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1.
J Am Geriatr Soc ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441771

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug-drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. OBJECTIVES: We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking which would interact with hydroxychloroquine. METHODS: We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug-drug interactions with hydroxychloroquine that might exclude them from participation in a typical coronavirus disease 2019 (COVID-19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as being potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. RESULTS: The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and anti-diabetic agents. CONCLUSION: The COVID-19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID-19. This article is protected by copyright. All rights reserved.

2.
Thorac Cancer ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281272

RESUMO

BACKGROUND: Treatment for stage III non-small cell lung cancer (NSCLC) of unresectable disease mainly involves concurrent chemoradiation (CRT). Post-CRT consolidation treatment with durvalumab is a major therapeutic advance that provides survival benefit in this group of patients. However, the performance of this treatment strategy remains to be studied in a real-world setting. METHODS: A total of 31 patients who had disease control post-CRT were included in the durvalumab early access program (EAP) as an intent-to-treat cohort and retrospectively reviewed for post-CRT progression-free survival (PFS) and time to metastatic disease or death (TMDD). The neutrophil-to-lymphocyte ratio (NLR) at the initiation of durvalumab was analyzed in 29 patients. RESULTS: The median time from the completion of concurrent CRT to the initiation of durvalumb was 2.8 months. The objective response was 25.8% and the 12 month PFS and TMDD-free rate were 56.4% and 66.9%, respectively. The low NLR patients showed a significantly longer post-CRT PFS (not reach vs. 12.0 months [95% CI: 5.5-not estimable]; P = 0.040; the hazard ratio for disease progression or death, 0.23 [95% CI: 0.05-1.00]; P = 0.048) and the 12 month post-CRT PFS rate (82.5 vs. 42.6%). The post-CRT TMDD (not reach vs. 12.6 months, [95% CI: 10.8-not estimable]; P = 0.010; the hazard ratio for distant metastasis or death, 0.11 [95% CI: 0.01-0.88]; P = 0.037) and 12 month post-CRT TMDD-free rate (90.9 vs. 57.1%) were also significantly higher in the low NLR patients. CONCLUSIONS: Durvalumab consolidation treatment in real-world patients showed substantial efficacy and the correlation with the NLR level warrants further investigation.

3.
Biochim Biophys Acta Mol Cell Res ; 1867(4): 118645, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31926209

RESUMO

p21-activated protein kinase (PAK2) is a unique member of the PAK family kinases that plays important roles in stress signaling. It can be activated by binding to the small GTPase, Cdc42 and Rac1, or by caspase 3 cleavage. Cdc42-activated PAK2 mediates cytostasis, whereas caspase 3-cleaved PAK2 contributes to apoptosis. However, the relationship between these two states of PAK2 activation remains elusive. In this study, through protein biochemical analyses and various cell-based assays, we demonstrated that full-length PAK2 activated by Cdc42 was resistant to the cleavage by caspase 3 in vitro and within cells. When mammalian cells were treated by oxidative stress using hydrogen peroxide, PAK2 was highly activated through caspase 3 cleavage that led to apoptosis. However, when PAK2 was pre-activated by Cdc42 or by mild stress such as serum deprivation, it was no longer able to be cleaved by caspase 3 upon hydrogen peroxide treatment, and the subsequent apoptosis was also largely inhibited. Furthermore, cells expressing active mutants of full-length PAK2 became more resistant to hydrogen peroxide-induced apoptosis than inactive mutants. Taken together, this study identified two states of PAK2 activation, wherein Cdc42- and autophosphorylation-dependent activation inhibited the constitutive activation of PAK2 by caspase cleavage. The regulation between these two states of PAK2 activation provides a new molecular mechanism to support PAK2 as a molecular switch for controlling cytostasis and apoptosis in response to different types and levels of stress with broad physiological and pathological relevance.

