Prevalence of Cardiovascular Risk Factors among Cancer Patients in the United States

Background: Cancer and cardiovascular diseases (CVDs) are leading causes of morbidity and mortality. We analyzed national data to examine the prevalence of CVD risk factors among adult cancer survivors in the United States. Methods: Participants included adults ≥18 years of age from the National Health and Nutrition Examination Survey 2001-2002 to 2013-2014. CVD risk factors included hypertension, diabetes, dyslipidemia, obesity, smoking, and physical activity. Prevalence of 1, 2, or ≥3 CVD risk factors was compared between cancer and noncancer participants. All CVD risk factors were adjusted for age and smoking and additionally for sex. Differences in CVD risk factors among cancer and noncancer participants were identified using logistic regression analysis. Results: Among 35,379 eligible participants, 2906 (8.4%) had a history of cancer. The proportion of participants having a single CVD risk factor was lower among cancer survivors compared with noncancer participants (25.8% vs. 33.9%, P \u3c 0.001). The proportions of participants having two CVD risk factors (33.5% vs. 24.6%, P \u3c 0.001) and ≥3 CVD risk factors (27.4% vs. 16.4%, P \u3c 0.001) were higher among cancer survivors. However, these associations lost significance upon adjusting for age. The odds of total hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI]: 1.11-1.40) and total diabetes (OR 1.33, 95% CI: 1.08-1.65) were significantly higher among cancer survivors. Conclusions: Our study showed that adult cancer survivors in the United States had higher levels of CVD risk factors primarily due to age-related factors, in addition to cancer complications. There is a significant need for improved CVD risk assessment and prevention services for cancer survivors

Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial

Background: Spine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. Methods/design: This is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. Discussion: The primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. Trial registration: ClinicalTrials.gov NCT04375891 . Registered on 5 May 2020. Keywords: Bone metastasis; Radiation therapy; Radiofrequency ablation; Randomized controlled trial; Spine; Vertebrae; Vertebral augmentation

NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting the ubiquitin proteasome system (UPS) has been successful. Likewise, laboratory studies have demonstrated that inhibition of the UPS might provide a promising avenue for the treatment of KSHV-associated diseases. The largest class of E3 ubiquitin ligases are the cullin-RING ligases (CRLs) that are activated by an additional ubiquitin-like protein, NEDD8. We show that pharmacological inhibition of NEDDylation (using the small molecule inhibitor MLN4924) is cytotoxic to PEL cells by inhibiting NF-κB. We also show that CRL4B is a novel regulator of latency as its inhibition reactivated lytic gene expression. Furthermore, we uncovered a requirement for NEDDylation during the reactivation of the KSHV lytic cycle. Intriguingly, inhibition prevented viral DNA replication but not lytic cycle-associated gene expression, highlighting a novel mechanism that uncouples these two features of KSHV biology. Mechanistically, we show that MLN4924 treatment precluded the recruitment of the viral pre-replication complex to the origin of lytic DNA replication (OriLyt). These new findings have revealed novel mechanisms that regulate KSHV latency and reactivation. Moreover, they demonstrate that inhibition of NEDDylation represents a novel approach for the treatment of KSHV-associated malignancies

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Clinical Trial-Related Workload Tool for Research Managers

INTRODUCTION: Identifying whether research staff is overburdened and quantifying it in a clinical trial setting is a challenge for research managers. Quantifying workload could help managers to equitably distribute burden and to accurately staff for better functioning of clinical trials. In this study we developed a workload tool for quantifying the workload of Clinical Research Coordinators in a cancer clinical trial setting. METHODS: We adapted the ASCO Clinical Trial Workload Assessment Tool for application in a cancer clinical trial setting. First we assigned all active clinical trials to one of four categories with the assignment of a complexity score. Then we categorized the workload of Clinical Research Coordinators into static and dynamic works. Static works are those independent of the number of patients seen by Clinical Research Coordinators and dynamic works are those dependent on the number of patients (active patients versus follow-up patients). Thereafter we developed an equation to quantify the workload of each Clinical Research Coordinator with a score of 100 indicating ideal burden; those with a score of \u3e100 were considered overburdened. Based on this we could calculate the number of additional Clinical Research Coordinators needed for better functioning of clinical trials. RESULTS: We measured the workload of Clinical Research Coordinators from June 2018 to March 2019. During this period, there were a median number of 12 (range: 11-15) Clinical Re-search Coordinators working for median of 37 (range: 29-39) clinical trials. The median active patients were 170 (range: 100-196) and follow-up patients were 13 (range: 2-19). During the study period, a median number of 9 (range: 6-14) Clinical Research Coordinators were working above their ideal workload. After applying the equation, a median of 3.2 (range: 2-4) extra Clinical Re-search Coordinators were needed to complete their jobs without additional burden. CONCLUSION: The workload tool could be used to accurately identify the number of prospective employees needed based on the number and complexity of active clinical trials. The workload tool showed consistent results indicating good precision. However, statistical validation is required to confirm the accuracy and reliability of the tool. We have further adapted our workload tool to assess burden in other research roles including Research Assistants, Research Finance Specialists, Budget and Contract Analysts, Research Registered Nurses, Infusion Registered Nurses, Quality Assurance Specialists, and Regulatory Coordinators. Future applications of the workload tool include use for budget justification of current and future research staff and use in performance improvement initiatives

Prevalence of Cardiovascular Risk Factors Among Cancer Patients in the United States

Background: Cancer and cardiovascular diseases (CVDs) are leading causes of morbidity and mortality. We analyzed national data to examine the prevalence of CVD risk factors among adult cancer survivors in the United States. Methods: Participants included adults ≥18 years of age from the National Health and Nutrition Examination Survey 2001-2002 to 2013-2014. CVD risk factors included hypertension, diabetes, dyslipidemia, obesity, smoking, and physical activity. Prevalence of 1, 2, or ≥3 CVD risk factors was compared between cancer and noncancer participants. All CVD risk factors were adjusted for age and smoking and additionally for sex. Differences in CVD risk factors among cancer and noncancer participants were identified using logistic regression analysis. Results: Among 35,379 eligible participants, 2906 (8.4%) had a history of cancer. The proportion of participants having a single CVD risk factor was lower among cancer survivors compared with noncancer participants (25.8% vs. 33.9%, P \u3c 0.001). The proportions of participants having two CVD risk factors (33.5% vs. 24.6%, P \u3c 0.001) and ≥3 CVD risk factors (27.4% vs. 16.4%, P \u3c 0.001) were higher among cancer survivors. However, these associations lost significance upon adjusting for age. The odds of total hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI]: 1.11-1.40) and total diabetes (OR 1.33, 95% CI: 1.08-1.65) were significantly higher among cancer survivors. Conclusions: Our study showed that adult cancer survivors in the United States had higher levels of CVD risk factors primarily due to age-related factors, in addition to cancer complications. There is a significant need for improved CVD risk assessment and prevention services for cancer survivors