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Specific pediatric populations have exhibited disparate responses to triiodothyronine (T3) repletion during and after cardiopulmonary bypass (CPB). Objective: To determine if T3 supplementation improves outcomes in children undergoing CPB. We searched randomized controlled trials (RCT) evaluating T3 supplementation in children aged 0-3 years undergoing CPB between 1/1/2000 and 1/31/2022. We calculated Hazard ratios (HR) for time to extubation (TTE), ICU length of stay (LOS), and hospital LOS. 5 RCTs met inclusion criteria with available patient-level data. Two were performed in United States (US) and 3 in Indonesia with 767 total subjects (range 29- 220). Median (IQR) age 4.1 (1.6, 8.0) months; female 43%; RACHS-1 scores: 1-1%; 2-55%; 3-27%; 4-13%; 5-0.1%; 6-3.9%; 54% of subjects in US vs 46% in Indonesia. Baseline TSH and T3 were lower in Indonesia (p < 0.001). No significant difference occurred in TTE between treatment groups overall [HR 1.09 (CI, 0.94-1.26)]. TTE numerically favored T3-treated patients aged 1-5 months [HR 1.24 (CI, 0.97-1.60)]. TTE HR for the Indonesian T3 group was 1.31 (CI, 1.04-1.65) vs. 0.95 (CI, 0.78-1.15) in US. The ICU LOS HR for the Indonesian T3 group was 1.19 vs. 0.89 in US (p = 0.046). There was a significant T3 effect on hospital LOS [HR 1.30 (CI, 1.01-1.67)] in Indonesia but not in US [HR 0.99 (CI, 0.78-1.23)]. T3 supplementation in children undergoing CPB is simple, inexpensive, and safe, showing benefit in resource-limited settings. Differences in effects between settings likely relate to depression in baseline thyroid function often associated with malnutrition.
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Puente Cardiopulmonar , Triyodotironina , Humanos , Triyodotironina/sangre , Lactante , Preescolar , Tiempo de Internación/estadística & datos numéricos , Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Indonesia , Recién Nacido , FemeninoRESUMEN
BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.
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Productos Biológicos/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Pulmón/efectos de los fármacos , Fosfolípidos/administración & dosificación , Surfactantes Pulmonares/administración & dosificación , Anciano , Productos Biológicos/efectos adversos , Broncoscopía , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/fisiopatología , Estudios de Factibilidad , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Fosfolípidos/efectos adversos , Proyectos Piloto , Surfactantes Pulmonares/efectos adversos , Respiración Artificial , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To prospectively evaluate the acute impact of Kawasaki disease (KD) on health-related quality of life (HRQoL) and to assess deterioration in the HRQoL experienced by children with KD compared with other childhood diseases. STUDY DESIGN: We merged the Outcomes Assessment Program database obtained prospectively with the existing KD database and queried for KD admissions between 1 month and 13 years of age. HRQoL was evaluated with the parent-proxy Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core and Infant Scales. We compared the KD HRQoL results with those obtained from newly diagnosed patients with cancer and pneumonia, matched for age, sex and race. PedsQL total scores over time were assessed with ANCOVA models, adjusted for matching variables and PedsQL score prior to admission. RESULTS: We identified 89 patients with KD and compared 65 subjects with an equal number with pneumonia and with 67 subjects with newly diagnosed cancer. Patients with demonstrated lower PedsQL total score on admission and suffered a significantly greater HRQoL decline from baseline to admission than the other groups. KD diagnostic subtype (complete or incomplete) and coronary artery dilatation were not associated with HRQoL outcomes. However, non-intravenous immunoglobulin responders showed greater HRQoL decline than responders (P = .03). CONCLUSIONS: Children with KD suffer acute and significant HRQoL impairment exceeding that of children newly diagnosed with cancer. Lack of immediate treatment response may exert an additional HRQoL burden, whereas KD subtype and coronary artery dilatation do not.
