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We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC. [ABSTRACT FROM AUTHOR]

The treatment of osteoarticular infections in pediatric patients with sickle cell disease (SCD) is a challenging task for the practitioner. The aim of this study is to evaluate cefixime for the treatment of osteoarticular infections in pediatric SCD patients by retrospective design. This study was done in the pediatric hospital of King Saud Medical City, Riyadh, Saudi Arabia. The data was obtained from medical records of patients aged 1–16 years admitted between January 2019 to December 2020, diagnosed with SCD and received cefixime for the treatment of OI. A descriptive study for pediatric patients admitted between January 2019 to December 2020 diagnosed with sickle cell disease and diagnosed with osteoarticular infection. All patients were treated with cefixime. Medians and interquartile ranges (IQRs) were used for the descriptive analysis. A total of 260 patients were screened, and 51 cases [osteomyelitis (OM), n = 43, and septic arthritis (SA), n = 8] met the inclusion criteria. The median age of OM patients was 7 years, with males making up 67.4% of the cohort. The median length of IV antibiotics and hospital stays were 10 days and 11 days, respectively. The median total duration of antibiotic use was 37 and 25 days for OM and SA, respectively. The treatment success rate was 88% in OM cases and 100% in SA patients. Readmission was noted in 39.5% of the OM patients, while only 25% of the SA patients were recorded for reinfection. The study's findings revealed that Cefixime is a viable oral alternative for treating osteoarticular infection in pediatric SCD patients. Nonetheless, a prospective investigation is required to corroborate the findings of this study. [ABSTRACT FROM AUTHOR]

The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32–20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88–15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15–10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0−14.54]. These results were confirmed in the PSM and IPSW analyses. In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care. [ABSTRACT FROM AUTHOR]

We conducted this systematic review and meta-analysis to evaluate the impact of obstructive sleep apnea (OSA) on gut barrier dysfunction as represented by the following biomarkers: zonulin, lipopolysaccharide, lipopolysaccharide binding protein, intestinal fatty acid binding protein, and lactic acid. A comprehensive search of the literature was conducted in Ovid MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov without language restrictions from inception to October 2022. The analysis of all outcomes was performed using a random-effects model. We included eight studies (seven cross sectional and one case control) in the final quantitative synthesis with a total of 897 patients. We concluded that OSA was associated with higher levels of gut barrier dysfunction biomarkers [Hedges' g = 0.73 (95%CI 0.37–1.09, p < 0.01). Biomarker levels were positively correlated with the apnea-hypopnea index [r = 0.48 (95%CI 0.35–0.6, p < 0.01)] and oxygen desaturation index [r = 0.30 (95%CI 0.17–0.42, p < 0.01)], and negatively correlated with the nadir oxygen desaturation values [r = −0.45 (95%CI - 0.55 – - 0.32, p < 0.01). Our systematic review and meta-analysis suggests that OSA is associated with gut barrier dysfunction. Furthermore, OSA severity appears to be correlated with higher biomarkers of gut barrier dysfunction. CRD42022333078. [ABSTRACT FROM AUTHOR]

Background: Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio®) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients. Methods: Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level. Results: There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72 h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes. Conclusion: Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG ≥ 2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with lower rates of adverse CIN/FN events in elderly and non-elderly patients, and should be further evaluated in prospective randomized trials. [ABSTRACT FROM AUTHOR]

