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Introduction: Tobacco use disorder (TUD), previously known as nicotine dependence, was associated with increased risk of lung cancer. However, little is known about the prevalence of TUD and symptom manifestation in smokers with lung cancer. Objectives: The aim of the present study was to investigate the prevalence of TUD using DSM-5 diagnostic criteria in patients diagnosed with lung cancer and analyze their tobacco use characteristics. Methods: A total of 200 histologically confirmed lung cancer patients who used tobacco within the prior 12-month period at the time of diagnosis were recruited for this study. Participants were assessed using interviewer-administered questionnaires to determine TUD symptoms and smoking-related behaviors, and self-administered Fagerstrom Test for Nicotine Dependence (FTND) was also administered. Results: The prevalence of DSM-5 TUD was 92.0% (n = 184). Of a total of 200 subjects, 23 (11.5%), 35 (17.5%), and 126 (63.0%) were classified into mild, moderate, and severe TUD categories, respectively. A total of 19 (81.3%) moderate TUD and 98 (77.8%) severe TUD patients had attempted smoking cessation. Of these subjects, 21 (21.4%) severe TUD and 12 (63.2%) moderate TUD patients tried more than three times. The number of satisfied criteria under DSM-5 TUD was positively correlated with FTND score, cumulative lifetime smoking amount, and daily smoking levels. Conclusions: Smokers diagnosed with lung cancer showed a high prevalence of DSM-5 TUD. Their heavy and consistent tobacco use suggests reduced motivation to abstain from smoking. [ABSTRACT FROM AUTHOR]

Background: The capability of electronic cigarette devices (e-cigs) to deliver nicotine is key to their potential to replace combustible cigarettes. We compared nicotine delivery and subjective effects associated with the use of two classes of e-cigarettes and cigarettes. Methods: 14 e-cigarette users were instructed to vape their own e-cigarette device every 20 seconds for 10 minutes while blood was drawn at 1, 2, 4, 6, 8, 10,12, and 15 minutes after initiating vaping. Users rated withdrawal symptoms and side effects before and after vaping. E-cigarette devices were classified as first-generation (same size as cigarette, no activation button) or advanced (larger than cigarette with an activation button). Separately, 10 cigarette smokers completed a similar protocol. Fisher’s Exact Test and two-sided t-tests were used as appropriate to determine differences in outcomes between first-generation e-cigarette users, advanced e-cigarette users, and smokers. Results: Compared to first-generation devices, advanced devices were associated with greater serum nicotine Cmax (ng/ml) (11.5 v. 2.8, p = 0.0231) and greater nicotine boost (ng/ml) (10.8 v. 1.8, p = 0.0177). Overall, e-cigarettes users experienced a significant reduction in withdrawal and craving, although there were no significant differences between users of first-generation and advanced devices. Comparing e-cigarettes overall to cigarettes, cigarettes were associated with greater Cmax (25.9 v. 9.0, p = 0.0043) and greater nicotine boost (21.0 v. 8.2, p = 0.0128). Conclusions: Advanced e-cigarettes delivered significantly more nicotine than first-generation devices but less than combustible cigarettes. Overall, e-cigarette use was associated with a reduction in withdrawal and craving with no reported side effects. The wide variation in nicotine absorption from different e-cigarette devices should be considered in studies of e-cigarettes for smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Medicines regulatory harmonization has been recommended as one way to improve access to quality-assured medicines in low- and middle-income countries. The rationale is that by lowering barriers to entry more manufacturers will be enticed to enter the market, while the capacity at the national medicines regulatory authorities is strengthened. The African Medicines Regulatory Harmonization Initiative, agreed in 2009, is developing regional platforms with harmonized regulatory procedures for the registration of medicines. The first region to implement medicines regulatory harmonization was the East African Community (EAC). The harmonization was based on the existing EAC Free Trade Agreement, which officially launched the free movement of goods and services in 2010. Methods and findings: In this study we conducted semi-structured interviews and performed document reviews. The main target group for our interviews was pharmaceutical companies. We interviewed 18 companies, including 64% of the total companies who had experienced the EAC joint product assessment procedure, and two EAC-based national medicines regulatory authorities. We found that generally pharmaceutical companies are supportive of the African-based MRH efforts and appreciative of the progress being achieved. However, many companies are now hesitant to use the joint product assessment procedure until efficiency improvements are made. Common frustrations were the length of time to receive the actual marketing authorization; unexpectedly higher quality standards than national procedures; and challenges in getting all EAC countries to recognize EAC approvals. Smaller, less attractive markets have not yet become more attractive from a corporate perspective, and there is no free trade of pharmaceuticals in the EAC region. Conclusions: Pharmaceutical companies agree that medicines regulatory harmonization is the way forward. However, regulatory medicines harmonization must actually result in quicker access to the harmonized markets for quality-assured medicines. At this time, improvements are required to the current EAC processes to meet the vision of harmonization. [ABSTRACT FROM AUTHOR]

