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1.
Am Heart J ; 243: 77-86, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34529944

RESUMO

BACKGROUND: Regulatory agencies have endorsed more limited approaches to clinical trial site monitoring. However, the impact of different monitoring strategies on trial conduct and outcomes is unclear. METHODS: We conducted a patient-level block-randomized controlled trial evaluating the effect of intensive versus limited monitoring on cardiovascular clinical trial conduct and outcomes nested within the CoreValve Continued Access and Expanded Use Studies. Intensive monitoring included complete source data verification of all critical datapoints whereas limited monitoring included automated data checks only. This study's endpoints included clinical trial outcome ascertainment as well as monitoring action items, protocol deviations, and adverse event ascertainment. RESULTS: A total of 2,708 patients underwent transcatheter aortic valve replacement (TAVR) and were randomized to either intensive monitoring (n = 1,354) or limited monitoring (n = 1,354). Monitoring action items were more common with intensive monitoring (52% vs 15%; P < .001), but there was no difference in the percentage of patients with any protocol deviation (91.6% vs 90.4%; P = .314). The reported incidence of trial outcomes between intensive and limited monitoring was similar for mortality (30 days: 4.8% vs 5.5%, P = .442; 1 year: 20.3% vs 21.3%, P = .473) and stroke (30 days: 2.8% vs 2.4%, P = .458), as well as most secondary trial outcomes with the exception of bleeding (intensive: 36.3% vs limited: 32.0% at 30 days, P = .019). There was a higher reported incidence of cardiac adverse events reported in the intensive monitoring group at 1 year (76.7% vs 72.4%; P = .019). CONCLUSIONS: Tailored limited monitoring strategies can be implemented without influencing the integrity of TAVR trial outcomes.

3.
JAMA Cardiol ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787635

RESUMO

Importance: Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care. Objective: To examine the association between zip code-level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs. Design, Setting, and Participants: This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas. Exposure: Receipt of TAVR. Main Outcomes and Measures: The association between zip code-level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries. Results: Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities. Conclusions and Relevance: Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.

4.
Bioengineering (Basel) ; 8(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821734

RESUMO

Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens in old age via the Maillard reaction, potentiating the accumulation of intramuscular collagen and stiffening the microenvironment through collagen cross-linking. This review contextualizes known aspects of skeletal muscle extracellular matrix (ECM) aging, especially the role of collagens and AGE cross-linking, and underpins the motor nerve's role in this aging process. Specific directions for future research are also discussed, with the understudied role of AGEs in skeletal muscle aging highlighted. Despite more than a half century of research, the role that intramuscular collagen aggregation and cross-linking plays in sarcopenia is well accepted yet not well integrated with current knowledge of AGE's effects on muscle physiology. Furthermore, the possible impact that motor nerve aging has on intramuscular cross-linking and muscular AGE levels is posited.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34779656

RESUMO

Background: Frailty is associated with a higher risk for adverse outcomes after aortic valve replacement (AVR) for severe aortic valve stenosis, but whether or not frail patients derive differential benefit from transcatheter (TAVR) vs. surgical (SAVR) AVR is uncertain. Methods: We linked adults ≥ 65 years old in the US CoreValve High Risk (HiR) or Surgical or Transcatheter Aortic-Valve Replacement in Intermediate Risk Patients (SURTAVI) trial to Medicare claims, 2/2/2011-9/30/2015. Two frailty measures, a deficit-based (DFI) and phenotype-based (PFI) frailty index, were generated. The treatment effect of TAVR vs. SAVR was evaluated within frailty index (FI) tertiles for the primary endpoint of death and non-death secondary outcomes, using multivariable Cox regression. Results: Of 1,442 (linkage rate = 60.0%) individuals included, 741 (51.4%) individuals received TAVR and 701 (48.6%) received SAVR (mean age 81.8 ± 6.1 years, 44.0% female). Though 1-year death rates in the highest FI tertiles (DFI 36.7%, PFI 33.8%) were 2-3-fold higher than the lowest tertiles (DFI 13.4%, HR 3.02, 95% CI 2.26-4.02, p < 0.001; PFI 17.9%; HR 2.05, 95% CI 1.58-2.67, p < 0.001), there were no significant differences in the relative or absolute treatment effect of SAVR vs. TAVR across FI tertiles for all death, non-death, and functional outcomes (all interaction p-values > 0.05). Results remained consistent across individual trials, frailty definitions, and when considering the non-linked trial data. Conclusions: Two different frailty indices based on Fried and Rockwood definitions identified individuals at higher risk of death and functional impairment but no differential benefit from TAVR vs. SAVR.

