Case-finding for HPV vaccination eligibility within a dental office with concurrent development of a dialogue tool.

Background: Human papillomavirus (HPV) immunization can prevent cancers, but uptake has been incomplete (and worse with the COVID-19 pandemic). Dental clinicians already screen for oral cancers, many of which are caused by HPV, and could identify vaccination candidates, but this requires a case-finding strategy. Objective: The purpose of this study was (1) to develop and test a case-finding approach to identify patients who were candidates for HPV vaccinations, (2) to test an HPV vaccination intervention by dental professionals on vaccination uptake. Methods: Design: Prospective, non-randomized feasibility case finding study with a 4-week enrollment period and a 6 week follow up period in general dental offices.Setting: Two general and non-commercial dentistry offices in Edmonton, Alberta Canada.Subjects: Consecutive scheduled (non-emergent) patients who met the Health Canada criteria for HPV vaccination: immunocompetent males and females aged 9-45 years and those who are immunocompromised. Consent for the discussion was obtained from each subject or parent.Intervention: Scheduled dental patients meeting the inclusion criteria were flagged by a research assistant who reviewed the appointment schedule each week for 4 weeks. For these subjects, dental clinicians (dentists and dental hygienists) used our Dental Dialogue Tool to discuss HPV vaccination and answer questions. Participating patients who consented to receive the HPV vaccine were given a prescription by the attending dentist and were directed to follow-up with a local pharmacy to have the vaccine administered. Each participant that was provided with an HPV prescription was contacted after 6 weeks to identify if they received the first dose of vaccine.Outcomes: Yield of our case-finding strategy and receipt of a patient's first HPV vaccine dose during 6 weeks post vaccine prescription. Results: Our case-finding strategy assessed 656 scheduled patients over 4 weeks. From this screening,179 (a case-finding yield of 20.4 %), were candidates for HPV vaccine discussion. Forty-three of these 179 patients (24 %) were already vaccinated.. Two patients (1.1 %) did not consent to be spoken with and 134 (74.8 %) consented to the HPV vaccine discussion.. Forty-eight of 134 patients (35.8 %) of patients accepted a prescription from the dentist after speaking with the dental clinician. Ultimately, 8/48 (16 %) (patients received their first dose of the HPV vaccine by the 6 week of follow-up call. However, this is only 4.5 % (8/177) of those patients who did consent for the discussion of HPV cancers and vaccination from their dentist. Conclusion: We demonstrated that case-finding for HPV vaccine candidates in general dental offices was feasible, with a reasonable yield. While the dental dialogue tool was described as a great resource to explain the facts and answer questions, very few patients were vaccinated after 6 weeks of follow-up. Further work is necessary to sharpen the intervention, perhaps including follow-up discussions with the dental clinicians.

Barriers to Surgical Intervention and Factors Influencing Motor Outcomes in Patients with Severe Peripheral Nerve Injury: A Province Wide Cohort Study.

INTRODUCTION: Despite the importance of timing of nerve surgery after peripheral nerve injury, optimal timing of intervention has not been clearly delineated. The goal of this study is to explore factors that may have a significant impact on clinical outcomes of severe peripheral nerve injury that requires reconstruction with nerve transfer or graft. MATERIALS AND METHODS: Adult patients who underwent peripheral nerve transfer or grafting in Alberta were reviewed. Clustered multivariable logistic regression analysis was used to examine the association of time to surgery, type of nerve repair, and patient characteristics on strength outcomes. Cox proportional hazard regression analysis model was used to examine factors correlated with increased time to surgery. RESULTS: Of the 163 patients identified, the median time to surgery was 212 days. For every week of delay, the adjusted odds of achieving Medical Research Council strength grade ≥ 3 decreases by 3%. An increase in preinjury comorbidities was associated with longer overall time to surgery (aHR 0.84, 95% CI 0.74-0.95). Referrals made by surgeons were associated with a shorter time to surgery compared to general practitioners (aHR 1.87, 95% CI 1.14-3.06). In patients treated with nerve transfer, the adjusted odds of achieving antigravity strength was 388% compared to nerve grafting; while the adjusted odds decreased by 65% if the injury sustained had a pre-ganglionic injury component. CONCLUSION: Mitigating delays in surgical intervention is crucial to optimizing outcomes. The nature of initial nerve injury and surgical reconstructive techniques are additional important factors that impact postoperative outcomes.

