing strategies were mapped to the intervention functions of the BCW and linked to specific Behaviour Change Techniques (BCT). RESULTS: Searches yielded 6871 citations of which 43 were included. Nineteen studies were randomized, 24 were non-randomized. Studies evaluated deprescribing in terms of medication changes, feasibility, and prescriber/patient perspectives. Deprescribing strategies involved various professionals (physicians, pharmacists, nurses), as well as patients and were generally multifaceted. A wide range of intervention functions were identified, with 41 BCTs mapped to Environmental restructuring, 38 BCTs mapped to Enablement, and 34 BCTs mapped to Persuasion. CONCLUSIONS: Deprescribing strategies in primary health care have used a variety of BCTs to address individual professionals (e.g. education) as well as strategies that addressed the practice setting, including support from additional team members (e.g. pharmacists, nurses and patients). Further research is warranted to determine comparative effectiveness of different BCTs, which can help facilitate implementation of deprescribing strategies, thereby reducing polypharmacy, in primary health care.

Prescribing Patterns and Patient Outcomes for Bone and Joint Infections Treated with Cefazolin and Probenecid: A Retrospective Observational Study.

BACKGROUND: Previous studies have described the use of cefazolin with probenecid to treat uncomplicated skin and soft-tissue infections. Some prescribers are extrapolating from this evidence to treat more invasive infections, which have a greater potential for poor outcomes, including treatment failure that could lead to increased morbidity and mortality. Information supporting cefazolin with probenecid as effective treatment in this context is needed. OBJECTIVES: To describe prescribing patterns and outcomes for patients who received cefazolin with probenecid for the treatment of bone and joint infections. METHODS: This single-centre retrospective study involved adult outpatients for whom cefazolin and probenecid were prescribed for bone and joint infections between April 1, 2012, and March 31, 2017. Patient charts were reviewed, and data were collected for clinical and microbiological variables using a standardized data collection form. RESULTS: In a total of 80 cases, the patient received cefazolin and probenecid for treatment of a bone or joint infection, of which 69 cases met the inclusion criteria. In most cases (n = 67), the patients were treated with cefazolin 2 g IV plus probenecid 1 g PO, both given twice daily. Completion of prescribed treatment occurred in 56 patient cases (81%), resolution of signs and symptoms in 53 (77%), readmission to hospital in 11 (16%), recurrence of infection in 6 (9%), and treatment failure requiring a change in therapy in 7 (10%). CONCLUSIONS: The effectiveness of cefazolin and probenecid for the treatment of bone and joint infections appears to be similar to that of standard treatment, as reported in the literature. Antibiotic effectiveness is difficult to determine conclusively in a retrospective analysis, so these results should be interpreted with caution, but they may stimulate further research.

CONTEXTE: Des études précédentes ont décrit l'utilisation de la céfazoline et du probénécide pour traiter les infections cutanées et les infections de tissus mous. Quelques prescripteurs extrapolent ces éléments probants pour traiter des infections plus invasives, dont les résultats risquent d'être défavorables, comme un échec du traitement pouvant entraîner une morbidité et une mortalité accrues. De l'information supplémentaire étayant l'efficacité du traitement à l'aide de la céfazoline et du probénécide dans ce contexte est nécessaire. OBJECTIFS: Décrire les modes de prescription et les résultats obtenus par des patients ayant reçu de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires. MÉTHODES: Cette étude rétrospective unicentrique porte sur des patients ambulatoires adultes à qui on a prescrit de la céfazoline et du probénécide pour traiter des infections osseuses et articulaires entre le 1er avril 2012 et le 31 mars 2017. L'examen des dossiers médicaux des patients a permis la récolte de données sur les variables cliniques et microbiologiques à l'aide d'un formulaire de recueil de données standard. RÉSULTATS: Les patients, soit 80 cas en tout, ont reçu de la céfazoline et du probénécide pour traiter une infection osseuse ou articulaire et 69 de ces cas répondaient aux critères d'inclusion. Dans la plupart des cas (n = 67), les patients étaient traités avec de la céfazoline IV dosée à 2 g et du probénécide dosé à 1 g PO, les deux produits étant administrés deux fois par jour. Le traitement a été appliqué au complet dans 56 cas (81 %), la résolution des signes et des symptômes a eu lieu dans 53 cas (77 %), la réadmission à l'hôpital s'est produite dans 11 cas (16 %), les infections ont récidivé dans 6 cas (9 %) et le traitement s'est soldé par un échec et a nécessité un changement de thérapie dans 7 cas (10 %). CONCLUSIONS: L'efficacité de la céfazoline et du probénécide dans le traitement des infections osseuses et articulaires semble être similaire à celle des traitements standard, comme le rapporte la littérature scientifique. L'efficacité des antibiotiques est difficile à déterminer de façon concluante dans une analyse rétrospective, ces résultats doivent donc être interprétés avec prudence, mais ils pourraient stimuler des recherches supplémentaires.

Ethaninidothioic acid (R5421) is not a selective inhibitor of platelet phospholipid scramblase activity.

BACKGROUND AND PURPOSE: Ethaninidothioic acid (R5421) has been used as a scramblase inhibitor to determine the role of phospholipid scrambling across a range of systems including platelet procoagulant activity. The selectivity of R5421 has not been thoroughly studied. Here, we characterised the effects of R5421 on platelet function and its suitability for use as a scramblase inhibitor. EXPERIMENTAL APPROACH: Human platelet activation was measured following pretreatment with R5421 and stimulation with a range of agonists. Phosphatidylserine exposure was measured using annexin V binding. Integrin αIIb ß3 activation and α-granule release were measured by flow cytometry. Cytosolic Ca2+ signals were measured using Cal520 fluorescence. An in silico ligand-based screen identified 16 compounds which were tested in these assays. KEY RESULTS: R5421 inhibited A23187-induced phosphatidylserine exposure in a time- and temperature-dependent manner. R5421 inhibited Ca2+ signalling from the PAR1, PAR4 and glycoprotein VI receptors as well as platelet αIIb ß3 integrin activation and α-granule release. R5421 is therefore not a selective inhibitor of platelet scramblase activity. An in silico screen identified the pesticide thiodicarb as similar to R5421. It also inhibited platelet phosphatidylserine exposure, Ca2+ signalling from the PAR1 and glycoprotein VI, αIIb ß3 activation and α-granule release. Thiodicarb additionally disrupted Ca2+ homeostasis in unstimulated platelets. CONCLUSION AND IMPLICATIONS: R5421 is not a selective inhibitor of platelet scramblase activity. We have identified the pesticide thiodicarb, which had similar effects on platelet function to R5421 as well as additional disruption of Ca2+ signalling which may underlie some of thiodicarb's toxicity.