One Molecule, Many Faces: Repositioning Cardiovascular Agents for Advanced Wound Healing.

Chronic wound treatments pose a challenge for healthcare worldwide, particularly for the people in developed countries. Chronic wounds significantly impair quality of life, especially among the elderly. Current research is devoted to novel approaches to wound care by repositioning cardiovascular agents for topical wound treatment. The emerging field of medicinal products' repurposing, which involves redirecting existing pharmaceuticals to new therapeutic uses, is a promising strategy. Recent studies suggest that medicinal products such as sartans, beta-blockers, and statins have unexplored potential, exhibiting multifaceted pharmacological properties that extend beyond their primary indications. The purpose of this review is to analyze the current state of knowledge on the repositioning of cardiovascular agents' use and their molecular mechanisms in the context of wound healing.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Effect of amlodipine on the circulating renin-angiotensin-aldosterone system in healthy cats.

BACKGROUND: Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin-angiotensin-aldosterone system (RAAS) in cats is incompletely characterized. HYPOTHESIS/OBJECTIVES: To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. ANIMALS: Twenty healthy client-owned cats. METHODS: Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4-week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time-weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank-sum testing. RESULTS: Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%-86%; P = .009), angiotensin I (59% increase; IQR 27-101%; P = .006), angiotensin II (56% increase; IQR 5-70%; P = .023), angiotensin IV (42% increase; -19% to 89%; P = .013); and angiotensin 1-7 (38% increase; IQR 9-118%; P = .015). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.

Frequency domain analysis of photoplethysmographic and arterial pressure waveforms for assessing hemodynamics in children with congenital heart surgery.

BACKGROUND: Time-domain parameters are less reliable in children due to increased arterial and chest wall compliance. We assessed the ability of indices derived from frequency analysis of photoplethysmography (PPG) and arterial blood pressure (ABP) waveforms to predict the hemodynamic state in children undergoing congenital heart surgery. METHODS: We analyzed waveforms after cardiopulmonary bypass period in 76 children who underwent total repair of congenital heart disease. Amplitude density of baseline and amplitude modulation in PPG and ABP by respiratory frequency were obtained using fast Fourier transform analysis and normalized by cardiac pulse height (representing respiratory modulations in venous blood [PPG-DC%] and in amplitude [PPG-AC%] at respiratory frequency). The ratio of amplitude density of PPG at the cardiac frequency (CF) to ABP-CF was used to assess vascular compliance. We assessed volume replacement (ml/kg) and vasoactive inotropic score (VIS). RESULTS: Children requiring volume replacement > 10 ml/kg (15.8%) showed higher PPG-DC% than those not requiring it (median: 52.4%, 95% CI [24.8, 295.1] vs. 36.7% [10.7, 125.7], P = 0.017). In addition, children with a VIS > 7 (22.4%) showed higher PPG-CF/ABP-CF (3.6 [0.91, 10.8] vs. 1.2 [0.27, 5.5], P = 0.008). On receiver operating characteristic curve analysis, PPG-DC% predicted a higher fluid requirement (area under the curve: 0.71, 95% CI [0.604, 0.816], P = 0.009), while PPG-CF/ABP-CF predicted a higher VIS (0.714, [0.599, 0.812], P = 0.004). CONCLUSIONS: Frequency domain analysis of PPG and ABP may assess hemodynamic status requiring fluid or vasoactive inotropic therapy after congenital heart surgery.

Nurse management of noradrenaline infusions in intensive care units: An observational study.

