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Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. Methods Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI Results Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (−1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (−0.3; P < .003), bleeding (−0.3; P < .0002) and urgency (−0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. Conclusions In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Real-world data comparing the effectiveness of tofacitinib to ustekinumab are limited. We compared 52-week outcomes of tofacitinib vs ustekinumab for UC after antitumor necrosis factor (anti-TNF) failure. Methods In this retrospective cohort study, adults initiated tofacitinib or ustekinumab for UC after anti-TNF failure May 1, 2018 to April 1, 2021, at a US academic medical center. The primary outcome was steroid-free clinical remission (SFCR) at 12 and 52 weeks. The secondary outcome was drug survival (ie, time to drug discontinuation due to nonresponse). Adverse events (AEs) were also assessed. Results Sixty-nine patients initiated tofacitinib, and 97 patients initiated ustekinumab with median follow-up of 88.0 and 62.0 weeks, respectively. After inverse probability of treatment-weighted logistic and Cox regression, there was no association of tofacitinib vs ustekinumab with SFCR at 12 weeks (odds ratio, 1.65; 95% CI, 0.79-3.41), SFCR at 52 weeks (odds ratio, 1.14; 95% CI, 0.55-2.34), or drug survival (hazard ratio, 1.37; 95% CI, 0.78-2.37). Kaplan-Meier analysis demonstrated no separation in drug survival curves. Regression results were similar after excluding patients with prior tofacitinib or ustekinumab exposure. During available follow-up, 17 AEs were reported for tofacitinib (most commonly shingles, n = 4), and 10 AEs were reported for ustekinumab (most commonly arthralgia and rash, each n = 2). Two patients discontinued treatment due to AEs (1 tofacitinib for elevated liver enzymes, 1 ustekinumab for arthralgia). Conclusions In a real-world UC cohort, tofacitinib and ustekinumab demonstrated similar effectiveness at 52 weeks. Adverse events were consistent with the known safety profiles of these agents.

BACKGROUND Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. AIMS To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI). METHODS This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8-week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database. Methods Patients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation). Results Among patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3–6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib. Conclusions Among patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

Underuse of hydralazine/nitrate (HYD/NIT) in black patients with heart failure and reduced ejection fraction (HFrEF) has been previously described, but whether this important treatment gap persists in contemporary practice is unknown. Sacubitril/valsartan has become a part of guideline-directed medical therapy for HFrEF but data on utilization of this therapy in black patients is lacking. This study addressed these issues by assessing the frequency of HYD/NIT and sacubitril/valsartan use in black patients with HFrEF in the Change the Management of Patients with Heart Failure Registry, a multicenter cohort study. The association of race with utilization rates of these agents was also evaluated. Clinical and medication data at baseline and during 12 months of follow-up from black and nonblack registry patients without documented contraindications or intolerance to the medications of interest were analyzed. Data were available from December 2015 to October 2017, in 4,848 HFrEF patients, of whom 853 were black (18%) and 3995 were nonblack. Black patients were younger, more likely to be female, and had lower ejection fractions compared with nonblacks. Only 11% of black patients were receiving HYD/NIT therapy at baseline and 13% at 1 year. The percentage of black patients treated at baseline with sacubitril/valsartan was also low at 18% and remained unchanged at 1 year. After adjustment for covariates, race was independently associated with HYD/NIT use (odds ratio 8.32; 95% confidence interval 6.12 to 11.3; p0.0001), but not for sacubitril/valsartan. In conclusion, study findings demonstrate a marked persistent treatment gap for HYD/NIT and similar poor utilization of sacubitril/valsartan in black patients with HFrEF despite current guideline recommendations.

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database.Patients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation).Among patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3-6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib.Among patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

This study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).Although therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown.Health status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.Multivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p 0.001) over a median (interquartile range [IQR]) of 57 (32 to 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively.In routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients' symptoms, functions, and quality of life.

Objectives The aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients’ medications with changes in health status. Background Alleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients’ health status is unknown. Methods The association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression. Results Among 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: −3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: −4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p Conclusions In routine care of patients with HFrEF, changes in HFrEF medications were associated with significant improvements in patients’ health status, suggesting that health status–based performance measures can quantify the benefits of titrating medicines in patients with HFrEF.

BackgroundGuidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown.ObjectivesThis study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes.MethodsAmong 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up.ResultsAt baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12months,&nbsp

Objectives This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories. Background Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied. Methods Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. Results Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP Conclusions In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI

Tofacitinib is an oral, small molecule Janus kinase (JAK) inhibitor for the treatment of ulcerative colitis (UC). This study assessed the cost-effectiveness of tofacitinib versus other available treatments for patients with moderate to severe UC following an inadequate response to conventional treatment and who are either naïve to or have failed previous biologics in Germany. A Markov cohort model was developed to evaluate the differences in long-term costs and outcomes between tofacitinib and its comparators from the perspective of German statutory health insurance (SHI) for patients either naïve or exposed to biologics. Tofacitinib was compared to infliximab, infliximab biosimilar, adalimumab, adalimumab biosimilar, golimumab, vedolizumab, ustekinumab, and conventional therapy. Health states modeled were remission, treatment response, active UC, and post-colectomy. Patients not responding to treatment could switch to a different treatment. Treatment efficacy for induction and maintenance phases were assessed by a systematic literature review (SLR) and network meta-analysis (NMA). The model included costs associated with drug administration, adverse events, and medical resource use. Extensive deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Over a life-time horizon, patients treated with tofacitinib gained 0.035–0.083 quality-adjusted life-years (QALYs) and had direct cost savings to the SHI of €4,228–€17,184 compared to biologic treatments other than adalimumab biosimilar. When compared to adalimumab biosimilar, treatment with tofacitinib resulted in an incremental cost-effectiveness ratio (ICER) of €17,497 per QALY gained and can be considered a cost-effective alternative. Compared with conventional therapy, tofacitinib resulted in a lower ICER than all other biologics. The DSA showed that the model results were most influenced by differences in treatment efficacy. The PSA suggested confidence in the base-case results considering uncertainty around parameters. The results of this economic model suggest tofacitinib is a cost-effective treatment option for patients with moderate to severe UC in Germany.

