Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK.

Ferric derisomaltose (FDI; Monofer) is used in clinical practice to treat iron deficiency, but the safety and efficacy of FDI has not been robustly evaluated in a large real-world study. This retrospective, multicentre, audit-based, observational study provides pragmatic information about safety and clinical responses with FDI across therapy areas and patient populations, helping to facilitate treatment decisions. Participating sites provided data from the medical records of adults who had received ≥ 1 FDI infusion. The primary outcome was the incidence of adverse reactions within 24 hours of the FDI infusion. Secondary outcomes included the change from baseline in haemoglobin and ferritin up to 12 months post infusion. In total, 19 sites provided data for a total of 7354 FDI-treated patients; 64.3% of patients were female, and 42.2% were aged ≥ 70 years. Surgery was the main hospital specialty (34.5%). The incidence of any recorded adverse reactions, hypersensitivity reactions, and anaphylaxis were 1.7%, 0.4%, and < 0.1%, respectively, regardless of baseline anaemia status. Statistically significant increases in haemoglobin and ferritin were observed between baseline and Month 4 following FDI treatment (p < 0.0001). Improvements in haemoglobin were more pronounced for hospital specialties where operative blood loss is expected (surgery/obstetrics) compared with those where blood loss is not expected. This study provides real-world clinical evidence for the low risk of adverse reactions with FDI across diverse patient populations, providing reassurance that intravenous iron is not associated with serious toxicity. These findings may inform changes in intravenous iron delivery to provide effective therapy to more patients in need.

Exploring factors influencing uptake and adherence to a home-based prehabilitation physical activity and exercise intervention for patients undergoing chemotherapy before major surgery (ChemoFit): a qualitative study.

OBJECTIVES: Preoperative exercise training can improve cardiorespiratory fitness before major surgery. However, little is known about what influences participation and adherence in high-risk patient groups. We identified barriers and facilitators to uptake, engagement and adherence to a presurgical, home-based physical activity and exercise intervention called ChemoFit delivered during chemotherapy and before major oesophagogastric surgery. DESIGN: A qualitative study using focus group discussions and individual semi-structured interviews was conducted. All were audio-recorded, transcribed verbatim and data thematically analysed. SETTING: Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust. PARTICIPANTS: Patients with oesophagogastric cancer who participated in the ChemoFit intervention recruited between March 2020 and January 2021. INTERVENTION: A home-based physical activity and exercise intervention involving cardiovasular and strength exercise using resistance bands and pedometers to monitor step count. Weekly telephone calls provided feedback, support and positive reinforcement. RESULTS: Twenty-two participants (18 men, 4 women; aged 67±8 years old) took part in a focus group discussion (n=17) or a semi-structured interview (n=5). Fifteen themes were identified from the data generated. Participants reported that the intervention was physically and mentally beneficial, and data highlighted features of the intervention that influenced uptake and adherence. An opportunity to increase the likelihood of surviving the pending operation was reported by participants as the most salient factor to engagement, and using the intervention as a distraction from illness and taking steps to positively influence the situation were the most salient factors to adherence. CONCLUSIONS: Uptake to the ChemoFit intervention was encouraged by provision of information that participation could reduce surgical risk and that participants could play an active role in risk reduction. Adherence was facilitated by the intervention being considered a positive distraction and participants being able to do something that could ultimately provide benefit. While participants reported difficulties and avoidance with some of the exercises recommended, understanding the importance of physical activity and exercise as part of their treatment regimen led to individual adaptations to intervention components to reach individual goals. TRIAL REGISTRATION NUMBER: NCT04194463.

A feasibility trial of prehabilitation before oesophagogastric cancer surgery using a multi-component home-based exercise programme: the ChemoFit study.

BACKGROUND: Treatment for locally advanced oesophagogastric adenocarcinoma involves neoadjuvant chemotherapy which has a negative impact on patient fitness. Using 'prehabilitation' to increase activity levels and fitness may affect physiology, postoperative outcomes and improve patient wellbeing and quality of life. The aims of the trial were to address the feasibility and acceptability of recruiting participants to a home-based prehabilitation programme and provide data to allow design of future studies. METHODS: We recruited patients to a single-arm feasibility trial of home-based exercise prehabilitation. Eligible patients were aged ≥18years, had operable oesophageal or gastric adenocarcinoma and were receiving neoadjuvant chemotherapy at our tertiary referral hospital. All participants commenced a home-based exercise programme utilising pedometers and step counting to target daily aerobic exercise sessions alongside daily strengthening exercises. A weekly telephone consultation directed the exercise programme and facilitated weekly data collection. The primary (feasibility) outcomes for the trial were (a) recruitment rate, (b) completion rate, (c) engagement with the programme (use of pedometers, recording step counts, telephone consultations) and (d) compliance with exercise sessions, exercise intensity and strengthening exercises. RESULTS: There were 42 patients recruited, and the recruitment rate was 72.4% (42/58). 92.3% (36/39) of patients completed the exercise programme. There was 98.7% (IQR 93.2-100.0%) compliance with wearing a pedometer and recording data, and 100.0% (IQR 93.1-100.0%) compliance with a weekly telephone consultation. Exercise sessions and strengthening exercises were completed 70.2% (IQR 53.1-88.9%) and 69.4% (IQR 52.1-84.3%) of the time, respectively. Appropriate exercise intensity was recorded 96% (IQR 85.4-99.4%) of the time. There were no adverse events. Participants were enrolled in the exercise programme for a median of 91 days (IQR 84 to 105 days). CONCLUSIONS: The results of this trial support the feasibility and acceptability of recruiting participants to an appropriately powered randomised controlled trial of prehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04194463 . Registered on 11th December 2019-retrospectively registered.