Background Evidence is needed on the clinicometric properties of single-item or short measures as alternatives to comprehensive measures. Objectives We examined whether two single-item fatigue measures (i.e., Likert scale, numeric rating scale) or a short fatigue measure were comparable to a comprehensive measure in reliability (i.e., internal consistency and test–retest reliability) and validity (i.e., convergent, concurrent, and predictive validity) in Korean young adults. Methods For this quantitative study, we selected the Functional Assessment of Chronic Illness Therapy–Fatigue for the comprehensive measure and the Profile of Mood States–Brief, Fatigue subscale for the short measure; and constructed two single-item measures. A total of 368 students from four nursing colleges in South Korea participated. We used Cronbach’s alpha and item-total correlation for internal consistency reliability and intraclass correlation coefficient for test–retest reliability. We assessed Pearson’s correlation with a comprehensive measure for convergent validity, with perceived stress level and sleep quality for concurrent validity and the receiver operating characteristic curve for predictive validity. Results The short measure was comparable to the comprehensive measure in internal consistency reliability (Cronbach’s alpha = 0.81 vs. 0.88); test–retest reliability (intraclass correlation coefficient = 0.66 vs. 0.61); convergent validity ( r with comprehensive measure = 0.79); concurrent validity ( r with perceived stress = 0.55, r with sleep quality = 0.39) and predictive validity (area under curve = 0.88). Single-item measures were not comparable to the comprehensive measure. Conclusions A short fatigue measure exhibited similar levels of reliability and validity to the comprehensive measure in Korean young adults. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the real-world effectiveness of vildagliptin and vildagliptin/metformin, combined with patient engagement, on glycemic outcomes. Patient engagement included both clinicians' engaging patients through education and counseling; and patients' self-engagement through disease awareness, lifestyle changes, and medication adherence.Methods: Prospective, observational, open-label, multi-center, pharmacoepidemiologic study of type 2 diabetes mellitus (T2DM) patients treated de novo with vildagliptin or vildagliptin/metformin. Data were collected at baseline (treatment initiation), 105±15d, and ≥145d.Results: The evaluable sample included 896 mainly male (58%), overweight (mean±SD BMI=30.3±5.4kg/m(2)), in later middle age (mean±SD age=64±11years) patients. Over the three visits, mean(±SD) HbA1c levels declined from 8.1%(±1.0) to 7.3%(±1.0) to 7.2%(±0.9); HbA1c control rates rose from 7% to 36% to 43%. Mean±SD FPG levels decreased from 170(±49) to 141(±41) to 139(±42)mg/dL; control rates increased from 12% to 39% to 43% (all p<0.0001). Weight decreased nominally by 2kg (p=0.0290) and BMI by 0.8kg/m(2) (p<0.0001). Modeling showed patient engagement activities by clinicians and by patients to be major determinants of glycemic outcomes. No unknown safety signals were detected.Conclusions: Vildagliptin and vildagliptin/metformin are effective and safe oral agents in the management of T2DM, especially if part of a treatment program with active patient engagement by clinicians and empowered patients. [ABSTRACT FROM AUTHOR]

Background Integrating long depression-screening instruments into routine clinical practice and research studies is often impractical, necessitating short-item if not single-item measures with comparable psychometric properties. Objective To examine whether single-item or short depression-screening measures are comparable to a comprehensive screening measure in reliability (i.e., internal consistency and test–retest reliability) and validity (i.e., convergent, concurrent, and predictive validity) in Korean young adults within a Classical Testing Theory framework. Method A total of 458 students from six nursing colleges in South Korea completed three depression measures: the 20-item Center for Epidemiologic Studies-Depression screening instrument (CES-D; comprehensive measure); the five-item Profile of Mood States-Brief depression subscale (POMS-B depression subscale; short measure); a single-item Likert measure; and a single-item numeric rating scale. Internal consistency reliability was tested by Cronbach's alpha and item-total correlations; test–retest reliability by intraclass correlation coefficient (ICC); convergent validity by correlation with the CES-D; concurrent validity by the correlation with perceived stress level and sleep quality; and predictive validity by receiver operating characteristic curve to predict the two groups with different depression levels. Results The POMS-B depression subscale was comparable to the comprehensive CES-D scale in internal consistency reliability (alpha = .85); test–retest reliability (ICC = .76); and convergent ( r = .81 with CES-D), concurrent ( r = .64 with perceived stress level, r = .34 with sleep quality), and predictive validity (area under the curve = .88). The two single-item options were not comparable to the comprehensive CES-D. Conclusion The short POMS-B depression subscale shows an acceptable balance between practical clinical and research needs and psychometric quality. [ABSTRACT FROM AUTHOR]

