Clinical characteristics of symptomatic young patients with colonic adenomas.

Background: The incidence of colonic adenomas and colorectal cancer has been on the rise among young patients. In this study, we aimed to describe the characteristics of young patients (<50 years) with adenomatous polyps and to characterize those polyps. We also aimed to determine appropriate surveillance intervals for young patients. Methods: We performed a retrospective chart review of patients <50 years of age who had polypectomy of 1 or more adenomatous polyps on colonoscopy between 2008 and 2021. Patient demographics, colonoscopy indication and polyp characteristics were obtained from the chart. Timing and findings on surveillance colonoscopies were recorded. Results: A total of 610 patients were included: mean age 42.9±5.9 years, 61% males, body mass index 27.5±4.7 kg/m2, and over 50% smokers. The most common indications were abdominal pain (23.3%), rectal bleeding (22.3%), and change in bowel habits (17.6%). Almost half of the patients who had adenomas (299) were younger than 45 years. Tubular adenoma was the most frequently encountered type of polyp (571; 93.6%). Mean polyp size was 1.1±0.9 cm. The most common location of adenomas was the sigmoid colon (41%). Of patients with adenomas, 156 (26%) had surveillance colonoscopy within 2.9±2.3 years; 74 patients (47.4%) were found to have new adenomas. Conclusions: Patients aged <50 years with colonic adenomas were mostly males, overweight, and smokers. Further adenomas were found in 47% of surveillance colonoscopies, and most were encountered within 5 years. High rates of recurrent adenomas in people <50 years of age may warrant frequent surveillance.

Influence of nicotine form and nicotine flux on puffing behavior and mouth-level exposure to nicotine from electronic nicotine delivery systems.

BACKGROUND: Nicotine form (freebase/protonated) and nicotine flux (rate at which nicotine is emitted) are two factors that can affect the dose of nicotine inhaled by individuals using electronic nicotine delivery systems (ENDS) because they can influence puffing behavior. The nicotine dose for each puff also is directly proportional to nicotine flux (i.e., dose/puff=nicotine flux*puff duration). This study examines the effect of nicotine form and flux on puffing parameters and mouth-level nicotine exposure. METHODS: Thirty-two dual ENDS and combustible cigarette participants completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35µg/sec); a zero-nicotine condition was a negative control. Participants used a Subox Mini C ENDS, powered at 20W, during a 10-puff directed bout (B1) followed by a one-hour ad libitum bout (B2). Puffing parameters and mouth-level nicotine exposure were assessed using the American University of Beirut REALTIME instrument. RESULTS: Relative to protonated nicotine, freebase nicotine was associated with lower total puff duration (puff duration*number of puffs), lower flow rate in B1, lower liquid consumption, and lower mouth-level nicotine exposure. Increasing nicotine flux from 14 to 35µg/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption. Increasing nicotine flux was associated with higher mouth-level nicotine exposure in B1 only. CONCLUSION: ENDS with protonated nicotine may enhance nicotine exposure by promoting longer puffing and thus greater dose delivered. This work highlights the importance of accounting for interactions between nicotine form and flux when considering nicotine regulation for ENDS.

Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials.

INTRODUCTION: Electronic cigarette (EC) use has increased rapidly in the last decade, especially among youth. Regulating nicotine delivery from ECs could help curb youth uptake and leverage EC use in harm reduction yet is complicated by varying device and liquid variables that affect nicotine delivery. Nicotine flux, the nicotine emission rate, is a parameter that incorporates these variables and focuses on the performance rather than the design of an EC. Nicotine flux therefore could be a powerful regulatory tool if it is shown empirically to predict nicotine delivery and subjective effects related to dependence. METHODS AND ANALYSIS: This project consists of two complementary clinical trials. In Trial I, we will examine the relationship between nicotine flux and the rate and dose of nicotine delivery from ECs, hence, impacting abuse liability. It will also examine the extent to which this relationship is mediated by nicotine form (i.e., freebase versus protonated). At Yale School of Medicine (YSM), study participants will puff EC devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. In Trial II, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut (AUB), participants will use EC devices with varying nicotine fluxes and forms, while dependency measures, such as the urge to use ECs, nicotine craving, and withdrawal symptoms, will be assessed. We will also monitor puffing intensity and real-time exposure to toxicants. ETHICS AND DISSEMINATION: The protocol of Trial I and Trial II was approved by YSM and AUB IRBs, respectively. We will disseminate study results through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT05706701 for Trial I and NCT05430334 for Trial II.

Mucormycosis: A 14-Year Retrospective Study from a Tertiary Care Center in Lebanon.

