Multiple Pharmacotherapy Adaptations for Smoking Cessation Based on Treatment Response in Black Adults Who Smoke: A Randomized Clinical Trial.

Importance: Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. Objective: To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily. Design, Setting, and Participants: This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023. Interventions: Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment. Main Outcomes and Measures: Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data. Results: Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001). Conclusions and Relevance: In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03897439.

Protocol from a randomized clinical trial of multiple pharmacotherapy adaptations based on treatment response in African Americans who smoke.

Background: The standard of care in tobacco treatment is to continue individuals who smoke on the same cessation medication, even when they do not stop smoking. An alternative strategy is to adapt pharmacotherapy based on non-response. A handful of studies have examined this approach, but they have adapted pharmacotherapy only once and/or focused on adaptation distal rather than proximal to a failed quit attempt. Few studies have included racial/ethnic minorities who have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. Methods: The current study is comparing the efficacy of optimized (OPT) versus enhanced usual care (UC) for smoking cessation in African Americans (AA) who smoke cigarettes. AAs who smoke (n = 392) are randomized 1:1 to OPT or UC. Participants in both groups receive 7 sessions of smoking cessation counseling and18-weeks of pharmacotherapy with long-term follow-up through Week 26. OPT participants receive nicotine patch and up to two pharmacotherapy adaptations to varenicline and bupropion plus patch based on carbon monoxide verified smoking status (≥6 ppm) at Weeks 2 and 6. UC participants receive patch throughout the duration of treatment. We hypothesize that OPT will be more effective than UC on the primary outcome of biochemically verified abstinence at Week 12. Discussion: If effective, findings could broaden the scope of tobacco dependence treatment and move the field toward optimization strategies that impro ve abstinence for AA who smoke. Trial registration: NCT03897439.

Renin-Angiotensin Blockade Reduces Readmission for Acute Chest Syndrome in Sickle Cell Disease.

Rationale Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD. Acute chest syndrome appears similar to pulmonary fat embolism (PFE), a complication of severe skeletal trauma or orthopedic procedures from pulmonary micro-vessel blockage by bone marrow fat. Vascular obstruction and bone marrow necrosis occur in PFE and ACS.  Pulmonary fat embolism rat models have shown that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) mitigate damage in PFE. These medications could work similarly in ACS. We hypothesize that time to readmission after one hospitalization for ACS will be reduced in patients taking ACEI or ARB compared to patients who are not. Methods This is a retrospective cohort study. Inclusion criteria are adults (18 to 100 years) with sickle cell anaemia (HbSS), hemoglobin SC (HbSC) disease, sickle cell thalassemia (HbSßThal), hospitalized with ACS over 16 years (January 1, 2000, to March 31, 2016); patients who take and don't take ACEI or ARB. Children (<18 years old), elderly adults (>100 years old), pregnant patients, and patients with sickle cell trait were excluded. Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of hospitals in which Cerner© has a data use agreement. Kaplan-Meier estimates explored a time-to-event model of ACS readmission. Multivariable analysis (age, gender, smoking history) was conducted using Cox proportional hazards regression. Results were reported around a 95% confidence interval. Results There were 6972 patients in total. Of which, 9.6% (n = 667) reported taking ACEI or ARB. Results for the covariates were: average age of 38 years old; 63% female (n = 4366/6969); 16% smokers (n = 1132). Readmission rates were higher for patients not taking ACEI/ARB than those who did: 0.44 (95% CI 0.43, 0.46) versus 0.28 (95% CI 0.24, 0.31) at one year, and 0.56 (95% CI 0.55, 0.58) versus 0.33 (95% CI 0.29, 0.37) at two years. Age had the strongest effect on readmission rates for patients taking ACEI/ARB (adjusted hazards ratio 0.78 [95% CI 0.68, 0.91]). Conclusion Patients with SCD who reported taking ACEI or ARB had lower readmission rates for ACS; age was the strongest covariate. Our results may have a significant impact on the prevention of ACS. Prospective studies comparing ACEI or ARB therapy versus placebo are needed to confirm this preventative effect.

Organizing Pneumonia Secondary to Pulmonary Actinomycosis: A Case Report and Literature Review.