IMPORTANCE: The extent to which levels of high-sensitivity C-reactive protein (hs-CRP), a known marker of increased cardiovascular risk, are elevated and are associated with standard cardiovascular risk factors in patients with a history of myocardial infarction (MI) is unknown. OBJECTIVES: To determine the pattern and determinants of the distribution of hs-CRP in those with a prior MI in the United States using a nationally representative sample. DESIGN AND PARTICIPANTS: Adults with hs-CRP data in the National Health and Nutrition Examination Surveys from 1999–2010. RESULTS: Among 1296 individuals in our cohort, the median age was 65 years and the median hs-CRP level was 2.69 mg/L, measured an average of 7.1 years after the MI. Among these patients, 22% had hs-CRP levels of

Background Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. The degree to which gaps in medication use and dosing persist in contemporary outpatient practice is unclear. Objectives This study sought to characterize patterns and factors associated with use and dose of HFrEF medications in current practice. Methods The CHAMP-HF (Change the Management of Patients with Heart Failure) registry included outpatients in the United States with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA). Patient-level factors associated with medication use were examined. Results Overall, 3,518 patients from 150 primary care and cardiology practices were included. Mean age was 66 ± 13 years, 29% were female, and mean EF was 29 ± 8%. Among eligible patients, 27%, 33%, and 67% were not prescribed ACEI/ARB/ARNI, beta-blocker, and MRA therapy, respectively. When medications were prescribed, few patients were receiving target doses of ACEI/ARB (17%), ARNI (14%), and beta-blocker (28%), whereas most patients were receiving target doses of MRA therapy (77%). Among patients eligible for all classes of medication, 1% were simultaneously receiving target doses of ACE/ARB/ARNI, beta-blocker, and MRA. In adjusted models, older age, lower blood pressure, more severe functional class, renal insufficiency, and recent HF hospitalization generally favored lower medication utilization or dose. Social and economic characteristics were not independently associated with medication use or dose. Conclusions In this contemporary outpatient HFrEF registry, significant gaps in use and dose of guideline-directed medical therapy remain. Multiple clinical factors were associated with medication use and dose prescribed. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

While high-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and higher cardiovascular risk, its association with health status (symptoms, function and quality of life) after acute myocardial infarction (AMI) is unknown.Among 3410 patients with AMI from the TRIUMPH (N = 1301) and VIRGO (N = 2109) studies, we compared 1-year generic (Medical Outcome Study Short Form-12 and Euro Quality of Life Visual Analog Scale) and disease-specific (Seattle Angina Questionnaire) health status outcomes in those with hs-CRP ≥2 mg/L vs.2 mg/L. In hierarchical linear regression models, we examined the association of 30-day hs-CRP levels with 1-year health status without adjustment, after adjusting for 30-day health status, and after adjusting for demographic, socioeconomic, disease severity/comorbidities and treatment characteristics.The median (25th, 75th percentiles) 30-day hs-CRP was 2.6 (1.1, 6.1) mg/L and 59% had hs-CRP ≥2 mg/L. Statin therapy was used in 92% of patients at hospital discharge. Thirty-day hs-CRP ≥2 mg/L was inversely associated with all 1-year health status measures in unadjusted and partially adjusted models, but not in fully-adjusted models. Results were similar when hs-CRP was analyzed as a continuous variable.While elevated hs-CRP 30 days after AMI was associated with worse health status in unadjusted analyses, this was not significant after adjusting for comorbidities, suggesting that hs-CRP may be a marker of comorbidities associated with worse health status. Whether reducing inflammation in AMI patients will improve health status should be tested in ongoing trials.

OBJECTIVE The aim of this study was to assess health care utilization and costs related to acute pancreatitis (AP) in patients with severe hypertriglyceridemia (sHTG) levels. METHODS Patients with sHTG levels 1000 mg/dL or higher were identified from January 1, 2007, to June 30, 2013. The first identified incident triglyceride level was labeled as index date. All-cause, AP-related health care visits, and mean total all-cause costs in patients with and without AP were compared during 12 months postindex. A generalized linear model regression was used to compare costs while controlling for patient characteristics and comorbidities. RESULTS Five thousand five hundred fifty sHTG patients were identified, and 5.4% of these patients developed AP during postindex. Patients with AP had significantly (P < 0.05) more all-cause outpatient visits, hospitalizations, longer length of stays during the hospital visits, and emergency department visits versus patients without AP. Mean (SD) unadjusted all-cause health care costs in the 12 months postindex were $25,343 ($33,139) for patients with AP compared with $15,195 ($24,040) for patients with no AP. The regression showed annual all-cause costs were 49.9% higher (P < 0.01) for patients with AP versus without AP. CONCLUSIONS Patients who developed AP were associated with higher costs; managing patients with sHTG at risk of developing AP may help reduce unnecessary costs.

Background The Short Form-36 Health Survey version 2 (SF-36v2) is a generic health-related quality-of-life (HRQoL) instrument [1]. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In these exploratory analyses the concordance between total and partial Mayo scores and SF-36v2 scores was evaluated in patients with UC in the Phase 3 tofacitinib 8-week OCTAVE Induction 1&2 (NCT01465763; NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Methods A repeated measures regression model was used to evaluate the relationship between total and partial Mayo scores (as predictor) and SF-36v2 component and domain scores. A sensitivity analysis to assess the linearity assumption was performed using Mayo score as a categorical anchor (represented by integer values 0–12 [total] or 0–9 [partial]). Previous analyses identified clinically important differences (CIDs) in total and partial Mayo scores as changes of 3 points and 2.25 points, respectively [2]. Mean differences in SF-36v2 component and domain scores were compared with their recommended group-level CID thresholds [3]. Results Clinically meaningful differences of 3 points and 2.25 points in total and partial Mayo scores, respectively, were generally associated with clinically meaningful differences in SF-36v2 component and domain scores, with the exception of Role-Emotional with partial Mayo score in the pooled induction studies and with total Mayo score in the maintenance study. In the induction studies, a 3-point difference in total Mayo score was associated with a mean difference exceeding CIDs in both the SF-36v2 Physical Component Summary score (mean improvement 4.5; 95% confidence interval [CI] 4.2, 4.7) and Mental Component Summary score (mean improvement 5.0; 95% CI 4.6, 5.3). Results were closely aligned when Mayo score was used as a categorical or continuous anchor, supporting a linear relationship between Mayo score and SF-36v2 scores (Figure). Similar results were observed in the maintenance study, and when assessing the relationship of partial Mayo score with SF-36v2 scores. Conclusion Clinically meaningful decreases in disease activity, as measured by Mayo score, were associated with clinically meaningful benefits in HRQoL, as measured by SF-36v2 component and domain scores. These findings highlight the impact that disease activity has on HRQoL and may assist with articulating the treatment effect of tofacitinib on specific domains. References

The aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients' medications with changes in health status.Alleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients' health status is unknown.The association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression.Among 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p 0.001). Among patients whose medications were adjusted, 26% had very large clinical improvement (≥20 points) compared with 14% whose regimens were not changed.In routine care of patients with HFrEF, changes in HFrEF medications were associated with significant improvements in patients' health status, suggesting that health status-based performance measures can quantify the benefits of titrating medicines in patients with HFrEF.

Background Current guidelines recommend sacubitril/valsartan for patients with heart failure with reduced ejection fraction, but the rate of adoption in the United States has been slow. Methods and Results Using data from CHAMP-HF (Change the Management of Patients With Heart Failure), we described current sacubitril/valsartan use and identified patient, provider, and practice characteristics associated with its use. We considered patients to be on sacubitril/valsartan if they were prescribed it before enrollment or initiated on it at the baseline visit. We excluded patients with a contraindication to sacubitril/valsartan and practices with P P P P Conclusions Despite current guideline recommendations, adoption of sacubitril/valsartan remains low. Provider and practice characteristics associated with sacubitril/valsartan use were related to general practice size and were not associated with practice characteristics specific for heart failure. Further research is needed to identify strategies for effective quality improvement interventions in chronic heart failure with reduced ejection fraction.

Background The US Food and Drug Administration approved sacubitril/valsartan for patients with chronic heart failure (HF) with reduced ejection fraction in 2015 on the basis of the results of the PARADIGM ‐ HF (Prospective Comparison of ARNI [Angiotensin Receptor Neprilysin Inhibitor] With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. There are limited data assessing the generalizability of PARADIGM ‐ HF trial participants to a broader population of patients with HF with reduced ejection fraction routinely encountered in outpatient clinical practice. Methods and Results We compared the baseline characteristics of patients in the PARADIGM ‐ HF trial with those in the CHAMP ‐HF (Change the Management of Patients With Heart Failure) study a large US outpatient registry of patients with HF with reduced ejection fraction. Patients in the PARADIGM ‐ HF trial (n=8442) were similar to those in the CHAMP ‐ HF registry (n=3497) in terms of age (mean, 64 versus 66 years), sex (22% versus 29% women), New York Heart Association class III to IV (25% versus 32%), systolic blood pressure (mean, 121 versus 121 mm Hg), left ventricular ejection fraction (mean, 29% versus 29%), and other key baseline characteristics. The median (25th–75 th percentile) Meta‐Analysis Global Group in Chronic Heart Failure risk scores were similar for the 2 studies (20 [16–24] versus 22 [8–27]). Despite this, only 13% of patients in the CHAMP ‐ HF registry were prescribed sacubitril/valsartan at baseline. Conclusions These data suggest participants randomized in the PARADIGM ‐ HF trial have similar baseline characteristics to those encountered in routine outpatient clinical practice, but there is a substantial lag in the adoption of sacubitril/valsartan for patients with chronic HF with reduced ejection fraction.

Background There is limited information about the long‐term survival of older patients after myocardial infarction ( MI ). Methods and Results CRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged ≥65 years in CRUSADE to their Medicare data to ascertain long‐term mortality (defined as 8 years post index event). Long‐term unadjusted Kaplan–Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post‐ MI was conducted. We used multivariable Cox regression to compare mortality risks between ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction patients. Among 22 295 MI patients ≥ age 65 years (median age 77 years), we observed high rates of evidence‐based medication use at discharge: aspirin 95%, β‐blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65% at 8 years. Eight‐year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post‐ MI (59%). Median survival was 4.8 years (25th, 75th percentiles 1.1, 8.5); among patients aged 65–74 years it was 8.2 years (3.3, 8.9) while for patients aged ≥75 years it was 3.1 years (0.6, 7.6). Eight‐year mortality was lower among ST‐segment–elevation myocardial infarction than non–ST‐segment–elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88–1.00). Conclusions Long‐term mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year.

OBJECTIVES:This study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES). BACKGROUND:Although a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown. METHODS:In the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients from 140 U.S. clinics. SES was categorized by total household income. Hierarchical multivariate linear regression estimated differences in KCCQ-os score after adjusting for 31 patient characteristics and 10 medications. RESULTS:Overall mean KCCQ-os scores were 64.2 ± 24.0 but lower for women (29% of sample; 60.3 ± 24.0 vs. 65.9 ± 24.0, respectively; p < 0.001), for blacks (60.5 ± 25.0 vs. 64.9 ± 23.0, respectively; p < 0.001), for Hispanics (59.1 ± 21.0 vs. 64.9 ± 23.0, respectively; p < 0.001), and for those with the lowest income (

Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. The degree to which gaps in medication use and dosing persist in contemporary outpatient practice is unclear.This study sought to characterize patterns and factors associated with use and dose of HFrEF medications in current practice.The CHAMP-HF (Change the Management of Patients with Heart Failure) registry included outpatients in the United States with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA). Patient-level factors associated with medication use were examined.Overall, 3,518 patients from 150 primary care and cardiology practices were included. Mean age was 66 ± 13 years, 29% were female, and mean EF was 29 ± 8%. Among eligible patients, 27%, 33%, and 67% were not prescribed ACEI/ARB/ARNI, beta-blocker, and MRA therapy, respectively. When medications were prescribed, few patients were receiving target doses of ACEI/ARB (17%), ARNI (14%), and beta-blocker (28%), whereas most patients were receiving target doses of MRA therapy (77%). Among patients eligible for all classes of medication, 1% were simultaneously receiving target doses of ACE/ARB/ARNI, beta-blocker, and MRA. In adjusted models, older age, lower blood pressure, more severe functional class, renal insufficiency, and recent HF hospitalization generally favored lower medication utilization or dose. Social and economic characteristics were not independently associated with medication use or dose.In this contemporary outpatient HFrEF registry, significant gaps in use and dose of guideline-directed medical therapy remain. Multiple clinical factors were associated with medication use and dose prescribed. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

