GLA:D to Be Walking Better: Change in Self-Reported Difficulty Walking After Exercise Therapy and Education in Persons With Knee Osteoarthritis.

OBJECTIVE: Difficulty walking is a primary reason that individuals with knee osteoarthritis (OA) seek care. We examined the change in self-reported difficulty walking after participating in the Good Life With Osteoarthritis in Denmark (GLA:D) 8-week education and exercise program and assessed patient factors associated with improvement in difficulty walking. METHODS: This was a registry-based cohort study of individuals in Denmark with knee OA who enrolled in GLA:D. Assessments were administered at baseline, program completion (~3 months), and 12 months. Our prespecified primary outcome was change in self-reported difficulty walking assessed using the EuroQol 5-dimension 5-level walking item. Exposures included sociodemographic factors, measures of OA illness severity, comorbidities, and psychological factors. In those with baseline moderate/severe difficulty walking, using multivariable regression analysis, we assessed the relationship between exposures of interest and improvement to no/slight difficulty walking. RESULTS: We included 5262 participants. Of 2178 (41.4%) individuals with baseline moderate/severe difficulty walking, 51.4% and 58.3% reported no/slight difficulty walking at 3 and 12 months, respectively. Greater self-efficacy, younger age, female sex, lower BMI, less intense knee pain, and better function at baseline were associated with greater likelihood of improvement in difficulty walking, whereas severe difficulty walking at baseline and back pain intensity were associated with decreased likelihood of improvement. CONCLUSION: More than half of those with baseline difficulty walking experienced substantial improvement after completing GLA:D and this improvement was maintained at 12 months. Several patient factors were associated with the outcome, suggesting that some individuals may require additional support and extended treatment.

Intracluster correlation coefficients in osteoarthritis cluster randomized trials: A systematic review.

OBJECTIVES: The design, analysis, and interpretation of cluster randomized clinical trials (RCTs) require accounting for potential correlation of observations on individuals within the same cluster. Reporting of observed intracluster correlation coefficients (ICCs) in cluster RCTs, as recommended by Consolidated Standards of Reporting Trials (CONSORT), facilitates sample size calculation of future cluster RCTs and understanding of the trial statistical power. Our objective was to summarize observed ICCs in osteoarthritis (OA) cluster RCTs. DESIGN: Systematic review of knee/hip OA cluster RCTs. We searched Cochrane Central Register of Controlled Trials for trials published from 2012, when CONSORT cluster RCTs extension was published, to September 2022. We calculated the proportion of cluster RCTs that reported observed ICCs. Of those that did, we extracted observed ICCs. PROSPERO: CRD42022365660. RESULTS: We screened 1121 references and included 20 cluster RCTs. Only 5 trials (25%) reported the observed ICC for at least one outcome variable. ICC values for pain outcomes were: 0, 0.01, 0.18; for physical function outcomes were: 0, 0.06, 0.13 (knee)/0.27 (hip); Western Ontario and McMaster Universities Arthritis Index (WOMAC) total: 0.02, 0.02; symptoms of anxiety/depression: 0.22; disability: 0; and global change: 0. One out of four (25%) trials reported an ICC that was larger than the ICC used for sample size calculation and thus was underpowered. CONCLUSIONS: Despite CONSORT statement recommendations for reporting cluster RCTs, few OA trials reported the observed ICC. Given the importance of the ICC to interpretation of trial results and future trial design, this reporting gap warrants attention.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations.

Minimal clinically important difference for improvement in six-minute walk test in persons with knee osteoarthritis after total knee arthroplasty.

