Rates Of Safety Events Research Articles

Outcome of patients with previous coronary artery bypass grafting and severe calcific aortic stenosis receiving transfemoral transcatheter aortic valve replacement.

To evaluate the impact of previous coronary artery bypass grafting (CABG) on early safety at 30 days and 1-year mortality in patients receiving transcatheter aortic valve replacement (TAVR). The use of TAVR in patients with previous CABG suffering from severe aortic stenosis has increased in the last years. Consecutive TAVR patients were stratified according to previous CABG versus no previous cardiac surgery (control). All-cause 1-year mortality and early safety at 30 days were evaluated. In the unmatched cohort and compared to control (n = 2,364), CABG (n = 260) were younger, more often male and suffered more often from comorbidities leading to an increased STS-score (p < .001). The rate of early safety events at 30 days was comparable between CABG and control (21.2% vs. 24.6%, p = .22) with a higher mortality in CABG (9.6% vs. 5.3%, p = .005). All-cause 1-year mortality was higher in CABG compared to controls (HR 1.51 [95%-CI 1.15-1.97], p = .003). Applying Cox regression analysis, both 30-day (HR 1.57 [95%-CI 0.97-2.53], p = .067) and all-cause 1-year mortality (HR 1.24 [95%-CI 0.91-1.70], p = .174) were not significantly different between groups. After propensity-score matching, the rate of early safety events at 30 days was lower in CABG compared to controls (21.6% vs. 31.7%, p = .02). Thirty-day (9.1% vs. 7.7%, p = .596) and all-cause 1-year mortality (24.0% vs. 23.1%, p = .520, HR 1.14 [95%-CI 0.77-1.69], p = .520) were not different between groups. In patients receiving TAVR, previous CABG was not associated with an increase in periprocedural complications and all-cause 1-year mortality when adjusted for other comorbidities.

Real-World Outcomes of Rivaroxaban Treatment in Patients with Both Nonvalvular Atrial Fibrillation and a History of Ischemic Stroke/Transient Ischemic Attack

Introduction: Prior stroke is a risk factor for stroke and bleeding during anticoagulation in patients with atrial fibrillation (AF). Although rivaroxaban is widely prescribed to reduce their risk of stroke in patients with nonvalvular AF (NVAF), the real-world evidence on rivaroxaban treatment is limited. We aimed to examine the outcomes of rivaroxaban treatment in NVAF patients with prior ischemic stroke/transient ischemic attack (TIA) by using the data of the Xarelto Post-Authorization Safety and Effectiveness Study in Japanese ­Patients with AF, a prospective, single-arm, observational study. Methods: The clinical outcomes of 9,578 patients who completed the 1-year follow-up were evaluated. Safety and effectiveness outcomes were compared between patients with and without prior ischemic stroke/TIA. Results: Among the patients, 2,153 (22.5%) had prior ischemic stroke/TIA. They were significantly older and had lower body weight, lower creatinine clearance, higher CHADS₂, CHA₂DS₂-VASc, and modified HAS-BLED scores as compared to those without prior ischemic stroke/TIA. Any bleeding (9.1 vs. 7.2 events per 100 patient-years), major bleeding (2.3 vs. 1.6 events per 100 patient-years), and stroke/non-central nervous system systemic embolism/myocardial infarction (3.4 vs. 1.3 events per 100 patient-years) were more frequent in patients with prior ischemic stroke/TIA. Stepwise regression analysis suggested that body weight of ≤50 kg and diabetes mellitus were predictive of major bleeding in patients with prior ischemic stroke/TIA. Conclusions: Safety and effectiveness event rates were higher in patients with prior ischemic stroke/TIA than those without. This might be explained by differences in several risk profiles including age, body weight, renal function, and risk scores such as CHADS₂ between the groups. Clinicaltrials.gov: NCT01582737.

Root cause analysis: A framework using principles of high reliability.