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Topical Vancomycin and Risk of Sternal Wound Infections: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The use of topical vancomycin in the reduction of sternal wound infection (SWI) risk has become a point of contention. The earlier literature consists of observational studies and 1 unblinded trial. Hence, the objective of this study was to assess whether vancomycin reduces the incidence of SWI in a double-blind randomized controlled trial. METHODS: Patients were randomized 1:1 to either vancomycin-soaked (vancomycin) or saline-soaked (control) sponges. The sponges were applied once the sternum was opened and were removed just before sternal closure. Patients were followed up at 3 months and at 1 year postoperatively to determine the incidence of SWI in each group. Results were analyzed according to the modified intention-to-treat principle. RESULTS: This study assessed 1038 patients for eligibility and enrolled 1037 patients. There were 517 patients randomized to the vancomycin group and 520 patients randomized to the control group. Analysis was performed on 1021 patients. At 3 months postoperatively, there was no significant difference in the incidence of SWI between the vancomycin and control groups (2.7% vs 4.1%; P = .23). There was also no significant difference between the vancomycin and control groups in the risk of superficial, deep, and organ-space infections. Similar findings were observed 1 year postoperatively. The most common organism isolated was coagulase-negative Staphylococcus. CONCLUSIONS: The use of vancomycin applied to the sternum during cardiac surgery does not reduce the incidence of SWI.

Ups and downs of hypertension control in Canada: critical factors and lessons learned / Altibajos en el control de la hipertensión en Canadá: factores críticos y lecciones aprendidas / Altos e baixos no controle da hipertensão no Canadá: fatores críticos e lições aprendidas

ABSTRACT As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

RESUMEN La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

RESUMO O controle populacional da hipertensão arterial - o maior fator de risco de morte - representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Epidemiologic Characteristics of Acute Kidney Injury During Cisplatin Infusions in Children Treated for Cancer.

Importance: Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective: To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants: This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Exposures: Cisplatin infusions. Main Outcomes and Measures: The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. Results: A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). Conclusions and Relevance: The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.

Are Preeclampsia and Adverse Obstetrical Outcomes Predictors of Cardiovascular Disease? A Case-Control Study of Women With Heart Disease.

OBJECTIVE: This study sought to determine whether preeclampsia; gestational diabetes; and adverse obstetrical outcomes such as placental abruption, intrauterine growth restriction, and preterm delivery are independent risk factors for cardiovascular disease later in life. METHODS: This was a retrospective, age-matched, case-control study that surveyed 244 cases (women with confirmed coronary artery disease) and 246 controls (women who did not have coronary artery disease) on their obstetrical history and outcomes, as well as traditional cardiovascular risk factors. Analyses were performed using SAS software version 9.1.3. (Canadian Task Force Classification II-2). RESULTS: Women with coronary artery disease had significantly higher rates of maternal complications such as gestational hypertension (odds ratio [OR] 3.34; 95% confidence interval [CI] 1.03-10.9), as well as conventional vascular risk factors such as dyslipidemia (OR 5.38; 95% CI 2.70-10.7), hypertension (OR 2.40; 95% CI 1.23-4.70), diabetes (OR 2.32; 95% CI 1.07-5.01), and smoking (current smoker: OR; 4.82 95% CI 1.66-14.00; former smoker: OR 2.86; 95% CI 1.43-5.71). There were more cases with preeclampsia (9.8%, vs. 5.4% in controls); however, the difference was not statistically significant. CONCLUSION: Among the adverse maternal conditions, there was more gestational hypertension in women with coronary artery disease. In this study, hypertensive disorders of pregnancy were the most important maternal risk factors for cardiovascular disease later in life and should be flagged early for close monitoring and/or intervention.

Remunerated patient care services and injections by pharmacists: An international update.