Nicotine is known to affect cell proliferation and differentiation, two processes vital to proper development of the mandible. The mandible, the lower jaw in mammals and fish, plays a crucial role in craniofacial development. Malformation of the jaw can precipitate a plethora of complications including disrupting development of the upper jaw, the palate, and or impeding airway function. The purpose of this study was to test the hypothesis that in utero nicotine exposure alters the development of the murine mandible in a dose dependent manner. To test this hypothesis, wild type C57BL6 mice were used to produce in utero nicotine exposed litters by adding nicotine to the drinking water of pregnant dams at concentrations of 0 μg/ml (control), 50 μg/ml (low), 100 μg/ml (medium), 200 μg/ml (high) throughout pregnancy to birth of litters mimicking clinically relevant nicotine exposures. Resultant pups revealed no significant differences in body weight however, cephalometric investigation revealed several dimensions affected by nicotine exposure including mandibular ramus height, mandibular body height, and molar length. Histological investigation of molars revealed an increase in proliferation and a decrease in apoptosis with nicotine exposure. These results demonstrate the direct effects of nicotine on the developing mandible outside the context of tobacco use, indicating that nicotine use including tobacco alternatives, cessation methods, and electronic nicotine delivering products may disrupt normal growth and development of the craniofacial complex. [ABSTRACT FROM AUTHOR]

It is estimated that around five to 10.0% of hospital admissions occur due to clinical conditions resulting from pharmacotherapy. Clinical pharmacist's activity can enhance drug therapy's effectiveness and safety through pharmacotherapy interventions (PIs), thus minimizing drug-related problems (DRPs) and optimizing the allocation of financial resources associated with health care. This study aimed to estimate the DRPs prevalence, evaluate PI which were performed by clinical pharmacists in the Neurology Unit of a Brazilian tertiary teaching hospital and to identify factors associated with the occurrence of PI-related DRP. A single-arm trial included adults admitted in the referred Unit from 2012 July to 2015 June. Patients were evaluated during their hospitalization period and PIs were performed based on trigger DRPs that were detected in medication reconciliation (admission or discharge) or during inpatient follow-up. Student's t-test, Chi-square test, Pearson and Multiple logistic regression models to analise the association among age, number of drugs, hospitalization period, and number of diagnoses with occurrence of DRPs. Analyses level of significance was 5%. In total 409 inpatients were followed up [51.1% male, mean age of 49.1 (SD 16.5)]. Patients received, on average, 11.9 (SD 5.8) drugs, ranging from two to 38 drugs per patient, and 54.3% of the sample presented at least one DRP whose most frequent description was "untreated condition". From all 516 performed PIs that resulted from DRPs, 82.8% were accepted and the majority referred to "drug introduction" (27.5%). Multiple logistic regression showed that age, length of hospital stay, number of drugs used, diagnosis of epilepsy, multiple sclerosis and myasthenia gravis would be clinical variables associated with DRP (p < 0,05). Monitoring the use of drugs allowed the clinical pharmacist to detect DRPs and to suggest interventions that promote rational pharmacotherapy. [ABSTRACT FROM AUTHOR]