Mucormycosis (MCM) is a serious invasive fungal disease (IFD) that is associated with high mortality, particularly in immunocompromised patients. A global surge in MCM cases was reported with the COVID-19 pandemic. We analyzed all recorded cases of MCM at the American University of Beirut Medical Center (AUBMC), a tertiary care center in Lebanon, over 14 years. We aimed to identify the incidence, seasonal variation, clinical characteristics of the patients, and predictors of mortality. We conducted a retrospective chart review between 1 January 2008 and 1 January 2023. All patients with proven or probable MCM were included in the study. Proven or probable MCM was defined by positive histopathology and/or positive cultures. A total of 43 patients were identified as having MCM. Their median age was 53 years, and the majority were males (58.1%). Most of the cases were diagnosed in the autumn season. In total, 67.4% of the patients had hematological malignancies (HMs), and 34.9% had uncontrolled diabetes mellitus (DM). The most common site of involvement was rhino-orbital-cerebral MCM (ROCM) (74%). The annual cases of MCM per 100,000 patient days increased markedly during the years of the COVID-19 pandemic (from 0 to 4.4 cases/100,000 patient days to 7.5 cases/100,000 during 2020 and 2021). Liposomal amphotericin (Ampho) B was used as a first-line agent in most of the patients (86%). The median duration of total in-hospital antifungal therapy was 21 days and 51.2% of the patients received step-down therapy with azoles. Surgical debridement and isolated ROCM were significantly associated with survival (p-value: 0.02 and <0.001, respectively). All-cause mortality was 46.7%, with chronic renal disease being significantly associated with mortality (p-value < 0.05). The incidence of MCM has been increasing at our institution, particularly since the COVID-19 pandemic. Early diagnosis, treatment, and surgical debridement improve patient outcomes and overall survival.

Developing Capacity in Dissemination and Implementation Research in the Eastern Mediterranean Region: Evaluation of a Training Workshop.

As the demand for dissemination and implementation (D&I) research grows globally, there is a need for D&I capacity building in regions where D&I science is underrepresented. The Workshop on Dissemination and Implementation Research in Health (WONDIRH) was aimed for participants in the Eastern Mediterranean region to (1) appreciate the complex process of bridging research and practice in a variety of real-world settings, and (2) develop research that balances rigor with relevance and employs study designs and methods appropriate for the complex processes involved in D&I. The present exploratory study investigates participants' satisfaction with the workshop, the enhancement of their self-rated confidence in D&I skills, as well as their intention to apply the learned content into practice. The workshop included four weekly 90-min virtual interactive training sessions in conjunction with open access content from the National Cancer Institute Training Institute in Implementation and Dissemination Research in Cancer (TIDIRC). We applied a one-group pre-post design for the evaluation of workshop. Participants were invited to self-rate their confidence in D&I competencies (15 items, pre and post workshop). At the end of the workshop, participants additionally were asked to rate their satisfaction (5 items, 1-5 scales), and their intention to apply the learned content into practice (4 items, 1-5 scales). Of the 77 workshop participants, 34 completed the evaluation. Confidence improved between pre- and post-workshop assessments in all 15 self-rated D&I competencies. Respondents were generally satisfied with the workshop (mean satisfaction range 3.82-4.26 across the 5 items) and endorsed intentions to apply workshop topics (mean intention range 4.03-4.35 across the 4 items). This initial workshop demonstrated the ability to attract and engage participants to enhance their confidence in D&I research competencies and skills and to build capacity in D&I research. Future efforts should consider offering targeted training for researchers at different stages and to clearly articulate learning objectives. Supplementary Information: The online version contains supplementary material available at 10.1007/s43477-022-00067-y.

Assessing cognitive behavioral therapy for insomnia in individuals with cannabis use disorder utilizing actigraphy and serum biomarkers: A pilot study.

OBJECTIVE/BACKGROUND: This pilot study aims to assess the effect of Cognitive Behavioral Therapy for insomnia (CBTi) in individuals with cannabis use disorder and insomnia. It also aims to investigate the effect of CBTi on levels of serum inflammatory markers in relation to insomnia symptoms. METHODS/PATIENTS: Individuals with cannabis use disorder and insomnia symptoms were recruited over 18 months. Data collected included demographics, self-reported sleep parameters, and cannabis use. Blood samples were drawn to measure IL-2, IL-6, CRP, and cortisol. Participants completed the Insomnia Severity Index questionnaire (ISI) and the Patient Health Questionnaire-4 (PHQ-4), and they were provided with an actigraphy (wrist) device for 1 week before CBTi and a subsequent week after completing the 4 CBTi sessions. RESULTS: Nineteen participants were enrolled in the study. The mean ISI score decreased from moderately severe insomnia at baseline to no clinically significant insomnia after CBTi with a sustained decrease at 3- and 6-months follow-up. Actigraphy showed a significant decrease in sleep onset latency (SOL) after CBTi. Three months after CBTi, 80% of participants reported a decrease in their cannabis use. There was also a significant and sustained decrease in mean PHQ-4 scores after CBTi. Although only trending towards significance, the levels of three out of four biomarkers (IL-2, IL-6, CRP) were decreased 6 months after CBTi. CONCLUSIONS: CBTi is effective as a short- and long-term treatment of insomnia and comorbid anxiety/depression in individuals who regularly use cannabis. A potential added benefit is a reduction in cannabis consumption and inflammatory serum biomarkers.