Background: Elevated hs-CRP is associated with worse cardiovascular outcomes in patients with acute myocardial infarction (AMI), but little is known about predictors of elevated hs-CRP after AMI. Methods: TRIUMPH and VIRGO are prospective AMI registries that assessed hs-CRP levels 30 days after AMI. TRIUMPH assessed hs-CRP levels at 6 months. Multivariable regression analysis was conducted to examine predictors of elevated hs-CRP [≥2.0 mg/L] at 30 days and at 6 months after an AMI (TRIUMPH only). Results: Of 3410 patients in both registries, 58.6% had elevated hs-CRP 30 days post AMI. Patients with elevated hs-CRP were more likely to be female, black, obese, smokers, to have had higher LDL-C at the time of their AMI, with more peripheral vascular disease and history of heart failure, and were less likely to have had a prior PCI (Table). In TRIUMPH, baseline hs-CRP ≥2 mg/L (n=1301) was significantly associated with elevated hs-CRP at 6 months (p Conclusions: hs-CRP remains elevated in a large proportion of patients following AMI. We identified several predictors of elevated hs-CRP at 1 and 6 months post AMI. Further studies are needed to validate the findings and understand the utility of routine screening of hs-CRP in post AMI patients.

Background: C-reactive protein can be measured by a high-sensitivity assay (hsCRP) to detect persistent low grade vascular inflammation predictive of cardiovascular (CV) risk in patients with history of myocardial infarction (MI). However, the real-world use of hsCRP testing among patient with history of MI, and hence the contemporary usage to address residual inflammatory risk, is unknown Methods: Patients with ≥1 claim with an inpatient, primary diagnosis for MI (ICD-9-CM code: 410.xx) between 01 October 2011 to 30 September 2014 (the most recent set as an index) in MarketScan and 1 year continuous enrolment pre- and post-hospital admission were included Results: A total of 71,071 patients (mean age 63.6 years, 67.6% males) were included. The hsCRP measurement was performed in 3.3% patients (CCAE: 4.7%; Medicare: 1.3%) with a mean time of 4.3 months after the index MI; 81.7% of patients were tested ≥30 days after the index MI. Patient characteristics and resource uses were similar among hsCRP tested and non-tested patients (Table 1) Conclusion: hsCRP testing with a potential to evaluate residual inflammatory CV risk is not used widely in routine clinical practice in US patients with history of MI. No systematic effect of hsCRP testing was observed with respect to patient characteristics and resource use. Further research is warranted to understand and describe the real-world usage of hsCRP testing to evaluate residual inflammatory risk and the associated patient characteristics, outcomes and burden of disease

Background: Elevated hs-CRP has been shown to correlate with adverse outcomes in patients with coronary disease, however, little is known about the patterns of hs-CRP levels at the time of, and following, AMI. We sought to describe these patterns and patient characteristics associated with persistently elevated hs-CRP. Methods: TRIUMPH was a prospective observational AMI registry that assessed hs-CRP levels at baseline, 1 and 6 months after AMI. Patients were divided into groups based on their hs-CRP levels at baseline and follow up (1 and 6 months) with elevated hs-CRP defined as ≥ 2 mg/L. Results: Among patients with available baseline and 1 month hs-CRP (n=801), 753 (94%) of patients had hs-CRP ≥2 at baseline, of which 427 (56.7%) still had hs-CRP ≥2 at 1 month (Figure). Of 48 patients with hs-CRP Conclusions: Approximately half of patients with elevated hs-CRP at the time of an AMI have persistently elevated hs-CRP at 1 and 6 months. Further investigation is needed to better illuminate the optimal risk reduction strategies for this higher-risk cohort.

Background Sacubitril/valsartan is recommended by current guidelines for patients with heart failure with reduced ejection fraction (HFrEF), but the rate of adoption in the US has been slow. We examined factors associated with sacubitril/valsartan use in the US. Methods Using baseline data from CHAMP-HF, a large US outpatient registry of HFrEF patients, we described current sacubitril/valsartan use and identified patient and practice characteristics associated with its use. Patients with a contraindication to sacubitril/valsartan and practices with Results Of 4216 patients enrolled from 121 US sites between December 2015 and August 2017, 616 (15%) were treated with sacubitril/valsartan, 2506 (59%) with an ACEI/ARB, and 1094 (26%) with neither. Patients treated with sacubitril/valsartan were younger (63 years vs 66 years ACEI/ARB vs 69 years neither, p Table ). After adjusting for patient and provider characteristics, the number of advanced practice providers was independently associated with sacubitril/valsartan use (adjusted odds ratio 1.08, 95% CI 1.03, 1.14). Conclusions Despite current guideline recommendations, adoption of sacubitril/valsartan among eligible HFrEF patients remains low and use is associated with patient factors and larger practice size. There remains an opportunity to improve patient outcomes with broader implementation of novel strategies in chronic HFrEF.

Introduction A principal goal in treating patients with heart failure with reduced ejection fraction (HFrEF) is to minimize their symptoms, improve their function and optimize their quality of life. Patient-reported outcome measures, such as the Kansas City Cardiomyopathy Questionnaire (KCCQ), have been proposed to measure healthcare quality. In previous research, we found substantial variation in mean KCCQ scores across practices. We now explore whether medication adjustments are associated with changes in KCCQ scores over time. Methods Using data from CHAMP-HF, a multicenter observational study of outpatients with HFrEF (LVEF Results Among 3313 patients from 140 practices, we observed marked changes and variability in patients' KCCQ scores at 3 months (Figure). Overall, 23.8% of patients' KCCQ scores worsened and 46.4% improved. At least 1 medication was adjusted in 727 (22%) patients. Adjustment in patients' HF medications was associated with significantly greater improvement in patients' KCCQ scores compared with no adjustment to any HF medications [+7.3 (IQR: -3.1, 20.8) vs + 3.1 (IQR: -4.7, 12.5) points; p Conclusion The health status of patients with HFrEF varies over time and is associated with treatment adjustments recommended by clinicians. Measuring patients' health status may encourage providers to adjust therapy to improve the symptoms, function and quality of life of patients' with HFrEF.

