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OBJECTIVE: To assess the role of the systolic blood pressure polygenic risk score (SBP-PRS) in antihypertensive treatment initiation and its comparative efficacy with coronary artery calcium (CAC) scores. PATIENTS AND METHODS: This retrospective cohort study included participants with whole genome sequencing data who underwent CAC scanning between 1971 and 2008, were free of prevalent cardiovascular disease (CVD), and were not taking antihypertensive medications. The cohort was stratified by blood pressure (BP) treatment group and SBP-PRS (low/intermediate, first and second tertiles; high, third tertile) and CAC score (0 vs >0) subgroups. The primary outcome was the first occurence of adjudicated coronary heart disease, heart failure, or stroke during 10-year follow-up. The 10-year number needed to treat (NNT) to prevent 1 event of the primary outcome was estimated. A relative risk reduction of 25% for the primary outcome based on the treatment effect of intensive control (SBP <120 mm Hg) of hypertension in SPRINT (Systolic Blood Pressure Intervention Trial) was used for estimating the NNT. RESULTS: Among the 5267 study participants, the median age was 59 years (interquartile range, 51-68 years); 2817 (53.5%) were women and 2880 (54.7%) were non-White individuals. Among 1317 individuals with elevated BP/low-risk stage 1 hypertension not recommended treatment, the 10-year incidence rate of the primary outcome was 5.6% for low/intermediate SBP-PRS and 6.3% for high SBP-PRS with NNTs of 63 and 59, respectively. Similarly, the 10-year incidence rate of the primary outcome was 2.9% for CAC score 0 and 9.7% for CAC score greater than 0, with NNTs of 117 and 37, respectively. CONCLUSION: Including genetic information in risk estimation of individuals with elevated BP/low-risk stage 1 hypertension has modest value in the initiation of antihypertensive therapy. Genetic risk and CAC both have efficacy in personalizing antihypertensive therapy.
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Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n = 35,167, mean: -0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n = 39, mean: -0.5 (0.3)] (p:<0.001). A standard deviation decrease in transthyretin levels increases the risk of heart failure [HRadj: 1.17 (95% Confidence Interval = 1.08-1.26)] and all-cause mortality [HRadj: 1.18 (95% Confidence Interval = 1.14-1.24)]. This study shows that individuals with low transthyretin levels, such as those carrying the V142I variant, are at a higher risk of heart failure and mortality.
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Bancos de Muestras Biológicas , Prealbúmina , Humanos , Femenino , Prealbúmina/genética , Prealbúmina/metabolismo , Masculino , Reino Unido/epidemiología , Persona de Mediana Edad , Anciano , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/mortalidad , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Adulto , Presión Sanguínea , Índice de Masa Corporal , Factores de Riesgo , Biobanco del Reino UnidoRESUMEN
Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the combination could be immunosuppressive. Lysosomes have previously been identified as a target for obinutuzumab cytotoxicity in CLL cells, but the mechanism remains unclear. In addition, studies have shown that lysosomotropic agents can cause synergistic cell death in vitro when combined with the BTK inhibitor, ibrutinib, in primary CLL cells. This indicates that targeting lysosomes could be a treatment strategy for CLL. In this study, we have shown that obinutuzumab induces lysosome membrane permeabilization (LMP) and cathepsin D release in CLL cells. Inhibition of cathepsins reduced obinutuzumab-induced cell death in CLL cells. We further determined that the lysosomotropic agent siramesine in combination with venetoclax increased cell death in primary CLL cells through an increase in reactive oxygen species (ROS) and cathepsin release. Siramesine treatment also induced synergistic cytotoxicity when combined with venetoclax. Microenvironmental factors IL4 and CD40L or incubation with HS-5 stromal cells failed to significantly protect CLL cells from siramesine- and venetoclax-induced apoptosis. We also found that siramesine treatment inhibited autophagy through reduced autolysosomes. Finally, the autophagy inhibitor chloroquine failed to further increase siramesine-induced cell death. Taken together, lysosome-targeting drugs could be an effective strategy in combination with venetoclax to overcome drug resistance in CLL.