Pulmonary actinomycosis is a common clinical infection caused by Actinomyces species. Although its treatment is very effective with Intravenous (IV) antibiotics, its diagnosis is challenging and easily missed. Organizing Pneumonia (OP) can be cryptogenic or secondary to different clinical diseases. Herein, we discuss a case of acute hypoxemic respiratory failure that was found to be due to OP, secondary to pulmonary actinomycosis, with a brief review of the literature. A 64-year-old male presented with acute hypoxemic respiratory failure two days after undergoing elective right total hip arthroplasty. Chest imaging with CT scan showed symmetric bilateral ground-glass opacities most pronounced within the upper lung lobes. The patient was treated initially with IV diuresis, steroids, and broad-spectrum antibiotics. However, his clinical status continued to worsen and his chest imaging showed worsening lung opacities. Video-assisted thoracoscopic lung biopsy (VATS) was done, and pathology results showed features of organizing pneumonia. Tissue culture confirmed Actinomyces species. The patient had clinical improvement after treatment with IV methylprednisolone and IV penicillin G. Pulmonary actinomycosis is very rarely associated with OP but this bacterial infection should always be in the differential diagnosis when OP is confirmed as the treatment is effective with IV antibiotics.

Use of Laboratory Tests and Their Prognostic Value in Patients with Stable Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is not merely a lung disease as the name indicates. Patients with COPD experience associated complications with systemic inflammation, heart strain, muscle wasting, poor functional performance, and psychological issues. An assessment of these patients based only on lung function tests or functional capacity would be inadequate. Many studies have reported the significance and prognostic value of several laboratory tests. Troponin, C-reactive protein (CRP), hemoglobin, and carbon dioxide are older tests but compared with the newly developed tests, they are relatively inexpensive to measure and widely available. This article will review laboratory tests used for COPD and discuss their prognostic value. The laboratory tests that can identify high-risk patients will be discussed. We will explore the role of these tests in clinical practice.

Gastroesophageal Reflux Disease-Associated Chronic Cough: A Population-Based Analysis of Patient Presentations in the United States.

Gastroesophageal reflux disease is an extremely prevalent illness in the United States; however, clinicians report that its association with chronic cough is often overlooked and undiagnosed. We used the CERNER Health Facts® database to analyze the statistical prevalence. Our findings indicate that there is a minority of patients who are untreated for this common complaint. We propose considering this on the differential diagnosis and following current treatment guidelines with proton pump inhibitors to effectively treat this complaint.

The Use of Direct Oral Anticoagulants in the Management of Venous Thromboembolism in Patients With Obesity.

Introduction The use of direct oral anticoagulants (DOACs) has gained significant traction given the lack of therapeutic monitoring and the need for anticoagulant bridging. There is a paucity of data on their effectiveness in obese patients with venous thromboembolism (VTE). Preliminary subgroup and pharmacokinetic analyses suggest reduced efficacy in those with a bodyweight >120 kg or body mass index (BMI) ≥40 kg per m2 and it is currently not recommended that these agents be used as first-line agents. We aimed to assess the rate of VTE recurrence in obese patients diagnosed with VTE and treated with DOAC therapy. Methods We utilized the Health Facts Center National Data Warehouse (Cerner) to perform a retrospective analysis of patients with VTE (acute deep venous thrombosis (DVT) or pulmonary embolism) that presented to the hospital between 2010 and 2016 and were managed with DOACs. The cohort of patients diagnosed with DVT or PE were identified using International Classification of Disease (ICD-9-CM, ICD-10-CM). Patients were divided into two groups based on their weight: 1) weight <120 kg or 2) weight>120 kg. Six-month VTE recurrence rates were recorded. Summary and univariate statistics were performed. Results A total of 18,147 patients with a mean (±SD) age of 62 (17) years were included; 48% (n=8732) were male. A total of 2,419 (13%) patients weighed >120 kg while the rest (N=15,728, 87%) weighed <120 kg. There were significantly more female patients weighing<120 kg (54% vs 42%, p<0.0001); otherwise, there was no significant difference in age or tobacco use between both groups (p>0.05). There was no significant difference in six-month readmission rates for VTE recurrence in patients that weighed <120 kg (34%) in comparison with patients >120 kg (36%) (p=0.08). Conclusion Our study suggests that the use of DOACs in obese patients is equally efficacious with similar VTE recurrence rates in comparison with non-obese patients. This study paves the way for prospective multi-institutional randomized control trials to further reinforce the safe use of such agents in this patient population.

The Dangers of Vaping.

As our nation turns away from smoking tobacco and toward legalization of marijuana, vaporization of both plants has increased in popularity. There are medical and cultural implications of this new trend which are just recently being reported and investigated. The purpose of this article is to review the scientific and sociological literature as it pertains to the vaporization of both marijuana and tobacco products and the potential medical and cultural implications of this new phenomenon.

The Vaping Epidemic in Adolescents.