BACKGROUND: The interpretability of the six-minute walk test (6MWT) in individuals with knee osteoarthritis (OA) is unclear. We aimed to determine the minimal clinically important difference (MCID) for improvement in 6MWT in persons with knee OA at 12 months after total knee arthroplasty (TKA), and if it differed by baseline walking ability. METHODS: Participants with knee OA were assessed 1 month pre- and 12 months post-TKA, including completion of 6MWT. At 12 months, participant-perceived change in walking ability was assessed on an 8-point Likert scale ranging from "extremely worse" to "extremely better". Using logistic regression, ROC curves examined the ability of change in 6MWT distance to discriminate those who perceived walking was improved. MCID was selected overall and then by quartile of baseline 6MWT distance using the Youden method. RESULTS: Two hundred seventy-eight participants were included: mean age 67 years (SD 8.5), 65.5% female, mean pre-TKA 6MWT distance 323.1 (SD 104.7) m, and mean 12-mo 6MWT distance 396.0 (SD 111.9) m. The overall MCID was 74.3 m (AUC 0.65). Acceptable model discrimination (AUC > 0.70) was achieved for individuals in the lowest quartiles of baseline 6MWT distance: Quartile 1: MCID 88.63 m (AUC 0.73); Quartile 2: MCID 84.47 m (AUC 0.72). CONCLUSIONS: In persons with knee OA 12 months post-TKA, 6MWT MCID is dependent on baseline walking ability. Poor model discrimination for those in the highest (best) quartiles of baseline walking ability raise questions about 6MWT use across the full spectrum of walking ability. Further research is needed to better understand use of 6MWT as a performance-based measure of physical function for persons with knee OA.

Trends in oral contraceptive and intrauterine device use among reproductive-aged women in the US from 1999 to 2017.

PURPOSE: Since the 1960s, increasing oral contraceptive (OC) use has mirrored decreasing ovarian cancer incidence. The impact of intrauterine devices (IUDs) on cancer risk is less well established. With improved access and increased options, we must consider how changing usage can affect cancer risks. METHODS: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 1999-2016) and the National Survey for Family Growth (NSFG, 2006-2017) were used to evaluate contraceptive use over time in premenopausal women (NHANES n = 13,179; NSFG n = 26,262). Trends were assessed overall and by race, age, pregnancy history, education, and body mass index. RESULTS: The average annual absolute increase in self-reported IUD use was 0.81% (NSFG), while OC use decreased 0.49% in NSFG and 0.47% in NHANES. This represents a significant decrease in OC use in NSFG [annual percent change (APC) - 2.2% (95% CI - 3.4, - 1.0%), p < 0.01]. Trends in OC use varied somewhat by pregnancy history in NHANES (p-interaction = 0.054). In contrast, IUD use increased 6.2% annually [(1.4, 11.2%), p = 0.03] and varied significantly by pregnancy history (p-interaction < 0.01). Nulligravid women increased IUD use 11.0% annually [(2.6, 20.1%), p = 0.02] compared to women with prior pregnancy at 5.2% [(0.4, 10.2%), p = 0.04]. In 2015-2017, IUD use was 76.5% hormonal (71.1, 81.8%) and 22.9% copper (17.4, 28.3%) with greater hormonal IUD use in obese women [89.4%, (82.9, 95.9%)]. CONCLUSION: Increasing IUD use outpaced declining OC use in premenopausal US women. There may be a resulting decreased gynecologic cancer risk as more women gain access to potentially risk-reducing contraceptives.

Reporting and variability of constructing medication treatment episodes in pharmacoepidemiology studies: A methodologic systematic review using the case study of DPP-4 inhibitors and cardiovascular outcomes.

PURPOSE: In pharmacoepidemiologic studies, estimating medication adherence, persistence, and exposure patterns is critical. Constructing medication treatment episodes from prescription claims data involves assumptions related to grace period, carry-over, and lag effect, but there are no guidelines for these assumptions. We evaluated reporting and variability of these parameters in pharmacoepidemiology studies, using a case study of antihyperglycemic medications and major adverse cardiovascular events (MACE). METHODS: We conducted a systemic review using MEDLINE and EMBASE for studies published prior to January 2, 2020 comparing the risk of MACE between dipeptidyl peptidase 4 (DPP-4) inhibitors and active comparators. We extracted study characteristics and results, including grace period, carry-over, and lag effect. Risk of bias was assessed by the Newcastle-Ottawa scale, and assessments for prevalent user, immortal time, time lag, and time window biases. RESULTS: A total of 14/1850 studies identified were included. Grace period was not reported in 5 (35.7%) studies and ranged from 0 days to 180 days when reported. Carry-over was not reported in 10 studies (71.4%). Lag effect was not reported in nine (71.4%) studies and ranged from 0 days to 180 days when reported. No studies conducted sensitivity analyses examining the effects of these assumptions on study findings. Predominant biases were inadequate follow-up time, comparability of cohorts, prevalent use, and lag time bias. CONCLUSIONS: Use of grace period, carry-over, and lag effect were poorly reported and highly variable. Future pharmacoepidemiology studies should improve reporting, justify ranges for these parameters, and conduct sensitivity analyses to evaluate effects of these assumptions.