4.
Ann Surg ; 271(2): 283-289, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30048320

RESUMO

OBJECTIVE: To compare the accuracy of the modified Fried Index (mFI) and the Clinical Frailty Scale (CFS) to predict death or patient-reported new disability 90 days after major elective surgery. BACKGROUND: The association of frailty with patient-reported outcomes, and comparisons between preoperative frailty instruments are poorly described. METHODS: This was a prospective multicenter cohort study. We determined frailty status in individuals ≥65 years having elective noncardiac surgery using the mFI and CFS. Outcomes included death or patient-reported new disability (primary); safety incidents, length of stay (LOS), and institutional discharge (secondary); ease of use, usefulness, benefit, clinical importance, and feasibility (tertiary). We measured the adjusted association of frailty with outcomes using regression analysis and compared true positive and false positive rates (TPR/FPR). RESULTS: Of 702 participants, 645 had complete follow up. The CFS identified 297 (42.3%) with frailty, the mFI 257 (36.6%); 72 (11.1%) died or experienced a new disability. Frailty was significantly associated with the primary outcome (CFS adjusted odds ratio, OR, 2.51, 95% confidence interval, CI, 1.50-4.21; mFI adjusted-OR 2.60, 95% CI 1.57-4.31). TPR and FPR were not significantly different between instruments. Frailty was the only significant predictor of death or new disability in a multivariable analysis. Need for institutional discharge, costs and LOS were significantly increased in individuals with frailty. The CFS was easier to use, required less time and had less missing data. CONCLUSIONS: Older people with frailty are significantly more likely to die or experience a new patient-reported disability after surgery. Clinicians performing frailty assessments before surgery should consider the CFS over the mFI as accuracy was similar, but ease of use and feasibility were higher.

5.
PLoS One ; 14(12): e0225423, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790451

RESUMO

INTRODUCTION: Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock. METHODS: The study retrospectively recruited patients with septic shock from the intensive care unit of a tertiary care hospital. Multiple organ dysfunction syndrome (MODS) was identified as sequential organ failure assessment (SOFA) score ≥ 2 in more than one organ system. The CFB is the sum of all daily intake and output. An independent t-test, single and multivariate logistic regression, the receiver operating characteristic (ROC) curves, and the Pearson correlation coefficient were used to determine whether a relationship exists between CFB and the development of MODS and mortality. RESULTS: Among the 104 patients enrolled in the study, 58 (55.8%) survived more than 28 days, and 73 (70.2%) developed MODS on day 3. The values of CFB in the first 24 hours and 72 hours after diagnosis of septic shock in patients with MODS were higher than these in patients without MODS (1086.6 ± 176.3 vs. 325.5 ± 205.7 ml, p = 0.013 and 2408 ± 361 vs. 873.1 ± 489 ml, p < 0.0001). In a multivariate logistic regression, the independent factors associated with the development of MODS on day 3 were APACHE II score at ICU admission (27.6 ± 7.6 in patients with MODS vs. 20.5 ± 6.4 in those without; O.R. 1.18; 95% C.1 I. 1.08-1.30; p < 0.001), disseminated intravascular coagulopathy (DIC) (n = 28; 38.4% vs. n = 2; 6.5%; O.R. 23.67; 95% C.I. 3.58-156.5; p = 0.001), and CFB in the first 72 hours (72-hr CFB) > median (1767.50ml) (n = 41; 56.2% vs. n = 11; 35.5%; O.R. 3.67; 95% C.I., 1.18-11.40; p = 0.024). Moreover, a multivariate logistic regression also identified neoplasm (n = 25; 54.3% vs. n = 17; 29.3%; O.R. 3.45; 95% C.I. 1.23-10.0; p = 0.019) and 72-hr CFB > median (n = 30; 65.2% vs. n = 21; 36.2%; O.R. 4.13; 95% C.I. 1.34-12.66; p = 0.013) as independent factors associated with 28-day mortality. 72-hr CFB values were strongly correlated with the SOFA score (r = 0.445, p < 0.0001). The area under the ROC curve revealed that 72-hr CFB has good discriminative power in associating the development of MODS (0.644, p = 0.002) and predicting subsequent 28-day mortality (0.704, p < 0.0001). CONCLUSIONS: 72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.

6.
Thorac Cancer ; 10(12): 2274-2281, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613427

RESUMO

BACKGROUND: Approximately 3%-5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum-based chemotherapy as front-line treatment for patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the direct comparison between them in the front-line setting remains lacking. METHODS: A total of 48 patients with ALK-positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front-line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed. RESULTS: Patients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression-free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log-rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08-0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause-specific hazard ratio, 0.21; 95% CI 0.06-0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment. CONCLUSION: Ceritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front-line treatment of ALK-positive advanced NSCLCs.