Electronic cigarette (e-cigarette) use has recently risen to the forefront of medical discussions across the country. A significant increase in e-cigarette use by adolescents has been observed over the last decade. This article discusses the targeting of adolescents by e-cigarette companies. It looks at how teenagers are uniquely affected by nicotine and at risk for progressing to using combustible cigarettes and marijuana. Lastly, it discusses the role of physicians in combating the spread of e-cigarettes.

Vaping Associated Lung Injury (EVALI): An Explosive United States Epidemic.

As of November 5, 2019, there have been 2051 cases of e-cigarette, or vaping, product use associated lung injury (EVALI), with 39 deaths reported in the United States, over four months. The rapidly increasing popular habits of vaping and e-cigarette use has suddenly turned deadly in the United States. This epidemic of vaping-associated illness appears to be limited to the United States with few reported cases and no deaths from the rest of the world.

Acute chest syndrome in sickle cell disease.

Acute chest syndrome (ACS) is a leading complication of sickle cell disease (SCD) with significant morbidity and mortality. ACS is the most common cause of death and the second most common cause of hospitalization in patients with SCD. Delineating the specific cause of ACS is often difficult, and multiple risk factors that precipitate ACS frequently coexist. The prominent risk factors include infection, hypoxia, bronchial hyperresponsiveness, the SCD genotype, and opioid use. The key to the successful treatment of ACS is early recognition and initiation of treatment without delay. The main goal is to prevent and treat acute respiratory failure and, thus, minimize irreversible lung damage. This review focuses on the risk factors, pathogenesis, clinical presentation, and management of ACS.

Effect of Long-term Nicotine Replacement Therapy vs Standard Smoking Cessation for Smokers With Chronic Lung Disease: A Randomized Clinical Trial.

Importance: Smokers with chronic obstructive pulmonary disease (COPD) have particular difficulty quitting. Long-term nicotine replacement therapy (LT-NRT) might offer a strategy for reducing harm from cigarettes and provide a pathway for later cessation. Objective: To compare the effect of LT-NRT vs standard smoking cessation (SSC) on exposure to cigarette smoke, harm related to smoking, and cessation among smokers with COPD. Design, Setting, and Participants: This unblinded, randomized clinical trial recruited smokers who self-reported a diagnosis of COPD at any level of readiness to quit from May 23, 2014, through November 30, 2015. The 12-month follow-up was completed December 6, 2016. Patients were recruited at a clinical research unit of an academic medical center. Analysis was based on intention to treat and performed from March 8 through November 30, 2017. Interventions: Standard smoking cessation treatment included 10 weeks of NRT and 4 follow-up counseling sessions for those willing to make a quit attempt. Long-term NRT included 12 months of NRT and 6 follow-up counseling sessions regardless of initial willingness to quit. Overall, 198 patients were randomized to SSC, and 197 were included in the primary analysis; 200 patients were randomized to LT-NRT, and 197 were included in the primary analysis. Main Outcomes and Measures: The primary outcome was 7-day abstinence verified by carbon monoxide (CO) levels at 12 months. Secondary outcomes included cigarettes smoked per day (CPD), exposure to CO, urinary excretion of 4-methylnitrosamino-1-3-pyridyl-1-butanol (NNAL) (a smoking-related carcinogen), and adverse events. Results: Among 398 patients who were randomized (59.8% female; mean [SD] age, 56.0 [9.3] years), the mean (SD) CPD was 23.1 (12.3). Twelve-month follow-up was completed by 373 participants (93.7%), and 394 (99.0%) were included in the primary analysis. At 12 months, CO-verified abstinence occurred in 23 of 197 participants (11.7%) in the SSC arm and 24 of 197 (12.2%) in the LT-NRT arm (risk difference, 0.5%; 95% CI, -5.9% to 6.9%). Continuing smokers in the SSC and LT-NRT arms had similar, significantly reduced harms caused by smoking, including cigarette consumption by 12.4 and 14.5 CPD, respectively, exhaled CO level by 5.5 and 7.8 ppm, respectively, and mean urinary NNAL excretion by 21.7% and 23.0%, respectively. In multivariate analyses, continuing smokers with greater adherence to NRT experienced less reduction in NNAL exposure. The frequency of major adverse cardiac events was similar in both groups. Conclusions and Relevance: Similar rates of cessation and similar reductions in exposure to tobacco smoke resulted with LT-NRT and SSC. Among continuing smokers, ongoing use of NRT was not associated with reductions in smoke exposure. Trial Registration: ClinicalTrials.gov Identifier: NCT02148445.

Factors associated with depressive symptoms in uncontrolled asthmatics.

