Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Redo aortic valve replacement versus valve-in-valve trans-catheter aortic valve implantation: a UK propensity-matched analysis.

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicenter UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients underwent valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. The mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR versus 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including intra-aortic balloon pump support (p=0.02), early re-operation (p<0.001), arrhythmias (p<0.001), respiratory and neurological complications (p=0.02 and p=0.03) and multi-organ failure (p=0.01). The valve-in-valve TAVI group had a shorter intensive care unit and hospital stay (p<0.001 for both). However, moderate aortic regurgitation at discharge and higher post-procedural gradients were more common after valve-in-valve TAVI (p<0.001 for both). Survival probabilities in patients who were successfully discharged from the hospital were similar after valve-in-valve TAVI and redo-AVR over the 6-year follow-up (log-rank p=0.26). In elderly patients with a degenerated aortic bioprosthesis, valve-in-valve TAVI provides better early outcomes as opposed to redo-AVR, although there was no difference in mid-term survival in patients successfully discharged from the hospital.

Core training and surgical opportunities: A UK-based analysis.

Background and Aim: The COVID-19 pandemic, the new Intercollegiate Surgical Curriculum Programme curriculum and the European Work Time Directive significantly reduced surgical exposure for trainees. This study analyzed the operative experience of Phase 1 trainees (CT1/ST1 vs. CT2/ST2) against the Annual Review of Competence Progression (ARCP) criterion of 120 procedures yearly. Methods: National survey research in October 2021. Study end-point was the completion of >4 weekly procedures, equivalent to 120 cases per year. Chi-square test and multivariate regression analysis were performed. Results: 205 participants from 5 Deaneries were included, 48.3% were CT1/ST1 and 51.7% were CT2/ST2. About 54.5% of year-1 and 50% of year-2 trainees were 28 30 years old, 55.6% and 50.9% were male, and 39.4% and 38.7% were White British. About 39.4% of CT1/ST1 and 22.6% of CT2/ST2 performed <4 weekly procedures (P = 0.01), with no difference in the "Observed" (P = 0.6) or "Assisted" (P = 0.3) number of cases. CT2/ST2 recorded more "ST-S" (p 0.04), "S-TU" (P = 0.03), and "Performed" (P = 0.02) operations. For CT1/ST1, older age (HR 2.4, 95% CI [1.1; 5.3], P = 0.02) and southern deaneries (HR 1.7, 95% CI [1.2; 2.4], P = 0.004) were independent factor for <4 weekly procedures. For CT2/ST2, northern regions were associated with more favorable training (HR 1.4, 95% CI [1.1; 1.7], P = 0.01). Conclusion: Over one third of Phase 1 trainees do not meet the ARCP requirement of >120 procedures annually. Age and region of training are independent factors in the number of logbook cases. Relevance for Patients: This research focuses on training opportunities for junior surgical residents across the United Kingdom. The degree and type of exposure to the operating theatre have a significant impact on the development of surgical competencies. These are undoubtedly related to patient outcomes, as the quality of care delivered to patients and relatives greatly relies on the training background of future consultant surgeons.

Short-term and long-term impact of diagnosed and undiagnosed chronic obstructive pulmonary disease on coronary artery bypass grafting surgery.

OBJECTIVES: This study sought to compare clinical outcomes between three categories of patients: non-chronic obstructive pulmonary disease (COPD), diagnosed COPD and undiagnosed COPD in coronary artery bypass grafting surgery. METHODS: A single-centred retrospective study from January 2010 to December 2019. Primary outcomes were postoperative complications, length of ITU admission and in-hospital staying. Secondary outcomes were reintervention rate, in-hospital and long-term mortality. RESULTS: A total of 4020 patients were analysed and divided into three cohorts: non-COPD (group A) (74.55%, n=2997), diagnosed COPD (group B) (14.78%, n=594) and undiagnosed COPD (group C) (10.67%, n=429). The rate of respiratory complications was noted in this order: group B>group C>group A (p 0.00000002). Periooperative acute kidney injury and wound complications were higher in group B (p 0.0004 and p 0.03, respectively). Prolonged in-hospital staying (days) resulted in group B (p 0.0009). Finally, long-term mortality was statistically higher in group B and C compared with group A (p 0.0004). No difference in long-term mortality was noted in relation to the expected FEV1% in group B (p 0.29) and group C (p 0.82). CONCLUSIONS: In CABG surgery, COPD is a well-known independent risk factor for morbidity. Patients with preoperative spirometry results indicative of COPD result in the same outcomes of known patients with COPD. As a result of that, greater value should be given to the preoperative spirometry in the EuroSCORE. Finally, the expected FEV1% appears not be a predictor for long-term survival.