Perioperative intravenous iron to treat patients with fractured hip surgery: A systematic review and meta-analysis.

Background: Treatment of preoperative anemia with intravenous iron is common within elective surgical care pathways. It is plausible that this treatment may improve care for people with hip fractures many of whom are anemic because of pre-existing conditions, fractures, and surgery. Objective: To review the evidence for intravenous iron administration on outcomes after hip fracture. Design: We followed a predefined protocol and conducted a systematic review and meta-analysis of the use of intravenous iron to treat anemia before and after emergency hip fracture surgery. The planned primary outcome was a difference in length of stay between those treated with intravenous iron and the control group. Other outcomes analyzed were 30-day mortality, requirement for blood transfusion, changes in quality of life, and hemoglobin concentration on discharge from the hospital. Data Sources: EMBASE, MEDLINE, The Cochrane Library (CENTRAL, DARE) databases, Clinicaltrials.gov, and ISRCTN trial registries. Date of final search March 2022. Eligibility Criteria: Adult patients undergoing urgent surgery for hip fracture. Studies considered patients who received intravenous iron and were compared with a control group. Results: Four randomized controlled trials (RCT, 732 patients) and nine cohort studies (2986 patients) were included. The RCTs were at low risk of bias, and the nonrandomized studies were at moderate risk of bias. After metanalysis of the RCTs there was no significant difference in the primary outcome, length of hospital stay, between the control group and patients receiving intravenous iron (mean difference: -0.59, 95% confidence interval [CI]; -1.20 to 0.03; I 2 = 30%, p = 0.23). Intravenous iron was not associated with a difference in 30-day mortality (n = 732, OR: 1.14, 95% CI: 0.62-2.1; I 2 = 0%, p = 0.50), nor with the requirement for transfusion (n = 732, OR: 0.85, 95% CI: 0.63-1.14; I 2 = 0%, p < 0.01) in the analyzed RCTs. Functional outcomes and quality of life were variably reported in three studies. Conclusion: The evidence on the use of intravenous iron in patients with hip fracture is low quality and shows no difference in length of acute hospital stay and transfusion requirements in this population. Improved large, multicentre, high-quality studies with patient-centered outcomes will be required to evaluate the clinical and cost-effectiveness of this treatment.

Identifying the limitations of cardiopulmonary exercise testing prior to esophagectomy using a pooled analysis of patient-level data.

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of aerobic fitness in patients undergoing surgery. While peak oxygen uptake during exercise (VO2peak) and anaerobic threshold have demonstrated a moderate correlation with the development of complications following esophagectomy, no clinically useful threshold values have been defined. By pooling patient level data from existing studies, we aimed to define optimal thresholds for preoperative CPET parameters to predict patients at high risk of postoperative complications. Studies reporting on the relationship between preoperative CPET variables and post-esophagectomy complications were determined from a comprehensive literature search. Patient-level data were obtained from six contributing centers for pooled-analyses. Outcomes of interest included cardiopulmonary and non-cardiopulmonary complications, unplanned intensive care unit readmission, and 90-day and 12-month all-cause mortality. Receiver operating characteristic curves and logistic regression models estimated the predictive value of CPET parameters for each individual outcome of interest. This analysis comprised of 621 patients who underwent CPET prior to esophagectomy during the period from January 2004 to March 2017. For both anaerobic threshold and VO2peak, none of the receiver operating characteristic curves achieved an area under the curve value > 0.66 for the outcomes of interest. The discriminatory ability of CPET for determining high-risk patients was found to be poor in patients undergoing an esophagectomy. CPET may only carry an adjunct role to clinical decision-making.

Does Cardiopulmonary Testing Help Predict Long-Term Survival After Esophagectomy?

