Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery.

BACKGROUND: Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied. METHODS: This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type. RESULTS: The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type. CONCLUSIONS: The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study.

BACKGROUND: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. OBJECTIVE: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. DESIGN: Retrospective cohort study. SETTING: U.S. hospitals in the Premier Healthcare Database. PATIENTS: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. INTERVENTIONS: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). MEASUREMENTS: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. RESULTS: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. LIMITATION: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. CONCLUSION: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. PRIMARY FUNDING SOURCE: National Institute on Aging.

Receipt of Smoking Cessation Medications Among People With and Without Human Immunodeficiency Virus in the Veterans Aging Cohort Study (2003-2018).

Background: Nicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown. Methods: We identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003-2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0-365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH. Results: The sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994-1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040-1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036-1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004-1.009]). Conclusions: In a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking.

Delirium among people aging with and without HIV: Role of alcohol and Neurocognitively active medications.

BACKGROUND: People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs. METHODS: Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, race/ethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The case/control date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Medication exposure was measured from 45 to 3 days prior to index date; medications were classified as anticholinergic NCAM, non-anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses. RESULTS: PWH experienced a higher incidence of delirium (5.6, [95% CI 5.3-5.9/1000 PY]) than PWoH (5.0, [95% CI 4.8-5.1/1000 PY]). In multivariable analysis, anticholinergic and non-anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose-response associations with delirium. CONCLUSIONS: Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH.

Sex and Gender in Lung Diseases and Sleep Disorders: A State-of-the-Art Review: Part 2.

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder.

Receipt and predictors of smoking cessation pharmacotherapy among veterans with and without HIV.

Smoking is highly prevalent among people living with HIV (PLWH) and increases cardiovascular risk. Pharmacotherapies such as nicotine replacement therapy (NRT), bupropion, and varenicline help to reduce smoking, though rates of receipt among PLWH compared with HIV-uninfected persons are unknown. Among 814 PLWH and 908 uninfected patients enrolled in the Veterans Aging Cohort Study (2012-2017) who reported current smoking, we used marginal multivariable log-linear regression models to estimate adjusted relative risks (ARR) of receiving pharmacotherapy by HIV status. We also assessed patient-level factors associated with pharmacotherapy receipt within each group. In multivariable analyses, receipt of NRT was less likely among PLWH relative to uninfected participants (ARR 0.77, 95% CI 0.67, 0.89). In both populations, documented mental health disorders and contemplation to quit were associated with greater likelihood of receiving pharmacotherapy. Further research is needed to explore potential treatment disparities.

Improved Diagnostic Yield and Specimen Quality With Endobronchial Ultrasound-Guided Forceps Biopsies: A Retrospective Analysis.

BACKGROUND: Endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) has a high diagnostic yield when evaluating mediastinal and hilar lymphadenopathy (LAD). Having previously demonstrated the safety of EBUS-guided cautery-assisted transbronchial nodal forceps biopsy (ca-TBFB), we report disease-specific improvements in diagnostic yield and tissue acquisition when supplementing the EBUS-TBNA-based standard of care (SOC) with ca-TBFB. METHODS: We retrospectively reviewed 213 patients who sequentially underwent SOC and ca-TBFB during the same procedure. We determined 3 clinical scenarios of interest based on preprocedural imaging: isolated mediastinal/hilar LAD, LAD associated with a nodule or mass suspicious for malignancy, and LAD associated with parenchymal findings suggestive of sarcoidosis. Using validated methods, we assessed diagnostic yield on a per-patient basis and specimen quality on a per-node basis on the 136 patients meeting diagnostic criteria. RESULTS: Administration of disease-specific SOC with ca-TBFB yielded gains that varied by diagnosis. Diagnostic yields of SOC and its supplementation with ca-TBFB were 91.8% and 93.4% (P = .50) of the 61 patients diagnosed with solid-organ malignancy, 62.7% and 94.9% (P < .001) of the 59 patients diagnosed with sarcoidosis, and 62.5% and 93.8% (P = .042) of the 16 patients diagnosed with lymphoma, the. For each disease process, specimens obtained with ca-TBFB exhibited statistically higher quality. CONCLUSIONS: We suggest that relative to SOC, ca-TBFB improves diagnostic yield for sarcoidosis and lymphoma while providing uniformly better tissue quality and cellularity. We propose a protocol for use of this innovative technique.

GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance.

Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.

Longitudinal Trends and Variation in Antipsychotic Use in Older Adults After Cardiac Surgery.