Permanent Pacemaker Post Cardiac Surgery: where do we Stand?

Abstract Cardiac arrhythmias and requirement for permanent pacemaker (PPM) post open-heart surgery are some of the complications that can contribute to significant morbidities postoperatively and delay in normal recovery if not treated promptly. The reported rate of a PPM following isolated, elective coronary artery bypass grafting is < 1%, while following aortic or mitral valve surgery it is reported to be < 5%. There are several perioperative factors that can contribute to the increased likelihood of PPM requirement including preoperative rhythm, severity and location of cardiac ischaemia, perioperative variables, and the cardiac procedures performed. Optimization of such factors can possibly lead to a lower rate of PPM and, therefore, a lower rate of complications. This literature review focuses on PPM following each procedural type and how to minimize it.

Permanent pacemaker post-valve surgery: Do valve type and position matter? A propensity score matching study.

BACKGROUND AND AIM: This study evaluates whether aortic valve replacement (AVR) or mitral valve replacement (MVR) with biological versus mechanical prostheses is independent risk factors for permanent pacemaker (PPM) post-cardiac surgery, alongside traditionally accepted determinants. METHODS: This study focused on single-centre retrospective analysis of 10 years of activity. Case-control 1-to-9 matching was performed for 7 pre-operative and 2 intraoperative confounding factors. RESULTS: After matching, 617 patients were included for analysis: AVR (79.4% n=490) and MVR (20.6% n=127). PPM was implanted in 3.7% (n=18) and 3.1% (n=4), P=0.8, respectively. A further analysis for PPM rate in biological versus mechanical prostheses did not provide any significant result (P=0.6 AVR and P=0.8 MVR). Post-operative complications in AVR and MVR groups were as follows: Reopening (4.5% vs. 6.3%, P=0.4), myocardial infarction (0.8% vs. 3.2%, P=0.04), pulmonary (32.9% vs. 38.6%, P=0.3), neurological (9.2% vs. 11.8%, P=0.4), renal (9.8% vs. 7.9%, P=0.5), wound (1.4% vs. 2.4%, P=0.5), infective (5.5% vs. 8.7%, P=0.2), and multiple organ failure (4.9% vs. 5.5%, P=0.6). The length of intensive care unit (hours) and hospital stay (days) was 71±163.8 versus 106.5±243.7 (P=0.5) and 14.7±14.7 versus 18.9±20.8 (P=0.01). In-hospital mortality resulted in 4.1% for AVR and 3.9% for MVR, P=0.9. CONCLUSION: Valve position and valve type do not affect the likelihood of requiring permanent pacing in patients undergoing isolated aortic and MVR. RELEVANCE FOR PATIENTS: A significant proportion of patients undergoing cardiac surgery develop arrhythmias and conduction disturbances postoperatively, often requiring the implantation of a PPM. Determining factors associated with an increase likelihood of permanent pacing would allow the optimization of per- and intra-operative care, with the aim of reducing the incidence of patients requiring post-operative PPM insertion.

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review.

OBJECTIVE: To comprehensively understand cardiac surgeryassociated acute kidney injury (CSA-AKI) and methods of prevention of such complication in cardiac surgery patients. METHODS: A comprehensive literature search was performed using the electronic database to identify articles describing acute kidney injury (AKI) in patients that undergone cardiac surgery. There was neither time limit nor language limit on the search. The results were narratively summarized. RESULTS: All the relevant articles have been extracted; results have been summarized in each related section. CSA-AKI is a serious postoperative complication and it can contribute to a significant increase in perioperative morbidity and mortality rates. Optimization of factors that can reduce CSA-AKI, therefore, contributes to a better postoperative outcome. CONCLUSION: Several factors can significantly increase the rate of AKI; identification and minimization of such factors can lead to lower rates of CSA-AKI and lower perioperative morbidity and mortality rates.

