High response rate with extended dosing of cemiplimab in advanced cutaneous squamous cell carcinoma.

BACKGROUND: Cemiplimab (Libtayo®), a human monoclonal immunoglobulin G4 antibody to the programmed cell death-1 receptor, is approved for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC), who are not candidates for curative surgery or curative radiation, using an every-3-weeks (Q3W) dosing interval. Pharmacokinetic modeling indicated that Ctrough of extended intravenous dosing of 600 mg every 4 weeks (Q4W) would be comparable to the approved intravenous dosage of 350 mg Q3W. We examined the efficacy, pharmacokinetics, and safety of cemiplimab dosed Q4W. METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review. RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n=14) achieving complete response and 40% (n=25) achieving partial response. The most common treatment-emergent adverse events were diarrhea, pruritus, and fatigue. CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen.

Impact of Mandatory Infectious Disease Specialist Approval on Hospital-Onset Clostridioides difficile Infection Rates and Testing Appropriateness.

BACKGROUND: Inappropriate Clostridioides difficile testing is common in the hospital setting, leading to potential overdiagnosis of infection when single-step nucleic acid amplification testing is used. The potential role of infectious diseases (ID) specialists in enforcing appropriate C. difficile testing is unclear. METHODS: At a single 697-bed academic hospital, we performed a retrospective study from 1 March 2012 to 31 December 2019 comparing hospital-onset C. difficile infection (HO-CDI) rates during 3 consecutive time periods: baseline 1 (37 months, no decision support), baseline 2 (32 months, computer decision support), and intervention period (25 months, mandatory ID specialist approval for all C. difficile testing on hospital day 4 or later). We used a discontinuous growth model to assess the impact of the intervention on HO-CDI rates. RESULTS: During the study period, we evaluated C. difficile infections across 331 180 admission and 1 172 015 patient-days. During the intervention period, a median of 1 HO-CDI test approval request per day (range, 0-6 alerts/day) was observed; adherence by providers with obtaining approval was 85%. The HO-CDI rate was 10.2, 10.4, and 4.3 events per 10 000 patient-days for each consecutive time period, respectively. In adjusted analysis, the HO-CDI rate did not differ significantly between the 2 baseline periods (P = .14) but did differ between the baseline 2 period and intervention period (P < .001). CONCLUSIONS: An ID-led C. difficile testing approval process was feasible and was associated with a >50% decrease in HO-CDI rates, due to enforcement of appropriate testing.

Random variation drives a critical bias in the comparison of healthcare-associated infections.

OBJECTIVE: To evaluate random effects of volume (patient days or device days) on healthcare-associated infections (HAIs) and the standardized infection ratio (SIR) used to compare hospitals. DESIGN: A longitudinal comparison between publicly reported quarterly data (2014-2020) and volume-based random sampling using 4 HAI types: central-line-associated bloodstream infections, catheter-associated urinary tract infections, Clostridioides difficile infections, methicillin-resistant Staphylococcus aureus infections. METHODS: Using 4,268 hospitals with reported SIRs, we examined relationships of SIRs to volume and compared distributions of SIRs and numbers of reported HAIs to the outcomes of simulated random sampling. We included random expectations into SIR calculations to produce a standardized infection score (SIS). RESULTS: Among hospitals with volumes less than the median, 20%-33% had SIRs of 0, compared to 0.3%-5% for hospitals with volumes higher than the median. Distributions of SIRs were 86%-92% similar to those based on random sampling. Random expectations explained 54%-84% of variation in numbers of HAIs. The use of SIRs led hundreds of hospitals with more infections than either expected at random or predicted by risk-adjusted models to rank better than other hospitals. The SIS mitigated this effect and allowed hospitals of disparate volumes to achieve better scores while decreasing the number of hospitals tied for the best score. CONCLUSIONS: SIRs and numbers of HAIs are strongly influenced by random effects of volume. Mitigating these effects drastically alters rankings for HAI types and may further alter penalty assignments in programs that aim to reduce HAIs and improve quality of care.

Cross-sectional analysis of avoidable emergency department visits before and during the COVID-19 pandemic.