BACKGROUND: Intensive care nurse management of noradrenaline (norepinephrine) infusions is a common and essential clinical competency for patient haemodynamic support. Nurses titrate and wean noradrenaline infusions to a target blood pressure in a dynamic, high-risk, and unpredictable environment. Titration and weaning are complex interventions, and blood pressure goals are often variable. OBJECTIVES: The aim was to examine how nurses used blood pressure targets when escalating, weaning, and titrating noradrenaline in intensive care patients admitted for haemodynamic management and explore patient blood pressure responses to changes in noradrenaline doses. METHODS: In this naturalistic observational study, noradrenaline dose changes were classified as escalation, weaning, and titration changes and analysed to explore nursing practice. The study was undertaken in two adult medical/surgical intensive care units in Melbourne, Australia. Participants included intensive care nurses and patients who received noradrenaline infusions for haemodynamic support. RESULTS: Observations of 14 nurse-patient dyads provided 25 h of blood pressure and noradrenaline dose data. Patient participants received weight-adjusted maximum noradrenaline doses of between 0.06 mcg/kg/min and 0.87 mcg/kg/minute, with those in the escalation group receiving dose increases of up to 5 mcg to achieve blood pressure goals. During weaning, patients maintained or increased their blood pressure as noradrenaline doses were decreased. Nurses consistently maintained blood pressures at higher than target goals, and despite constant fluctuations, they only documented blood pressure readings hourly. CONCLUSIONS: Intensive care nurses managed noradrenaline to achieve mean arterial pressure targets that were variable and not evidence based. The disconnection between observed blood pressure fluctuations and nurse documentation of patient blood pressures was reflected in titration practices. Discrepancies between documented and actual blood pressures raised issues about data used by nurses and doctors to inform clinical practice on noradrenaline management.

Adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit: the contribution of the VIS score and the RACHS-1 / Eventos adversos em pós-operatório cardíaco em uma unidade de terapia intensiva pediátrica: a contribuição do escore VIS e do RACHS-1

ABSTRACT Objective: To evaluate the occurrence of adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit and to find any patient characteristics that can predict such events. Methods: This was a historical cohort study of patients recovering in the pediatric intensive care unit for the first 7 days after cardiac surgery between April and December 2019, by reviewing the medical records. The following were reviewed: demographic, clinical, and laboratory characteristics; patient severity scores; and selected adverse events, grouped into device-related, surgical, and nonsurgical. Results: A total of 238 medical records were included. At least one adverse event occurred in 110 postoperative patients (46.2%). The total number of adverse events was 193 (81%). Vascular catheters were the most common cause, followed by cardiac arrest, bleeding, and surgical reexploration. In the univariate analysis, the vasoactive-inotropic score (VIS), Risk Adjustment in Congenital Heart Surgery (RACHS-1) score, age, Pediatric Index of Mortality (PIM-2), cardiopulmonary bypass and aortic clamping duration were significantly associated with adverse events. In the multivariate analysis, VIS ≥ 20 (OR 2.90; p = 0.004) and RACHS-1 ≥ 3 (OR 2.11; p = 0.019) were significant predictors, while age and delayed sternal closure showed only trends toward significance. To predict the occurrence of adverse events from VIS and RACHS-1, the area under the curve was 0.73 (95%CI 0.66 - 0.79). Conclusion: Adverse events were quite frequent in children after cardiac surgery, especially those related to devices. The VIS and RACHS-1, used together, predicted the occurrence of adverse events well in this pediatric sample.

RESUMO Objetivo: Avaliar a ocorrência de eventos adversos em pós-operatório cardíaco em uma unidade de terapia intensiva pediátrica e estabelecer eventuais associações das características dos pacientes e a possibilidade de predizer tais eventos. Métodos: Coorte histórica de 7 dias de pós-operatório cardíaco, de abril a dezembro de 2019, por revisão de prontuários de pacientes com recuperação em unidade de terapia intensiva pediátrica. Foram revisados: características demográficas e clínico-laboratoriais, escores de gravidade dos pacientes e eventos adversos selecionados agrupados em: relacionados a dispositivos, a aspectos cirúrgicos e a aspectos não cirúrgicos. Resultados: Foram incluídos 238 prontuários. Ocorreu pelo menos um evento adverso em 110 pós-operatórios (46,2 %). O número total de eventos adversos foi 193 (81%), sendo mais frequente a complicação com cateteres vasculares, seguida de parada cardíaca, sangramento e reexploração cirúrgica. Na análise univariada, escore vasoativo-inotrópico (VIS- vasoactive-inotropic score), Risk Adjustment in Congenital Heart Surgery (RACHS-1) score, idade, Pediatric Index of Mortality (PIM-2), tempo de circulação extracorpórea e de clampeamento aórtico foram estatisticamente significantes com eventos adversos. Na análise multivariável, VIS ≥ 20 (OR 2,90; p = 0,004) e RACHS-1 ≥ 3 (OR 2,11; p = 0,019) mostraram-se relevantes e com significância estatística, enquanto idade e fechamento tardio do esterno possuíam apenas tendência a essa associação. Considerando a previsão de ocorrência de eventos adversos a partir dos valores de escore vasoativo-inotrópico e de RACHS-1, a área sob a curva mostrou valor de 0,73 (IC95% 0,66 - 0,79). Conclusão: A frequência de eventos adversos foi expressiva e aqueles relacionados a dispositivos foram os mais frequentes. O VIS e o RACHS-1, utilizados em conjunto, foram capazes de predizer a ocorrência de eventos adversos nesta amostra pediátrica.