Latino smokers in the United States (US) are known to experience smoking cessation treatment disparities due to their under-utilization of services, limited access to health care, and poor smoking cessation treatment outcomes. A limited number of studies have focused on developing and testing smoking cessation treatments for Latino smokers in the US. The objectives of this study were to conduct a feasibility pilot randomized trial testing three smoking cessation interventions for Latinos. Twenty-five adult Latino smokers were randomized to one of three groups: Culturally-Tailored Smoking Cessation plus Adherence Enhancement (CT+AE), Culturally-Tailored Smoking Cessation (CTSC), and a Health Education (HE) control group. All participants received three counseling sessions along with nicotine replacement therapy (NRT). Data relating to intervention acceptability and NRT adherence were collected. Self-reported 7-day point prevalence smoking was collected at 3 and 6 month follow-up and biochemically verified with expired carbon monoxide testing. Overall, the interventions demonstrated high levels of feasibility and acceptability. Days of nicotine patch use were found to be higher in the CT+AE group (mean (M) = 81.3;standard deviation (SD) = 3.32) than the CTSC (M = 68.6;SD = 13.66) and HE (M = 64;SD = 17.70) groups. At 3-month follow-up, approximately 50% of the CT+AE group were smoking abstinent, 25% of the CTSC group, and 44% of the HE group. At 6-month follow-up, 37.5% of the CT+AE group were abstinent, 25% of the CTSC group, and 44.4% of the HE group. This study is the first to target Latino smokers in the US with a culturally-tailored intervention that addresses treatment adherence. Results support the preliminary feasibility and acceptability of the CT+AE intervention. Trial Registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess the reliability of online information, as provided by three major search engines in China, about the usage of antiepileptic drugs (AEDs) during pregnancy. Method: Over eight weeks, six physicians conducted a literature search on six computers and six smartphones at a frequency of once per week. During each web search on each computer and smartphone, three major search engines in China were used, namely, Baidu, Sogou and 360. The search terms used were a combination of words, including one AED name (valproate/oxcarbazepine/levetiracetam/lamotrigine) and one Chinese word ("huaiyun" or "renshen", which means pregnancy in Chinese). The top ten websites retrieved from each search were recorded. After the content of each website was evaluated, the sites were categorized into 9 types. Meanwhile, commercial advertisements on each web page were also registered. Results: A total of 16,411 search results were assessed. After excluding the redundant web pages, 4840 search results were included in the data analysis. Only 12.05% of the search results were reliable, 47.75% were partly reliable, and 40.21% were unreliable. A total of 4139 (85.52%) webpages contained commercial advertisements. The results from a multivariate analysis suggested that websites with no advertisements and professional websites have an independent positive impact on reliability. Conclusion: Overall, little information on AED usage during pregnancy provided by major search engines in China was reliable. Practice implications: Accurate and professional online information for female patients with epilepsy should be provided through major efforts by the government, search engine companies, professional websites and epilepsy physicians. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this trial was to investigate the effect of a continuous infusion of a neuromuscular blockade (NMB) in comatose out-of-hospital cardiac arrest (OHCA) subjects who underwent targeted temperature management (TTM). Methods: In this open-label, multicenter trial, subjects resuscitated from OHCA were randomly assigned to receive either NMB (38 subjects) or placebo (43 subjects) for 24 hours. Sedatives and analgesics were given according to the protocol of each hospital during TTM. The primary outcome was serum lactate levels at 24 hours after drug infusion. The secondary outcomes included in-hospital mortality, a poor neurological outcome at hospital discharge, changes in lactate levels, changes in the PaO2:FiO2 ratio over time and muscle weakness as assessed by the Medical Research Council (MRC) scale. Results: Eighty-one subjects (NMB group: median age, 65.5 years, 30 male patients; placebo group: median age, 61.0 years, 29 male patients) were enrolled in this trial. No difference in the serum lactate level at 24 hours was observed between the NMB (2.8 [1.2–4.0]) and placebo (3.6 [1.8–5.2]) groups (p = 0.238). In-hospital mortality and a poor neurologic outcome at discharge did not differ between the two groups. No significant difference in the PaO2:FiO2 ratio over time (p = 0.321) nor the MRC score (p = 0.474) was demonstrated. Conclusions: In OHCA subjects who underwent TTM, a continuous infusion of NMB did not reduce lactate levels and did not improve survival or neurological outcome at hospital discharge. Our results indicated a limited potential for the routine use of NMB during early TTM. However, this trial may be underpowered to detect clinical differences, and future research should be conducted. [ABSTRACT FROM AUTHOR]