7.
Anesth Analg ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569165

RESUMO

BACKGROUND: Guidelines recommend routine preoperative frailty assessment for older people. However, the degree to which frailty instruments improve predictive accuracy when added to traditional risk factors is poorly described. Our objective was to measure the accuracy gained in predicting outcomes important to older patients when adding the Clinical Frailty Scale (CFS), Fried Phenotype (FP), or Frailty Index (FI) to traditional risk factors. METHODS: This was an analysis of a multicenter prospective cohort of elective noncardiac surgery patients ≥65 years of age. Each frailty instrument was prospectively collected. The added predictive performance of each frailty instrument beyond the baseline model (age, sex, American Society of Anesthesiologists' score, procedural risk) was estimated using likelihood ratio test, discrimination, calibration, explained variance, and reclassification. Outcomes analyzed included death or new disability, prolonged length of stay (LoS, >75th percentile), and adverse discharge (death or non-home discharge). RESULTS: We included 645 participants (mean age, 74 [standard deviation, 6]); 72 (11.2%) participants died or experienced a new disability, 164 (25.4%) had prolonged LoS, and 60 (9.2%) had adverse discharge. Compared to the baseline model predicting death or new disability (area under the curve [AUC], 0.67; R, 0.08, good calibration), prolonged LoS (AUC, 0.73; R, 0.18, good calibration), and adverse discharge (AUC, 0.78; R, 0.16, poor calibration), the CFS improved fit per the likelihood ratio test (P < .02 for death or new disability, <.001 for LoS, <.001 for discharge), discrimination (AUC = 0.71 for death or new disability, 0.76 for LoS, 0.82 for discharge), calibration (good for death or new disability, LoS, and discharge), explained variance (R = 0.11 for death or new disability, 0.22 for LoS, 0.25 for discharge), and reclassification (appropriate directional reclassification) for all outcomes. The FP improved discrimination and R for all outcomes, but to a lesser degree than the CFS. The FI improved discrimination for death or new disability and R for all outcomes, but to a lesser degree than the CFS and the FP. These results were consistent in internal validation. CONCLUSIONS: Frailty instruments provide meaningful increases in accuracy when predicting postoperative outcomes for older people. Compared to the FP and FI, the CFS appears to improve all measures of predictive performance to the greatest extent and across outcomes. Combined with previous research demonstrating that the CFS is easy to use and requires less time than the FP, clinicians should consider its use in preoperative practice.

8.
JAMA Netw Open ; 2(9): e1910756, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539073

RESUMO

Importance: Adverse drug events (ADEs) account for up to 16% of emergency department (ED) visits and 7% of hospital admissions. Medication reconciliation is required for hospital accreditation because it can reduce medication discrepancies, but there is no evidence that reducing discrepancies reduces ADEs or other adverse outcomes. Objective: To evaluate whether electronic medication reconciliation reduces ADEs, medication discrepancies, and other adverse outcomes compared with usual care. Design, Setting, and Participants: This cluster randomized trial involved 3491 patients who were discharged from 2 medical units and 2 surgical units at the McGill University Health Centre, Montreal, Quebec, Canada, between October 2014 and November 2016. Data analysis took place from July 2017 to July 2019. Intervention: The RightRx intervention electronically retrieved community drugs from the provincial insurer and aligned them with in-hospital drugs to facilitate reconciliation and communication at care transitions. Main Outcomes and Measures: The primary outcome was ADEs in 30 days after discharge. Secondary outcomes included medication discrepancies, ED visits, hospital readmissions, and a composite outcome of ED visits, readmissions, and death up to 90 days after discharge. Results: Of 4656 eligible patients, 3567 (76.6%) consented to participate (2060 [57.8%] men; mean [SD] age, 69.8 [14.9] years). Overall, 76 patients died during the hospital stay, so 3491 patients were included in the analysis. There was no significant difference in the risk of ADEs between intervention and control groups (76 [4.6%] vs 73 [4.0%]; OR, 0.97; 95% CI, 0.33-1.48), ED visits (433 [26.2%] vs 488 [26.6%]; OR, 0.83; 95% CI, 0.36-1.42), hospital readmission (170 [10.3%] vs 261 [14.2%]; OR, 0.22; 95% CI, 0.06-1.14), or the composite outcome (447 [27.0%] vs 506 [27.6%]; OR, 0.75; 95% CI, 0.34-1.27) at 30 days. Medication discrepancies were significantly reduced in the intervention group compared with the control group (437 [26.4%] vs 1029 [56.0%]; OR, 0.24; 95% CI, 0.12-0.57). Changes made to community medications (OR, 1.05; 95% CI, 1.01-1.10) and new medications (OR, 1.09; 95% CI, 1.01-1.18) were significant risk factors for ADEs. Conclusions and Relevance: Electronic medication reconciliation reduced medication discrepancies but did not reduce ADEs or other adverse outcomes. Hospital accreditation should focus on interventions that reduce the risk of adverse events for patients with multiple changes to community medications. Trial Registration: ClinicalTrials.gov identifier: NCT01179867.