6.
Eur Heart J ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662382

RESUMO

AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

7.
Vasc Med ; : 1358863X211042930, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606385

RESUMO

Catheter-directed thrombolysis (CDT) has been utilized as an adjunct to anticoagulant therapy in selected patients with deep vein thrombosis (DVT) for approximately 30 years. CDT used to be limited to patients with DVT causing acute limb threat and those exhibiting failure of initial anticoagulation, but has expanded over time. Randomized trials evaluating the first-line use of CDT for proximal DVT have demonstrated that CDT does not produce a major reduction in the occurrence of post-thrombotic syndrome (PTS) and that it is poorly suited for elderly patients and those with limited thrombus extent or major risk factors for bleeding. However, CDT does offer selected patients with acute iliofemoral DVT improvement in reducing early DVT symptoms, in achieving reduction in PTS severity, and in producing an improvement in health-related quality of life (QOL). Clinical practice guidelines from medical and surgical societies are now largely aligned with the randomized trial results. This review offers the reader an update on the results of recently completed clinical trials, and additional guidance on appropriate selection of patients with DVT for catheter-directed thrombolytic therapy.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34718485

RESUMO

AIMS: In contrast to patient-reported health status measures (such as the Kansas City Cardiomyopathy Questionnaire [KCCQ]), New York Heart Association (NYHA) Class is based on a physician's assessment of heart failure symptoms and functional limitations on behalf of the patient. We sought to determine the concordance and predictors of physician under- and overestimation of symptoms prior to and after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: The analytic cohort included 172,667 patients within the STS/ACC TVT Registry who underwent transfemoral TAVR. At baseline, physicians underestimated patients' symptoms in 47.4%, correctly assessed symptoms in 26.6%, and overestimated symptoms in 26.0%. At 30 days after TAVR, these proportions were 22.8%, 50.3%, and 26.9%, respectively. Using nominal logistic regression with random intercepts to account for within hospital clustering, we found that physicians were more likely to incorrectly estimate patients' symptoms when patients were older, women, had a prior stroke, had severe lung disease, had atrial fibrillation, or were more obese. There was marked variability in the rates of underestimation, correct estimation, and overestimation across the 641 sites. CONCLUSION: Among patients undergoing treatment for severe aortic stenosis, physicians estimate patients' symptoms and functional status poorly both prior to and after TAVR, with different patterns. These findings emphasize the need to collect patient-reported health status to more reliably assess the benefits of TAVR in routine clinical practice.

9.
Ann Thorac Surg ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34711394

RESUMO

Data for nearly all patients undergoing transcatheter edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR) with an approved device in the United States is captured in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. All data submitted for TEER or TMVR between 2014 and March 31, 2020, are reported. A total of 37,475 patients underwent a mitral transcatheter procedure, including 33,878 TEER and 3,597 TMVR. Annual procedure volumes for TEER have increased from 1,152 per year in 2014 to 10,460 per year in 2019 at 403 sites and for TMVR from 84 per year to 1,120 per year at 301 centers. Mortality rates have decreased for TEER at 30 days (5.6%-4.1%) and 1 year (27.4%-22.0%). Early off-label use data on TMVR in mitral valve-in-valve therapy led to approval by the U.S. Food and Drug Administration in 2017, and the 2019 30-day mortality rate was 3.9%. Overall improvements in outcomes over the last 6 years are apparent. (STS/ACC TVT Registry Mitral Module; NCT02245763).

10.
J Am Coll Cardiol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34711430

RESUMO

Data for nearly all patients undergoing transcatheter edge-to-edge repair (TEER) and transcatheter mitral valve replacement (TMVR) with an approved device in the United States is captured in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. All data submitted for TEER or TMVR between 2014 and March 31, 2020, are reported. A total of 37,475 patients underwent a mitral transcatheter procedure, including 33,878 TEER and 3,597 TMVR. Annual procedure volumes for TEER have increased from 1,152 per year in 2014 to 10,460 per year in 2019 at 403 sites and for TMVR from 84 per year to 1,120 per year at 301 centers. Mortality rates have decreased for TEER at 30 days (5.6%-4.1%) and 1 year (27.4%-22.0%). Early off-label use data on TMVR in mitral valve-in-valve therapy led to approval by the U.S. Food and Drug Administration in 2017, and the 2019 30-day mortality rate was 3.9%. Overall improvements in outcomes over the last 6 years are apparent. (STS/ACC TVT Registry Mitral Module; NCT02245763).

