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BACKGROUND: Intermittent androgen deprivation therapy (iADT) alleviates some side effects of continuous (c) ADT in patients with prostate cancer (PC), but its relative impact on ADT-associated comorbidities is uncertain. We assessed real-world use of iADT and cADT and associated risk of cardiovascular and endocrine/metabolic events in patients with nonmetastatic (nm) PC. METHODS: This retrospective longitudinal cohort study included patients with nmPC initiating systemic ADT with gonadotropin-releasing hormone agonists (goserelin, histrelin, leuprolide, and triptorelin) or antagonists (degarelix) in the US Surveillance, Epidemiology and End Results-Medicare database (2010-2017), who had ≥ 36 months of continuous insurance coverage, unless death occurred, and did not receive chemotherapy or next-generation hormonal therapies during follow-up (through 2019). Risk of major adverse cardiovascular events (MACE [myocardial infarction, stroke, cardiomyopathy/heart failure, pulmonary embolism, ischemic heart disease, all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, and osteoporosis) were examined between cohorts. Inverse probability of treatment-weighted Cox regression models estimated adjusted hazard ratios (HRs) of the outcomes. RESULTS: Of 10,655 eligible patients, 2,095 (19.7%) received iADT and 8,560 (80.3%) cADT. Median follow-up was 43.9 and 48.4 months and median ADT duration (excluding iADT gaps) was 22.0 and 13.5 months for the iADT and cADT cohorts, respectively. Patients receiving cADT had a lower risk of MACE vs. iADT (HR 0.90; 95% confidence interval [CI] 0.83-0.96). No difference in risk of endocrine/metabolic events was observed (HR 0.97; 95% CI 0.92-1.03). Subgroup analysis found that the difference in MACE was maintained in patients with a history of cardiovascular disease (HR 0.90; 95% CI 0.83-0.98) and eliminated in patients without (HR 0.94; 95% CI 0.82-1.08). CONCLUSIONS: Patients with nmPC who received cADT had a lower risk of MACE and similar risk of endocrine/metabolic events vs. those who received iADT. Further research assessing both regimens is needed to inform treatment decisions.
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ABSTRACT: Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) can develop hypogammaglobulinemia, a form of secondary immune deficiency (SID), from the disease and treatments. Patients with hypogammaglobulinemia with recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). This study evaluated patterns of immunoglobulin G (IgG) testing and the effectiveness of IgRT in real-world patients with CLL or NHL. A retrospective, longitudinal study was conducted among adult patients diagnosed with CLL or NHL. Clinical data from the Massachusetts General Brigham Research Patient Data Registry were used. IgG testing, infections, and antimicrobial use were compared before vs 3, 6, and 12 months after IgRT initiation. Generalized estimating equation logistic regression models were used to estimate odds ratios, 95% confidence intervals, and P values. The study population included 17 192 patients (CLL: n = 3960; median age, 68 years; NHL: n = 13 232; median age, 64 years). In the CLL and NHL cohorts, 67% and 51.2% had IgG testing, and 6.5% and 4.7% received IgRT, respectively. After IgRT initiation, the proportion of patients with hypogammaglobulinemia, the odds of infections or severe infections, and associated antimicrobial use, decreased significantly. Increased frequency of IgG testing was associated with a significantly lower likelihood of severe infection. In conclusion, in real-world patients with CLL or NHL, IgRT was associated with significant reductions in hypogammaglobulinemia, infections, severe infections, and associated antimicrobials. Optimizing IgG testing and IgRT are warranted for the comprehensive management of SID in patients with CLL or NHL.