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Costo de Enfermedad , Síndrome Mucocutáneo Linfonodular/psicología , Calidad de Vida , Adolescente , Niño , Preescolar , Infecciones Comunitarias Adquiridas/psicología , Bases de Datos Factuales , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Masculino , Neoplasias/psicología , Padres , Neumonía/psicología , Estudios Prospectivos , Psicometría/métodosRESUMEN
BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery, but is associated with diaphragm paralysis. One solution may be performing brachial plexus blocks more distally. This noninferiority study evaluated analgesia for blocks at the supraclavicular and anterior suprascapular levels, comparing them individually to the interscalene approach. METHODS: One hundred-eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to this double-blind trial and randomized to interscalene, supraclavicular, or anterior suprascapular block using 15 ml, 0.5% ropivacaine. The primary outcome was numeric rating scale pain scores analyzed using noninferiority testing. The predefined noninferiority margin was one point on the 11-point pain scale. Secondary outcomes included opioid consumption and pulmonary assessments. RESULTS: All subjects completed the study through the primary outcome analysis. Mean pain after surgery was: interscalene = 1.9 (95% CI, 1.3 to 2.5), supraclavicular = 2.3 (1.7 to 2.9), suprascapular = 2.0 (1.4 to 2.6). The primary outcome, mean pain score difference of supraclavicular-interscalene was 0.4 (-0.4 to 1.2; P = 0.088 for noninferiority) and of suprascapular-interscalene was 0.1 (-0.7 to 0.9; P = 0.012 for noninferiority). Secondary outcomes showed similar opioid consumption with better preservation of vital capacity in the anterior suprascapular group (90% baseline [P < 0.001]) and the supraclavicular group (76% [P = 0.002]) when compared to the interscalene group (67%). CONCLUSIONS: The anterior suprascapular block, but not the supraclavicular, provides noninferior analgesia compared to the interscalene approach for major arthroscopic shoulder surgery. Pulmonary function is best preserved with the anterior suprascapular nerve block.
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Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Anestésicos Locales/administración & dosificación , Artroscopía/efectos adversos , Bloqueo del Plexo Braquial/métodos , Dolor Postoperatorio/prevención & control , Hombro/cirugía , Adulto , Anciano , Procedimientos Quirúrgicos Ambulatorios/métodos , Artroscopía/métodos , Clavícula/efectos de los fármacos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/diagnóstico , Estudios Prospectivos , Ropivacaína/administración & dosificación , Escápula/efectos de los fármacosRESUMEN
BACKGROUND: Adductor canal blocks have shown promise in reducing postoperative pain in total knee arthroplasty patients. No randomized, controlled studies, however, evaluate the opioid-sparing benefits of a continuous 0.2% ropivacaine infusion at the adductor canal. We hypothesized that a continuous adductor canal block would decrease postoperative opioid consumption. METHODS: Eighty subjects presenting for primary unilateral total knee arthroplasty were randomized to receive either a continuous ultrasound-guided adductor canal block with 0.2% ropivacaine or a sham catheter. All subjects received a preoperative single-injection femoral nerve block with spinal anesthesia as is standard of care at our institution. Cumulative IV morphine consumption 48 hours after surgery was evaluated with analysis of covariance, adjusted for baseline characteristics. Secondary outcomes included resting pain scores (numeric rating scale), peak pain scores during physical therapy on postoperative days 1 and 2, quadriceps maximum voluntary isometric contraction, distance ambulated during physical therapy, postoperative nausea and vomiting, and satisfaction with analgesia. RESULTS: Eighty subjects were randomized, and 76 completed the study per-protocol. The least-square mean difference in cumulative morphine consumption over 48 hours (block-sham) was--16.68 mg (95% confidence interval, -29.78 to -3.59, P = 0.013). Total morphine use between 24 and 48 hours (after predicted femoral nerve block resolution) also differed by least-square mean -11.17 mg (95% confidence interval,: -19.93 to -2.42, P = 0.013). Intention-to-treat analysis was similar to the per-protocol results. Functional outcomes revealed subjects in the adductor canal catheter group had better quadriceps strength (P = 0.010) and further distance ambulated (P = 0.034) on postoperative day 2. CONCLUSIONS: A continuous adductor canal block for total knee arthroplasty reduces opioid consumption compared with that of placebo in the first 48 hours after surgery. Other outcomes including quadriceps strength, distance ambulated, and pain scores all show benefit from an adductor canal catheter after total knee arthroplasty but require further study before being interpreted as conclusive.