Acute kidney injury associated with cardiac surgery: a comprehensive literature review

Abstract Objective: To comprehensively understand cardiac surgeryassociated acute kidney injury (CSA-AKI) and methods of prevention of such complication in cardiac surgery patients. Methods: A comprehensive literature search was performed using the electronic database to identify articles describing acute kidney injury (AKI) in patients that undergone cardiac surgery. There was neither time limit nor language limit on the search. The results were narratively summarized. Results: All the relevant articles have been extracted; results have been summarized in each related section. CSA-AKI is a serious postoperative complication and it can contribute to a significant increase in perioperative morbidity and mortality rates. Optimization of factors that can reduce CSA-AKI, therefore, contributes to a better postoperative outcome. Conclusion: Several factors can significantly increase the rate of AKI; identification and minimization of such factors can lead to lower rates of CSA-AKI and lower perioperative morbidity and mortality rates.

A real-world study assessing the use of bone-targeted agents and their impact on bone metastases in patients with prostate cancer treated in clinical practice in Europe.

BACKGROUND: Bone metastases (BMs) are common in patients with prostate cancer and can lead to skeletal-related events (SREs), which are associated with increased pain and reduced quality of life (QoL). Bone-targeted agents (BTAs), such as zoledronic acid and denosumab, reduce the incidence of SREs and delay progression of bone pain. METHODS: We evaluated the management of BMs and pain in six European countries (Belgium, France, Germany, Italy, Spain and the UK) using the Adelphi Prostate Cancer Disease Specific Programme. Patient-reported outcomes (PROs) were used to assess the impact of BMs on pain and QoL. RESULTS: In total, 358 physicians completed Patient Record Forms, of whom 246 were oncologists and 112 were urologists. Data were collected on 3667 patients with prostate cancer, including 1971 with BMs and 551 with metastases at sites other than bone (non-BMs). PROs were assessed in 573 patients with BMs and 220 with non-BMs. Most patients with BMs (74%) received a BTA and 53% received treatment within 3 months of BM diagnosis. Patients treated by oncologists were more likely than those treated by urologists to receive a BTA (78% vs. 60%) and to have treatment initiated within 3 months of BM diagnosis (56% vs. 43%). For patients who did not receive a BTA, the main reasons for not treating were very recent BM diagnosis and a perceived low risk of bone complications. Data collected by physicians showed that most patients with BMs (97%) were taking analgesics, with 30% receiving strong opioids. Despite this, 70% were currently experiencing bone pain and 28% were experiencing moderate to severe pain. PRO pain measures showed that 70% of patients with BMs were experiencing moderate to extreme pain, suggesting a disparity between pain levels reported by physicians and by patients. CONCLUSIONS: Although most patients with BMs receive a BTA, there remain a proportion of patients who are not receiving adequate treatment to prevent SREs or manage pain. Oncologists are more likely to adhere to clinical guidelines than urologists for the prescription of BTAs. Bone pain is common and undertreated. Increasing awareness of SRE prevention and bone pain management might improve patient care.

Bone-targeted agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the United States.

OBJECTIVE: Bone metastases are common among patients with advanced breast cancer, putting patients at increased risk of skeletal-related events (SREs). This study described impact of bone metastases, utilization of bone-targeted agents (BTAs) and physicians' decision processes for BTA use in advanced breast cancer. METHODS: Data were collected using the Adelphi Breast Cancer Disease-Specific Programme in the United States. Physicians completed a detailed record for eligible patients (women ≥18 years, with stage IIIB-IV breast cancer). RESULTS: Data available from 1276 patients with advanced breast cancer included 485 (38%) with bone metastases. Most (80%) reported pain at bone metastasis diagnosis; of those reporting pain, 55% reported moderate to severe pain. Among patients with bone metastasis, 69% received a BTA. Reasons for initiating BTAs were bone pain (32%) and an estimated high risk of SREs (25%). Reasons for not treating with BTAs were very recent diagnosis (37%), poor Karnofsky performance status (14%), perceived low risk of SREs (11%) and short life expectancy (11%). Zoledronic acid (48%) and denosumab (42%) were commonly used BTAs; the main reasons for initiating BTA treatment were long-term safety (28% and 32%, respectively) and efficacy in delaying SREs (15% and 31%, respectively). The analysis was not adjusted for age or other possible confounders. CONCLUSION: Bone pain is a common and sometimes severe symptom of bone metastases in advanced breast cancer and a common reason for initiating BTA treatment. Safety and efficacy were the main factors considered by physicians when selecting BTAs.

Physicians' preferences for bone metastases treatments in France, Germany and the United Kingdom.

