Factors Associated With Physical Inactivity of Recipients of a Kidney Transplant: Results From the ADHERE BRAZIL Multicenter Study.

OBJECTIVE: Physical activity is recommended for recipients of a kidney transplant. However, ADHERE BRAZIL study found a high prevalence (69%) of physical inactivity in Brazilian recipients of a kidney transplant. To tackle this behavior, a broad analysis of barriers is needed. This study aimed to identify factors (patient and transplant center levels) associated with physical inactivity among recipients of a kidney transplant. METHODS: This was a subproject of the ADHERE BRAZIL study, a cross-sectional, multicenter study of 1105 recipients of a kidney transplant from 20 kidney transplant centers. Using a multistage sampling method, patients were proportionally and randomly selected. Applying the Brief Physical Activity Assessment questionnaire, patients were classified as physically active (≥150 min/wk) or physically inactive (<150 min/wk). On the basis of an ecological model, 34 factors associated with physical inactivity were analyzed by sequential logistic regression. RESULTS: At the patient level, physical inactivity was associated with smoking (odds ratio = 2.43; 95% CI = 0.97-6.06), obesity (odds ratio = 1.79; 95% CI = 1.26-2.55), peripheral vascular disease (odds ratio = 3.18; 95% CI = 1.20-8.42), >3 posttransplant hospitalizations (odds ratio = 1.58; 95% CI = 1.17-2.13), family income of >1 reference salary ($248.28 per month; odds ratio = 0.66; 95% CI = 0.48-0.90), and student status (odds ratio = 0.58; 95% CI = 0.37-0.92). At the center level, the correlates were having exercise physiologists in the clinical team (odds ratio = 0.54; 95% CI = 0.46-0.64) and being monitored in a teaching hospital (undergraduate students) (odds ratio = 1.47; 95% CI = 1.01-2.13). CONCLUSIONS: This study identified factors associated with physical inactivity after kidney transplantation that may guide future multilevel behavioral change interventions for physical activity. IMPACT: In a multicenter sample of recipients of a kidney transplant with a prevalence of physical inactivity of 69%, we found associations between this behavior and patient- and center-level factors. At the patient level, the chance of physical inactivity was positively associated with smoking, obesity, and patient morbidity (peripheral vascular disease and hospitalization events after kidney transplantation). Conversely, a high family income and a student status negatively correlated with physical inactivity. At the center level, the presence of a dedicated professional to motivate physical activity resulted in a reduced chance of physical inactivity. A broad knowledge of barriers associated with physical inactivity can allow us to identify patients at a high risk of not adhering to the recommended levels of physical activity.

How external and agency characteristics are related to coordination in homecare - findings of the national multicenter, cross-sectional SPOTnat study.

BACKGROUND: Homecare client services are often distributed across several interdependent healthcare providers, making proper care coordination essential. However, as studies exploring care coordination in the homecare setting are scarce, serious knowledge gaps exist regarding how various factors influence coordination in this care sector. To fill such gaps, this study's central aim was to explore how external factors (i.e., financial and regulatory mechanisms) and homecare agency characteristics (i.e., work environment, workforce, and client characteristics) are related to care coordination in homecare. METHODS: This analysis was part of a national multicentre, cross-sectional study in the Swiss homecare setting that included a stratified random sample of 88 Swiss homecare agencies. Data were collected between January and September 2021 through agency and employee questionnaires. Using our newly developed care coordination framework, COORA, we modelled our variables to assess the relevant components of care coordination on the structural, process, and outcome levels. We conducted both descriptive and multilevel regression analyses-with the latter adjusting for dependencies within agencies-to explore which key factors are associated with coordination. RESULTS: The final sample size consisted of 1450 employees of 71 homecare agencies. We found that one explicit coordination mechanism ("communication and information exchange" (beta = 0.10, p <.001)) and four implicit coordination mechanisms-"knowledge of the health system" (beta = -0.07, p <.01), "role clarity" (beta = 0.07, p <.001), "mutual respect and trust" (beta = 0.07, p <.001), and "accountability, predictability, common perspective" (beta = 0.19, p <.001)-were significantly positively associated with employee-perceived coordination. We also found that the effects of agency characteristics and external factors were mediated through coordination processes. CONCLUSION: Implicit coordination mechanisms, which enable and enhance team communication, require closer examination. While developing strategies to strengthen implicit mechanisms, the involvement of the entire care team is vital to create structures (i.e., explicit mechanisms) that enable communication and information exchange. Appropriate coordination processes seem to mitigate the association between staffing and coordination. This suggests that they support coordination even when workload and overtime are higher.