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Artroplastia de Reemplazo de Rodilla/métodos , Bloqueo Nervioso/métodos , Ultrasonografía Intervencional , Anciano , Analgesia , Analgesia Controlada por el Paciente , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestesia Intravenosa , Anestésicos Intravenosos/administración & dosificación , Cateterismo , Método Doble Ciego , Ambulación Precoz , Femenino , Nervio Femoral/diagnóstico por imagen , Humanos , Periodo Intraoperatorio , Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/uso terapéutico , Fuerza Muscular/fisiología , Bloqueo Nervioso/efectos adversos , Satisfacción del Paciente , Propofol/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: The saphenous nerve block using a landmark-based approach has shown promise in reducing postoperative pain in patients undergoing arthroscopic medial meniscectomy. We hypothesized that performing an ultrasound-guided adductor canal saphenous block as part of a multimodal analgesic regimen would result in improved analgesia after arthroscopic medial meniscectomy. METHODS: Fifty patients presenting for ambulatory arthroscopic medial meniscectomy under general anesthesia were prospectively randomized to receive an ultrasound-guided adductor canal block with 0.5% ropivacaine or a sham subcutaneous injection of sterile saline. Our primary outcome was resting pain scores (numerical rating scale; NRS) upon arrival to the postanesthesia care unit (PACU). Secondary outcomes included NRS at six hours, 12 hr, 18 hr, and 24 hr; postoperative nausea; and postoperative opioid consumption. RESULTS: There was a statistically significant difference in mean NRS pain scores upon arrival to the PACU (P = 0.03): block group NRS = 1.71 (95% confidence interval [CI] 0.73 to 2.68) vs sham group NRS = 3.25 (95% CI 2.27 to 4.23). Cumulative opioid consumption (represented in oral morphine equivalents) over 24 hr was 71.8 mg (95% CI 56.5 to 87.2) in the sham group vs 44.9 mg (95% CI 29.5 to 60.2) in the block group (P = 0.016). CONCLUSIONS: An ultrasound-guided block at the adductor canal as part of a combined multimodal analgesic regimen significantly reduces resting pain scores in the PACU following arthroscopic medial meniscectomy. Furthermore, 24-hr postoperative opioid consumption and pain scores were also reduced.
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Artroscopía/métodos , Meniscos Tibiales/cirugía , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Adulto , Anciano , Procedimientos Quirúrgicos Ambulatorios/métodos , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/epidemiología , Náusea y Vómito Posoperatorios/epidemiología , Estudios Prospectivos , Factores de Tiempo , Ultrasonografía Intervencional/métodosRESUMEN
Cardiopulmonary bypass (CPB) profoundly suppresses circulating thyroid hormone levels in infants. We performed a multicenter randomized placebo controlled trial to determine if triiodothyronine (T3) supplementation improves reduces time to extubation (TTE) in infants after CPB. Infants (n = 220) undergoing cardiac surgery with CPB and stratified into 2 age cohorts: ≤30 days and >30 days to <152 days were randomization to receive either intravenous triiodothyronine or placebo bolus followed by study drug infusion until extubated or at 48 hours, whichever preceded. T3 did not significantly alter the primary endpoint, TTE (hazard ratio for chance of extubation (1.08, 95% CI: 0.82-1.43, P = 0.575) in the entire randomized population with censoring at 21 days. T3 showed no significant effect on TTE (HR 0.82, 95% CI:0.55-1.23, P = 0.341) in the younger subgroup or in the older (HR 1.38, 95% CI:0.95-2.2, P = 0.095). T3 also did not significantly impact TTE during the first 48 hours while T3 levels were maintained (HR 1.371, 95% CI:0.942-1.95, P = 0.099) No significant differences occurred for arrhythmias or other sentinel adverse events in the entire cohort or in the subgroups. This trial showed no significant benefit on TTE in the entire cohort. T3 supplementation appears safe as it did not cause an increase in adverse events. The study implementation and analysis were complicated by marked variability in surgical risk, although risk categories were balanced between treatment groups.