Subject(s)
Immunoglobulin G , Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, Non-Hodgkin , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Aged , Middle Aged , Male , Female , Immunoglobulin G/blood , Lymphoma, Non-Hodgkin/therapy , Lymphoma, Non-Hodgkin/complications , Retrospective Studies , Infections/etiology , Agammaglobulinemia/complications , Agammaglobulinemia/therapy , Agammaglobulinemia/etiology , Treatment Outcome , Longitudinal Studies , Aged, 80 and over , Adult , Immunization, Passive/methodsABSTRACT
INTRODUCTION: Despite national guidelines against contralateral prophylactic mastectomy (CPM) in low- to moderate-risk breast cancer, CPM use continues to rise. Breast reconstruction improves health-related quality of life and satisfaction among women undergoing mastectomy. Given the lack of data regarding factors associated with reconstruction after CPM and the known benefits of reconstruction, we sought to investigate whether disparities exist in receipt of reconstruction after CPM. METHODS: The 2004-2017 National Cancer Database was queried to identify women diagnosed with breast cancer who underwent unilateral mastectomy with CPM. Patients were divided into two groups: those who underwent planned reconstruction at any timepoint and those who did not. A secondary analysis comparing types of reconstruction (tissue, implant, combined) was conducted. Patient, tumor, and demographic characteristics were analyzed using chi-square test and odds ratios were calculated using generalized estimating equations. RESULTS: The cohort included 1,73,249 women: 95,818 (55.3%) underwent reconstruction and 77,431 (45.7%) did not. Both the rate CPM and the proportion of women undergoing reconstruction after CPM increased between 2004 and 2017. Of the women who had reconstruction, 40,840 (51.7%) received implants, 29,807 (37.7%) had tissue, and 8352 (10.6%) had combined reconstruction. After adjusted analysis, factors associated with reconstruction were young age, Hispanic ethnicity, private insurance, and living in an area with the highest education and median income (P < 0.01). Patients who underwent reconstruction were less likely to have radiation (P < 0.01) and chemotherapy (P < 0.01), more likely to have stage I disease (P < 0.01), and to be treated at an integrated cancer center (P < 0.01). CONCLUSIONS: Reconstruction after CPM is disproportionately received by younger women, Hispanics, those with private insurance, and higher socioeconomic status and education. While the rate of reconstruction after CPM is increasing, there remain significant disparities. Conscious efforts must be made to eliminate these disparities, especially given the known benefits of reconstruction after mastectomy.
Subject(s)
Breast Neoplasms , Healthcare Disparities , Mammaplasty , Prophylactic Mastectomy , Humans , Female , Prophylactic Mastectomy/statistics & numerical data , Middle Aged , Mammaplasty/statistics & numerical data , Adult , Breast Neoplasms/surgery , Breast Neoplasms/prevention & control , Healthcare Disparities/statistics & numerical data , Aged , Retrospective Studies , United States/epidemiologyABSTRACT
Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.
Subject(s)
Darbepoetin alfa , Hematinics , Renal Dialysis , Humans , Renal Dialysis/adverse effects , Hematinics/adverse effects , Hematinics/therapeutic use , Hematinics/administration & dosage , Female , Male , Retrospective Studies , Aged , Middle Aged , Darbepoetin alfa/therapeutic use , Darbepoetin alfa/adverse effects , Darbepoetin alfa/administration & dosage , United States/epidemiology , Cardiovascular Diseases/mortality , Epoetin Alfa/therapeutic use , Epoetin Alfa/adverse effects , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/complications , Anemia/drug therapy , Medicare , Delayed-Action Preparations , Aged, 80 and over , Erythropoietin , Recombinant ProteinsABSTRACT
BACKGROUND: Some epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. METHODS: We conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012-2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. RESULTS: We identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56-2.73). Results were consistent across sensitivity and subgroup analyses. CONCLUSION: This study did not find an association between DAAs and PD among patients with HCV infection.