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis.

Importance: Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed. Objective: To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery. Data Sources: MEDLINE, EMBASE, and CINAHL from inception to May 2020. Study Selection: Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020. Data Extraction and Synthesis: Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data. Main Outcomes and Measures: The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD. Results: A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index <18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for >10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72). Conclusions and Relevance: In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.

Randomized clinical trial to evaluate a cancer pain self-management intervention for outpatients.

Objective: Unrelieved pain is common in patients with advanced cancer. Although psychoeducational interventions were found to decrease pain, effects were moderate. The purpose of this study was to evaluate the efficacy of a pain self-management intervention compared with usual care and to explore participants' experiences with pain management and study participation. Methods: A multicenter randomized controlled trial design with post-trial interviews was used. Outpatients with cancer pain and their family caregivers were recruited from three Swiss university hospitals. The intervention group (IG) received the six-week intervention consisting of education, skills building, and nurse coaching. The control group (CG) received usual care. Outcome variables were analyzed using multilevel models. Interpretive description guided the qualitative study part. Results: Twenty-one patients with advanced cancer and seven family caregivers completed the study. The group x time effect showed a statistically significant decrease in average pain (P â€‹= â€‹0.04), but no significant group x time effect for worst pain (P â€‹= â€‹0.06). Pain scores, pain-related knowledge, Pain Management Index, self-efficacy, and performance status improved in the IG (P â€‹< â€‹0.05). Almost all of the interviewed participants perceived the pain management diary, tailored intervention sessions, and weekly support as useful. None experienced study participation as burdensome. Conclusions: This study was the first to test the efficacy of a psychoeducational cancer pain self-management intervention in a German-speaking context, with most patients receiving palliative care. Clinicians can recommend the use of pain management diaries. Tailoring interventions to an individual's situation and dynamic pain trajectory may improve patients' pain self-management. Registration number: This study has been registered via ClinicalTrials.gov: NCT02713919.https://clinicaltrials.gov/ct2/show/NCT02713919?term=NCT02713919&draw=2&rank=1.

Risk score for the exclusion of arrhythmic events in arrhythmogenic right ventricular cardiomyopathy at first presentation.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder associated with an increased risk of life-threatening arrhythmias in some patients. Risk stratification remains challenging. Therefore, we sought a non-invasive, easily applicable risk score to predict sustained ventricular arrhythmias in these patients. METHODS: Cohort of Patients who fulfilled the 2010 ARVC task force criteria were consecutively recruited. Detailed clinical data were collected at baseline and during follow up. The clinical endpoint was a composite of recurrent sustained ventricular arrhythmias and hospitalization due to ventricular arrhythmias. Multivariable logistic regression was used to develop models to predict the arrhythmic risk. A cohort including patients from other registries in UK, Canada and Switzerland was used as a validation population. RESULTS: One hundred and thirty-five patients were included of whom 35 patients (31.9%) reached the endpoint. A model consisting of filtered QRS duration on signal-averaged ECG, non-sustained VT (NSVT) on 24 h-ECG, and absence of negative T waves in lead aVR on 12­lead surface ECG was able to predict arrhythmic events with a sensitivity of 81.8%, specificity of 84.0% and a negative predictive value of 95.5% at the first presentation of the disease. This risk score was validated in international ARVC registry patients. CONCLUSION: A risk score consisting of a filtered QRS duration ≥117 ms, presence of NSVT on 24 h-ECG and absence of negative T waves in lead aVR was able to predict arrhythmic events at first presentation of the disease.

Chemotherapy-induced neutropenia/febrile neutropenia prophylaxis with biosimilar filgrastim in solid tumors versus hematological malignancies: MONITOR-GCSF study.