Background. Lapatinib is an oral small molecule dual tyrosine kinase inhibitor that has been shown to improve time to progression versus capecitabine in women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab. Objective. To describe extent, predictors, and consequences of nonadherence with lapatinib in women with MBC who were previously treated with trastuzumab. Methods. This was a retrospective observational study using data from a large health insurance claims databases spanning January 2000 to March 2010. Measures of lapatinib adherence included medication possession ratio (MPR), time to discontinuation (end of supply), time to first treatment interruption (gap during treatment of 30 days without supply), and duration of continuous therapy (time to gap of 30 days without supply or end of supply). Predictors of nonadherence to lapatinib and the association between nonadherence and outcomes, utilization, and costs were examined using multiple regression analysis. Results. A total of 666 patients met all inclusion criteria. Mean initial lapatinib dosage was 1161 mg daily; 63% received index lapatinib in combination with capecitabine. Mean MPR was 87%; 22% of patients had MPR < 80%. Median time to lapatinib discontinuation was 9.1 months (95% confidence interval = 8.0-10.2). Twenty-seven percent of patients had one or more treatment interruptions during follow-up. Median duration of continuous therapy was 5.9 months (95% confidence interval = 5.1-6.1). Concomitant therapy with a taxane was a predictor of nonadherence (odds ratio for MPR < 80% = 10.30; P < .001). There was a statistically significant association between nonadherence to lapatinib and greater number of outpatient visits ( P = .028). Conclusions. In women with MBC who were previously treated with trastuzumab, mean adherence to lapatinib in typical clinical practice is relatively high overall, although there is a small group of patients with high nonadherence. Targeted efforts to improve adherence to lapatinib in this subgroup may be warranted.

We examine the association between prior C-section and subsequent pre-eclampsia; and describe the effect of gestational age at prior C-section, and obesity status on this association. The study population included women with two subsequent singleton births in Missouri between 1998 and 2005. The risk for pre-eclampsia/eclampsia was assessed among women with and without prior cesarean delivery. The two groups were followed to their second pregnancy and the occurrence of pre-eclampsia was documented. Additionally, the history of pre-eclampsia, prior cesarean at preterm, and obesity status were examined for their differential effects on the risk of pre-eclamsia. Women with prior C-section were 28% more likely to have pre-eclampsia in their subsequent pregnancy [OR = 1.28; 95% CI = 1.20–1.37]. However, this result was not significant when women with pre-eclampsia in their first pregnancy were excluded. After this exclusion, a more than threefold increased risk for subsequent pre-eclampsia was observed in women with prior early C-section [OR = 3.15; 95% CI= 2.43–4.08], while the level of risk did not change in the prior late C-section group [OR = 0.90; 95% CI= 0.82–1.00]. Subgroup analysis suggested that obesity status modified the risk of prior early C-section but did not affect the risk for prior late C-section. Preterm C-section in the first pregnancy may be associated with subsequent pre-eclampsia regardless of prior pre-eclampsia status.

Background Patients with heart failure and reduced ejection fraction (HFrEF) often do not receive target doses of guideline-directed medical therapy (GDMT). Low systolic blood pressure (SBP) may limit GDMT intensification. We examined the prevalence of low SBP as a potential barrier to the use of target doses of GDMT in a contemporary, multi-center cohort of outpatients with HFrEF. Methods In 3095 patients without documented intolerance to ACE-inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blockers (BB) enrolled in the CHAMP-HF registry, we assessed the proportion receiving ≥100% target dose at baseline visit for each drug class before and after stratifying patients by SBP ≥110 or Results Patients were more often male (70.6%), ≥65 years old (59.6%), Caucasian (73.8%) and had SBP≥110 mmHg (78.2%). For each medication class, most patients were receiving ≤50 % of target doses ( Fig 1 a-c). Overall, the proportion of the total population receiving target doses were 10.8% (95% CI: 9.7 - 11.9) for ACEIs/ARBs, 18.7% (95% CI: 17.3 - 20.0) for BB and 2% (1.5 - 2.5) for ARNI ( Fig 1 a). Among those with SBP Fig 1 b). Among those with SBP≥110 (n=2421), target doses were prescribed in 19% (17.4 - 20.6) for BB, 12.1% (10.8 - 13.4) for ACE-I/ARB, and 2% (1.5 - 2.6) for ARNI ( Fig 1 c). Among patients eligible for both BB and ACE-I/ARB/ARNI (n= 1619), only 8.8% (n= 142) were receiving target doses of both ( Fig 1 d). Conclusion In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BB, ACE-I/ARB and ARNI, less than 1 in 5 were receiving target doses, even among those with SBP ≥110 mmHg. SBP alone may not be a major barrier to medication intensification. Other factors should be evaluated to implement novel strategies to improve prescription of GDMT doses.

We sought to estimate the association between prenatal smoking and stillbirth in a longitudinal cohort using two study designs: a case-control study and a bidirectional case-crossover study. The analysis was conducted using the Missouri maternally linked cohort dataset from 1978 through 1997. In the case-control study, each mother contributed only one birth to the analysis. For the bidirectional crossover design, analysis was restricted to women who gave birth to at least one stillbirth, and the controls comprised all live births before and after the stillbirth. The independent association between prenatal smoking and stillbirth was computed using nonconditional (case-control design) and conditional (bidirectional case-crossover design) logistic regression. Prenatal smoking decreased from 29.7% in 1978 to 21.2% by 1997 (p.001). The absolute risk of stillbirth was greater among smokers (7.7/1000) than nonsmokers (5.3/1000), p.001. In the case-control design, the risk of stillbirth was 34% greater among smokers than nonsmokers (OR = 1.34, 95% CI 1.26-1.43). For each 10-unit increase in the number of cigarettes consumed per day prenatally, the likelihood of stillbirth rose by about 14% (p.001). In the bidirectional case-crossover design, the association between stillbirth and smoking during pregnancy was confirmed, although the magnitude of the relationship was smaller (OR = 1.20, 95% CI 1.03-1.39). In conclusion, we found prenatal smoking to be a risk factor for stillbirth even after minimizing the influence of known and unknown sources of confounding as well as changes in temporal trend in prenatal smoking.

