Bleeding risk from anticoagulant thromboprophylaxis in patients with multiple myeloma: a MarketScan analysis.

Background: Multiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Anticoagulant prophylaxis is frequently recommended but underutilized partly due to the absence of studies assessing bleeding risk. Objectives: To determine the rate of severe (hospitalized) bleeding from thromboprophylaxis in patients treated for MM and identify clinical risk factors for bleeding in this population. Methods: Using the MarketScan database, we analyzed 6656 patients treated for MM between 2013 and 2021. Concomitant thromboprophylaxis was defined using prescription claims. Hospitalized bleeding was identified through the Cunningham algorithm. Bleeding rates were compared by thromboprophylaxis status, and Cox regression identified risk factors for bleeding. Results: Anticoagulant thromboprophylaxis was used in 6.6% (436) patients treated for MM. Patients on thromboprophylaxis had a higher rate of immunomodulatory-based therapy (63.8% vs 46.7%; P < .01) and lower rate of antiplatelet use (2.1% vs 4.7%; P < .01). Bleeding occurred in 1.4% of them during median follow-up of 1.3 years. Rate of severe bleeding was not different between those on prophylaxis (7.8 per 1000 person-years) and those not on prophylaxis (10.1 per 1000 person-years). No association was identified between thromboprophylaxis and bleeding. Factors associated with increased bleeding included age (hazard ratio [HR], 1.38 per 10 years increase in age), comorbidity index (HR, 1.18 per SD increase), history of bleeding (HR, 1.54), hypertension (HR, 1.87), and renal disease (HR, 1.56). Conclusion: Risk of serious bleeding from thromboprophylaxis in patients treated for MM was low, and concomitant anticoagulant therapy did not result in increased bleeding risk. Clinical risk factors for bleeding included age, comorbidity index, bleeding history, hypertension, and renal disease.

Continuing Professional Development at Two Rural Hospitals in Ecuador.

Background: E-learning Continuing Professional Development (CPD) is an activity demonstrated to improve the quality of healthcare delivery. The CPD of medical and nursing staff in high income countries (HICs) is commonplace. CPD of administrative staff is less common, but increasingly frequent. In low- and middle-income countries (LMICs), CPD of any kind is infrequent, particularly in rural and remote areas. Objective: The aim of this study was to describe a hospital-based e-learning CPD program for clinical and non-clinical personnel as a unique example of a successful, ongoing educational pilot, quality improvement program involving a broad cohort of employees, in a country that does not require such activities. Methods: Using the online educational platform Chamilo, e-learning modules were created for eight groups including clinical and non-clinical employees. Upon completion of each module, one to two paragraph discussions were provided for each incorrect answer submitted. Two additional chances were offered for the employee to achieve a passing score of 70%. This study reports on the first 10-month period of the program. Findings: All participants achieved the 70% passing threshold after the first or second attempt. There was 100% participation by the employees required to complete the e-learning modules. Employee feedback suggested the modules were good for continuing education, but some felt the CPD was imposed on them. Conclusion: E-learning CPD is an important and emerging element for CPD and may provide opportunities for healthcare service quality improvement as part of broader pedagogical modalities, such as conferences and directed readings, in rural and remote areas of LMICs. These pilot programs could provide important information to develop Spanish-language e-learning CPD programs across a broader region, promote collaboration with regional professional societies, and possibly contribute to the establishment of national health program CPD standards.

Impact of preexisting autoimmune disease on myelodysplastic syndromes outcomes: a population analysis.

