Prediction of Sjögren's disease diagnosis using matched electronic dental-health record data.

BACKGROUND: Sjögren's disease (SD) is an autoimmune disease that is difficult to diagnose early due to its wide spectrum of clinical symptoms and overlap with other autoimmune diseases. SD potentially presents through early oral manifestations prior to showing symptoms of clinically significant dry eyes or dry mouth. We examined the feasibility of utilizing a linked electronic dental record (EDR) and electronic health record (EHR) dataset to identify factors that could be used to improve early diagnosis prediction of SD in a matched case-control study population. METHODS: EHR data, including demographics, medical diagnoses, medication history, serological test history, and clinical notes, were retrieved from the Indiana Network for Patient Care database and dental procedure data were retrieved from the Indiana University School of Dentistry EDR. We examined EHR and EDR history in the three years prior to SD diagnosis for SD cases and the corresponding period in matched non-SD controls. Two conditional logistic regression (CLR) models were built using Least Absolute Shrinkage and Selection Operator regression. One used only EHR data and the other used both EHR and EDR data. The ability of these models to predict SD diagnosis was assessed using a concordance index designed for CLR. RESULTS: We identified a sample population of 129 cases and 371 controls with linked EDR-EHR data. EHR factors associated with an increased risk of SD diagnosis were the usage of lubricating throat drugs with an odds ratio (OR) of 14.97 (2.70-83.06), dry mouth (OR = 6.19, 2.14-17.89), pain in joints (OR = 2.54, 1.34-4.76), tear film insufficiency (OR = 27.04, 5.37-136.), and rheumatoid factor testing (OR = 6.97, 1.94-25.12). The addition of EDR data slightly improved model concordance compared to the EHR only model (0.834 versus 0.811). Surgical dental procedures (OR = 2.33, 1.14-4.78) were found to be associated with an increased risk of SD diagnosis while dental diagnostic procedures (OR = 0.45, 0.20-1.01) were associated with decreased risk. CONCLUSION: Utilizing EDR data alongside EHR data has the potential to improve prediction models for SD. This could improve the early diagnosis of SD, which is beneficial to slowing or preventing complications of SD.

Responses of cyanobacterium Microcystis aeruginosa under single and repeated ofloxacin exposure.

Antibiotics are omnipresent and pseudo-persistent in the environment. Yet, their potential ecological risks under repeated exposure, which is more environmentally relevant, are understudied. Therefore, this study used ofloxacin (OFL) as the probe chemical to investigate the toxic effects of different exposure scenarios-single dose of high concentration (4.0 µg/L) and multiple additions of low concentrations-towards the cyanobacterium Microcystis aeruginosa. Flow cytometry was employed to measure a collection of biomarkers, including endpoints related with biomass, single cell properties and physiological status. Results showed that the single dose of the highest OFL level inhibited cellular growth, chl-a content and cell size of M. aeruginosa. In contrast, OFL induced stronger chl-a autofluorescence and higher doses tended to have more remarkable effects. Repeated low OFL doses can more significantly increase the metabolic activity of M. aeruginosa than a single high dose. Viability and cytoplasmic membrane were not affected by OFL exposure. Oxidative stress was observed for the different exposure scenarios, with fluctuating responses. This study demonstrated the different physiological responses of M. aeruginosa under different OFL exposure scenarios, providing novel insights into the toxicity of antibiotics under repeated exposure.

Assessment of human exposure to benzophenone-type UV filters: A review.

To avoid the harmful effects of UV radiation, benzophenone-type UV filters (BPs) are widely used in personal care products and other synthetic products. Biomonitoring studies have shown the presence of BPs in various human biological samples, raising health concerns. However, there is a paucity of data on the global human exposure to this group of contaminants. In this study, we compiled data on the body burden of BPs along with the possible exposure routes and biotransformation pathways. BPs can easily penetrate the skin barrier and thus, they can be absorbed through the skin. In the human body, BPs can undergo Phase I (mainly demethylation and hydroxylation) and Phase II (mainly glucuronidation and sulfation) biotransformations. From a total of 158 studies, most of the studies are related to urine (concentration up to 92.7 mg L-1), followed by those reported in blood (up to 0.9 mg L-1) and milk (up to 0.8 mg L-1). Among BPs, benzophenone-1 and benzophenone-3 are the most commonly detected congeners. The body burden of BPs is associated with various factors, including the country of residence, lifestyle, income, education level, and ethnicity. The presence of BPs in maternal urine (up to 1.1 mg L-1), placenta (up to 9.8 ng g-1), and amniotic fluid (up to 15.7 µg L-1) suggests potential risks of prenatal exposure. In addition, transplacental transfer of BPs is possible, as demonstrated by their presence in maternal serum and cord serum. The possible association of BPs exposure and health effects was discussed. Future human biomonitoring studies and studies on the potential health effects are warranted. Overall, this review provides a summary of the global human exposure to BPs and can serve as supporting evidence to guide usage in order to protect humans from being exposed to BPs.