233 Background: Medical errors are the 4th leading cause of death in the US. Oncology providers are not immune to errors. A network of hospitals and outpatient centers recognized an opportunity to enhance and standardize our approach to root cause analyses (RCAs). As leaders, we have an imperative to prevent issues that can result in a safety event; yet we have an even greater moral obligation to correct causes once an event occurs to prevent it from happening again. Methods: A framework was established to prevent recurrence through a focus upon root solutions. Recognizing that human error is not the cause of the failure but a symptom, the goal is to understand why it made sense for individuals to do what they did by reconstructing the world in which they found themselves at the time of the event. The includes: 1) training staff on high reliability; 2) assigning an executive to remove barriers; 3) creating a charter; 4) conducting 1:1 interviews; 5) deploying tools (such as sequence of event diagramming, validation and verification of raw data, human error type classification; individual/system failure and event/causal factor charting); 6) transporting findings; and 7) action planning with controls. A 3-meeting model was embraced. Results: As of April 2019, 9 events have been investigated. Event types include: infusion hours/splitting orders, incorrect lab order, retained object, wrong patient medication administration, patient brachytherapy underdosing, wrong site delayed treatment, rapid response call delay, and delay in care for extravasation. The 12-month rolling average serious safety event rate per 10,000 patient days decreased from 1.93 to 1.33 since implementation. With 6 months experience under the enhanced framework, plans also exist to monitor events from similar root causes as a success measure. Summaries allowing this level of analyses include event description, immediate actions, proximate versus root causes, and corrective actions. Conclusions: The capacity to learn from experience is essential to patient safety. Adherence to the framework ensures movement beyond proximate to root causes. It is a means to spread knowledge using proven tools based upon principles of high reliability.

Real-world outcomes of rivaroxaban treatment in elderly Japanese patients with nonvalvular atrial fibrillation

Direct oral anticoagulants (DOACs), such as rivaroxaban, reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). However, it is still unclear whether the stroke reduction benefit outweighs the bleeding risk in elderly Japanese patients with NVAF. The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a real-world, prospective observational, post-marketing surveillance study on the safety and effectiveness of rivaroxaban in Japanese clinical practice. This sub-analysis evaluated the clinical outcomes of elderly patients aged ≥ 75 years. At the 1-year follow-up, there were 4,685 (48.91%) and 4,893 (51.09%) patients aged ≥ 75 and < 75 years, respectively. Safety and effectiveness outcomes were compared between patients aged ≥ 75 years and those aged < 75 years, and among 3 elderly sub-populations (age ranges: 75–79, 80–84, and ≥ 85 years). Patients aged ≥ 75 years had higher rates of major bleeding [2.22 vs. 1.35 events per 100 patient-years, hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.17–2.28] and composite of stroke (ischemic or hemorrhagic)/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI) (2.41 vs. 1.21 events per 100 patient-years, HR 1.97, 95% CI 1.40–2.77) compared to patients aged < 75 years. Intracranial hemorrhage rates were < 1 event per 100 patient-years in both groups (0.85 vs. 0.59 events per 100 patient-years, HR 1.43, 95% CI 0.85–2.40). Kaplan–Meier curves of major bleeding and stroke/non-CNS SE/MI showed that no significant differences of cumulative event rates were identified among the 3 elderly sub-populations. Stepwise Cox regression analyses revealed that creatinine clearance (CrCl) (<50 mL/min), hepatic impairment, and hypertension were specific predictors for major bleeding and no specific predictors were found for stroke/non-CNS SE/MI in patients aged ≥ 75 years. In conclusion, safety and effectiveness event rates were higher in patients aged ≥ 75 years compared with those aged < 75 years, yet, no distinct differences were observed among the 3 elderly sub-populations.

Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD.

Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment.We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed.Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40-211 days) for AAT and 140 days (IQR 72-142 days) for placebo (p=0.0952). The mean yearly rate of all exacerbations was 3.12 in the AAT-treated group and 2.67 in the placebo group (p=0.31). More patients receiving AAT reported treatment-related treatment-emergent adverse events compared to placebo (57.5% versus 46.9%, respectively) and they were more likely to withdraw from the study. After the first year of the study, when modifications to the handling of the nebuliser were introduced, the rate of safety events in the AAT-treated group dropped to that of the placebo group.We conclude that in AATD patients with severe COPD and frequent exacerbations, AAT inhalation for 50 weeks showed no effect on time to first exacerbation but may have changed the pattern of the episodes.