Background: An increasing number of people are living with multiple chronic conditions and it is unclear which quality indicators should be used to guide care for this population. Objective: To critically appraise and select the most appropriate set of quality indicators for ambulatory care for older adults with five selected disease combinations. Methods: A two-round web-based Delphi process was used to critically appraise and select quality of care indicators for older adults with diabetes and comorbidities. A fifteen-member Canadian expert panel with broad geographical and clinical representation participated in this study. The panel evaluated process indicators for meaningfulness, potential for improvements in clinical practice, and overall value of inclusion, while outcome indicators were evaluated for importance, modifiability and overall value of inclusion. A 70% agreement threshold was required for high consensus, and 60–69% for moderate consensus as measured on a 5-point Likert type scale. Results: Twenty high-consensus and nineteen medium-consensus process and outcome indicators were selected for assessing care for older adults with selected disease combinations, including 1) concordant (conditions with a common management plan), 2) discordant (conditions with unrelated management plans), and 3) both types. Panelists reached rapid consensus on quality indicators for care for older adults with concordant comorbid conditions, but not for those with discordant conditions. All selected indicators assess clinical aspects of care. The feedback from the panelists emphasized the importance of developing indicators related to patient-centred aspects of care, including patient self-management, education, patient-physician relationships, and patient’s preferences. Conclusions: The selected quality indicators are not intended to provide a comprehensive tool set for measuring quality of care for older adults with selected disease combinations. The recommended indicators address clinical aspects of care and can be used as a starting point for ambulatory care settings and development of additional quality indicators. [ABSTRACT FROM AUTHOR]

Few data are available regarding hypoxic hepatitis (HH) and acute liver failure (ALF) in patients resuscitated from cardiac arrest (CA). The aim of this study was to describe the occurrence of these complications and their association with outcome. All adult patients admitted to the Department of Intensive Care following CA were considered for inclusion in this retrospective study. Exclusion criteria were early death (<24 hours) or missing biological data. We retrieved data concerning CA characteristics and markers of liver function. ALF was defined as a bilirubin >1.2 mg/dL and an international normalized ratio ≥1.5. HH was defined as an aminotransferase level >1000 IU/L. Neurological outcome was assessed at 3 months and an unfavourable neurological outcome was defined as a Cerebral Performance Categories (CPC) score of 3–5. A total of 374 patients (age 62 [52–74] years; 242 male) were included. ALF developed in 208 patients (56%) and HH in 27 (7%); 24 patients developed both conditions. Patients with HH had higher mortality (89% vs. 51% vs. 45%, respectively) and greater rates of unfavourable neurological outcome (93% vs. 60% vs. 59%, respectively) compared to those with ALF without HH (n = 184) and those without ALF or HH (n = 163; p = 0.03). Unwitnessed arrest, non-shockable initial rhythm, lack of bystander cardiopulmonary resuscitation, high adrenaline doses and the development of acute kidney injury were independent predictors of unfavourable neurological outcome; HH (OR: 16.276 [95% CIs: 2.625–81.345; p = 0.003), but not ALF, was also a significant risk-factor for unfavourable outcome. Although ALF occurs frequently after CA, HH is a rare complication. Only HH is significantly associated with poor neurological outcome in this setting. [ABSTRACT FROM AUTHOR]

There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10–5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts. [ABSTRACT FROM AUTHOR]