The association of antidepressant monotherapy and weight change in a Middle Eastern psychiatric population.

Genetic and lifestyle factors influence weight changes secondary to antidepressants. However, the association between antidepressants and weight changes is seldom studied in Middle Eastern populations who have a unique genetic, lifestyle and dietary profile. This is a chart-based retrospective longitudinal study that describes the 6-month evolution of weight in outpatient Lebanese adults initiated on serotonin reuptake inhibitor (SRI) antidepressant monotherapy, with the exclusion of confounders with metabolic implications. A linear mixed model was used to estimate the association of weight with time. Demographic factors were tested for interaction with the model. The sample consisted of 200 antidepressant trials. After adjusting for baseline weight, age, and sex, weight did not change significantly from week 1 to week 4 (P = 0.530) but significantly increased by 0.15 kg/week from week 4 to week 24 (P < 0.05). Sex, baseline weight, alcohol use, tobacco use, and presence of metabolic condition(s) did not affect weight change (P > 0.05). The same changes were observed across all SRIs and diagnoses. Our results show that SRI monotherapy is associated with weight gain throughout the treatment course in a Middle Eastern population. We recommend judicious prescription of SRIs and clinical vigilance over weight throughout the course of treatment in these populations.

Cigarette Smoking Is Associated With Lower Quadriceps Cross-sectional Area and Attenuation in Older Adults.

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed. RESULTS: Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with ß= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and ß = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, ß = -0.08, 95% CI = -0.16 to -0.01 and ß = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (ß = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.

Cigarette smoking and gray matter brain volumes in middle age adults: the CARDIA Brain MRI sub-study.

Cigarette smoking has been associated with dementia and dementia-related brain changes, notably gray matter (GM) volume atrophy. These associations are thought to reflect the co-morbidity of smoking and vascular, respiratory, and substance use/psychological conditions. However, the extent and localization of the smoking-GM relationship and the degree to which vascular, respiratory, and substance use/psychological factors influence this relationship remain unclear. In the Coronary Artery Risk Development in Young Adults CARDIA cohort (n = 698; 52% women; 40% black participants; age = 50.3 (SD = 3.5)), we examined the associations of smoking status with total GM volume and GM volume of brain regions linked to neurocognitive and addiction disorders. Linear regression models were used to adjust for vascular, respiratory, and substance use/psychological factors and to examine whether they modify the smoking-GM relationship. Compared to never-smokers, current smokers had smaller total GM volume (-8.86 cm3 (95%CI = -13.44, -4.29). Adjustment for substance use/psychological - but not vascular or respiratory - factors substantially attenuated this association (coefficients = -5.54 (95% CI = -10.32, -0.76); -8.33 (95% CI = -12.94, -3.72); -7.69 (95% CI = -6.95, -4.21), respectively). There was an interaction between smoking and alcohol use such that among alcohol non-users, smoking was not related to GM volumes and among alcohol users, those who currently smoked had -12 cm3 smaller total GM, specifically in the frontal and temporal lobes, amygdala, cingulate, and insula. Results suggest a large-magnitude association between smoking and smaller GM volume at middle age, accounting for vascular, respiratory, and substance use/psychological factors, and that the association was strongest in alcohol users. Regions suggested to be most vulnerable are those where cognition and addiction processes overlap.

Cigarette smoking and cerebral blood flow in a cohort of middle-aged adults.

Cigarette smoking is often associated with dementia. This association is thought to be mediated by hypoperfusion; however, how smoking behavior relates to cerebral blood flow (CBF) remains unclear. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (mean age = 50; n = 522), we examined the association between smoking behavior (status, cumulative pack-years, age at smoking initiation, and years since cessation) and CBF (arterial spin labeling) in brain lobes and regions linked to dementia. We used adjusted linear regression models and tested whether associations differed between current and former-smokers. Compared to never-smokers, former-smokers had lower CBF in the parietal and occipital lobes, cuneus, precuneus, putamen, and insula; in contrast, current-smokers did not have lower CBF. The relationship between pack-years and CBF was different between current and former-smokers (p for interaction < 0.05): Among current-smokers, higher pack-years were associated with higher occipital, temporal, cuneus, putamen, insula, hippocampus, and caudate CBF; former-smokers had lower caudate CBF with increasing pack-years. Results show links between smoking and CBF at middle-age in regions implicated in cognitive and compulsive/addictive processes. Differences between current and former smoking suggest that distinct pathological and/or compensatory mechanisms may be involved depending on the timing and history of smoking exposure.

Cigarette smoking and hip volumetric bone mineral density and cortical volume loss in older adults: The AGES-Reykjavik study.

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility.