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Background: While antibiotics are recommended for treatment of nontuberculous mycobacterial lung disease (NTMLD), the impact of early antibiotic initiation on healthcare resource utilisation is unclear. This study compared healthcare resource utilisation with early versus delayed antibiotic initiation in NTMLD. Methods: A retrospective, claims database study (Merative MarketScan) of patients diagnosed with NTMLD between 1 July 2015 and 30 June 2019. Patients were divided into early antibiotic initiation, i.e. ≤3â months after the first medical claim for NTMLD (index date), and delayed antibiotic initiation groups. Hospitalisations and outpatient visits during a 2-year post-index period were compared to baseline per treatment group; a difference-in-difference analysis compared early and delayed antibiotic initiation groups adjusting for confounding. Results: Out of 481 NTMLD treated patients, 364 (76%) and 117 (24%) comprised the early and delayed antibiotic initiation groups, respectively. The early antibiotic initiation group showed significant reductions from baseline in hospitalisations (all-cause, respiratory) and emergency department (ED) visits at follow-up. A significant increase from baseline in mean number of hospitalisations per patient was observed in the delayed antibiotic initiation group in year 1 post-index. Compared to delayed antibiotic initiation, the early antibiotic initiation group showed significantly greater reductions in all-cause hospitalisations in years 1 and 2 post-index (relative risk 0.62 (95% CI 0.41-0.95) and 0.62 (95% CI 0.39-0.98), respectively), and in respiratory-related hospitalisations. Conclusions: The early antibiotic initiation group showed significant reductions from baseline in hospitalisations and ED visits over time. Compared to delayed antibiotic initiation, early antibiotic initiation was associated with significantly greater reductions in hospitalisations.
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INTRODUCTION: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab. METHODS: This retrospective observational study used data from a US-based nationwide database of deidentified, electronic health record-derived data. Patients diagnosed with OC during the study period (1 January 2011-30 November 2022, inclusive) were eligible if they received 1L chemotherapy plus bevacizumab treatment followed by 1LM niraparib monotherapy, initiated between 1 January 2017 (inclusive) and 2 September 2022. Patients were followed from index date (initiation of niraparib 1LM) until the first occurrence of death, end of follow-up, or end of study. Clinical outcomes were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Kaplan-Meier curves were used to estimate TTD, TTNT, and 95% confidence intervals (CIs). RESULTS: Among 93 patients selected, median age at index was 67 years (interquartile range [IQR] 60-72 years). Most patients had BRCA wild-type/homologous recombination (HR)-proficient or BRCA wild-type/HR unknown disease (75.3%). In all, 18 (19.4%) patients had HR-deficient disease. Five (5.4%) patients had unknown test results for both BRCA and HR deficiency status. Median follow-up time was 16.3 months (IQR 8.7-25.4 months), and median time from end of 1L therapy to 1LM initiation was 35.0 days (IQR 25.0-53.9 days). Median TTD was 9.3 months (95% CI 6.1-11.3 months). Median TTNT was 12.9 months (95% CI 11.5-19.0 months). CONCLUSIONS: This real-world study provided insights into switch maintenance with 1LM niraparib monotherapy, which may be a viable treatment option for patients with advanced OC.
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Background: Dilated cardiomyopathy (DCM) contributes significantly to heart failure prevalence, yet supporting epidemiologic data is sparse. This study sought to estimate the period prevalence of DCM and the proportion of idiopathic DCM in the United States using a large, diverse electronic health records (EHR) database. Methods: This retrospective, observational study included 56,812,806 deidentified patients in Optum EHR with visits between 2017 and 2019. Suspected DCM cases were identified using ICD-10 coding. Deidentified clinical notes from 1000 randomly selected cases were manually reviewed to determine the diagnosis of DCM and estimate the proportion of idiopathic DCM. The period prevalence and clinical burden of DCM and idiopathic DCM were estimated. Results: Manual clinical review demonstrated that our definition had a positive predictive value of 92.5% for DCM, with 46.3% estimated as the idiopathic DCM proportion. The estimated period prevalence of DCM between 2017 and 2019 was 118.33 per 100,000. Prevalence increased for adults ≥65 years of age, males, and African Americans. Extrapolation to the 2019 US population led to an overall estimated burden of roughly 388,350 patients. Adjusting for the proportion of cases with idiopathic DCM yielded an idiopathic DCM prevalence of 59.23 per 100,000 and a burden of 194,385 patients. Evidence of clinical genetic testing in this population was scarce, with less than 0.43% of DCM cases reporting a testing code. Conclusions: This study establishes a conservative period prevalence for DCM and idiopathic DCM and demonstrates very low molecular genetic testing for DCM. These findings suggest that the clinical burden of genetic DCM may be underestimated.