Background: The linkage of routine data collections are valuable for population-based evaluation of smoking cessation pharmacotherapy in pregnancy where little is known about the utilisation or safety of these pharmacotherapies antenatally. The use of routine data collections to study smoking cessation pharmacotherapy is limited by disparities among data sources. This study developed an algorithm to resolve disparity between the evidence of pharmacotherapy utilisation for smoking cessation and the recording of smoking in pregnancy, examined its face validity and assessed the implications on estimates of smoking cessation pharmacotherapy utilisation. Methods: Perinatal records (n = 1,098,203) of women who gave birth in the Australian States of Western Australia and New South Wales (2004–2012) were linked to hospital admissions and pharmaceutical dispensing data. An algorithm, based on dispensing information about the type of smoking therapy, timing and quantity of supply reclassified certain groups of women as smoking during pregnancy. Face validity of the algorithm was tested by examining the distribution of factors associated with inaccurate recording of smoking status among women that the algorithm classified as misreporting smoking in pregnancy. Rate of utilisation among smokers, according to original and reclassified smoking status, was measured, to demonstrate the utility of the algorithm. Results: Smoking cessation pharmacotherapy were dispensed to 2184 women during pregnancy, of those 1013 women were originally recorded as non-smoking as per perinatal and hospital data. Application of the algorithm reclassified 730 women as smoking during pregnancy. The algorithm satisfied the test of face validity—the expected demographic factors of marriage, private hospital delivery and higher socioeconomic status, were more common in women whom the algorithm identified as misreporting their smoking status. Application of the algorithm resulted in smoking cessation pharmacotherapy utilisation estimates ranging from 2.3–3.6% of all pregnancies. Conclusion: Researchers can use the algorithm presented herein to improve the identification of smoking among women who use cessation pharmacotherapies during pregnancy. Improved identification can improve the validity of safety analyses of smoking cessation pharmacotherapy—providing clinicians with valuable evidence to use when counselling women on the role of pharmacotherapy for smoking cessation during pregnancy. [ABSTRACT FROM AUTHOR]

Background: The potential of electronic nicotine delivery systems (ENDS) to reduce the cardiovascular and other disease risks of smoking is of great interest. While many smokers report using ENDS for cessation, their impact under real-world use patterns and conditions on adult smokers’ quitting behavior is uncertain. The objective of this study was to generate more recent and comprehensive evidence on the effect of “real world” ENDS use on the population quit rates of adult smokers while taking account of frequency and duration of use, device type, e-liquid flavor, and reasons for use. Methods and findings: We conducted a population-based, prospective cohort study of a random probability sample of 1284 U.S. adult smokers recruited in August/September 2015 and re-contacted one-year later (September 2016) from GfK’s KnowledgePanel, a national, probability-based web-panel designed to be representative of non-institutionalized U.S. adults. Among the 1081 baseline smokers who remained members of KnowledgePanel, 858 completed the follow-up survey. The primary outcome was smoking abstinence for at least 30 days prior to follow-up. Secondary outcomes were making a quit attempt during the 12-month study period and number of cigarettes smoked per day at follow-up. The adjusted odds of quitting smoking were lower for those that used ENDS at baseline (9.4%, 95% CI = 5.22%-16.38%; AOR = 0.30, 95% CI = 0.13–0.72) compared to smokers who did not use at ENDS (18.9%, 95% CI = 14.24%-24.68%). Smokers who used ENDS daily at some point during the study period were also less likely to quit smoking than nonusers (AOR = 0.17; 95% CI = 0.04–0.82). Limited ability to draw causal inferences from the observational design and a lack of biochemical verification of quitting smoking or ENDS use are limitations of this study. Conclusions: We found no evidence that ENDS use, within context of the 2015–2016 US regulatory and tobacco/vaping market landscape, helped adult smokers quit at rates higher than smokers who did not use these products. Absent any meaningful changes, ENDS use among adult smokers is unlikely to be a sufficient solution to obtaining a meaningful increase in population quit rates. Additional research is needed to reconcile the divergent literature and monitor the impact of ENDS in an environment of rapidly evolving markets and regulatory policies. [ABSTRACT FROM AUTHOR]

Background: Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement.Methods and Findings: We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris's move from public denial to public affirmation of nicotine's addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government's filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine's (IoM's) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris's public statements reinforce the idea that nicotine's pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis.Conclusions: Philip Morris's research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine's pharmacology, the industry's continued aggressive advertising, lobbying, and litigation against effective tobacco control policies promotes various nonpharmacological determinants of addiction. To help tobacco users quit, policy makers should increase attention on the social and environmental dimensions of addiction alongside traditional cessation efforts. [ABSTRACT FROM AUTHOR]

