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In order to enhance interdisciplinary collaboration and promote better medication management, a partnered pharmacist medication charting (PPMC) model was piloted in the emergency department (ED) of an Australian referral hospital. The primary objective of this study was to evaluate the impact of PPMC on the timeliness of time-critical medicines (TCMs), completeness of medication orders, and assessment of venous thromboembolism (VTE) risk. This concurrent controlled retrospective pragmatic trial involved individuals aged 18 years and older presenting to the ED from 1 June 2020 to 17 May 2021. The study compared the PPMC approach (PPMC group) with traditional medical officer-led medication charting approaches in the ED, either an early best-possible medication history (BPMH) group or the usual care group. In the PPMC group, a BPMH was documented promptly soon after arrival in the ED, subsequent to which a collaborative discussion, co-planning, and co-charting of medications were undertaken by both a PPMC-credentialled pharmacist and a medical officer. In the early BPMH group, the BPMH was initially obtained in the ED before proceeding with the traditional approach of medication charting. Conversely, in the usual care group, the BPMH was obtained in the inpatient ward subsequent to the traditional approach of medication charting. Three outcome measures were assessed -the duration from ED presentation to the TCM's first dose administration (e.g., anti-Parkinson's drugs, hypoglycaemics and anti-coagulants), the completeness of medication orders, and the conduct of VTE risk assessments. The analysis included 321 TCMs, with 107 per group, and 1048 patients, with 230, 230, and 588 in the PPMC, early BPMH, and usual care groups, respectively. In the PPMC group, the median time from ED presentation to the TCM's first dose administration was 8.8 h (interquartile range: 6.3 to 16.3), compared to 17.5 h (interquartile range: 7.8 to 22.9) in the early BPMH group and 15.1 h (interquartile range: 8.2 to 21.1) in the usual care group (p < 0.001). Additionally, PPMC was associated with a higher proportion of patients having complete medication orders and receiving VTE risk assessments in the ED (both p < 0.001). The implementation of the PPMC model not only expedited the administration of TCMs but also improved the completeness of medication orders and the conduct of VTE risk assessments in the ED.
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Introduction: Partnered pharmacist medication charting (PPMC), a process redesign hypothesised to improve medication safety and interdisciplinary collaboration, was trialed in a tertiary hospital's emergency department (ED). Objective: To evaluate the health-related impact and economic benefit of PPMC. Methods: A pragmatic, controlled study compared PPMC to usual care in the ED. PPMC included a pharmacist-documented best-possible medication history (BPMH), followed by a clinical conversation between a pharmacist and a medical officer to jointly develop a treatment plan and chart medications. Usual care included medical officer-led traditional medication charting in the ED, without a pharmacist-obtained BPMH or clinical conversation. Outcome measures, assessed after propensity score matching, were length of hospital or ED stay, relative stay index (RSI), in-hospital mortality, 30-day hospital readmissions or ED revisits, and cost. Results: A total of 309 matched pairs were analysed. The median RSI was reduced by 15.4% with PPMC (p = 0.029). There were no significant differences between the groups in the median length of ED stay (8 vs. 10 h, p = 0.52), in-hospital mortality (1.3% vs. 1.3%, p > 0.99), 30-day readmission rates (21% vs. 17%; p = 0.35) and 30-day ED revisit rates (21% vs. 19%; p = 0.68). The hospital spent approximately $138.4 for the cost of PPMC care per patient to avert at least one medication error bearing high/extreme risk. PPMC saved approximately $1269 on the average cost of each admission. Conclusion: Implementing the ED-based PPMC model was associated with a significantly reduced RSI and admission costs, but did not affect clinical outcomes, noting that there was an additional focus on medication reconciliation in the usual care group relative to current practice at our study site.