Preexisting autoimmune disease affects between 10% and 30% of patients with myelodysplastic syndromes (MDS). Studies comparing outcomes in patients with MDS with and without autoimmune disease show discordant results. Using the Surveillance, Epidemiology, and End Results Medicare database, we conducted a population analysis to define the impact of autoimmunity on MDS outcomes. Cases were ascertained between 2007 and 2017 and claim algorithms used to identify autoimmune disease, demographic characteristics, comorbidity scores, MDS histology, transfusion burden, treatment with hypomethylating agents, and hematopoietic stem cell transplantation. Cox regression models estimated the impact on survival, and competing-risk regression models defined the effect on leukemic transformation. We analyzed 15 277 patients with MDS, including 2442 (16%) with preexisting autoimmune disease. The epidemiologic profile was distinctive in cases with preexisting autoimmunity, who were younger, were predominantly female, and had higher transfusion burden without difference in MDS histologic distribution. Autoimmune disease was associated with 11% decreased risk of death (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.94; P < .001). The effect on risk of leukemic transformation differed based on MDS histology. In low-risk MDS histologies, autoimmunity was associated with a 1.9-fold increased risk of leukemia (HR, 1.87; 95% CI, 1.17-2.99; P = .008), whereas no significant effect was seen in other groups. These results suggest that autoimmune disease affects survival in MDS and is associated with decreased mortality. The survival effect was evident in low-risk histologies despite higher risk of progression to leukemia. This could represent inflammation-driven hematopoiesis, simultaneously favoring less aggressive phenotypes and clonal expansion, which warrants further investigation.

Alpha-methyl acetyl-coA racemase deficiency. Magnetic resonance imaging findings of three patients with encephalopathy, epilepsy, and stroke-like episodes.

Alpha-methyl acyl-CoA racemase deficiency (AMACRD) is a rare peroxisomal disorder that results in the accumulation of pristanic acid and 16 cases have been reported in the literature. Here, we present three additional patients, two confirmed by genomic study and one suspected. Three siblings who were born to healthy unrelated parents developed recurrent episodes of encephalopathy, seizures, and behavioral disturbances. In all 3, brain MRI showed lesions in the thalami, cerebral peduncles, and mesencephalic tegmentum, as well as brain volume loss. In addition, one patient had a chronic hemispheric infarct and an acute contralateral infarct, and another had a subacute infarct involving multiple vascular territories without abnormalities on MR angiography.

Venous thromboembolism mortality and trends in older US adults, 2011-2019.

Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011-2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0-3.2) at 30 days and 19.6% (95% CI 19.2-20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16-0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.

Bleeding risk in patients with multiple myeloma treated for venous thromboembolism: a MarketScan analysis.

Background: Multiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Thromboprophylaxis is thoroughly studied in MM. Contrarily, studies assessing the risk of bleeding in people with MM on anticoagulation are lacking. Objectives: To determine the rate of serious bleeding in patients with MM receiving anticoagulation for VTE and the clinical factors associated with bleeding risk. Methods: Using the MarketScan commercial database, we identified 1298 people with MM treated with anticoagulation for incident VTE events between 2011 and 2019. Hospitalized bleeding was identified using the Cunningham algorithm. Rates of bleeding were calculated and Cox regression identified risk factors for bleeding. Results: Bleeding occurred in 51 (3.9%) cases during median follow-up of 1.13 years. Rate of bleeding among patients with MM on anticoagulation was 24.0 per 1000 person-years. In adjusted regression, factors associated with increased bleeding included age (HR, 1.31 per 10-year increase; 95% CI, 1.03-1.65), Charlson comorbidity index (HR, 1.29 per SD increase; 95% CI, 1.02-1.58), use of antiplatelet agents (HR, 2.4; 95% CI, 1.03-5.68), diabetes (HR, 1.85; 95% CI, 1.06-3.26), and renal disease (HR, 1.80; 95% CI, 1.05-3.16). Cumulative incidence of bleeding was 4.7%, 3.2%, and 3.4% for warfarin, low molecular weight heparin, and direct oral anticoagulants, respectively. Conclusion: In this real-world analysis, the rate of bleeding in people with MM on anticoagulation was comparable to those in other subsets of cancer-related VTE. Bleeding rate was lower with low molecular weight heparin and direct oral anticoagulants than warfarin. Higher comorbidity index, diabetes, antiplatelet agent use, and renal disease were risk factors for serious bleeding.

Outcome of Stem Cell Transplantation in HTLV-1-Associated North American Adult T-Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.