A Recent Advance on Phytochemicals, Nutraceutical and Pharmacological Activities of Buckwheat.

Buckwheat, a member of the Fagopyrum genus in the Polygonaceae family, is an ancient pseudocereal with noteworthy nutraceutical properties that have been relatively less explored. This crop holds great promise for the future due to its gluten-free protein, wellbalanced amino acid profile, and the presence of bioactive flavonoids that promote good health. With its gluten-free nature and a combination of beneficial nutritional components, buckwheat shows significant potential for a variety of health benefits. The objective of the present review aims to explore various nutritional and pharmacological properties of buckwheat. With the help of various search engines Pubmed, Google and Semantic Scholar, research and review papers. Data were analyzed and summarized in a comprehensive review. A fascinating spectrum of nutritional and pharmacological activities of common buckwheat and Tartary buckwheat were explored such as antidiabetic, anti-inflammatory, neurological disorders, antiobesity, anticancer, cardiovascular agents and many more. This review provides a concise overview of the current understanding of the chemical composition of both common buckwheat and Tartary buckwheat and the captivating spectrum of pharmacological activity and also underscoring their immense potential for future advancements.

Impact of Concomitant Cardiovascular Therapies on Efficacy and Safety of Relugolix vs Leuprolide: Subgroup Analysis from HERO Study in Advanced Prostate Cancer.

INTRODUCTION: Cardiovascular (CV) events are the leading cause of death in prostate cancer. Men with prostate cancer are likely to have CV risk factors and use CV-related concomitant medications. In the phase 3 HERO study, a 54% lower incidence of major adverse cardiac events was reported in men treated with the oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, vs leuprolide. Herein, we characterize the impact of concomitant CV therapies on efficacy and safety in the HERO study. METHODS: In HERO, 930 men with advanced prostate cancer (APC) were randomized 2:1 and treated with relugolix (120 mg orally once daily; after single 360 mg loading dose) or leuprolide (injections every 3 months) for 48 weeks. Subgroups analyzed included men who received antihypertensives, antithrombotics, or lipid-modifying therapies (LMAs), as well as the most common drug classes (> 10%) and single most common agent within each class. Assessments included sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks and safety. RESULTS: Antihypertensives, antithrombotics, and LMAs were utilized by 52.7%, 39.1%, and 39.6% of men in HERO, respectively. In the main subgroups, point estimates for sustained castration rates were generally consistent with overall estimates of relugolix and leuprolide observed in the overall population. Sustained castration rates were also mostly consistent for men taking the most common drug classes and individual agents in each class (losartan [n = 103]: relugolix, 95.4% vs leuprolide, 80.6%; amlodipine [n = 229]: 97.2% vs 85.5%; metoprolol [n = 88]: 95.7% vs 86.9%; acetylsalicylic acid [n = 259]: 97.0% vs 92.1%; clopidogrel [n = 43]: 96.4% vs 86.7%; simvastatin [n = 78]: 98.0% vs 87.3%). Incidence and types of adverse events (AEs) among men who received these medications were mostly consistent with overall population results, with some increases in grade ≥ 3 and fatal AEs. CONCLUSION: Relugolix suppressed testosterone and was generally well tolerated when given with concomitant CV agents. TRIAL REGISTRATION: Clinical Trial ID NCT03085095. PRIOR PRESENTATION: Data presented at 15th Annual Genitourinary Cancers Symposium; February 17-19, 2022, San Francisco, CA, USA [Abstract 101, Poster board E11]. The published abstract from this presentation can be found at https://ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.101 .

Polypill-based strategy vs. usual care for secondary prevention of cardiovascular disease: a meta-analysis of randomized controlled trials.