Ecological momentary assessment of temptations and lapses in non-daily smokers.

RATIONALE: Little is known about relapse among non-daily, intermittent smokers (ITS), who have difficulty quitting, despite a lack of dependence. OBJECTIVES: To analyze situations associated with temptations to smoke and smoking lapses among ITS trying to maintain abstinence. METHODS: Participants were 130 initially abstinent ITS in the placebo arm of a smoking cessation study. EMA data captured participants' situations and states in temptations (n = 976), including those that eventuated in lapses (n = 147), for up to 6 weeks. Randomly timed assessments assessed background states (n = 11,446). Participants also reported coping performed to prevent lapses. Multilevel analyses compared temptations to background situations, and lapse episodes to resolved temptations. RESULTS: Temptations were marked by exposure to smoking cues, including others smoking, lax smoking restrictions, and alcohol consumption, as well as more negative affect. Lapses did not differ from resolved temptations in craving intensity, but were more often associated with smoking cues and availability of cigarettes, alcohol consumption, and worse affect, and were more often attributed to good moods. Both behavioral and cognitive coping responses were associated with avoiding lapsing, but behavioral coping had much larger effects. The effects of affective distress on lapse risk were mediated by its effects on coping. CONCLUSIONS: Smoking cues play a major role in ITS' temptations and lapses, perhaps indicating a degree of behavioral dependence. Affective distress also played a role in ITS lapses, undermining the idea that the affective distress seen in daily smokers' lapses is due to nicotine withdrawal. The data reinforce the important role of coping in preventing lapses.

Effectiveness of nicotine gum in preventing lapses in the face of temptation to smoke among non-daily smokers: a secondary analysis.

BACKGROUND AND AIMS: Non-daily smokers (NDS) comprise a large fraction of US smokers. Despite little or no dependence, as typically assessed, intermittent smokers (ITS) have difficulty quitting smoking. A randomized clinical trial comparing the effect of nicotine gum with placebo on quitting smoking in non-daily smokers did not find an effect on overall abstinence. We undertook an analysis to assess whether using nicotine gum versus placebo when tempted to smoke could reduce incidence of lapses in those situations. DESIGN: Within a 6-week randomized, placebo-controlled clinical trial of nicotine gum, analyses contrasted the outcome of temptation episodes where gum was or was not used. SETTING: Smoking cessation research clinic in Pittsburgh, PA, USA. PARTICIPANTS: A total of 255 adult ITS (131 nicotine gum, 124 placebo) seeking help for smoking cessation. INTERVENTION: Nicotine gum (2 mg) versus placebo for up to 8 weeks, with as-needed dosing instructions. MEASUREMENTS: Outcome was lapsing in temptation episodes, as reported by participants via ecological momentary assessment (EMA). Propensity scores predicting gum use from situational factors (e.g. mood, social setting, smoking cues) served as a control variable. FINDINGS: Participants reported 2713 temptation episodes, 46.0% (1248) of which resulted in smoking (lapsing). There was a significant gum use × active treatment interaction (P = 0.0009). Using nicotine gum decreased the odds of lapsing by 55% compared with using placebo [odds ratio (OR) = 0.45; 0.22-0.94]; when gum was not used, the assigned gum condition made no significant difference (OR = 1.53; 0.78-3.01; Bayes factor = 0.14). The nicotine effect was not reliably different when participants were trying to achieve abstinence versus when trying to maintain abstinence (OR = 0.44; 0.10, 2.03; P = 0.294; Bayes factor = 0.11), for men and women (OR = 1.68; 0.58, 4.87; P = 0.343; Bayes factor = 0.10), or for participants with some or no dependence (OR = 0.88; 0.30, 2.59; P = 0.811; Bayes factor = 0.06). CONCLUSIONS: When used in response to temptation to smoke, 2 mg nicotine gum can help to prevent lapses among non-daily smokers.