Association between peripheral blood cytopenia and cancer mortality: A race-specific risk factor for cancer death.

BACKGROUND: Cytopenia is associated with cancer through mechanisms including clonal hematopoiesis and chronic inflammation. Cytopenia is more prevalent in Black people but its relationship with racial disparities in cancer mortality is unknown. METHODS: Cytopenia was defined in 19,028 Black and White participants recruited between 2003 and 2007 for the REasons for Geographic and Racial Differences in Stroke cohort, based on age-, sex-, and race-adjusted ranges for blood counts. Cancer death was ascertained from Social Security Death and National Death Indexes. Multivariable Cox models estimated the risk of cancer mortality associated with cytopenia, adjusting for demographics (model1), anemia and cancer risk factors (model2), and socioeconomics (model3). Racial differences in the cytopenia-cancer death association were tested by cross-product interaction terms. RESULTS: Cytopenia was identified in 383 (2%) participants, 250 (65%) White, and 113 (35%) Black people. With median follow-up 11.3 years, 1,224 (6.4%) cancer deaths occurred. Cytopenia was associated with increased risk of cancer mortality in model1 (HR = 1.57, 95%CI 1.15-2.24), model2 (HR = 1.67, 95%CI 1.22-2.30), and model3 (HR = 1.59, 95%CI 1.17-2.17). Participants with cytopenia had twofold increased cumulative incidence of cancer death (13% vs. 6.5%, p < 0.01). Race by cytopenia interaction terms showed higher HR for cancer death in Black compared to White participants: 2.01 versus 1.41 (pinteraction  = 0.016, model1), 2.12 versus 1.45 (pinteraction  = 0.009, model2), and 1.82 versus 1.44 (pinteraction  = 0.04, model3). CONCLUSION: In this large, observational biracial prospective study, cytopenia was a risk factor for cancer death, with stronger association in Black than White people. Though race impacted the association of cytopenia with cancer mortality, cytopenia was not a mediator of the racial disparity in cancer mortality.

Geographic disparities in cardiovascular mortality among patients with myelodysplastic syndromes: A population-based analysis.

INTRODUCTION: Clonal hematopoiesis, a precursor to myelodysplastic syndromes (MDS), constitutes a novel cardiovascular disease (CVD) risk factor, causing growing interest in cardiovascular outcomes in MDS. Rurality is associated with increased CVD but studies on cardiovascular geographic disparities in MDS are lacking. METHODS: Using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry, we identified 52,750 MDS patients between 2001 and 2016. Rurality was defined using Rural-Urban Continuum Codes. Cox regression estimated the association of rurality and cardiovascular death. RESULTS: MDS incidence was equal in urban and rural populations (6.7 per 100,000). Crude probability of cardiovascular death was higher among rural MDS patients. Adjusting for age, sex, race/ethnicity, marital status, insurance, and MDS risk (defined from histology), rural patients had 12% increased risk of CVD death compared to urban patients (HR=1.12, 95%CI 1.03-1.21). HR for CVD death was 1.22 (95%CI 1.01-1.5) in patients from the most rural areas (less than 2500 urban population). Among MDS patients younger than 65 years, rurality was associated with 25% increased risk of CVD death (HR=1.25, 95%CI 1.01-1.59). DISCUSSION: This population-based analysis suggests that rural residence is linked to higher burden of cardiovascular death in patients with MDS. The disparity is not explained by demographic factors or MDS risk. Interventions targeting CVD may improve outcomes in rural MDS patients.

Unrelated Allogeneic Stem Cell Transplant in Relapsed/Refractory AML: Widening the Yellow Brick Road.

A sizable proportion of patients with acute myeloid leukemia (AML) fail to achieve remission. Hematopoietic stem cell transplantation (HSCT) is the only intervention with potential of long-term survival. A recent Acute Leukemia Working Party (ALWP)/European Society for Blood and Marrow Transplantation (EBMT) analysis reports substantial posttransplant survival gains for patients with active disease who received transplants. Decreased relapse was the largest contributor to survival, a cause for optimism in this challenging population. See related article by Nagler et al., p. 4258.