AIMS: We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of a polypill-based strategy (PBS) on therapeutic adherence and cardiovascular outcomes compared with usual care for secondary prevention of cardiovascular diseases (CVDs). METHODS AND RESULTS: We systematically searched PubMed, Cochrane, and Scopus databases from inception to January 2023, including RCTs comparing PBS with usual care in patients with prior CVD. We assessed efficacy outcomes of therapeutic adherence, systolic blood pressure (SBP), and LDL-cholesterol (LDL-C) and safety outcomes of all-cause and cardiovascular mortality. Statistical analysis was performed with Review Manager 5.4.1 and R Version 4.2.1. A total of 8 RCTs with a population of 6541 individuals were included, of whom 3318 (50.7%) were treated with the PBS. Follow-up ranged from 6 to 60 months. The polypill-based strategy was associated with a significantly increased therapeutic adherence [risk ratio (RR) 1.22; 95% confidence interval (CI) 1.10-1.34; P < 0.001]. Cardiovascular mortality (RR 0.61; 95% CI 0.44-0.85; P = 0.004), SBP [mean difference (MD) -1.47 mmHg; 95% CI -2.86 to -0.09; P = 0.04], and LDL-C (MD -3.83 mg/dL; 95% CI -6.99 to -0.67; P = 0.02) were significantly lower in the PBS group. The incidence of all-cause mortality was similar between groups (RR 0.83; 95% CI 0.54-1.29; P = 0.41). CONCLUSION: In patients with pre-existing CVD, a PBS is associated with lower cardiovascular mortality and improved therapeutic adherence, along with a modest decrease in SBP and LDL-C compared with usual care. Thus, a PBS may be considered a preferred option for this patient population.

Adherence to medical therapy plays a critical role in the prevention of atherosclerotic events. Previous studies have shown that a polypill-based strategy (PBS) increases treatment adherence in the context of primary prevention of cardiovascular diseases. However, the effectiveness of this strategy in secondary prevention is yet to be determined. Herein, we demonstrate the following: Polypill-based strategy improved therapeutic adherence and reduced LDL-cholesterol and systolic blood pressure levels.There was a reduction in cardiovascular mortality with the use of the PBS; however, no significant difference was found in all-cause mortality between groups.

Persistence and Adherence to Cardiovascular Medicines in Australia.

Background The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. Methods and Results Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. Conclusions Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence.

Risk of antidepressant initiation among users of cardiovascular agents and metformin. Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway: Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway.

Cardiovascular disease and diabetes are risk factors for depression, yet the relationship between the drug treatments for these diseases and the risk of antidepressant initiation remains unclear. This study aimed to examine possible associations between the use of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), beta-blockers (BB), calcium channel blockers (CCB), diuretics, or metformin and risk of antidepressant initiation. The Trøndelag Health Study (HUNT3), Norway, was linked to the Norwegian Prescription Database (NorPD). Participants with no prescriptions of cardiovascular agents, metformin, or antidepressants for at least 6 months before HUNT3 (baseline) were eligible and followed for 10 years. The exposure was the use of cardiovascular agents or metformin, defined as mono- or polytherapy from baseline to end of follow-up. The outcome was the initiation of antidepressant use, indicated by the first drug dispensation during the study period and expressed as hazard ratios (HRs) with 95% confidence intervals (CI). Among 20 227 adults aged 40-70 years at baseline, we observed different associations between cardiovascular agents or metformin and the risk of antidepressant initiation. ARBs or CCB monotherapy was associated with a lower risk of initiating antidepressant use (HR 0.70; 95%CI 0.56-0.88 and HR 0.81; 95%CI 0.61-1.06, respectively) compared to no use of any drugs included in the study (reference). Reduced risk of antidepressant initiation was among ASA or statin polytherapy users, whereas there was a small increased risk among participants on ASA monotherapy. In contrast, there was no statistical evidence of associations between ACEI, BB, diuretics, or metformin and increased or decreased risk of antidepressant initiation. Our mixed findings indicate the possibility that some cardiovascular agents may be associated with a reduced risk of initiating antidepressant use while others may not. However, bias due to the limitations of the study design is possible.

Nurse decision-making when managing noradrenaline in the intensive care unit: A naturalistic observational study.