Using Nicotine Gum to Assist Nondaily Smokers in Quitting: A Randomized Clinical Trial.

INTRODUCTION: Non-daily intermittent smokers (ITS) comprise 30% of US adult smokers. ITS smoke for nicotine and have trouble quitting, but tend to smoke in particular situations. This study tested the effect of nicotine gum, used to prevent or react to situational temptations, for helping ITS quit. METHODS: ITS (smoking 4-27 days/month) seeking help quitting were randomized to 2 mg nicotine gum (n = 181) or placebo (n = 188), to be used to anticipate or react to temptations to smoke, for 8 weeks. Participants received up to six sessions of behavioral counseling. The primary outcome was 6-month biochemically verified continuous abstinence; analyses also examined 14-day point-prevalence abstinence at multiple time points, and used event-history analyses to assess progression to abstinence, lapsing, and relapsing. Analyses adjusted for group differences in age and baseline smoking, and considered several potential moderators of treatment effects. RESULTS: Nicotine gum did not significantly improve outcomes on any measure. Biochemically verified 6-month continuous abstinence rates were 7.2% for active gum and 5.3% for placebo (AOR = 1.39, 0.58-3.29, p > .25). ITS with any degree of dependence (Fagerstrom Test of Nicotine Dependence scores >0) showed poorer outcomes on multiple endpoints, and did more poorly on active gum on some outcomes. Gum use was low, starting at 1 gum per day on average and declining over time. CONCLUSIONS: Nicotine gum (2 mg), used intermittently, did not improve cessation rates among ITS, including those demonstrating some degree of dependence. IMPLICATIONS: Nicotine replacement has been extensively tested with daily smokers, especially those who smoke relatively heavily. Nondaily smoking is now common, creating a need for treatment for ITS. Despite evidence that ITS' smoking is motivated by nicotine-seeking, a theoretically and empirically derived situational approach to using acute nicotine replacement was not successful at helping ITS quit. Gum use was low; whether higher or more frequent dosing is needed, or whether an entirely different approach is needed, is not clear. Effective treatment options are needed for ITS, especially those with some degree of dependence.

Very-low-nicotine-content cigarettes and dependence among non-daily smokers.

BACKGROUND: The US Food and Drug Administration is considering reductions in the nicotine content of cigarettes to reduce smoking and tobacco dependence. A randomized study showed that even non-daily, intermittent smokers (ITS) reduced their cigarette consumption when switched to very-low-nicotine-content cigarettes (VLNCCs). This paper assesses whether switching ITS to VLNCCs results in decreased dependence and whether subsequent cigarette consumption is mediated by decreased dependence. METHODS: ITS randomized to VLNCCs (n = 118) or normal nicotine content cigarettes (n = 120) completed multiple measures of dependence (Fagerstrom Test of Nicotine Dependence [FTND], Nicotine Dependence Syndrome Scale [NDSS], Wisconsin Inventory of Smoking Dependence Motives [WISDM], and Hooked on Nicotine Checklist [HONC]) at Baseline and 2, 6, and 10 weeks after randomization. A principal component factor score captured common variance among these measures (except FTND). Cigarettes per day (CPD) was assessed by three convergent methods. RESULTS: Switching ITS to VLNCCs reduced dependence on all measures except the WISDM Secondary Dependence Motives and HONC. Except for the effects on the factor score, these effects of VLNCCs could be accounted for by contemporaneous CPD. Week-2 dependence measures did not prospectively predict weeks 3-4 CPD, once antecedent dependence and CPD were accounted for. "Cheating" among participants who appear to have smoked conventional cigarettes did not affect the findings. DISCUSSION: Among ITS, switching to VLNCCs results in reduced tobacco dependence. However, the reductions in dependence appear to be secondary to effects on cigarette consumption, and do not appear to be an independent predictor or cause of reduced cigarette consumption.

Do non-daily smokers compensate for reduced cigarette consumption when smoking very-low-nicotine-content cigarettes?