BACKGROUND: COVID-19 had a significant impact on Emergency Departments (ED) with early data suggesting an initial decline in avoidable ED visits. However, the sustained impact over time is unclear. In this study, we analyzed ED discharges over a two-year time period after the COVID-19 pandemic began and compared it with a control time period pre-pandemic to evaluate the difference in ED visit categories, including total, avoidable, and unavoidable visits. METHODS: This was a retrospective, cross-sectional study assessing the distribution of visits with ED discharges from two hospitals within a health system over a three-year time period (1/1/2019-12/31/2021). Visits were categorized using the expanded NYU-EDA algorithm modified to include COVID-19-related visits. Categories included: Emergent - Not Preventable/Avoidable, Emergent - Preventable/Avoidable, Emergent - Primary Care Treatable, Non-Emergent, Mental Health, Alcohol, Substance Abuse, Injury, and COVID-19. Chi-square testing was conducted to investigate differences within the time period before COVID-19 (1/1/2019-12/31/2019) and both initial (1/1/2020-12/31/2020) and delayed (1/1/2021-12/31/2021) COVID-19 time frames and ED visit categories, as well as post hoc testing using Fisher's exact tests with Bonferroni correction. ANOVA with post hoc Bonferroni testing was used to determine differences based on daily census for each ED visit category. RESULTS: A total of 228,010 ED discharges (Hospital #1 = 126,858; Hospital #2 = 101,152) met our inclusion criteria over the three-year period. There was a significant difference in the distribution of NYU-EDA categories between the two time periods (pre-COVID-19 versus during COVID-19) for the combined hospitals (p < 0.001), Hospital #1 (p < 0.001), and Hospital #2 (p < 0.001). When examining daily ED discharges, there was a decline in all categories from 2019 to 2020 except for "Emergent - Not Preventable/Avoidable" which remained stable and "Substance Abuse" which increased. From 2020 to 2021, there were no differences in ED avoidable visits. However, there were increases in discharged visits related to "Injuries", "Alcohol", and "Mental health" and a decrease in "COVID-19". CONCLUSION: Our study identified a sustained decline in discharged avoidable ED visits during the two years following the beginning of the COVID-19 pandemic, which was partially offset by the increase in COVID-19 visits. This work can help inform ED and healthcare systems in resource allocation, hospital staffing, and financial planning during future COVID-19 resurgences and pandemics.

Effects of a prescribed, supervised exercise programme on tumour disease progression in oncology patients undergoing anti-cancer therapy: a retrospective observational cohort study.

BACKGROUND: Exercise promotes numerous advantages in both health and disease, and is increasingly being acknowledged to improve overall survival in cancer patients. Preclinical studies indicate a direct effect on tumour behaviour, but human data on the effect of exercise on tumour progression are lacking. AIMS: To capture preliminary clinical data regarding the impact of a prescribed, supervised exercise programme on cancer disease progression. METHODS: Retrospective cohort study of 137 matched pairs of patients. All patients referred to LIFT Cancer Care Services (LIFT) supervised exercise programme between 2018 and 2019 were matched with non-LIFT patients from the oncology practice database. Disease progression via staging computed tomography scans ± tumour markers was compared for each match. Secondary outcomes were changes in neutrophil-to-lymphocyte ratio (NLR) and death. Results were analysed by logistical regression and adjusted for potential confounders. RESULTS: Patients from the LIFT group had a 66% (OR = 0.34, 95% CI 0.19 to 0.61) decreased odds of disease progression and 76% (OR = 0.24, 95% CI 0.12-0.47) decreased odds of death compared with the non-LIFT group. No effect on the number of LIFT sessions on disease progression was demonstrated. The LIFT group had a mean final NLR reading 3.48 (-5.89 to -1.09) lower than the non-LIFT group. CONCLUSION: Supervised exercise programmes have the potential to significantly improve outcomes in cancer patients due to an effect on tumour progression.

Variation in the Reporting of Elective Surgeries and Its Influence on Patient Safety Indicators.