11.
Circ Cardiovasc Qual Outcomes ; 14(11): e008260, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34670405

RESUMO

BACKGROUND: Despite the benefits of novel therapeutics, inequitable diffusion of new technologies may generate disparities. We examined the growth of transcatheter aortic valve replacement (TAVR) in the United States to understand the characteristics of hospitals that developed TAVR programs and the socioeconomic status of patients these hospitals served. METHODS: We identified fee-for-service Medicare beneficiaries aged 66 years or older who underwent TAVR between January 1, 2012, and December 31, 2018, and hospitals that developed TAVR programs (defined as performing ≥10 TAVRs over the study period). We used linear regression models to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs and described the association between core-based statistical area level markers of socioeconomic status and TAVR rates. RESULTS: Between 2012 and 2018, 583 hospitals developed new TAVR programs, including 572 (98.1%) in metropolitan areas, and 293 (50.3%) in metropolitan areas with preexisting TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated fewer patients with dual eligibility for Medicaid (difference of -2.83% [95% CI, -3.78% to -1.89%], P≤0.01), higher median household incomes (difference $2447 [95% CI, $1348-$3547], P=0.03), and from areas with lower distressed communities index scores (difference -4.02 units [95% CI, -5.43 to -2.61], P≤0.01). After adjusting for the age, clinical comorbidities, race and ethnicity and socioeconomic status, areas with TAVR programs had higher rates of TAVR and TAVR rates per 100 000 Medicare beneficiaries were higher in core-based statistical areas with fewer dual eligible patients, higher median income, and lower distressed communities index scores. CONCLUSIONS: During the initial growth phase of TAVR programs in the United States, hospitals serving wealthier patients were more likely to start programs. This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/cirurgia , Hospitais , Humanos , Medicare , Fatores de Risco , Fatores Socioeconômicos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Estados Unidos/epidemiologia
12.
J Am Heart Assoc ; 10(21): e022910, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34713717

RESUMO

Background Hospitalization rates after transcatheter aortic valve replacement (TAVR) remain high, given the age and comorbidities of patients undergoing TAVR. To better understand the impact of TAVR on hospitalization, we sought to compare hospitalization rates before and after TAVR and to examine if underlying patient comorbidities are associated with a differential effect of TAVR on hospitalizations. Methods and Results We used the Nationwide Readmissions Database to identify patients who underwent TAVR. As Nationwide Readmissions Database data do not cross over calendar years, we limited our index admission to hospitalizations during April to September of each calendar year to allow 90 days of observation before and after TAVRs. We calculated the daily risk of all-cause hospitalization and used a mixed-effects logistic regression model to explore interactions between patient characteristics, TAVR, and hospitalization risk. Among 39 249 patients who underwent TAVR in 2014 to 2017 (median age, 82 years [interquartile range, 76-87 years]; 45.7% women), 32.0% had at least one hospitalization in the 90 days before TAVR compared with 23.2% in the 90 days post-TAVR (relative reduction, 27.5%; P<0.001). In the mixed-effects logistic regression model, TAVR was associated with decreased all-cause hospitalization rate after TAVR in all comorbidity subgroups. However, younger patients and those with heart failure and reduced ejection fraction appeared to have more robust reduction in hospitalizations. Conclusions Although patients who are treated with TAVR have high rates of rehospitalization, TAVR is associated with an overall reduction in all-cause hospitalizations regardless of underlying patient comorbidities.

14.
J Urol ; : 101097JU0000000000002291, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694154

RESUMO

PURPOSE: High-quality evidence comparing supine to prone percutaneous nephrolithotomy (PCNL) for the treatment of complex stones is lacking. This study aimed to compare the outcomes of supine position (SUP) and prone position (PRO) PCNL. MATERIALS AND METHODS: A noninferior randomized controlled trial was performed according to the CONSORT (Consolidated Standards for Reporting Trials) criteria. The inclusion criteria were patients over 18 years of age with complex stones. SUP was performed in the Barts flank-free modified position. Except for positioning, all the surgical parameters were identical. The primary outcome was the difference in the success rate on the first postoperative day (POD1) between groups. The secondary outcome was the difference in the stone-free rate (SFR) on the 90th postoperative day (final SFR). A noninferiority margin of 15% was used. Demographic, operative, and safety variables were compared between the groups. Statistical significance was set at p <0.05. RESULTS: Overall, 112 patients were randomized and their demographic characteristics were comparable. The success rates on POD1 were similar (SUP: 62.5% vs PRO: 57.1%, p=0.563). The difference observed (-5.4%) was lower than the predefined limit. The final SFRs were also similar (SUP: 55.4% vs PRO: 50.0%, p=0.571). SUP had a shorter operative time (mean±SD 117.9±39.1 minutes vs 147.6±38.8 minutes, p <0.001) and PRO had a higher rate of Clavien ≥3 complications (14.3% vs 3.6%, p=0.045). CONCLUSIONS: Positioning during PCNL for complex kidney stones did not impact the success rates; consequently, both positions may be suitable. However, SUP might be associated with a lower high-grade complication rate.

