Effectiveness of tisagenlecleucel versus real-world standard of care in relapsed/refractory follicular lymphoma.

Aim: To contextualize the effectiveness of tisagenlecleucel versus real-world standard of care (SoC) in relapsed/refractory follicular lymphoma. Materials & methods: A retrospective indirect matched comparison study using data from the phase II ELARA trial and the US Flatiron Health Research Database. Results: Complete response rate was 69.1 versus 17.7% and the overall response rate was 85.6 versus 58.1% in tisagenlecleucel versus SoC, post weighting by odds. For overall survival, an estimated reduction in the risk of death was observed in favor of tisagenlecleucel over SoC. The hazard ratio for progression-free survival was 0.45 (95% CI: 0.26, 0.88), and for time-to-next treatment was 0.34 (95% CI: 0.15, 0.78) with tisagenlecleucel versus SoC. Conclusion: A consistent trend toward improved efficacy end points was observed in favor of tisagenlecleucel versus SoC.

Variation in Risk-standardized Rates and Causes of Unplanned Hospital Visits Within 7 Days of Hospital Outpatient Surgery.

OBJECTIVES: The objectives of this study were to compare risk-standardized hospital visit ratios of the predicted to expected number of unplanned hospital visits within 7 days of same-day surgeries performed at US hospital outpatient departments (HOPDs) and to describe the causes of hospital visits. SUMMARY OF BACKGROUND DATA: More than half of procedures in the US are performed in outpatient settings, yet little is known about facility-level variation in short-term safety outcomes. METHODS: The study cohort included 1,135,441 outpatient surgeries performed at 4058 hospitals between October 1, 2015 and September 30, 2016 among Medicare Fee-for-Service beneficiaries aged ≥65 years. Hospital-level, risk-standardized measure scores of unplanned hospital visits (emergency department visits, observation stays, and unplanned inpatient admissions) within 7 days of hospital outpatient surgery were calculated using hierarchical logistic regression modeling that adjusted for age, clinical comorbidities, and surgical procedural complexity. RESULTS: Overall, 7.8% of hospital outpatient surgeries were followed by an unplanned hospital visit within 7 days. Many of the leading reasons for unplanned visits were for potentially preventable conditions, such as urinary retention, infection, and pain. We found considerable variation in the risk-standardized ratio score across hospitals. The 203 best-performing HOPDs, at or below the 5th percentile, had at least 22% fewer unplanned hospital visits than expected, whereas the 202 worst-performing HOPDs, at or above the 95th percentile, had at least 29% more post-surgical visits than expected, given their case and surgical procedure mix. CONCLUSIONS: Many patients experience an unplanned hospital visit within 7 days of hospital outpatient surgery, often for potentially preventable reasons. The observed variation in performance across hospitals suggests opportunities for quality improvement.

Combined Smoking Cues Enhance Reactivity and Predict Immediate Subsequent Smoking.

Introduction: Cue reactivity (CR) research has reliably demonstrated robust cue-induced responding among smokers exposed to common proximal smoking cues (eg, cigarettes, lighter). More recent work demonstrates that distal stimuli, most notably the actual environments in which smoking previously occurred, can also gain associative control over craving. In the real world, proximal cues always occur within an environment; thus, a more informative test of how cues affect smokers might be to present these two cue types simultaneously. Methods: Using a combined-cue counterbalanced CR paradigm, the present study tested the impact of proximal (smoking and neutral) + personal environment (smoking and nonsmoking places) pictorial cues, on smokers' subjective and behavioral CR; as well as the extent to which cue-induced craving predicts immediate subsequent smoking in a within-subjects design. Results: As anticipated, the dual smoking cue combination (ProxS + EnvS) led to the greatest cue-induced craving relative to the other three cue combinations (ProxS + EnvN, ProxN + EnvS, and ProxN ± EnvN), ps < .004. Dual smoking cues also led to significantly shorter post-trial latencies to smoke, ps < .01. Overall CR difference score (post-trial craving minus baseline craving) was predictive of subsequent immediate smoking indexed by: post-trial latency to smoke [B = -2.69, SE = 9.02; t(143) = -2.98, p = .003]; total puff volume [B = 2.99, SE = 1.13; t(143) = 2.65, p = .009]; and total number of puffs [B = .053, SE = .027; t(143) = 1.95, p = .05]. Conclusions: The implications of these findings for better understanding the impact of cues on smoking behavior and cessation are discussed. Implications: This novel cue reactivity study examined smokers' reactivity to combined proximal and distal smoking cues. Exposure to a combination of two smoking cues (proximal and environment) led to the greatest increases in cue-induced craving and smoking behavior compared to all other cue combinations. Further, the overall magnitude of cue-induced craving was found to significantly predict immediate subsequent smoking. This work provides new insight on how exposure to various cues and cue combinations directly affect smokers' craving and actual smoking behavior, as well as the relationship between those two indices of reactivity.