OBJECTIVES: Recognizing pharmacists' increasing roles as primary care providers, programs offering remuneration for patient care services and the administration of injections by pharmacists continue to be implemented. The objective of this article is to provide an update on remuneration programs available to pharmacists internationally for nondispensing services. DATA SOURCES: Systematic searches for relevant articles published from January 2013 to February 2018 across PubMed (MEDLINE), Embase, International Pharmaceutical Abstracts, Cochrane Library, Econlit, Scopus and Web of Science. Gray literature searches, including targeted searches of websites of payers and pharmacy associations, were also performed. STUDY SELECTION: Programs were included if they were newly introduced or had changes to patient eligibility criteria and fees since previously published reviews and if they were established programs offered by third-party payers for activities separate from dispensing. DATA EXTRACTION: Descriptive information on each program was extracted, including the program's jurisdiction (country and state, provincial or regional level, as applicable), payer, service description, patient eligibility criteria and fee structure. RESULTS: Over the 5-year period studied, 95 new programs for noninjection patient care services and 37 programs for pharmacist-administered injections were introduced. Large ranges in fees offered for similar programs were observed across programs, even within the same country or region, at an average of $US 71 for an initial medication review, $19 for follow-ups to these reviews, $18 for prescription adaptations and $13 for injection administration. Apart from some smoking cessation programs in England, which offered incentive payments for successful quits, all services were remunerated on a fee-for-service basis, often in the form of a flat fee regardless of the time spent providing the service. CONCLUSION: Although funding for pharmacists' activities continues to show growth, concerns identified in previous reviews persist, including the great variability in remunerated activities, patient eligibility and fees. These issues may limit opportunities for multijurisdictional program and service outcome evaluation. Can Pharm J (Ott) 2019;152:xx-xx.

Remunerated patient care services and injections by pharmacists: An international update.

OBJECTIVES: Recognizing pharmacists' increasing roles as primary care providers, programs offering remuneration for patient care services, and the administration of injections by pharmacists continue to be implemented. The objective of this article is to provide an update on remuneration programs available to pharmacists internationally for nondispensing services. DATA SOURCES: Systematic searches for relevant articles published from January 2013 to February 2018 across Pubmed (Medline), Embase, International Pharmaceutical Abstracts, Cochrane Library, Econlit, Scopus, and Web of Science. Gray literature searches, including targeted searches of websites of payers and pharmacy associations, were also performed. STUDY SELECTION: Programs were included if they were newly introduced or had changes to patient eligibility criteria and fees since previously published reviews and if they were established programs offered by third-party payers for activities separate from dispensing. DATA EXTRACTION: Descriptive information on each program was extracted, including the program's jurisdiction (country and state, provincial, or regional level, as applicable), payer, service description, patient eligibility criteria, and fee structure. RESULTS: Over the 5-year period studied, 95 new programs for noninjection patient care services and 37 programs for pharmacist-administered injections were introduced. Large ranges in fees offered for similar programs were observed across programs, even within the same country or region, at an average of $US 71 for an initial medication review, $19 for follow-ups to these reviews, $18 for prescription adaptations, and $13 for injection administration. Apart from some smoking cessation programs in England, which offered incentive payments for successful quits, all services were remunerated on a fee-for-service basis, often in the form of a flat fee regardless of the time spent providing the service. CONCLUSION: Although funding for pharmacists' activities continues to show growth, concerns identified in previous reviews persist, including the great variability in remunerated activities, patient eligibility, and fees. These issues may limit opportunities for multijurisdictional program and service outcome evaluation.

Effectiveness of Pharmacist Interventions on Cardiovascular Risk in Patients With CKD: A Subgroup Analysis of the Randomized Controlled RxEACH Trial.