15.
J Med Econ ; 24(1): 1115-1123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34493144

RESUMO

AIMS: Obstructive hypertrophic cardiomyopathy (oHCM) is a disease of the cardiomyocyte in which dynamic left ventricular outflow track obstruction may lead to heart failure, valvular disease, and sudden death. Little is known about healthcare resource utilization (HRU) and costs associated with oHCM. This study investigated the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM. METHODS: We used the US IBM MarketScan Commercial and Medicare Supplemental database to identify patients with oHCM (January 2009-March 2019). Control patients without cardiomyopathy were matched to each patient with oHCM based on age, sex, region, and index year (3:1 ratio). One-year HRU and cost data were compared between all oHCM, symptomatic oHCM, and asymptomatic oHCM subgroups, and their respective controls. RESULTS: Among 11,401 eligible patients with oHCM (mean age 57 years, 42% female), 5,667 (50%) were symptomatic (23% chest pain, 57% dyspnea, 29% fatigue, 17% syncope). oHCM was associated with significant increases in all-cause hospitalizations, hospital days, outpatient visits, and total healthcare costs (mean ± standard deviation: $26,929 ± 77,720 vs. $6,808 ± 25,712, p<.001) compared with matched controls. These differences were driven mainly by the clinical and economic burden of symptomatic oHCM, which was associated with significant increases in 1-year hospitalization rates (38.0 vs. 6.9%), hospital days (3.7 ± 9.9 vs. 0.4 ± 3.0), and total healthcare costs ($43,586 ± 103,756 vs. $6,768 ± 27,618; all p<.001). Adjustment for comorbidities had minimal impact on these differences. LIMITATIONS: The use of claims data relies on International Classification of Diseases (ICD-9 and ICD-10) diagnosis codes, which might be inaccurate. Only commercially insured patients were included. CONCLUSION: In a real-world population, oHCM was associated with substantial increases in HRU and incremental costs of ∼$20,000/year when compared with matched controls-a difference that increased to ∼$35,000/year among symptomatic patients. Further studies are warranted to understand the potential impact of specific therapies on HRU and the economic burden of oHCM.


Assuntos
Cardiomiopatia Hipertrófica , Efeitos Psicossociais da Doença , Idoso , Cardiomiopatia Hipertrófica/epidemiologia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Medicare , Estudos Retrospectivos , Estados Unidos/epidemiologia
16.
J Am Heart Assoc ; 10(19): e022150, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34585597

RESUMO

Background In aortic valve disease, the relationship between claims-based frailty indices (CFIs) and validated measures of frailty constructed from in-person assessments is unclear but may be relevant for retrospective ascertainment of frailty status when otherwise unmeasured. Methods and Results We linked adults aged ≥65 years in the US CoreValve Studies (linkage rate, 67%; mean age, 82.7±6.2 years, 43.1% women), to Medicare inpatient claims, 2011 to 2015. The Johns Hopkins CFI, validated on the basis of the Fried index, was generated for each study participant, and the association between CFI tertile and trial outcomes was evaluated as part of the EXTEND-FRAILTY substudy. Among 2357 participants (64.9% frail), higher CFI tertile was associated with greater impairments in nutrition, disability, cognition, and self-rated health. The primary outcome of all-cause mortality at 1 year occurred in 19.3%, 23.1%, and 31.3% of those in tertiles 1 to 3, respectively (tertile 2 versus 1: hazard ratio, 1.22; 95% CI, 0.98-1.51; P=0.07; tertile 3 versus 1: hazard ratio, 1.73; 95% CI, 1.41-2.12; P<0.001). Secondary outcomes (bleeding, major adverse cardiovascular and cerebrovascular events, and hospitalization) were more frequent with increasing CFI tertile and persisted despite adjustment for age, sex, New York Heart Association class, and Society of Thoracic Surgeons risk score. Conclusions In linked Medicare and CoreValve study data, a CFI based on the Fried index consistently identified individuals with worse impairments in frailty, disability, cognitive dysfunction, and nutrition and a higher risk of death, hospitalization, bleeding, and major adverse cardiovascular and cerebrovascular events, independent of age and risk category. While not a surrogate for validated metrics of frailty using in-person assessments, use of this CFI to ascertain frailty status among patients with aortic valve disease may be valid and prognostically relevant information when otherwise not measured.

17.
Eur Heart J ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423374

RESUMO

AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.