BACKGROUND: Esophagectomy is associated with a high rate of morbidity and mortality. Preoperative cardiopulmonary fitness has been correlated with outcomes of major surgery. Variables derived from cardiopulmonary exercise testing (CPET) have been associated with postoperative outcomes. It is unclear whether preoperative cardiorespiratory fitness of patients undergoing esophagectomy is associated with long-term survival. This study aimed to evaluate whether any of the CPET variables routinely derived from patients with esophageal cancer may aid in predicting long-term survival after esophagectomy. METHODS: Patients undergoing CPET followed by trans-thoracic esophagectomy for esophageal cancer with curative intent between January 2013 and January 2017 from single high-volume center were retrospectively analyzed. The relationship between predictive co-variables, including CPET variables and survival, was studied with a Cox proportional hazard model. Receiver operation curve (ROC) analysis was performed to find cutoff values for CPET variables predictive of 3-year survival. RESULTS: The study analyzed 313 patients. The ventilatory equivalent for carbon dioxide (VE/VCO2) at the anerobic threshold was the only CPET variable independently predictive of long-term survival in the multivariable analysis (hazard ratio [HR], 1.049; 95% confidence interval [CI], 1.011-1.088; p = 0.011). Pathologic stages 3 and 4 disease was the other co-variable found to be independently predictive of survival. An ROC analysis of the VE/VCO2 failed to demonstrate a predictive cutoff value of 3-year survival (area under the curve, 0.564; 95% CI, 0.499-0.629; p = 0.056). CONCLUSIONS: A high VE/VCO2 before esophagectomy for malignant disease is an independent predictor of long-term survival and may be an important variable for clinicians to consider when counseling patients.

The Role of Cardiopulmonary Exercise Testing as a Risk Assessment Tool in Patients Undergoing Oesophagectomy: A Systematic Review and Meta-analysis.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is an objective method of assessing functional capacity to meet the metabolic demands of surgery and has been adopted as a preoperative risk-stratification tool for patients undergoing major procedures. The two main measures are the peak rate of oxygen uptake during exercise ([Formula: see text]O2peak) and anaerobic threshold (AT), the point at which anaerobic metabolism exceeds aerobic metabolism during exercise. This systematic review and meta-analysis evaluates the predictive value of CPET for patients undergoing oesophagectomy. METHODS: A systematic literature search was conducted in databases of CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and Scopus to identify studies that examined associations between preoperative CPET variables and postoperative outcomes following oesophagectomy. Results were presented as standardised mean difference (SMD) with 95% confidence interval. RESULTS: Seven studies were included in this review. Preoperative [Formula: see text]O2peak moderately correlated with cardiopulmonary complications [SMD = - 0.43; 95% confidence interval (CI) - 0.77 to - 0.09; p = 0.013; I2 = 80.4%], unplanned ICU admissions (SMD = - 0.34; 95% CI - 0.60 to - 0.08; p = 0.011; I2 = 0.0%), and 1-year survival (SMD = 0.31; 95% CI 0.02-0.61; p = 0.045; I2 = 0.0%). Preoperative AT values moderately correlated with unplanned ICU admissions (SMD = - 0.34; 95% CI - 0.61 to - 0.07; p = 0.014; I2 = 0.0%), and 1-year survival (SMD = 0.34; 95% CI 0.00-0.68; p = 0.049; I2 = 7.4%). Neither [Formula: see text]O2peak nor AT demonstrated prognostic value for noncardiopulmonary complications. CONCLUSIONS: [Formula: see text]O2peak and AT, where measured by preoperative CPET testing, are inversely associated with postoperative cardiopulmonary complications, unplanned ICU admissions, and 1-year survival following oesophagectomy. This meta-analysis was not able to identify an absolute cutoff value for CPET variables to discriminate between patients of varying levels of operative risk.

Intra- and interobserver variability in skeletal muscle measurements using computed tomography images.

PURPOSE: The progressive loss of skeletal muscle and function (known as sarcopenia) has been shown to be associated with various adverse outcome measures. Sophisticated measurements of body composition are increasingly being incorporated into research studies to stratify patients into those with or without sarcopenia, monitor treatment effects, and predict complications. A typical approach is to select axial image(s) at the mid-lumbar level and use semi-automated software to identify and quantify the skeletal muscle area. This area is then used to estimate whole-body parameters. This approach is somewhat subjective, and in this study we investigate its reproducibility, both within and between observers. MATERIALS AND METHODS: Repeated muscle measurements were performed on a cohort of 29 patients by 3 radiologists, to examine their intra- and interobserver reproducibility. RESULTS AND DISCUSSION: Mean muscle area for the cohort was 156 cm2, with a wide range (98 - 261 cm2). There was good intraobserver agreement between measurements, with a mean absolute difference between repeated measurements on the same patient of 0.98 cm2, and a measurement variability of 2.92 cm2. Much of the variability was shown to be due to the choice of a different slice when performing the repeated measurement. Averaging two slices provided a small but non-significant improvement in comparison to the single slice approach. Interobserver results showed good agreement, though there was a small bias for one observer, who measured slightly larger volumes compared to the other two. We conclude that the approach described provides reproducible skeletal muscle area measurements, and offer three specific recommendations to minimise variability.