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STUDY DESIGN: This study was a retrospective propensity-matched study of patients receiving opioid sparing anesthesia (OSA) and those who did not receive an opioid sparing anesthesia regimen. OBJECTIVES: To determine whether patients undergoing spine fusion for deformity fared better with an OSA regimen than those not having an OSA regimen. SUMMARY OF BACKGROUND DATA: There has been a tremendous focus on opioid overuse. Accordingly, OSA regimens are being introduced to reduce narcotic use. However, OSA has not been studied in the adult spine deformity population. METHODS: 43 patients undergoing fusion of at least five levels in the thoracolumbar spine received OSA. They were matched to 43 patients who did receive an OSA regimen. We analyzed a number of metrics including blood loss, anesthesia time, post anesthesia care unit (PACU) pain scores, postoperative pain scores, complications, length of stay, and readmissions. RESULTS: The OSA group had significantly lower pain scores both before transfer to (4.6 vs. 7.6, P=0.000) and after transfer from (4.2 vs. 6.2 P=0.002) the PACU. Opioid use was significantly lower in the OSA group (454 vs. 241 MMEs by POD4, P=0.022). Fewer patients required blood transfusion in the OSA (1 vs. 28, P=0.000) group. Fewer patients in the OSA group had constipation and urinary retention (1 vs. 9, P=0.015). There was no difference in discharge home or to a facility. The lengths of hospital (4.33 vs. 6.19, P=0.009) and ICU (0.12 vs. 0.70 days, P=0.009) stay were significantly shorter in the OSA group. CONCLUSION: OSA regimens have numerous benefits in patients undergoing spinal deformity surgery including less opioid use, fewer postoperative complications, and a reduced length of stay.
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BACKGROUND AND AIMS: The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD). METHODS: Among 14,051 participants (mean age 54 [SD 6 years]) from the Atherosclerosis Risk in Communities study, we categorized PAD status as symptomatic PAD (intermittent claudication or leg revascularization), asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 without clinical history of symptoms), and ABI 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and >1.30. We evaluated their associations with two kidney outcomes: ESKD (the need of renal replacement therapy or death due to kidney disease) and CKD (ESKD cases or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models. RESULTS: Over â¼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups. CONCLUSIONS: Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent.
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Introduction: Xylazine is a veterinary anesthetic increasingly present alongside illicit fentanyl in the US and Canada, presenting novel health risks. Although xylazine remains less common in the Western US, Mexican border cities serve as key trafficking hubs and may have higher prevalence of novel substances, but surveillance has been limited. Methods: We examined deidentified records from the Prevencasa harm reduction clinic in Tijuana, describing urine and paraphernalia testing from patients reporting using illicit opioids within 24 hr. Xylazine (two types), fentanyl, opiate, methamphetamine, amphetamine, benzodiazepine, and nitazene test strips were used to test urine and paraphernalia samples. Paraphernalia samples were also analyzed with mass spectrometry. Results: The study consisted of 23 participants that provided both urine and paraphernalia samples. Of the participants studied, 100 %, 91.3 %, and 69.6 % reported using China White/fentanyl, methamphetamine, and tar heroin, respectively. The mean age was 41.7 years, 95.7 % were male, 65.2 % were unhoused, and 30.4 % had skin wounds at the time of sample collection.Xylazine positivity in urine, for the two types used, was 82.6 % and 65.2 %. For paraphernalia testing, the xylazine positivity was 65.2 % and 47.8 %. Confirmatory testing of paraphernalia samples by mass spectrometry indicated a 52.2 % xylazine positivity. This testing also revealed positivity rates for fentanyl (73.9 %), fluorofentanyl (30.4 %), tramadol (30.4 %), and lidocaine (30.4 %).The mass spectrometry results suggest lidocaine triggered n = 3 and n = 0 false positives among the xylazine test strip types. A total of n = 0 and n = 1 false negatives were also observed. Discussion: Xylazine is present on the U.S.-Mexico border, requiring public health intervention. High lidocaine positivity complicates the clinical detection of xylazine via testing strips. Xylazine was found to be more prevalent in urine than in paraphernalia samples. Confirmatory urine studies are needed to better understand possible complications of using test strips for toxicological testing.
