Sustainability of an Opt-Out Electronic-Health Record-based Tobacco Treatment Consult Service at a large safety-net hospital: A 6-year Analysis.

INTRODUCTION: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception. METHODS: We analyzed data collected between July 2016-June 2022 of patients documented as 'currently smoking' in the EHR. Across the 6 years, we used Pearson's correlation analysis to compare Adoption (clinician acceptance of the BPA+order-set, thus generating consultation to the TTC service); Reach (number of consultations completed by the TTC service); and Effectiveness (receipt of pharmacotherapy orders between patients receiving and not receiving consultations). RESULTS: Among 39,558 adult admissions (July 2016-June 2022) with "currently smoking" status in the EHR for whom the BPA triggered, clinicians accepted the TTC order-set on 50.4% (19,932/39,558), though acceptance varied across services [e.g., Cardiology (71%) and Obstetrics-Gynecology (12%)]. The TTC service consulted on 17% (6779/39,558) of patients due to staffing constraints. Consultations ordered (r=-0.28, p=0.59) and completed (r= 0.45, p=0.37) remained stable over six-years. Compared to patients not receiving consultations, patients receiving consultations were more likely to receive pharmacotherapy orders overall (inpatient: 50.8% vs 35.1%, p<.0001; at discharge: 27.1% vs 10%, p<.0001) and in each year. CONCLUSIONS: The "opt-out" EHR-based TTC service is sustainable, though many did not receive consultations due to resource constraints. Healthcare systems should elevate priority of hospital-based tobacco treatment programs to increase reach to underserved populations. IMPLICATIONS: Our study shows that opt-out approaches that utilize the EHR are a sustainable approach to provide evidence-based tobacco treatment to all hospitalized individuals who smoke, regardless of readiness to stop smoking and clinical condition.

Image analysis comparison of nerve staining with food dye, methylene blue or tissue marker.

OBJECTIVE: Novel locoregional techniques use dye studies to confirm successful nerve targeting. The goal was to objectively quantify and compare nerve staining characteristics of dye mixtures commonly reported in the literature using image analysis software. STUDY DESIGN: Prospective, randomized cadaveric study. METHODS: Thirty-six brachial plexus nerves from unpreserved pig cadavers were randomized into three groups of 12: FD (1:10 mixture of blue food dye and bupivacaine 0.5%), MB (methylene blue 1%) and TM (0.1:10 mixture of blue tissue marker and lidocaine 2%). Nerves were immersed in dye for 1, 15, 30 or 60 minutes (n = 3 each). Images of nerves before immersion (baseline) and at each time point with epineurium intact (superficial staining) and after longitudinal bisection (deep staining) were processed using image analysis software. Color saturation values were divided into quartiles (dark, medium-dark, medium-light or light). Percentage of stained nerve area in each quartile was calculated and compared using two-way anova. RESULTS: Superficially, at minute 1, dark saturation covered 40% of nerve area in FD versus 19% in MB (p = 0.04) and 0% in TM (p < 0.0001). In bisected nerves, dark and medium-dark saturations occurred only in FD; medium-light saturation comprised anywhere from 4% to 22.5% over time in FD versus <1% at any time in MB (p = 1.000; p = 0.343; p = 0.383; p = 0.262). Deep staining was not found in TM at any point. CONCLUSION AND CLINICAL RELEVANCE: Food dye rapidly stains superficial and deep nerve layers. Based on these characteristics, investigators can choose the appropriate dye for their study.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Evaluation of transpulmonary ultrasound dilution cardiac output in piglets: accuracy, precision and trending ability with room temperature injectate.