This meta-analysis with longitudinal prospective cohort studies aimed to (a) determine whether chemotherapy is associated with time-dependent subjective cognitive impairment outcomes in breast cancer patients, and (b) identify the time point with the highest impact of chemotherapy on subjective cognitive impairment. Data were gathered from PubMed, EMBASE, CINAHL, PsycInfo, and the Cochrane Library. The mean differences of the subjective cognitive impairment level between the chemotherapy-treated patients and controls (patients not treated by chemotherapy and healthy subjects) were calculated using effect sizes (Hedges' g) by clinical time periods. The five clinical time periods were (a) baseline, (b) during chemotherapy, (c) within 1 month postchemotherapy, (d) within 1 year postchemotherapy, and (e) 1 year or longer postchemotherapy. Longitudinal data from nine data sets from 13 studies were pooled and analyzed. At baseline, chemotherapy-treated patients showed slightly better subjective cognitive impairment compared to patients not treated by chemotherapy and did not differ from healthy controls. Yet, the chemotherapy-treated patients had significantly worse subjective cognitive impairment compared to both type of controls after initiating chemotherapy. The effect sizes for the group differences were larger for the group comparison with healthy controls than the nonchemotherapy control (−0.50 vs. −0.19). The largest effects were found within 1 month postchemotherapy (−0.85), suggesting the acute impact of chemotherapy. Chemotherapy is associated with subjective cognitive impairment. The impact of chemotherapy appears to be an acute rather than a chronic side effect. Clinicians must consider including the assessment and management of subjective cognitive impairment in their routine practice. • Subjective cognitive impairment is a frequently occurring, detrimental symptom in cancer patients. • Chemotherapy may be an important contributing factor. Yet, the impact of chemotherapy on subjective cognitive impairment has been inconclusive. • We found chemotherapy impacts patients' subjective cognitive impairment, particularly immediately after the treatment completion. • Clinicians must be aware of the existence of the chemotherapy-associated subjective cognitive impairment and consider including the assessment and management for this symptom in their routine practice. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The Anemia Cancer Treatment study assessed hemoglobin (Hb) outcomes following treatment with erythropoiesis-stimulating agents (ESA) in anemic (Hb≤11g/dL) patients in Europe. We replicated the original analyses stratifying by age, namely patients aged ≥70 (n=637) versus those aged<70 (n=1555). Materials and methods: A secondary analysis of Hb outcomes was assessed over 8–10weeks. Treatment response criteria included increases of Hb≥1g/dL, Hb≥1g/dL over 8weeks, and Hb≥2g/dL over the course of the study period. Results: Mean Hb increased from similar levels of 9.5g/dL [p=not significant (ns)] at visit one to 10.9g/dL (p=ns) at visit three (both p<0.001). Patients aged≥70 had higher mean Hb at visit two (10.6g/dL vs. 10.3g/dL, p<0.001). Cohorts did not differ in treatment response rates (all p=ns). Mean performance status differed between cohorts at each visit (all p≤0.011); both groups showed significant improvements (both p<0.001). Immediacy of response was a consistent determinant but was more pronounced among patients aged≥70. Less consistent determinants included performance status in the age≥70 group, as well as hematological malignancy and Hb at ESA start in the age<70 group. The proportion of variance in Hb outcomes attributable to treatment center ranged from 0.090 to 0.289 in the age≥70 cohort and 0.126 to 0.361 in the age<70 cohort. Conclusions: Both groups achieved similar Hb levels with the age≥70 cohort showing a higher initial evolution rate and potentially a different Hb response trajectory. Patients age≥70 were more likely to benefit from ESAs if showing an early erythropoietic response and exhibiting no or little impairment in performance status. Differential attribution of variability in older vs. younger adults suggests that individualization of ESA therapy may facilitate Hb response in geriatric patients with cancer. [Copyright &y& Elsevier]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Achieving guideline-recommended blood pressure targets is difficult in older adults with hypertension. We completed a subgroup analysis of patients 65 years of age or older enrolled in PREVIEW, a prospective, multicenter, pharmacoepidemiological study of the determinants and outcomes of second-line antihypertensive treatment with valsartan in Belgium. Multilevel modeling was used to identify physician- and patient-level determinants of blood pressure values and practice guideline-derived definitions of blood pressure control. Data on 1560 patients and 504 physicians were used in this analysis. Blood pressure control rates for patients age 65 and over were lower for systolic (34.2% vs. 38.6%) and combined systolic/diastolic blood pressure (31.2% vs. 34.4%) compared to the entire PREVIEW sample. Twenty-seven percent of the variability in systolic, and 32% in diastolic pressure after 90 days of treatment were attributable to such variables as physicians’ knowledge and adherence to evidence-based guidelines, practice patterns, and experience; with the remaining variance attributable to various demographic, behavioral, and clinical patient-related factors. Several independent predictors of uncontrolled blood pressure after 90 days of treatment were identified, largely confirming factors identified as determinants of blood pressure values. Recommendations for managing hypertension in the elderly are made in view of these findings. [Copyright &y& Elsevier]

Abstract: Objectives: This study investigated Belgian hospital nurses’ perceptions on work environment and workforce issues, quality of care, job satisfaction and professional decision making. Methods: All eligible nurses in a selection of 22 hospitals received the BELIMAGE questionnaire for a total of 13,958 potential respondents. Of these, 9941 returned study materials (response rate=71.2%) of which 9638 were valid and useable for statistical analysis (valid response rate=69.1%). Results: The study identified several areas of tension in the nursing profession. The commitment to being competent providers of quality care was remarkably strong among the nurses, but they also perceived the barriers in the work environment to be multiple and complex. Concerns about the quality of leadership and management, insufficient staff, time demands and stressful work environment are experienced as obstacles in providing good nursing care. Four out of ten nurses (39.2%) would not choose nursing again as a career and more than half of the nurses (54.3%) have contemplated leaving the profession at some point in time. Conclusions: To effectively tackle the professional and workforce issues in nursing, investments should focus on redesigning a work environment that supports nurses in providing comprehensive professional care. [Copyright &y& Elsevier]