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Antiviral Agents , Hepatitis C, Chronic , Parkinson Disease , Humans , Parkinson Disease/epidemiology , Parkinson Disease/drug therapy , Male , Female , Antiviral Agents/therapeutic use , Middle Aged , Retrospective Studies , Aged , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/complications , Adult , United States/epidemiology , Incidence , Proportional Hazards Models , Young AdultABSTRACT
BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has been an unprecedented healthcare crisis, one that threatened to overwhelm health systems and prompted an urgent need for early treatment options for patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. Randomised clinical trials established the safety and efficacy of monoclonal antibodies (mAbs) early in the pandemic; in vitro data subsequently led to use of the mAbs being discontinued, without clear evidence on how these data were linked to outcomes. In this study, we describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19 treated with sotrovimab versus untreated patients. METHODS: Electronic health records from the National COVID Cohort Collaborative (N3C) were used to identify US patients (aged ≥ 12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (27 September 2021-30 April 2022) who met Emergency Use Authorization (EUA) high-risk criteria. Patients receiving the mAb sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort, with the day of infusion as the index date. Untreated patients (no evidence of early mAb treatment, prophylactic mAb or oral antiviral treatment) were assigned to the untreated cohort, with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion in the sotrovimab cohort. The primary endpoint was hospitalisation or death (both all-cause) within 29 days of index, reported as descriptive rate and adjusted [via inverse probability of treatment weighting (IPTW)] odds ratio (OR) and 95% confidence interval (CI). RESULTS: Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis period, 4992 met the criteria for the sotrovimab cohort, and 541,325 were included in the untreated cohort. Before weighting, significant differences were noted between the cohorts; for example, patients in the sotrovimab cohort were older (60 years versus 54 years), were more likely to be white (85% versus 75%) and met more EUA criteria (mean 3.1 versus 2.2) versus the untreated cohort. The proportions of patients with 29-day hospitalisation or death were 3.5% (176/4992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts, respectively (unadjusted OR: 0.78; 95% CI: 0.67, 0.91; p = 0.001). In adjusted analysis, sotrovimab was associated with a 25% reduction in the odds of hospitalisation or death compared with the untreated cohort (IPTW-adjusted OR: 0.75; 95% CI: 0.61, 0.92; p = 0.005). CONCLUSIONS: Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalisation, mortality) in the period 27 September 2021-30 April 2022, which included Delta and Omicron BA.1 variants and an early surge of Omicron BA.2 variant.
Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal , Administration, OralABSTRACT
BACKGROUND: Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitant CCB-SSRI users initiating cytochrome P450 3A4 (CYP3A4)-inhibiting SSRIs versus non-CYP3A4 inhibiting SSRIs. METHODS: This retrospective cohort study used IBM MarketScan commercial claims and Medicare Supplemental database (2007-2019). We included adults diagnosed with hypertension and depression, newly initiating SSRIs while being treated with CCBs (ie, concomitant CCB-SSRI users) and those who did not (ie, CCB-only users). Primary outcome was the first occurrence of any fracture. We used stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores to balance baseline risk between groups. Cox proportional hazard regression modeling was used to compare fracture risk. RESULTS: We identified 191 352 concomitant CCB-SSRI and 956 760 CCB-only users (mean age = 56 years, 50.1% males). After sIPTW, compared with CCB-only users, CCBs-SSRIs users had a higher risk of fractures (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.22-1.66). No difference in the risk of fractures between concomitant users of CCB-CYP3A4-inhibiting SSRIs and those of CCB-non-CYP3A4 inhibiting SSRIs (HR: 1.10, 95% CI: 0.87-1.40) was observed. CONCLUSION AND RELEVANCE: Short-term concomitant CCB-SSRI use was associated with increased fracture risk. Concomitant CCBs and CYP3A4-inhibiting SSRIs compared with CCBs and non-CYP3A4 inhibiting SSRIs use was not associated with increased risk.
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OBJECTIVE: To determine if upper airway characteristics and airway pressure change significantly between low risk, healthy non-OSA subjects, and OSA subjects during respiration using cone-beam computed tomography (CBCT) imaging and steady-state k-ω model computational fluid dynamics (CFD) fluid flow simulations, respectively. MATERIALS AND METHODS: CBCT scans were collected at both end-inhalation and end-exhalation for 16 low-risk non-OSA subjects and compared to existing CBCT data from 7 OSA subjects. The CBCT images were imported into Dolphin Imaging and the upper airway was segmented into stereolithography (STL) files for area and volumetric measurements. Subject models that met pre-processing criteria underwent CFD simulations using ANSYS Fluent Meshing (Canonsburg, PA) in which unstructured mesh models were generated to solve the standard dual equation turbulence model (k-ω). Objective and supplemental descriptive measures were obtained and statistical analyses were performed with both parametric and non-parametric tests to evaluate statistical significance at P < .05. RESULTS: Regarding area and volumetric assessments, there were statistically significant mean differences in Total Volume and Minimum CSA between non-OSA and OSA groups at inhalation and exhalation (P = .002, .003, .004, and .007), respectively. There were also statistically significant mean differences in volume and min CSA between the inhalation and exhalation for the non-OSA group (P < .001 and .002), respectively. CONCLUSION: While analysis of the CFD simulation was limited by the collected data available, a finding consistent with published literature was that the OSA subject group simulation models depicted the point of lowest pressure coinciding with the area of maximum constriction.
Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Hydrodynamics , Sleep Apnea, Obstructive/diagnostic imaging , Cone-Beam Computed Tomography/methods , NoseABSTRACT
Background: This retrospective study gathered medical/pharmacy claims data on patients with inflammatory bowel disease (IBD) between January 01, 2000 and March 31, 2019 from the IBM MarketScan commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with IBD. Methods: Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims), and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs were compared between cases and controls. Results: Matched IBD cohorts (21 321 cases/21 321 controls) were identified (42% Crohn's disease [CD] and 58% ulcerative colitis [UC]) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P < .001) and all-cause hospitalizations (IRR [95% CI]: 1.92 [1.81, 2.04], P < .001); as well as significantly higher all-cause total direct healthcare costs (mean: $24 620 vs. $15 324; P < .001). Similar findings were observed for IBD-related outcomes, as well as in CD- and UC-specific subgroups. Conclusions: Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.
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BACKGROUND: This study aims to formulate and characterize sorafenib-loaded resealed erythrocytes (SoRE) and investigate their anticancer activity in a rat model of hepatocellular carcinoma. METHODS: SoRE were prepared by hypotonic dialysis of red blood cells obtained from Wistar rats using a range of drug-containing dialysis mediums (2-10 mg/ml) and osmosis time (30-240 mins). Optimized SoRE (8 mg/mL and 240 mins) were characterized for size, morphology, stability, entrapment efficiency, in vitro release profiles, and in vivo efficacy evaluations. For efficacy studies, optimized SoRE were intravenously administered to Wistar rats having hepatocellular lesions induced by aflatoxin B and monitored for in vivo antineoplastic activity. RESULTS: The amount of sorafenib entrapped was directly proportional to the drug concentration in the dialysis medium and duration of osmosis; highest for 10 mg/mL and 240 minutes and lowest for 2 mg/mL and 30 minutes, respectively. Optimized SoRE were biconcave with a size of 112.7 nm and zeta potential of -11.95 ± 2.25 mV. Osmotic and turbulence fragility were comparable with native erythrocytes. CONCLUSION: Drug release follows the first-order pattern. In vivo investigations reveal better anticancer activity of SoRE formulation compared to sorafenib standard preparation. Resealed erythrocytes loaded with sorafenib displayed first-order in vitro release and promising anticancer activity in a rat model of hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Rats , Animals , Sorafenib/pharmacology , Carcinoma, Hepatocellular/drug therapy , Rats, Wistar , Liver Neoplasms/drug therapy , Renal Dialysis , ErythrocytesABSTRACT
PURPOSE: To assess variability in interpretation of electroencephalogram (EEG) background activity and qualitative grading of cerebral dysfunction based on EEG findings, including which EEG features are deemed most important in this determination. METHODS: A web-based survey (Qualtrics) was disseminated to electroencephalographers practicing in institutions participating in the Critical Care EEG Monitoring Research Consortium between May 2017 and August 2018. Respondents answered 12 questions pertaining to their training and EEG interpretation practices and graded 40 EEG segments (15-second epochs depicting patients' most stimulated state) using a 6-grade scale. Fleiss' Kappa statistic evaluated interrater agreement. RESULTS: Of 110 respondents, 78.2% were attending electroencephalographers with a mean of 8.3 years of experience beyond training. Despite 83% supporting the need for a standardized approach to interpreting the degree of dysfunction on EEG, only 13.6% used a previously published or an institutional grading scale. The overall interrater agreement was fair ( k = 0.35). Having Critical Care EEG Monitoring Research Consortium nomenclature certification (40.9%) or EEG board certification (70%) did not improve interrater agreement ( k = 0.26). Predominant awake frequencies and posterior dominant rhythm were ranked as the most important variables in grading background dysfunction, followed by continuity and reactivity. CONCLUSIONS: Despite the preference for a standardized grading scale for background EEG interpretation, the lack of interrater agreement on levels of dysfunction even among experienced academic electroencephalographers unveils a barrier to the widespread use of EEG as a clinical and research neuromonitoring tool. There was reasonable agreement on the features that are most important in this determination. A standardized approach to grading cerebral dysfunction, currently used by the authors, and based on this work, is proposed.
