Potentially Inappropriate Prescribing and Potential Prescribing Omissions and Their Association with Adverse Drug Reaction-Related Hospital Admissions.

BACKGROUND: This study aimed to determine the prevalence of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) and their association with ADR-related hospital admissions in patients aged ≥ 65 years admitted acutely to the hospital. METHODS: Information on medications and morbidities was extracted from the Adverse Drug Reactions in an Ageing Population (ADAPT) cohort (N = 798: N = 361 ADR-related admissions; 437 non-ADR-related admissions). PIP and PPOs were assessed using Beers Criteria 2019 and STOPP/START version 2. Multivariable logistic regression (adjusted odds ratios (aOR), 95%CI) was used to examine the association between PIP, PPOs and ADR-related admissions, adjusting for covariates (age, gender, comorbidity, polypharmacy). RESULTS: In total, 715 (90%; 95% CI 87-92%) patients had ≥1 Beers Criteria, 555 (70%; 95% CI 66-73%) had ≥ 1 STOPP criteria and 666 patients (83%; 95% CI 81-86%) had ≥ 1 START criteria. Being prescribed at least one Beers (aOR = 1.66, 95% CI = 1.00-2.77), or meeting STOPP (aOR = 1.07, 95% CI = 0.79-1.45) or START (aOR = 0.72; 95%CI = 0.50-1.06) criteria or the number of PIP/PPO criteria met was not significantly associated with ADR-related admissions. Patients prescribed certain drug classes (e.g., antiplatelet agents, diuretics) per individual PIP criteria were more likely to have an ADR-related admission. CONCLUSION: There was a high prevalence of PIP and PPOs in this cohort but no association with ADR-related admissions.

A novel abuse liability assessment of e-cigarettes in young adults ii: Reinforcement enhancement and follow-up assessment.

A double-blind study was performed to test the abuse liability of electronic nicotine delivery systems (ENDS) in young adults; in particular, the influence of nicotine on reward sensitivity was assessed. A total of 53 healthy nonusers participated in experimental sessions during which they played a video game made available on a progressive ratio schedule of reinforcement and self-administered nicotine via ENDS. Participants were randomized into one of three groups. Two groups received either a dedicated concentration of nicotine (6 and 12 mg) or a placebo, and whether they received the placebo or their dedicated nicotine dose was randomly determined on a session-by-session basis to mask the sequencing of drug administration. The third group received only a 0 mg (placebo) vaping device during all sessions. In comparison to all placebo conditions, nicotine-induced reward sensitization was evidenced on behavioral measures of video game reinforcement, but not subjective appraisals of the vaping experience. A 1-month follow-up survey provided evidence that reinforcement enhancement by nicotine predicts increased abuse liability of ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.

Context: Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications. Objective: The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain. Evidence acquisition: A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function. Evidence synthesis: After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain. Conclusions: Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain. Patient summary: Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.

A systematic review and meta-analysis of interventions to induce attempts to quit tobacco among adults not ready to quit.

The prevalence of past-year smoking cessation remains below 10% in the U.S. Most who smoke are not ready to quit in the near future. Cessation requires both (a) initiating a quit attempt (QA) and (b) maintaining abstinence. Most research has focused on abstinence among people already motivated to quit. We systematically reviewed interventions to promote QAs among people not motivated to quit tobacco. We searched PubMed, CENTRAL, PsycINFO, Embase, and our personal libraries for randomized trials of tobacco interventions that reported QAs as an outcome among adults not ready to quit. We screened studies and extracted data in duplicate. We pooled findings of the 25 included studies using Mantel-Haenszel random effects meta-analyses when ≥ 2 studies tested the same intervention. Most (24) trials addressed cigarettes and one addressed smokeless tobacco. Substantial heterogeneity among trials resulted in a series of small meta-analyses. Findings indicate varenicline may increase QAs more than no varenicline, n = 320; RR = 1.4, 95% CI [1.1, 1.7]; I² = 0%, and nicotine replacement therapy (NRT) may increase QAs more than no NRT, n = 2,568; RR = 1.1, 95% CI [1.02, 1.3]; I² = 0%. Pooled effects for motivational counseling, reduction counseling, and very low nicotine content cigarettes showed no clear evidence of benefit or harm. The evidence was judged to be of medium to very low certainty due to imprecision, inconsistency, and risk of bias, suggesting that further research is likely to change interpretation of our results. Findings demonstrate the need for more high-quality research on interventions to induce QAs among adults not ready to quit tobacco. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The interactive effects of JUUL flavor and nicotine concentration on addiction potential.