Spirituality and eating disorder risk factors in African American women.

PURPOSE: The increased prevalence of body dissatisfaction and eating disordered behaviors (EDBs) among African American women warrants further examination of critical factors that may contribute to this recent trend. This study sought to investigate whether ethnic identification, spirituality, and internalization of the thin ideal would be associated with decreased body dissatisfaction and EDBs. METHOD: A convenience sample of 55 African American college women was recruited from a college campus. The Eating Attitudes Test, Eating Disorders Inventory, Multigroup Ethnic Identity Measure, Sociocultural Attitudes toward Appearance Questionnaire, Life Regard Index-R, and Spiritual Transcendence Index were administered. RESULTS: Body dissatisfaction and internalization of the thin ideal were positively associated with EDBs. Higher scores on meaning in life were negatively associated with body dissatisfaction. Spiritual transcendence and internalization of the thin ideal were positively associated with body dissatisfaction. Spiritual transcendence was positively associated with meaning in life. CONCLUSIONS: These findings highlight the importance of exploring spirituality and ethnic identification in efforts to understand the relationships among the internalization of a thin ideal, body dissatisfaction, and EDBs in African American women. LEVEL OF EVIDENCE: Level V, Evidence obtained from a cross-sectional descriptive study.

The impact of hip and knee osteoarthritis on the subsequent risk of incident diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: This study examined the relationship between hip/knee osteoarthritis and incident diabetes. We hypothesised that hip/knee osteoarthritis would be independently related to an increased risk of incident diabetes and that this relationship would be due, at least in part, to walking difficulty. We also hypothesised a stronger relationship with incident diabetes for knee than hip osteoarthritis because of the higher prevalence in the former of obesity/the metabolic syndrome. METHODS: A population cohort aged ≥55 years recruited from 1996 to 1998 was followed through provincial health administrative data to 2014. Participants with baseline diabetes were excluded. Hip/knee osteoarthritis was defined as swelling, pain or stiffness in any joint lasting 6 weeks in the past 3 months and indication on a joint homunculus that a hip/knee was 'troublesome'. Walking limitation was defined as self-reported difficulty standing or walking in the last 3 months (yes/no). Using Cox regressions, we examined the relationship of baseline hip/knee osteoarthritis with incident diabetes as defined from health administrative data, controlling for age, sex, BMI, income, prior hypertension, cardiovascular disease and primary care exposure. We tested whether the observed effect was mediated through walking limitation. RESULTS: In total, 16,362 participants were included: median age 68 years and 61% female. Of these, 1637 (10%) individuals met the criteria for hip osteoarthritis, 2431 (15%) for knee osteoarthritis and 3908 (24%) for walking limitation. Over a median follow-up of 13.5 years (interquartile range 7.3-17.8), 3539 individuals (22%) developed diabetes. Controlling for confounders, a significant relationship was observed between number of hip/knee joints with osteoarthritis and incident diabetes: HR for two vs no osteoarthritic hips 1.25 (95% CI 1.08, 1.44); HR for two vs no osteoarthritic knees 1.16 (95% CI 1.04, 1.29). From 37% to 46% of this relationship was explained by baseline walking limitation. CONCLUSIONS/INTERPRETATION: In a large population cohort aged ≥55 years who were free of diabetes at baseline, and controlling for confounders, the presence and burden of hip/knee osteoarthritis was a significant independent predictor of incident diabetes. This association was partially explained by walking limitation. Increased attention to osteoarthritis and osteoarthritis-related functional limitations has the potential to reduce diabetes risk.

Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features.

Impairment of ubiquitin-proteasome system activity involving ubiquitin ligase genes UBE3A, UBE3B, and HUWE1 and deubiquitinating enzyme genes USP7 and USP9X has been reported in patients with neurodevelopmental delays. To date, only a handful of single-nucleotide variants (SNVs) and copy-number variants (CNVs) involving TRIP12, encoding a member of the HECT domain E3 ubiquitin ligases family on chromosome 2q36.3 have been reported. Using chromosomal microarray analysis and whole-exome sequencing (WES), we have identified, respectively, five deletion CNVs and four inactivating SNVs (two frameshifts, one missense, and one splicing) in TRIP12. Seven of these variants were found to be de novo; parental studies could not be completed in two families. Quantitative PCR analyses of the splicing mutation showed a dramatically decreased level of TRIP12 mRNA in the proband compared to the family controls, indicating a loss-of-function mechanism. The shared clinical features include intellectual disability with or without autistic spectrum disorders, speech delay, and facial dysmorphism. Our findings demonstrate that E3 ubiquitin ligase TRIP12 plays an important role in nervous system development and function. The nine presented pathogenic variants further document that TRIP12 haploinsufficiency causes a childhood-onset neurodevelopmental disorder. Finally, our data enable expansion of the phenotypic spectrum of ubiquitin-proteasome dependent disorders.

Factor Eight Inhibitor Bypassing Agent (FEIBA) for Reversal of Target-Specific Oral Anticoagulants in Life-Threatening Intracranial Bleeding.

INTRODUCTION: As increasing number of patients present to emergency departments with life threatening hemorrhages, particularly intracranial hemorrhage on anticoagulation physicians must be cognizant of the limitations of the available reversal options. Based upon the available literature, our institution formulated a reversal algorithm for patients with life-threatening bleeding on factor Xa inhibitors by administering factor eight inhibitor bypassing agent (FEIBA) 20 units/kg. METHODS: A retrospective chart review was performed to include all patients who received FEIBA per institutional protocol. This case series excluded patients who received FEIBA for reversal of dabigatran. Pre and post FEIBA CT scans were compared for changes. Finally, patients were stratified by estimated mortality rates calculated based on pre-intervention characteristics via published risk models. RESULTS: Thirteen patients were initially included in this study yet two patients were excluded because they were on dabigatran. Fifty-five percent of patients demonstrated stable ICH on CT scan after FEIBA administration while thirty-six percent showed worsening scans. Two patients developed thrombotic events after FEIBA administration. DISCUSSION: FEIBA is a treatment option in patients on a TSOA with acute intracranial hemorrhage with evidence of at least partial pharmacologic reversal of their anticoagulation status. There does not appear to be any major risk of thromboembolic complications associated with FEIBA. Much larger study sizes will be necessary to establish statically significant clinical efficacy for FEIBA use in this patient population. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency medicine physicians are first-line caretakers for patients with life threatening intracranial hemorrhages whether spontaneous or traumatic. FEIBA is a potentially safe option to reverse TSOA in this patient population.

The association of sleep quality, delirium, and sedation status with daily participation in physical therapy in the ICU.