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BACKGROUND: Rheumatoid arthritis (RA) patients have a lowered immune response to infection, potentially due to the use of corticosteroids and immunosuppressive drugs. Predictors of severe COVID-19 outcomes within the RA population have not yet been explored in a real-world setting. OBJECTIVES: To identify the most influential predictors of severe COVID-19 within the RA population. STUDY DESIGN: Retrospective cohort study. SETTING: Research was conducted using Optum's de-identified Clinformatics® Data Mart Database (2000-2021Q1), a US commercial claims database. METHODS: We identified adult patients with index COVID-19 (ICD-10-CM diagnosis code U07.1) between March 1, 2020, and December 31, 2020. Patients were required to have continuous enrollment and have evidence of one inpatient or 2 outpatient diagnoses of RA in the 365 days prior to index. RA patients with COVID-19 were stratified by outcome (mild vs severe), with severe cases defined as having one of the following within 60 days of COVID-19 diagnosis: death, treatment in the intensive care unit (ICU), or mechanical ventilation. Baseline demographics and clinical characteristics were extracted during the 365 days prior to index COVID-19 diagnosis. To control for improving treatment options, the month of index date was included as a potential independent variable in all models. Data were partitioned (80% train and 20% test), and a variety of machine learning algorithms (logistic regression, random forest, support vector machine [SVM], and XGBoost) were constructed to predict severe COVID-19, with model covariates ranked according to importance. RESULTS: Of 4,295 RA patients with COVID-19 included in the study, 990 (23.1%) were classified as severe. RA patients with severe COVID-19 had a higher mean age (mean [SD] = 71.6 [10.3] vs 63.4 [13.7] years, P < 0.001) and Charlson Comorbidity Index (CCI) (3.8 [2.4] vs 2.4 [1.8], P < 0.001) than those with mild cases. Males were more likely to be a severe case than mild (29.1% vs 18.5%, P < 0.001). The top 15 predictors from the best performing model (XGBoost, AUC = 75.64) were identified. While female gender, commercial insurance, and physical therapy were inversely associated with severe COVID-19 outcomes, top predictors included a March index date, older age, more inpatient visits at baseline, corticosteroid or gamma-aminobutyric acid analog (GABA) use at baseline or the need for durable medical equipment (i.e., wheelchairs), as well as comorbidities such as congestive heart failure, hypertension, fluid and electrolyte disorders, lower respiratory disease, chronic pulmonary disease, and diabetes with complication. LIMITATIONS: The cohort meeting our eligibility criteria is a relatively small sample in the context of machine learning. Additionally, diagnoses definitions rely solely on ICD-10-CM codes, and there may be unmeasured variables (such as labs and vitals) due to the nature of the data. These limitations were carefully considered when interpreting the results. CONCLUSIONS: Predictive baseline comorbidities and risk factors can be leveraged for early detection of RA patients at risk of severe COVID-19 outcomes. Further research should be conducted on modifiable factors in the RA population, such as physical therapy.
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Artritis Reumatoide , COVID-19 , Humanos , Adulto , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Prueba de COVID-19 , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake. METHODS: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed. RESULTS: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups. CONCLUSION: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD.
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Analgésicos Opioides/uso terapéutico , Cesárea , Trabajo de Parto/fisiología , Alta del Paciente , Adulto , Femenino , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Embarazo , ComprimidosRESUMEN
Many biological studies require the capture of individuals for sampling, for example for measurement of morphological or physiological traits, or for marking individuals for later observations. Capture methods employed often vary both within and between studies, and these differing methods could be more or less effective in capture of different individuals based on their morphology or behavior. If individuals that are prone to capture by the selected method differ with respect to traits of interest, such sampling bias could generate misleading or simply inaccurate results. The selection of capture methods could introduce two different forms of sampling bias, with the individuals that are sampled differing from the population at large or with individuals sampled via one method differing from individuals that could be sampled using a different method. We investigated this latter form of sampling bias by comparing individual birds sampled using two common capture techniques. We caught free-ranging black-capped chickadees (Poecile atricapillus) using walk-in traps baited with seed and mist nets paired with playback of an audio stimulus (conspecific mobbing calls). We measured 18 traits that we expect might vary among birds that are trappable by these differing methods-one that targets birds that are food motivated and potentially less neophobic and another that targets birds that respond readily to a perceived predation risk. We found no differences in the sex, morphology, initial and stress-induced corticosterone concentrations, behavioral response to a novel object, or behavioral response to a predator between individuals captured by these two methods. Individual variation in the behavioral response to a novel object was greater among birds caught by mist nets, suggesting this method might provide a sample that better reflects population-level individual variation. We do not know if the birds caught by these two methods provide a representative sample of the population at large, but can conclude that selection of either of these two common capture methods can similarly sample mean trait values of a population of interest. To accurately assess individual variation, particularly in behavior, mist nets might be preferable.