Eculizumab Safety: Five-Year Experience From the Global Atypical Hemolytic Uremic Syndrome Registry

IntroductionEculizumab has transformed outcomes for patients with atypical hemolytic uremic syndrome (aHUS). Its efficacy and safety profile was well characterized in the clinical trial program. The long-term safety profile was not previously assessed or compared against nontreated patients in an observational registry setting.MethodsThe Global aHUS Registry recruits patients with clinical diagnoses of aHUS. This analysis includes baseline characteristics and targeted safety events from adult and pediatric patients who were “ever treated” versus “never treated” with eculizumab in the first 5 years of the registry, through January 26, 2017.ResultsOverall, 1321 patients (adult, n = 842; pediatric, n = 479; ever treated, n = 865; never treated, n = 456) were enrolled. A higher proportion of ever-treated versus never-treated adult and pediatric patients had renal, cardiovascular, pulmonary, central nervous system, gastrointestinal symptoms, and hepatic impairment. No differences in safety event rates between ever-treated and never-treated patients were observed, except serious infections in pediatric patients (5.15 versus 1.12 events/100 patient-years for ever- and never-treated patients, respectively). Deaths were more frequent in adult (4.7% and 9.9% of ever- and never-treated patients) compared with pediatric patients (1.8% of ever-treated patients; no deaths in never-treated patients).Three meningococcal infections were reported in ever-treated patients; 1 infection led to a fatal outcome.ConclusionIn this large observational dataset covering 5 years of registry enrollment, no new safety concerns were identified for adult or pediatric eculizumab-treated patients with aHUS, confirming a positive benefit−risk profile in a real-world setting.

Safety Events and Privilege Utilization Rates in Advanced Practice Physical Therapy Compared to Traditional Primary Care: An Observational Study

The general practitioner shortage in the United States coupled with a growing number of Americans living with disability has fueled speculation of non-physician providers assuming a greater role in musculoskeletal healthcare. Previous physician shortages have been similarly addressed, and expanding physical therapy (PT) scope of practice may best serve to fill this need. Resistance to expanding PT practice focuses on patient safety as PTs assume the roles traditionally performed by primary care providers. While studies have shown advanced practice PT to be safe, none have compared safety events in advanced practice PT compared to primary care to determine if there are increased patient risks. Therefore, the purpose of our study is to examine the rate of safety events and utilization of services in an advanced practice PT clinic compared to a primary care clinic. A secondary aim of our study was to report safety events associated with spinal manipulation and dry needling procedures. Productivity and safety data were retrospectively collected from Malcolm Grow Medical Center from 2015 to 2017 for the Family Health Clinic (FHC) and an advanced practice Physical Therapy Clinic (PTC). Chi-square tests for independence, risk ratios (RR) and 95% confidence intervals (95%) were used to compare the relationship between the frequency of (1) patient encounters and clinical procedures and (2) clinical procedures and safety events. Seventy-five percent (12/16) of safety events reported in the PTC were defined as near misses compared to 50% (28/56) within the FHC (RR 1.5; 95% CIs: 1.0 to 2.2). Safety events were more likely to reach patients in the FHC compared to the PTC (RR 1.9; 95% CIs: 0.8 to 4.7). Safety events associated with minor harm to patients was n = 4 and n = 3 in the FHC and PTC respectively. No sentinel events, intentional harm events, nor actual events with more than minor harm were reported in either clinic. Significant relationships indicated that prescriptions, laboratory studies, imaging studies and referrals, were all more likely to be ordered in the FHC than the PTC (p < 0.01). The PTC ordered one diagnostic imaging study for every 37 encounters compared to one in every 5 encounters in the FHC. The PTC similarly referred one patient to another healthcare provider for every 52 encounters, fewer than the one per every 3 encounters in the FHC. There was a significant relationship between encounters and diagnoses, indicating a higher number of diagnoses per encounter in the FHC, though the difference of 0.31 diagnoses per encounter may not be clinically meaningful (p < 0.01). A total of 1,818 thrust manipulations and 2,910 dry needling procedures were completed without any reported safety events. These results suggest advanced practice PT has a similar safety profile to primary care. The authority to order musculoskeletal imaging and refer to other clinicians were among the most commonly utilized privileges and may be of primary importance when establishing an advanced practice PT clinic. These results support research showing advanced practice PT may lead to reductions in specialty referrals, diagnostic imaging, and pharmaceutical interventions.