BACKGROUND: Several bone-targeted agents (BTAs) are available for preventing skeletal-related events (SREs), but they vary in terms of efficacy, safety and mode of administration. This study assessed data on European physicians' treatment preferences for preventing SREs in patients with bone metastases from solid tumours. METHODS: Physicians completed a web-based discrete-choice experiment survey of 10 choices between pairs of profiles of hypothetical BTAs for a putative patient. Each profile included five attributes within a pre-defined range (primarily based on existing BTAs' prescribing information): time (months) until the first SRE; time (months) until worsening of pain; annual risk of osteonecrosis of the jaw (ONJ); annual risk of renal impairment; and mode of administration. Choice questions were developed using an experimental design with known statistical properties. A separate main-effects random parameters logit model was estimated for each country and provided the relative preference for the treatment attributes in the study. RESULTS: A total of 191 physicians in France, 192 physicians in Germany, and 197 physicians in the United Kingdom completed the survey. In France and the United Kingdom, time until the first SRE and risk of renal impairment were the most important attributes; in Germany, time until the first SRE and delay in worsening of pain were the most important. In all countries, a 120-min infusion every 4 weeks was the least preferred mode of administration (p < 0.05) and the annual risk of ONJ was judged to be the least important attribute. CONCLUSIONS: When making treatment decisions regarding the choice of BTA, delaying the onset of SREs/worsening of pain and reducing the risk of renal impairment are the primary objectives for physicians.

Bone-targeted agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in real-world practice in six European countries.

BACKGROUND: Bone metastases (BMs) are common in patients with breast cancer and can lead to skeletal-related events (SREs), which are associated with increased pain and reduced quality of life (QoL). Bone-targeted agents (BTAs), like zoledronic acid and denosumab, reduce the incidence of SREs and delay progression of bone pain. MATERIALS AND METHODS: We evaluated the management of BMs and pain in six European countries (Belgium, France, Germany, Italy, Spain, and UK) using the Adelphi Breast Cancer Disease Specific Programme, which included a physician survey and patient-reported outcomes (PROs) to assess the impact of BMs on pain and QoL. RESULTS: 301 physicians completed patient record forms for 2984 patients with advanced breast cancer; 1408 with BMs and 1136 with metastases at sites other than bone (non-BMs). Most patients with BMs (88%) received a BTA, with 81% receiving treatment during 3 months following BM diagnosis. For those who did not receive a BTA, the main reasons given were: very recent BM diagnosis, perceived low risk of bone complications, and short life expectancy. Most patients with BMs (68%) were experiencing bone pain and, of these, 97% were taking analgesics (including 28% receiving strong opioids). Despite this, moderate to severe pain was reported in 20% of patients who were experiencing pain. PROs were assessed in 766 patients with advanced breast cancer (392 with BMs, 374 with non-BMs). Overall, patients with BMs reported worse pain and QoL outcomes than those with non-BMs, those not receiving a BTA reported worse pain. CONCLUSION: Despite the large proportion of patients receiving BTAs in this study, some patients with BMs are still not receiving early treatment to prevent SREs or to manage pain. Improving physicians' understanding of the role of BTAs and the importance of early treatment following BM diagnosis has the potential to improve patient care.

An observational time and motion study of denosumab subcutaneous injection and zoledronic acid intravenous infusion in patients with metastatic bone disease: results from three European countries.

PURPOSE: Denosumab (administered via subcutaneous injection) demonstrated superior efficacy versus the intravenously administered zoledronic acid in the prevention of skeletal-related events in an integrated analysis of three head-to-head phase III trials in patients with bone metastases secondary to solid tumors. To date, no studies have evaluated treatment administration duration endpoints of these two agents. METHODS: A multinational, multi-site, observational time and motion study conducted in 10 day oncology units (DOUs) across Belgium, Germany, and Italy. Observations of process time included task time and active healthcare professional (HCP) time for pre-defined tasks. Patient time measurements included entering/exiting the DOU, treatment room, and treatment chair or examination table. RESULTS: A total of 189 patients were enrolled (82 received zoledronic acid and 107 received denosumab) and 238 observations were recorded (104 for zoledronic acid and 134 for denosumab). Mean total task time was reduced by 81% when denosumab was used versus zoledronic acid (8.4 versus 44.2 min; p < 0.0001; pooled analysis across all countries). Pooled estimates for active HCP time were 12.2 min for zoledronic acid and 6.9 min for denosumab (44% reduction; p < 0.0001). CONCLUSIONS: In the countries studied, using denosumab compared with zoledronic acid reduced total task time and active HCP time. Thus, HCPs have more time to dedicate to other patients or care activities. An ability to increase the volume of appointments within DOUs could reduce waiting lists in sites operating at full capacity and increase overall productivity and efficiency in hospital processes.