OBJECTIVE: Transpulmonary ultrasound dilution (TPUD) is a minimally invasive technique to measure cardiac output (CO) using a 1 mL kg-1 isotonic 37 °C saline injectate indicator. The objective was to evaluate the performance of TPUD using a room temperature saline injectate. STUDY DESIGN: Prospective experimental trial. ANIMALS: A total of seven anesthetized male Yorkshire piglets. METHODS: Piglets aged 1 month and weighing 7.7-9.0 kg were anesthetized with detomidine-ketamine-hydromorphone-isoflurane and a pulmonary artery flow probe (PAFP) placed via a median sternotomy. The thoracic cavity remained open during measurement of CO by PAFP and TPUD. The TPUD indicators of 1 mL kg-1 0.9% saline at 37 °C and 20 °C were compared during infusions of phenylephrine and dobutamine, blood withdrawal and replacement. Bias, limits of agreement (LoAs) and percentage error (PE) between each iteration of PAFP and TPUD were measured with Bland-Altman plots. Trending ability via concordance, angular bias and radial LoA were compared. RESULTS: Bland-Altman plots showed negligible bias with varying LoAs. PEs of 22% and 38% were found for 37 °C and 20 °C saline injectates, respectively. In the four-quadrant plots, the concordance rate was 94% and 100% for measurements obtained with 37 °C and 20 °C saline injectates, respectively. Angular bias for both were < ±5 °, with radial LoA < ±7 °. CONCLUSIONS: TPUD was accurate when using 1 mL kg-1 of isotonic saline at 37 °C in a range of CO within 0.2-0.8 L minute-1, and it reliably tracked positive and negative changes in CO. Room temperature (20 °C) indicator was less accurate but equally able to track direction of changes in CO. CLINICAL RELEVANCE: The use of room temperature injectates allows an easy, readily available clinical application of TPUD CO monitoring while preserving the trending ability of the monitor.

Comparison of two sedation protocols, with and without analgesia, in pigs: Assessment of sedation end points and propofol requirements.

OBJECTIVE: To compare the effects of intramuscular premedication with a novel nonanalgesic [alfaxalone-midazolam-acepromazine (AMA)] and an analgesic [ketamine-midazolam-detomidine (KMD)] protocol on sedation end points and propofol requirements for induction of anesthesia in swine. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 27 Yorkshire cross gilts weighing approximately 30 kg. METHODS: Two sedation protocols, AMA and KMD, were compared. Time from intramuscular injection to ataxia, recumbency and nonresponsiveness to tactile stimulation was recorded. The propofol dose requirement for induction of general anesthesia and tracheal intubation, and any adverse events (paddling, twitching), were recorded. Data were tested for normality using a Shapiro-Wilk test. Propofol requirements were compared using a Student's t test. Times from injection to sedation end points were compared using a Mood's test, and significance was confirmed using a Kaplan-Meier curve with Wilcoxon test survival analysis. RESULTS: Sedation end points were reached significantly faster with KMD than with AMA. Nonresponsiveness occurred in 5 (0-16) and 9.5 (5-36) minutes for KMD and AMA, respectively (p = 0.011). No significant difference (p = 0.437) was found between propofol doses used in either group (KMD; 64.38 ± 5.98 mg, AMA; 72.00 ± 7.57 mg). More adverse events were noted with AMA (11/16 pigs) than with KMD (1/11 pigs). CONCLUSIONS AND CLINICAL RELEVANCE: In pigs, AMA can be used as a reliable sedation protocol. Frequency of adverse events and time to reach sedation end points between AMA and KMD differed, but the dose of propofol needed to induce general anesthesia was not significantly different.

Treatment of pulmonary hypertension in patients with Hereditary Hemorrhagic Telangiectasia - A case series and systematic review.