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Phage-encoded anti-CRISPR (Acr) proteins inhibit CRISPR-Cas systems to allow phage replication and lysogeny maintenance. Most of the Acrs characterized to date are stable stoichiometric inhibitors, and while enzymatic Acrs have been characterized biochemically, little is known about their potency, specificity, and reversibility. Here, we examine AcrIF11, a widespread phage and plasmid-encoded ADP-ribosyltransferase (ART) that inhibits the Type I-F CRISPR-Cas system. We present an NMR structure of an AcrIF11 homolog that reveals chemical shift perturbations consistent with NAD (cofactor) binding. In experiments that model both lytic phage replication and MGE/lysogen stability under high targeting pressure, AcrIF11 is a highly potent CRISPR-Cas inhibitor and more robust to Cas protein level fluctuations than stoichiometric inhibitors. Furthermore, we demonstrate that AcrIF11 is remarkably specific, predominantly ADP-ribosylating Csy1 when expressed in P. aeruginosa. Given the reversible nature of ADP-ribosylation, we hypothesized that ADPr eraser enzymes (macrodomains) could remove ADPr from Csy1, a potential limitation of PTM-based CRISPR inhibition. We demonstrate that diverse macrodomains can indeed remove the modification from Csy1 in P. aeruginosa lysate. Together, these experiments connect the in vitro observations of AcrIF11's enzymatic activity to its potent and specific effects in vivo, clarifying the advantages and drawbacks of enzymatic Acrs in the evolutionary arms race between phages and bacteria.
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Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen Pseudomonas aeruginosa, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes.
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BACKGROUND: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex. METHODS: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mmâ Hg; diastolic blood pressure ≥80 mmâ Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mmâ Hg or diastolic blood pressure ≥90 mmâ Hg) using unadjusted and comorbidity-adjusted models. RESULTS: The prevalence of hypertension increased from 40% (ages, 43-46 years) to 93% (ages, 91-94 years). Within hypertensive individuals, the prevalence of uncontrolled hypertension was higher in men (33%) than women (23%) at ages 43 to 46 years but became higher in women than men starting at ages 61 to 64, with 56% of women and 40% men having uncontrolled hypertension at ages 91 to 94. This sex difference was not explained by differences in coronary heart disease, diabetes, body mass index, estimated glomerular filtration rate, number of antihypertension medications, classes of medications, or adherence to medications. In both sexes, uncontrolled hypertension was associated with a higher risk for chronic kidney disease progression (hazard ratio, 1.5 [1.2-1.9]; P=4.5×10-4), heart failure (hazard ratio, 1.6 [1.4-2.0]; P=8.1×10-7), stroke (hazard ratio, 2.1 [1.6-2.8]; P=1.8×10-8), and mortality (hazard ratio, 1.5 [1.3-1.6]; P=6.2×10-19). CONCLUSIONS: Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course.
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Eosinophilic esophagitis (EoE) is a disease marked by a surplus of eosinophils, a type of white blood cell that causes inflammation and irritation. The current diagnostic and monitoring procedure for EoE is endoscopy with biopsy, which is invasive, expensive, and leads to tissue tearing in patients. A biomarker in plasma would offer a much less invasive form of disease monitoring for patients with EoE. Eosinophils have been shown to make eosinophil peroxidase, an enzyme that produces hypobromous acid, reacts with primary amines, and forms bromoamides. One product of this biochemical reaction is 3-bromotyrosine. We have optimized a selective, sensitive, and reproducible method to detect and quantify L-tyrosine and 3-bromotyrosine in human plasma using high-pressure liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Our sample preparation and analysis method requires fewer steps and provides a faster analysis than previous methods. Method validation yielded limits of quantification of 50 ng mL-1 for L-tyrosine and 10 ng mL-1 for 3-bromotyrosine. Calibration curves for quantification were linear from 50 to 500 ng mL-1 with an R2 value of 0.9995 for L-tyrosine and 10 to 300 ng mL-1 with an R2 value of 0.9998 for 3-bromotyrosine. Method variability was assessed resulting in relative standard deviations of 0.98-4.6% for 3-bromotyrosine (n = 18) and 0.20-0.58% for L-tyrosine (n = 18). Method applicability was tested with patients with a confirmed diagnosis of EoE, initially suggesting little to no correlation between eosinophil count and 3-bromotyrosine concentration in plasma. However, we do observe a relationship between eosinophil count and esophageal deformities. More research must be conducted to determine a more definitive correlation.