We sought to estimate the risk of stillbirth recurrence among relatively low-risk women, a group defined as maternal age35 years; absence of congenital anomalies; gestational age range of 20-44 weeks inclusive; singleton births; and non-smokers. The Missouri maternally linked data containing births from 1978 to 1997 were used for the study. We identified the study group (low-risk gravidae who experienced a stillbirth in the first pregnancy) and a comparison group (low-risk gravidae who delivered a live birth in their first pregnancy) and compared the stillbirth risks in the second pregnancy between both groups. Analysis was based on 261 384 women with information on first and second pregnancies [1050 (0.5%) women with stillbirth]. Of the 947 cases of stillbirth in the second pregnancy, 20 cases occurred in women with a history of stillbirth (stillbirth rate 19.0 per 1000 births) and 927 in the comparison group (stillbirth rate 3.6 per 1000 births; P0.001). The adjusted risk of stillbirth was almost six times higher in women with a prior stillbirth (hazard ratio [HR] 5.8, [95% CI 3.7, 9.0]). Analysis by stillbirth subtype in the second pregnancy showed that history of stillbirth conferred greater risk for subsequent early (fetal deaths between 20 and 28 weeks) (HR 10.3, [95% CI 6.1, 17.2]) than late stillbirths (fetal deaths ator=29 weeks) (HR 2.5, [95% CI 1.0, 6.0]); and for intrapartum (HR 12.2, [95% CI 4.5, 33.3]) than antepartum (HR 4.2, [95% CI 2.3, 7.7]) stillbirths. Among relatively low-risk women, history of stillbirth was associated with increased recurrence, with substantial heterogeneity by timing of stillbirth.

Background A subset of patients hospitalized with acute heart failure experiences in-hospital worsening heart failure , defined as persistent or worsening signs or symptoms requiring an escalation of therapy. Methods We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) >12hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples. Results We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample ( c statistic, 0.74) and validation sample ( c statistic, 0.72). Conclusions The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure.

To evaluate patient characteristics, treatment patterns, comorbidities, and risk factors associated with the development of acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG) in an integrated health care delivery system.We identified a retrospective cohort of severe HTG patients with a fasting triglyceride level ≥ 1000 mg/dL during January 1, 2007 to June 30, 2013 (index date) in an integrated health care delivery system. Patients were aged ≥18 years on index date and had 12 months of continuous membership and drug eligibility before the index date and during postindex including index date. Baseline patient characteristics, comorbidities, and risk factors were evaluated during 12-month preindex. Outcomes such as development of AP, treatment patterns, adherence to index therapy, and change in triglyceride (TG) laboratory levels were evaluated during postindex. Descriptive statistics were used to identify differences between patients developing AP vs no development of AP. A stepwise multivariate logistic regression and backward elimination method were used to assess statistically significant predictive factors associated with development of AP vs no AP.We identified 5550 patients with severe HTG, and 5.4% of these patients developed AP during postindex. Patients were mostly male (≥70%) in both groups; however, younger in the AP group (45 years ± 10.6) vs no AP group (50 years ± 11.4) with P value .0001. The AP group had higher baseline Charslon Comorbidity Index score, alcohol abuse history (42.2%), any pancreatitis history (51.5%), diabetes (47%), and hypertension (55%), vs the no AP group (P values .05). Patients in the AP group had higher baseline mean TG levels (2148, SD ± 1578) vs the no AP group (1559, SD ± 861), P value .0001. Over 50% of the patients were prescribed their index therapy by a primary care provider. Predictive factors associated with the development of AP included younger age, alcohol use, and prior history of any pancreatitis, hypertension, renal disease stage 4, and other prescriber specialty. From parameters estimates, for each 100 mg/dL unit of increase in the TG level above 1000 mg/dL, there was a 3 percent increase in risk of developing AP.Patients with severe HTG are at a higher risk of developing AP. A number of comorbidities, risk factors, and baseline TG levels are associated with an increased incidence of AP. Patients with severe HTG are underdiagnosed, undertreated and are nonadherent to their index lipid therapy. There is a need to better define optimal approaches to treating severe HTG so as to reduce the incidence of AP. Economic studies are also needed to evaluate the burden of AP on various health care systems.

Background: A subset of patients hospitalized with acute heart failure (HF) experience in-hospital worsening heart failure (WHF), defined as persistent or worsening signs or symptoms requiring an escalation of therapy. These patients are at increased risk for mortality and readmission resulting in increased costs, yet predictors for the development of WHF remain poorly characterized and an in-hospital WHF risk model has not been derived and validated. Methods: We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital WHF. Based on previous work, in-hospital WHF was defined by any of the following: use of inotropes or vasodilators >12 hours after admission; initiation of mechanical circulatory support, hemodialysis, or ventilation after the first inpatient day; or transfer to an intensive care unit. We considered candidate risk prediction variables routinely assessed on admission including age, medical history, biomarkers and renal function. Logistic regression with robust standard errors was used to generate a risk model for in-hospital WHF in a 66% random derivation sample; the model was validated in the remaining 34% sample. We evaluated the calibration and discrimination of the model in both samples. Results: We evaluated 23,696 patients hospitalized with acute HF. Baseline characteristics were well-matched in the derivation and validation samples. The mean age was 81 years (standard deviation [SD] 7.7), mean systolic BP was 145 mm Hg (SD 29.8), and mean creatinine was 1.5 mg/dL (SD 0.9). The occurrence of in-hospital WHF was similar in the derivation, 15.4% (2403 of 15,640), and validation samples, 15.6% (1257 of 8056). After multivariable adjustment, the strongest predictors of in-hospital WHF were positive admission troponin and admission creatinine (Table). The model was well-calibrated. The risk model had strong discrimination in the derivation (c statistic=0.74) and validation samples (c statistic=0.72). Conclusion: The ADHERE WHF risk model is a validated clinical tool with good discrimination for use in hospitalized acute HF patients to identify patients at risk for in-hospital WHF. This tool may be useful to target treatment strategies for patients at high risk for in-hospital WHF.