Prior research suggests that flavors can influence the pharmacological effects of nicotine. We used commercially available JUUL pods to examine whether preferred menthol versus tobacco flavor increased the addictive potential of nicotine per se. This study recruited 15 regular JUUL e-cigarette users to complete a 2 × 2 factorial crossover trial using an entirely remote video format. Participants completed a sampling baseline session to identify preferred JUUL flavor (menthol vs. tobacco) followed by four counterbalanced experimental sessions separated by ≥ 48 hr: (a) low-nicotine dose (3% JUUL)/nonpreferred flavor; (b) low dose/preferred flavor; (c) high-nicotine dose (5% JUUL)/nonpreferred flavor; and (d) high dose/preferred flavor. In each experimental session, participants completed a puffing procedure followed by subjective ratings of e-cigarette liking and wanting (ELW), urges, and reinforcement using a JUUL pod purchase task. There was a dose-by-flavor interaction for average ELW (F = 4.58, p = .041) in which ELW was significantly greater for the preferred than the nonpreferred flavor at the low-nicotine dose but not the high-nicotine dose. There were also dose-by-flavor interactions for pre- to post-puffing change in overall urge to vape (F = 5.97, p = .021) and urge strength (F = 4.96, p = .049), with greater reductions in overall urge/strength for the preferred compared to the nonpreferred flavor at the low but not the high dose. We found no significant interaction effects for purchase task outcomes. Using a fully remote experimental puffing procedure, our findings suggest preferred flavors increase the rewarding effects most for lower nicotine e-cigarettes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.

'It's helped me to learn to deal with it': a mixed methods service evaluation of a multicomponent fibromyalgia service.

OBJECTIVES: To evaluate the Royal London Hospital for Integrated Medicine (RLHIM) multicomponent fibromyalgia service. METHODS: Mixed methods approach consisting of the completion of validated quantitative outcome measures (Patient Health Questionnaire-9; Generalised Anxiety Disorder-7; Pain Catastrophising Scale; Patient Self-Efficacy Questionnaire) pre- and post-treatment to explore the impact of treatment; and qualitative focus groups with patients at their follow-up appointments to explore patients' experiences and perspectives on the service. RESULTS: 138 fibromyalgia patients attended the RLHIM group fibromyalgia service during the period of the evaluation. Baseline scores demonstrate that patients were significantly impaired pre-treatment according to all outcome measures. At the end of the course of treatment, scores for all outcome measures showed clinically and statistically significant improvements. These improvements were maintained at both 6- and 9-month follow-up appointments. Qualitative analysis indicated that those participating valued the multicomponent treatment approach, and perceived the service as having a positive impact on their fibromyalgia and overall quality of life, enabling patients to effectively manage their condition. CONCLUSIONS: Patients attending the RLHIM multicomponent fibromyalgia service appear to have demonstrable improvements in presenting symptoms, and quality of life. The findings support a multicomponent approach to the treatment of fibromyalgia.

Reinforcement enhancement by nicotine: A novel abuse-liability assessment of e-cigarettes in young adults.

Nicotine can act as a primary positive reinforcer, and as negative reinforcer to relieve withdrawal; we tested whether it can also enhance the reinforcing efficacy of non-drug reinforcers. Young-adult never-users were delivered nicotine via e-cigarette, and a videogame reinforcer was used to test nicotine enhancement. Three dose groups were tested (placebo-only, 6 or 12-mg nicotine), and participants returned to the lab for several sessions over the course of 1 month. Those in the two nicotine-dose groups received placebo on some occasions and nicotine on others; nicotine enhancement of the videogame reinforcer was assessed in a within-subjects fashion by comparing each of the two nicotine groups' dedicated nicotine dose to placebo. In the placebo-only group, progressive-ratio (PR) schedule breakpoints did not alter as a function of videogame exposure, suggesting that the videogame retained its basic-reinforcing properties throughout the study. For the two groups that received nicotine, both doses of nicotine increased PR-schedule breakpoints for the videogame reinforcer relative to the placebo condition. Although nicotine was associated with greater subjective evaluation of the enjoyment of the videogame, it was unrelated to the enjoyment of the e-cigarette device. No evidence was found that nicotine elevated either anhedonia or withdrawal symptoms in the timeframe of the study. The results provide initial evidence that nicotine enhancement, via electronic cigarettes, occurs in non-frequent users of nicotine products and may be a reason they can develop nicotine dependence in the absence of withdrawal and direct effects of nicotine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Contexts and mechanisms relevant to General Practitioner (GP) based interventions to reduce adverse drug events (ADE) in community dwelling older adults: a rapid realist review.