9.
BMJ Qual Saf ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270254

RESUMO

BACKGROUND: We have designed a prospective adverse event (AE) surveillance method. We performed this study to evaluate this method's performance in several hospitals simultaneously. OBJECTIVES: To compare AE rates obtained by prospective AE surveillance in different hospitals and to evaluate measurement factors explaining observed variation. METHODS: We conducted a multicentre prospective observational study. Prospective AE surveillance was implemented for 8 weeks on the general medicine wards of five hospitals. To determine if population factors may have influenced results, we performed mixed-effects logistic regression. To determine if surveillance factors may have influenced results, we reassigned observers to different hospitals midway through surveillance period and reallocated a random sample of events to different expert review teams. RESULTS: During 3560 patient days of observation of 1159 patient encounters, we identified 356 AEs (AE risk per encounter=22%). AE risk varied between hospitals ranging from 9.9% of encounters in Hospital D to 35.8% of encounters in Hospital A. AE types and severity were similar between hospitals-the most common types were related to clinical procedures (45%), hospital-acquired infections (21%) and medications (19%). Adjusting for age and comorbid status, we observed an association between hospital and AE risk. We observed variation in observer behaviour and moderate agreement between clinical reviewers, which could have influenced the observed rate difference. CONCLUSION: This study demonstrated that it is possible to implement prospective surveillance in different settings. Such surveillance appears to be better suited to evaluating hospital safety concerns within rather than between hospitals as we could not definitively rule out whether the observed variation in AE risk was due to population or surveillance factors.

10.
J Am Geriatr Soc ; 67(9): 1843-1850, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250427

RESUMO

OBJECTIVES: Polypharmacy is common, costly, and harmful for hospitalized older adults. Scalable strategies to reduce the burden of potentially inappropriate medications (PIMs) are needed. We sought to leverage medication reconciliation in hospitalized older adults by pairing with MedSafer, an electronic decision support tool for deprescribing. DESIGN: This was a nonrandomized controlled before-and-after study. SETTING: The study took place on four internal medicine clinical teaching units. PARTICIPANTS: Subjects were aged 65 years and older, had an expected prognosis of 3 or more months, and were taking five or more usual home medications. INTERVENTION: In the baseline phase, patients received usual care that was medication reconciliation. Patients in the intervention arm also had a "deprescribing opportunity report" generated by MedSafer and provided to their in-hospital treating team. MEASUREMENTS: The primary outcome was ascertained at the time of hospital discharge and was the proportion of patients who had one or more PIMs deprescribed. RESULTS: A total of 1066 patients were enrolled, and deprescribing opportunities were present for 873 (82%; 418 during the control and 455 during the intervention phases, respectively). The proportion of patients with one or more PIMs deprescribed at discharge increased from 46.9% in the control period to 54.7% in the intervention period with an adjusted absolute risk difference of 8.3% (2.9%-13.9%). Not all classes of drugs in the intervention arm were associated with an increase in deprescribing, and new PIM starts were equally common in both arms of the study. CONCLUSION: Using an electronic decision support tool for deprescribing, we increased the proportion of patients with one or more PIMs deprescribed at hospital discharge as compared with usual care. Although this type of intervention may help address medication overload in hospitalized patients, it also underscores the importance of powering future trials for a reduction in adverse drug events. TRIAL REGISTRATION: NCT02918058. J Am Geriatr Soc 67:1843-1850, 2019.

11.
Ann Surg ; 270(1): 102-108, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29672410

RESUMO

OBJECTIVE: To develop and validate a preoperative frailty index (pFI) for use in population-based health administrative (HA) data. SUMMARY BACKGROUND DATA: Frailty is a robust predictor of adverse postoperative outcomes. Population-level frailty measures used in surgical studies have significant methodological limitations. Frailty indices (FIs) are a well-defined approach to measuring frailty with well-described methods for development and evaluation. An appropriate preoperative FI in HA data has not been derived or evaluated. METHODS: Retrospective cohort study using linked HA data in Canada. We identified people >65 years (2002-2015) who had major elective or emergency surgery. Standardized methods were used to construct a 30-variable pFI. Unadjusted and multilevel, multivariable adjusted models were used to measure the association of the pFI with 1-year mortality and institutional discharge. Elective patients were the derivation cohort, emergency patients were the validation cohort. Prespecified sensitivity analyses were performed. RESULTS: We identified 415,704 elective, and 95,581 emergency patients. The elective 1-year mortality rate was 4.7%. Thirty percent of population-level deaths occurred in people with frailty. Every 0.1-unit increase in the pFI was associated with a 2.20-fold increase in the adjusted odds of mortality (95% CI 2.15-2.26; c-statistic 0.81), and a 1.70-fold increase in institutional discharge (95% CI 1.59-1.80; c-statistic 0.71). pFI performance was similar in emergency patients, and was robust to changes in index composition. CONCLUSIONS: A preoperative FI derived from HA data is a robust method to measure frailty in elective and emergency patients. Generalizable FIs should be considered a standard approach to population-level study of surgical frailty.