BACKGROUND: Affecting a substantial proportion of adults, chronic kidney disease (CKD) is considered a major risk factor for cardiovascular (CV) events. It has been reported that patients with CKD are underserved when it comes to CV risk reduction efforts. STUDY DESIGN: Prespecified subgroup analysis of a randomized controlled trial. SETTING & PARTICIPANTS: Adults with CKD and at least 1 uncontrolled CV risk factor were enrolled from 56 pharmacies across Alberta, Canada. INTERVENTION: Patient, laboratory, and individualized CV risk assessments; treatment recommendations; prescription adaptation(s) and/or initiation as necessary; and regular monthly follow-up for 3 months. OUTCOMES: The primary outcome was change in estimated CV risk from baseline to 3 months after randomization. Secondary outcomes were change between baseline and 3 months after randomization in individual CV risk factors (ie, low-density lipoprotein cholesterol, blood pressure, and hemoglobin A1c), risk for developing end-stage renal disease, and medication use and dosage; tobacco cessation 3 months after randomization for those who used tobacco at baseline; and the impact of rural versus urban residence on the difference in change in estimated CV risk. MEASUREMENTS: CV risk was estimated using the Framingham, UK Prospective Diabetes Study, and international risk assessment equations depending on the patients' comorbid conditions. RESULTS: 290 of the 723 participants enrolled in RxEACH had CKD. After adjusting for baseline values, the difference in change in CV risk was 20% (P<0.001). Changes of 0.2mmol/L in low-density lipoprotein cholesterol concentration (P=0.004), 10.5mmHg in systolic blood pressure (P<0.001), 0.7% in hemoglobin A1c concentration (P<0.001), and 19.6% in smoking cessation (P=0.04) were observed when comparing the intervention and control groups. There was a larger reduction in CV risk in patients living in rural locations versus those living in urban areas. LIMITATIONS: The 3-month follow-up period can be considered relatively short. It is possible that larger reduction in CV risk could have been observed with a longer follow up period. CONCLUSIONS: This subgroup analysis demonstrated that a community pharmacy-based intervention program reduced CV risk and improved control of individual CV risk factors. This represents a promising approach to identifying and managing patients with CKD that could have important public health implications.

Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study.

BACKGROUND: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited. OBJECTIVE: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension). DESIGN: This is a 3-year observational prospective cohort study. SETTING: The study includes 12 Canadian pediatric oncology centers. PATIENTS: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 or a pre-existing renal transplantation at baseline. MEASUREMENTS: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected. METHODS: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines. Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes). LIMITATIONS: The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved. CONCLUSIONS: ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs.

MISE EN CONTEXTE: Les survivants d'un cancer infantile éprouvent des effets indésirables dus à leurs traitements, ce qui leurs engendrent des problèmes de santé à vie. L'équipe The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) vise à valider des biomarqueurs d'effets indésirables causés par les traitements contre le cancer et identifier les enfants à risque de développer des complications associées aux problèmes de coagulation, à la maladie du greffon contre l'hôte, la perte auditive et l'insuffisance rénale. La chimiothérapie cisplatine cause des dommages aux reins à court et à long terme. Relativement peu de données existent sur les biomarqueurs d'insuffisance rénale aigüe (IRA) et sur les problèmes rénaux à long terme chez les enfants traités avec le cisplatine. OBJECTIFS: Décrire les méthodologies de l'étude pancanadienne néphrotoxique ABLE qui vise à évaluer si les biomarqueurs urinaires (neutrophil gelatinase-associated lipocalin [NGAL] et kidney injury molecule-1[KIM-1]) peuvent diagnostiquer l'IRA, et s'ils peuvent prédire le risque de développer l'insuffisance rénale chronique (IRC) et l'hypertension artérielle à long terme. CADRE ET TYPE D'ÉTUDE: Étude prospective observationnelle de 3 ans dans 12 centres d'oncologie pédiatrique canadiens. PARTICIPANTS: cible de 150 patients âgés <18 ans recevant du cisplatine. Critères d'exclusion: Débit de filtration glomérulaire estimé (DFGe)<30 mL/min/1.73m2 ou avoir reçu une transplantation rénale. MESURES: Créatinine sérique, NGAL/KIM-1 sont mesurés pendant les infusions de cisplatine (échantillonnage avant l'infusion, après, et avant la sortie de l'hôpital). Visites de suivi: DFGe, microalbuminurie et tension artérielle sont mesurés; les résultats sont recueillis. MÉTHODOLOGIE: Critères d'évaluation: L'IRA est définie selon les critères de créatinine sérique de la classification Kidney Disease: Improving Global Outcomes (KDIGO). L'IRC est définie comme ayant un DFGe<90 mL/min/1.73m2 ou un ratio d'albumine/créatinine ≥3mg/mmol. L'hypertension est définie selon les lignes directrices. Procédure: Le recrutement: à lieu au premier ou deuxième cycle de cisplatine. Les patients sont évalués pendant deux infusions de cisplatine (validation des biomarqueurs d'IRA) et 3, 12 et 36 mois après le cisplatine (évaluation des problèmes rénaux à long terme). LIMITES DE L'ÉTUDE: La taille de l'échantillon est relativement modérée et la durée du suivi est moyennement courte. Il pourrait potentiellement avoir de la variabilité dans la collecte de données car plusieurs sites d'études sont impliqués. CONCLUSIONS: ABLE génèrera une plateforme nationale pour étudier les biomarqueurs de complications à long terme des traitements contre le cancer. L'étude néphrotoxique ABLE est une étude novatrice des biomarqueurs de l'IRA chez les enfants traités avec le cisplatine qui contribuera grandement à identifier les problèmes rénaux à long terme causés par le cisplatine et la nécessité de suivis cliniques.