OBJECTIVES: To evaluate temporal trends and between-hospital variation in off-label antipsychotic medication (APM) use in older adults undergoing cardiac surgery. DESIGN: Retrospective cohort study. SETTING: National administrative database including 465 U.S. hospitals. PARTICIPANTS: Individuals aged 65 and older without known indications for APMs who underwent cardiac surgery from 2004 to 2014 (N=293,212). MEASUREMENTS: Postoperative exposure to any APMs and potentially excessive dosing were examined. Hospital-level APM prescribing intensity was defined as the proportion of individuals newly treated with APMs in the postoperative period. RESULTS: The rate of APM use declined from 8.8% in 2004 to 6.2% in 2014 (p<.001). Use of haloperidol (parenteral 7.0% to 4.5%, p<.001; oral: 1.9% to 0.5%, p<.001), and risperidone (1.1% to 0.3%, p<.001) declined, whereas quetiapine use tripled (0.6% to 1.9%, p=.03). Hospital APM prescribing intensity varied widely, from 0.3% to 35.6%, across 465 hospitals. Treated individuals at higher-prescribing hospitals were more likely to receive APMs on the day of discharge (highest vs lowest quintile: 15.1% vs 9.6%; p<.001) and for a longer duration (4.8 vs 3.7 days; p<.001) than those at lower-prescribing hospitals. Delirium was the strongest risk factor for APM exposure (odds ratio=9.73, 95% confidence interval=9.02-10.5), whereas none of the hospital characteristics were significantly associated. The rate of potentially excessive dosing declined (60.7% to 44.9%, p<.001), and risk factors for potentially excessive dosing were similar to those for any APM exposure. CONCLUSIONS: Our findings suggest highly variable prescribing cultures and raise concerns about inappropriate use, highlighting the need for better evidence to guide APM prescribing in hospitalized older adults after cardiac surgery.

Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis.

RATIONALE: Vascular endothelial growth factor down-regulates microRNA-1 (miR-1) in the lung endothelium, and endothelial cells play a critical role in tumor progression and angiogenesis. OBJECTIVES: To examine the clinical significance of miR-1 in non-small cell lung cancer (NSCLC) and its specific role in tumor endothelium. METHODS: miR-1 levels were measured by Taqman assay. Endothelial cells were isolated by magnetic sorting. We used vascular endothelial cadherin promoter to create a vascular-specific miR-1 lentiviral vector and an inducible transgenic mouse. KRASG12D mut/Trp53-/- (KP) mice, lung-specific vascular endothelial growth factor transgenic mice, Lewis lung carcinoma xenografts, and primary endothelial cells were used to test the effects of miR-1. MEASUREMENTS AND MAIN RESULTS: In two cohorts of patients with NSCLC, miR-1 levels were lower in tumors than the cancer-free tissue. Tumor miR-1 levels correlated with the overall survival of patients with NSCLC. miR-1 levels were also lower in endothelial cells isolated from NSCLC tumors and tumor-bearing lungs of KP mouse model. We examined the significance of lower miR-1 levels by testing the effects of vascular-specific miR-1 overexpression. Vector-mediated delivery or transgenic overexpression of miR-1 in endothelial cells decreased tumor burden in KP mice, reduced the growth and vascularity of Lewis lung carcinoma xenografts, and decreased tracheal angiogenesis in vascular endothelial growth factor transgenic mice. In endothelial cells, miR-1 level was regulated through phosphoinositide 3-kinase and specifically controlled proliferation, de novo DNA synthesis, and ERK1/2 activation. Myeloproliferative leukemia oncogene was targeted by miR-1 in the lung endothelium and regulated tumor growth and angiogenesis. CONCLUSIONS: Endothelial miR-1 is down-regulated in NSCLC tumors and controls tumor progression and angiogenesis.

Association Between Hospital Readmission and Acute and Sustained Delays in Functional Recovery During 18 Months After Elective Surgery: The Successful Aging after Elective Surgery Study.

OBJECTIVES: To examine the effect of hospital readmission on functional recovery after elective surgery in older adults. DESIGN: Prospective cohort of individuals aged 70 and older undergoing elective surgery, enrolled from June 2010 to August 2013. SETTING: Two academic medical centers. PARTICIPANTS: Community-dwelling older adults (N = 566; mean age ± standard deviation 77 ± 5) undergoing major elective surgery and expected to be admitted for at least 3 days. MEASUREMENTS: Readmission was assessed in multiple interviews with participants and family members over 18 months and validated against medical record review. Physical function was assessed according to ability to perform instrumental activities of daily living (IADLs) and activities of daily living (ADL), Medical Outcomes Study 12-item Short-Form Survey Physical Component Summary score, and a standardized functional composite. RESULTS: Two hundred fifty-five (45%) participants experienced 503 readmissions. Readmissions were associated with delays in functional recovery in all measures of physical function. Having two or more readmissions over 18 months was associated with persistent and significantly greater risk of IADL dependence (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.5-2.3) and ADL dependence (RR = 3.3, 95% CI = 1.7-6.4). Degree of functional impairment increased progressively with number of readmissions. Readmissions within 2 months resulted in delayed functional recovery to baseline by 18 months, and readmissions between 12 and 18 months after surgery resulted in loss of functional recovery previously achieved. CONCLUSION: Readmission after elective surgery may contribute to delays in functional recovery and persistent functional deficits in older adults.