AIM: This study aimed to report patterns of biosimilar filgrastim prophylaxis and outcomes of chemotherapy-induced neutropenia (CIN)/febrile neutropenia (FN) in patients with hematological malignancies or solid tumors. PATIENTS & METHODS: MONITOR-GCSF is a real-world study of 1447 cancer patients receiving CIN/FN prophylaxis with biosimilar filgrastim (solid tumors: 77.2%; hematological malignancies: 22.8%). RESULTS: Differences in prophylaxis intensity and day of initiation relative to guideline recommendations were observed. In hematology patients, higher rates of CIN and FN occurred at cycle level, and rate of FN was higher at patient level (9.1 vs 5.0% in solid tumor patients). CONCLUSION: Adequate GCSF support in hematology and solid tumor patients is important to prevent CIN/FN and related hospitalizations and chemotherapy disturbances.

Outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (Zarzio®) initiated "same-day" (< 24 h), "per-guidelines" (24-72 h), and "late" (> 72 h): findings from the MONITOR-GCSF study.

PURPOSE: Granulocyte colony-stimulating factors (G-CSFs) are indicated for prophylaxis or management of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Guidelines recommend G-CSF 24-72 h following chemotherapy; however, some evidence suggests that G-CSF initiated < 24 h may benefit some patients. METHODS: MONITOR-GCSF was a prospective, observational, multicenter, pan-European study of 1447 chemotherapy-treated patients receiving daily biosimilar (standard) filgrastim (Zarzio®/Zarxio®, filgrastim-sndz, Hexal AG, Sandoz Inc.). In this analysis, cycles were classified as same-day, per-guidelines, or late if G-CSF support was initiated < 24 h, 24-72 h, and > 72 h after chemotherapy. Outcomes included occurrence of CIN of any grade (CIN1/4), grade 3 or 4 (CIN3/4), grade 4 (CIN4), or FN: CIN/FN-related hospitalization or CIN/FN-related chemotherapy disturbance. RESULTS: A total of 5930 chemotherapy cycles from 1423 evaluable patients from MONITOR-GCSF had data for day of G-CSF initiation: 795 cycles (13.4%) classified as same-day, 3320 (56.0%) as per-guidelines, and 1815 (30.6%) as late. Groups did not differ as to CIN1/4 and FN episodes, or CIN/FN-related hospitalizations or chemotherapy disturbances. Patients in the same-day and per-guidelines groups had statistically similar odds of not experiencing any outcomes of interest in any given cycle. Patients in the late group had worse odds of experiencing CIN1/4, CIN3/4, and CIN4 episodes in any given cycle. Proportions of patients reporting clinical events of interest were generally similar. CONCLUSIONS: This real-world evidence indicates that CIN/FN prophylaxis initiated with biosimilar filgrastim within 24-72 h post-chemotherapy is effective and safe. Filgrastim administration on the day of chemotherapy may be appropriate in some patients.

Correlates and outcomes of alcohol use after single solid organ transplantation: A systematic review and meta-analysis.

BACKGROUND: Reviews on alcohol use in transplant recipients focus on liver recipients and their risk of post-transplant rejection, but do not assess alcohol use in kidney, heart, or lung transplant recipients. This systematic review and meta-analysis aims to synthesize the evidence on correlates and outcomes of any alcohol use and at-risk drinking after solid organ transplantation (Tx). METHODS: We searched 4 databases for quantitative studies in adult heart, liver, kidney and lung Tx recipients, investigating associations between post-Tx alcohol use and correlates and/or clinical, economic or quality of life outcomes. Paper selection, data extraction and quality assessment were performed by 2 reviewers independently. A pooled odds ratio (OR) was computed for each correlate/outcome reported ≥5 times. RESULTS: Of the 5331 studies identified, 76 were included in this systematic review (93.3% on liver Tx; mean sample size 148.9 (SD = 160.2); 71.9% male; mean age 48.9 years (SD = 6.5); mean time post-Tx 57.7 months (SD = 23.1)). On average, 23.6% of patients studied used alcohol post-transplant. Ninety-three correlates of any post-Tx alcohol use were identified, and 9 of the 19 pooled ORs were significantly associated with a higher odds for any post-Tx alcohol use: male gender, being employed post-transplant, smoking pre-transplant, smoking post-transplant, a history of illicit drug use, having first-degree relatives who have alcohol-related problems, sobriety <6 months prior to transplant, a history of psychiatric illness, and having received treatment for alcohol-related problems pre-transplant. On average 15.1% of patients had at-risk drinking. A pooled OR was calculated for 6 of the 47 correlates of post-Tx at risk drinking investigated, of which pre-transplant smoking was the only correlate being significantly associated with this behavior. None of the outcomes investigated were significantly associated with any use or at-risk drinking. CONCLUSION: Correlates of alcohol use remain under-investigated in solid organ transplant recipients other than liver transplantation. Further research is needed to determine whether any alcohol use or at-risk drinking is associated with poorer post-transplant outcomes. Our meta-analysis highlights avenues for future research of higher methodological quality and improved clinical care. PROTOCOL REGISTRATION: PROSPERO protocol CRD42015003333.

