In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA, respectively. In this paper, the active targeting properties of B-F87-PLA and B-P85-PLA nanoparticles in vitro were investigated through a three-step biotin-avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells. The loading and release behavior of paclitaxel loaded in B-Pluronic-PLA nanoparticles were also studied. Paclitaxel loaded in both B-F87-PLA and B-P85-PLA nanoparticles shows an initial rapid release followed by a slow release period. Compared with SKOV-3 cells, the cytotoxicity results implied that paclitaxel-loaded B-Pluronic-PLA nanoparticles were delivered more effectively to OVCAR-3 cells due to the specific interaction between the biotin groups on the surface of B-Pluronic-PLA nanoparticles and the avidin/biotinylated MAb X306/CA-125 antigen complexes on the surface of OVCAR-3 cells. The active targeting properties of B-F87-PLA nanoparticles were further confirmed by FM.
Randomized trials have shown that medical and interventional therapies improve outcomes for acute myocardial infarction (AMI) patients. The extent to which hospital quality improvement translates into better patient outcomes is unclear.
To determine hospital cardiac management markers associated with improved outcomes. RESEARCH DESIGN, SUBJECTS: Population-based longitudinal cohort study of 98,115 adults hospitalized with first episode of AMI during 2000 to 2006 in 77 Ontario hospitals with >50 annual AMI admissions.
Rates of 30-day and 1-year mortality, readmissions for AMI or death, and major cardiac events (readmissions for AMI, angina, heart failure, or death) within 6 months, according to index hospital cardiac management markers, including appropriate initial emergency department (ED) assessment (rate of high acuity triage) high-acuity and intensity of interventional (30-day cardiac catheterization rate) and medical (discharge statin prescribing rate) therapy.
Thirty-day risk-adjusted mortality varied 2.3-fold (7.2%-16.9%) and major cardiac events rates varied 2-fold (18.2%-35.6%) across hospitals in 2006. Patients admitted to hospitals with the highest versus lowest rates of combined medical and interventional management had lower rates of 30-day mortality (adjusted relative rate [aRR] = 0.84, 95% CI, 0.78-0.91), 1-year mortality (aRR = 0.86, 0.81-0.91), AMI readmissions or death (aRR = 0.74, 0.69-0.78), and major cardiac event (aRR = 0.65, 0.61-0.68). Patients admitted to EDs with the highest rates of appropriate initial assessment had lower 30-day (aRR = 0.93, 0.88-0.98) and 1-year mortality (aRR = 0.96, 0.93-1.00).
Hospitals with higher levels of both medical and interventional management and higher quality initial ED assessment had better outcomes. Readmissions were particularly sensitive to care processes. In the face of the unwarranted variations in outcomes across hospitals, strategies that promote better ED and inpatient management of AMI patients are needed.
Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.
We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.
Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians.
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Severe acute kidney injury among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who survive to hospital discharge.
To assess the risk of chronic dialysis and all-cause mortality in individuals who experience an episode of acute kidney injury requiring dialysis.
We conducted a population-based cohort study of all adult patients in Ontario, Canada, with acute kidney injury who required in-hospital dialysis and survived free of dialysis for at least 30 days after discharge between July 1, 1996, and December 31, 2006. These individuals were matched with patients without acute kidney injury or dialysis during their index hospitalization. Matching was by age plus or minus 5 years, sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury requiring dialysis. Patients were followed up until March 31, 2007.
The primary end point was the need for chronic dialysis and the secondary outcome was all-cause mortality.
We identified 3769 adults with acute kidney injury requiring in-hospital dialysis and 13 598 matched controls. The mean age was 62 years and median follow-up was 3 years. The incidence rate of chronic dialysis was 2.63 per 100 person-years among individuals with acute kidney injury requiring dialysis, and 0.91 per 100 person-years among control participants (adjusted hazard ratio, 3.23; 95% confidence interval, 2.70-3.86). All-cause mortality rates were 10.10 and 10.85 per 100 person-years, respectively (adjusted hazard ratio, 0.95; 95% confidence interval, 0.89-1.02).
Acute kidney injury necessitating in-hospital dialysis was associated with an increased risk of chronic dialysis but not all-cause mortality.
Comment In: JAMA. 2010 Jan 20;303(3):229; author reply 229-3020085947
Restrictions on non-urgent hospital care imposed to control the 2003 Toronto severe acute respiratory syndrome outbreak led to substantial disruptions in hospital clinical practice, admission, and transfer patterns.
We assessed whether there were unintended health consequences to seriously ill hospitalized patients. STUDY DESIGN, SETTING, AND POPULATION: Population-based longitudinal cohort study of patients residing in Toronto or an urban control region with an incident admission for 1 of 7 serious conditions in the 3 years before, or the 4 months during or after restrictions.
Short-term mortality, overall readmissions, cardiac readmissions for acute myocardial infarction patients, serious complications for very low birth weight babies, and quality of care measures, comparing adjusted rates across time periods within regions.
Mortality, readmission, and complication rates did not change for any condition during or after severe acute respiratory syndrome restrictions. Although rates of invasive cardiac procedures for acute myocardial infarction patients decreased 11-37% in Toronto, rates of nonfatal cardiac outcomes did not change.
