Real-World Use and Effectiveness Outcomes in Patients with Rheumatoid Arthritis Treated with Upadacitinib: An Analysis from the CorEvitas Registry.

INTRODUCTION: Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA. METHODS: Data were collected from the CorEvitas® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy. RESULTS: Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy. CONCLUSIONS: UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.

Treatment of Chronic Kidney Disease-Related Metabolic Acidosis With Fruits and Vegetables Compared to NaHCO3 Yields More and Better Overall Health Outcomes and at Comparable Five-Year Cost.

OBJECTIVES: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with Na+-based alkali but base-producing fruits and vegetables (F + V) might yield more and better health outcomes, making the intervention cost-effective. DESIGN AND METHODS: In this post hoc analysis of a clinical trial we randomized 108 macroalbuminuric, nondiabetic CKD stage 3 participants with metabolic acidosis to receive F + V (n = 36) calculated to reduce dietary acid by half, oral NaHCO3 (HCO3-, n = 36) 0.3 mEq/kg body weight/day, or Usual Care (UC, n = 36) assessed annually for 5 years. We calculated a mean overall health score for the groups as follows: 1 for improved, 0 for no change, and -1 for worsened at 5 years for plasma total CO2, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, change in medication dose (reduction = 1, increased = -1, no change = 0), and 1 for met goal and 0 for not meeting goal for estimated glomerular filtration rate (>30 mL/min/1.73 m2) and systolic blood pressure (<130 mm Hg). We also assessed the number of participants with cardiovascular disease events (myocardial infarctions + strokes) and group medication and hospitalization costs. RESULTS: Net plasma total CO2 increase at 5 years was no different between HCO3- and F + V. Average health scores at 5 years differed among groups (P < .01) with F + V (7.4 [mean] ± 1.6 [standard deviation]) being descriptively larger than HCO3- and UC (2.9 ± 1.6 and 1.2 ± 1.6, respectively). The number of participants suffering cardiovascular disease events differed among groups (P = .009) with none (0) in F + V, 6 in UC, and 2 in HCO3-. Total 5-year household cost per beneficial health outcome differed among groups (P = .005) with UC being highest and that for HCO3- and F + V being comparable. CONCLUSIONS: Metabolic acidosis improved comparably with F + V or standard oral NaHCO3, but F + V yielded ancillary beneficial health outcomes, fewer participants with adverse cardiovascular events, and per-household cost that was comparable to NaHCO3.

Efficacy of Liposomal Bupivacaine Compared with Multimodal Periarticular Injections for Postoperative Pain Control following Total Knee Arthroplasty.

Single-dose long-acting periarticular anesthetics have been shown to be an effective method of postoperative analgesia in total knee arthroplasty (TKA). This study retrospectively compares the efficacy of multimodal periarticular injection consisting of a combination of ropivacaine, duramorph, epinephrine, and toradol (HC) with liposomal bupivacaine (LB) periarticular injection in TKA. This study was a retrospective matched comparative chart review of two cohorts of patients who underwent TKA within a single health care system and cared for by one provider. We compared 22 patients who were treated with LB intraoperatively (LBG) with 41 matched controls who were treated with HC periarticular injection (HCG). These cases were retrospectively reviewed at 0 to 6, 6 to 12, 12 to 24, 24 to 48, and 48 to 72 hours. We reviewed pain scores and opioid use per the preceding time period, total opioid use, length of stay (LOS), and wound complications between the two groups. The two groups showed no statistical difference in total opioids used. In both the 6- to 12-hour and 12- to 24-hour intervals, the LBG required significantly more opioids than the HCG, with p-values of 0.0039 and 0.0061, respectively. Pain scores were not significantly different for any time period. We found no difference in LOS. The LBG tended to have lower doses of antiemetics than the HCG. No significant difference was found in postoperative pain scores and total opioid use between LB and multimodal periarticular intraoperative injections in TKA. Our data demonstrated decreased opioid consumption in the HC group compared with the LB group in both the 6- to 12-hour and 12- to 24-hour time intervals postoperatively. At our institution, LB costs US$314.99, whereas HC costs US$95.

NSQIP-Based Quality Improvement Curriculum for Surgical Residents.