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Apoptosis , Autofagia , Compuestos Bicíclicos Heterocíclicos con Puentes , Catepsina D , Leucemia Linfocítica Crónica de Células B , Lisosomas , Sulfonamidas , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Sulfonamidas/farmacología , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Catepsina D/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sinergismo Farmacológico , Línea Celular TumoralRESUMEN
Background: In 2022, the Life's Simple 7 (LS7) score was replaced with the Life's Essential 8 (LE8) score as a tool to measure cardiovascular health. The risk prediction values of LE8 and LS7 scores for mortality have not been compared. Additionally, the risk prediction value of these scores has not been compared with the pooled cohort equations (PCE) in individuals aged 40 to 79 years. Objectives: This study compared the risk prediction value of the: 1) LE8 and LS7 scores in the overall population; and 2) LE8 score, LS7 score, and PCE in the 40- to 79-year-old age group for all-cause and cardiovascular mortality in a nationally representative US population. Methods: The LS7 and LE8 scores and the PCE were calculated in the National Health and Nutrition Examination Survey cycles 2007 to 2018. All-cause and cardiovascular mortality were identified by linking the participants to the National Death Index. The C-statistics of the respective weighted Cox models were used to compare the risk prediction value of the standardized scores. Results: Among 21,721 individuals included, the C-statistics for all-cause mortality were 0.823 (95% CI: 0.803-0.843) and 0.819 (95% CI: 0.799-0.838) in the LE8 and LS7 score-based models, respectively. The C-statistics for cardiovascular mortality were 0.887 (95% CI: 0.857-0.905) for the LE8 score-based model and 0.883 (95% CI: 0.861-0.905) for the LS7 score-based model. Among 12,943 individuals aged 40 to 79 years, the C-statistics for the outcome of all-cause mortality were 0.756 (95% CI: 0.732-0.779), 0.674 (95% CI: 0.646-0.701), and 0.681 (95% CI: 0.656-0.706) for the PCE, LS7 score, and LE8 score-based models, respectively. Conclusions: The LS7 and LE8 scores had similar risk prediction values for all-cause and cardiovascular mortality. Among 40- to 79-year-old individuals, the PCE had better risk discrimination in the LE8 and LS7 scores in predicting all-cause mortality.
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OBJECTIVES: Anemia and iron deficiency in patients having cardiac surgery increases their perioperative risk. Nonanemic iron deficiency (NAID) in this group is less well-described. We aimed to investigate the incidence and outcomes of patients with NAID undergoing cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single, tertiary referral center. PARTICIPANTS: Adult patients who were preassessed and underwent cardiac surgery during the study period had data collected. We enrolled 537 patients enrolled and divided them into 4 groups according to hemoglobin and ferritin: NAID, nonanemic iron replete, iron-deficiency anemia (IDA), and non-iron-deficiency anemia. INTERVENTIONS: This study was not interventional, but assessed the impact of anemia and iron deficiency on patient outcomes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of NAID. Secondary outcomes included the number of patients who became anemic awaiting surgery, allogeneic transfusion burden, length of stay, postoperative complications, and death. 179 of 537 patients (33.3%) had NAID. Seventeen patients (9.5%) became anemic in the NAID group compared with 7 (3.3%) in the nonanemic iron replete group while awaiting for surgery (p = 0.02). Patients with NAID were more likely to receive allogeneic transfusions (33% vs 23%; p = 0.04) and had poorer recovery of hemoglobin at follow-up (13.2 ± 1.46 g/dL vs 13.9 ± 1.46 g/dL; p < 0.001). CONCLUSIONS: NAID is common and can lead to progression to anemia and increased transfusion. Iron replacement should be considered in patients with NAID in the preoperative setting. A prospective interventional trial is required to demonstrate the benefit of being iron replete.