18.
Andrology ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464514

RESUMO

BACKGROUND: Peyronie's Disease (PD) is a connective tissue disorder that affects the tunica albuginea (TA) of the penis causing curvature and erectile dysfunction. The pathophysiology is not well understood and, for this reason, treatment options are limited. OBJECTIVE: The aim of the present study is to analyze and compare whether single or multiple instillations of plasma in the TA of rats is capable of triggering macroscopic, histopathological, and molecular changes consistent with PD. MATERIAL/METHODS: Fifty male Wistar rats were divided into four groups: Group 1: a single instillation of plasma in the TA; Group 2: a single instillation of distilled water in the TA; Group 3: four instillations of plasma in the TA (1x per week); and Group 4: four instillations of distilled water in the TA (1× per week). Forty-five days after the last instillation a manual inspection of the corpus cavernosum, a penile erection test and a penectomy were performed to obtain material for histopathological and molecular analysis. RESULTS: It was observed that 31.25% of the rats that received repeated instillations of plasma presented penile curvature according to the erection test, while none of the rats from the control group or group with one instillation of plasma presented curvature. In the animals that received four instillations of plasma, the following differences were observed in relation to the control group: increase in fibrosis and the deposition of collagen I. The protein expression of heparanase (HPSE) and TGF-ß increased in the groups that received a single or four instillations of plasma, and the protein expression of heparanase-2 (HPSE-2), metalloproteinases (MMP-2, MMP-9) and metalloproteinase inhibitor (TIMP-2) showed an increase in the group that received four instillations of plasma. There was a significant increase in the gene expression of HPSE, MMP-9, and TGF-ß in the group that received four instillations of plasma. In the analysis of the glycosaminoglycans, an increase was observed in the secretion of galactosaminoglycans chondroitin sulfate and dermatan sulfate (CS/DS) in the group that received four instillations of plasma. DISCUSSION: Previous studies have demonstrated increased protein expression. of HPSE, MMP-9 and TGF-ß with instillation of blood in the TA; however, there was no increase in gene expression. In the present study, the increase in the expression of TGF-ß with plasma instillations, proved to be more reliable. The two models with plasma (one or four instillations) demonstrated significant histopathological and molecular changes when compared to the control group. However, only in the group with four plasma instillations there was a macroscopic change. The idea is that repeatedly extravasation of TGF-ß present in plasma of predisposed individuals acts as a trigger for the development and maintenance of changes in the extracellular matrix that perpetuate an anomalous inflammatory process present in PD. CONCLUSION: The present study shows that the repeated instillation of plasma is a low cost in vivo model for the study of PD.

20.
Bone ; 153: 116145, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34390886

RESUMO

Metabolic bone is highly innervated by both sensory and sympathetic nerves. In addition to skeletal development, neural regulation participates in local bone remodeling, which is important for successful osseointegration of titanium implants. Neurectomy is a model used to investigate the lack of neural function on bone homeostasis, but the relative impacts of direct denervation to bone or denervation-induced muscle paralysis are less well defined. To investigate this difference, we used two nerve intervention models, sciatic and femoral neurectomy (SFN) v. botox-induced muscle paralysis (BTX) and assessed the resulting femoral bone phenotype and Ti implant osseointegration. Male Sprague Dawley rats (19) were randomly divided into three groups: implant control (n = 5), SFN (n = 7), and BTX (n = 7). Ti implants (microrough/hydrophilic [modSLA], Institut Straumann AG) were placed in the distal metaphysis of each femur on day 24 post-SFN or BTX. Bone and muscle were examined on day 28 after implant insertion. Both nerve intervention models impaired osseointegration. MicroCT and histology indicated that both models had reduced trabecular bone formation. Only BTX reduced cortical bone formation and increased cortical bone porosity. BTX resulted in more bone loss characterized by the least trabecular and cortical bone, as well as osseointegration. Osteoblasts isolated from the tibia exhibited a model-specific phenotype when they were grown on Ti substrates in vitro. Neurectomy caused more severe muscle atrophy than botox injection. These results indicate that neural regulation directly modulates bone formation and osseointegration. Muscle paralysis modulated the effects of loss of neural inputs into bone, supporting the hypothesis that mechanical loading of bone is a factor in achieving successful osseointegration. The different effects of botox and neurectomy on bone phenotype indicated that the sensory and sympathetic nerves had a role in the osseointegration process.


Assuntos
Toxinas Botulínicas Tipo A , Osseointegração , Animais , Denervação , Masculino , Músculos , Paralisia/induzido quimicamente , Fenótipo , Ratos , Ratos Sprague-Dawley , Titânio
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