New-onset obesity after liver transplantation-outcomes and risk factors: the Swiss Transplant Cohort Study.

Weight gain after liver transplantation (LTx) facilitates development of new-onset obesity; however, its risk factors and outcomes are poorly understood. We identified the impact of new-onset obesity on cardiovascular events (CVEs) and patient survival, and risk factors for new-onset obesity. Multiple Cox regression models examined risk factors for CVEs, patient survival, and new-onset obesity in 253 adults (mean age 52.2 ± 11.6 years, male gender 63.6%, mean follow up 5.7 ± 2.1 years). Cumulative incidence of post-LTx CVE was 28.1%; that of new-onset obesity was 21.3%. Regardless of CVE at LTx, post-LTx CVEs were predicted by new-onset obesity [Hazard Ratio (HR), 2.95; P = 0.002] and higher age at LTx (HR, 1.05; P < 0.001). In patients without known pre-LTx CVEs (n = 214), risk factors for post-LTx CVEs were new-onset obesity (HR, 2.59; P = 0.014) and higher age (HR, 1.04; P = 0.001). Survival was not associated with new-onset obesity (P = 0.696). Alcoholic liver disease predicted new-onset obesity (HR, 3.37; P = 0.025), female gender was protective (HR, 0.39; P = 0.034). In 114 patients with available genetic data, alcoholic liver disease (HR, 12.82; P = 0.014) and hepatocellular carcinoma (HR, 10.02; P = 0.048) predicted new-onset obesity, and genetics remained borderline significant (HR, 1.07; P = 0.071). Early introduction of post-LTx weight management programs may suggest a potential pathway to reduce CVE risk.

The international prevalence and variability of nonadherence to the nonpharmacologic treatment regimen after heart transplantation: Findings from the cross-sectional BRIGHT study.

INTRODUCTION: Heart transplant (HTx) recipients need to follow a complex therapeutic regimen. We assessed the international prevalence and variability in nonadherence to six nonpharmacologic treatment components (physical activity, sun protection, diet, alcohol use, nonsmoking, and outpatient follow-up visits). METHODS: We used self-report data of 1397 adult HTx recipients from the 36-HTx-center, 11-country, 4-continent, cross-sectional BRIGHT study (ClinicalTrials.gov ID: NCT01608477). The nonadherence definitions used were as follows: Physical activity: <3 times/wk 20 minutes' vigorous activity, <5 times/wk 30 minutes' moderate activity, or <5 times/wk a combination of either intensity; Sun protection: not "always" applying any sun protection; Diet: not "often" or "always" following recommended diet(s); Alcohol use: >1 alcoholic drink/d (women) or >2 drinks/d (men); Smoking: current smokers or stopped <1 year before; Follow-up visits: missing ≥1 of the last 5 outpatient follow-up visits. Overall prevalence figures were adjusted to avoid over- or underrepresentation of countries. Between-country variability was assessed within each treatment component via chi-square testing. RESULTS: The adjusted study-wide nonadherence prevalence figures were as follows: 47.8% for physical activity (95% CI [45.2-50.5]), 39.9% for sun protection (95% CI [37.3-42.5]), 38.2% for diet recommendations (95% CI [35.1-41.3]), 22.9% for alcohol consumption (95% CI [20.8-25.1]), 7.4% for smoking cessation (95% CI [6.1-8.7]), and 5.7% for follow-up visits (95% CI [4.6-6.9]). Significant variability was observed between countries in all treatment components except follow-up visits. CONCLUSION: Nonadherence to the post-HTx nonpharmacologic treatment regimen is prevalent and shows significant variability internationally, suggesting a need for tailored adherence-enhancing interventions.