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Background: Nutritional assessment is important for optimization of patients undergoing elective total joint arthroplasty (TJA). Preoperative nutritional intervention is a potentially modifiable optimization target, but the outcomes of such intervention are not well-studied. The purpose of this study is to assess the impact of nutritional interventions on elective TJA outcomes. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to perform a systematic review of the Ovid Medline, Embase, and Cochrane Library systems. Included studies were comprised of patients greater than 18 years of age undergoing a primary unilateral TJA who received a perioperative dietitian-led intervention. Data analyzed included nutritional intervention protocol, patient demographics, length of stay (LOS), postoperative labs and complications, among others. Results: Our initial search identified a total of 1766 articles. Four studies representing 5006 patients met inclusion criteria. The studies utilized a protein-dominant diet, with or without a carbohydrate solution accompanied by dietitian assessment or education. The 4 studies found that the intervention group had significantly decreased LOS, fewer albumin infusions, less wound drainage, lower rates of hypocalcemia and hypokalemia, reduced C-reactive protein (CRP) values, improved time out of bed, and decreased overall costs. Conclusion: The findings support the potential benefits of perioperative dietitian-led intervention on key outcomes for patients undergoing primary TJA. Surgeons should consider nutritional intervention in their preoperative optimization protocols. Future studies could help elucidate the optimum nutritional regimens and monitoring for idealized intervention and surgical timing. Prospero registration number: CRD4202338494.
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Phosphodiesterase 3A (PDE3A) gene mutations have recently been associated with hypertension and brachydactyly syndrome (HTNB). This report shows how the recent recognition of the role of the PDE3A gene in HTNB facilitated the diagnosis of HTNB in a 20-year-old female who could not be diagnosed at her initial presentation at 6 years of age.
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The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates METHODS: This study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009-2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. RESULTS: Elective and asymptomatic patient admissions declined 2009-2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. CONCLUSIONS: The publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA's conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA's findings in managing unruptured brain AVMs.
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Embolización Terapéutica , Análisis de Series de Tiempo Interrumpido , Malformaciones Arteriovenosas Intracraneales , Humanos , Malformaciones Arteriovenosas Intracraneales/terapia , Estados Unidos , Embolización Terapéutica/métodos , Femenino , Pacientes Internos , Microcirugia , Masculino , Radiocirugia/tendencias , Adulto , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Tricuspid valve annuloplasty (TA) during mitral valve repair (MVr) is associated with increased risk of permanent pacemaker (PPM) implantation, but the magnitude of risk and long-term clinical consequences have not been firmly established. OBJECTIVES: This study assesses the incidence rates of PPM implantation after isolated MVr and following MVr with TA as well as the associated long-term clinical consequences of PPM implantation. METHODS: State-mandated hospital discharge databases of New York and California were queried for patients undergoing MVr (isolated or with concomitant TA) between 2004 and 2019. Patients were stratified by whether or not they received a PPM within 90 days of index surgery. After weighting by propensity score, survival, heart failure hospitalizations (HFHs), endocarditis, stroke, and reoperation were compared between patients with or without PPM. RESULTS: A total of 32,736 patients underwent isolated MVr (n = 28,003) or MVr + TA (n = 4,733). Annual MVr + TA volumes increased throughout the study period (P < 0.001, trend), and PPM rates decreased (P < 0.001, trend). The incidence of PPM implantation <90 days after surgery was 7.7% for MVr and 14.0% for MVr + TA. In 90-day conditional landmark-weighted analyses, PPMs were associated with reduced long-term survival among MVr (HR: 1.96; 95% CI: 1.75-2.19; P < 0.001) and MVr + TA recipients (HR: 1.65; 95% CI: 1.28-2.14; P < 0.001). In both surgical groups, PPMs were also associated with an increased risk of HFH (HR: 1.56; 95% CI: 1.27-1.90; P < 0.001) and endocarditis (HR: 1.95; 95% CI: 1.52-2.51; P < 0.001), but not with stroke or reoperation. CONCLUSIONS: Compared to isolated MVr, adding TA to MVr was associated with a higher risk of 90-day PPM implantation. In both surgical groups, PPM implantation was associated with an increase in mortality, HFH, and endocarditis.
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Marcapaso Artificial , Válvula Tricúspide , Humanos , Femenino , Masculino , Anciano , Marcapaso Artificial/efectos adversos , Válvula Tricúspide/cirugía , Persona de Mediana Edad , Válvula Mitral/cirugía , Estudios Retrospectivos , Anuloplastia de la Válvula Cardíaca/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.