Differences in Colonoscopy Quality Among Facilities: Development of a Post-Colonoscopy Risk-Standardized Rate of Unplanned Hospital Visits.

BACKGROUND & AIMS: Colonoscopy is a common procedure, yet little is known about variations in colonoscopy quality among outpatient facilities. We developed an outcome measure to profile outpatient facilities by estimating risk-standardized rates of unplanned hospital visits within 7 days of colonoscopy. METHODS: We used a 20% sample of 2010 Medicare outpatient colonoscopy claims (331,880 colonoscopies performed at 8140 facilities) from patients ≥65 years or older, and developed a patient-level logistic regression model to estimate the risk of unplanned hospital visits (ie, emergency department visits, observation stays, and inpatient admissions) within 7 days of colonoscopy. We then used the patient-level risk model variables and hierarchical logistic regression to estimate facility rates of risk-standardized unplanned hospital visits using data from the Healthcare Cost and Utilization Project (325,811 colonoscopies at 992 facilities), from 4 states containing 100% of colonoscopies per facility. RESULTS: Outpatient colonoscopies were followed by 5412 unplanned hospital visits within 7 days (16.3/1000 colonoscopies). Hemorrhage, abdominal pain, and perforation were the most common causes of unplanned hospital visits. Fifteen variables were independently associated with unplanned hospital visits (c = 0.67). A history of fluid and electrolyte imbalance (odds ratio [OR] = 1.43; 95% confidence interval [CI]: 1.29-1.58), psychiatric disorders (OR = 1.34; 95% CI: 1.22-1.46), and, in the absence of prior arrhythmia, increasing age past 65 years (aged >85 years vs 65-69 years: OR = 1.87; 95% CI: 1.54-2.28) were most strongly associated. The facility risk-standardized unplanned hospital visits calculated using Healthcare Cost and Utilization Project data showed significant variation (median 12.3/1000; 5th-95th percentile, 10.5-14.6/1000). Median risk-standardized unplanned hospital visits were comparable between ambulatory surgery centers and hospital outpatient departments (each was 10.2/1000), and ranged from 16.1/1000 in the Northeast to 17.2/1000 in the Midwest. CONCLUSIONS: We calculated a risk-adjusted measure of outpatient colonoscopy quality, which shows important variation in quality among outpatient facilities. This measure can make transparent the extent to which patients require follow-up hospital care, help inform patient choices, and assist in quality-improvement efforts.

Examining the relationship between cue-induced craving and actual smoking.

Smoking cue-reactivity studies have consistently demonstrated heightened self-report craving, as well as moderate autonomic reactivity, among smokers exposed to salient drug-related cues. However, significantly fewer studies have examined whether exposure to smoking cues affects smokers' actual smoking, or examined the predictive relationship between cue-induced craving and smoking behavior. Using our well-tested pictorial cues in a cue-reactivity paradigm, we investigated the impact of smoking-related cues relative to neutral cues on subjective craving and smoking behavior (assessed via CReSS; Plowshare Technologies, Baltimore, MD) measures of latency to smoke, puff volume, and number of puffs). Further, we examined the predictive value of cue-induced craving on subsequent smoking behavior. Sixty nondeprived daily smokers completed 2 experimental sessions involving exposure to either smoking-related or neutral pictorial cues. Following initial exposure to cues, smokers rated their craving and were then allowed to smoke freely if they chose to during a subsequent 6-min cue exposure period. Result showed that exposure to smoking cues relative to neutral predicted significantly greater craving and increases in smoking behavior. Likewise, the magnitude of the difference in cue-induced craving when exposed to smoking cues relative to neutral cues (i.e., the cue-reactivity effect) was highly predictive of shorter latency to smoke, as well as increased number of puffs and puff volume.