Subject(s)
Brain Diseases , Electroencephalography , Humans , Surveys and Questionnaires , Critical Care , Brain , Observer VariationABSTRACT
Objective: Because time to treatment has been shown to be associated with increase in the risk of death for Non Small Cell Lung Cancer (NSCLC) patients, we examined the prevalence and magnitude of racial disparities in mean time to radiation therapy (TTRT) for Stage I-III non-small cell lung cancer patients across a variety of treatment facilities. Methods: Utilizing the United States National Cancer Database (NCDB), we determined differences in TTRT between different races and different treatment facilities. Results: Concordant with past research, we found that non-White patients and patients treated at academic facilities, regardless of race, have longer mean TTRT, and that racial disparities in TTRT extend across all treatment facilities (all p<0.05). Conclusions: These findings shed light on the potential presence of and impact of structural racism on patients seeking cancer treatment, and the need for further investigation behind the reasonings behind longer TTI for non-White patients. To elucidate the real-world applicability of these results, further investigation into the societal determinants that perpetuate disparity in time to radiation therapy, and potential interventions in the clinical setting to improve cultural and racial sensitivity among healthcare professionals is recommended.
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BACKGROUND: Limited evidence exists regarding long-term effectiveness and safety of aldosterone antagonists (AAs) versus beta blockers (BBs) as fourth-line antihypertensive agents in patients with resistant hypertension (RH). We evaluated the comparative effectiveness and safety of aldosterone AA versus BB. METHODS: We conducted a real-world retrospective cohort study using IBM MarketScan commercial claims and Medicare Supplemental claims (2007-2019). Patients with RH entered the cohort (ie, index date) when they newly initiated either AA or BB. The effectiveness outcome was major adverse cardiovascular events. Safety outcomes were hyperkalemia, gynecomastia, and kidney function deterioration. Potential confounding was addressed by adjustment for baseline characteristics via stabilized inverse probability of treatment weighting (SIPTW) based on propensity scores. Cox proportional hazards regression with SIPTWs were used to estimate adjusted hazard ratio (aHR) and 95% CI comparing risk for outcomes between AA and BB groups. RESULTS: We identified 80 598 patients with RH (mean age: 61 years, 51% males), of which 6626 initiated AA and 73 972 initiated BB as the fourth antihypertensive agent. Among patients with RH, initiation of AA as a fourth-line antihypertensive agent did not significantly reduce major adverse cardiovascular event risk relative to BB initiation (aHR, 0.77 [95% CI, 0.50-1.19]) but did substantially increase the risk of hyperkalemia (aHR, 3.86 [95% CI, 2.78-5.34]), gynecomastia (aHR, 9.51 [95% CI, 5.69-15.89]), and kidney function deterioration (aHR, 1.63 [95% CI, 1.34-1.99]). CONCLUSIONS: Long-term clinical trials powered to assess major adverse cardiovascular events are necessary to understand the risk-benefit trade-off of AA as fourth-line therapy for RH.