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Cardiopatías Congénitas , Triyodotironina , Lactante , Humanos , Puente Cardiopulmonar/efectos adversos , Cardiopatías Congénitas/cirugía , Resultado del Tratamiento , Suplementos DietéticosRESUMEN
INTRODUCTION: Interscalene brachial plexus blocks are a commonly performed procedure to reduce pain following total shoulder arthroplasty. Liposomal bupivacaine has been purported to prolong the duration of brachial plexus blocks for up to 72 hours; however, there has been controversy surrounding the analgesic benefits of this drug. Our hypothesis was that an interscalene block performed with bupivacaine alone would be non-inferior to a combination of liposomal bupivacaine and bupivacaine with respect to opioid consumption following total shoulder arthroplasty. METHODS: Subjects presenting for primary total shoulder arthroplasty were randomized in a 1:1 ratio to an ultrasound-guided, single-injection interscalene block with either a combination of liposomal bupivacaine and bupivacaine (LB group) or bupivacaine without additive (Bupi group). The primary outcome of this study was 72-hour postoperative cumulative opioid consumption (in oral morphine equivalents) with a non-inferiority margin of 22.5 mg. Secondary outcomes included pain scores, patient satisfaction with analgesia and patient reported duration of sensory block. RESULTS: Seventy-six subjects, 38 from the Bupi group and 38 from the LB group, completed the study. Analysis of the primary outcome showed a 72-hour cumulative geometric mean oral morphine equivalent consumption difference of 11.9 mg (95% CI -6.9 to 30.8) between groups (calculated on the log scale). This difference constitutes approximately 1.5 tablets of oxycodone over 3 days. No secondary outcomes showed meaningful differences between groups. DISCUSSION: Interscalene brachial plexus blocks performed with bupivacaine alone did not demonstrate non-inferiority compared to a mixture of liposomal bupivacaine plus bupivacaine with regards to 72-hour cumulative opioid consumption following total shoulder arthroplasty. However, the difference between groups did not appear to be clinically meaningful.
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Artroplastía de Reemplazo de Hombro , Bloqueo del Plexo Braquial , Humanos , Bupivacaína/efectos adversos , Bloqueo del Plexo Braquial/efectos adversos , Bloqueo del Plexo Braquial/métodos , Artroplastía de Reemplazo de Hombro/efectos adversos , Analgésicos Opioides , Anestésicos Locales/efectos adversos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Dimensión del Dolor , MorfinaRESUMEN
OBJECTIVE: To prospectively evaluate the long-term impact of Kawasaki disease (KD) hospitalization on health-related quality of life (HRQoL). METHODS: We merged the Outcomes Assessment Program and KD databases and queried for KD admissions between 1 month and 18 years of age. Patients with a diagnosis of community-acquired pneumonia were included as a comparison group. HRQoL was evaluated with the parent proxy Pediatric Quality of Life Inventory (PedsQL). Long-term follow-up PedsQL surveys were performed at least 1 year after initial diagnosis and hospitalization. Results for the entire cohort adjusted for significant differences were calculated. Propensity score-matched cohorts were constructed from the unmatched cohorts of patients with long-term survey responses. Subgroup analysis for the KD group was performed. RESULTS: Patients with KD (n = 61) versus pneumonia (n = 80) had a lower PedsQL total score on admission and experienced a significantly greater HRQoL decline from baseline to admission. At long-term follow-up, no difference occurred in HRQoL between patients with KD and pneumonia, and 89% of patients with KD reached their baseline PedsQL scores. KD diagnostic subtype, coronary artery dilatation, and need for longer follow-up were not associated with HRQoL outcomes at any time point. Intravenous immunoglobulin nonresponders demonstrated lower HRQoL at admission, which did not persist at follow-up. CONCLUSIONS: Children with KD experience acute and significant HRQoL impairment exceeding that of children with newly diagnosed pneumonia, but the scores return to baseline at long-term follow-up. The recoveries at short- and long-term intervals are similar to patients with pneumonia.