In-hospital complications associated with reoperations of implantable cardioverter defibrillators.

Repeat implantable cardioverter defibrillator (ICD) procedures are increasing and may be associated with higher risks for complications. To provide more information for clinical decision making, especially in light of recent defibrillator advisories, we examined a large national cohort to characterize repeat ICD procedural outcomes. Using data from the National Cardiovascular Data Registry (ICD Registry), we compared patient characteristics, reasons for ICD implantation, and associated in-hospital adverse events among 92,751 patients receiving their first device and 81,748 patients who underwent repeat procedures with (n = 31,057) and without (n = 50,691) lead involvement. Hierarchical multivariable logistic regression was used to determine the predictors of in-hospital complications. Complication rates were higher in those who underwent repeat ICD procedures with lead involvement (lead implantation or revision), compared with patients who underwent initial implants (3.2% vs 2.6%, p <0.001) or versus those with pocket-only (e.g., generator change only) procedures (3.2% vs 0.6%, p <0.001). There were significantly more in-hospital deaths, lead dislodgements, and infections requiring antibiotics in the lead involvement cohort. Compared with those who had a pocket-only procedure, the multivariable adjusted odds ratio of any complication were increased at 4.20 (95% confidence interval: 3.66 to 4.82, p <0.001) in patients who underwent repeat procedures with lead involvement excluding lead extraction or 7.11 (95% confidence interval: 5.96 to 8.48, p <0.001) in procedures involving lead extractions. In conclusion, repeat ICD procedures, when involving the addition or revision of a lead with or without concurrent lead extraction, are associated with higher complication rates compared with initial implants and with those who underwent pocket-only procedures.

Variation in hospital-level risk-standardized complication rates following elective primary total hip and knee arthroplasty.

BACKGROUND: Little is known about the variation in complication rates among U.S. hospitals that perform elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. The purpose of this study was to use National Quality Forum (NQF)-endorsed hospital-level risk-standardized complication rates to describe variations in, and disparities related to, hospital quality for elective primary THA and TKA procedures performed in U.S. hospitals. METHODS: We conducted a cross-sectional analysis of national Medicare Fee-for-Service data. The study cohort included 878,098 Medicare fee-for-service beneficiaries, sixty-five years or older, who underwent elective THA or TKA from 2008 to 2010 at 3479 hospitals. Both medical and surgical complications were included in the composite measure. Hospital-specific complication rates were calculated from Medicare claims with use of hierarchical logistic regression to account for patient clustering and were risk-adjusted for age, sex, and patient comorbidities. We determined whether hospitals with higher proportions of Medicaid patients and black patients had higher risk-standardized complication rates. RESULTS: The crude rate of measured complications was 3.6%. The most common complications were pneumonia (0.86%), pulmonary embolism (0.75%), and periprosthetic joint infection or wound infection (0.67%). The median risk-standardized complication rate was 3.6% (range, 1.8% to 9.0%). Among hospitals with at least twenty-five THA and TKA patients in the study cohort, 103 (3.6%) were better and seventy-five (2.6%) were worse than expected. Hospitals with the highest proportion of Medicaid patients had slightly higher but similar risk-standardized complication rates (median, 3.6%; range, 2.0% to 7.1%) compared with hospitals in the lowest decile (3.4%; 1.7% to 6.2%). Findings were similar for the analysis involving the proportion of black patients. CONCLUSIONS: There was more than a fourfold difference in risk-standardized complication rates across U.S. hospitals in which elective THA and TKA are performed. Although hospitals with higher proportions of Medicaid and black patients had rates similar to those of hospitals with lower proportions, there is a continued need to monitor for disparities in outcomes. These findings suggest there are opportunities for quality improvement among hospitals in which elective THA and TKA procedures are performed.