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OBJECTIVE: The aim of this study was to use real-world data to evaluate potential interactions between age, treatment, and the risk of developing four adverse events (AEs) common in the elderly: congestive heart failure, serious infections, non-melanoma skin cancer, and interstitial lung disease. These AEs were identified as important in a prior age-based analysis (≤ 65 vs > 65 years) of etanercept- or placebo-treated patients with rheumatoid arthritis (RA) in controlled clinical trials. METHODS: Real-world data (1 January 2013 to 31 January 2018) were obtained from the IBM Watson Health MarketScan® Database. Patients were included if aged ≥ 18 years, enrolled for ≥ 1 year prior to RA diagnosis, and without any of the four AEs of interest prior to RA diagnosis or between RA diagnosis and first etanercept exposure. Logistic regression analysis was applied following propensity matching of patients receiving or not receiving etanercept based on age at diagnosis, age status at the beginning of observation (> 65 years or not), sex, geographic region, and follow-up duration. RESULTS: The overall cohort comprised 403,689 patients. The absolute risk of each of the four AEs increased with age. In propensity-matched cohorts, etanercept was associated with significantly higher odds of developing each of the four AEs (p < 0.001 for all). However, the relative risk of experiencing the four AEs in patients who received etanercept versus those who did not was similar between patients ≤ 65 years of age and those > 65 years of age. CONCLUSIONS: In patients with RA, the relative increase in etanercept-associated risk of experiencing congestive heart failure, serious infection, non-melanoma skin cancer, or interstitial lung disease was similar between elderly and non-elderly.
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Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Etanercept/efectos adversos , Adolescente , Factores de Edad , Anciano , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Estudios de Cohortes , Bases de Datos Factuales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Etanercept/administración & dosificación , Etanercept/uso terapéutico , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIMS: Pre-operatively diagnosed patent foramen ovale (PFO) is associated with an increased risk of ischaemic stroke within 30 days after surgery. This study aimed to assess the PFO-attributable ischaemic stroke risk beyond the perioperative period. METHODS AND RESULTS: This observational study of adult patients without history of stroke undergoing non-cardiac surgery with general anaesthesia examined the association of PFO with ischaemic stroke 1 and 2 years after surgery using multivariable logistic regression. Of the 144 563 patients included, a total of 1642 (1.1%) and 2376 (1.6%) ischaemic strokes occurred within 1 and 2 years after surgery, 54 (4.7%) and 76 (6.6%) among patients with PFO, and 1588 (1.1%) and 2300 (1.6%) among patients without PFO, respectively. The odds of ischaemic stroke within 1 and 2 years after surgery were increased in patients with PFO: adjusted odds ratio (aOR) 2.01, 95% confidence interval (CI) 1.51-2.69; P < 0.001 and aOR 2.10, 95% CI 1.64-2.68; P < 0.001, respectively. Among patients who underwent contrast transoesophageal echocardiography, the frequency of PFO was 27%, and the increased stroke risk in patients with PFO was robust (aOR 3.80, 95% CI 1.76-8.23; P = 0.001 for year 1). The PFO-attributable risk was mitigated by post-operative prescription of combination antithrombotic therapy (odds ratio 0.41, 95% CI 0.22-0.75; P for interaction = 0.004). CONCLUSION: Patients with PFO are vulnerable to ischaemic stroke for an extended period of time after surgery. Physicians should consider implementing PFO screening protocols in patients scheduled for major non-cardiac surgery.