RATIONALE: Pulmonary Arterial Hypertension (PAH), a rare complication of HHT is associated with poor outcome. There are no trials to date that have investigated whether pulmonary vasodilator therapy improves hemodynamics or survival in this disease. OBJECTIVE: To determine whether pulmonary vasodilator therapy improves survival, exercise capacity, or hemodynamics in HHT patients with pre-capillary PH. METHODS: We performed a before-and-after observational study on a multicenter cohort of subjects with HHT-PAH who received intravenous prostanoid therapy. We then conducted a systematic review, searching Medline and EMBASE through December 2019. Studies that enrolled HHT-PAH subjects and reported treatment outcomes were selected. PROSPERO #158179. RESULTS: Twenty-one articles were selected. Studies were before-and-after observational studies, case reports, and case series. Among all subjects with HHT-PAH, both mPAP (65 ± 19 pre-treatment vs 51 ± 16 mmHg post-treatment p = 0.04) and PVR (12 ± 6 pre-treatment vs 8 ± 4 WU post-treatment p = 0.01) improved with treatment. The mPAP improved with either oral (57 ± 17 pre-treatment versus 44 ± 13 mmHg post-treatment, p = 0.03) or intravenous (80 ± 15 pre-treatment versus 64 ± 16 mmHg post-treatment, p = 0.017) therapy. PVR also improved with either oral (10 ± 4 pre-treatment versus 6 ± 3 WU post-treatment, p = 0.004) or intravenous (17 ± 5 pre-treatment versus 10 ± 4 WU post-treatment, p = 0.04) therapy. Survival among HHT-PAH patients who received oral or intravenous therapy was not different (p = 0.2). Unadjusted survival among HHT-PAH patients was longer than that of IPAH patients (p = 0.008). There was no difference in side effects among HHT-PAH patient who received oral or intravenous therapy (p = 0.1). CONCLUSION: Pulmonary vasodilator therapy is effective in improving hemodynamics of subjects with HHT-PAH and was not associated with increased risk of side effects.

A Feasibility Study for a Novel Trans-infraorbital Canal Approach to the Maxillary Nerve in Pigs (Sus domesticus).

Experimental maxillofacial surgery is commonly performed in pigs; however, locoregional anesthesia of this area has not been described. This study evaluated the feasibility of a novel maxillary nerve block approach. In part I, cadavers were used to determine anatomic landmarks and assess maxillary nerve dye staining by using 0.03 mL kg-1 of a 1:10 mixture of commercial food dye and 0.5% bupivacaine. In part II, 10 additional pig cadavers underwent bilateral ultrasound-guided maxillary nerve blocks by using trans-infraorbital canal needle placement. The maxillary nerve was harvested and scored based on degree of staining (0 and 1, absent or incomplete staining; 2, staining; >1 cm circumferentially). Intracranial and intraconal spread of dye was evaluated. A Kruskal-Wallis test was used to compare infraorbital canal length estimated either externally via landmarks, internally via ultrasound, or actually measured after dissection. In 18 of 20 (90%) injections, successful staining (score = 2) of maxillary nerves was obtained for a nerve length of 2.4 ± 0.3 cm. Two of 20 cases (10%) had inadequate staining (score <2). At dissection of these 2 cases, the needle tip was observed to have collided with an unerupted tooth (third molar). No intracranial or intraconal spread of dye was observed. We detected no statistical differences between the estimated external, estimated internal, or actual dissection methods for measurement of infraorbital canal length (P = 0.3). Ultrasound-guided trans-infraorbital maxillary nerve block in pigs is a feasible technique, warranting further work to evaluate its in vivo efficacy and safety.

Efficacy of flow restrictors in limiting access of liquid medications by young children.

OBJECTIVE: To assess whether adding flow restrictors (FRs) to liquid medicine bottles can provide additional protection against unsupervised medication ingestions by young children, even when the child-resistant closure is not fully secured. STUDY DESIGN: In April and May 2012, we conducted a block randomized trial with a convenience sample of 110 3- and 4-year-old children from 5 local preschools. Participants attempted to remove test liquid from an uncapped bottle with an FR and a control bottle without an FR (with either no cap or an incompletely closed cap). RESULTS: All but 1 (96%; 25 of 26) of the open control bottles and 82% (68 of 83) of the incompletely closed control bottles were emptied within 2 minutes. Only 6% (7 of 110) of the bottles with FRs were emptied during the 10-minute testing period, none before 6 minutes. Overall, children removed less liquid from the bottles with FRs than from the open or incompletely closed control bottles without FRs (both P < .001). All children assigned open control bottles and 90% of those assigned incompletely closed control bottles removed ≥ 25 mL of liquid. In contrast, 11% of children removed ≥ 25 mL of liquid from uncapped bottles with FRs. Older children (aged 54-59 months) were more successful than younger children at removing ≥ 25 mL of liquid (P = .002) from bottles with FRs. CONCLUSION: Our findings suggest that adding FRs to liquid medicine bottles limits the accessibility of their contents to young children and could complement the safety provided by current child-resistant packaging.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction.