BACKGROUND: Poor sleep is common in the ICU setting and may represent a modifiable risk factor for patient participation in ICU-based physical therapy (PT) interventions. This study evaluates the association of perceived sleep quality, delirium, sedation, and other clinically important patient and ICU factors with participation in physical therapy (PT) interventions. METHOD: This was a secondary analysis of a prospective observational study of sleep in a single academic medical ICU (MICU). Perceived sleep quality was assessed using the Richards-Campbell Sleep Questionnaire (RCSQ) and delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU). Other covariates included demographics, pre-hospitalization ambulation status, ICU admission diagnosis, daily mechanical ventilation status, and daily administration of benzodiazepines and opioids via bolus and continuous infusion. Associations with participation in PT interventions were assessed among patients eligible for PT using a multinomial Markov model with robust variance estimates. RESULTS: Overall, 327 consecutive MICU patients completed ≥1 assessment of perceived sleep quality. After adjusting for all covariates, daily assessment of perceived sleep quality was not associated with transitioning to participate in PT the following day (relative risk ratio [RRR] 1.02, 95 % CI 0.96-1.07, p = 0.55). However, the following factors had significant negative associations with participating in subsequent PT interventions: delirium (RRR 0.58, 95 % CI 0.41-0.76, p <0.001), opioid boluses (RRR 0.68, 95 % CI 0.47-0.99, p = 0.04), and continuous sedation infusions (RRR 0.58, 95 % CI 0.40-0.85, p = 0.01). Additionally, in patients with delirium, benzodiazepine boluses further reduced participation in subsequent PT interventions (RRR 0.25, 95 % CI 0.13-0.50, p <0.001). CONCLUSIONS: Perceived sleep quality was not associated with participation in PT interventions the following day. However, continuous sedation infusions, opioid boluses, and delirium, particularly when occurring with administration of benzodiazepine boluses, were negatively associated with subsequent PT interventions and represent important modifiable factors for increasing participation in ICU-based PT interventions.

A Pilot Study of the Tongue Pull-Back Exercise for Improving Tongue-Base Retraction and Two Novel Methods to Add Resistance to the Tongue Pull-Back.

This pilot study investigated the tongue pull-back (TPB) exercise to improve tongue-base retraction as well as two methods to add resistance to the TPB. Surface electromyography (sEMG) to the submental triangle was used as an indication of tongue-base activity on 13 healthy adults during: (1) saliva swallow, (2) 15 mL water swallow, (3) effortful swallow, (4) unassisted TPB, (5) TPB with added resistance by holding the tongue with gauze (finger-resisted TPB), and (6) TPB with the tongue clipped to a spring-loaded tension resistance device (device-resisted TPB). Order of the exercises was randomized. The exercises fell into two groups-weak and intense. Weak exercises included saliva swallow, water swallow, and unassisted TPB (mean sEMG = 19.07 µV, p = .593). Intense exercises included effortful swallow, finger-resisted TPB, and device-resisted TPB (mean sEMG = 36.44 µV, p = .315). Each intense exercise resulted in significantly higher mean sEMG peak amplitude than each weak exercise (p < .05), with one exception; the effortful swallow was not significantly different than the unassisted TPB (p = .171). This study provides preliminary evidence that the unassisted TPB may not be any more helpful for improving tongue-base retraction than normal swallowing. Adding resistance to the TPB by holding the tongue with gauze may be an effective alternative. This study also demonstrates proof-of-concept for creating a device to attach to the tongue and provide tension resistance during the TPB exercise. Further research with a more sophisticated design is needed before such a device can be fully developed and implemented clinically.

Aneuploidy and Tetraploidy as Distinct Patterns During Melanomagenesis.

Melanoma is characterized by a high degree of chromosome instability (CIN), the loss or gain of entire chromosomes or pieces of chromosomes. Also, CIN is likely to drive the progression of benign melanocytic lesions to malignant tumors, although very little is known about the acquisition of the mechanisms that promote CIN along this progression. Here, we describe the development of a model system to study the progression of melanomagenesis starting with normal human melanocytes followed by inactivation of the p53 and pRb tumor suppressors by addition of the E6/E7 proteins. The cells were then transduced with a growth-promoting, constitutionally-active mutant NRAS. The addition of E6/E7 and E6/E7 NRAS was found to give a growth advantage to the cells compared to normal melanocytes and a statistically significant gain of aneuploidy; aneuploidy was 24.7% in primary melanocytes, 33.8% in E6/E7 melanocytes, and 70.5% in E6/E7 NRAS melanocytes. Further, we found an increase in tetraploid cells in the cell model which was statistically significant between primary melanocytes and E6/E7, NRAS melanocytes. We also observed an increase in aneuploid cells between three population doublings in primary melanocytes, whereas this increase was not seen in the E6/E7 melanocytes. Together, these data demonstrate that this model system utilizing stepwise addition of genetic mutations driving melanomagenesis is a useful tool to study CIN and could even be used to study the mechanisms responsible for these alterations in genetic makeup.