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Isquemia Encefálica/prevención & control , Embolia Paradójica/etiología , Foramen Oval Permeable/complicaciones , Accidente Cerebrovascular/patología , Adulto , Anciano , Estudios de Casos y Controles , Medios de Contraste/administración & dosificación , Quimioterapia Combinada , Ecocardiografía Transesofágica/efectos adversos , Femenino , Fibrinolíticos/uso terapéutico , Foramen Oval Permeable/cirugía , Humanos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Cuidados Posoperatorios/métodos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex. METHODS: We conducted a retrospective cohort study using 2010-2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12-55 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region. RESULTS: After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. No interaction was found in adjusted sampling-weighted model between sex and race/ethnicity on the odds of receiving opioids (P = .74). There was no difference in opioid administration to males as compared to females (odds ratio [OR] = 0.96, 95% CI, 0.87-1.06; P = .42) or to non-Caucasians as compared to Caucasians (OR = 0.99, 95% CI, 0.89-1.10; P = .84). In adjusted weighted models, non-Caucasian males, 123,121/239,457 (51.4%) did not differ from Caucasian non-Hispanic males, 317,427/525,434 (60.4%), on odds of receiving opioids, aOR = 0.88, 95% CI, 0.39-1.99; P = .75. Non-Caucasian females, 547,709/847,675 (64.6%) also did not differ from Caucasian females, 621,638/1,010,360 (61.5%), on odds of receiving opioids, aOR = 1.01, 95% CI, 0.53-1.90; P = .98. Across both sexes, non-Caucasians did not differ from Caucasians on receipt of nonopioid analgesics or antiemetics. Neither wait time to see a provider nor the length of the hospital visit was significantly different between sexes or race/ethnicities. CONCLUSIONS: Based on National Hospital Ambulatory Medical Care Survey data from 2010 to 2014, there is no statistically significant interaction between race/ethnicity and sex for administration of opioid analgesia to people presenting to the ED with appendicitis or gallbladder disease. These results suggest that the joint effect of patient race/ethnicity and sex may not manifest in disparities in opioid management.
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Analgésicos Opioides/administración & dosificación , Medicina de Emergencia/métodos , Etnicidad , Manejo del Dolor/métodos , Factores Sexuales , Adolescente , Adulto , Analgésicos , Apendicitis/epidemiología , Apendicitis/cirugía , Niño , Servicio de Urgencia en Hospital , Femenino , Enfermedades de la Vesícula Biliar/epidemiología , Enfermedades de la Vesícula Biliar/cirugía , Encuestas de Atención de la Salud , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Humanos , Masculino , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Probabilidad , Estudios Retrospectivos , Clase Social , Estados Unidos , Adulto JovenRESUMEN
Patients with autism spectrum disorder (ASD) often require sedation or general anesthesia. ASD is thought to arise from deficits in GABAergic signaling leading to abnormal neurodevelopment. We sought to investigate differences in how ASD patients respond to the GABAergic drug propofol by comparing the propofol-induced electroencephalogram (EEG) of ASD and neurotypical (NT) patients. This investigation was a prospective observational study. Continuous 4-channel frontal EEG was recorded during routine anesthetic care of patients undergoing endoscopic procedures between July 1, 2014 and May 1, 2016. Study patients were defined as those with previously diagnosed ASD by DSM-V criteria, aged 2-30 years old. NT patients were defined as those lacking neurological or psychiatric abnormalities, aged 2-30 years old. The primary outcome was changes in propofol-induced alpha (8-13 Hz) and slow (0.1-1 Hz) oscillation power by age. A post hoc analysis was performed to characterize incidence of burst suppression during propofol anesthesia. The primary risk factor of interest was a prior diagnosis of ASD. Outcomes were compared between ASD and NT patients using Bayesian methods. Compared to NT patients, slow oscillation power was initially higher in ASD patients (17.05 vs. 14.20 dB at 2.33 years), but progressively declined with age (11.56 vs. 13.95 dB at 22.5 years). Frontal alpha power was initially lower in ASD patients (17.65 vs. 18.86 dB at 5.42 years) and continued to decline with age (6.37 vs. 11.89 dB at 22.5 years). The incidence of burst suppression was significantly higher in ASD vs. NT patients (23.0% vs. 12.2%, p < 0.01) despite reduced total propofol dosing in ASD patients. Ultimately, we found that ASD patients respond differently to propofol compared to NT patients. A similar pattern of decreased alpha power and increased sensitivity to burst suppression develops in older NT adults; one interpretation of our data could be that ASD patients undergo a form of accelerated neuronal aging in adolescence. Our results suggest that investigations of the propofol-induced EEG in ASD patients may enable insights into the underlying differences in neural circuitry of ASD and yield safer practices for managing patients with ASD.