Pesticide-Residue Analysis in Soils by the QuEChERS Method: A Review.

Pesticides are among the most important contaminants worldwide due to their wide use, persistence, and toxicity. Their presence in soils is not only important from an environmental point of view, but also for food safety issues, since such residues can migrate from soils to food. However, soils are extremely complex matrices, which present a challenge to any analytical chemist, since the extraction of a wide range of compounds with diverse physicochemical properties, such as pesticides, at trace levels is not an easy task. In this context, the QuEChERS method (standing for quick, easy, cheap, effective, rugged, and safe) has become one of the most green and sustainable alternatives in this field due to its inherent advantages, such as fast sample preparation, the minimal use of hazardous reagents and solvents, simplicity, and low cost. This review is aimed at providing a critical revision of the most relevant modifications of the QuEChERS method (including the extraction and clean-up steps of the method) for pesticide-residue analysis in soils.

Cancer Care in the Wake of a Cyberattack: How to Prepare and What to Expect.

PURPOSE: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR). METHODS: This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested. RESULTS: The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care. CONCLUSION: Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact.

Fractura triplanar del extremo distal del radio: reporte de caso / Triplanar fracture of the distal end of the radius: case report

Triplanar fractures are those that occur in 3 separate planes at the end of an immature long bone. They typically cross the epiphysis in the sagittal plane, physis in the transverse plane, and metaphysis in the coronal plane. Due to their nature, they are considered an intra-articular injury. Radiographically, these fractures often resemble a Salter-Harris type III epiphyseal slip injury on the anterior-posterior view and a Salter-Harris type II on the lateral view and are consequently considered a Salter-Harris type IV. Only 5 cases of triplanar fracture of the distal end of the radius have been reported so far in the literature, the second case managed with open reduction and internal fixation is reported. This is a 12-year-old patient with a history of trauma to the right wrist after a traffic accident, with deformity and functional limitation and diagnostic images that confirm a fracture at the metaphyseal level of the distal end of the right radius with radial displacement and a stroke. fracture that goes through the epiphysis, physis and metaphysis. An open reduction and internal fixation was performed. 2 years after the injury, the patient is asymptomatic, with preserved ranges of joint mobility and diagnostic images with evidence of adequate consolidation of the fracture, absence of alteration of the physis and consequent normal growth of the radius. Level of Evidence: IV.

Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a "cytopenia phenotype," reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), that enrolled 30 239 Black and White participants aged ≥45 years between 2003 and 2007. Median follow up was ≈9 years. The current study included 19 864 participants from REGARDS study (37.9% men, 40% Black participants) who have complete blood count available at study enrollment. We defined a cytopenia phenotype based on age-, sex-, and race-adjusted lowest fifth percentile of blood counts. Multivariable Cox proportional hazards models estimated the hazard ratios (HR) and 95% CI of cytopenia for mortality and incident cardiovascular disease in adjusted models. Mean age of the study participants was 64 years (SD:9.7). The prevalence of cytopenia was 1.9% (n=378). Cytopenia was associated with increased risk of all-cause mortality (HR, 1.73; 95% CI, 1.34-2.22) and cardiovascular disease mortality (HR, 1.56; 95% CI, 1.11-2.29). Cytopenia was associated with stroke risk in Black but not White participants (HR, 1.96 versus 0.86; P-interaction for race=0.08) and was not associated with coronary heart disease risk. Conclusions We defined a cytopenia phenotype with clinical implications for mortality and stroke risk in a large biracial and geographically diverse population. Whether generated through somatic mutations or decreased organ function, cytopenia was associated with mortality risk and was a race-specific risk factor for stroke.

Ruxolitinib in CMML: A Case Study of Innovative Trial Design in a Rare Cancer.

Alternative statistical designs cannot fully mitigate the limitations of traditional clinical trials in rare cancers. Creative study designs that integrate early clinical data and correlative outcomes from concomitant translational and laboratory models to evaluate the efficacy of druggable targets can potentially expedite access to novel therapies for these patients.See related article by Hunter et al., p. 6095.

Quality of life and self-efficacy in patients with type 2 diabetes mellitus in a Peruvian public hospital.

Quality of life and self-efficacy assessments are increasingly applied in research with type 2 diabetes mellitus patients due to the impact of the disease on their lives. This study aimed to describe the quality of life and self-efficacy in type 2 diabetes mellitus patients and describe the association of quality of life and self-efficacy with demographic, metabolic, and clinical variables. This is a secondary data analysis from a cross-sectional study: Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country. Data were obtained by standardized interviews and evaluation of medical records. The evaluation tools used were the Diabetes 39 questionnaire (D-39) to measure the quality of life and the General Self-Efficacy scale (GSE) for self-efficacy. The median scores of the D-39 and GSE were 34.6 and 34, respectively. The D-39 dimension with the highest score was anxiety and concern. Better quality of life was associated with being older than 65 years old, not having complications, and the absence of depression. No significant association was found between self-efficacy and the quality of life score. Results suggest patients with type 2 diabetes mellitus have a poor quality of life. Patient-centered strategies for type 2 diabetes mellitus care must consider these psychosocial factors to improve disease control and quality of life.

La calidad de vida y la evaluación de autoefiacia se aplican cada vez más en la valoración de los pacientes con diabetes mellitus tipo 2 debido al alto impacto de la enfermedad en sus vidas. Este estudio tiene como objetivo describir la calidad de vida y autoeficacia en pacientes con diabetes mellitus tipo 2 y describir la asociación de calidad de vida y autoeficacia con variables demográficas, metabólicas y clínicas. Este estudio es un análisis secundario del estudio transversal: “Control metabólico en pacientes con diabetes mellitus tipo 2 en un hospital público del Perú: estudio de corte transversal en un país de bajos y medianos ingresos”. Los datos se obtuvieron mediante cuestionarios estandarizadas y evaluación de historias clínicas. Las herramientas de evaluación utilizadas fueron el cuestionario Diabetes -39 (D-39) para medir la calidad de vida y la escala de autoeficacia general para medir autoeficacia (GSE). Las medias del D-39 y GSE fueron 34,6 y 34, respectivamente. La dimensión con la puntuación más alta del D-39 fue "ansiedad y preocupación". Una mejor calidad de vida estuvo asociada con ser mayor de 65 años, no tener complicaciones microvasculares y la ausencia de depresión. No se encontró una asociación significativa entre la autoeficacia y calidad de vida. Los resultados sugieren que los pacientes con diabetes mellitus tipo 2 tienen una pobre calidad de vida. Las estrategias centradas en el cuidado del paciente con diabetes mellitus tipo 2 deben considerar estos factores psicosociales para mejorar el control de la enfermedad y la calidad de vida.

Comprehensive health evaluation of an urban wetland using quality indices and decision trees.

In a world where pristine water is becoming scarcer, the need to reuse water becomes imperative. In this context explaining the water quality, purpose fitness and the parameters or conditions of the water body to adjust so as to improve its quality, are of great relevance. The goal of the present study was the use of water, riverine, and biodiversity quality indices to assess the condition of the studied urban wetland, since no single index can provide a complete health assessment of a water body. Decision trees were also used to elucidate the best water parameters to mend in order to recover the overall health of the urban wetland. The decision trees identified relevant physicochemical parameters as well as their approximate concentration at which a healthy water environment can be sustained for zooplankton and proved to be a powerful and simple alternative to customary approaches. Suspended particles and phosphates proved to be important parameters with concentrations approximately lower than 88 mg L-1 and 11 mg L-1, respectively, for a good biodiversity index of zooplankton. Ammonia, total coliforms, BOD, nitrates, and sodium were the main parameters that affected the water quality index. The vegetation coverage and its structure were the driving factors in the riverine quality index of the wetland.