Introduction: The use of Swedish oral moist snuff, known as snus, has for a long time been limited to the Scandinavian countries. With declining cigarette sales in the western world, tobacco companies have looked to the development of alternative tobacco products. In 2006 snus products were launched in the US. Even though several studies have demonstrated negative health effects, snus is often depicted as harmless. The aim of the present study was to investigate acute vascular effects of snus as measured by arterial stiffness as well as blood pressure and heart rate. Methods: Two separate randomized double-blind crossover studies with the same study design were pooled for analysis. Twenty-nine healthy snus-users (17 females, 12 males) were included. Snus (Göteborgs Rapé) and tobacco free snus (Onico) were administered in a randomized order at two separate visits. Arterial stiffness, blood pressure and heart rate were measured at baseline as well as every five minutes for 40 minutes during exposure. Following snus removal, measurements continued for 30 minutes post exposure. Arterial stiffness was measured using pulse wave velocity (Vicorder) and pulse wave analysis (Sphygmocor). Results: Compared to placebo, snus significantly increased systolic and diastolic blood pressure as well as heart rate, however, only in females (p = 0.004, p = 0.006 and p<0.001 respectively). No changes were seen in arterial stiffness measurements in either gender. Conclusion: We observed an increase in blood pressure and heart rate only in females, but not in males due to snus usage as compared to placebo. This novel finding was surprising and needs to be further investigated considering most of the earlier studies have mainly focused on male snus users and the increasing usage of snus among females. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (e-cigarettes) may help cigarette smokers quit smoking, yet they may also facilitate cigarette smoking for never-smokers. We quantify the balance of health benefits and harms associated with e-cigarette use at the population level. Methods and findings: Monte Carlo stochastic simulation model. Model parameters were drawn from census counts, national health and tobacco use surveys, and published literature. We calculate the expected years of life gained or lost from the impact of e-cigarette use on smoking cessation among current smokers and transition to long-term cigarette smoking among never smokers for the 2014 US population cohort. Results: The model estimated that 2,070 additional current cigarette smoking adults aged 25–69 (95% CI: -42,900 to 46,200) would quit smoking in 2015 and remain continually abstinent from smoking for ≥7 years through the use of e-cigarettes in 2014. The model also estimated 168,000 additional never-cigarette smoking adolescents aged 12–17 and young adults aged 18–29 (95% CI: 114,000 to 229,000), would initiate cigarette smoking in 2015 and eventually become daily cigarette smokers at age 35–39 through the use of e-cigarettes in 2014. Overall, the model estimated that e-cigarette use in 2014 would lead to 1,510,000 years of life lost (95% CI: 920,000 to 2,160,000), assuming an optimistic 95% relative harm reduction of e-cigarette use compared to cigarette smoking. As the relative harm reduction decreased, the model estimated a greater number of years of life lost. For example, the model estimated-1,550,000 years of life lost (95% CI: -2,200,000 to -980,000) assuming an approximately 75% relative harm reduction and -1,600,000 years of life lost (95% CI: -2,290,000 to -1,030,000) assuming an approximately 50% relative harm reduction. Conclusions: Based on the existing scientific evidence related to e-cigarettes and optimistic assumptions about the relative harm of e-cigarette use compared to cigarette smoking, e-cigarette use currently represents more population-level harm than benefit. Effective national, state, and local efforts are needed to reduce e-cigarette use among youth and young adults if e-cigarettes are to confer a net population-level benefit in the future. [ABSTRACT FROM AUTHOR]

Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet–induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR). Nicotine further increased SBP, O2- and impaired eNOS and EDR in obese rats. In the peritoneal macrophages from obese rats, tumor necrosis factor (TNF) α, interleukin 1β and CD36 were increased, and were further increased in nicotine-treated obese rats. Using PCR array we found that 3 of 84 target proinflammatory genes were increased by 2–4 fold in the aorta of obese rats, 11 of the target genes were further increased in nicotine-treated obese rats. HUVECs, incubated with conditioned medium from the peritoneal macrophages of nicotine treated-obese rats, exhibited reduced eNOS and increased NADPH oxidase subunits gp91phox and p22phox expression. Those effects were partially prevented by adding anti-TNFα antibody to the conditioned medium. Our results suggest that nicotine aggravates the CV effects of diet–induced obesity including the oxidative stress, vascular inflammation and endothelial dysfunction. The underlying mechanisms may involve in targeting endothelium by enhancement of macrophage-derived TNFα. [ABSTRACT FROM AUTHOR]