We sought to estimate levels of risk for stillbirth subtypes associated with twin gestations among pediatric mothers (10–14 years). Analysis was on twin pregnancies covering the period 1989 to 2000 in the United States. We classified stillbirth as term, preterm, small-for-gestational-age (SGA) or preterm-SGA. We then assessed the risks of these stillbirth subtypes in pediatric mothers using two comparison groups consisting of women aged 15 to 19 years old (adolescent mothers) and 20 to 24 years old (mature mothers). Adjusted risk estimates were by means of hazard ratios generated from a Cox proportional hazards regression model. We adjusted for dependence of observations within twin clusters using the robust sandwich estimator. The rate of stillbirth was highest among pediatric mothers (56/1000), followed by adolescent gravidas (29/1000) and lowest in mature mothers (20/1000; p for trend < .01). Overall, preterm stillbirth was the most frequent stillbirth phenotype while term stillbirth was the least frequent. Not a single case of term stillbirth was recorded in pediatric mothers. Among pediatric gravidas, the risk for preterm stillbirth was more than tripled (adjusted hazard ratio [AHR] = 3.4; 95% confidence interval [CI] = 2.5–4.6), and that of preterm-SGA stillbirth more than doubled (AHR = 2.6; 95% CI = 1.8–3.7) that of mature mothers respectively. The 30% risk elevation for SGA stillbirth among pediatric mothers was not found to be statistically significant (AHR = 1.1; 95% CI = 0.3–4.3). Pediatric motherhood is a risk factor for stillbirth in twin gestation, especially, preterm and preterm-SGA stillbirth phenotypes. Prevention of stillbirth among this category of mothers should target the period preceding full term.

OBJECTIVE We sought to assess whether small for gestational age is a risk factor for stillbirth of a subsequent sibling. METHODS The Missouri maternally linked cohort data set, containing data on births from 1978 through 1997, was used. We identified the study group (women who delivered a SGA infant in the first pregnancy) and a comparison group (women who delivered a non-SGA infant in their first pregnancy) and compared the outcome (stillbirth) in the second pregnancy between both groups. RESULTS We analyzed information on the first and second pregnancies of 402,015 women (43,549 [10.8%] in the study arm and 358,466 [89.2%] in the comparison arm). Of the 1,883 cases of stillbirth in the second pregnancy, 314 cases occurred in mothers with a history of SGA (stillbirth rate 7.2/1,000) and 1,569 in the comparison group (stillbirth rate 4.4/1,000), P < .001. The adjusted risk of stillbirth was 60% higher in women with a prior SGA (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.8). The risk for stillbirth in the second pregnancy increased with decreasing gestational age at birth of the SGA infant in the first pregnancy (term: OR 1.4, 95% CI 1.2-1.6; preterm: OR 2.8, 95% CI 2.0-3.8; and very preterm: OR 4.2, 95% CI 2.4-7.3), P for trend < .001. CONCLUSION Small for gestational age is a marker for subsequent stillbirth, and the risk rises with decreasing gestational age of the SGA birth. This information is potentially useful for counseling parents of SGA infants. LEVEL OF EVIDENCE II-2.

We describe an approach to quantify birthweight discordance in quadruplets and assessed its potential use in predicting infant mortality. Retrospective cohort study on quadruplets delivered in the United States from 1995 through 2000 inclusive. The main outcome measures were infant, neonatal, and postneonatal mortality. A total of 2692 quadruplet live births (673 complete clusters) with complete information on gestational age, birthweight, and survival within the first year. Of the total 673 quadruplet clusters, discordance occurred in 180 sets (26.7%). The predominant discordant type was a single discordant individual within a cluster (177 sets or 99.8%), whereas only three sets (0.2%) recorded up to two discordant quadruplets within a cluster. The period of pronounced risk for the occurrence of birthweight discordance was between 28 and 35 gestational weeks. Discordant individuals exhibited elevated risk for infant (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [CI], 1.4 to 3.0), neonatal (aOR = 1.8; 95% CI, 1.2 to 2.6), and postneonatal (aOR = 2.9; 95% CI, 1.1 to 8.4) mortality. After adjusting for small for gestational age, the risk for postneonatal mortality among discordant infants quadrupled (aOR = 4.1; 95% CI, 1.5 to 10.8). The population-attributable risks were 18, 20, and 46% for neonatal, infant, and postneonatal mortality, respectively. The new method is predictive of mortality at all stages of infancy. Discordance accounts for 18 to 46% of all quadruplet deaths during infancy in the United States.

Objective To clarify the association between childhood pregnancy and risk of stillbirth. Study design We analyzed singleton and twin pregnancies that occurred in children (10-14 years old) in the United States from 1989 to 2000. We estimated the absolute and relative risks of stillbirth by using 15- to19-year-old and 20- to 24-year-old mothers as comparison groups. Results The analysis involved 17.8 million singletons and 337,904 individual twins. The rate of stillbirth was highest in pediatric mothers for both singletons (12.8/1000) and twins (56/1000) compared with adolescent (6.8/1000 in singletons and 29/1000 in twins) and mature (5.5/1000 in singletons and 20/1000 in twins) mothers. After adjusting for confounding characteristics, pediatric mothers continued to exhibit significantly elevated risk for stillbirth in both singletons (odds ratio, 1.57; 95%CI, 1.49-1.66) and twins (odds ratio, 1.97; 95%CI, 1.42-2.73). Preterm birth rather than small size for gestational age was revealed by means of sequential modeling to account for the excess risk of stillbirth observed in pediatric gravidas. Conclusion Pregnancy in childhood is a risk factor for stillbirth; shortened gestation rather than reduction in fetal growth is the mediating pathway.