RATIONALE: Recent epidemiological data indicate that approximately 6.7% of US adults suffer from depression in any given year. The purpose of the study is to identify factors associated with depressive symptoms in a large diverse group of patients with poorly controlled asthma. The factors include quality of life (QOL), lung function, asthma knowledge, attitudes, self-efficacy, symptoms and control of disease. METHODS: Baseline characteristics of a cohort of 599 subjects with asthma recruited from twenty Asthma Clinical Research Centers across the United States were examined. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to stratify subjects into those with depressive symptoms (CES-D score ≥ 16) and those without depressive symptoms (CES-D < 16). Bivariate statistics were used to compare the two groups; additionally, logistic regression was used to determine factors that have the greatest association with depressive symptoms. RESULTS: Subjects with depressive symptoms had significantly lower QOL scores and less knowledge about their disease than subjects with no depression; however, lung function (FEV1%) and asthma control were not significantly associated with depressive symptoms in the logistic regression analysis. Subjects who were non-white had lower household income, high school diploma or less, and those who were unemployed or disabled had significantly higher scores for depressive symptoms. CONCLUSION: Subjects with depressive symptoms have significantly less knowledge of their disease and poorer QOL compared to those without depressive symptoms. Evaluating depressive symptoms in subjects with asthma will provide a more complete picture of their overall condition. The role of asthma education on depressive symptoms in this population needs to be further investigated. The effect of QOL on treating depression in asthma patients also needs to be studied.

Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents.

Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant.

Hepatic hydrothorax: clinical review and update on consensus guidelines.

Hepatic Hydrothorax (HH) is defined as a pleural effusion greater than 500 ml in association with cirrhosis and portal hypertension. It is an uncommon complication of cirrhosis, most frequently seen in association with decompensated liver disease. The development of HH remains incompletely understood and involves a complex pathophysiological process with the most acceptable explanation being the passage of the ascetic fluid through small diaphragmatic defects. Given the limited capacity of the pleural space, even the modest pleural effusion can result in significant respiratory symptoms. The diagnosis of HH should be suspected in any patient with established cirrhosis and portal hypertension presenting with unilateral pleural effusion especially on the right side. Diagnostic thoracentesis should be performed in all patients with suspected HH to confirm the diagnosis and rule out infection and alternative diagnoses. Spontaneous bacterial empyema and spontaneous bacterial pleuritis can complicate HH and increase morbidity and mortality. HH can be difficult to treat and in our review below we will list the therapeutic modalities awaiting the evaluation for the only definitive therapy, which is liver transplantation.

Fluid flow and particle transport in mechanically ventilated airways. Part I. Fluid flow structures.

A large eddy simulation-based computational study of fluid flow and particle transport in upper tracheobronchial airways is carried out to investigate the effect of ventilation parameters on pulmonary fluid flow. Respiratory waveforms commonly used by commercial mechanical ventilators are used to study the effect of ventilation parameters and ventilation circuit on pulmonary fluid dynamics. A companion paper (Alzahrany et al. in Med Biol Eng Comput, 2014) reports our findings on the effect of the ventilation parameters and circuit on particle transport and aerosolized drug delivery. The endotracheal tube (ETT) was found to be an important geometric feature and resulted in a fluid jet that caused an increase in turbulence and created a recirculation zone with high wall shear stress in the main bronchi. Stronger turbulence was found in lower airways than would be found under normal breathing conditions due to the presence of the jet caused by the ETT. The pressure-controlled sinusoidal waveform induced the lowest wall shear stress on the airways wall.

Fluid flow and particle transport in mechanically ventilated airways. Part II: particle transport.

The flow mechanisms that play a role on aerosol deposition were identified and presented in a companion paper (Timothy et al. in Med Biol Eng Comput. doi: 10.1007/s11517-015-1407-3 , 2015). In the current paper, the effects of invasive conventional mechanical ventilation waveforms and endotracheal tube (ETT) on the aerosol transport were investigated. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by jet caused by the ETT. The orientation of the ETT toward right bronchus resulted in a substantial deposition inside right lung compared to left lung. The deposition inside right lung was ~12-fold higher than left lung for all considered cases, except for the case of using pressure-controlled sinusoidal waveform where a reduction of this ratio by ~50 % was found. The total deposition during pressure constant, volume ramp, and ascending ramp waveforms was similar and ~1.44 times higher than deposition fraction when using pressure sinusoidal waveform. Varying respiratory waveform demonstrated a significant role on the deposition enhancement factors and give evidence of drug aerosol concentrations in key deposition sites, which may be significant for drugs with negative side effects in high concentrations. These observations are thought to be important for ventilation treatment strategy.