Assuntos
Idoso Fragilizado , Fragilidade/diagnóstico , Indicadores Básicos de Saúde , Cuidados Pré-Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Idoso de 80 Anos ou mais , Canadá , Feminino , Seguimentos , Fragilidade/mortalidade , Humanos , Masculino , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
Anesthesiology ; 129(6): 1121-1131, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30273269

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS MANUSCRIPT TELLS US THAT IS NEW: BACKGROUND:: Substantial variation in primary anesthesia type for hip fracture surgery exists. Previous work has demonstrated that patients cared for at hospitals using less than 20 to 25% neuraxial anesthesia have decreased survival. Therefore, the authors aimed to identify sources of variation in anesthesia type, considering patient-, anesthesiologist-, and hospital-level variables. METHODS: Following protocol registration (NCT02787031), the authors conducted a cross-sectional analysis of a population-based cohort using linked administrative data in Ontario, Canada. The authors identified all people greater than 65 yr of age who had emergency hip fracture surgery from April 2002 to March 2014. Generalized linear mixed models were used to account for hierarchal data and measure the adjusted association of hospital-, anesthesiologist-, and patient-level factors with neuraxial anesthesia use. The proportion of variation attributable to each level was estimated using variance partition coefficients and the median odds ratio for receipt of neuraxial anesthesia. RESULTS: Of 107,317 patients, 57,080 (53.2%) had a neuraxial anesthetic. The median odds ratio for receiving neuraxial anesthesia was 2.36 between randomly selected hospitals and 2.36 between randomly selected anesthesiologists. The majority (60.1%) of variation in neuraxial anesthesia use was explained by patient factors; 19.9% was attributable to the anesthesiologist providing care and 20.0% to the hospital where surgery occurred. The strongest patient-level predictors were absence of preoperative anticoagulant or antiplatelet agents, absence of obesity, and presence of pulmonary disease. CONCLUSIONS: While patient factors explain most of the variation in neuraxial anesthesia use for hip fracture surgery, 40% of variation is attributable to anesthesiologist and hospital-level practice. Efforts to change practice patterns will need to consider hospital-level processes and anesthesiologists' intentions and behaviors.


Assuntos
Anestesiologistas/estatística & dados numéricos , Fraturas do Quadril/cirurgia , Hospitais/estatística & dados numéricos , Bloqueio Nervoso , Procedimentos Ortopédicos/métodos , Pacientes/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anestésicos , Anticoagulantes/efeitos adversos , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Pneumopatias/complicações , Masculino , Obesidade/complicações , Fatores de Risco , Resultado do Tratamento
13.
BMJ Open ; 8(6): e022057, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29934394

RESUMO

INTRODUCTION: Exercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent. METHODS AND ANALYSIS: We will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4). The intervention consists of > 3 weeks of exercise prehabilitation (strength, aerobic and stretching). The primary outcome is the 6 min walk test at the first postoperative clinic visit. Secondary outcomes include the short physical performance battery, health-related quality of life, disability-free survival, complications and health resource utilisation. The primary outcome will be analysed by intention to treat using analysis of covariance. Outcomes up to 1 year after surgery will be ascertained through linkage to administrative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by our ethics review board (Protocol Approval #2016009-01H). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media. TRIAL REGISTRATION NUMBER: NCT02934230; Pre-results.


Assuntos
Terapia por Exercício/métodos , Fragilidade/reabilitação , Neoplasias/cirurgia , Cuidados Pré-Operatórios , Procedimentos Cirúrgicos Eletivos , Humanos , Tempo de Internação , Modelos Lineares , Modelos Logísticos , Cooperação do Paciente , Complicações Pós-Operatórias , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
BMC Geriatr ; 18(1): 55, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29466947