Multilevel factors are associated with immunosuppressant nonadherence in heart transplant recipients: The international BRIGHT study.

Factors at the level of family/healthcare worker, organization, and system are neglected in medication nonadherence research in heart transplantation (HTx). The 4-continent, 11-country cross-sectional Building Research Initiative Group: Chronic Illness Management and Adherence in Transplantation (BRIGHT) study used multistaged sampling to examine 36 HTx centers, including 36 HTx directors, 100 clinicians, and 1397 patients. Nonadherence to immunosuppressants-defined as any deviation in taking or timing adherence and/or dose reduction-was assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale© (BAASIS© ) interview. Guided by the Integrative Model of Behavioral Prediction and Bronfenbrenner's ecological model, we analyzed factors at these multiple levels using sequential logistic regression analysis (6 blocks). The nonadherence prevalence was 34.1%. Six multilevel factors were associated independently (either positively or negatively) with nonadherence: patient level: barriers to taking immunosuppressants (odds ratio [OR]: 11.48); smoking (OR: 2.19); family/healthcare provider level: frequency of having someone to help patients read health-related materials (OR: 0.85); organization level: clinicians reporting nonadherent patients were targeted with adherence interventions (OR: 0.66); pickup of medications at physician's office (OR: 2.31); and policy level: monthly out-of-pocket costs for medication (OR: 1.16). Factors associated with nonadherence are evident at multiple levels. Improving medication nonadherence requires addressing not only the patient, but also family/healthcare provider, organization, and policy levels.

Are written information or counseling (WOMAN-PRO II program) able to improve patient satisfaction and the delivery of health care of women with vulvar neoplasms? Secondary outcomes of a multicenter randomized controlled trial / Können schriftliche Informationen oder eine Beratung (WOMAN-PRO II Programm) bei Frauen mit vulvären Neoplasien die Patientenzufriedenheit und den Versorgungsprozess verbessern? Sekundäre Outcomes einer multizentrischen randomisiert kontrollierten Studie

Background: Patients with vulvar neoplasms report a lack of information, missing support in self-management and a gap in delivery of health care. Aim: The aim of the study was to investigate if written information or counseling based on the WOMAN-PRO II program are able to improve patient satisfaction and the delivery of health care from the health professional's perspective of women with vulvar neoplasms. Method: Patient satisfaction and the delivery of health care have been investigated as two secondary outcomes in a multicenter randomized controlled parallel-group phase II study (Clinical Trial ID: NCT01986725). In total, 49 women, from four hospitals (CH, AUT), completed the questionnaire PACIC-S11 after written information (n = 13) and counseling (n = 36). The delivery of health care was evaluated by ten Advanced Practice Nurses (APNs) by using the G-ACIC before and after implementing counseling based on the WOMAN-PRO II program. Results: There were no significant differences between the two groups identified (p = 0.25). Only few aspects were rated highly by all women, such as the overall satisfaction (M = 80.3 %) and satisfaction with organization of care (M = 83.0 %). The evaluation of delivery of health care by APNs in women who received counseling improved significantly (p = 0.031). Conclusions: There are indications, that the practice of both interventions might have improved patient satisfaction and counseling the delivery of health care. The aspects that have been rated low in the PACIC-S11 and G-ACIC indicate possibilities to optimize the delivery of health care.

Over- and under-prophylaxis for chemotherapy-induced (febrile) neutropenia relative to evidence-based guidelines is associated with differences in outcomes: findings from the MONITOR-GCSF study.

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.

Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in elderly versus non-elderly cancer patients: Patterns, outcomes, and determinants (MONITOR-GCSF study).

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 24-72h. 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.

Perceived Health-Related Quality of Life in Women With Vulvar Neoplasia: A Cross Sectional Study.