Endobronchial Ultrasound-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is important in the evaluation of thoracic lymphadenopathy. Reliably providing excellent diagnostic yield for malignancy, its diagnosis of sarcoidosis is inconsistent. Furthermore, TBNA may not suffice when larger "core biopsy" samples of malignant tissue are required. The primary objective of this study was to determine if the sequential use of TBNA and a novel technique called cautery-assisted transbronchial forceps biopsy (ca-TBFB) was safe. Secondary outcomes included sensitivity and successful acquisition of tissue. METHODS: The study prospectively enrolled 50 unselected patients undergoing convex-probe EBUS. All lymph nodes exceeding 1 cm were sequentially biopsied under EBUS guidance using TBNA and ca-TBFB. Safety and sensitivity were assessed at the nodal level for 111 nodes. Results of each technique were also reported for each patient. RESULTS: There were no significant adverse events. In nodes determined to be malignant, TBNA provided higher sensitivity (100%) than ca-TBFB (78%). However, among nodes with granulomatous inflammation, ca-TBFB exhibited higher sensitivity (90%) than TBNA (33%). On the one hand, for analysis based on patients rather than nodes, 6 of the 31 patients with malignancy would have been missed or understaged if the diagnosis were based on samples obtained by ca-TBFB. On the other hand, 3 of 8 patients with sarcoidosis would have been missed if analysis were based only on TBNA samples. In some patients, only ca-TBFB acquired sufficient tissue for the core samples needed in clinical trials of malignancy. CONCLUSIONS: The sequential use of TBNA and ca-TBFB appears to be safe. The larger samples obtained from ca-TBFB increased its sensitivity to detect granulomatous disease and provided adequate specimens for clinical trials of malignancy when specimens from needle biopsies were insufficient. For thoracic surgeons and advanced bronchoscopists, we advocate ca-TBFB as an alternative to TBNA in select clinical scenarios.

Comparison of Transbronchial and Cryobiopsies in Evaluation of Diffuse Parenchymal Lung Disease.

BACKGROUND: Diffuse parenchymal lung diseases (DPLDs) are common. An accurate diagnosis is essential due to differences in etiology, clinicopathologic features, therapeutic options, and prognosis. Transbronchial lung biopsies (TBLBs) are often limited by small specimen size, crush artifact, and other factors. Transbronchial lung cryobiopsies (TBLCs) are under investigation to overcome these limitations. METHODS: We conducted a retrospective study of 56 patients in a single, tertiary-care academic center to compare the yield of both techniques when performed in the same patient. Patients underwent flexible bronchoscopy using moderate sedation with TBLB followed by TBLC in the most radiographically abnormal areas. Clinical data and postprocedural outcomes were reviewed, with a final diagnosis made utilizing a multidisciplinary approach. RESULTS: The mean age of patients was 60 years and 54% were male. Comorbidities included COPD (14%) and prior malignancy (48%). The number of TBLB specimens ranged from 1 to 10 per patient (mean 4) and size varied from 0.1 to 0.8 cm. The number of TBLC specimens ranged from 1 to 4 per patient (mean 2) and size ranged from 0.4 to 2.6 cm. Both techniques provided the same diagnosis in 26 patients (46%). An additional 11 (20%) patients had a diagnosis established by adding TBLC to TBLB. Compared with TBLB, TBLC had a higher diagnostic yield in patients with hypersensitivity pneumonitis and interstitial lung disease. Only 2 patients required video-assisted thoracoscopic surgery to establish a diagnosis. Complications included pneumothorax (20%) and massive hemoptysis (2%). CONCLUSION: TBLC used with TBLB can improve the diagnostic yield of flexible bronchoscopy in patients with DPLD.

Association of COPD With Risk for Pulmonary Infections Requiring Hospitalization in HIV-Infected Veterans.