OBJECTIVE: Intensive care nurses care for critically ill patients in a complex, fast paced environment. Management of noradrenaline (norepinephrine) is core business for intensive care nurses and nurse decision-making on noradrenaline is poorly understood. The study objective was to investigate decision-making processes nurses use when caring for intensive care unit patients receiving noradrenaline. RESEARCH METHODOLOGY: A qualitative exploratory design used the Cognitive Continuum Theory as a framework for naturalistic observations and interviews in two medical/surgical intensive care units in Melbourne, Australia. MAIN OUTCOME MEASURES: Observational and interview data from field notes and audiovisual recordings were transcribed and coded to develop themes using reflexive thematic analysis. FINDINGS: Fourteen nurse and patient dyads were recruited to observational sessions from December 2019 to June 2021. Three major themes developed were Learning through doing; Individualised patient care; and Clinical expertise, with six supporting sub-themes. Nurses learned to manage noradrenaline experientially and developed titration and weaning strategies to support decision-making. Blood pressure targets and monitor alarms were used consistently to aid decision-making processes. Nurses were observed practicing across the cognitive continuum depending on knowledge structure, complexity of interventions, response time, and patient acuity. CONCLUSION: Experiential learning of complex and high-risk interventions in the absence of guidelines or algorithms meant nurses developed their own titration and weaning strategies based on constant evaluation and re-evaluation of patient cues. Patient heterogeneity, cue ambiguity and a dynamic practice environment contributed to decision-making complexity that would benefit from development of evidence-based practice resources. IMPLICATIONS FOR CLINICAL PRACTICE: Nurses learn to manage noradrenaline through experiential learning, using blood pressure targets and monitor alarms to support decision-making when titrating and weaning noradrenaline. Nurses develop noradrenaline titration and weaning strategies to support decision-making in the absence of guidelines or algorithms. Supporting nurse decision-making and streamlining practice would reduce practice variation and cognitive workload.

The influence of intensive care unit culture and environment on nurse decision-making when managing vasoactive medications: A qualitative exploratory study.

BACKGROUND: Nurses working in intensive care units make autonomous decisions to manage high-risk vasoactive medications in critically ill patients. Noradrenaline (norepinephrine) is a vasoactive medication commonly administered to patients in intensive care units. The influence of unit culture and environment on nurse-decision-making on noradrenaline (norepinephrine) management is unknown. AIMS: The study aimed to investigate nurses' perceptions of the impact of interpersonal interactions, socialisation, and the intensive care environment on decision-making when managing noradrenaline (norepinephrine). MATERIALS & METHODS: An exploratory qualitative study applied thematic analysis to focus group data. A purposive sample of nineteen nurses participated in four focus groups at two intensive care units in Melbourne, Australia, from March to June 2021. The COREQ checklist was used to guide study development and no patients or members of the public were involved in focus groups. RESULTS: Three themes were generated from the researcher's interaction with data, Nursing and Medications; Culture and Decision-making; and a Safe Practice Environment. Nurses reported decision-making challenges associated with learning to manage noradrenaline (norepinephrine) early in their intensive care career and discussed feelings of isolation due to staffing resources, and the configuration of the intensive care environment. Nurses developed titration and weaning strategies to support decision-making in the absence of evidence-based algorithms. DISCUSSION: Empathetic patient allocation early in nurses' intensive care careers facilitated a safer learning environment, and reduced isolation inherent in single room intensive care units. Nurses developed and used titration and weaning strategies, often learnt from other clinicians to manage practice uncertainty. CONCLUSIONS: Management of noradrenaline (norepinephrine) is core business for intensive care nurses worldwide. Development of titration and weaning strategies by nurses indicated unmet need for guidelines to support decision-making. Identifying contextual elements that impact nurse management of high-risk medications can guide development of environments, resources and policies that support nurse decision-making, and reduce nurse anxiety and disempowerment.

Consensus validation of a screening tool for cardiovascular pharmacotherapy in geriatric patients: the RASP_CARDIO list (Rationalization of Home Medication by an Adjusted STOPP list in Older Patients).