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Síndrome Mucocutáneo Linfonodular , Calidad de Vida , Niño , Hospitalización , Humanos , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/terapia , Padres , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Arthroscopic hip surgery is associated with significant postoperative pain. Femoral nerve blocks have been shown to improve postoperative analgesia at the expense of quadriceps weakness. The pericapsular nerve group (PENG) block could be an alternative that may improve postoperative analgesia while preserving quadriceps strength. Our hypothesis was that a PENG block would provide superior postoperative analgesia compared with a sham block following arthroscopic hip surgery. METHODS: Subjects presenting for arthroscopic hip surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection PENG block (PENG group) with 20 mL of 0.5% ropivacaine or a sham injection with 5 mL of 0.9% normal saline (Sham group) prior to receiving general anesthesia. The primary outcome of this study was worst pain score within 30 min of emergence from anesthesia. Secondary outcomes included opioid consumption, patient satisfaction with analgesia, opioid-related adverse events, and persistent opioid use at 1 week. RESULTS: Sixty-eight subjects, 34 from the PENG group and 34 from the Sham group, completed the study per protocol. Analysis of the primary outcome demonstrated a mean difference in pain scores of -0.79 (95% CI -1.96 to 0.37; p=0.17) between the PENG and Sham groups immediately following surgery. No secondary outcomes showed statistically significant differences between groups. DISCUSSION: This study demonstrates that a preoperative PENG block does not improve analgesia following arthroscopic hip surgery. TRIAL REIGSTRATION NUMBER: NCT04508504.
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Survival analysis following oncological treatments require specific analysis techniques to account for data considerations, such as failure to observe the time of event, patient withdrawal, loss to follow-up, and differential follow up. These techniques can include Kaplan-Meier and Cox proportional hazard analyses. However, studies do not always report overall survival (OS), disease-free survival (DFS), or cancer recurrence using hazard ratios, making the synthesis of such oncologic outcomes difficult. We propose a hierarchical utilization of methods to extract or estimate the hazard ratio to standardize time-to-event outcomes so that study inclusion into meta-analyses can be maximized. We also provide proof-of concept results from a statistical analysis that compares OS, DFS, and cancer recurrence for robotic surgery to open and non-robotic minimally invasive surgery. In our example, use of the proposed methodology would allow for the increase in data inclusion from 108 hazard ratios reported to 240 hazard ratios reported or estimated, resulting in an increase of 122%. While there are publications summarizing the motivation for these analyses, and comprehensive papers describing strategies to obtain estimates from published time-dependent analyses, we are not aware of a manuscript that describes a prospective framework for an analysis of this scale focusing on the inclusion of a maximum number of publications reporting on long-term oncologic outcomes incorporating various presentations of statistical data.
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Oncología Médica/normas , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Neoplasias/cirugía , Procedimientos Quirúrgicos Robotizados/normas , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Laparoscopía/efectos adversos , Laparoscopía/normas , Neoplasias/epidemiología , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Transversus abdominis plane (TAP) blocks are associated with an improvement in postoperative analgesia following kidney transplant surgery. However, these blocks carry inherent risk and require a degree of expertise to perform successfully. Continuous intravenous lidocaine may be an effective alternative. In this randomized, non-inferiority study, we hypothesized that a continuous lidocaine infusion provides similar postoperative analgesia to a TAP block. METHODS: Subjects presenting for kidney transplant surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection TAP block (TAP group) or a continuous infusion of lidocaine (Lido group). The primary outcome of this non-inferiority study was opioid consumption within the first 24 hours following surgery. Secondary outcomes included pain scores, patient satisfaction, opioid-related adverse events, time to regular diet, and persistent opioid use. RESULTS: One hundred and twenty subjects, 59 from the TAP group and 61 from the Lido group, completed the study per protocol. Analysis of the primary outcome showed a cumulative geometric mean intravenous morphine equivalent difference between the TAP (14.6±3.2 mg) and Lido (15.9±2.4 mg) groups of 1.27 mg (95% CI -4.25 to 6.79; p<0.001), demonstrating non-inferiority of the continuous lidocaine infusion. No secondary outcomes showed clinically meaningful differences between groups. CONCLUSIONS: This study demonstrates that a continuous infusion of lidocaine offers non-inferior postoperative analgesia compared with an ultrasound-guided unilateral, single-injection TAP block in the first 24 hours following kidney transplant surgery. TRIAL REGISTRATION NUMBER: NCT03843879.
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Trasplante de Riñón , Lidocaína , Músculos Abdominales/diagnóstico por imagen , Analgésicos Opioides , Humanos , Trasplante de Riñón/efectos adversos , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & controlRESUMEN
BACKGROUND: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. METHODS: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. RESULTS: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). CONCLUSIONS: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.
