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Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

Background: Endoscopically visualized spine surgery has become an essential tool that aids in identifying and treating anatomical spine pathologies that are not well demonstrated by traditional advanced imaging, including MRI. These pathologies may be visualized during endoscopic lumbar decompression (ELD) and categorized into primary pain generators (PPG). Identifying these PPGs provides crucial information for a successful outcome with ELD and forms the basis for our proposed personalized spine care protocol (SpineScreen). Methods: a prospective study of 412 patients from 7 endoscopic practices consisting of 207 (50.2%) males and 205 (49.8%) females with an average age of 63.67 years and an average follow-up of 69.27 months was performed to compare the durability of targeted ELD based on validated primary pain generators versus image-based open lumbar laminectomy, and minimally invasive lumbar transforaminal interbody fusion (TLIF) using Kaplan-Meier median survival calculations. The serial time was determined as the interval between index surgery and when patients were censored for additional interventional and surgical treatments for low back-related symptoms. A control group was recruited from patients referred for a surgical consultation but declined interventional and surgical treatment and continued on medical care. Control group patients were censored when they crossed over into any surgical or interventional treatment group. Results: of the 412 study patients, 206 underwent ELD (50.0%), 61 laminectomy (14.8%), and 78 (18.9%) TLIF. There were 67 patients in the control group (16.3% of 412 patients). The most common surgical levels were L4/5 (41.3%), L5/S1 (25.0%), and L4-S1 (16.3%). At two-year f/u, excellent and good Macnab outcomes were reported by 346 of the 412 study patients (84.0%). The VAS leg pain score reduction was 4.250 ± 1.691 (p < 0.001). No other treatment during the available follow-up was required in 60.7% (125/206) of the ELD, 39.9% (31/78) of the TLIF, and 19.7% (12/61 of the laminectomy patients. In control patients, only 15 of the 67 (22.4%) control patients continued with conservative care until final follow-up, all of which had fair and poor functional Macnab outcomes. In patients with Excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients (p < 0.001). The overall survival time in control patients was eight months with a standard error of 0.942, a lower boundary of 6.154, and an upper boundary of 9.846 months. In patients with excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients versus control patients at seven months (p < 0.001). The most common new-onset symptom for censoring was dysesthesia ELD (9.4%; 20/206), axial back pain in TLIF (25.6%;20/78), and recurrent pain in laminectomy (65.6%; 40/61) patients (p < 0.001). Transforaminal epidural steroid injections were tried in 11.7% (24/206) of ELD, 23.1% (18/78) of TLIF, and 36.1% (22/61) of the laminectomy patients. The secondary fusion rate among ELD patients was 8.8% (18/206). Among TLIF patients, the most common additional treatments were revision fusion (19.2%; 15/78) and multilevel rhizotomy (10.3%; 8/78). Common follow-up procedures in laminectomy patients included revision laminectomy (16.4%; 10/61), revision ELD (11.5%; 7/61), and multilevel rhizotomy (11.5%; 7/61). Control patients crossed over into ELD (13.4%), TLIF (13.4%), laminectomy (10.4%) and interventional treatment (40.3%) arms at high rates. Most control patients treated with spinal injections (55.5%) had excellent and good functional outcomes versus 40.7% with fair and poor (3.7%), respectively. The control patients (93.3%) who remained in medical management without surgery or interventional care (14/67) had the worst functional outcomes and were rated as fair and poor. Conclusions: clinical outcomes were more favorable with lumbar surgeries than with non-surgical control groups. Of the control patients, the crossover rate into interventional and surgical care was 40.3% and 37.2%, respectively. There are longer symptom-free intervals after targeted ELD than with TLIF or laminectomy. Additional intervention and surgical treatments are more often needed to manage new-onset postoperative symptoms in TLIF- and laminectomy compared to ELD patients. Few ELD patients will require fusion in the future. Considering the rising cost of surgical spine care, we offer SpineScreen as a simplified and less costly alternative to traditional image-based care models by focusing on primary pain generators rather than image-based criteria derived from the preoperative lumbar MRI scan. [ABSTRACT FROM AUTHOR]