BACKGROUND: Pulmonary infections remain more common in HIV-infected (HIV+) compared with uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients. METHODS: We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort from 1996 to 2009. Using International Classification of Diseases, Ninth Revision codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB), and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within 2 years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRRs) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4 cell count, HIV viral load, smoking status, substance use, vaccinations, and calendar year at baseline. RESULTS: Unadjusted incidence rates of CAP, TB, and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; P ≤ 0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB, and PCP (IRR: 1.94, 95% confidence interval [CI]: 1.64 to 2.30; IRR: 2.60, 95% CI: 1.70 to 3.97; and IRR: 1.48, 95% CI: 1.10 to 2.01, respectively). CONCLUSIONS: COPD is an independent risk factor for CAP, TB, and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.

Mortality among patients with pleural effusion undergoing thoracentesis.

Of the 1.5 million people diagnosed with pleural effusion in the USA annually, ~178 000 undergo thoracentesis. While it is known that malignant pleural effusion portends a poor prognosis, mortality of patients with nonmalignant effusions has not been well studied.This prospective cohort study evaluated 308 patients undergoing thoracentesis. Chart review was performed to obtain baseline characteristics. The aetiology of the effusions was determined using standardised criteria. Mortality was determined at 30 days and 1 year.247 unilateral and 61 bilateral thoracenteses were performed. Malignant effusion had the highest 30-day (37%) and 1-year (77%) mortality. There was substantial patient 30-day and 1-year mortality with effusions due to multiple benign aetiologies (29% and 55%), congestive heart failure (22% and 53%), and renal failure (14% and 57%, respectively). Patients with bilateral, relative to unilateral, pleural effusion were associated with higher risk of death at 30 days and 1 year (17% versus 47% (hazard ratio (HR) 2.58, 95% CI 1.44-4.63) and 36% versus 69% (HR 2.32, 95% CI 1.55-3.48), respectively).Patients undergoing thoracentesis for pleural effusion have high short- and long-term mortality. Patients with malignant effusion had the highest mortality followed by multiple benign aetiologies, congestive heart failure and renal failure. Bilateral pleural effusion is distinctly associated with high mortality.

Patient-Centered Outcomes Following Thoracentesis.

BACKGROUND: Pleural effusions impact over 1.5 million people annually in the United States and cause significant morbidity. Although therapeutic thoracentesis is associated with improvement in respiratory parameters, unanswered questions remain regarding its impact. OBJECTIVE: The purpose of this study was to investigate patient-centered outcomes, the need for additional pleural interventions, and mortality in the 30 days following thoracentesis. METHODS: This prospective observational cohort study was performed in a tertiary care academic medical center between December 2010 and December 2011. Adult patients referred for thoracentesis were offered enrollment. The following characteristics were evaluated both before and at 30 days postprocedure: dyspnea using modified BORG (mBORG), physical and mental quality of life (QoL) using the short form 12, and basic activities of daily living (BADLs). The primary outcomes included changes in these parameters 30 days after thoracentesis. Secondary outcomes included the need for additional pleural procedures and mortality within 30 days of the thoracentesis. Multivariable logistic regression was used for analysis. RESULTS: Of the 284 patients who underwent thoracentesis, 80 (28.2%) died within 30 days of the procedure. Of the 163 patients comprising the analytical cohort, 35 (21.5%) patients required an additional pleural intervention within 30 days of the index procedure. Patients who survived more than 30 days following thoracentesis had a sustained improvement in dyspnea and mental QoL, but a minority had improvement in physical QoL or BADLs. Surviving patients demonstrated no significant associations between bilateral and unilateral thoracentesis, volume of fluid removed, or the etiology of the effusion (malignant vs nonmalignant) and improvement in QoL, dyspnea, and BADLs. Relative to nonmalignant etiology, the presence of a malignant effusion was strongly associated with the need for an additional intervention, yielding an odds ratio (95% confidence interval [95% CI]) of 16.92 (5.47-52.37). Patients with hepatic hydrothorax and infectious etiologies of their effusion were also likely to require additional pleural interventions. CONCLUSION: The majority of patients in this cohort demonstrated sustained improvement in dyspnea and the mental aspect of QoL 30 days following thoracentesis, independent of the etiology and regardless of the volume of pleural fluid removed. A minority experienced sustained improvements in the physical aspect of QoL and BADLs. Although 28.2% of patients died within 30 days, nearly 1 in 5 survivors required an additional pleural intervention. These results emphasize the significant clinical impact, morbidity, and mortality experienced by patients who undergo thoracentesis for pleural effusions.

Advanced diagnostic bronchoscopy using conscious sedation and the laryngeal nerve block: tolerability, thoroughness, and diagnostic yield.