Cue reactivity as a predictor of successful abstinence initiation among adult smokers.

The association between smokers' cue-induced craving and subsequent ability to initiate abstinence is unclear. Dependent smokers (N = 158) completed a single cue-reactivity session prior to participating in a larger within-subjects study, which independently examined predictors of initiating quitting during 5 days each on nicotine versus placebo patch. In the larger study, all smokers used nicotine and placebo patch (double blind) for 1 week each following a preceding week of ad lib smoking, in a 2 × 2 cross-over design. Generalized estimating equation (GEE) models determined the predictive ability of cue-induced craving (cue reactivity) on subsequent success at initiating a quit attempt (at least 24 hr quit) for each patch condition. Smokers who exhibited greater craving during exposure to smoking cues had significantly greater odds of successfully initiating abstinence during either quit attempt week (i.e., the nicotine or placebo patch week). This relationship was not statistically significant for self-reported craving in response to neutral cues. However, a greater smoking-neutral cue difference score for cue-induced craving was also a significant predictor of successfully initiating abstinence, but only among those not monetarily reinforced. Implications of these seemingly counterintuitive findings are discussed.

Expectancy for negative affect relief due to smoking may not be predictive under acute mood situations.

Smoking behavior may be more persistent among those who expect that smoking will relieve negative affect (NA). Assessing smoking expectancies temporally close to mood situations could enhance the predictive value of that assessment. Dependent smokers (n = 71; 43 male, 28 female) participated in five laboratory sessions, each involving mood induction. The NA relief scale of the Smoking Consequences Questionnaire-Adult (SCQ-A), a very common measure of smoking expectancies during hypothetical situations, was assessed during initial screening. The SCQ-A was compared with a modified acute version administered each session, in which items asked about immediate expectancy for NA relief by smoking "right now" (termed Immediate Negative Affect Relief, or INAR). Actual NA relief due to smoking was measured each session by change on the NA scale of the Diener & Emmons Mood Form. The five sessions (counterbalanced) involved three different negative mood tasks, the negative mood condition of overnight smoking abstinence, and neutral mood (control). Generalized estimating equations showed that temporal proximity to the mood situation slightly enhanced the ability of expectancy to predict actual change in NA due to smoking, as the interaction with condition was significant for the INAR but marginal for the SCQ-A. However, the acute INAR predicted NA relief due to smoking only after overnight smoking abstinence and not during the other specific mood induction conditions, contrary to expectations, while the SCQ-A was not significant during any of the individual conditions. In sum, assessment of expectancy for NA relief may be of limited use in predicting actual NA relief from smoking during a current mood situation, aside from NA due to overnight abstinence.

Puffing behavior during the smoking of a single cigarette in tobacco-dependent adolescents.

INTRODUCTION: Adult and adolescent smokers regulate their nicotine and smoke intake by smoking low-yield cigarettes more intensely than high-yield cigarettes. One likely mechanism of nicotine regulation is altered puffing topography, which has been demonstrated in adult smokers. The purpose of this study was to examine the pattern of puffing behavior during the smoking of a single cigarette in adolescents. METHODS: Tobacco-dependent adolescents (n = 89) were enrolled in a treatment trial testing the efficacy of nicotine replacement therapy. About 1 week before their quit date, participants smoked ad libitum one of their usual brand of cigarettes during a laboratory session. Smoking topography measures included puff volume, puff duration, puff velocity, and interpuff interval. RESULTS: Controlling for sex, race, and number of puffs, puff volume and puff duration decreased 12.8% and 24.5%, respectively, from the first 3 to the last 3 puffs. Puff velocity and interpuff interval increased 14.8% and 13.5%, respectively. Puff volume was positively correlated with puff duration and puff velocity, whereas puff duration and puff velocity were negatively correlated. However, none of the topography measures were correlated with smoking history variables. DISCUSSION: These results suggest that adolescent smokers, like adults, are able to regulate smoke and nicotine intake on a puff-by-puff basis, therefore indicating that this aspect of smoking control is acquired early in the tobacco-dependence process.