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Medication errors are more prevalent in settings with acutely ill patients and heavy workloads, such as in an emergency department (ED). A pragmatic, controlled study compared partnered pharmacist medication charting (PPMC) (pharmacist-documented best-possible medication history [BPMH] followed by clinical discussion between a pharmacist and medical officer to co-develop a treatment plan and chart medications) with early BPMH (pharmacist-documented BPMH followed by medical officer-led traditional medication charting) and usual care (traditional medication charting approach without a pharmacist-collected BPMH in ED). Medication discrepancies were undocumented differences between medication charts and medication reconciliation. An expert panel assessed the discrepancies' clinical significance, with 'unintentional' discrepancies deemed 'errors'. Fewer patients in the PPMC group had at least one error (3.5%; 95% confidence interval [CI]: 1.1% to 5.8%) than in the early BPMH (49.4%; 95% CI: 42.5% to 56.3%) and usual care group (61.4%; 95% CI: 56.3% to 66.7%). The number of patients who need to be treated with PPMC to prevent at least one high/extreme error was 4.6 (95% CI: 3.4 to 6.9) and 4.0 (95% CI: 3.1 to 5.3) compared to the early BPMH and usual care group, respectively. PPMC within ED, incorporating interdisciplinary discussion, reduced clinically significant errors compared to early BPMH or usual care.
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Erros de Medicação , Farmacêuticos , Humanos , Estudos Prospectivos , Erros de Medicação/prevenção & controle , Serviço Hospitalar de EmergênciaRESUMO
Background: COVID-19 medicines delivery units (CMDU) were established in late December 2021 to deliver early antiviral therapy to patients classified as at risk with the aim of preventing hospitalization. Methods: We performed a service evaluation at 4 CMDUs in England. We assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy, and the rate of subsequent hospitalizations within 2 weeks of CMDU referral. Results: Over a 3-week period, 4788 patients were referred and 3989 were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The overall rate of admission within 14â days was 1%. Patients who were admitted were significantly older than those who did not require hospitalization. Of patients prescribed molnupiravir and sotrovimab, 1.8% and 3.2%, respectively, were admitted. Conclusions: There was a high volume of referrals to CMDU service during the initial surge of the Omicron wave in the United Kingdom. A minority of patients were judged to be eligible for therapy. In a highly vaccinated population, the overall hospitalization rate was low.
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BACKGROUND: Adverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs. OBJECTIVES: This trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12-24 months following hospital discharge. METHODS: The study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression. SUMMARY: It is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Alta do Paciente , Assistência ao Convalescente , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitalização , Hospitais , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Mouse and human data implicate the NOD1 and NOD2 sensors of the intestinal microbiome and the associated signal transduction via the receptor interacting protein kinase 2 (RIPK2) as a potential key signaling node for the development of inflammatory bowel disease (IBD) and an attractive target for pharmacological intervention. The TRUC mouse model of IBD was strongly indicated for evaluating RIPK2 antagonism for its effect on intestinal inflammation based on previous knockout studies with NOD1, NOD2, and RIPK2. We identified and profiled the BI 706039 molecule as a potent and specific functional inhibitor of both human and mouse RIPK2 and with favorable pharmacokinetic properties. We dosed BI 706039 in the spontaneous TRUC mouse model from age 28 to 56 days. Oral, daily administration of BI 706039 caused dose-responsive and significant improvement in colonic histopathological inflammation, colon weight, and terminal levels of protein-normalized fecal lipocalin (all P values <0.001). These observations correlated with dose responsively increasing systemic levels of the BI 706039 compound, splenic molecular target engagement of RIPK2, and modulation of inflammatory genes in the colon. This demonstrates that a relatively low oral dose of a potent and selective RIPK2 inhibitor can modulate signaling in the intestinal immune system and significantly improve disease associated intestinal inflammation.NEW & NOTEWORTHY The RIPK2 kinase at the apex of microbiome immunosensing is an attractive target for pharmacological intervention. A low oral dose of a RIPK2 inhibitor leads to significantly improved intestinal inflammation in the murine TRUC model of colitis. A selective and potent inhibitor of the RIPK2 kinase may represent a new class of therapeutics that target microbiome-driven signaling for the treatment of IBD.
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Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/antagonistas & inibidores , Animais , Disponibilidade Biológica , Células Cultivadas , Colite Ulcerativa/enzimologia , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/enzimologia , Colo/patologia , Doença de Crohn/enzimologia , Doença de Crohn/patologia , Citocinas/genética , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Fezes/química , Humanos , Mediadores da Inflamação/metabolismo , Lipocalinas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Modelos Biológicos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteínas com Domínio T/genéticaRESUMO
Structure activity relationship (SAR) investigation of an oxadiazole based series led to the discovery of several potent FLAP inhibitors. Lead optimization focused on achieving functional activity while improving physiochemical properties and reducing hERG inhibition. Several compounds with favorable in vitro and in vivo properties were identified that were suitable for advanced profiling.