PURPOSE: Although bronchoscopy has conventionally been performed using conscious sedation, advanced diagnostic techniques like endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), peripheral EBUS, and electromagnetic navigational bronchoscopy add to procedural complexity. The adaptation of these techniques by bronchoscopists of varied backgrounds is expanding. It is not clear how patients will tolerate these advanced procedures when they are performed using traditional conscious sedation. METHODS: We prospectively studied patients that underwent diagnostic bronchoscopic procedures using conscious sedation over a 1-year period. The primary outcome was patient tolerability measured with four questions soliciting subjective responses. Secondary outcomes included required dosage of medications, thoroughness of the procedure, diagnostic yield, and occurrence of complications. RESULTS: A total of 181 patients were enrolled. Compared to patients in whom conventional bronchoscopy with transbronchial biopsies were performed, there was no difference in patient tolerability using the advanced techniques. Although some of the advanced procedures added to the procedure time, the required amount of medication was within commonly accepted dosages. When EBUS-TBNA was performed, a mean of 2.8 lymph node stations per patient were sampled. A specific diagnosis was obtained in 55.9 % of patients who solely underwent EBUS-TBNA. The diagnostic yield increased to 75.7 % when a parenchymal abnormality prompted additional biopsies. One patient required sedation reversal. Complications were minimal. CONCLUSIONS: This study suggests that advanced diagnostic bronchoscopic procedures are well tolerated using conscious sedation with no compromise of thoroughness, diagnostic yield, or safety. This may be useful for bronchoscopists using these techniques who do not have ready access to general anesthesia.

MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury.

Sepsis is a systemic inflammatory response to infection and a major cause of death worldwide. Because specific therapies to treat sepsis are limited, and underlying pathogenesis is unclear, current medical care remains purely supportive. Therefore targeted therapies to treat sepsis need to be developed. Although an important mediator of sepsis is thought to be mitochondrial dysfunction, the underlying molecular mechanism is unclear. Modulation of mitochondrial processes may be an effective therapeutic strategy in sepsis. Here, we investigated the role of the kinase MKK3 in regulation of mitochondrial function in sepsis. Using clinically relevant animal models, we examined mitochondrial function in primary mouse lung endothelial cells exposed to LPS. MKK3 deficiency reduces lethality of sepsis in mice and by lowering levels of lung and mitochondrial injury as well as reactive oxygen species. Furthermore, MKK3 deficiency appeared to simultaneously increase mitochondrial biogenesis and mitophagy through the actions of Sirt1, Pink1, and Parkin. This led to a more robust mitochondrial network, which we propose provides protection against sepsis. We also detected higher MKK3 activation in isolated peripheral blood mononuclear cells from septic patients compared with nonseptic controls. Our findings demonstrate a critical role for mitochondria in the pathogenesis of sepsis that involves a previously unrecognized function of MKK3 in mitochondrial quality control. This mitochondrial pathway may help reveal new diagnostic markers and therapeutic targets against sepsis.

Mortality of Hospitalized Patients with Pleural Effusions.

BACKGROUND: Each year in the United States an estimated 1.5 million people develop pleural effusions and approximately 178,000 thoracenteses (12%) are performed. While it has been established that malignant effusions are associated with increased mortality, the association between mortality and all-cause pleural effusions in a medical population has not been previously evaluated. Our objective was to evaluate associations between 30-day and 12-month all-cause mortality among patients with a pleural effusion. METHODS: All patients admitted to the medical service at Yale-New Haven Hospital during March 2011 were screened for pleural effusion. Pleural effusions were documented by the attending radiologist and the medical record was reviewed for admitting diagnosis, severity of illness and whether a thoracenteses was performed. The outcomes were 30-day and 12-month mortality after identification of the pleural effusion. RESULTS: One-hundred and four patients admitted to the medical service had pleural effusions documented by the attending radiologist. At 30-days, 15% of these patients had died and by 12-months mortality had increased to 32%. Eleven (10.6%) of the 104 patients underwent a thoracenteses. Severity of illness and malignancy were associated with 30-day mortality. For 12-month mortality, associations were found with age, severity of illness, malignancy, and diagnosis of pulmonary disease. Although sample size precluded statistical significance with mortality, the hazard ratio for thoracenteses and 30-day mortality was protective, suggesting a possible short term survival benefit. CONCLUSIONS: In hospitalized medical patients with a pleural effusion, age, severity of illness and malignancy or pulmonary disease were associated with higher 12-month mortality. Thoracenteses may provide a protective effect in the first 30 days, but larger studies are needed to detect a short-term survival benefit. The presence of a pleural effusion indicates a high risk of death, with 15% of patients dying within 30 days and 32% dead within one-year of hospital admission.