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Patients with recurrent patellofemoral instability in whom prior medial patellofemoral ligament (MPFL) reconstruction fails present unique challenges for revision soft-tissue stabilization owing to scar tissue formation, limited patellar bone stock for anchor placement, and increased risk of patellar fracture. We describe a technique for revision patellofemoral soft-tissue stabilization that combines MPFL and medial quadriceps tendon-femoral ligament reconstruction techniques through combined fixation to the patella with 1 suture anchor and soft-tissue fixation to the quadriceps tendon. The proposed technique maximizes restoration of resistance to lateral translation by attempting to re-create the native MPFL attachment and minimizes patellar fracture risk in the setting of poor bone stock through the use of a single 1.8-mm all-suture suture anchor rather than bone tunnels or multiple anchor placement for bony fixation.
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Introduction Although transforaminal interbody fusion (TLIF) and anterior lumbar interbody fusion (ALIF) combined with posterior fusion (AP) have similar fusion rates, it is unclear if choice of approach has an impact on post-operative complications. Research question Is the incidence of residual leg and/or back pain requiring additional treatment after one- or two-level TLIF and AP similar? Material and methods Adult patients who underwent one- or two-level TLIF or AP for degenerative pathology were identified and matched using age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA), insurance status, smoking status, revision and number of levels fused. The incidence of radicular leg and back pain requiring emergency department visit/readmission or same level surgical intervention was compared between the two groups. Results Of the 319 TLIF and 288 AP cases, 119 cases in each cohort were matched. TLIF patients had shorter operative times (203 min vs 258 min, P<0.001) and hospital stays than the AP patients (3.76 days vs 4.98 days, P<0.001). The incidence of residual leg pain (7 vs 5, P=0.769) and back pain (13 vs 15, P=0.841) was similar between the two groups. Except for constipation, which was more common in the AP group, the incidence of complications was similar between the two groups. Conclusions Patients undergoing one- or two-level TLIF showed shorter operative time and hospital stay compared with those undergoing AP. The incidence of leg radiculopathy and back pain was similar between the two groups. Surgeons should consider these findings as part of the decision-making process regarding which approach to use in patients requiring a lumbar interbody fusion.
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Understanding the initiation of T-helper (Th)-2 immunity is crucial for addressing allergic diseases that have been linked to the commensal microbiota. However, Th2 responses are notably absent from known host-microbiota intestinal immune circuits. Notably, the commensal protist Tritrichomonas induces a transient innate ILC2 circuit rather than a chronic Th2 circuit. Canonical Th2 responses rely on the induction of IL-4 production by innate cells. This study shows that the absence of Tet2 , a DNA demethylase, reprograms naïve T cells to autonomously produce IL-4 upon T cell receptor stimulation, bypassing the need for IL-4 from innate cells for Th2 differentiation. Loss of this checkpoint induces chronic Th2 responses to Tritrichomonas , associated with IL-25-dependent barrier dysfunction and increased susceptibility to allergic pathology in response to dietary antigens. Sentence Summary: Regulation of cell autonomous IL-4 in T cells is critical to prevent dysregulated Th2 immunity to commensals and predisposition to allergy.
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Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.