Subject(s)
Gynecomastia , Hyperkalemia , Hypertension , Adrenergic beta-Antagonists/adverse effects , Aged , Antihypertensive Agents/adverse effects , Female , Gynecomastia/chemically induced , Gynecomastia/drug therapy , Humans , Hyperkalemia/chemically induced , Hyperkalemia/epidemiology , Hypertension/chemically induced , Hypertension/drug therapy , Male , Medicare , Middle Aged , Mineralocorticoid Receptor Antagonists/adverse effects , Retrospective Studies , United States/epidemiologyABSTRACT
BACKGROUND AND OBJECTIVES: In 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration-recommended erythropoietin-stimulating agent labeling for Medicare-insured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006-2010) and postpolicy (2012-2016) implementation using interrupted time series and Cox proportional hazards regression models. RESULTS: Of 481,564 patients, erythropoietin-stimulating agent use immediately decreased by 84.8 per 1000 persons (P<0.001), with a significant decrease in the slope of the trend line (both P=0.001). Blood transfusion use rapidly increased by 8.34 per 1000 persons in April 2012 and then gradually decreased (both P=0.001). The percentage of patients with hemoglobin >11 g/dl decreased from 68% in January 2006 to 28% in December 2016, whereas those with hemoglobin <9 g/dl increased from 5% to 9%. Overall major adverse cardiovascular event (adjusted hazard ratio, 0.95; 95% confidence interval, 0.94 to 0.96), stroke (adjusted hazard ratio, 0.83; 95% confidence interval, 0.80 to 0.86), all-cause mortality (adjusted hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89), cardiovascular mortality (adjusted hazard ratio, 0.81; 95% confidence interval, 0.79 to 0.83), and heart failure (adjusted hazard ratio, 0.86; 95% confidence interval, 0.84 to 0.88) risks were lower. Acute myocardial infarction risk (adjusted hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.06) was higher after policies changed. CONCLUSIONS: The Medicare reimbursement policy and Food and Drug Administration-recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis.
Subject(s)
Anemia , Erythropoietin , Heart Failure , Hematinics , Kidney Failure, Chronic , Myocardial Infarction , Stroke , Adult , Aged , Anemia/drug therapy , Epoetin Alfa , Heart Failure/complications , Hematinics/adverse effects , Hemoglobins , Humans , Kidney Failure, Chronic/complications , Medicare , Policy , Renal Dialysis/adverse effects , Retrospective Studies , United StatesABSTRACT
STUDY OBJECTIVE: To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression. DESIGN: Retrospective cohort study. DATA SOURCE: IBM MarketScan® commercial claims database and Medicare Supplemental claims database from 2007 to 2019. PATIENTS: Patients aged 18 years or older with stable treated hypertension and depression who newly initiate either serotonin norepinephrine reuptake inhibitors or SSRIs. INTERVENTION: Serotonin norepinephrine reuptake inhibitors versus SSRIs. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were: (1) TI (first occurrence of antihypertensive regimen augmentation or dose escalation); (2) MACE (first occurrence of stroke or acute myocardial infarction). Baseline risk between the two groups was balanced via 1:1 propensity score (PS) matching. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). After 1:1 PS matching, we included 19,160 patients in the study cohort (mean age: 52 years, 62% females) of which 9580 initiated serotonin norepinephrine reuptake inhibitors and 9580 initiated SSRIs. Patients who initiated serotonin norepinephrine reuptake inhibitors had 15 MACE events (incidence rate per 1000 person-years [IR], 3.9) and 1675 TI events (IR, 540.2), compared with 17 MACE events (IR, 4.0) and 1774 TI events (IR, 518.5) in the SSRI group. The risk of TI (aHR: 1.01, [95% CI: 0.94, 1.08]) and MACE (aHR: 0.98, [95% CI: 0.49, 1.96]) did not differ among patients initiated serotonin norepinephrine reuptake inhibitors versus SSRIs. CONCLUSIONS: Among patients with stable hypertension and depression, initiation of serotonin norepinephrine reuptake inhibitors had a similar risk of antihypertensive TI and MACE compared to initiation of SSRIs. Future study with a larger sample size is needed to confirm our findings.
Subject(s)
Hypertension , Stroke , Aged , Antihypertensive Agents/adverse effects , Depression/drug therapy , Depression/epidemiology , Female , Humans , Hypertension/drug therapy , Male , Medicare , Middle Aged , Norepinephrine , Retrospective Studies , Serotonin , Selective Serotonin Reuptake Inhibitors/adverse effects , Stroke/epidemiology , United States/epidemiologyABSTRACT
Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p < 0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p < 0.01) and higher daily cost (USD 3246 vs. USD 2679, p < 0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.