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Hybrid coronary revascularization (HCR) combines a minimally invasive surgical approach with percutaneous coronary intervention (PCI) for the treatment of multivessel coronary artery disease. Despite decades of use, widespread acceptance has been limited. In this review, we conduct a comparative assessment of HCR in relation to traditional coronary artery bypass graft surgery and multivessel PCI. Although large-scale randomized data are still lacking, numerous studies have demonstrated that HCR may offer benefits regarding resource utilization and short-term morbidity while delivering comparable mid- and long-term survival compared with traditional bypass surgery. Compared with PCI, HCR may offer similar periprocedural morbidity while mitigating the need for repeat revascularization by providing a surgical arterial bypass graft to the left anterior descending artery.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/métodos , Puente de Arteria Coronaria/métodos , Revascularización Miocárdica/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
OBJECTIVE: To evaluate the association of carpal tunnel syndrome (CTS) with incident heart failure and incident amyloidosis and to assess the risk of CTS in pathogenic TTR genetic variant carriers. METHODS: This prospective cohort study included multiethnic US adults 18 years of age and older without prevalent heart failure and amyloidosis with available genotypic data from the All of Us Research Program. The primary outcomes were incident heart failure and incident amyloidosis. The association of incident heart failure and incident amyloidosis with CTS was assessed using multivariable adjusted Cox models accounting for age, sex, race and ethnicity, obesity, hypertension, diabetes, statin use, and smoking status. RESULTS: Of the 166,987 individuals included, the median age was 54 (38 to 66) years; 105,279 (63.0%) were female, and 92,780 (55.6%) were non-Hispanic White individuals; CTS was identified in 12,407 (7.4%) individuals. Compared with individuals without CTS, the adjusted hazard ratio for incident heart failure was 1.13 (95% CI, 1.02 to 1.26) in individuals with CTS. The risk of amyloidosis was â¼3-fold higher (adjusted hazard ratio, 2.86; 95% CI, 1.71 to 4.77) in individuals with CTS compared with those without CTS. Individuals carrying a pathogenic TTR variant had an approximately 40% higher risk (adjusted hazard ratio, 1.38; 95% CI, 1.16 to 1.65) for development of CTS compared with noncarriers. CONCLUSION: Cardiac amyloidosis screening programs may use CTS as a sentinel event and use genetic testing to identify individuals at a higher risk of TTR amyloidosis.
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Neuropatías Amiloides Familiares , Síndrome del Túnel Carpiano , Insuficiencia Cardíaca , Humanos , Síndrome del Túnel Carpiano/genética , Síndrome del Túnel Carpiano/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/epidemiología , Neuropatías Amiloides Familiares/complicaciones , Estudios Prospectivos , Estados Unidos/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/etiología , Anciano , Adulto , Incidencia , Prealbúmina/genética , Factores de RiesgoRESUMEN
BACKGROUND: Significant heterogeneity exists regarding patient reported outcome measures (PROMs) used in total hip (THA) and knee (TKA) arthroplasty randomized controlled trials (RCTs). This study investigates the PROMs used as primary and secondary outcomes in contemporary arthroplasty RCTs. METHODS: A literature search identified THA and TKA RCTs that were published in top ten impact factor orthopaedic journals from 2017 to 2021. Screening identified 241 trials: 76 THA, 157 TKA, and eight combined. Data were extracted to identify PROMs utilized as either primary or secondary outcomes and the time period of measurement. RESULTS: Visual Analog Scale (VAS) Pain was the most reported primary PROM in THA (9.2%) and TKA (22.9%) trials. This was followed by Numeric Rating Scale (NRS) Pain (7.9%) and the Harris Hip score (6.6%) in THA trials and NRS Pain (4.5%) and the Knee Society score (4.5%) in TKA trials. Many THA (37.0%) and TKA (52.1%) trials did not clearly specify primary outcome time points. Only pain scales were reported at time points less than one week, while various joint-specific functional outcomes were reported at later time points. As secondary outcomes, the Harris Hip score (28.9%) was most common in THA trials and the Knee Society score (26.1%) was most common in TKA trials. Indeterminate primary or secondary outcomes were reported in 18.2% of studies. CONCLUSIONS: Contemporary THA and TKA trials exhibit heterogeneity of PROMs as study outcomes after the first postoperative week. Our findings highlight the need for consensus in PROM reporting and better methodological reporting to improve the interpretability of RCT outcomes. PROSPERO REGISTRATION NUMBER: CRD42022337255.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Medición de Resultados Informados por el Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Dimensión del DolorRESUMEN
Catheter kinking is not an uncommon scenario during cardiac catheterization via transradial access in patients with tortuous vascular anatomy. Several noninvasive and invasive methods have been described to unkink and retrieve the kinked catheter out of the vessel. We present a novel mother-daughter technique to retrieve a kinked radial artery catheter.
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Madres , Arteria Radial , Femenino , Humanos , Arteria Radial/diagnóstico por imagen , Núcleo Familiar , Angiografía Coronaria , Resultado del Tratamiento , Catéteres , Cateterismo Cardíaco/métodosRESUMEN
BACKGROUND: One third of South African children live in households with no employed adult. Telemedicine may save patients and the strained public health sector significant resources. We aimed to determine the safety and benefits of telephonic post-operative follow-up of patients who presented for day case surgery at CHBAH from 1 January-31 March 2023. METHODS: A prospective descriptive study on patients undergoing day case surgery was performed. Healthy patients greater than 6 years old whose caregivers spoke English and had access to a smartphone were included. Data on the total number of telephonic follow-ups, operative complications, need for in person review, satisfaction with telephonic follow-up, and savings in transport costs and time by avoiding in person follow-up were collected. RESULTS: A total of 38 telephonic follow-ups were performed. Six (15.8%) patients presented for in person review due to the detection of major complications (2, 5.3%), minor complications (2, 5.3%), and parental concern (2, 5.3%) during telephonic follow-up. All caregivers reported being satisfied with telephonic follow-up. Total savings in transport costs were R4452 (US $ 248.45). The majority of patients (29, 76.3%) had at least one unemployed parent. Seven caregivers (18.4%) avoided taking paid leave and 2 (5.3%) unpaid leave from work due to follow-up being performed telephonically. CONCLUSIONS: Innovation is necessary in order to expand access to safe, affordable, and timely care. In this selected group, telephonic follow-up was a safe, acceptable, and cost-effective intervention. The expansion of such a program has the potential for significant savings for patients and the healthcare system.
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Procedimientos Quirúrgicos Ambulatorios , Telemedicina , Humanos , Proyectos Piloto , Estudios Prospectivos , Niño , Femenino , Masculino , Procedimientos Quirúrgicos Ambulatorios/economía , Sudáfrica , Telemedicina/economía , Teléfono , Estudios de Seguimiento , Adolescente , Satisfacción del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/economía , Cuidados Posteriores/economía , Cuidados Posteriores/métodosRESUMEN
There has been an exponential increase in randomized controlled trials (RCTs) on cerebrovascular disease within neurosurgery. The goal of this study was to review, outline the scope, and summarize all phase 2b and phase 3 RCTs impacting cerebrovascular neurosurgery practice since 2018. We searched PubMed, MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for relevant RCTs published between January 1, 2018, and July 1, 2022. We searched for studies related to eight major cerebrovascular disorders relevant to neurosurgery, including acute ischemic stroke, cerebral aneurysms and subarachnoid hemorrhage, intracerebral hemorrhage, subdural hematomas, cerebral venous thrombosis, arteriovenous malformations, Moyamoya disease and extracranial-intracranial bypass, and carotid and intracranial atherosclerosis. We limited our search to phase 2b or 3 RCTs related to cerebrovascular disorders published during the study period. The titles and abstracts of all relevant studies meeting our search criteria were included. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded. From an initial total of 2,797 records retrieved from the database searches, 1,641 records were screened after duplicates and studies outside of our time period were removed. After screening, 511 available reports within our time period of interest were assessed for eligibility. Pediatric studies, stroke studies related to rehabilitation or cardiovascular disease, study protocols without published results, prospective cohort studies, registry studies, cluster randomized trials, and nonrandomized pivotal trials were excluded. We found 80 unique phase 2b or 3 RCTs that fit our criteria, with 165 topic-relevant articles published within the study period. Numerous RCTs in cerebrovascular neurosurgery have been published since 2018. Ischemic stroke, including mechanical thrombectomy and thrombolysis, accounted for a majority of publications, but there were large trials in intracerebral hemorrhage, subdural hemorrhage, aneurysms, subarachnoid hemorrhage, and cerebral venous thrombosis, among others. This review helps define the scope of the large RCTs published in the last four years to guide future research and clinical care.