Restrictions on non-urgent hospital utilization and hospital transfers may be a safe public health strategy to employ to control nosocomial outbreaks or provide hospital surge capacity for up to several months, in large, well-developed healthcare systems with good availability of community-based care.
Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks.
We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individual's likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89-0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77-0.91), and all-cause mortality (0.87; 95% CI 0.84-0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized.
Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.
Survivors of severe acute kidney injury remain at high risk of death well after apparent recovery from the initial insult. Here we determine whether early nephrology follow-up after a hospitalization complicated by severe acute kidney injury associates with patient survival. This consisted of a cohort study of all hospitalized adults in Ontario from 1996 to 2008 with acute kidney injury who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. Propensity scores were used to match individuals with early nephrology follow-up, defined as a visit with a nephrologist within 90 days of discharge, to those without. The outcome was time to all-cause mortality of 3877 patients who met the eligibility criteria within a maximum follow-up of 2 years. A total of 1583 patients had early nephrology follow-up of whom 1184 were successfully matched 1:1 to those not receiving early follow-up. The incidence of all-cause mortality was lower in those patients with early nephrology follow-up compared with those without (8.4 compared with 10.6 per 100-patient years, hazard ratio 0.76 (95% CI: 0.62-0.93)). Thus, early nephrology follow-up after hospitalization with acute kidney injury and temporary dialysis was associated with improved survival. This finding requires definitive testing in a randomized controlled trial.
Transitions between health care settings represent vulnerable periods for medical error. Discontinuation of long-term medication use may occur during discharge from the hospital to the community.
We performed a population-based, cohort study using administrative records from Ontario, Canada, between April 1, 1997, and September 30, 2002. We studied all residents 66 years and older with continuous use of warfarin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), or beta-blocker ophthalmic drops for 1 or more years. Those who had an overnight hospitalization for selected elective surgical procedures were compared with 2 control groups: one that had an ambulatory procedure and one that had no procedures. All groups were assessed for the outcome of failure to renew the prescription within 6 months.
Rates of drug treatment discontinuation after overnight hospitalizations, after ambulatory procedures, and after no procedures were 11.4%, 7.5%, and 4.8%, respectively, in the warfarin group; 4.0%, 3.9%, and 3.9%, respectively, in the statin group; and 8.4%, 8.9%, and 7.9%, respectively, in the ophthalmic drops group. The adjusted odds ratio (OR) was 2.6 (95% confidence interval [CI], 2.0-3.4) for discontinuation of warfarin therapy after overnight hospitalizations and 1.6 (95% CI, 1.4-1.7) after ambulatory procedures. In contrast, there was no increased risk of discontinuing treatment with either statins (OR for overnight hospitalization, 1.0 [95% CI, 0.9-1.2]; OR for ambulatory procedure, 1.0 [95% CI 1.0-1.1]) or ophthalmic drops (OR for overnight hospitalization, 1.0 [95% CI, 0.8-1.5]; OR for ambulatory procedure, 1.1 [95% CI, 1.0-1.2]).
Patients prescribed long-term therapy with warfarin were at risk for potentially unintended medication discontinuation after elective procedures. Patients prescribed statins or beta-blocker ophthalmic drops were not at increased risk.
Department of Anesthesia, Toronto General Hospital, University Health Network, Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. firstname.lastname@example.org
When comparing transfused versus nontransfused patients, erythrocyte transfusion is consistently associated with increased mortality. Nonetheless, unmeasured confounding may unduly influence this comparison. This unmeasured risk may have less influence on comparisons of patients undergoing surgery at hospitals with differing transfusion rates.
Administrative databases were used to conduct a population-based cohort study of patients who underwent elective hip- or knee-replacement surgery from 1999 to 2008 in Ontario, Canada. The authors used Cox proportional-hazards models to determine the adjusted association of hospital-specific erythrocyte transfusion rates (i.e., comparing hospitals with differing transfusion rates) with postoperative mortality. For comparison, they also determined the adjusted association of patient receipt of transfusion (i.e., comparing transfused vs. nontransfused patients) with mortality.
Of 162,190 patients, 23% (n=37,015) were transfused. Hospital-specific transfusion rates at the 66 included hospitals ranged from 10.3 to 57.9%. Compared with nontransfused patients, transfused patients experienced increased adjusted 30-day (hazard ratio 2.32; 95% CI, 1.91-2.83) and 1-yr mortality (hazard ratio 1.75; 95% CI, 1.60-1.91). However, when hospitals were categorized into quartiles based on hospital-specific transfusion rates, mortality rates were similar (highest transfusion quartile vs. lowest transfusion quartile: 30-day mortality, hazard ratio 1.11, 95% CI 0.82-1.50; 1-yr mortality, hazard ratio 1.02, 95% CI 0.82-1.26).
The association of transfusion with postoperative mortality differed significantly when comparing transfused versus nontransfused patients, as opposed to comparing hospitals with differing transfusion rates. This discrepancy raises questions about the true relationship between transfusion and mortality.