Delirium transitions in the medical ICU: exploring the role of sleep quality and other factors.

OBJECTIVES: Disrupted sleep is a common and potentially modifiable risk factor for delirium in the ICU. As part of a quality improvement project to promote sleep in the ICU, we examined the association of perceived sleep quality ratings and other patient and ICU risk factors with daily transition to delirium. DESIGN: Secondary analysis of prospective observational study. SETTING: Medical ICU over a 201-day period. PATIENTS: Two hundred twenty-three patients with greater than or equal to one night in the medical ICU in between two consecutive days of delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily perceived sleep quality ratings were measured using the Richards-Campbell Sleep Questionnaire. Delirium was measured twice daily using the Confusion Assessment Method for the ICU. Other covariates evaluated included age, sex, race, ICU admission diagnosis, nighttime mechanical ventilation status, prior day's delirium status, and daily sedation using benzodiazepines and opioids, via both bolus and continuous infusion. Perceived sleep quality was similar in patients who were ever versus never delirious in the ICU (median [interquartile range] ratings, 58 [35-76] vs 57 [33-78], respectively; p = 0.71), and perceived sleep quality was unrelated to delirium transition (adjusted odds ratio, 1.00; 95% CI, 0.99-1.00). In mechanically ventilated patients, receipt of a continuous benzodiazepine and/or opioid infusion was associated with delirium transition (adjusted odds ratio, 4.02; 95% CI, 2.19-7.38; p < 0.001), and patients reporting use of pharmacological sleep aids at home were less likely to transition to delirium (adjusted odds ratio, 0.40; 95% CI, 0.20-0.80; p = 0.01). CONCLUSIONS: We found no association between daily perceived sleep quality ratings and transition to delirium. Infusion of benzodiazepine and/or opioid medications was strongly associated with transition to delirium in the ICU in mechanically ventilated patients and is an important, modifiable risk factor for delirium in critically ill patients.

A comparison of ED and direct admission care of cancer patients with febrile neutropenia.

OBJECTIVE: We compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. METHODS: We conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm(3)) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score-based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. RESULTS: One hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score-based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). CONCLUSION: The quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study.

Factors associated with ciprofloxacin-resistant Escherichia coli urinary tract infections in discharged ED patients.

BACKGROUND: We sought to identify factors associated with Escherichia coli resistance to ciprofloxacin among discharged emergency department (ED) patient visits treated for a urinary tract infection (UTI). We hypothesized that specific historical factors available upon ED presentation would be associated with increased odds of ciprofloxacin resistance in this population. METHODS: We conducted a retrospective, observational cohort study of consecutive discharged adult ED patient visits with a primary diagnosis of UTI caused by E coli to a single center from 2011 to 2014. Two investigators separately abstracted to a preconstructed data collection form the following independent variables on each included visit: patient age, sex, residence, active immunosuppressive condition or medication, chronic indwelling Foley catheter, hospitalization or antibiotic use within 90 days prior to presentation, and history of recurrent UTIs. We used multivariable logistic regression after taking into account colinearity to identify those independent variables associated with increased odds of ciprofloxacin resistance and report descriptive characteristics of the study cohort, odds ratios (ORs) with 95% confidence interval (CI) and model strength. RESULTS: Age at least 65 years (OR, 3.15; 95% CI, 1.44-6.87; P=.004), recurrent UTI (OR, 6.23; 95% CI, 2.38-16.30; P<.001), and recent hospitalization (OR, 3.99; 95% CI, 1.56-10.23; P=.004) were significantly associated with ciprofloxacin-resistant E coli UTIs in relevant visits. CONCLUSION: In this single-center study, age at least 65 years, recurrent UTI, and recent hospitalization were most clearly associated with increased odds of ciprofloxacin-resistant UTIs in discharged adult ED patient visits. If validated, these factors should suggest that alternative antimicrobial agents should be considered in the treatment of this condition among discharged adult ED patients.