RESUMO

BACKGROUND: Giant cell arteritis (GCA) is an immune mediated inflammatory disease of medium and large arteries which afflicts older people. The classical presentation features include: headache, visual disturbances, and jaw claudication. Patients diagnosed with GCA have also been observed to be at higher risk for the subsequent development of strokes. CASE PRESENTATION: We describe a case of an 84-year old right-handed man who presented to hospital with dysarthria, dysphagia, right-sided facial drop, a history of generalized weakness and multiple falls. He was admitted to geriatric medicine with the working diagnosis of a posterior circulation stroke syndrome. He was also started on antibiotic treatment for a possible community-acquired pneumonia because of the presence of a low-grade fever and a chest radiograph showing ill-defined left lower lobe airspace disease. Initial lab results were remarkable for an erythrocyte sedimentation rate (ESR) of 112 mm/h and a C-reactive protein (CRP) level of 110 mg/L consistent with an active inflammatory state. Neurovascular imaging showed mild atherosclerotic changes of the aortic arch and proximal great vessels without significant stenosis. The patient was started on daily high-dose prednisone because of the possibility of a cerebral vasculitis. Bilateral biopsy of temporal arteries showed giant cell arteritis. The patient's neurologic status and inflammatory markers significantly improved (ESR 52 mm/h, CRP 7.0 mg/L) and he was eventually discharged to a seniors home with services. CONCLUSION: The initial presentation of giant cell arteritis as a stroke syndrome, especially in the posterior circulation territory, is exceedingly rare. Other atypical presenting symptoms may include chronic cough and fever of unknown origin. The elevated ESR and CRP levels were clues to the diagnosis and clinical decision-making should be driven by a high index of suspicion since no single test (ESR, CRP, temporal artery biopsy) has perfect sensitivity. Elevated CRP may have a role in increasing stroke risk. This case report illustrates that in older people clinicians must consider atypical presentations of disease more often since timely diagnosis and initiation of treatment can result in optimal outcomes.


Assuntos
Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Diagnóstico Diferencial , Arterite de Células Gigantes/sangue , Humanos , Masculino , Acidente Vascular Cerebral/sangue , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia
15.
Implement Sci ; 13(1): 7, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321043

RESUMO

BACKGROUND: Drug expenditures are responsible for an increasing proportion of health costs, accounting for $1.1 trillion in annual expenditure worldwide. As hundreds of billions of dollars are being spent each year on overtreatment with prescribed medications that are either unnecessary or are in excess of lowest cost-effective therapy, programs are needed that optimize fiscally appropriate use. We evaluated whether providing physicians with information on the patient out-of-pocket payment consequences of prescribing decisions that were in excess of lowest cost-effective therapy would alter prescribing decisions using the treatment of uncomplicated hypertension as an exemplar. METHODS: A single-blind cluster randomized trial was conducted over a 60-month follow-up period in 76 primary care physicians in Quebec, Canada, and their patients with uncomplicated hypertension who were using the MOXXI integrated electronic health record for drug and health problem management. Physicians were randomized to an out-of-pocket expenditure module that provided alerts for comparative out-of-payment costs, thiazide diuretics as recommended first-line therapy, and tools to monitor blood pressure targets and medication compliance, or alternatively the basic MOXXI system. System software and prescription claims were used to analyze the impact of the intervention on treatment choice, adherence, and overall and out-of-pocket payment costs using generalized estimating equations. RESULTS: Three thousand five-hundred ninety-two eligible patients with uncomplicated hypertension were enrolled, of whom 1261 (35.1%) were newly started (incident patient) on treatment during follow-up. There was a statistically significant increase in the prescription of diuretics in the newly treated intervention (26.6%) compared to control patients (19.8%) (RR 1.65, 95% CI 1.17 to 2.33). For patients already treated (prevalent patient), there was a statistically significant interaction between the intervention and patient age, with older patients being less likely to be switched to a diuretic. Among the incident patients, physicians with less than 15 years of experience were much more likely to prescribe a diuretic (OR 10.69; 95% CI 1.49 to 76.64) than physicians with 15 to 25 years (OR 0.67; 95%CI 0.25 to 1.78), or more than 25 years of experience (OR 1.80; 95% CI 1.23 to 2.65). There was no statistically significant effect of the intervention on adherence or out-of-pocket payment cost. CONCLUSIONS: The provision of comparative information on patient out-of-pocket payments for treatment of uncomplicated hypertension had a statistically significant impact on increasing the initiation of diuretics in incident patients and switching to diuretics in younger prevalent patients. The impact of interventions to improve the cost-effectiveness of prescribing may be enhanced by also targeting patients with tools to participate in treatment decision-making and by providing physicians with comparative out-of-pocket information on all evidence-based alternatives that would enhance clinical decision-making. TRIAL REGISTRATION: ISRCTN96253624.