BACKGROUND: US hospital safety is routinely measured via Patient Safety Indicators (PSIs). Receiving a score for most PSIs requires a minimum number of qualifying cases to meet specific criteria; for example, whether an admission was elective. Because admission type is determined by hospitals' internal policies, the study team suspected that hospitals may be exempted from elective-based PSI scores as a result of their internal admission classification policies. METHODS: Multiple regression was combined with machine learning to analyze Medicare inpatient claims data reported by 3,484 hospitals during the 2015-2017 PSI measurement period. The researchers examined the average percentage of elective admissions across surgical diagnosis-related groups (DRGs) (average percent elective [APE]) in relation to hospital characteristics, surgical claims volumes, and numbers and types of surgical DRGs. This study asked whether hospitals with exceptionally low APE shared particular characteristics, reported claims for similar DRGs, or were disproportionately exempted from elective-based PSIs. RESULTS: Cross-validated multiple regression explained 73.9% of variation in APE among hospitals and identified surgical claims volume and 16 surgical DRGs as consistently important variables. However, the exceptionally low APE of 96 hospitals could not be explained by surgical claims volume, surgical DRGs among claims, or hospital characteristics. These outliers were disproportionately exempt from elective-based PSI scores. CONCLUSION: Some hospitals may have classified admissions in a way that exempted them from elective-based PSI scores. Transparency into admission classification policies is needed to ensure fair and reliable use of PSIs when ranking hospitals and adjusting payments. Alternatively, PSIs may need modifications to rely on externally validated criteria.

Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel.

Importance: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. Objective: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. Design, Setting, and Participants: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. Exposures: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. Main Outcome and Measures: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. Results: Among 24 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). Conclusions and Relevance: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.

Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing.

BACKGROUND: Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498). METHODS: The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability. RESULTS: For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%). CONCLUSION: In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498.

Dose modification for haematological toxicity: a survey of Australian medical oncologists.

BACKGROUND: Evidence supporting dose modifications to reduce serious treatment-related adverse events of antineoplastic therapy is limited and frequently based on clinical trial protocols, which are not always generalisable to community patients. eviQ is an online resource with treatment protocols and recommendations for dose modification formulated by expert opinion and evidence-based review. Original recommended haematological thresholds to delay treatment were: neutrophil count <1.5 × 109 /L and platelet count <100 × 109 /L. AIMS: To evaluate the current practices of Australian medical oncologists with regard to haematological dose modifications for antineoplastic treatments, and to determine rates of adherence to eviQ recommendations. METHODS: An online survey regarding haematological dose modifications was distributed to over 400 Medical Oncology Group of Australia members and eviQ medical oncology reference committee members via email. Responses were collated on 18 December 2017. RESULTS: Of 153 respondents, 67% indicated that they did not follow the eviQ haematological dose modification guidelines; 8% delayed curative intent treatment at neutrophil counts <1.5 × 109 /L, compared with 36% for palliative treatment; most delayed treatment at neutrophil counts <1.0 × 109 /L (94% curative and 97% palliative respectively). 70% of clinicians delayed palliative treatment at platelet counts <100 × 109 /L, compared to 34% with curative treatment. No respondents indicated the original haematological cut-off levels were too aggressive. CONCLUSION: The majority of responding medical oncologists indicated that they did not follow the eviQ haematological dose modification guidelines, which were viewed as too conservative. Subsequent to this survey, eviQ reviewed and updated haematological dose modification recommendations.

Immunotherapy and other systemic therapies for cutaneous SCC.

Contrary to the impression that non-melanoma skin cancer is a banal and relatively trivial malignancy it causes about 1% of all cancer deaths. Cutaneous Squamous Cell carcinoma (CuSCC) make up a significant part of these deaths either from incurable loco-regional disease or metastatic disease. As is typical of the disease itself, these patients are often of advanced age, but the immunocompromised from organ transplantation or haematological malignancy are important populations. Systemic therapies have a long history in palliative therapy for CuSCC, but not a particularly extensively studied one. Cytotoxic chemotherapy is active with response rates derived from multiple small studies of 17-85%; as is often the case in solid tumour oncology responses are rarely durable. The Epidermal Growth Factor Receptor has been targeted with both small molecular inhibitors and monoclonal antibodies. Disease control rates of the order of 50-70% were seen but again durability remains an issue. Immunotherapy using interferon with retinoids also showed significant response rates in very small trials. The high rates of mutation seen in CuSCC and relationship with immunosuppression suggested that checkpoint inhibitors might be active. Checkpoint inhibition immunotherapy with PD-1 antibodies like cemiplimab have demonstrated response rates of the order of 40% and durability is encouraging: response duration was over a year in 75% of responders in the initial trial. We review the latest data with current immunotherapy drugs and consider the future directions such therapy may take us as well as the role of these therapies in special populations.