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]

Abstract: This paper reports data on the professional self-image of 9638 nurses employed in 22 Belgian general hospitals with the goal of identifying problems affecting recruitment and retention. Nurses reported having a positive self-image. Most were proud to be a nurse and considered themselves competent health professionals having great responsibility. Although they reported that an ideal practice requires effective teamwork, supportive management, societal recognition, and sufficient time to perform their duties, they also felt that these essential conditions were absent in daily practice. [Copyright &y& Elsevier]

• Hematologists benefit from knowing how to manage treatment costs and access. • Conversion to prophylaxis with biosimilar GCSF generates significant cost-savings. • Savings can be reallocated budget-neutrally to increase access to treatment. • We simulated savings with biosimilar pegfilgrastim-cbqv in 20,000 patients. • Up to 13,999 additional cycles or 2333 6-cycle regimens of R-CHOP can be purchased. This pharmacoeconomic simulation (1) assessed the cost-efficiency of converting a panel of 20,000 patients at risk of chemotherapy-induced (febrile) neutropenia (CIN/FN) from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv; (2) estimated how savings can be used to provide budget-neutral expanded access to R-CHOP therapy for non-Hodgkin lymphoma patients; and 3) determined the number-needed-to-convert (NNC) to purchase one additional dose of R-CHOP (US payer perspective). Model inputs included biosimilar conversion from pre-filled syringe [PFS] or on-body injector [OBI] reference pegfilgrastim; age-proportional blended costs for reference pegfilgrastim PFS and OBI, pegfilgrastim-cbqv and R-CHOP; medication administration costs; biosimilar conversion rates of 10–100 %; and 1–6 cycles of prophylaxis. Cost-savings were used to estimate the number of doses of R-CHOP that could be purchased and the NNC to purchase one additional dose. Converting a panel of 20,000 patients requiring CIN/FN prophylaxis to biosimilar pegfilgrastim-cbqv from a low of 1 cycle and 10 % conversion to a high of 6 cycles and 100 % conversion yielded savings from $1,567,195 to $96,668,126. The budget-neutral acquisition of R-CHOP doses afforded by these savings ranged from 227 to 13,999 doses, the latter enabling 2333 patients to receive 6 cycles of R-CHOP treatment with no additional cost to the payer. These results are achieved if all 20,000 panel patients requiring GCSF support are prophylacted with biosimilar pegfilgrastim-cbqv for 6 cycles, yielding an NNC of 1.43 patients per additional R-CHOP dose. This simulation underscores the clinic-economic benefit of prophylaxis with biosimilar growth factor and pegfilgrastim-cbqv specifically. [ABSTRACT FROM AUTHOR]

• Second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to limited information comparing the available options and the influence of newly expanding first-line (1L) choices. • Based on overall survival (OS) and progression-free survival (PFS), the combination Lenvatinib+everolimus yielded superior, followed by cabozantinib and lenvatinib monotherapies • Nivolumab and pazopanib had the lowest odds of severe adverse events (SAEs). • The availability of newer front-line combinations of immune-checkpoint inhibitors and tyrosine-kinase inhibitors will influence 2L decision-making. Deciding on the optimal second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to the limited information comparing each of the available options and the influence of the newly expanding first-line (1L) agents. We identified phase II/III randomized controlled trials (RCTs) evaluating 2L treatments in metastatic ccRCC. This Network Meta-analysis (NMA) evaluates the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE). We used normal likelihood model to incorporate log hazard ratios (HRs), odds ratios (OR), and 95%-confidence-intervals (CI). Treatment p-scores were used for ranking. Data was analyzed in a fixed-effects model using the netmeta package in R v.1.5-0. All therapies demonstrated some benefits over placebo. Lenvatinib + everolimus ranked first for OS (HR = 0.44; 95%CI = 0.24–0.82; p-score = 0.92), PFS (HR = 0.13; 95%CI = 0.07–0.24, p-score = 0.98), and ORR (OR = 35.95; 95%CI = 11.55–111.87; p-score = 0.93) compared to placebo, though with a higher SAE (OR = 5.27; p-score = 0.23). Cabozantinib ranked second for OS (HR = 0.57, p-score = 0.80), PFS (HR = 0.19; p-score = 0.86), and ORR (OR = 27.24, p-score = 0.84). Nivolumab was third for ORR (p-score = 0.79), fourth for OS (p-score = 0.69), fifth for PFS (p-score = 0.61), and last for SAE (p-score = 0.83). Lenvatinib monotherapy ranked worst SAE (OR = 5.89, p-score = 0.17) and third for OS and PFS. The latest drug, tivozanib, was sixth for PFS, OS, and ORR. The NMA matrix revealed no differential OS benefit between cabozantinib, lenvatinib + everolimus, and nivolumab. Other regimens had no significant OS benefit when compared to placebo. Based on OS and PFS, the lenvtatinib + everolimus combination yielded superior, followed by cabozantinib and Lenvatinib monotherapies; all were limited by a worse SAE profile. Nivolumab and pazopanib had the lowest odds of SAEs. [ABSTRACT FROM AUTHOR]