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Importance: Perioperative stroke is a major complication for patients undergoing surgery. Patent foramen ovale (PFO) represents a possible anatomical link between venous thrombosis and stroke. Objective: To determine whether a preoperatively diagnosed PFO is associated with increased risk of perioperative ischemic stroke. Design, Setting, and Participants: Retrospective cohort study from Massachusetts General Hospital and 2 affiliated community hospitals between January 1, 2007, and December 31, 2015. Participants were 182â¯393 consecutive adults undergoing noncardiac surgery with general anesthesia. Exposures: Preoperatively diagnosed PFO. Main Outcomes and Measures: Perioperative ischemic stroke occurring within 30 days of surgery; stroke subtype by Oxfordshire Community Stroke Project classification and stroke severity by National Institute of Health Stroke Scale (NIHSS). Results: Among the 150â¯198 patient cases analyzed (median [SD] age, 55 [16] years), 1540 (1.0%) had a diagnosis of PFO before surgery. A total of 850 (0.6%) ischemic strokes occurred within 30 days of surgery (49 [3.2%] among patients with PFO and 801 [0.5%] among patients without PFO). In adjusted analyses, patients with PFO had an increased risk of ischemic stroke compared with patients without PFO (odds ratio, 2.66 [95% CI, 1.96-3.63]; P < .001). The estimated risks of stroke were 5.9 for every 1000 patients with PFO and 2.2 for every 1000 patients without PFO (adjusted absolute risk difference, 0.4% [95% CI, 0.2%-0.6%). Patients with PFO also had an increased risk of large vessel territory stroke (relative risk ratio, 3.14 [95% CI, 2.21-4.48]; P < .001) and a more severe stroke-related neurologic deficit measured by NIHSS (median, 4 [interquartile range {IQR}, 2-10] vs median, 3 [IQR, 1-6] for those without PFO; P = .02). Conclusions and Relevance: Among adult patients undergoing noncardiac surgery at 3 hospitals, having a preoperatively diagnosed PFO was significantly associated with increased risk of perioperative ischemic stroke within 30 days after surgery. Further research is needed to confirm these findings and to determine whether interventions would decrease this risk.
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Foramen Oval Permeable/complicaciones , Accidente Cerebrovascular/etiología , Adulto , Anciano , Área Bajo la Curva , Isquemia Encefálica/etiología , Comorbilidad , Ecocardiografía , Femenino , Foramen Oval Permeable/diagnóstico por imagen , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: The perioperative assessment of right ventricular (RV) function remains a challenge. Tricuspid annular plane systolic excursion (TAPSE) using M-mode is a widely used measure of RV function. However, accurate alignment of the ultrasound beam with the direction of annular movement can be difficult with transesophageal echocardiography (TEE) to measure TAPSE, precluding effective use of M-mode to measure annular excursion. Tracking of specular reflectors in the myocardium may provide an angle-independent method to assess annular motion with TEE. We hypothesized that TEE speckle tracking of the lateral tricuspid annular motion represents a comparable measurement to the well-validated M-mode TAPSE on transthoracic echocardiogram (TTE), and may be considered as a reasonable alternative to TAPSE. METHODS: This is a prospective, observational cohort study. We included all patients, who were in sinus rhythm, with a preoperative TTE within 3 months of scheduled cardiac surgery that required intraoperative TEE. Tissue motion annular displacements (TMAD) of the lateral (L), septal (S), and midpoint (M) tricuspid annulus were measured (QLAB Cardiac Motion Quantification; Philips Medical, Andover, MA) after induction of general anesthesia. This was compared to the preoperative M-mode TAPSE on TTE. RESULTS: Seventy-two consecutive patients who met eligibility requirements were enrolled from September to November 2016. Twelve were excluded due to poor image quality, allowing TMAD to be analyzed in 60 patients. TMAD was analyzed offline and TMAD analysis was able to track tricuspid annular motion in all patients. The mean TMAD (L), TMAD (S), and TMAD (M) were 17.4 ± 5.2, 10.2 ± 4.8, and 14.2 ± 4.8 mm, respectively. TMAD (L) showed close correlation with M-mode TAPSE on TTE (r = 0.87, 95% confidence interval, 0.79-0.92; P < .01). All patients with a preoperative TAPSE <17 mm had a TMAD (L) <17 mm, while 71% of those with a TAPSE ≥ 17 mm had a TMAD (L) ≥ 17 mm. There was strong positive correlation between TMAD (L) and intraoperative RV fractional area change (r = 0.86, 95% confidence interval, 0.77-0.91; P < .01). Reproducibility analysis of TMAD within and across observers showed excellent correlation. CONCLUSIONS: TMAD is a quick and angle-independent method to quantitatively assess RV longitudinal function by TEE. It correlates strongly with M-mode TAPSE on TTE. Because TMAD and TAPSE were not simultaneously measured in this study, their correlation is subject to differences in loading conditions, general anesthesia, and changes in the disease process. TMAD may be easily applied in routine clinical settings and its role in the perioperative environment deserves to be further explored.