Safety of guselkumab in patients with psoriasis treated through 100 weeks

Psoriasis is a long‐term skin condition that causes extra skin cells to form scaly red plaques that can be itchy and painful. Guselkumab is a biologic drug that blocks a molecule linked to psoriasis, interleukin‐23, and is approved for the treatment of psoriasis. Two large clinical trials (called VOYAGE 1 and VOYAGE 2) showed that guselkumab was more effective than adalimumab (another biologic treatment for psoriasis) and was safe to use for a year. Because psoriasis is a disease which reoccurs, understanding the safety of newer treatments over long periods of time is important. Therefore, VOYAGE 1 and VOYAGE 2 were extended to five years. The study designs were the same, with three treatment groups, guselkumab, placebo followed by guselkumab, or adalimumab, for the first six months. Then, depending on the study, patients were switched from one treatment to the other at different times during the next year and/or remained on the same treatment through two years. Rates of safety events, including common adverse events (unwanted side effects), serious adverse events, serious infections, malignancies (cancers), and major adverse cardiovascular events were calculated across studies to assess the safety of each treatment. Because of the complicated study design, data were compared in different ways: (1) one year versus two years of guselkumab treatment, and (2) before versus after transition from adalimumab to guselkumab. Results showed that cumulative safety event rates after two years of guselkumab treatment were generally consistent with those after one year. No safety concerns were found for adalimumab‐treated patients after they switched to guselkumab. In summary, guselkumab is safe for both longer‐term treatment for up to two years and after transition from adalimumab in patients with psoriasis.

Continued Versus Interrupted Oral Anticoagulation During Transfemoral Transcatheter Aortic Valve Implantation and Impact of Postoperative Anticoagulant Management on Outcome in Patients With Atrial Fibrillation

The role of continued versus interrupted oral anticoagulation (OAC) in patients with atrial fibrillation (AF) who underwent transfemoral transcatheter aortic valve implantation (TF-TAVI) for severe aortic stenosis is uncertain. The aim of this retrospective investigation was to evaluate the impact (1) of continued versus interrupted OAC on early safety and (2) of postoperative anticoagulant management on the 1-year mortality in patients with AF who underwent TF-TAVI. Consecutive patients with AF and on OAC at admission (n = 598) were stratified according to interrupted (iVKA) versus continued vitamin K antagonist (cVKA) versus continued direct oral anticoagulants (DOAC) at the time of TF-TAVI. Valve Academic Research Consortium-2 early safety was the primary outcome measure. Patients with iVKA (n = 299), cVKA (n = 117), and DOAC (n = 182) had comparable baseline characteristics including age (p = 0.25), gender (p = 0.33), and STS-Score (p = 0.072). The proportion of patients having a CHA2DS2-VASc-Score ≥3 (p = 0.791) and HAS-BLED-Score ≥3 (p = 0.185) was not different between groups. The rate of early safety events (with lower values indicating superior safety) was lowest in DOAC (13.2%) and not increased in cVKA (19.7%) compared to iVKA (23.1%) (p = 0.029). Valve Academic Research Consortium-2 defined stroke (p = 0.527) and bleeding (p = 0.097) did not differ between groups. Renal failure occurred more often in iVKA compared to cVKA and DOAC (p = 0.02). All-cause 1-year mortality was 20.1% in iVKA, 13.7% in cVKA, and 8.8% in DOAC (p = 0.015). Multivariate analysis revealed DOAC to be associated with reduced all-cause 1-year mortality (HR 0.56 (95%-CI 0.32 to 0.99), p = 0.047) whereas cVKA was comparable to iVKA (HR 0.75 (95%-CI 0.43 to 1.31), p = 0.307). In conclusion, cVKA did not increase the rate for the composite end point of early safety at 30 days in this cohort of patients. Treatment with a DOAC was associated with a significantly reduced rate of early safety end points at 30 days and lower 1-year mortality.

Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials.

SummaryBackgroundAlthough existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate‐to‐severe chronic plaque psoriasis.ObjectivesTo consider the benefits and risks of tofacitinib in patients with moderate‐to‐severe psoriasis.MethodsData were pooled from one phase II, four phase III and one long‐term extension study comprising 5204 patient‐years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of ‘clear’ or ‘almost clear’, ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure.ResultsTofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients’ quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID.ConclusionsTofacitinib has a benefit–risk profile in moderate‐to‐severe psoriasis consistent with that of other systemic treatments.