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

Pulmonary Arterial Hypertension in Patients Infected with the Human Immunodeficiency Virus.

It is important to recognize and treat human immunodeficiency virus-associated pulmonary arterial hypertension (HIV-PAH) because of the associated morbidity and mortality. With the introduction of antiretroviral therapies (ART), improved survival has changed the focus of treatment management from immunodeficiency-related opportunistic infections to chronic cardiovascular complications, including HIV-PAH. The 2018 6th World Symposium of Pulmonary Hypertension recommended a revised definition of PAH that might result in a greater number of patients with HIV-PAH; however, the implication of this change is not yet clear. Here, we review the current literature on the diagnosis, management, and outcomes of patients with HIV-PAH.

Pirfenidone in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Data Extraction: Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Synthesis: Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.

Nintedanib in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Data Extraction: Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Two relevant studies were selected. The annual decline in forced vital capacity was less in the nintedanib arm in the overall study population (mean difference [MD], 107 ml/yr; 95% confidence interval [CI], 65.4 to 148.5 ml/yr) and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis (MD, 128.2 ml/yr; 95% CI, 70.8 to 185.6 ml/yr), non-UIP patterns of pulmonary fibrosis (MD, 75.3 ml/yr; 95% CI, 15.5 to 135.0 ml/yr), fibrotic connective tissue disease-related ILD (MD, 106.2 ml/yr; 95% CI, 10.6 to 201.9 ml/yr), fibrotic idiopathic nonspecific interstitial pneumonia (MD, 141.7 ml/yr; 95% CI, 46.0 to 237.4 ml/yr), and fibrotic occupational ILD (MD, 252.8 ml/yr; 95% CI, 79.2 to 426.5 ml/yr), but not fibrotic hypersensitivity pneumonitis (MD, 72.9 ml/yr; 95% CI, -8.9 to 154.7 ml/yr), fibrotic sarcoidosis (MD, -20.5 ml/yr; 95% CI, -337.1 to 296.1 ml/yr), or unclassified fibrotic ILD (MD, 68.5 ml/yr; 95% CI, -31.3 to 168.4 ml/yr) when compared with placebo. Gastrointestinal side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in gastrointestinal side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.

Transbronchial Lung Cryobiopsy in Patients with Interstitial Lung Disease: A Systematic Review.

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Antacid Medication and Antireflux Surgery in Patients with Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.

Use of a Genomic Classifier in Patients with Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.

L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-beta (Abeta)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg L-NBP by oral gavage for 18 weeks. L-NBP treatment significantly improved learning deficits, as well as long-term spatial memory, compared with vehicle control treatment. L-NBP treatment significantly reduced total cerebral Abeta plaque deposition and lowered Abeta levels in brain homogenates but had no effect on fibrillar Abeta plaques, suggesting preferential removal of diffuse Abeta deposits. Furthermore, we found that L-NBP markedly enhanced soluble amyloid precursor protein secretion (alphaAPPs), alpha-secretase, and PKCalpha expression but had no effect on steady-state full-length APP. Thus, L-NBP may direct APP processing toward a non-amyloidogenic pathway and preclude Abeta formation in the 3xTg-AD mice. The effect of l-NBP on regulating APP processing was further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP(695) (SK-N-SH APPwt). L-NBP treatment in 3xTg-AD mice also reduced glial activation and oxidative stress compared with control treatment. L-NBP shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of Alzheimer's disease.