Significant progress has been made in the prevention and management of hypercoagulation. Unfractionated heparin (UF) and low molecular weight heparin (LMWH) are indicated for acute cerebral vein thrombosis with or without intracranial hemorrhage (ICH). A recent meta-analysis of four trials comparing UF and LMWH aimed to evaluate the efficacy and safety of both agents in terms of disability, intracranial hemorrhage, and mortality. However, several methodological aspects of the meta-analysis warrant further discussion. It appears that the disability outcome was not sufficiently harmonized by design or statistical standardization, some inputs could not be validated, incorrect statistical analyses were performed, major results could not be replicated, and conclusions were not supported by the statistical results. The conclusion of a statistically significant reduction in mortality is not supported by the data. • Disability scales were not harmonized or standardized. • Unable to replicate findings of mortality and disability. • Incorrect statistical analysis by selecting random effect model. • Non-significant heterogeneity shouldn't be used as surrogate for model selection. • Conclusion couldn't be supported by statistical results. [ABSTRACT FROM AUTHOR]

• Plerixafor is approved for CD34+ cell mobilization, but cost considerations limit its routine use. • Our center needed to improve collection efficiency to enhance apheresis resource utilization. • Plerixafor was administered to all myeloma patients undergoing mobilization. • This change resulted in improved collection efficiency without increasing overall costs. The stem cell mobilization agent plerixafor significantly improves CD34+ stem cell procurement in patients with multiple myeloma undergoing autologous stem cell transplant. We compared mobilization success rates and costs of two regimens of plerixafor administration: pre-emptive (P-PL, initiated the evening prior to the first day of stem cell collection) and standard (S-PL, initiated the evening prior to the second day of stem cell collection in the event of inadequate collection on the first day). Patients with multiple myeloma undergoing mobilization were categorized as either P-PL or S-PL. Stem cell collection success was evaluated using logistic regression models. Associated costs were aggregated in terms of average collections per patient in each mobilization option (patient level), and escalated to a panel of 5000 patients (population level). 299 patients were evaluable; 241 received P-PL and 58 received S-PL. Patients receiving P-PL had higher median CD34+ count pre-collection and higher median total CD34+ cell harvest on the first collection (6.75 × 106/kg for P-PL, 1.96 × 106/kg for S-PL; P< 0.01). In multivariable analyses, P-PL remained significantly associated with the ability to collect ≥2 × 106/kg CD34+ on the first day (OR = 4.05, 95% CI, 1.19–13.83, P = 0.03) and ≥5 × 106/kg CD34+ in total (OR = 3.09, 95% CI, 1.04–9.23, P = 0.04). P-PL saved $11,248 (46%) per patient compared with S-PL. P-PL significantly enhanced collection efficiency, with most patients completing collection in 1 day, resulting in substantial cost savings. [ABSTRACT FROM AUTHOR]

This study examined (a) whether there are a subgroup of cancer patients experiencing the selected psycho-neurological symptoms as a cluster (depression, cognitive impairment, fatigue, sleep disturbance, and pain); (b) whether demographic and clinical characteristics and pro-inflammatory cytokines (IL-1α, IL-1β, IL-4, IL-6, TNF-alpha) are associated with subgroup membership; and (c) whether the activity of indolamine-2.3 dioxygenase(IDO) is associated with pro-inflammatory cytokine activity and psycho-neurological symptom cluster experience. This was a prospective cohort study where 149 hematologic patients were recruited from a university hospital and 65 healthy volunteers provided control data. Latent profile analyses were conducted to identify subgroups at two time points: the last day of chemotherapy and 1 week after chemotherapy completion. Influencing factors of subgroup membership were examined by logistic regression. A substantial number of patients (33%, 34% at each time point) experienced the selected psycho-neurological symptoms as a cluster. Older age and elevated IL-1α and IL-6 were associated with experiencing the psycho-neurological symptom cluster. IDO activity was higher in the patients experiencing psycho-neurological symptom cluster; and was positively associated with IL-6. Symptom severity, IL-1α, IL-6, and IDO activity were all significantly higher in cancer patients than in the healthy controls. The findings were preserved across time points. The activation of pro-inflammatory cytokines and their cross-talk with IDO may be a common biological mechanism, underlying a psycho-neurological symptom cluster experience. The novel approaches for symptom assessment and management can be developed by assessing multiple psycho-neurological symptoms as a cluster and by targeting their common biological pathway. • Cancer patients experience multiple psycho-neurological symptoms as a cluster. • These co-occurring psycho-neurological symptoms may share a biological mechanism. • Proinflammatory cytokines (IL-1 alpha, IL-6) may be a common biological pathway. • Cross-talk between cytokine and IDO activity is linked with symptom experience. • Alterations in tryptophan catabolite system may be a final pathway. [ABSTRACT FROM AUTHOR]

Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to simulate for the European Union G5 countries the potential cost savings of converting patients from originator granulocyte colony-stimulating factor (G-CSF) filgrastim and pegfilgrastim to a biosimilar filgrastim, to evaluate how reallocating these savings could increase patient access to antineoplastic therapy, and to estimate the number of patients needed to convert to provide antineoplastic treatment to one patient. Methods: Three models were built: (1) to estimate the costs of using originator G-CSFs and the savings generated from switching to a biosimilar G-CSF, (2) to estimate the incremental number of patients who could be provided antineoplastic therapy--rituximab or trastuzumab--in a hypothetical panel of 10,000 patients with cancer, and (3) to calculate the number of patients needed to convert to provide access to anticancer therapy. Scenarios were developed in which the rate of conversion was varied to estimate the effect on total cost savings. This study took the perspective of the payer in the European Union. Findings: The savings associated with the biosimilar filgrastim over the originator filgrastim ranged from €785 (day 4) to €2747 (day 14) and increased with longer duration of therapy. By contrast, the savings associated with the biosimilar filgrastim over pegfilgrastim decreased over time, ranging from €6199 (day 4) to €471 (day 14). In a hypothetical panel of 10,000 patients with cancer, the savings associated with the biosimilar filgrastim over the originator filgrastim and the expanded access to antineoplastic therapy improved over time, irrespective of conversion rates. Conversely, in the same hypothetical panel, the savings associated with the biosimilar filgrastim over pegfilgrastim reduced over time, irrespective of conversion rates, along with the expanded access to antineoplastic treatment. Under conversion of the originator filgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 4 to 14 patients, and the number needed to convert to expand access to trastuzumab ranged from 11 to 38 patients. Under conversion of pegfilgrastim to the biosimilar filgrastim, the number needed to convert to expand access to rituximab ranged from 2 to 24 patients, and the number needed to convert to expand access to trastuzumab ranged from 5 to 63 patients. Implications: Use of biosimilar G-CSFs for supportive cancer care could yield potential cost savings and improve patient access to antineoplastic therapy in a budget neutral way--a financial effect with an ethical perspective. [ABSTRACT FROM AUTHOR]

Abstract: The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio® in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies from the social and behavioral sciences; assesses factors predictive of poor treatment response; and evaluates the congruence of treatment with EORTC guidelines and the approved label. This pan-European study will recruit at least 1000 patients from a minimum of 75 centers and follow them for maximum 6 cycles of chemotherapy. Apart from descriptive and associative procedures, statistical analysis will include variance attribution methods; hierarchical linear, logistic, and Poisson modeling; Kaplan–Meier time-to-event analysis, Mantel–Cox log-rank or generalized Wilcoxon–Breslow tests, and Cox proportional hazards modeling; and clustering and related data mining techniques. [Copyright &y& Elsevier]

Abstract: Background: Hip fractures represent an increasing public health burden with a simple fall to the floor as the most common cause. Because nursing home residents are particularly at risk, nursing homes should implement a broad range of fall prevention strategies. However, not all fall incidents can be avoided and external hip protectors may contribute to prevent hip fractures. A major problem in studying the effectiveness of hip protectors is residents’ poor adherence. In nursing homes, adherence is dependent not only on the resident, but also on staff knowledge of and attitudes about hip protectors. Objectives: To describe (1) attitudes of day versus night shift caregivers towards the use of a soft hip protector, (2) residents’ adherence about the use of such protectors, and (3) differences in characteristics between adherent and non-adherent residents. Design: Survey and observational study. Setting: Nursing home. Participants/methods: : Survey of care staff (n =37) in a nursing home after 8 months of continued application of a soft hip protector policy in residents (n =68). Adherence to wearing the hip protector, measured by weekly unannounced, randomly determined checks during day and night in the 8 months after the start of the study. Results: Overall, 85% agreed to wear a hip protector. At 8 months, only 29% was still wearing their hip protector; with significant differences between day and night shifts. Although virtually all caregivers (97%) considered a hip protector policy in residential care as feasible, the attitude towards hip protectors was found to be significantly different between day and night caregivers. Pain and discomfort, patient insight in the usefulness of these devices, interference with incontinence materials, and the overall resident mix and care acuity were reported as major barriers. Conclusion: Implementing a hip protector policy for injury prevention in long-term care is not an issue of whether or not to use the devices. Rather, it is a continued clinical nursing decision process about when and when not, by whom and by whom not, why and why not, for how long, and to what clinical benefit – considering both the needs of the individual resident and the feasibility of such a policy in the context of resident mix and nursing staff. [Copyright &y& Elsevier]