Skin toxicity and quality of life during treatment with panitumumab for RAS wild-type metastatic colorectal carcinoma: results from three randomised clinical trials.

PURPOSE: Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC). METHODS: The studies were randomised, open-label trials comparing standard treatment (first-line FOLFOX4 [n = 456], second-line FOLFIRI [n = 381], or best supportive care [n = 114]) with or without panitumumab in adults with KRAS/NRAS (RAS) wild-type mCRC. QoL was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) measures. Impact of skin toxicity on changes in QoL scores was estimated using a linear mixed-effects model. Worst skin toxicity was defined in separate models as a subgroup variable or as a measure over time. RESULTS: Regardless of analysis method, there were no statistically significant differences between the panitumumab and comparator arms in any of the studies in terms of change in HSI or OHR scores. There were no statistically significant differences in QoL outcomes between patients with worst skin toxicity grade <3 and those with grade ≥3. In addition, there were no statistically significant differences between the panitumumab and comparator arms in subgroups of patients with worst skin toxicity of grade <3 and ≥3. CONCLUSIONS: Addition of panitumumab to chemotherapy in RAS wild-type mCRC has no statistically significant negative effect on overall QoL, despite skin toxicity. Skin toxicity of worst grade ≥3 appeared to have similar impact on QoL as skin toxicity of grade <3.

Patient, Caregiver, and Nurse Preferences for Treatments for Bone Metastases from Solid Tumors.

BACKGROUND: Bone-targeted agents (BTAs) used for the prevention of skeletal-related events (SREs) associated with metastatic bone disease possess different attributes that factor into treatment decisions. OBJECTIVE: The aim of this study was to evaluate preferences of patients, caregivers, and nurses for features of BTAs used to prevent SREs in patients with a self-reported physician diagnosis of bone metastasis from solid tumors. METHODS: Patients (n = 187), primary caregivers (n = 197), or nurses (n = 196) completed a web-enabled discrete-choice experiment (10-question survey) in which they chose between pairs of hypothetical profiles of BTAs. Each profile was defined by six key treatment attributes, including efficacy and safety (two each) and route/frequency of administration and cost (one each). The relative importance of treatment attributes and levels was estimated. RESULTS: The most important treatment attribute for patients and nurses was out-of-pocket cost, and for caregivers, treatment-related risk of renal impairment. Risk of renal impairment was the second most important attribute for patients and nurses, while time until first SRE was the third most important attribute for all respondents. For nurses, risk of osteonecrosis of the jaw was least important, and for patients and caregivers, mode of administration was least important. LIMITATIONS: Respondents considered hypothetical medications; therefore, their decisions may not have the same consequences as actual decisions. CONCLUSIONS: The perspectives of patients, caregivers, and nurses are integral when making treatment decisions about BTAs to prevent SREs associated with solid tumors. Identifying the relative importance of attributes of BTAs will aid in the proper selection of therapy in this setting, which may improve patient outcomes.

Physicians' preferences for bone metastases drug therapy in the United States.

OBJECTIVE: Several characteristics of bone-targeted agents are considered when making treatment decisions. This study evaluated physicians' therapy preferences for preventing skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors. METHODS: A Web-enabled, discrete-choice experiment online survey was conducted among physicians who treated patients with bone metastases and solid tumors in the United States. Respondents chose between pairs of hypothetical medications defined by combinations of six attributes at varying levels for two hypothetical patients. Preference weights for attribute levels were estimated using a random-parameters logit model. RESULTS: In total, 200 physicians completed the survey. Their mean age was 52 years, 57% were in practice for more than 15 years, 37% were oncologists, and 65% treated 10 or fewer patients with bone metastases weekly. Out-of-pocket cost to patients was the most important attribute overall. Among clinical outcomes, time to first SRE and risk of renal impairment were the most important attributes. Statistically significant preferences were observed for all attribute levels for time to first SRE, risk of renal impairment, and mode of administration. Predicted choice probability analysis showed that physicians preferred a hypothetical medication with attributes similar to those of denosumab over one with attributes similar to those of zoledronic acid. CONCLUSIONS: Physicians indicated that clinical attributes are important when considering bone-targeting therapy for bone metastases, but consistent with the current health care landscape, patient out-of-pocket cost was the most important. With health care costs being increasingly shifted to patients, physicians require accurate information about co-pays and assistance programs to avoid patients receiving less costly, yet potentially inferior, treatment.