OBJECTIVE We estimate the impact of increasing fetal number on fetal and infant mortality among Hispanic mothers. METHODS Retrospective cohort study involving singletons, twins, and triplets delivered in the United States from 1995 through 2000, except for the analysis on infant mortality in singletons (1995 through 1999). Main outcome measures were stillbirth (> or = 20 weeks) and infant mortality (< 365 days). RESULTS A total of 37,489,600 individual births were reviewed, consisting of 36,840,704 singletons, 613,930 twins, and 34,966 triplets. Hispanics accounted for 6,848,027 (18.6%) singletons, 85,887 (14.0%) individual twins, and 2,725 (7.8%) individual triplets. Among singletons, stillbirth (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.90-0.92) and infant mortality (OR 0.85, 95% CI 0.84-0.86) were both lower in Hispanics than in whites. Among twins, Hispanics had a lower risk for infant mortality (OR 0.93, 95% CI 0.88-0.97) but a comparable risk for stillbirth (OR 1.06, 95% CI 0.98-1.13). Although the risk for infant mortality in Hispanic triplets was comparable to that of whites (OR 1.20, 95% CI 0.94-1.54), Hispanic triplets had a 50% higher likelihood of dying in utero (OR 1.50, 95% CI 1.06-2.14). CONCLUSION Although Hispanic infants generally show better or comparable survival indices compared with whites, the risk for fetal and infant death in Hispanics increases in fetal number in a dose-dependent fashion, thereby obliterating the Hispanic advantage. The elevated risk for stillbirth among Hispanic triplets is particularly noteworthy and underscores the need for caution in making generalizations of favorable birth outcomes in Hispanics.

Background: Meig’s and Pseudo-Meig’s syndromes have been reported in association with several malignancies but the concomitant existence of multiple synchronous benign and malignant tumors in association with Pseudo-Meigs’ syndrome has not been reported in the published literature. Case: A 55-year old African American woman presented with mild asthma exercebation, right ovarian mass, hydrothorax and elevated CA-125 levels. Histological examination confirmed a right ovarian carcinoid tumor embedded within a mature cystic teratoma while the left ovary, fallopian tube and the uterus contained a poorly differentiated adenocarcinoma of the endometrium. Conclusion: This is the first case report of Pseudo-Meig’s syndrome in association with ovarian carcinoid tumor and multiple synchronous benign and malignant pelvic tumors.

Background A subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes. Methods and Results We analyzed inpatient data from the Acute Decompensated Heart Failure National Registry linked to Medicare claims to examine the prevalence and outcomes of patients with worsening heart failure, defined as the need for escalation of therapy at least 12 hours after hospital presentation. We compared patients with worsening heart failure to patients with an uncomplicated hospital course and patients with a complicated presentation. Of 63 727 patients hospitalized with acute heart failure, 11% developed worsening heart failure. These patients had the highest observed rates of mortality, all‐cause readmission, and Medicare payments at 30 days and 1 year after hospitalization ( P CI , 2.34 to 2.80) compared with an uncomplicated course and 1.29 (99% CI , 1.17 to 1.42) compared with a complicated presentation. The adjusted cost ratios for postdischarge Medicare payments at 30 days were 1.35 (99% CI , 1.24 to 1.46) compared with an uncomplicated course and 1.11 (99% CI , 1.02 to 1.22) compared with a complicated presentation. Conclusions In‐hospital worsening heart failure was common and was associated with higher rates of mortality, all‐cause readmission, and postdischarge Medicare payments. Prevention and treatment of in‐hospital worsening heart failure represents an important goal for patients hospitalized with acute heart failure.

Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF.We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (0.3 mg/dL) or persistent WRF (≥ 0.3 mg/dL). We examined unadjusted rates and adjusted associations between 90-day outcomes and WRF status.Among 27,309 patients, 18,568 (68.0%) had no WRF, 3,205 (11.7%) had transient WRF, and 5,536 (20.3%) had persistent WRF. Patients with WRF had higher observed rates of 90-day postdischarge all-cause readmission and 90-day postadmission mortality (P.001). After multivariable adjustment, transient WRF (hazard ratio [HR] 1.19, 99% CI 1.05-1.35) and persistent WRF (HR 1.73, 99% CI 1.57-1.91) were associated with higher risks of 90-day postadmission mortality (P.001 for both). Compared with transient WRF, persistent WRF was associated with a higher risk of 90-day postadmission mortality (HR 1.46, 99% CI 1.28-1.66, P.001).Transient and persistent WRF during hospitalization for acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes.

Background: A subset of patients hospitalized with acute heart failure (AHF) experiences worsening clinical status while hospitalized and require escalation of therapy. This phenomenon, termed in-hospital worsening heart failure (WHF), is an endpoint for many clinical trials but limited data exist on the prevalence of WHF in clinical practice and associated outcomes. Methods: We analyzed inpatient data from Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims data to describe outcomes and health care utilization of patients that developed WHF. In-hospital WHF was defined by any of the following: use of inotropes or intravenous vasodilators >12 hours after admission; initiation of mechanical circulatory support, hemodialysis, or ventilation after the first inpatient day; or transfer to the ICU after initial admission to a regular hospital ward. Patients with WHF were compared to those with an uncomplicated hospital course and those that had a complicated hospital presentation, defined as requiring the above advanced therapies on arrival. Results: The study population consisted of 63,727 patients hospitalized between 01/2001 and 12/2004. Of these, WHF developed in 7032 (11%), 15,361 (24%) presented with a complicated presentation and 41,334 (65%) with an uncomplicated hospital course. Observed mean length of stay was longest in the WHF cohort (10.0 days) followed by complicated presentation (6.3 days) and uncomplicated course (4.8 days). Patients with WHF also had higher observed rates of mortality and all-cause readmission at 30 days and 1 year after discharge (P Conclusion: In a large, multicenter registry, in-hospital WHF was common and associated with higher rates of mortality, all-cause readmission, and Medicare payments. Preventing and treating WHF represents an important therapeutic target among patients hospitalized with AHF.