Seven prospective real-world studies conducted in general practices in Belgium of antihypertensive treatment with valsartan-centric regimens were pooled to examine similarities and differences in determinants of blood pressure (BP) values (mmHg) and BP control rates between female and male patients. Pooled analysis of a total evaluable sample of 17,044 patients, including 8273 (48.5%) women and 8771 men (51.5%) treated over approximately 90 days with valsartan-centric regimens in second or later line. Hierarchical linear and logistic regressions were applied to identify patient- and physician-related determinants of BP outcomes and a potential physician class effect. Reductions in BP (mmHg) over 90 days were similar for women and men, and so were changes in BP control rates. Approximately a quarter of the variance in 90 day BP values was attributable to a physician class effect. Both gender groups shared some patient- and physician-related determinants of BP outcomes, though often varying in degree of influence. Analyses also revealed gender-specific determinants. Among others, modifiable/manageable patient-related determinants included BP at hypertension diagnosis (proxy for time of diagnosis), risk factors, antihypertensive treatment and adherence; while among the physician-related determinants clinical experience in hypertension treatment was modifiable/manageable. Valsartan-centric treatment regimens are associated with significant reductions in BP level and improvement in BP control in both women and men. The determinants revealed in modeling provide guidance to clinicians in the common and differential management of hypertension in female and male patients. [ABSTRACT FROM AUTHOR]

Background: Severe asthma affects 5–10% of the 350 million people with asthma worldwide. Findings from the authors' previous meta-analysis supported omalizumab use as an adjuvant treatment for severe allergic asthma. The publication of fourteen new articles necessitates an update of the meta-analysis. Objective: To evaluate the 'real-world' effectiveness of omalizumab in the treatment of acute allergic asthma in adults by calculating pooled effects estimates from data in published articles. Methods: Articles on omalizumab effectiveness in 'real-world' settings were identified. Effect sizes, including point estimates of the proportion of patients who met a given criteria, mean improvements relative to baseline, and change in the proportion of patients requiring oral corticosteroids compared to baseline were extracted. Meta-analysis of proportions was conducted to pool effect sizes based on proportions. Standardized mean differences (Hedges' g) were calculated from means and standard deviations. Relative risk was calculated from changes in proportions. Variability within and between studies was evaluated. Results: Omalizumab increases the percentage of individuals rated 'good' or 'excellent' on the Global Evaluation of Treatment Effectiveness Scale. Omalizumab also improves respiratory function, quality-of-life, and asthma control while reducing medication usage, exacerbations, hospitalizations, and adverse events. Conclusion: 'Real-world' evidence continues to support the use of omalizumab as adjuvant treatment for severe allergic asthma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate long-term, real-world treatment patterns and outcomes of ranibizumab 0.5 mg for neovascular age-related macular degeneration (nAMD) in a Belgian cohort. Patients and Methods: This Belgian (BE) cohort of the 5-year global observational LUMINOUS study included 229 patients with nAMD. Outcomes included visual acuity (VA), central retinal thickness (CRT) and safety. Results: The mean age was 79.5± 7.7 years. The majority of patients (67.7%) were female and all patients were Caucasian. Most patients previously received ranibizumab with only 17.5% of patients being treatment-naïve. The injection frequency declined over time irrespective of prior treatment status (p< 0.0001), with treatment-naïve eyes receiving a mean of 4.2± 2.9 yearly injections and prior-ranibizumab eyes 3.6± 2.7. Regression analysis confirmed first-year VA increases for treatment-naïve eyes (p=0.002) followed by a slight decrease of − 1.8 letters per year. For prior-ranibizumab eyes, the visual changes over 1 year were statistically non-significant (p=0.90) but declined slightly after year one (p< 0.0001). Anatomically, the CRT of treatment-naïve eyes decreased over time from baseline (p< 0.0001), whereas the CRT of prior-ranibizumab eyes remained stable (p=0.43). No new safety findings were identified. Conclusion: LUMINOUS-BE reconfirms the well-characterized benefit-risk profile of ranibizumab for nAMD treatment. The observed low injection frequency reflects a need for more rigorous treatment in real-world settings. Clinical Trial Registration: NCT01318941. [ABSTRACT FROM AUTHOR]

Background: Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration.Objective: To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer.Methods: Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim.Results: A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group.Limitations: The study was retrospective in design and utilized a historical control for the comparator.Conclusions: Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI. [ABSTRACT FROM AUTHOR]