The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis

BackgroundLymphangioleiomyomatosis (LAM) is a rare lung disease and the mammalian target of the rapamycin (mTOR) inhibitors has been used as an effective therapy. Here we conducted a systematic review and meta-analysis with the aims to quantify the efficacy and safety of mTOR inhibitors in LAM patients.MethodsThe following databases were searched for clinical trials regarding LAM patients treated with mTOR inhibitors until December 2017: Pubmed, Embase, Cochrane Library and OVID medicine. Random effect models were used for the quantitative analysis.ResultsNine eligible studies were included in our systematic review, 7 of which were used for the meta-analysis. In LAM patients, mTOR inhibitors improved forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) significantly, with the weighted mean difference (WMD) 0.15 L (95%CI: 0.08 to 0.22, P < 0.01, I2 = 0%) and 0.22 L (95%: 0.11 to 0.32, P < 0.01, I2 = 0%) respectively. There was no significant change in neither the diffusing capacity for carbon monoxide (WMD: 0.51 ml/mm Hg/min, 95%CI: -0.48 to 1.49, P = 0.31, I2 = 0%) nor 6-min walking distance (WMD: 5.29 m, 95%CI: -18.01 to 28.59, P = 0.66, I2 = 1%). The weighted partial response rate was 0.68 (95%CI: 0.53 to 0.84, P < 0.01, I2 = 72%) for renal angiomylipoma. The cumulative incidence rates of common safety events were 50, 40, 23, 20 and 19% for oral mucositis, hyperlipidemia, headache, bone marrow suppression, and diarrhea, respectively. And most events were low grade and tolerant.ConclusionsIn LAM patients, there are improvements of FEV1 and FVC after the application of mTOR inhibitors and over a half achieved the shrinkage of renal angiomyolipoma.Trial registrationPROSPERO registration number: CRD42018085470. Registered 22 January 2018.

Quantifying the utilization of medical devices necessary to detect postmarket safety differences: A case study of implantable cardioverter defibrillators.

To estimate medical device utilization needed to detect safety differences among implantable cardioverter defibrillators (ICDs) generator models and compare these estimates to utilization in practice. We conducted repeated sample size estimates to calculate the medical device utilization needed, systematically varying device-specific safety event rate ratios and significance levels while maintaining 80% power, testing 3 average adverse event rates (3.9, 6.1, and 12.6 events per 100 person-years) estimated from the American College of Cardiology's 2006 to 2010 National Cardiovascular Data Registry of ICDs. We then compared with actual medical device utilization. At significance level 0.05 and 80% power, 34% or fewer ICD models accrued sufficient utilization in practice to detect safety differences for rate ratios <1.15 and an average event rate of 12.6 events per 100person-years. For average event rates of 3.9 and 12.6 events per 100 person-years, 30% and 50% of ICD models, respectively, accrued sufficient utilization for a rate ratio of 1.25, whereas 52% and 67% for a rate ratio of 1.50. Because actual ICD utilization was not uniformly distributed across ICD models, the proportion of individuals receiving any ICD that accrued sufficient utilization in practice was 0% to 21%, 32% to 70%, and 67% to 84% for rate ratios of 1.05, 1.15, and 1.25, respectively, for the range of 3 average adverse event rates. Small safety differences among ICD generator models are unlikely to be detected through routine surveillance given current ICD utilization in practice, but large safety differences can be detected for most patients at anticipated average adverse event rates.

Design and rationale of the non-interventional, edoxaban treatment in routiNe clinical prActice in patients with venous ThromboEmbolism in Europe (ETNA-VTE-Europe) study

BackgroundVenous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104–183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available.MethodsETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial.ConclusionsETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention.Trial registrationClinicalTrials.gov Identifier: NCT02943993.

Incidence of patient safety events and process-related human failures during intra-hospital transportation of patients: retrospective exploration from the institutional incident reporting system

BackgroundIntra-hospital transportation (IHT) might compromise patient safety because of different care settings and higher demand on the human operation. Reports regarding the incidence of IHT-related patient safety events and human...

Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

Background IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex.Methods and ResultsIn IMPROVE‐IT, patients with acute coronary syndrome and low‐density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in IMPROVE‐IT, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low‐density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79–0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90–1.01; P=0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71–0.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87–1.02; P=0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men.Conclusions IMPROVE‐IT demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid‐lowering therapy to optimize cardiovascular outcomes.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Brachytherapy patient safety events in an academic radiation medicine program

PurposeTo describe the incidence and type of brachytherapy patient safety events over 10 years in an academic brachytherapy program. Methods and MaterialsBrachytherapy patient safety events reported between January 2007 and August 2016 were retrieved from the incident reporting system and reclassified using the recently developed National System for Incident Reporting in Radiation Treatment taxonomy. A multi-incident analysis was conducted to identify common themes and key learning points. ResultsDuring the study period, 3095 patients received 4967 brachytherapy fractions. An additional 179 patients had MR-guided prostate biopsies without treatment as part of an interventional research program. A total of 94 brachytherapy- or biopsy-related safety events (incidents, near misses, or programmatic hazards) were identified, corresponding to a rate of 2.8% of brachytherapy patients, 1.7% of brachytherapy fractions, and 3.4% of patients undergoing MR-guided prostate biopsy. Fifty-one (54%) events were classified as actual incidents, 29 (31%) as near misses, and 14 (15%) as programmatic hazards. Two events were associated with moderate acute medical harm or dosimetric severity, and two were associated with high dosimetric severity. Multi-incident analysis identified five high-risk activities or clinical scenarios as follows: (1) uncommon, low-volume or newly implemented brachytherapy procedures, (2) real-time MR-guided brachytherapy or biopsy procedures, (3) use of in-house devices or software, (4) manual data entry, and (5) patient scheduling and handoffs. ConclusionsBrachytherapy is a safe treatment and associated with a low rate of patient safety events. Effective incident management is a key element of continuous quality improvement and patient safety in brachytherapy.

Real-Life Assessment of the Safety and Effectiveness of the New Tablet and Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal Infections via Analysis of 343 Courses.

Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. Delayed-release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis for patients with hematological malignancy. A retrospective cohort of all consecutive adult inpatients with hematological malignancy who received ≥3 days of tablet or intravenous posaconazole therapy for primary IFI prophylaxis at the M. D. Anderson Cancer Center between 1 December 2013 and 31 December 2015 was established. Clinical information was collected and correlated with low posaconazole serum levels (<700 ng/ml). Rates of IFIs and safety events were assessed. A total of 1,321 courses of posaconazole were administered at the M. D. Anderson Cancer Center during the study period, of which 343 courses were assessed for prophylactic safety and effectiveness. Seventy-nine patients (23%) had posaconazole serum level measurements available for interpretation. Acute myeloid leukemia was the primary malignancy (62%), with 20% of all patients having previously received a stem cell transplant. The median posaconazole level was 1,380 ng/ml (interquartile range, 864 to 1,860 ng/ml). Low posaconazole levels (<700 ng/ml) were observed for 14 patients (18%). Proven or probable breakthrough IFIs occurred in 8 patients (2%); posaconazole therapeutic drug monitoring (TDM) was performed for 6 of those patients, all with levels above 700 ng/ml. Overall, 19% of patients experienced grade 3 or 4 liver injury, manifesting primarily as hyperbilirubinemia and being correlated with serum levels of >1,830 ng/ml. Although hepatotoxicity in a small percentage of patients is of concern, posaconazole tablets appeared to be generally safe and effective. As all breakthrough IFIs for which TDM was performed occurred in patients with levels of >700 ng/ml, and a posaconazole level of >1,830 ng/ml was correlated with grade 3 or 4 liver toxicity, further studies are needed to assess the role of TDM.

Feasibility and Safety of a Powered Exoskeleton for Assisted Walking for Persons With Multiple Sclerosis: A Single-Group Preliminary Study

ObjectiveTo examine the feasibility, safety, and secondary benefit potential of exoskeleton-assisted walking with one device for persons with multiple sclerosis (MS). DesignSingle-group longitudinal preliminary study with 8-week baseline, 8-week intervention, and 4-week follow-up. SettingOutpatient MS clinic, tertiary care hospital. ParticipantsParticipants (N=13; age range, 38–62y) were mostly women with Expanded Disability Status Scale scores ranging from 5.5 to 7.0. InterventionExoskeleton-assisted walk training. Main Outcome MeasuresPrimary outcomes were accessibility (enrollment/screen pass), tolerability (completion/dropout), learnability (time to event for standing, walking, and sitting with little or no assistance), acceptability (satisfaction on the device subscale of the Quebec User Evaluation of Satisfaction with Assistive Technology version 2), and safety (event rates standardized to person-time exposure in the powered exoskeleton). Secondary outcomes were walking without the device (timed 25-foot walk test and 6-minute walk test distance), spasticity (Modified Ashworth Scale), and health-related quality of life (Patient-Reported Outcomes Measurement and Information System pain interference and Quality of Life in Neurological Conditions fatigue, sleep disturbance, depression, and positive affect and well-being). ResultsThe device was accessible to 11 and tolerated by 5 participants. Learnability was moderate, with 5 to 15 sessions required to walk with minimal assistance. Safety was good; the highest adverse event rate was for skin issues at 151 per 1000 hours' exposure. Acceptability ranged from not very satisfied to very satisfied. Participants who walked routinely improved qualitatively on sitting, standing, or walking posture. Two participants improved and 2 worsened on ≥1 quality of life domain. The pattern of spasticity scores may indicate potential benefit. ConclusionsThe device appeared feasible and safe for about a third of our sample, for whom routine exoskeleton-assisted walking may offer secondary benefits.

Improving safety in care homes: protocol for evaluation of the Walsall and Wolverhampton care home improvement programme

BackgroundImproving safety in care homes is becoming increasingly important. Care home residents typically have multiple physical and/or cognitive impairments, and adverse events like falls often lead to hospital attendance or admission. Developing a safety culture is associated with beneficial impacts on safety outcomes, but the complex needs of care home residents, coupled with staffing pressures in the sector, pose challenges for positive safety practices to become embedded at the individual and organisational levels. Staff training and education can positively enforce safety culture and reduce the incidence of harms, but improvement initiatives are often short lived and thorough evaluation is uncommon. This protocol outlines an evaluation of a large-scale care home improvement programme in the West Midlands.MethodsThe programme will run in 35 care homes across Walsall and Wolverhampton over 24 months, and we anticipate that 30 care homes will participate in the evaluation (n = 1500 staff). The programme will train staff and managers in service improvement techniques, with the aim of strengthening safety culture and reducing adverse safety event rates. The evaluation will use a pre-post design with mixed methods. Quantitative data will focus on: care home manager and staff surveys administered at several time points and analysis of adverse event rates. Data on hospital activity by residents at participating care homes will be compared to matched controls. Qualitative data on experience of training and the application of learning to practice will be collected via semi-structured interviews with staff (n = 48 to 64) and programme facilitators (n = 6), and staff focus groups (n = 36 to 48 staff). The primary outcome measure is the change in mean score on the safety climate domain of the Safety Attitudes Questionnaire between baseline and programme end.DiscussionThis mixed methods evaluation of a large-scale care home improvement programme will allow a substantial amount of qualitative and quantitative data to be collected. This will enable an assessment of the extent to which care home staff training can effectively improve safety culture, lower the incidence of adverse safety events such as falls and pressure ulcers, and potentially reduce care home resident’s use of acute services.

Baccalaureate nursing students’ confidence on patient safety

High rates of patient safety events led to media attention and litigation that sparked the patient safety movement. Gaining awareness of nursing students’ confidence levels on patient safety will reveal their perceptions of their competency. A quantitative descriptive cross-sectional method was employed. The Health Professional Education in Patient Safety Survey was used to determine how 458 baccalaureate nursing students from two nursing programs in Ontario, Canada rate their confidence levels on patient safety. Nursing students are the most confident on Clinical Safety topics and least confident on topics related to Human and Environmental Factors and Culture of Safety. Overall, they are more confident in the classroom than in the clinical settings with fourth year students expressing lower degrees of confidence on many of the areas. Education programs need to reinforce patient safety and educate students on their responsibilities to protect patients/clients. Programs need to target strategies to reduce student fears, promote error reporting, and system improvements.