Assuntos
Honorários Farmacêuticos/estatística & dados numéricos , Gastos em Saúde , Hipertensão/tratamento farmacológico , Atenção Primária à Saúde/organização & administração , Idoso , Canadá , Feminino , Humanos , Hipertensão/economia , Recém-Nascido , Masculino , Quebeque , Método Simples-Cego
16.
Curr Atheroscler Rep ; 20(1): 5, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29368179

RESUMO

PURPOSE OF REVIEW: Non-adherence to medications for the secondary prevention of myocardial infarction (MI) is a major contributor to morbidity and mortality in these patients. This review describes recent advances in promoting adherence to therapies for coronary artery disease (CAD). RECENT FINDINGS: Two large randomized controlled trials to "incentivize" adherence were somewhat disappointing; neither financial incentives nor "peer pressure" successfully increased rates of adherence in the post-MI population. Patient education and provider engagement appear to be critical aspects of improving adherence to CAD therapies, where the provider is a physician, pharmacist, or nurse and follow-up is performed in person or by telephone. Fixed-dose combinations of CAD medications, formulated as a so-called "polypill," have shown some early efficacy in increasing adherence. Technological advances that automate monitoring and/or encouragement of adherence are promising but seem universally dependent on patient engagement. For example, medication reminders via text message perform better if patients are required to respond. Multifaceted interventions, in which these and other interventions are combined together, appear to be most effective. There are several available types of proven interventions through which providers, and the health system at large, can advance patient adherence to CAD therapies. No single intervention to promote adherence will be successful in all patients. Further study of multifaceted interventions and the interactions between different interventions will be important to advancing the field. The goal is a learning healthcare system in which a network of interventions responds and adapts to patients' needs over time.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Adesão à Medicação , Infarto do Miocárdio/prevenção & controle , Doença da Artéria Coronariana/complicações , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Humanos , Adesão à Medicação/psicologia , Infarto do Miocárdio/etiologia , Educação de Pacientes como Assunto , Papel Profissional , Relações Profissional-Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistemas de Alerta , Prevenção Secundária
17.
Anesthesiology ; 128(3): 480-491, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28968275

RESUMO

BACKGROUND: There is consistent and significant variation in neuraxial anesthesia use for hip fracture surgery across jurisdictions. We measured the association of hospital-level utilization of neuraxial anesthesia, independent of patient-level use, with 30-day survival (primary outcome) and length of stay and costs (secondary outcomes). METHODS: We conducted a population-based cohort study using linked administrative data in Ontario, Canada. We identified all hip fracture patients more than 65 yr of age from 2002 to 2014. For each patient, we measured the proportion of hip fracture patients at their hospital who received neuraxial anesthesia in the year before their surgery. Multilevel, multivariable regression was used to measure the association of log-transformed hospital-level neuraxial anesthetic-use proportion with outcomes, controlling for patient-level anesthesia type and confounders. RESULTS: Of 107,317 patients, 57,080 (53.2%) had a neuraxial anesthetic; utilization varied from 0 to 100% between hospitals. In total, 9,122 (8.5%) of patients died within 30 days of surgery. Survival independently improved as hospital-level neuraxial use increased (P = 0.009). Primary and sensitivity analyses demonstrated that most of the survival benefit was realized with increase in hospital-level neuraxial use above 20 to 25%; there did not appear to be a substantial increase in survival above this point. No significant associations between hospital neuraxial anesthesia-use and other outcomes existed. CONCLUSIONS: Hip fracture surgery patients at hospitals that use more than 20 to 25% neuraxial anesthesia have improved survival independent of patient-level anesthesia type and other confounders. The underlying causal mechanism for this association requires a prospective study to guide improvements in perioperative care and outcomes of hip fracture patients. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B634.


Assuntos
Anestesia por Condução/mortalidade , Anestesia por Condução/estatística & dados numéricos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anestesia por Condução/métodos , Estudos de Coortes , Feminino , Lesões do Quadril/epidemiologia , Lesões do Quadril/cirurgia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Ontário/epidemiologia , Análise de Sobrevida , Resultado do Tratamento
18.
J Am Med Inform Assoc ; 25(5): 482-495, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040609