OBJECTIVE: The aim of the study was to determine health-related quality of life (HRQoL) of women with surgically treated vulvar intraepithelial neoplasia (VIN) and vulvar cancer (VC) during the first week after hospital discharge. Further objectives were to investigate differences between women with VIN and VC as well as to examine whether correlations exist between women's symptom experience and HRQoL. METHODS: This cross-sectional study was conducted in 8 hospitals in Germany and Switzerland. Women with VIN and VC rated HRQoL with the validated German Short-Form 36. Differences between HRQoL in women with VIN and VC were tested with Wilcoxon rank-sum score. The WOMen with vulvAr Neoplasia (WOMAN) - Patient reported Outcome (PRO) self-report instrument was used to measure women's symptom experience. Correlations between symptoms and HRQoL were calculated using Spearman correlation coefficient. RESULTS: Women with VIN and VC (n = 65) reported lower HRQoL in physical aspects (Physical Component Summary [PCS], 34.9) than that in mental aspects (Mental Component Summary, 40.5). Women with VC had lower HRQoL than women with VIN, as manifested by significant differences concerning the dimensions of "physical functioning" and "role-physical." "Difficulties in daily life" as a distressing symptom correlated with MCS and PCS. Wound-related symptoms correlated with PCS and psychosocial symptoms/issues with MCS. CONCLUSIONS: Analysis showed that women with vulvar neoplasia reported lower HRQoL in the physical and mental dimensions 1 week after discharge than comparable studies referring to months or years after surgery. Health-related quality of life is influenced by physical impairment because physical symptoms are prevalent 1 week after discharge. Patient education should focus on symptom management in an early postsurgical phase to enhance women's HRQoL.

Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study).

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.

Serious games for improving knowledge and self-management in young people with chronic conditions: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials assessing the effectiveness of serious games in improving knowledge and/or self-management behaviors in young people with chronic conditions. MATERIALS AND METHODS: The authors searched the databases PubMed, Cochrane Library, Web of Sciences, and PsychINFO for articles published between January 1990 and January 2014. Reference lists were hand-searched to retrieve additional studies. Randomized controlled trials that compared a digital game with either standard education or no specific education in a population of children and/or adolescents with chronic conditions were included. RESULTS: The authors identified 9 studies in which the effectiveness of serious games in young people with chronic conditions was evaluated using a randomized controlled trials design. Six studies found a significant improvement of knowledge in the game group from pretest to posttest; 4 studies showed significantly better knowledge in the game group than in the control group after the intervention. Two studies reported significantly better self-management in the game group than in the control group after the intervention. Seven studies were included in the meta-analysis. For knowledge, pooled estimate of Hedges' gu was 0.361 (95% confidence intervals, 0.098-0.624), demonstrating that serious games improve knowledge in patients. For self-management, pooled estimate of Hedges' gu was 0.310 (95% confidence intervals, 0.122-0.497), showing that gaming improves self-management behaviors. CONCLUSIONS: The authors' meta-analysis shows that educational video games can be effective in improving knowledge and self-management in young people with chronic conditions.

The effect of bright light therapy on sleep and circadian rhythms in renal transplant recipients: a pilot randomized, multicentre wait-list controlled trial.

This study assessed the effect and feasibility of morning bright light therapy (BLT) on sleep, circadian rhythms, subjective feelings, depressive symptomatology and cognition in renal transplant recipients (RTx) diagnosed with sleep-wake disturbances (SWD). This pilot randomized multicentre wait-list controlled trial included 30 home-dwelling RTx randomly assigned 1:1 to either 3 weeks of BLT or a wait-list control group. Morning BLT (10 000 lux) was individually scheduled for 30 min daily for 3 weeks. Wrist actimetry (measuring sleep and circadian rhythms), validated instruments (subjective feelings and cognition) and melatonin assay (circadian timing) were used. Data were analysed via a random-intercept regression model. Of 30 RTx recipients (aged 58 ± 15, transplanted 15 ± 6 years ago), 26 completed the study. While BLT had no significant effect on circadian and sleep measures, sleep timing improved significantly. The intervention group showed a significant get-up time phase advance from baseline to intervention (+24 min) [(standardized estimates (SE): -0.23 (-0.42; -0.03)] and a small (+14 min) but significant bedtime phase advance from intervention to follow-up (SE: -0.25 (-0.41; -0.09). Improvement in subjective feelings and depressive symptomatology was observed but was not statistically significant. Bright light therapy showed preliminary indications of a beneficial effect in RTx with sleep-wake disturbances. (ClinicalTrials.gov number: NCT01256983).