Medical Oncology Group of Australia position statement and membership survey on voluntary assisted dying.

The controversial topic of voluntary assisted dying (VAD) is receiving significant attention at state government levels and in the community. Acknowledging potential legalisation of VAD, the Medical Oncology Group of Australia (MOGA) undertook a survey of members to inform the development of a position statement on the subject. All MOGA members were invited to complete an anonymous online survey. The survey comprised 12 closed-response categorical questions. Descriptive statistics were used to summarise the survey data. Majority views expressed in the survey would form the basis of a MOGA position statement on VAD. A total of 362 members completed the questionnaire, representing 55% of the membership; 47% of respondents disagreed with VAD; 36% agreed with VAD and the remaining members (17%) were 'neutral'. A clear majority position was not established. Only 14% agreed that physicians involved in VAD should be required personally to administer the lethal medication; 94% supported conscientious objection of physicians to the VAD process; 95% agreed that a palliative care physician consultation should be required and 86% agreed with the need for the involvement of specialist psychiatry medical services before a patient can be deemed as suitable for VAD. The MOGA membership expressed a range of views on the topic of VAD. A clear majority-held view to support a MOGA position that either supports or opposes VAD was not established. The position statement that flows from the survey encourages informed debate on this topic and brings into focus important considerations.

The characteristics and impact of source of infection on sepsis-related ICU outcomes.

BACKGROUND: Source of infection is an independent predictor of sepsis-related mortality. To date, studies have failed to evaluate differences in septic patients based on the source of infection. METHODS: Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12month time period. RESULTS: Sepsis due to intravascular device and multiple sources had the highest number of positive blood cultures and microbiology whereas lung and abdominal sepsis had the least. The observed hospital mortality was highest for sepsis due to multiple sources and unknown cause, and was lowest when due to abdominal, genitourinary (GU) or skin/soft tissue. Patients with sepsis due to lungs, unknown and multiple sources had the highest rates of multi-organ failure, whereas those with sepsis due to GU and skin/soft tissue had the lowest rates. Those with multisource sepsis had a significantly higher median ICU length of stay and hospital cost. CONCLUSION: There are significant differences in patient characteristics, microbiology positivity, organs affected, mortality, length of stay and cost based on the source of sepsis. These differences should be considered in future studies to be able to deliver personalized care.

Prevention of Tracheostomy-Related Hospital-Acquired Pressure Ulcers.

Objective To determine if standardization of perioperative tracheostomy care procedures decreased the incidence of hospital-acquired tracheostomy-related pressure ulcers. Methods All patients at least 18 years old who underwent placement of a tracheostomy tube in the operating room from July 1, 2014, through June 30, 2015, were cared for postoperatively through an institutionally adopted quality improvement protocol. This included 4 elements: (1) placement of a hydrocolloid dressing underneath the tracheostomy flange in the postoperative period, (2) removal of plate sutures within 7 days of the tracheostomy procedure, (3) placement of a polyurethane foam dressing after suture removal, and (4) neutral positioning of the head. One year after the bundle was initiated, a retrospective analysis was performed to compare the percentage of tracheostomy patients who developed pressure ulcers versus the preintervention period. Results The incidence of tracheostomy-related pressure ulcers decreased from 20 of 183 tracheostomies (10.93%) prior to use of the standardized protocol to 2 of 155 tracheostomies (1.29%). Chi-square analysis showed a significant difference between the groups, with a P value of .0003. Discussion Adoption of this care bundle at our institution resulted in a significant reduction in the incidence of hospital-acquired tracheostomy-related pressure ulcers. The impact of any single intervention within our protocol was not assessed and could be an area of further investigation. Implications for Practice Adoption of a standardized posttracheostomy care bundle at the institution level may result in the improved care of patients with tracheostomies and specifically may reduce the incidence of pressure ulcers.

Impact of End-Stage Renal Disease and Acute Kidney Injury on ICU Outcomes in Patients With Sepsis.