RESUMO

Background and Objective: Many countries require hospitals to implement medication reconciliation for accreditation, but the process is resource-intensive, thus adherence is poor. We report on the impact of prepopulating and aligning community and hospital drug lists with data from population-based and hospital-based drug information systems to reduce workload and enhance adoption and use of an e-medication reconciliation application, RightRx. Methods: The prototype e-medical reconciliation web-based software was developed for a cluster-randomized trial at the McGill University Health Centre. User-centered design and agile development processes were used to develop features intended to enhance adoption, safety, and efficiency. RightRx was implemented in medical and surgical wards, with support and training provided by unit champions and field staff. The time spent per professional using RightRx was measured, as well as the medication reconciliation completion rates in the intervention and control units during the first 20 months of the trial. Results: Users identified required modifications to the application, including the need for dose-based prescribing, the role of the discharge physician in prescribing community-based medication, and access to the rationale for medication decisions made during hospitalization. In the intervention units, both physicians and pharmacists were involved in discharge reconciliation, for 96.1% and 71.9% of patients, respectively. Medication reconciliation was completed for 80.7% (surgery) to 96.0% (medicine) of patients in the intervention units, and 0.7% (surgery) to 82.7% of patients in the control units. The odds of completing medication reconciliation were 9 times greater in the intervention compared to control units (odds ratio: 9.0, 95% confidence interval, 7.4-10.9, P < .0001) after adjusting for differences in patient characteristics. Conclusion: High rates of medication reconciliation completion were achieved with automated prepopulation and alignment of community and hospital medication lists.


Assuntos
Sistemas de Informação em Farmácia Clínica , Serviços Comunitários de Farmácia/organização & administração , Registro Médico Coordenado , Reconciliação de Medicamentos/métodos , Serviço de Farmácia Hospitalar/organização & administração , Software , Adulto , Idoso , Feminino , Formulários Farmacêuticos como Assunto , Humanos , Masculino , Erros de Medicação/prevenção & controle , Pessoa de Meia-Idade , Segurança do Paciente , Quebeque
19.
Can Med Educ J ; 8(3): e49-e70, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29098048

RESUMO

Background: The effects of changes to resident physician duty hours need to be measureable. This time-motion study was done to record internal medicine residents' workflow while on duty and to determine the feasibility of capturing detailed data using a mobile electronic tool. Methods: Junior and senior residents were shadowed by a single observer during six-hour blocks of time, covering all seven days. Activities were recorded in real-time. Eighty-nine activities grouped into nine categories were determined a priori. Results: A total of 17,714 events were recorded, encompassing 516 hours of observation. Time was apportioned in the following categories: Direct Patient Care (22%), Communication (19%), Personal tasks (15%), Documentation (14%), Education (13%), Indirect care (11%), Transit (6%), Administration (0.6%), and Non-physician tasks (0.4%). Nineteen percent of the education time was spent in self-directed learning activities. Only 9% of the total on duty time was spent in the presence of patients. Sixty-five percent of communication time was devoted to information transfer. A total of 968 interruptions were recorded which took on average 93.5 seconds each to service. Conclusion: Detailed recording of residents' workflow is feasible and can now lead to the measurement of the effects of future changes to residency training. Education activities accounted for 13% of on-duty time.

20.
J Am Geriatr Soc ; 65(12): 2665-2672, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28971482

RESUMO

BACKGROUND/OBJECTIVES: Randomized and nonrandomized single-center studies suggest that preoperative geriatric evaluation improves postoperative outcomes in older adults. The generalizability and population-level effect of preoperative geriatric evaluation has not been determined. Our objective was to measure the adjusted association between preoperative geriatric evaluation and postoperative outcomes. DESIGN: Multilevel multivariable regression model analysis of a population-based historical cohort. SETTING: Publicly funded universal healthcare system in Ontario, Canada. PARTICIPANTS: All adults aged 65 and older having major, elective, noncardiac surgery from 2002 to 2014 (N = 266,499). INTERVENTION: We studied geriatric consultations and comprehensive assessments performed in the 4 months prior to surgery. These were identified using validated methods. MEASUREMENTS: Ninety-day survival (primary outcome), in-hospital complications, length of stay, 30-day readmissions, need for supported discharge, and 90-day costs of care. RESULTS: The 7,352 participants (2.8%) who had a preoperative geriatric evaluation had longer 90-day survival than those who who did not (adjusted hazard ratio = 0.81, 95% confidence interval = 0.68-0.95). Length of stay and complication rates did not differ between groups, but participants evaluated by a geriatrician preoperatively had higher rates of supported discharge, readmission rates, and costs of care. Sensitivity analyses supported the association between preoperative geriatric assessment and 90-day survival. CONCLUSION: In individuals aged 65 and older undergoing major, elective, noncardiac surgery, preoperative geriatric evaluation was associated with longer 90-day survival, but it is used infrequently. Given these results, and those of previous small studies, the influence of a geriatric evaluation on postoperative outcomes should be determined in a multicenter randomized trial.


Assuntos
Procedimentos Cirúrgicos Eletivos , Avaliação Geriátrica , Cuidados Pré-Operatórios/métodos , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Análise de Regressão , Taxa de Sobrevida , Resultado do Tratamento
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