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OBJECTIVE: Determine if knowledge of a third-trimester ultrasound diagnosis of large for gestational age (LGA) independently increases the risk of cesarean delivery (CD). STUDY DESIGN: Historical cohort comparing CD rate among patients diagnosed with an LGA fetus on a clinically indicated ultrasound from January 2017 to July 2021 with those without an LGA diagnosis at 34 weeks or later. LGA was defined as an ultrasound-estimated fetal weight greater than or equal to the 90th percentile for the gestational age. Univariate analysis was performed to identify significant confounding variables and was utilized as covariates for binary regression with CD rate as the primary outcome, and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated. Nulliparous term singleton vertex (NTSV) and multiparous CD rates were also compared. RESULTS: There were 447 patients diagnosed with an LGA fetus and 1971 patients without an LGA diagnosis on third-trimester ultrasound. The positive predictive value of LGA diagnosis was 50.1% and the false positive rate was 10.6%. Patients with a diagnosis of LGA had higher AOR of CD (OR 2.11, 95% CI 1.56-2.83), and higher AOR of NTSV CD (OR 1.88, 95% CI 1.14-3.13) compared with those without an LGA diagnosis. There was no difference in the rates of non-medically indicated CD, multiparous primary CD, and attempted and successful TOLAC. CONCLUSION: Our results suggest third-trimester ultrasound diagnosis of LGA independently increases odds of CD, specifically among nulliparous patients, and the potential bias may be one factor contributing to excessive CDs and NTSV CDs.
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Pathogen transmission pathways are fundamental to understanding the epidemiology of infectious diseases yet are challenging to estimate in nature, particularly in the ocean. Seagrass wasting disease (SWD), caused by Labyrinthula zosterae, impacts seagrass beds worldwide and is thought to be a contributing factor to declines; however, little is known about natural transmission of SWD. In this study, we used field and laboratory experiments to test SWD transmission pathways and temperature sensitivity. To test transmission modes in nature, we conducted three field experiments out-planting sentinel Zostera marina shoots within and adjacent to natural Z. marina beds (20 ± 5 and 110 ± 5 m from bed edge). Infection rates and severity did not differ among outplant locations, implicating waterborne transmission. The infectious dose of L. zosterae through waterborne exposure was assessed in a controlled laboratory experiment. The dose to 50% disease was 6 cells ml-1 and did not differ with the temperatures tested (7.5°C and 15°C). Our results show L. zosterae is transmissible through water without direct contact with infected plants. Understanding the transmission dynamics of this disease in the context of changing ocean conditions will improve Z. marina protection and restoration in critical coastal habitats worldwide.
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Peripheral perfusion in large anterolateral thigh flaps may be inadequate if perforator zones are not properly planned during flap design and harvest, and variations in vascular anatomy can contribute to operative difficulty and morbidity. Intraflap anastomosis of extrinsic perforators may allow for augmentation of perfusion while avoiding significant intramuscular dissection. Adaptation of the perforator exchange technique, previously described in autologous breast reconstruction, optimizes vascular flow in anterolateral thigh flaps. Here, we present a technique for intraflap perforator anastomosis (the thigh perforator exchange) and illustrate its use in a subset of patients. This technique is relatively simple and rapid to perform with no vascular complications observed in our series.
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Importance: Randomized clinical trials have shown that sacubitril-valsartan reduces the risks of mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), but patients with kidney failure requiring dialysis were excluded. Objective: To investigate the comparative effectiveness of sacubitril-valsartan vs angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) in patients with HFrEF requiring hemodialysis. Design, Setting, and Participants: This retrospective, 1:1 propensity score-matched comparative effectiveness study included patients who were 18 years or older with HFrEF, enrolled in Medicare Parts A, B, and D, and survived at least 90 days receiving in-center hemodialysis from July 8, 2015, to December 31, 2020. Patients were excluded for less than 180 days of continuous Medicare Parts A, B, and D primary payer coverage or prior dispensing of sacubitril-valsartan. Data analysis was conducted from September 23, 2023, to June 25, 2024. Exposures: New use of sacubitril-valsartan vs new or continued use of ACEIs or ARBs. Main Outcomes and Measures: The associations between initiation of sacubitril-valsartan therapy and all-cause mortality, cardiovascular mortality, all-cause hospitalization, and HF hospitalization were assessed using Cox proportional hazards regression models in a propensity score-matched sample. Results: Participants included 1:1 matched pairs of 1434 sacubitril-valsartan users and 1434 ACEI or ARB users (mean [SD] age, 64 [13] years). Of the 2868 matched participants, 996 (65%) were male; 987 (34%) were Black or African American and 1677 (58%) were White; and median dialysis vintage was 3.8 (IQR, 1.8-6.3) years. The median follow-up was 0.9 (IQR, 0.4-1.7) years. Sacubitril-valsartan (vs ACEI or ARB) therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.82 [95% CI, 0.73-0.92]) and all-cause hospitalization (HR, 0.86 [95% CI, 0.79-0.93]) but not cardiovascular mortality (HR, 1.01 [95% CI, 0.86-1.19]) or HF hospitalization (HR, 0.91 [95% CI, 0.82-1.02]). There was a decrease in hyperkalemia (HR, 0.71 [95% CI, 0.62-0.81]) and no difference in hypotension (HR, 0.99 [95% CI, 0.83-1.19]). Only 195 participants (14%) ever received the maximum combination dose of sacubitril (97 mg twice daily) and valsartan (103 mg twice daily). Conclusions and Relevance: In this comparative effectiveness study of patients with HFrEF requiring hemodialysis, sacubitril-valsartan therapy was associated with beneficial effects in all-cause mortality and all-cause hospitalization.
