Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.

Heart failure is an established risk factor for postoperative mortality, but how left ventricular ejection fraction and heart failure symptoms affect surgical outcomes is not fully described.OBJECTIVES To determine the risk of postoperative mortality among patients with heart failure at various levels of echocardiographic (left ventricular systolic dysfunction) and clinical (symptoms) severity compared with those without heart failure and to evaluate how risk varies across levels of surgical complexity. DESIGN, SETTING, AND PARTICIPANTS US multisite retrospective cohort study of all adult patients receiving elective, noncardiac surgery in the Veterans Affairs Surgical Quality Improvement Project database from 2009 through 2016. A total of 609 735 patient records were identified and analyzed with 1 year of follow-up after having surgery (final study follow-up: September 1, 2017). EXPOSURES Heart failure, left ventricular ejection fraction, and presence of signs or symptoms of heart failure within 30 days of surgery. MAIN OUTCOME AND MEASURE The primary outcome was postoperative mortality at 90 days. RESULTS Outcome data from 47 997 patients with heart failure (7.9%; mean [SD] age, 68.6 [10.1] years; 1391 women [2.9%]) and 561 738 patients without heart failure (92.1%; mean [SD] age, 59.4 [13.4] years; 50 862 women [9.1%]) were analyzed. Compared with patients without heart failure, those with heart failure had a higher risk of 90-day postoperative mortality (2635 vs 6881 90-day deaths; crude mortality risk, 5.49% vs 1.22%; adjusted absolute risk difference [RD], 1.03% [95% CI, 0.91%-1.15%]; adjusted odds ratio [OR], 1.67 [95% CI, 1.57-1.76]). Compared with patients without heart failure, symptomatic patients with heart failure (n = 5906) had a higher risk (597 deaths [10.11%]; adjusted absolute RD, 2.37% [95% CI, 2.06%-2.57%]; adjusted OR, 2.37 [95% CI, 2.14-2.63]). Asymptomatic patients with heart failure (n = 42 091) (2038 deaths [crude risk, 4.84%]; adjusted absolute RD, 0.74% [95% CI, 0.63%-0.87%]; adjusted OR, 1.53 [95% CI, 1.44-1.63]), including the subset with preserved left ventricular systolic function (1144 deaths [4.42%]; adjusted absolute RD, 0.66% [95% CI, 0.54%-0.79%]; adjusted OR, 1.46 [95% CI, 1.35-1.57]), also experienced elevated risk.CONCLUSIONS AND RELEVANCE Among patients undergoing elective noncardiac surgery, heart failure with or without symptoms was significantly associated with 90-day postoperative mortality. These data may be helpful in preoperative discussions with patients with heart failure undergoing noncardiac surgery.

A persistent problem for emergency physicians is the patient who returns unscheduled to the emergency department with a problem that either has not improved or has worsened. The purpose of this study was to evaluate the frequency of revisits and the nature of the problems. All patients returning within 72 hours of their initial visit were entered into the study. The charts were evaluated for classification of problem, unavoidable v avoidable returns, and errors in medical care or patient education. Of the 64,336 patients seen during the study, 255 returned within 72 hours. Eighty-three (32.5%) of the returns were found to be avoidable with better patient education or medical care on the initial visit. The revisit population is a high-risk group of patients who should be approached carefully by emergency physicians.