Background: Older adults in Ireland are at increased risk of adverse drug events (ADE) due, in part, to increasing rates of polypharmacy. Interventions to reduce ADE in community dwelling older adults (CDOA) have had limited success, therefore, new approaches are required.A realist review uses a different lens to examine why and how interventions were supposed to work rather than if, they worked. A rapid realist review (RRR) is a more focused and accelerated version.The aim of this RRR is to identify and examine the contexts and mechanisms that play a role in the outcomes relevant to reducing ADE in CDOA in the GP setting that could inform the development of interventions in Ireland. Methods: Six candidate theories (CT) were developed, based on knowledge of the field and recent literature, in relation to how interventions are expected to work. These formed the search strategy. Eighty full texts from 633 abstracts were reviewed, of which 27 were included. Snowballing added a further five articles, relevant policy documents increased the total number to 45. Data were extracted relevant to the theories under iteratively developed sub-themes using NVivo software. Results: Of the six theories, three theories, relating to GP engagement in interventions, relevance of health policy documents for older adults, and shared decision-making, provided data to guide future interventions to reduce ADEs for CDOA in an Irish setting. There was insufficient data for two theories, a third was rejected as existing barriers in the Irish setting made it impractical to use. Conclusions: To improve the success of Irish GP based interventions to reduce ADEs for CDOA, interventions must be relevant and easily applied in practice, supported by national policy and be adequately resourced. Future research is required to test our theories within a newly developed intervention.

Prevalence and Factors Associated with Potential Drug-Drug Interactions in Older Community-Dwelling Adults: A Prospective Cohort Study.

BACKGROUND: Older patients are at increased risk of drug-drug interactions (DDIs) due to polypharmacy. Cardiovascular and central nervous system (CNS) drugs are commonly implicated in serious DDIs. OBJECTIVES: This study aimed to determine the prevalence and factors associated with potential 'severe' cardiovascular and CNS DDIs among older (≥ 70 years) community-dwellers. METHODS: This was a prospective cohort study using linked data from a national pharmacy claims database and waves 1 and 2 of The Irish LongituDinal study on Ageing (TILDA). 'Severe' cardiovascular and CNS DDIs were identified using the British National Formulary 77 and Stockley's Drug Interactions. The prevalence of 'severe' DDIs (any DDI vs. none) was calculated. Logistic regression was used to examine the association between sociodemographic, functional ability, and medication-related factors and the risk of DDI exposure between waves 1 and 2. RESULTS: A total of 1466 patients were included [mean age (standard deviation) = 78 (5.5) years; female n = 795, 54.2%]. In total, 332 community-dwellers aged ≥ 70 years [22.65%, 95% confidence interval (CI) 20.58-24.86] were potentially exposed to at least one 'severe' cardiovascular or CNS DDI, with more than half (54.82%) of this cohort dispensed the same DDI for a prolonged time (≥ 3 consecutive claims). Aspirin-warfarin was the most frequently dispensed (co-prescribed) DDI (n = 34, 10.24%, 95% CI 7.39-14.00), followed by atorvastatin-clarithromycin (n = 19, 5.72%, 95% CI 3.64-8.81). Polypharmacy [≥ 10 vs. < 5 drugs, odds ratio (OR) 13.40, 95% CI 8.22-21.85] and depression (depressed vs. not, OR 2.12, 95% CI 1.34-3.34) were significantly associated with these DDIs, after multivariable adjustment. CONCLUSION: 'Severe' cardiovascular and CNS DDIs are prevalent in older community-dwellers in Ireland, and those with polypharmacy and depression are at a significantly increased risk.

Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Using a Mobile App-Based Video Recommender System of Patient Narratives to Prepare Women for Breast Cancer Surgery: Development and Usability Study Informed by Qualitative Data.