Background: We have previously examined the professional self-image of practicing nurses in Belgium and its association with various professional decisions, however there is limited knowledge about the professional self-image of nurses-to-be. Despite prior research on nursing students’ perceptions of nursing or their self-esteem, students’ professional image, defined as “the way students perceive themselves in their clinical practice environment and their anticipated work environment”, has not been described nor compared to that of practicing nurses. Objective: To describe the professional nursing self-image among students in their final year of baccalaureate education. Design: Cross-sectional survey. Settings: Nine geographically spread baccalaureate programs in the Flemish region of Belgium. Participants: 427 evaluable students from 455 recruited from 663 potential. Methods: Data collected in each school during regular hours using an adapted version of the BELIMAGE (Belgian professional self-image instrument for hospital nurses) including questions on personal demographics, education and competence, nursing care, team and practice environment. Voluntary participation with returned questionnaire deemed informed consent. Results: Respondents identified several curricular components as contributing to their perceived competence. They also identified several skills deemed important to professional nursing, however did not feel competent in all of these. Important nursing care aspects included individualizing patient care, detecting care problems and potential complications, and promoting patient well-being; within a care environment with open interdisciplinary communication, where care problems could be discussed with nursing colleagues, where one cares for the same patient regularly, and led by a team leader with vision. Society''s view of nursing was generally more negative than students’. Most students planned on working in nursing after their studies and many had thought about additional education at some point. Most were proud of becoming a nurse, would recommend nursing to others, and would choose nursing again as field of study. Conclusions: Students’ evolving professional self-image was positive, rich, and enthusiastic; and higher than that observed in working nurses in a prior study. There is a significant gap between nursing care aspects deemed important and perceived competence in these areas, which has implications for both educators and future employers. Once employed, students are likely to experience differences in their perceptions of professional self-image with those of senior colleagues; another area of attention for employers. [Copyright &y& Elsevier]

Abstract: Objectives: To examine anaemia management in cancer patients treated with erythropoiesis-stimulating agents (ESAs) in Europe. Methods: Retrospective pharmacoepidemiologic study of 2192 patients from 307 centres. Minimum of 3 visits over 8–10weeks with ESA treatment initiated at visit 1. Results: Most patients were treated per guidelines, except for low iron supplementation rates. Mean Hb rose from 9.54±0.95g/dl to 10.88±1.49g/dl at visit 3, without concomitant rise in WHO/ECOG score. Response rates were 65.0% (Hb increase ↑⩾1g/dl); 54.3% (Hb increase ↑⩾1g/dl in 8weeks); 38.9% (haematopoietic response); 33.7% (Hb increase ↑⩾2g/dl) and 18.8% (Hb between12.0 and 12.9g/dl) Conclusions: Treatment patterns were guideline congruent, except for (intravenous) iron supplementation. Hb increased by 1.34g/dl. A net erythropoiesis boost of Hb⩾1g/dl is attainable in two-thirds of patients and should be condensed to 8weeks on an individual patient basis. Anaemia management in Europe has improved significantly. The general effectiveness and relative safety of judicious ESA treatment are evident. [Copyright &y& Elsevier]

Abstract: Purpose: To model the relationship between scores for practicing in congruence (CSs; 0–10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system. Methods: Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs. Results: A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R 2 =0.40) and 0.56g/dL increase in Hb change from month 1–4 (R 2 =0.33). Each one-point increase in CS increased the odds of reaching Hb⩾11g/dL by 3.14 (R 2 =0.42) and Hb⩾12g/dL by 2.77 (R 2 =0.45). Conclusion: Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary. [Copyright &y& Elsevier]