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Inibidores da Proteína Ativadora de 5-Lipoxigenase/química , Proteínas Ativadoras de 5-Lipoxigenase/metabolismo , Oxidiazóis/química , Inibidores da Proteína Ativadora de 5-Lipoxigenase/metabolismo , Proteínas Ativadoras de 5-Lipoxigenase/química , Animais , Avaliação Pré-Clínica de Medicamentos , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/metabolismo , Meia-Vida , Humanos , Concentração Inibidora 50 , Masculino , Microssomos Hepáticos/metabolismo , Oxidiazóis/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Solubilidade , Relação Estrutura-AtividadeRESUMO
The use of glutaraldehyde-treated biological tissue in heart valve substitutes is an important option in the treatment of heart valve disease. These devices have limited durability, in part, because of tissue calcification and subsequent tearing of the valve leaflets. Components thought to induce calcification include lipids, cell remnants, and residual glutaraldehyde. We hypothesized that treatment of glutaraldehyde-treated bioprosthetic heart valve material using a short and long chain alcohol (LCA) combination, composed of 5% 1,2-octanediol in an ethanolic buffered solution, would reduce phospholipid content and subsequently lower the propensity of these tissues to calcify in vivo. Phospholipid content of glutaraldehyde-treated porcine valve leaflets and bovine pericardium was found to be 10.1 +/- 4.3 (n = 7) and 3.9 +/- 0.48 (n = 2) microg/mg dry tissue, respectively, which was reduced to 0.041 +/- 0.06 (n = 7) and 0.21 +/- 0.05 (n = 4) microg/mg dry tissue, respectively, after LCA treatment. Calcification potential of the treated tissues was assessed using a rat subcutaneous implant model. After 60 days of implantation, calcium levels were found to be 171 +/- 32 (n = 11) and 83 +/- 70 (n = 12) mg/g dry weight for glutaraldehyde-treated porcine leaflets and bovine pericardium, respectively, whereas prior LCA treatment resulted in reduced calcium levels of 1.1 +/- 0.6 (n = 12) and 0.82 +/- 0.1 (n = 12) mg/g dry weight, respectively. These data, taken together, support the notion that treatment of glutaraldehyde-treated tissue with a short and long chain alcohol combination will reduce both extractable phospholipids and the propensity for in vivo calcification.
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Bioprótese , Calcinose/patologia , Etanol/química , Glicóis/química , Próteses Valvulares Cardíacas , Animais , Calcinose/induzido quimicamente , Bovinos , Reagentes de Ligações Cruzadas/química , Glutaral/química , Lipídeos/química , Ratos , Ratos Sprague-Dawley , SuínosRESUMO
The PA(xpress) phayngeal airway (PA(x)) is a new single use airway device that might be used for airway maintenance during anaesthesia or cardiopulmonary resuscitation. We evaluated the performance of the PA(x) in 103 anaesthetised non-paralysed patients undergoing non-emergency anaesthesia. We recorded success of insertion, quality of airway achieved and complications of its use. We were successful in establishing a clear airway on the first attempt on 68 (67%) occasions. We were unable to establish a patent airway in nine (9%) patients. Partial or intermittent airway obstruction occurred during maintenance of anaesthesia in ten (11%) cases but none required removal of the device. Jaw thrust was used to assist insertion in all cases. A mean of 1.37 further manipulations per patient were required to establish an airway and 0.60 per patient were required during maintenance of anaesthesia. In the 94 patients in whom an airway was established, assisted ventilation was excellent in 77 (82%). Leak pressure was 20 cmH2O or above in 58% cases. Intracuff pressure was measured in 55 patients: mean pressure was 68 cmH2O and was above 100 cmH2O in ten (18%) cases. Complications occurred in 38 (37%) patients during insertion, in a further 12 (13%) during maintenance and in eight (9%) during emergence. The device was difficult to insert and associated with a high incidence of trauma: blood was visible on the device after removal in 56 (55%) cases. We conclude that the PA(x) is associated with too high a failure rate and too high an incidence of minor complications for routine airway maintenance.