OBJECTIVEThere is a paucity of literature on long-term neurosurgical outcomes in sub-Saharan Africa, and as neurosurgical services expand in each country, it would be beneficial to understand the impact of these services on the national population. Since follow-up can be inconsistent, the authors here used the novel method of telephone surveys to conduct the first-ever long-term follow-up in Uganda to elucidate the outcomes of pediatric head trauma patients treated at the national referral hospital.METHODSA prospectively maintained database of pediatric head trauma patients treated at the Mulago National Referral Hospital (MNRH) between 2014 and 2015 included 232 patients eligible for this study. Quality of life was assessed through phone surveys conducted by a Ugandan collaborator on site who performed all interviews with the guardian listed at the time of hospital admission, using each participant’s language.RESULTSPhone interviews were completed for 142 patients, resulting in a 61% response rate. Including inpatient deaths, the mortality rate was 10%. Almost half of the patients (48%) did not return to MNRH postdischarge, and 37% received no subsequent healthcare at all. Including inpatient deaths, the average Extended Glasgow Outcome Scale–Pediatric Revision (GOSE-Peds) scores for patients with severe, moderate, and mild head trauma were 5.68 ± 2.85, 4.79 ± 2.38, and 3.12 ± 2.08, respectively, at 1 year postinjury and 5.56 ± 2.58, 4.00 ± 2.45, and 2.21 ± 1.49, respectively, at 2 years postinjury.CONCLUSIONSThis first-ever long-term follow-up of pediatric head trauma patients in Uganda confirmed the feasibility of a novel phone follow-up method for patients throughout Uganda. The results at 2 years showed poor long-term recovery in patients who suffered moderate or severe head trauma but good recovery in patients who suffered mild head trauma. However, there was greater overall disability than that in comparable head trauma studies in the US. The current study lays the groundwork for phone follow-up in low- and middle-income countries as a viable way to obtain outcome data.

is an established risk factor for postoperative mortality, but how heart failure is associated with operative outcomes specifically in the ambulatory surgical setting is not well characterized.OBJECTIVE To assess the risk of postoperative mortality and complications in patients with vs without heart failure at various levels of echocardiographic (left ventricular systolic dysfunction) and clinical (symptoms) severity who were undergoing ambulatory surgery. DESIGN, SETTING, AND PARTICIPANTSIn this US multisite retrospective cohort study of all adult patients undergoing ambulatory, elective, noncardiac surgery in the Veterans Affairs Surgical Quality Improvement Project database during fiscal years 2009 to 2016, a total of 355 121 patient records were identified and analyzed with 1 year of follow-up after surgery (final date of follow-up September 1, 2017).EXPOSURES Heart failure, left ventricular ejection fraction, and presence of signs or symptoms of heart failure within 30 days of surgery. MAIN OUTCOMES AND MEASURESThe primary outcomes were postoperative mortality at 90 days and any postoperative complication at 30 days. RESULTS Among 355 121 total patients, outcome data from 19 353 patients with heart failure (5.5%; mean [SD] age, 67.9 [10.1] years; 18 841 [96.9%] male) and 334 768 patients without heart failure (94.5%; mean [SD] age, 57.2 [14.0] years; 301 198 [90.0%] male) were analyzed.Compared with patients without heart failure, patients with heart failure had a higher risk of 90-day postoperative mortality (crude mortality risk, 2.00% vs 0.39%; adjusted odds ratio [aOR], 1.95; 95% CI, 1.69-2.44), and risk of mortality progressively increased with decreasing systolic function. Compared with patients without heart failure, symptomatic patients with heart failure had a greater risk of mortality (crude mortality risk, 3.57%; aOR, 2.76; 95% CI, 2.07-3.70), as did asymptomatic patients with heart failure (crude mortality risk, 1.85%; aOR, 1.85; 95% CI, 1.60-2.15). Patients with heart failure had a higher risk of experiencing a 30-day postoperative complication than did patients without heart failure (crude risk, 5.65% vs 2.65%; aOR, 1.10; 95% CI, 1.02-1.19). CONCLUSIONS AND RELEVANCEIn this study, among patients undergoing elective, ambulatory surgery, heart failure with or without symptoms was significantly associated with 90-day mortality and 30-day postoperative complications. These data may be helpful in preoperative discussions with patients with heart failure undergoing ambulatory surgery.

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PURPOSE Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy. PATIENTS AND METHODS Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria. RESULTS One hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF. CONCLUSION Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.

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