Background: Both typical and atypical bacteria can cause community-acquired pneumonia (CAP); however, the need for empiric atypical coverage remains controversial. Our objective was to evaluate the impact of antibiotic regimens with atypical coverage (a fluoroquinolone or combination of a macrolide/doxycycline with a β-lactam) to a regimen without atypical antibiotic coverage (β-lactam monotherapy) on rates of clinical failure (primary endpoint), mortality, bacteriologic failure, and adverse events, (secondary endpoints).Methods: We searched the PubMed, EMBASE and Cochrane Library databases for relevant RCTs of hospitalized CAP adults. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model, but used a random-effects model if significant heterogeneity (I 2 ) was observed.Results: Five RCTs with a total of 2011 patients were retained. A statistically significant lower clinical failure rate was observed with empiric atypical coverage (RR, 0.851 [95% CI, 0.732-0.99; P = 0.037]; I 2  = 0%). The secondary outcomes did not differ between the two study groups: mortality (RR = 0.549 [95% CI, 0.259-1.165, P = 0.118], I 2  = 61.434%) bacteriologic failure (RR = 0.816 [95% CI, 0.523-1.272, P = 0.369], I 2  = 0%), diarrhea (RR = 0.746 [95% CI, 0.311-1.790, P = 0.512], I 2  = 65.048%), and adverse events requiring antibiotic discontinuation (RR = 0.83 [95% CI, 0.542-1.270, P = 0.39], I 2  = 0%).Conclusions: Empiric atypical coverage was associated with a significant reduction in clinical failure in hospitalized adults with CAP. Reduction in mortality, bacterial failure, diarrhea, and discontinuation due to adverse effects were not significantly different between groups, but all estimates favored atypical coverage. Our findings provide support for the current guidelines recommendations to include empiric atypical coverage. [ABSTRACT FROM AUTHOR]

Purpose: In the MONITOR-GCSF study of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim, 56.6% of patients were prophylacted according to amended EORTC guidelines, but 17.4% were prophylacted below and 26.0% above guideline recommendations.Methods: MONITOR-GCSF is a prospective, observational study of 1447 evaluable patients from 140 cancers centers in 12 European countries treated with myelosuppressive chemotherapy for up to 6 cycles receiving biosimilar GCSF prophylaxis. Patients were classified as under-, correctly-, or over-prophylacted with GCSF relative to guideline recommendations based on their chemotherapy risk, individual risk factors, and type of GCSF prophylaxis (primary versus secondary).Results: Differences between under- (17.4%), correctly- (56.6%), or over-prophylacted (26.0%) groups were found in terms of patient risk factors (age, performance status, history of FN, comorbid conditions) as well as prophylaxis patterns (type of prophylaxis, day of GCSF initiation, and GCSF duration). Rates of chemotherapy-induced neutropenia (CIN) (all grades), FN, and CIN-related hospitalizations were consistently lower in over-prophylacted patients relative to under- and correctly-prophylacted patients. No differences were observed between under- and correctly-prophylacted patients except for CIN/FN-related chemotherapy disturbances. No GCSF safety differences were found between groups (except for headaches).Conclusions: The real-world evidence provided by the MONITOR-GCSF study indicates that providing GCSF support may yield better CIN, FN, and CIN/FN-related hospitalization outcomes if patients are prophylacted at levels above guideline recommendations. Patients who are under-prophylacted are at higher risk for disturbances to their chemotherapy regimens. Our findings support the guideline recommendation that CIN/FN risk be assessed at the beginning of each chemotherapy cycle. [ABSTRACT FROM AUTHOR]

Anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) inhibitors have been shown to significantly improve survival in patients with metastatic cutaneous melanoma. However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta-analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti-CTLA-4 or anti-PD-1 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma. Progression-free survival (PFS) rate at 6 months was 28.5% versus 17.7% (RR: 0.84, 95% CI: 0.76-0.93), overall survival (OS) rate at 1 year was 51.2% versus 38.8% (RR: 0.72, 95% CI: 0.59-0.88), and overall response rate (ORR) at 6 months was 29.6% versus 17.7% (RR: 0.85, 95% CI: 0.76-0.95) favoring immune check point inhibitors over chemotherapies or vaccination. Immune check point inhibitors were associated with more frequent immune-related adverse events at 13.7% versus 2.4% of treated patients (RR: 6.74, 95% CI: 4.65-9.75). Subgroup analyses demonstrated significant PFS (RR: 0.92 vs. 0.74, P < 0.00001) and ORR (RR: 0.95 vs. 0.76, P = 0.0004) improvement with anti-PD-1 treatment compared to anti-CTLA-4 when each of them was compared to control treatments. Collectively, these results demonstrate that immune checkpoint inhibitors have superior outcomes compared to conventional chemotherapies or vaccination, and support the results of recent randomized trials that showed superior outcomes with anti-PD-1 agents over ipilimumab in unresectable metastatic cutaneous melanoma patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio®).Methods: MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio®. Data were analyzed using both the patient and cycle as unit of analysis.Results: Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients.Conclusions: The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: This cost-efficiency analysis of the granulocyte colony-stimulating factors (G-CSF) filgrastim (originator Neupogen® and biosimilar Zarzio®) and pegfilgrastim (Neulasta®) examined against a time horizon of 1–14 days of treatment and across the European Union G5 countries (a) when, cost-wise, using Neulasta® 6 mg versus Neupogen® or Zarzio® 300 µg may be cost-saving in reducing the incidence of chemotherapy-induced febrile neutropenia; and (b) if cost-wise, treatment with Zarzio® 300 µg yields a savings advantage over Neupogen® 300 µg.Methods: Cost-efficiency analysis of the direct costs a buyer or payer would incur when purchasing or covering any of these agents for managing one patient during one cycle of chemotherapy under regimens of 1–14 days of standard filgrastim using the population-weighted average unit dose cost of each agent per their public pack cost across the European G5 countries.Results: The cost of Neupogen® treatment ranged from €128.16 (1 day) to €1794.30 (14 days), compared to €95.46 and €1336.46 for Zarzio®, thus yielding potential cost savings from €32.70 to €457.84 for the latter. Neulasta® turns cost-saving at day 12 of Neupogen® treatment. At no point over a 14-day treatment period did Neulasta® yield a savings advantage over Zarzio®.Conclusion: Prophylaxis or treatment of febrile neutropenia with Zarzio® is cost-efficient under all possible treatment scenarios relative to Neupogen® and to Neulasta®. In the absence of convincing evidence that pegfilgrastim is pharmacotherapeutically superior to standard filgrastim, there is no cost-efficiency rationale to treat with Neulasta® over Zarzio®, though there may be a small window of approximately 3 days where Neulasta® is cost-efficient over Neupogen®. Regardless, our analysis shows Zarzio® to be the most cost-efficient approach to reducing the incidence of febrile neutropenia in chemotherapy-treated patients. [ABSTRACT FROM PUBLISHER]

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Objectives: Several chemoimmunotherapy and targeted treatment regimens are approved as front-line therapies in chronic lymphocytic leukemia. We estimated for the 10-year cost-effectiveness of these treatment regimens and the economic burden of following the estimated risk-stratified 21 040 patients with chronic lymphocytic leukemia diagnosed in 2020 for 10 years.Methods: A Markov model with 7 exclusive health states was specified over a 10-year time horizon. Treatment effectiveness inputs were obtained from a novel network meta-analysis on the progression-free survival, overall survival curves, and time to next treatment. Costs and utilities inputs were included for each health state for each treatment and discounted at 3.0%/year. Life-years (LYs) and quality-adjusted LYs (QALYs) for each treatment were determined. Using the lowest cost regimen as reference, the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were estimated. The 10-year per-patient cost was determined by risk status and by initial treatment.Results: Venetoclax-plus-obinutuzumab was the lowest cost regimen, hence the reference. Superior in effectiveness to all chemoimmunotherapies, it was cost saving. With the highest effectiveness gains at 6.26 LYs and 5.01 QALYs and despite being the most expensive regimen ($1 298 638 per patient), acalabrutinib-plus-obinutuzumab yielded the best ICER ($409 343/LY gained) and ICUR ($501 236/QALY gained). The remaining ICERs of targeted therapies ranged from $512 101/LY gained to $793 236/LY gained and the ICURs from $579 737/QALY gained to $869 300/QALY gained. The 10-year postdiagnosis low/high (venetoclax-plus-obinutuzumab/acalabrutinib-plus-obinutuzumab) economic burden ranges were $42 690 to $98 665 for low-risk, $141 339 to $326 660 for intermediate-risk, and $273 650 to $632 453 for high-risk patients.Conclusions: Compared with venetoclax-plus-obinutuzumab, chemoimmunotherapies are associated with less health benefits at higher cost. The targeted therapies achieve greater benefits at higher cost. [ABSTRACT FROM AUTHOR]