BACKGROUND: General surgery training has historically lacked a standardized approach to resident quality improvement (QI) education aside from traditional morbidity and mortality conference. In 2013, the ACGME formalized QI as a component of residency training. Our residency chose the NSQIP Quality In-Training Initiative (QITI) as the foundation for our QI training. We hypothesized that a focused curriculum based on outcomes would produce change in culture and improve the quality of patient care. STUDY DESIGN: Quality improvement curriculum design and implementation were retrospectively reviewed. Institutional NSQIP data pre-, during, and post-curriculum implementation were reviewed for improvement. RESULTS: A QITI project committee designed a 2-year curriculum, with 3 parts: didactics, focused on methods of data collection, QI processes, and techniques; review of current institutional performance, practice, and complication rates; and QI breakout groups tasked with creating "best practice" guidelines addressing common complications in our NSQIP semi-annual reports. Educational presentations were given to the surgical department addressing reduction of cardiac complications, pneumonia, surgical site infections (SSIs), and urinary tract infections (UTIs). Twenty-four residents completed both years of the QITI curriculum. National NSQIP decile ranks improved in known high outlier areas: cardiac complications, ninth to fourth decile; pneumonia, eighth to first decile; SSIs, tenth to second decile; and UTIs, eighth to third decile. Pneumonia and SSI rates demonstrated statistical improvement after curriculum implementation (p < 0.003). CONCLUSIONS: Implementing a QITI curriculum with a full resident complement is feasible and can positively affect surgical morbidity and nationally benchmarked performance. Resident QI education is essential to future success in delivering high quality surgical care.

Protocol-Driven Management of Suspected Common Duct Stones.

BACKGROUND: Common duct stones can be diagnosed by magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS)/ERCP, and intraoperative cholangiogram (IOC). In 2015, our group adopted a standard approach of preoperative EUS/ERCP followed by laparoscopic cholecystectomy for patients with an admission bilirubin >4.0 mg/dL. For bilirubin <4.0 mg/dL, laparoscopic cholecystectomy with IOC was the initial procedure. Postoperative EUS/ERCP with endoscopic sphincterotomy was pursued for positive IOC. Exclusions included clinical suspicion of malignancy and surgically altered anatomy making endoscopic management impractical. STUDY DESIGN: A retrospective comparison of protocol and pre-protocol (baseline) patients was performed, looking at patient demographics, presence of pancreatitis, common duct stone risk factors, comorbidities, length of hospitalization, and postoperative morbidity. Statistical analysis was performed with t-test, chi-square, and Wilcoxon rank-sum test with significance at p < 0.05. RESULTS: There were 56 patients in each group, with a mean ± SD age of 50.5 ± 20.88 years and 49.3 ± 20.92 years, respectively (p = NS). There were no significant differences between baseline and protocol patients with respect to individual and cumulative preoperative comorbidities, pancreatitis, elevation of liver function tests, bilirubin, common duct size, and postoperative morbidity. There were fewer endoscopies (22 vs 35; p = 0.014), and shorter length of stay in protocol patients (2.8 days vs 3.8 days; p = 0.025). CONCLUSIONS: Protocol-driven management of patients with suspected common duct stones reduced the number of endoscopies and length of hospitalization, with no change in postoperative morbidity. This approach has the potential to decrease endoscopy-related morbidity and overall cost without affecting quality of care.

High- versus low-dose leucovorin in the modified FOLFOX6 regimen for first-line treatment of metastatic colorectal cancer.