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Anestesia General , Ecocardiografía Transesofágica/estadística & datos numéricos , Monitoreo Intraoperatorio , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/fisiología , Función Ventricular Derecha/fisiología , Anciano , Anestesia General/métodos , Estudios de Cohortes , Ecocardiografía Transesofágica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Estudios ProspectivosRESUMEN
OBJECTIVES: Sleep, which comprises of rapid eye movement (REM) and non-REM stages 1-3 (N1-N3), is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function. The principal sedative drugs produce electroencephalogram beta oscillations, which have been associated with neurocognitive dysfunction. Pharmacological induction of altered arousal states that neurophysiologically approximate natural sleep, termed biomimetic sleep, may eliminate drug-induced neurocognitive dysfunction. METHODS: We performed a prospective, single-site, three-arm, randomized-controlled, crossover polysomnography pilot study (nâ¯=â¯10) comparing natural, intravenous dexmedetomidine- (1-µg/kg over 10 min [nâ¯=â¯7] or 0.5-µg/kg over 10â¯min [nâ¯=â¯3]), and zolpidem-induced sleep in healthy volunteers. Sleep quality and psychomotor performance were assessed with polysomnography and the psychomotor vigilance test, respectively. Sleep quality questionnaires were also administered. RESULTS: We found that dexmedetomidine promoted N3 sleep in a dose dependent manner, and did not impair performance on the psychomotor vigilance test. In contrast, zolpidem extended release was associated with decreased theta (â¼5-8â¯Hz; N2 and N3) and increased beta oscillations (â¼13-25â¯Hz; N2 and REM). Zolpidem extended release was also associated with increased lapses on the psychomotor vigilance test. No serious adverse events occurred. CONCLUSIONS: Pharmacological induction of biomimetic N3 sleep with psychomotor sparing benefits is feasible. SIGNIFICANCE: These results suggest that α2a adrenergic agonists may be developed as a new class of sleep enhancing medications with neurocognitive sparing benefits.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Fases del Sueño/efectos de los fármacos , Adulto , Nivel de Alerta , Ritmo beta , Femenino , Humanos , Masculino , Proyectos Piloto , Piridinas/farmacología , Ritmo Teta , ZolpidemRESUMEN
BACKGROUND: Esmolol is an ultrashort ß-1 receptor antagonist. Recent studies suggest a role for esmolol in pain response modulation. The authors performed a meta-analysis to determine if the intraoperative use of esmolol reduces opioid consumption or pain scores. METHODS: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, pubget, and Google Scholar were searched. Studies were included if they were randomized, placebo- or opioid-controlled trials written in English, and performed on patients 18 years of age or older. For comparison of opioid use, included studies tracked opioid consumption intraoperatively and/or in the postanesthesia care unit. Pain score comparisons were performed during the first hour after surgery. RESULTS: Seventy-three studies were identified, 23 were included in the systematic review, and 19 were eligible for 1 or more comparisons. In 433 patients from 7 trials, intraoperative esmolol decreased intraoperative opioid consumption (Standard Mean Difference [SMD], -1.60; 95% confidence interval [CI], -2.25 to -0.96; P ≤ .001). In 659 patients from 12 trials, intraoperative esmolol decreased postanesthesia care unit opioid consumption (SMD, -1.21; 95% CI, -1.66 to -0.77; P ≤ .001). In 688 patients from 11 trials, there was insufficient evidence of change in postoperative 1 hour pain scores (SMD, -0.60; 95% CI, -1.44 to 0.24; P = .163). CONCLUSIONS: This meta-analysis demonstrates that intraoperative esmolol use reduces both intraoperative and postoperative opioid consumption, with no change in postoperative pain scores.