Patients' preferences for bone metastases treatments in France, Germany and the United Kingdom.

PURPOSE: The aim of this study was to assess patients' preferences for efficacy, safety, and mode of administration in relation to available bone-targeted agents (BTA) for the prevention of skeletal-related events (SREs) associated with bone metastases in Europe. METHODS: Adults in France (n = 159), Germany (n = 166), and the United Kingdom (UK; n = 159) with a self-reported physician diagnosis of bone metastases secondary to a solid tumour completed an online discrete- choice experiment survey of ten questions, choosing between pairs of hypothetical BTA profiles. Profiles were defined by five treatment attributes: delay of first SRE, delay of worsening of pain, annual risk of osteonecrosis of the jaw (ONJ), annual risk of renal impairment, and mode of administration. Profiles were generated using an experimental design with known statistical properties. A main-effects random parameters logit (RPL) model was applied to relate participants' choices to the characteristics of the BTA profiles. RESULTS: The most important treatment attributes for patients across all three countries were time until first SRE, annual risk of renal complications and time until pain worsening. For these attributes, better levels of outcomes were significantly preferred to worse levels (p < 0.05). A 120-minutes infusion every 4 weeks was the least preferred mode of administration. Risk of ONJ was judged by patients in the UK and Germany to be the least important attribute. CONCLUSIONS: Patients consider delaying SREs, avoiding renal impairment and delaying pain worsening as the most important goals to consider when selecting treatment to prevent the bone complications commonly associated with bone metastases.

Patient preferences for treatments to delay bone metastases.

BACKGROUND: Most patients with advanced prostate cancer (PCa) develop bone metastases (BM) and present with bone complications like fracture. Bone-targeted agents that prevent metastasis-induced bone complications can cause adverse events. Understanding how patients view treatment options may optimize care. This study aimed to quantify how PCa patients value a hypothetical treatment that delays BM but can cause osteonecrosis of the jaw (ONJ). The study also assessed the value patients place on avoiding metastasis-induced bone complications versus increased survival. METHODS: PCa patients from the United Kingdom (n = 201) and Sweden (n = 200) on androgen-deprivation therapy or hormone therapy for ≥ 3 years completed a 10-question discrete-choice-experiment survey examining whether patients would accept a BM-delaying treatment. Two time-tradeoff questions assessed patients' willingness to tradeoff between survival and bone complications. Percentages of patients choosing treatment were summarized by levels of treatment efficacy and ONJ risk. Odds ratios from a logit model were used to evaluate how patient and medication characteristics affected treatment choice. Proportions of patients choosing each tradeoff scenario were calculated. RESULTS: A majority of patients accepted treatment at the lowest benefit level (5-month BM delay) and highest risk level (9% ONJ risk). PCa symptoms and prior treatment affected patient preferences. Nearly 80% of patients would tradeoff at least 3 months of survival to avoid bone complications. CONCLUSIONS: PCa patients in the U.K and Sweden may value a medication that delays BM, despite the risk of ONJ. Furthermore, patients were willing to tradeoff up to 5 months of survival for prevention of bone complications.

Inappropriateness of breast imaging: cost analysis.

PURPOSE: The aim of this study was to assess how an incorrect indication for an examination may affect the diagnostic workup and diagnosis as well as healthcare expenditure. MATERIALS AND METHODS: We considered all the requests for breast imaging (mammography, ultrasound and magnetic resonance imaging) received by our radiology department between October 2010 and December 2010, and assessed their appropriateness based on the patient's age and the clinical question, if present. We then analysed the unnecessary costs resulting from inappropriate requests. RESULTS: Out of a total of 1500 requests for ultrasound examination, the request was appropriate in 855 (57%) cases; out of a total of 2350 requests for mammography, the request was appropriate in 493 (21%) cases; out of a total of 100 requests for magnetic resonance imaging, the request was appropriate in 83 (83%) cases. The cost deriving from inappropriate requests was 51,235.04 Euros. CONCLUSIONS: Improving the timeliness of diagnosis is an important goal to be pursued by enhancing the available health services, improving communication and coordination of the different professionals involved and optimising diagnostic pathways in order to reduce healthcare spending.