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SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-diagnosed adults with hypertension, we assessed associations between antihypertensive exposure (ACEI/ARB vs. non-ACEI/ARB antihypertensives, as well as between ACEI- vs. ARB) at the time of COVID-19 diagnosis, using electronic health record data from PCORnet health systems. The primary outcomes were all-cause hospitalization or death (outpatient cohort) or all-cause death (inpatient), analyzed via Cox regression weighted by inverse probability of treatment weights. From February 2020 through December 9, 2020, 11,246 patients (3477 person-years) and 2200 patients (777 person-years) were included from 17 health systems in outpatient and inpatient cohorts, respectively. There were 1015 all-cause hospitalization or deaths in the outpatient cohort (incidence, 29.2 events per 100 person-years), with no significant difference by ACEI/ARB use (adjusted HR 1.01; 95% CI 0.88, 1.15). In the inpatient cohort, there were 218 all-cause deaths (incidence, 28.1 per 100 person-years) and ACEI/ARB exposure was associated with reduced death (adjusted HR, 0.76; 95% CI, 0.57, 0.99). ACEI, versus ARB exposure, was associated with higher risk of hospitalization in the outpatient cohort, but no difference in all-cause death in either cohort. There was no evidence of effect modification across pre-specified baseline characteristics. Our results suggest ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19.
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INTRODUCTION: Urological disease is prevalent in low- and middle-income countries. Concurrently, the inability to maintain employment or provide family care contributes to poverty. We assessed the microeconomic impacts of urological disease in Belize. METHODS: We conducted a prospective survey-based assessment of patients evaluated during surgical trips by the charity Global Surgical Expedition. Patients completed a survey focusing on impact of urological disease on work and caretaker responsibilities, as well as its economic impact. The primary study outcome was income loss resulting from work impairment or work time missed related to urological disease. Income loss was calculated using the validated Work Productivity and Activity Impairment Questionnaire. RESULTS: A total of 114 patients completed surveys. Overall, 87.7% and 37.2% of respondents reported a negative impact of urological disease on job and caretaking responsibilities, respectively. Nine (7.9%) patients were unemployed secondary to their urological disease. Sixty-one (53.5%) patients provided financial data sufficient for analysis. In this cohort, median weekly income was $250 Belize dollars (approximately $125 United States Dollars), while median weekly cost for urological disease treatment was $25 Belize dollars. Among the 21 (34.5%) patients who missed work due to urological disease, median weekly income loss was $35.6 Belize dollars, representing 55% of their total income. A vast majority (88.6%) of patients reported that cure of urological disease would increase ability to work and/or care for family. CONCLUSIONS: In Belize, urological disease results in significant impairment of work and caretaking responsibilities, as well as income loss. Efforts are necessary to provide urological surgeries in low- and middle-income countries as urological disease impacts not only quality of life, but also financial health.
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PURPOSE: Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. PATIENTS AND METHODS: This study was a non-interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The association between AH drug utilization on AJCC stage I-III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. RESULTS: The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer-specific mortality (HR: 0.79, 95% CI: 0.75-0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.87), beta-blockers (HR: 0.87, 95% CI: 0.84-0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80-0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer-specific mortality (HR: 0.94, 95% CI: 0.90-0.98). CONCLUSION: Further research needs to be performed, but AH medications may present a promising, low-cost pathway to supporting CRC treatment for stage I-III cancers.
Subject(s)
Antihypertensive Agents/therapeutic use , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Adrenergic beta-Antagonists/therapeutic use , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Colonic Neoplasms/blood supply , Confidence Intervals , Female , Humans , Immunity, Cellular/drug effects , Male , Medicare , Medication Adherence , Neoplasm Staging , Proportional Hazards Models , Protective Agents/therapeutic use , Rectal Neoplasms/blood supply , Retrospective Studies , SEER Program , Sodium Chloride Symporter Inhibitors , Tumor Microenvironment/immunology , United StatesABSTRACT
Objective: The seven-vaccine series protects infants from several preventable diseases, yet disparities in its use remain in the United States. Methods: We assessed the seven-vaccine immunization rate and its predictors in infants 19-35 months using the National Immunization Survey from 2009 to 2018. Results: The seven-vaccine series rate was 72.8%, well short of the healthy people 2020 target of 90%. African American infants, infants born to mothers with less than high school education, and infants in families with an income below poverty were less likely to get the complete series. Conclusion: Disparities still exist in protecting infants from preventable diseases in the United States.