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Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Analgésicos Opioides/administración & dosificación , Cuidados Intraoperatorios/métodos , Dolor Postoperatorio/prevención & control , Atención Perioperativa/métodos , Propanolaminas/administración & dosificación , Quimioterapia Combinada , Humanos , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Dolor Postoperatorio/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Análisis de RegresiónRESUMEN
BACKGROUND: Orthotopic liver transplantation (OLT) is characterized by significant intraoperative hemodynamic variability. Accurate and real-time cardiac output (CO) monitoring aids clinical decision making during OLT. The purpose of this study is to compare accuracy, precision, and trending ability of CO estimation obtained noninvasively using pulse wave transit time (estimated continuous cardiac output [esCCO; Nihon Kohden, Tokyo, Japan]) or thoracic bioimpedance (ICON; Osypka Medical GmbH, Berlin, Germany) to thermodilution cardiac output (TDCO) measured with a pulmonary artery catheter. METHODS: Nineteen patients undergoing OLT were enrolled. CO measurements were collected with esCCO, ICON, and thermodilution at 5 time points: (T1) pulmonary artery catheter insertion; (T2) surgical incision; (T3) portal reperfusion; (T4) hepatic arterial reperfusion; and (T5) abdominal closure. The results were analyzed with Bland-Altman plot, percentage error (the percentage of the difference between the CO estimated with the noninvasive monitoring device and CO measured with the thermodilution technique), 4-quadrant plot with concordance rate (the percentage of the total number of points in the I and III quadrant of the 4-quadrant plot), and concordance correlation coefficient (a measure of how well the pairs of observations deviate from the 45-degree line of perfect agreement). RESULTS: Although TDCO increased at T3-T5, both esCCO and ICON failed to track the changes of CO with sufficient accuracy and precision. The mean bias of esCCO and ICON compared to TDCO were -2.0 L/min (SD, ±2.7 L/min) and -3.3 L/min (SD, ±2.8 L/min), respectively. The percentage error was 69% for esCCO and 77% for ICON. The concordance correlation coefficient was 0.653 (95% confidence interval [CI], 0.283-0.853) for esCCO and 0.310 (95% CI, -0.167 to 0.669) for ICON. Nonetheless, esCCO and ICON exhibited reasonable trending ability of TDCO (concordance rate: 95% [95% CI, 88-100] and 100% [95% CI, 93-100]), respectively. The mean bias was correlated with systemic vascular resistance (SVR) and arterial elastance (Ea) for esCCO (SVR, r = 0.610, 95% CI, 0.216-0.833, P < .0001; Ea, r = 0.692, 95% CI, 0.347-0.872; P < .0001) and ICON (SVR, r = 0.573, 95% CI, 0.161-0.815, P < .0001; Ea, r = 0.612, 95% CI, 0.219-0.834, P < .0001). CONCLUSIONS: The noninvasive CO estimation with esCCO and ICON exhibited limited accuracy and precision, despite with reasonable trending ability, when compared to TDCO, during OLT. The inaccuracy of esCCO and ICON is especially large when SVR and Ea were decreased during the neohepatic phase. Further refinement of the technology is desirable before noninvasive techniques can replace TDCO during OLT.
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Gasto Cardíaco/fisiología , Impedancia Eléctrica , Trasplante de Hígado/métodos , Monitoreo Intraoperatorio/métodos , Análisis de la Onda del Pulso/métodos , Anciano , Femenino , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Termodilución/métodosRESUMEN
BACKGROUND: Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned. OBJECTIVE: The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population. STUDY DESIGN: A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE. RESULTS: Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = < 0.001). There were no significant differences in baseline characteristics between the groups of patients who did and did not lose efficacy of their therapy. However, those who experienced LOE had a baseline SCS therapy VAS score 3.09 points lower than those who did not (95% CI: 1.69 to 4.48, P = < 0.001). LIMITATIONS: This study had several limitations including the retrospective nature of its design, confounders to VAS scores, small sample size, missing data points, and the evaluation of only conventional, low-frequency SCS therapy. CONCLUSIONS: Patients who received a SCS had a significant increase in VAS scores over time. Our data did not show any baseline patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE. KEY WORDS: Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.