RATIONALE: The Food and Drug Administration is considering severely restricting the nicotine in cigarettes, to reduce smoking. A study showed that non-daily, intermittent smokers (ITS) randomized to very-low-nicotine-content cigarettes (VLNCCs) reduced their cigarette consumption. OBJECTIVES: To assess whether increased smoking intensity of VLNCCs compensated for some of the reduced cigarette consumption. METHODS: After a 2-week baseline smoking their own-brand cigarettes, 118 ITS were randomized to VLNCCs (~ 1 mg nicotine/g tobacco), and 120 to normal-nicotine-content cigarettes (NNCCs; ~ 16 mg/g) for 10 weeks. Laboratory measures of smoking intensity-total puff volume and carbon monoxide (CO) boost-assessed single cigarettes smoked in up to three laboratory topography sessions. Field measures assessed returned cigarette butts, averaged over up to five 2-week intervals: the mass of tobacco burned (computed from residual mass of butts) and the intensity of smoking (by scanning of returned filters). Analysis was by mixed model random effects models using baseline values as covariates. RESULTS: ITS in the VLNCC group puffed less smoke in topography sessions (-38.50 mL [-75.21, -1.78]; p < 0.04), but showed no difference in CO boost. Participants in the VLNCC group burned 0.02 [0.04, 0.002] grams less tobacco per cigarette (p < 0.03). Analysis of filters showed their smoking intensity declined over time, compared to NNCC participants (p < 0.04). "Cheating" by smoking normal cigarettes did not moderate these effects. CONCLUSIONS: ITS did not increase their smoking intensity when switched to VLNCCs; indeed, their smoking intensity decreased. Reductions in cigarette consumption seen when ITS are switched to VLNCCs were not compensated by increased smoking intensity.

Nondaily Smokers' Changes in Cigarette Consumption With Very Low-Nicotine-Content Cigarettes: A Randomized Double-blind Clinical Trial.

Importance: The US Food and Drug Administration is considering limiting cigarettes to very low nicotine levels. Cigarette consumption of nondaily intermittent smokers (ITS), who compose one-third of US adult smokers, could feasibly increase or could be unaffected if their smoking is not motivated by nicotine seeking. Objective: To compare cigarette consumption in ITS receiving very low-nicotine-content cigarettes (VLNCCs) or identical normal-nicotine-content cigarettes (NNCCs). Design, Setting, and Participants: This randomized double-blind clinical trial was conducted from June 2015 to July 2017 at a single US site. Volunteer ITS not planning to quit were recruited via media. Overall, 297 individuals enrolled, and 238 were randomized. Analyses were intent-to-treat. Interventions: After a 2-week baseline of smoking their own brand of cigarettes provided gratis, ITS were randomized to VLNCCs or NNCCs for 10 weeks. Main Outcomes and Measures: The number of cigarettes per day (CPD) was assessed by real-time reporting, timeline follow-back reports, and cigarette butt counts. The primary outcome was change in CPD from baseline to weeks 9 to 10 of intervention, adjusting for baseline CPD. Results: The mean (SD) age of the 238 randomized participants was 37.9 (13.8) years. Of 238 participants, 108 (45%) were men. At baseline, the mean (SD) CPD was 3.1 (2.9). In intent-to-treat analyses using multiple imputation to address missing data, the VLNCC group had a mean decrease of 1.6 CPD (95% CI, 1.1-2.0; 51% of baseline) vs 0.05 decrease with NNCCs (95% CI, -0.5 to 0.4; 2% of baseline). Treatment group differences were not materially moderated by sex, race/ethnicity, or history of daily smoking. Cheating with conventional cigarettes, inferred from cotinine assays, was more common in the VLNCC group (OR, 2.95; 95% CI, 1.54-5.66), but sensitivity analyses showed significant VLNCC effects among the compliant participants as well. In longitudinal analysis of CPD over time with random intercept and slope, the VLNCC and NNCC groups differed significantly in both linear (-0.15; 95% CI, -0.22 to -0.08; P < .001) and quadratic (0.0026; 95% CI, 0.0010-0.0042; P = .002) trends: CPD dropped by 43.8% in the VLNCC group over 4 weeks, then leveled off thereafter. Abstinence (intent-to-treat, biochemically verified) in weeks 9 to 10 postrandomization did not differ significantly by treatment group (VLNCC, 10.2% vs NNNC, 5.0%; P = .28). Conclusions and Relevance: Switching to VLNCCs caused substantial smoking reduction among ITS but did not significantly increase abstinence. Response to a VLNCC intervention suggests that nicotine-seeking motivates ITS' smoking. Trial Registration: ClinicalTrials.gov Identifier: NCT02228824.