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Anemia de Células Falciformes/epidemiología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/epidemiología , Adolescente , Adulto , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/epidemiología , Niño , Preescolar , Comorbilidad , Estudios Transversales , Femenino , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Prevalencia , Tanzanía/epidemiología , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
BACKGROUND: SLCO-encoded transporters have been associated with progression to castration-resistant prostate cancer (CRPC) after initiation of androgen deprivation therapy (ADT). Although expressed at lower levels than in CRPC tissues, SLCO-encoded transporters may also play a role in response of primary prostate cancer (PCa) to ADT and biochemical recurrence. METHODS: We systematically explored expression of the 11 human SLCO genes in a large sample of untreated and ADT-treated normal prostate (NP) and primary PCa tissues, including tumors treated with neoadjuvant abiraterone. RESULTS: Transporters with the most recognized role in steroid uptake in PCa, including SLCO2B1 (DHEAS) and 1B3 (testosterone), were consistently detected in primary PCa. SLCO1B3 was nearly 5-fold higher in PCa vs NP with no difference in Gleason 3 vs 4 and no change with ADT. SLCO2B1 was detected at 3-fold lower levels in PCa than NP but was nearly 7-fold higher in Gleason 4 vs Gleason 3 and increased 3-fold following ADT (p < 0.05 for all). CONCLUSIONS: We observed clear differences in SLCO expression in PCa vs NP samples, in Gleason 4 vs Gleason 3 tumors, and in ADT-treated vs untreated tissues. These findings are hypothesis generating due to small sample size, but suggest that baseline and ADT-induced changes in PCa OATP expression may influence steroid uptake and response to ADT, as well as uptake and response to drugs such as abiraterone and docetaxel which are also subject to OATP-mediated transport and are now being routinely combined with ADT in the metastatic castration sensitive setting.
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Antagonistas de Andrógenos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transportadores de Anión Orgánico/metabolismo , Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/metabolismo , Adulto , Anciano , Antagonistas de Andrógenos/uso terapéutico , Androstenos/farmacología , Androstenos/uso terapéutico , Sulfato de Deshidroepiandrosterona/metabolismo , Progresión de la Enfermedad , Docetaxel/farmacología , Docetaxel/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/cirugía , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Testosterona/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). The aim of this single-blind, randomised, controlled phase II trial is to compare auto-adjusting CPAP (APAP) with standard care to standard care alone in individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life. METHODS/DESIGN: Eligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16-22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist. The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment. DISCUSSION: Altering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events. TRIAL REGISTRATION: ISRCTN46012373 . Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015 Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.
Asunto(s)
Anemia de Células Falciformes/terapia , Encéfalo/fisiopatología , Presión de las Vías Aéreas Positiva Contínua/métodos , Trastornos Neurocognitivos/terapia , Apnea Obstructiva del Sueño/terapia , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/psicología , Atención , Automatización , Niño , Ensayos Clínicos Fase II como Asunto , Cognición , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Femenino , Humanos , Londres , Imagen por Resonancia Magnética , Masculino , Estudios Multicéntricos como Asunto , Trastornos Neurocognitivos/sangre , Trastornos Neurocognitivos/fisiopatología , Trastornos Neurocognitivos/psicología , Oximetría , Dimensión del Dolor , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Método Simple Ciego , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: The placement of thoracic epidurals can be technically challenging and requires a thorough understanding of neuraxial anatomy. Although ultrasound imaging of the thoracic spine has been described, no outcome studies on the use of this imaging have been performed. We evaluated whether preprocedural ultrasound of the thoracic spine would facilitate the process of epidural catheterization. METHODS: Subjects undergoing thoracic or upper abdominal surgery with planned thoracic epidural placement at T10 or higher were enrolled in this randomized double-blind study. Subjects were allocated into 1 of 2 groups for preoperative epidural placement: ultrasound guidance (group US) or palpation (group Palp). Subjects randomized to group US had a preprocedural ultrasound examination to identify pertinent spinal anatomy and make appropriate marks on the skin identifying midline and interlaminar spaces for targeted Tuohy needle insertion. Subjects in group Palp had a skin marking performed by palpation alone. Using the skin markings, all epidurals were performed using a loss of resistance to saline technique. Block levels were assessed with ice and pain scores obtained by a blinded nurse in the postanesthesia care unit. The primary outcome was procedural time from needle insertion to loss of resistance in the epidural space. RESULTS: Seventy subjects were recruited and completed the study protocol. The median time for epidural needle placement to achieve loss of resistance in group US and group Palp was 188.5 seconds (interquartile range [IQR], 79.0-515.0) and 242.0 seconds (IQR, 87.0-627.0), respectively (P = 0.188). Using ultrasound to mark the skin overlying the targeted epidural space took a median time of 85 seconds (IQR, 69-113) for group US and 35 seconds (IQR, 27-51) for group Palp (P < 0.001). The number of needle passes was not significantly different between the 2 groups (P = 0.31). The use of ultrasound assistance resulted in a decreased number of needle skin punctures to achieve loss of resistance (P = 0.005). Mean pain scores after surgery were lower in group US compared to group Palp: 3.0 versus 4.7, respectively (P = 0.015). CONCLUSIONS: This is the first randomized study to evaluate the efficacy of preprocedural ultrasound marking for placement of thoracic epidural catheters. We observed that preprocedural ultrasound did not significantly reduce the time required to identify the thoracic epidural space via loss of resistance. CLINICAL TRIALS REGISTRATION: NCT02785055 (https://clinicaltrials.gov/).