The Effectiveness of Pharmacist Interventions on Cardiovascular Risk: The Multicenter Randomized Controlled RxEACH Trial.

BACKGROUND: Despite the cardiovascular disease (CVD) risk associated with hypertension, diabetes, dyslipidemia, and smoking, these risk factors remain poorly identified and controlled. OBJECTIVES: The study sought to evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk. METHODS: The RxEACH (Alberta Vascular Risk Reduction Community Pharmacy Project) study was a randomized trial conducted in 56 community pharmacies. Participants were recruited by their pharmacist, who enrolled adults at high risk for CVD. Patients were randomized to usual care (usual pharmacist care with no specific intervention) or intervention, comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education. Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets. Subjects received monthly follow-up visits for 3 months. The primary outcome was difference in change in estimated CVD risk between groups at 3 months. CVD risk was estimated using the greater of the Framingham, International, or United Kingdom Prospective Diabetes Study risk scores. RESULTS: We enrolled 723 patients (mean 62 years of age; 58% male, and 27% smokers). After adjusting for baseline values and center effect, there was a 21% difference in change in risk for CVD events (p < 0.001) between the intervention and usual care groups. The intervention group had greater improvements in low-density lipoprotein cholesterol (-0.2 mmol/l; p < 0.001), systolic blood pressure (-9.37 mm Hg; p < 0.001), glycosylated hemoglobin (-0.92%; p < 0.001), and smoking cessation (20.2%; p = 0.002). CONCLUSIONS: The RxEACH study was the first large randomized trial of CVD risk reduction by community pharmacists, demonstrating a significant reduction in risk for CVD events. Engagement of community pharmacists with an expanded scope of practice could have significant public health implications. (The Alberta Vascular Risk Reduction Community Pharmacy Project: RxEACH [RxEACH]; NCT01979471).

Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases.

BACKGROUND: Differentiating asthma from other causes of chronic airflow limitation, such as chronic obstructive pulmonary disease (COPD), can be difficult in a typical outpatient setting. The inflammation of asthma typically is different than that of COPD, and the degree of inflammation and cellular damage varies with asthma severity. Metabolomics is the study of molecules created by cellular metabolic pathways. OBJECTIVES: We hypothesized that the metabolic activity of adults with asthma would differ from that of adults with COPD. Furthermore, we hypothesized that nuclear magnetic resonance spectroscopy (NMR) would measure such differences in urine samples. METHODS: Clinical and urine-based NMR data were collected on adults meeting the criteria of asthma and COPD before and after an exacerbation (n = 133 and 38, respectively) and from patients with stable asthma or COPD (n = 54 and 23, respectively). Partial least-squares discriminant analysis was performed on the NMR data to create models of separation (86 metabolites were measured per urine sample). Some subjects' metabolomic data were withheld from modeling to be run blindly to determine diagnostic accuracy. RESULTS: Partial least-squares discriminant analysis of the urine NMR data found unique differences in select metabolites between patients with asthma and those with COPD seen in the emergency department and even in follow-up after exacerbation. By using these select metabolomic profiles, the model could correctly diagnose blinded asthma and COPD with greater than 90% accuracy. CONCLUSION: This is the first report showing that metabolomic analysis of human urine samples could become a useful clinical tool to differentiate asthma from COPD.

Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass.

OBJECTIVES: Matrix metalloproteinase-2 proteolyzes intracellular proteins in the heart and induces acute myocardial contractile dysfunction in ischemia-reperfusion injury. Doxycycline, a matrix metalloproteinase inhibitor, prevented matrix metalloproteinase-2-induced troponin I cleavage in rat hearts and improved contractile function following ischemia-reperfusion. In patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass, increased atrial matrix metalloproteinase-2 activity was inversely correlated with cardiac mechanical function at 3 hours reperfusion. We performed a study in patients with coronary artery disease undergoing primary elective coronary artery bypass graft surgery with cardiopulmonary bypass to determine whether doxycycline reduces cardiac mechanical dysfunction, matrix metalloproteinase activity, and troponin I degradation after reperfusion. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: University of Alberta Hospital. PATIENTS: Forty-two patients with coronary artery disease undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized to receive either oral administration of 20 mg of doxycycline or matching placebo pill twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days. MEASUREMENTS AND MAIN RESULTS: Left ventricular stroke work index was examined prior to cardiopulmonary bypass and at 24 hours reperfusion. Right atrial biopsies were collected before cardiopulmonary bypass and 10 minutes after aortic cross-clamp release to determine matrix metalloproteinase-2 activity and troponin I level. Blood was collected to determine matrix metalloproteinase activity and interleukin-6, C-reactive protein, and troponin I levels. Cardiac 72-kDa matrix metalloproteinase-2 activity was lower upon reperfusion in biopsies from the doxycycline group (p = 0.01), and the increase of matrix metalloproteinase-2 activity in the placebo group due to reperfusion did not appear in the doxycycline group (p = 0.05). Doxycycline, however, did not ameliorate cardiac mechanical dysfunction following reperfusion or the cardiopulmonary bypass-coronary artery bypass graft-induced increased plasma matrix metalloproteinase-9, interleukin-6, and C-reactive protein levels. Cardiopulmonary bypass-coronary artery bypass graft or doxycycline did not change tissue or plasma troponin I levels at 10 minutes reperfusion. CONCLUSIONS: Although doxycycline did not improve myocardial stunning following coronary artery bypass graft surgery with cardiopulmonary bypass, it reduced cardiac matrix metalloproteinase-2 activity in these patients. A larger trial and/or higher dose of doxycycline may yet be warranted.

Pharmacist-initiated intervention trial in osteoarthritis: a multidisciplinary intervention for knee osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) is a commonly undiagnosed condition and care is often not provided. Pharmacists are uniquely placed for launching a multidisciplinary intervention for knee OA. METHODS: We performed a cluster randomized controlled trial with pharmacies providing either intervention care or usual care (14 and 18 pharmacies, respectively). The intervention included a validated knee OA screening questionnaire, education, pain medication management, physiotherapy-guided exercise, and communication with the primary care physician. Usual care consisted of an educational pamphlet. The primary outcome was the pass rate on the Arthritis Foundation's quality indicators for OA. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Lower Extremity Function Scale (LEFS), the Paper Adaptive Test-5D (PAT-5D), and the Health Utilities Index Mark 3 (HUI3). RESULTS: One hundred thirty-nine patients were assigned to the control (n = 66) and intervention (n = 73) groups. There were no differences between the groups in baseline measures. The overall quality indicator pass rate was significantly higher in the intervention arm compared to the control arm (difference of 45.2%; 95% confidence interval 34.5, 55.9). Significant improvements were observed for the intervention care group as compared to the usual care group in the WOMAC global, pain, and function scores at 3 and 6 months (all P < 0.01); the PAT-5D daily activity scores at 3 and 6 months (both P < 0.05); the PAT-5D pain scores at 6 months (P = 0.05); the HUI3 single-attribute pain scores at 3 and 6 months (all P < 0.05); and the LEFS scores at 6 months (P < 0.05). CONCLUSION: Pharmacists can launch a multidisciplinary intervention to identify knee OA cases, improve the utilization of treatments, and improve function, pain, and quality of life.