• Imatinib is an unforgiving drug with virtually no margin for non-adherence. • Compared to 90 %, 100 % adherence is associated with 2-fold increase in achieving optimal response. • Clinicians must assess and promote patient adherence. • Patients must be perfectly adherent to maximize chance of optimal response. Although adherence to imatinib is critical for attaining treatment responses in chronic myeloid leukemia, there is evidence of varying adherence among patients. Our aim was to model and determine the margin of tolerance, if any, required to ensure treatment responses among patients prescribed imatinib before treatment response is at risk. We performed post hoc analyses of the ADAGIO study conducted in Belgium on 169 evaluable patients (Blood 2009). Applying Kaplan-Meier methods using adherence instead of the conventional time variable, we modeled the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) response as a function of 90-day pill count adherence. Analyses showed that ∼100 % adherence of prescribed dose is associated with probabilities of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90 % adherence. Increasing intake of imatinib from 90 % to 100 % of the prescribed dose increased the likelihood of the various treatment responses by 1.95–2.35-fold. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response. [ABSTRACT FROM AUTHOR]

Abstract: The 2006 EORTC guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. Considering general concerns in medicine about clinicians’ adoption of evidence-based guidelines, it is critical to find ways of bringing guidelines to the point of care. We describe the rationale behind RESPOND, a web-based clinical guidance system based on the EORTC guidelines, and the methodologies of two studies conducted to validate the system. In a first descriptive study, experts are asked to rate the accuracy of every algorithm derived from the guidelines. In a second step and using a hybrid matched pre-post design, separate retrospective and prospective patient cohorts matched by type of cancer and similarity of chemotherapy regimen (33 pairs) are used to examine the extent to which clinicians’ practice patterns converge with the EORTC guidelines when they use or not use the RESPOND system. It is hypothesized that these studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool. [Copyright &y& Elsevier]

This study evaluated content validity, internal consistency and construct validity of the Strain of Care for Delirium Index (SCDI), a newly constructed instrument to measure the strain nurses experience in caring for patients with delirium.Content validity, evaluated by eight experts, reduced the initial pool of items from 38 to 28. Using a convenience sample of 190 nurses, Cronbach''s α for the 28-item version was 0.88. Using non-linear principal components analysis another eight items were eliminated and a four-factor structure was identified. The proportion of variance explained by the remaining 20 items was 61.51%.Preliminary psychometric evaluation of the SCDI supported content validity, internal consistency and construct validity; however additional psychometric evaluation is warranted. [Copyright &y& Elsevier]

Abstract: The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of biosimilar filgrastim in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. The background and methodology of this study are described in an article published concurrently in this journal. As important amendments have been made to the protocol, and the purpose of the prior article was to serve as a resource for future referencing, we detail these amendments in this present article: explicit statement about the use of biosimilar filgrastim for both primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia in the objectives and methodology of the study; length of observation; the addition of stage III and stage IV ovarian cancer and multiple myeloma to the tumor types studied; and the deletion of dose dense chemotherapy regimens as an exclusion criterion. [Copyright &y& Elsevier]

• AML-MRC patients express dynamic ranges of MYC oncoprotein. • High MYC expression is associated with inferior survival in the AML-MRC patients. • High MYC level is associated with higher rates of TP53 and DNMT3A mutations. MYC is an oncoprotein that coordinates the expression of genes involved in metabolism, cell differentiation and survival in various types of malignancies. However, the underlying oncogenic mechanisms and the clinical significance of MYC expression in the acute myeloid leukemia with myelodysplasia related changes (AML-MRC) remain to be answered. A total of 135 patients were retrospectively identified using Total Cancer Care (TCC) Moffitt Cancer Center (MCC) databases. Diagnosis of AML-MRC was based on the 2016 WHO classification utilizing bone marrow (BM) evaluation. MYC protein expression level was assessed by immunohistochemistry (IHC) staining using paraffin-embedded BM trephine biopsy samples obtained at the time of diagnosis or relapse. Concurrent somatic mutations were assessed using targeted next generation sequencing that include 54 genes. A total of 38% (n = 51) and 62% (n = 84) patients had high and low MYC expression, respectively. The most common somatic mutation in our cohort was TP53 followed by DNMT3A, and ASXL1. The median OS was significantly longer in low MYC patients (median OS 42.3 vs. 17.05 months, p = 0.0109). Multivariate analysis including MYC expression level, transplantation status, gender and age demonstrated high MYC expression (HR 1.77, 95% CI 1.004–3.104, p = 0.045) to be an independent poor prognostic factor. Further studies are needed to identify the underlying mechanism of MYC driven oncogenesis in AML-MRC. Additionally, the prognostic impact of MYC on the AML survival in a larger cohort that include diverse somatic mutations and chromosomal abnormalities requires further investigation. [ABSTRACT FROM AUTHOR]