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca , Diálisis Renal , Valsartán , Humanos , Compuestos de Bifenilo/uso terapéutico , Valsartán/uso terapéutico , Aminobutiratos/uso terapéutico , Masculino , Femenino , Anciano , Estudios Retrospectivos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Antagonistas de Receptores de Angiotensina/uso terapéutico , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Puntaje de Propensión , Anciano de 80 o más Años , Estados Unidos , Volumen Sistólico/efectos de los fármacosRESUMEN
Importance: Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. Objective: To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). Design, Setting, and Participants: This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. Exposures: GLP-1RAs or DPP-4is. Main Outcomes and Measures: The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). Results: A total of 33â¯280 individuals (13â¯633 using GLP-1RAs and 19â¯647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19â¯853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21â¯751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. Conclusions: In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.
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BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations, recurrent cardiovascular events, and chronic kidney disease (CKD) progression, and thus constitute a Class 1a recommendation in people with diabetes and atherosclerotic cardiovascular disease, HF, or CKD and in people with severe albuminuria or HF, regardless of diabetes status. OBJECTIVES: The purpose of this study was to comprehensibly characterize the rate of SGLT2 inhibitor prescriptions among people with a Class 1a recommendation for SGLT2 inhibitor use. METHODS: Among 3,189,827 adults from 28 U.S. health systems within Optum Labs Data Warehouse between April 1, 2022, and March 31, 2023, we assessed SGLT2 inhibitor prescription rates, stratified by presence of diabetes and Class 1a recommendation. RESULTS: Among 716,387 adults with diabetes, 63.4% had a Class 1a recommendation for SGLT2 inhibitor therapy. There was little difference by Class 1a recommendation status (present: 11.9%; 95% CI: 11.9%-12.0% vs absent: 11.4%; 95% CI: 11.3%-11.6%; standardized mean difference: 1.3%). Among 2,473,440 adults without diabetes, 6.2% had a Class 1a recommendation for SGLT2 inhibitor therapy, and 3.1% (3.0%-3.2%) of those received a prescription. Internists/family practitioners initiated SGLT2 inhibitor prescriptions most commonly among people with diabetes, whereas specialists initiated SGLT2 inhibitor prescriptions most commonly among people without diabetes. No health system had >25% SGLT2 inhibitor prescription rate among people with a Class 1a recommendation. Health systems with higher proportions of patients with commercial insurance and lower proportions with Medicare had higher SGLT2 inhibitor prescription rates. CONCLUSIONS: In this analysis of U.S. data from 2022 to 2023, SGLT2 inhibitor prescription among people with a Class 1a recommendation is low. Interventions are needed to increase uptake of guideline-recommended SGLT2 inhibitor use.
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Diabetes Mellitus Tipo 2 , Pautas de la Práctica en Medicina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Estados Unidos/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Adulto , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
BACKGROUND: Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10 kg. Intensive care unit (ICU) mortality in children ≤ 10 kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25 years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10 kg at hospital admission. PRIMARY AND SECONDARY OUTCOMES: ICU mortality and major adverse kidney events at 90 days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90 days, respectively. RESULTS: A total of 210 patients were included (median age 0.53 years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3 days (IQR 1, 9) after ICU admission and lasted a median 6 days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). CONCLUSIONS: We report on a contemporary cohort of children ≤ 10 kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90 days highlights the importance of close follow-up.
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BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.