Background In response to the national leucovorin shortage in 2008, our institution adjusted the modified FOLFOX6 (leucovorin, fluorouracil, and oxaliplatin) protocol to utilize a lower dose of leucovorin (20 mg/m2). This adjustment was based on prospective studies suggesting that lower doses of leucovorin may be equally effective in other fluorouracil containing regimens. This retrospective study evaluates outcomes in metastatic colorectal cancer (mCRC) patients treated with low- (20 mg/m2) vs. high-dose (400 mg/m2) leucovorin in the FOLFOX6 regimen for mCRC. Methods This retrospective analysis included consecutive mCRC patients from 2004 to 2011 if they received at least one cycle of modified FOLFOX6 as first line therapy. Patients who received an initial leucovorin dose other than 20 mg/m2 or 400 mg/m2 on their first cycle were excluded. Patient characteristics included demographics, metastatic site at initial diagnosis, and treatment history including chemotherapy and surgery. Primary outcome was date of death or last contact. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were utilized to evaluate the effect of leucovorin dose on overall survival. Log-rank tests were used to compare median survival times by dose group. Results Of the 93 mCRC patients who received first line modified FOLFOX6, leucovorin 400 mg/m2 was administered to 47 (51%) patients and 20 mg/m2 to 46 (49%) patients. There were no differences of baseline characteristics between the groups with exception of primary site of cancer ( p = 0.038). The overall survival time was 22.5 months (95% CI 16.6-29.6). The median survival time in the leucovorin 400 mg/m2 group was 23.1 months (95% CI 16.2-35.7) compared to leucovorin 20 mg/m2 which was 20.5 months (95% CI 14.2-34.2); p = 0.573. The median survival times in patients with one versus two or more sites with metastasis were statistically different (26.9 vs. 16.2 months, p = 0.009). Metastatic site removal or ablation showed differences in the median survival, 34.2 months (95% CI 20.8-50.9) vs. 16.6 months (95% CI 14.1-23.6) without metastatic disease removal ( p = 0.004). The odds of dying for patients with two metastatic sites was higher compared with the odds of those patients with one site, HR 1.8 (95% CI 1.08-3.0). Patients without metastatic site removal or ablation had higher odds of dying compared to those patients without this procedure, HR 0.47 (95% CI 0.27-0.81). Conclusion In this single center retrospective study, there was no difference in overall survival for mCRC patients treated with first line FOLFOX6 with low- vs. high-dose leucovorin.

Impact of obesity on postoperative 30-day outcomes in emergent open ventral hernia repairs.

BACKGROUND: Anecdotally, obese patients experience increased morbidity with emergent ventral hernia repair (VHR). We hypothesized obese patients are over-represented in emergent VHRs and experience increased 30-day morbidity. METHODS: American College of Surgeons National Surgical Quality Improvement Program database (2011 to 2013) was queried for patients undergoing open VHR. Patients were stratified by body mass index (BMI) categories: underweight, normal weight, overweight, and obesity classes I, II, and III; 30-day postoperative complications (surgical site infections, return to operating room, dehiscence, death) were evaluated across BMI for elective vs emergent VHR. RESULTS: In all, 39,822 patients were included: 7.3% emergent. Obese classes I to III represented higher percent of emergent VHRs (55.8% vs 68.9%). Complication rate doubled for emergent group (7.2% vs 14.5%), and likelihood of at least one complication increased with BMI for emergent vs normal weight-elective VHR (overweight odds ratio, 2.2; 95% confidence interval, 1.4 to 3.4; class III odds ratio, 4.0; 95% confidence interval, 2.9 to 5.5). CONCLUSIONS: Selection bias exists with obese patients and ventral hernias. Emergent VHR have increased complications. Elective BMI cutoffs require re-evaluation.

Tailoring surgical approach for elective ventral hernia repair based on obesity and National Surgical Quality Improvement Program outcomes.

BACKGROUND: Obesity's influence on postoperative complications in either laparoscopic ventral hernia repair (LVHR) or open ventral hernia repair (OVHR) has yet to be defined. Although 30-day postoperative complications increase with higher body mass index (BMI), we propose LVHR minimizes surgical site infections (SSIs) and surgical site occurrences (SSOs) for given BMI categories. METHODS: Retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2009 to 2012) for patients aged 18 years or more undergoing elective ventral hernia repair. Exclusion criteria included immunosuppression, disseminated malignancy, advanced liver disease, or pregnancy. Patients were stratified by BMI (20 to 25, 25 to 30, 30 to 35, 35 to 40, and >40 kg/m(2)), and 30-day SSOs evaluated across BMI groups for LVHR vs OVHR. RESULTS: A total of 106,968 patients met inclusion criteria, with 60% patients obese. LVHR decreased SSO for all patients (odds ratio, .4; confidence interval, .19 to .60). Obesity classes I/II/III have increased odds of superficial SSI, deep SSI, and dehiscence for OVHR compared with LVHR. Only obesity class III has increased odds of organ space SSI and reoperation for OVHR vs LVHR (P < .05). CONCLUSIONS: Obese patients are over-represented in VHRs. Thirty-day postoperative wound complications increase with higher BMI. LVHR minimizes both SSIs and SSOs, especially in higher obesity classes.