PURPOSE: Cardiovascular agents commonly used in geriatric patients, are linked to potentially avoidable harm and might hence be a suitable substrate for medication review practices. Therefore, we sought to update and validate the content of the cardiovascular segment of the previously published Rationalization of Home Medication by an Adjusted STOPP list in Older Patients (RASP) List. METHODS: A three-step study was conducted by the pharmacy department in collaboration with the geriatric medicine and cardiology department at the University Hospitals Leuven, Belgium. First, the cardiovascular segment of the RASP list version 2014 was updated taking into account published research, other screening tools and the input of end-users. Secondly, this draft was reviewed during three panel discussions with five expert cardiologists and three clinical pharmacists, all of whom had relevant expertise in geriatric pharmacotherapy. Thirdly, the content was validated using a modified Delphi Technique by a panel of European hospital pharmacists, cardiologists, geriatricians and an internal medicine physician. RESULTS: After the first and second step, the RASP_CARDIO list comprised 94 statements. Consensus (≥ 80% agreement) of all statements and one new statement about gliflozins in heart failure was achieved by a panel of seventeen experts across four European countries after two validation rounds. The final construct comprised a list of 95 statements related to potentially inappropriate prescribing of cardiovascular agents. CONCLUSION: The RASP_CARDIO list is an updated and validated explicit screening tool to optimize cardiovascular pharmacotherapy in geriatric patients.

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP-1RAs suggest that these medications are associated with a high prevalence of mild-moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP-1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic-induced weight gain is worth considering in Australia. This would bring us into line with other countries.

Riesgo de prolongación del intervalo QT asociado al tratamiento / The risk of treatment-induced QT interval prolongation

Objetivo: La prolongación del intervalo QT puede aumentar la estanciahospitalaria y la tasa de mortalidad de los pacientes. Esta investigacióndetermina la incidencia de prolongación del intervalo QT debido al usode medicamentos y evalúa el método más apropiado para realizar elmonitoreo electrocardiográfico.Método: Se realizó un estudio observacional retrospectivo en pacienteshospitalizados en el Hospital Clínica Bíblica durante el año 2018. Serevisaron los expedientes de los pacientes con hospitalización superiora 48 horas cuya historia clínica incluyera al menos tratamiento con unmedicamento que prolongara el intervalo QT y que las medidas manualesdel intervalo QT fueran corregidas con la fórmula Fridericia y Rautaharju,y las medidas automáticas con la fórmula Bazett. La valoración del riesgose realizó con la escala RISQ-PATH.Resultados: De los 141 pacientes analizados, 23 tenían una arritmia previaen su historia clínica y 14 de ellos sufrieron complicaciones durante la hospitalización.Un total de 113 (80%) pacientes tenían un valor alto RISQ‑PATHy sólo a 64 se les realizó un electrocardiograma al ingreso. En promedio,los pacientes recibieron tres medicamentos que aumentaban el intervalo QT.La mayoría de los QT obtenidos automáticamente fueron más cortos queaquellos obtenidos en forma manual. De todas las correcciones, los valoresdel intervalo QT más largos se obtuvieron con la fórmula de Bazett, y los máscortos con la fórmula Rautaharju. No ocurrieron eventos como taquicardiaventricular compleja o torsade de pointes durante el estudio.Conclusiones: Es necesario implementar estrategias que permitan una mejor monitorización del intervalo QT con el fin de prevenir las complicacionesderivadas en los pacientes ospitalizados

Objective: QT interval prolongation can increase patients’ hospitalstay and mortality rate. This study aims to determine the incidence ofdrug-induced QT interval prolongation and establish which QT intervalmeasurement method is the most appropriate for electrocardiographicmonitoring.Method: A retrospective observational study was conducted of patientsadmitted to the Clínica Bíblica Hospital during 2018. The electronic medicalrecords of patients hospitalized for longer than 48 hours and whosedrug regimen included at least one drug potentially able to prolong the QTinterval were reviewed. Manually-measured QT intervals were correctedusing Fridericia’s and Rautaharju’s formulae, while automatically-measuredQT intervals were corrected with Bazett’s formula. Risk was assessed usingthe RISQ-PATH scale.Results: Of the 141 patients analyzed, 23 had arrhythmia as per theirclinical history and 14 suffered a complication during their stay in hospital.A total of 113 (80%) had a high RISQ-PATH score and only 64 were subjectedto an electrocardiogram on admission. Patients received a meanof three potentially QT interval prolonging drugs. Most of the QT ntervalsmeasured automatically were shorter than those obtained manually. Of allcorrections, the longest QTc interval values were obtained with Bazett’sformula, and the shortest with Rautaharju’s formula. None of the patientsdeveloped TdP or complex ventricular tachycardia.Conclusions: Every effort should be made to implement strategies conducive to more effective monitoring of the QT interval to prevent QT intervalprolongation related complications in hospitalized patients