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Dolor Crónico/terapia , Estimulación de la Médula Espinal , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor , Dimensión del Dolor , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Following through on one's goals to study is essential for effective, self-regulated learning. This can be difficult for residents because of clinical demands and limited personal time. WOOP (Wish, Outcome, Obstacle, Plan) is a self-regulation strategy, also known as mental contrasting with implementation intentions. WOOP increases follow-through on goals in many domains, although it has not, to our knowledge, been evaluated in medical education. OBJECTIVE: We compared the effect of WOOP versus goal setting on time residents spent studying. METHODS: Through a prospective, randomized, comparative effectiveness study, during a 1-month, intensive care unit rotation, we clustered anesthesiology residents in single-blind fashion to WOOP versus goal setting. Both groups received organized study materials. The intervention group performed WOOP to study more; the comparison group set goals to study more. Residents tracked studying with daily diaries. The primary outcome was total time spent studying toward stated goals. Time spent studying "non-goal" medical material was a secondary outcome. RESULTS: Of 34 eligible residents, 100% participated. Sixteen residents were randomized to the WOOP group and 18 to the goal-setting group. The WOOP group spent significantly more time studying toward their goals compared with the goal-setting group (median = 4.3 hours versus 1.5 hours; P = .021; g = 0.66). There was no significant difference in time spent studying non-goal medical material between groups (median = 5.5 hours versus 5.0 hours, P = .99). CONCLUSIONS: WOOP increased the time residents spent studying toward their goals as compared with setting goals alone.
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Objetivos , Internado y Residencia , Investigación sobre la Eficacia Comparativa , Humanos , Unidades de Cuidados Intensivos , Estudios Prospectivos , Método Simple CiegoRESUMEN
BACKGROUND: Volatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness. METHODS: Sevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1-/- mice). Spatial distributions of GC-1α and the GC-2α subunit in the brain were visualized by in situ hybridization. Brain cGMP levels were measured in WT and GC-1-/- mice after inhaling oxygen with or without 1.2% sevoflurane for 20 min. RESULTS: Higher concentrations of sevoflurane were required to induce LORR in GC-1-/- mice than in WT mice (1.5 ± 0.1 vs. 1.1 ± 0.2%, respectively, n = 14 and 14, P < 0.0001). Similarly, RORR occurred at higher concentrations of sevoflurane in GC-1-/- mice than in WT mice (1.0 ± 0.1 vs. 0.8 ± 0.1%, respectively, n = 14 and 14, P < 0.0001). Abundant GC-1α and GC-2α mRNA expression was detected in the cerebral cortex, medial habenula, hippocampus, and cerebellum. Inhaling 1.2% sevoflurane for 20 min increased cGMP levels in the brains of WT mice from 2.6 ± 2.0 to 5.5 ± 3.7 pmol/mg protein (n = 13 and 10, respectively, P = 0.0355) but not in GC-1-/- mice. CONCLUSION: Congenital deficiency of GC-1α abolished the ability of sevoflurane anesthesia to increase cGMP levels in the whole brain, and increased the concentration of sevoflurane required to induce LORR. Impaired NO-cGMP signaling raises the threshold for producing sevoflurane-induced unconsciousness in mice.
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Anestésicos por Inhalación/farmacología , Guanilato Ciclasa/genética , Éteres Metílicos/farmacología , Animales , Encéfalo/metabolismo , Guanosina Monofosfato/metabolismo , Ratones Noqueados , Reflejo de Enderezamiento/efectos de los fármacos , SevofluranoRESUMEN
OBJECTIVES: To investigate migraine patterns in the United States using Google search data and utilize this information to better understand societal-level trends. Additionally, we aimed to evaluate time-series relationships between migraines and social factors. BACKGROUND: Extensive research has been done on clinical factors associated with migraines, yet population-level social factors have not been widely explored. Migraine internet search data may provide insight into migraine trends beyond information that can be gleaned from other sources. METHODS: In this longitudinal analysis of open access data, we performed a time-series analysis in which about 12 years of Google Trends data (January 1, 2004 to August 15, 2016) were assessed. Data points were captured at a daily level and Google's 0-100 adjusted scale was used as the primary outcome to enable the comparison of relative popularity in the migraine search term. We hypothesized that the volume of relative migraine Google searches would be affected by societal aspects such as day of the week, holidays, and novel social events. RESULTS: Several recurrent social factors that drive migraine searches were identified. Of these, day of the week had the most significant impact on the volume of Google migraine searches. On average, Mondays accumulated 13.31 higher relative search volume than Fridays (95% CI: 11.12-15.51, P ≤ .001). Surprisingly, holidays were associated with lower relative migraine search volumes. Christmas Day had 13.84 lower relative search volumes (95% CI: 6.26-21.43, P ≤ .001) and Thanks giving had 20.18 lower relative search volumes (95% CI: 12.55-27.82, P ≤ .001) than days that were not holidays. Certain novel social events and extreme weather also appear to be associated with relative migraine Google search volume. CONCLUSIONS: Social factors play a crucial role in explaining population level migraine patterns, and thus, warrant further exploration.