PURPOSE: To report the characteristics and outcomes of patients with sepsis in the intensive care unit (ICU) with end-stage renal disease (ESRD) and acute kidney injury (AKI) compared to patients with nonkidney injury (non-KI). METHODS: Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12-month time period. Data were obtained from the University Health Consortium database and a chart review of the electronic medical records. RESULTS: We identified 39 cases of ESRD, 106 cases of AKI, and 103 cases of non-KI. Intensive care unit mortality was 15.4% for ESRD, 30.2% for AKI, and 13.6% for non-KI ( P < .01). Hospital mortality was 20.5% for ESRD, 32.1% for AKI, and 13.6% for non-KI ( P < .01). Early AKI and late AKI had an ICU mortality of 24.4% versus 50% ( P <.01), hospital mortality of 26.8% versus 50% ( P = .03), ICU length of stay (LOS) of 3 and 6 days ( P = .04), and hospital LOS of 7 and 12.5 days ( P <.01), respectively. CONCLUSION: Patients with sepsis having AKI have a higher mortality rate than those with ESRD and non-KI. Hospital and ICU mortality rates for patients with ESRD were similar to non-KI patients. Late AKI compared to early AKI had a higher mortality and longer LOS.

Evaluating the Effectiveness of Written Dry Powder Inhaler Instructions and Health Literacy in Subjects Diagnosed With COPD.

BACKGROUND: Improper inhaler use results in decreased drug deposition in the lungs. The impact of health literacy and poor vision on the patient's ability to learn inhaler technique by reading instructions has not been confirmed. This study evaluated the effectiveness of learning inhaler technique from written instructions and the impact of health literacy for patients diagnosed with COPD who used a dry powder inhaler (DPI). METHODS: This pilot study recruited subjects diagnosed with COPD. A trained assessor scored subjects' inhaler technique before and after reading the appropriate American College of Chest Physicians handouts. Peak inspiratory flows (PIFs) were measured using an InCheck Dial. Health literacy was measured by the S-TOFHLA (Short Test of Functional Health Literacy in Adults), and visual acuity was measured by a Snellen chart. Associations between health literacy and visual acuity and changes in subjects' inhaler technique scores were assessed by Spearman's rho. Inhaler technique change scores were assessed by the Wilcoxon signed-rank test at P = .05. RESULTS: Of the 24 participants enrolled, 63% were female, mean age was 65.6 y, and 83% were Global Initiative for Chronic Obstructive Lung Disease air-flow limitation 2 or 3. Wilcoxon scores were significant for improved total scores for both the Diskus and HandiHaler, with medians improving from 6.5 to 7.0 (interquartile range 6.0-7.8) (P = .047) and from 6.0 to 7.5 (interquartile range 7.0-9.0) (P = .002), respectively. The minimum required PIF was achieved by 93.8% of the Diskus and 94.4% of the HandiHaler groups. There were no associations detected between the handout intervention (Diskus and HandiHaler) and health literacy level and vision. CONCLUSIONS: The educational handouts for DPIs helped participants already using a DPI to improve their inhaler technique. Stable participants diagnosed with COPD are able to generate appropriate PIFs to properly use DPIs. Neither vision nor health literacy was associated with the inability to learn inhaler technique from patient education inhaler device handouts.

Consumer Rankings and Health Care: Toward Validation and Transparency.

BACKGROUND: Differences between the Centers for Medicare & Medicaid Services (CMS)-measured rates of safety events for Rush University Medical Center (RUMC; Chicago) and the U. S. News & World Report (USNWR)-deter mined patient safety score were evaluated in an attempt to validate the USNWR patient safety score-based ranking. METHODS: The USNWR findings for Patient Safety Indicators (PSIs) were compared with findings derived from RUMC internal billing data, and sensitivity analyses were conducted using a simulated data set derived from the Healthcare Cost and Utilization Project (HCUP) state inpatient data sets. RESULTS: Discrepancies were found for PSIs 3 (Pressure Ulcer Rate), 9 (Perioperative Hemorrhage or Hematoma Rate), and 11 (Postoperative Respiratory Failure Rate)-an excess of 0.72, 0.63, and 0.26 cases/1,000 admissions, in USNWR versus RUMC, respectively). The sensitivity analysis, which included missing present on admission (POA) flags and dates, resulted in an increase of rates by 1.83 (95% confidence interval [CI] = 1.10-2.56) cases/1,000 hospital- izations, 2.72 (CI = 0.00-5.90) cases/1,000 hospitalizations, and 3.89 (CI = 1.60-6.20) cases/1,000 hospitalizations for PSI 3, 9, and 11, respectively. Regression modeling showed that each 1% increase in transfers was associated with an in- crease of 0.06 cases of PSI 3/1,000 admissions; each 1,000 increase in admissions was associated with an increase of 0.04 cases of PSI 9/1,000 admissions. CONCLUSION: The USNWR data set produced inaccurate PSI rates for RUMC, and false-positive event rates were more common among high-transfer and high-volume hos- pitals. More transparency and validation is needed for con- sumer-based benchmarking methods. In response to these findings and concerns raised by others, in 2016 USNWR made changes to its methodology and data sources and reported them in announcing its 2016-17 Best Hospitals.