Asunto(s)
Abdomen/cirugía , Analgesia Epidural/métodos , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Umbral del Dolor/efectos de los fármacos , Dolor Postoperatorio/prevención & control , Nervios Torácicos/diagnóstico por imagen , Procedimientos Quirúrgicos Torácicos , Vértebras Torácicas/diagnóstico por imagen , Ultrasonografía Intervencional , Adulto , Anciano , Analgesia Epidural/efectos adversos , Analgesia Epidural/instrumentación , Analgésicos Opioides/administración & dosificación , Puntos Anatómicos de Referencia , Anestésicos Locales/efectos adversos , Bupivacaína/efectos adversos , Catéteres de Permanencia , Método Doble Ciego , Femenino , Humanos , Hidromorfona/administración & dosificación , Infusión Espinal , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/fisiopatología , Palpación , Procedimientos Quirúrgicos Torácicos/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , WashingtónRESUMEN
BACKGROUND AND OBJECTIVES: Continuous brachial plexus blocks at the interscalene level are associated with known diaphragm dysfunction from phrenic nerve paresis. More distal blocks along the brachial plexus may provide postsurgical analgesia while potentially having less effect on diaphragm function. Continuous interscalene, continuous supraclavicular, and continuous suprascapular nerve blocks were evaluated for respiratory function and analgesia after total shoulder arthroplasty. METHODS: After ethics board approval, subjects presenting for total shoulder arthroplasty were planned for randomization in a 1:1:1 ratio of a continuous interscalene, supraclavicular, or suprascapular block. The primary outcome was the assessment of vital capacity after 24 hours of continuous nerve block infusion (6 mL/h; 0.2% ropivacaine), without an initial bolus of local anesthetic during catheter placement. Additional outcomes included diaphragm excursion, pain scores, opioid consumption, and adverse effects. RESULTS: Seventy-five subjects, 25 per group, completed the study. At 24 hours of continuous infusion only (no initial block bolus), the mean vital capacity reduction in the continuous interscalene control group was 991 mL (95% confidence interval [CI], 820-1162). Compared to the interscalene group, the continuous supraclavicular group had a mean vital capacity reduction of 803 mL (95% CI, 616-991; P = 0.322). The continuous suprascapular group had a significantly improved mean vital capacity reduction of 464 mL (95% CI, 289-639; P < 0.001) when similarly compared against the interscalene group. A relative compromise in ultrasound-measured diaphragm excursion was identified in the interscalene group compared to both the supraclavicular group (P = 0.012) and the suprascapular group (P < 0.001). Mean pain scores on an 11-point scale (2.2, 1.6, and 2.6) and 24-hour opioid consumption (13.8 mg, 9.9 mg, and 21.8 mg) for groups interscalene, supraclavicular, and suprascapular, respectively, did not show statistically significant differences. Less adverse effects (Horner syndrome, dyspnea, and hoarseness) were noted in the suprascapular group when compared with the interscalene group (P = 0.002). CONCLUSIONS: A continuous suprascapular block may be a useful analgesic alternative to the interscalene or supraclavicular approaches when the preservation of lung function is a priority after shoulder replacement surgery.