BACKGROUND: Women diagnosed with breast cancer are often bombarded with information. Such information overload can lead to misunderstandings and hamper women's capacity for making informed decisions about their care. For women with breast cancer, this uncertainty is particularly severe in the period before surgery. Personalized narratives about others' experiences can help patients better understand the disease course, the quality and type of care to be expected, the clinical decision-making processes, and the strategies for coping. Existing resources and eHealth apps rarely include experiential information, and no tools exist that tailor information for individual preferences and needs-offering the right information at the right time and in the right format. Combining high-quality experiential evidence with novel technical approaches may contribute to patient-centered solutions in this area. OBJECTIVE: This study aims to design and seek preliminary feedback on a mobile app that will improve information access about surgery for patients with breast cancer, by drawing on a qualitative collection of personal narratives from a diverse sample of Canadian women and using video and audio recordings or audio recordings from the Canadian Health Experiences Research Network. METHODS: In a previous study, we conducted in-depth interviews with 35 Canadian women and used video and audio recordings or audio recordings to collect stories about the lived experiences of breast cancer. The participants highlighted the need for more specific information between diagnosis and surgery that was relevant to their personal situations and preferences. They also wanted to learn from other women's experiences. We worked with patients, clinicians, and informatics experts to develop a mobile app that provides access to tailored experiential information relevant to women's personal situations and preferences. We completed focus groups and qualitative interviews, conducted a further analysis of the original qualitative data, designed novel software using artificial intelligence, and sought preliminary feedback from users on a new app via focus groups and a survey. RESULTS: The secondary analysis of the breast cancer narratives revealed key themes and their interconnections relevant to the experience of surgery, including preparation, treatment decisions, aftercare, reconstruction, prostheses, lumpectomy and mastectomy, and complications. These themes informed the development of the structure and content of the app. We developed a recommender system within the app by using content matching (user and speaker profiles and user interests and video content) and collaborative filtering to identify clips marked as relevant by the user and by similar users. A 2-minute animated introductory video for users was developed. Pilot testing revealed generally positive responses regarding the content and value of this type of e-tool. CONCLUSIONS: Developing reliable, evidence-based tools and apps that are based on diverse collections of people's experiences of illness offers a novel approach to help manage the plethora of information that women face after a diagnosis of breast cancer.

A feasibility trial of acupuncture in cancer patients undergoing radiotherapy treatment.

OBJECTIVE: We conducted a feasibility trial of acupuncture in cancer patients undergoing radiotherapy treatment. The trial included training radiographers to deliver acupuncture within patients' routine NHS care. METHODS: Mixed methods pragmatic randomized parallel-group exploratory feasibility trial comparing standard care to standard care plus acupuncture. RESULTS: Most aspects of the research design and acupuncture intervention were acceptable to the 101 participants. Participants' valued the opportunity to receive acupuncture within their NHS care, perceived the treatment as eliciting a number of beneficial effects, and had a positive impact on their NHS cancer treatment. However, quantitative analysis of outcome measure data revealed no consistent significant differences between those receiving standard care and those receiving standard care plus acupuncture. CONCLUSION: It is feasible to implement acupuncture in a busy radiotherapy unit provided by specially trained radiographers. The methodology employed appears acceptable for the evaluation of acupuncture for radiotherapy patients.

Surgery and opioids: evidence-based expert consensus guidelines on the perioperative use of opioids in the United Kingdom.

There are significant concerns regarding prescription and misuse of prescription opioids in the perioperative period. The Faculty of Pain Medicine at the Royal College of Anaesthetists have produced this evidence-based expert consensus guideline on surgery and opioids along with the Royal College of Surgery, Royal College of Psychiatry, Royal College of Nursing, and the British Pain Society. This expert consensus practice advisory reproduces the Faculty of Pain Medicine guidance. Perioperative stewardship of opioids starts with judicious opioid prescribing in primary and secondary care. Before surgery, it is important to assess risk factors for continued opioid use after surgery and identify those with chronic pain before surgery, some of whom may be taking opioids. A multidisciplinary perioperative care plan that includes a prehabilitation strategy and intraoperative and postoperative care needs to be formulated. This may need the input of a pain specialist. Emphasis is placed on optimum management of pain pre-, intra-, and postoperatively. The use of immediate-release opioids is preferred in the immediate postoperative period. Attention to ensuring a smooth care transition and communication from secondary to primary care for those taking opioids is highlighted. For opioid-naive patients (patients not taking opioids before surgery), no more than 7 days of opioid prescription is recommended. Persistent use of opioid needs a medical evaluation and exclusion of chronic post-surgical pain. The lack of grading of the evidence of each individual recommendation remains a major weakness of this guidance; however, evidence supporting each recommendation has been rigorously reviewed by experts in perioperative pain management.

Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. METHODS: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. RESULTS: Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. CONCLUSIONS: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

Tobacco and Nicotine Use Among US Adult "Never Smokers" in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: A common criterion for being labeled a "never smoker" is having smoked <100 lifetime cigarettes. This category is often used as an unexposed reference group to estimate the relative harm from cigarettes. We examined the amount of current and past cigarette and non-cigarette tobacco/nicotine use among adults who met this "never smoker" criterion. METHODS: We analyzed cross-sectional data from 17 179 adult "never smokers" (ie, reported <100 lifetime cigarettes) in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health (PATH) Study, a United States nationally representative sample. We used PATH-derived variables to describe "never smokers'" demographics as well as cigarette and non-cigarette tobacco/nicotine use. RESULTS: Approximately half of "never smokers" were young adults (49.3%). Most were white (68.6%) with some college or more (64.4%). Most "never smokers" had tried any cigarette or non-cigarette tobacco/nicotine in their lifetime (66.7%), 8.5% smoked cigarettes in the past 30 days, and 5.3% were current experimental (ie, some days or every day) cigarette smokers. By definition, "never smokers" reported smoking <100 lifetime cigarettes. One fifth (22.8%) had a lifetime history of established regular non-cigarette tobacco/nicotine use and 8.6% were current established regular non-cigarette tobacco/nicotine users. In total, 9.4% of "never smokers" were current experimental or established regular users of combustible tobacco. CONCLUSIONS: The 100-cigarette lifetime threshold includes substantial amounts of current and past tobacco use and thus does not represent lack of exposure to cigarette or non-cigarette tobacco. "Never smoker" reference groups may produce underestimates of the relative harms from cigarettes. IMPLICATIONS: The <100 lifetime cigarettes criterion may not capture what many would consider true "never smokers." Relying on the current definition of "never smokers" as a reference group will include a substantial number of those currently and recently using combustible tobacco and thus produce data that may underestimate the relative harm from cigarettes. Prospective longitudinal research is needed to compare how the 100-cigarette lifetime threshold versus other definitions of regular cigarette smoking differ in predictive validity of clinically meaningful outcomes and health harms to determine the optimal criteria to define established cigarette smoking.

Possible New Symptoms of Tobacco Withdrawal III: Reduced Positive Affect-A Review and Meta-analysis.

INTRODUCTION: Most descriptions of tobacco withdrawal have not changed in >30 years despite new research. This meta-analysis tested whether abstinence leads to decreased positive affect (PA) because abstinence-induced symptom changes are a core feature of the tobacco withdrawal syndrome. In addition, we examined whether reduced PA was due to withdrawal (ie, temporary decrease in a "U-shaped" curve) or offset (ie, return to baseline) effect. METHODS: Our main inclusion criterion was a prospective within-participant test of change in PA during abstinence conditions among people who smoke cigarettes daily who were not using a cessation medication. Our search of PubMed, PsycINFO, and personal libraries yielded a total of 32 tests with 2054 participants. RESULTS: There was a medium effect size indicating an overall decrease in PA following abstinence from cigarettes (Cohen's d = -0.40, 95% CI = -0.30 to -0.49). There was large heterogeneity (I2 = 70.7%). Most (79%) of the 24 trials that conducted significance tests reported that reduction in PA was significant. Seven tests were adequately designed to detect a withdrawal versus offset effect. Over half (57%) displayed a U-shaped curve for abstinence-induced change in PA indicative of a withdrawal symptom rather than offset effect. CONCLUSIONS: Abstinence from cigarettes is associated with a decrease in PA. Whether low PA should be added to withdrawal measures and diagnostic criteria requires replication of the time-course of change in PA and tests of whether abstinence-induced changes in PA and negative affect occur independently. IMPLICATIONS: Though there was substantial heterogeneity among trials, our findings suggest that (1) abstinence from cigarettes decreases positive affect and (2) this decrease may represent a withdrawal effect (vs. an offset effect). However, it is unclear whether abstinence-induced losses in positive affect are independent from increased negative affect.