Postoperative Bleeding Following Dental Extractions in Patients Anticoagulated With Warfarin.

PURPOSE: The practicing dentist must frequently advise on the risks involved with dental extractions in the patient taking an anticoagulant. This study assessed the risk of bleeding in a large heterogeneous cohort of patients on warfarin treated by practitioners in training (dental students and junior staff in a teaching hospital). MATERIALS AND METHODS: This was a retrospective case-and-control study of 439 patients on warfarin (1,022 extractions) and 439 matched controls (1,049 extractions). Patients with an international normalized ratio (INR) lower than 2.2 had no specific measures, those with an INR 2.2 to 4 received suturing and tranexamic acid mouthwash, and those with an INR higher than 4 did not undergo extraction. Bayesian methods were used to estimate posterior probabilities of bleeding. RESULTS: Of cases, 63% were men, 25% were older than 80 years, 40% had an INR lower than 2.2, and 9% had an INR higher than 3. Nine cases bled 0 to 10 days postoperatively, with 1 requiring admission and transfusion. Significant predictors of bleeding were INR and number of extractions (P < .001 for the 2 comparisons). There were no events of bleeding in controls or cases with an INR lower than 2.2 (95% credible interval [CrI] for difference, -0.7 to 1.6). The posterior mean of bleeding was 1% (CrI, 0.1-2.6) for an INR lower than 2.2, 2.3% (CrI, 0.9-4.5) for an INR of 2.2 to 3, and 8.4% (CrI, 3.5-15) for an INR higher than 3. CONCLUSION: Unselected patients taking an anticoagulant with an INR lower than 2.2 had a similar risk of bleeding as control patients. The risk was approximately 1 in 40 in those with an INR of 2.2 to 3, whereas the risk in patients with an INR higher than 3 was approximately 1 in 11.

A C-terminal crosslinking telopeptide test-based protocol for patients on oral bisphosphonates requiring extraction: a prospective single-center controlled study.

PURPOSE: Patients undergoing extraction are at risk for bisphosphonate-related osteonecrosis of the jaws (BRONJ). A C-terminal crosslinking telopeptide (CTX) level lower than 150 pg/mL has been suggested as a predictor of BRONJ risk. The authors aimed to increase the precision of estimates of the risk of BRONJ in osteoporosis after extraction and to assess value of CTX testing at extraction time in cases of BRONJ in a large prospective cohort. PATIENTS AND METHODS: All patients on oral bisphosphonates for osteoporosis referred for extractions over a period of 6.5 years were included in a standard protocol. Pre-extraction fasted CTX levels were obtained. All patients were followed until healing. If the CTX level was lower than 150 pg/mL, they were offered a drug holiday. If they declined, if the CTX level was above 150 pg/mL at baseline, or after the drug holiday, they had extractions performed under local anesthesia. Age-matched controls not on bisphosphonates were identified. RESULTS: Nine hundred fifty patients had 2,461 extractions. One hundred eighty-one patients had a CTX level lower than 150 pg/mL. Four patients developed BRONJ; all had a CTX level lower than 150 pg/mL. All were on alendronate. The case-control comparison approached significance (<150 pg/mL; P = .073). Alendronate was associated with a low CTX level (P < .05). A CTX level lower than 150 pg/mL had a sensitivity of 100% and specificity of 81%. Bayesian analysis yielded a population expected risk of BRONJ of 0.29% (95% confidence interval, 0.12-0.52); the expected risk was 0.42% for a CTX level lower than 150 pg/mL and 0.13% for a CTX level higher than 150 pg/mL. CONCLUSION: The risk of BRONJ for patients with osteoporosis on bisphosphonates having extractions is approximately 0.2%. A CTX level lower than 150 pg/mL is sensitive and is associated with an approximately 3-fold greater risk of BRONJ.