A link between adolescent nicotine metabolism and smoking topography.

Adult slow nicotine metabolizers have lower smoke exposure, carbon monoxide levels, and plasma nicotine levels than normal and fast metabolizers. Emerging evidence suggests nicotine metabolism influences smoking topography. This study investigated the association of nicotine metabolism (the ratio of plasma 3-hydroxycotinine to cotinine; 3OHCOT/COT) with smoking topography in adolescent smokers (n = 85; 65% female, 68% European American; mean age, 15.3 +/- 1.2 years; mean cigarettes per day, 18.5 +/- 8.5; mean Fagerström Test for Nicotine Dependence, 7.0 +/- 1.2) presenting for a nicotine replacement therapy trial. Measures obtained included puff volume, interpuff interval, number of puffs, puff duration, and puff velocity. Linear regression analysis controlling for hormonal contraception use showed that 3OHCOT/COT ratios predicted mean puff volume in the overall sample (t = 2.126; P = 0.037; adjusted R(2) = 0.067). After gender stratification, faster metabolism predicted higher mean puff volume (t = 2.81; P = 0.009; adjusted R(2) = 0.192) but fewer puffs (t = -3.160; P = 0.004; adjusted R(2) = 0.237) and lower mean puff duration (t = -2.06; P = 0.048; adjusted R(2) = 0.101) among boys only, suggesting that as nicotine metabolism increases, puff volume increases but puffing frequency decreases. No significant relationships were found between nicotine metabolism and total puff volume, mean puff duration, interpuff interval, or puff velocity. If confirmed in a broader sample of adolescent smokers, these findings suggest that as among dependent adult smokers, rate of metabolism among adolescent boys is linked to select parameters of puffing behavior that may affect cessation ability.

Does allowing adolescents to smoke at home affect their consumption and dependence?

Negative parental attitudes towards smoking decrease adolescent smoking initiation but limited research explores the relationship between parental attitudes and degree of adolescent smoking among established smokers. The aim of this study was to examine the relationship between parental allowance of smoking in the home and adolescent smoking behavior and level of dependence. Interviews from 408 youths seeking assistance to quit smoking showed that adolescents who were allowed to smoke at home smoked more cigarettes per day and had higher scores on the Fagerström Test of Nicotine Dependence than those not allowed to smoke at home. Studies that additionally evaluate parental smoking status and the temporal relationship of parental allowance of smoking with changes in adolescent smoking behavior are warranted to clarify public health implications of parental smoking interdictions.

Measuring nicotine intake among highly-dependent adolescent smokers: comparability of saliva and plasma cotinine concentrations.

Cotinine is the most common biomarker used to assess nicotine exposure and abstinence. It can be measured in various matrices including saliva, plasma, and urine. Previous research with adults has shown high correlations between saliva and plasma cotinine concentrations. However, the research has not examined this relationship in adolescents. Additionally, variability in saliva flow and metabolism across gender, ethnicity, and age may impact the relationship between saliva and plasma cotinine concentration. Our aim was to examine the relationship between saliva and plasma cotinine concentration in a group of nicotine-dependent adolescent smokers. Additionally, we examined these correlations across gender, ethnicity and age. The sample consisted of 66 adolescent smokers (age 15.1+/-1.3, 63.6% girls, 66.7% European American, CPD 18.3+/-8.5, FTND 7.1+/-1.3). Saliva and plasma specimens were collected before the treatment phase of a nicotine replacement therapy trial and analyzed. The relationship between saliva and plasma cotinine concentration was analyzed using Pearson's correlation coefficients. We performed a secondary analysis using multiple regressions to compare correlations across race, gender and age. Results indicated a positive correlation between saliva cotinine and plasma cotinine concentration (r=0.84, p<0.001). Differences in correlations across age were significant (t=3.03, p<0.01). Differences across ethnicity approached significance (t=-1.93, p=0.058). Future research should seek to further validate saliva-to-plasma cotinine concentration ratios in adolescents as well as characterize saliva-to-plasma concentration differences and their underlying mechanisms.