We conducted a systematic literature review and meta-analysis (ID: CRD42016051017) of smoking cessation interventions for patients with current depression. We examined the effectiveness of smoking cessation treatments in improving abstinence rates and depressive symptoms. The following electronic databases were used for potentially eligible studies: PUBMED, PSYCINFO, DIALNET and WEB OF KNOWLEDGE. The search terms used were: smoking cessation, depressive disorder, depression, mood, depressive, depressed, smoking, smokers, nicotine, nicotine dependence, and tobacco cigarette smoking. The methodological quality of included studies was assessed using the Effective Public Health Practice Project Quality assessment tool (EPHPP). Of the 6,584 studies identified, 20 were eligible and included in the review. Trial designs of studies were 16 randomized controlled trials and 4 secondary studies. Studies included three types of intervention: psychological (6/30%), pharmacological (6/30%) or combined (8/40%). Four trials comprised special populations of smokers. Four studies received a strong methodological quality, 7 were scored as moderate and 9 studies received a weak methodological rating. Analyses of effectiveness showed that smoking cessation interventions appear to increase short-term and long-term smoking abstinence in individuals with current depression. Subgroup analyses revealed stronger effects among studies that provided pharmacological treatments than in studies using psychological treatments. However, the evidence is weak due to the small number of studies. Smoking abstinence appears to be associated with an improvement in depressive symptoms. Heterogeneity in protocols in similar types of treatment also prevent firm conclusions being drawn on the effectiveness of any particular treatment model to optimally manage abstinence among depressed smokers. Further research is required to strengthen the evidence base. [ABSTRACT FROM AUTHOR]

Background: Finger opposition movements are the basis of many daily living activities and are essential in general for manipulating objects; an engineered glove quantitatively assessing motor performance during sequences of finger opposition movements has been shown to be useful to provide reliable measures of finger motor impairment, even subtle, in subjects affected by neurological diseases. However, the obtained behavioral parameters lack published reference values. Objective: To determine mean values for different motor behavioral parameters describing the strategy adopted by healthy people in performing repeated sequences of finger opposition movements, examining associations with gender and age. Methods: Normative values for finger motor performance parameters were obtained on a sample of 255 healthy volunteers executing sequences of finger-to-thumb opposition movements, stratified by gender and over a wide range of ages. Touch duration, inter-tapping interval, movement rate, correct sequences (%), movements in advance compared with a metronome (%) and inter-hand interval were assessed. Results: Increasing age resulted in decreased movement speed, advance movements with respect to a cue, correctness of sequences, and bimanual coordination. No significant performance differences were found between male and female subjects except for the duration of the finger touch, the interval between two successive touches and their ratio. Conclusions: We report age- and gender-specific normal mean values and ranges for different parameters objectively describing the performance of finger opposition movement sequences, which may serve as useful references for clinicians to identify possible deficits in subjects affected by diseases altering fine hand motor skills. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to identify factors associated with the results of smoking cessation attempts. Methods: Data were collected in Clermont-Ferrand from a smoking cessation clinic between 1999 and 2009 (1,361 patients). Smoking cessation was considered a success when patients were abstinent 6 months after the beginning of cessation. Multivariate logistic regression was used to investigate the association between abstinence and different factors. Results: The significant factors were a history of depression (ORadjusted = 0.57, p = 0.003), state of depression at the initial consultation (ORa = 0.64, p = 0.005), other psychoactive substances (ORa = 0.52, p<0.0001), heart, lung and Ear-Nose-Throat diseases (ORa = 0.65, p = 0.005), age (ORa = 1.04, p<0.0001), the Richmond test (p<0.0001; when the patient’s motivation went from insufficient to moderate, the frequency of abstinence was twice as high) and the Prochaska algorithm (p<0.0001; when the patient went from the ‘pre-contemplation’ to the ‘contemplation’ level, the frequency of success was four times higher). A high score in the Richmond test had a greater impact on success with increasing age (significant interaction: p = 0.01). In exclusive smokers, the contemplation level in the Prochaska algorithm was enough to obtain a satisfactory abstinence rate (65.5%) whereas among consumers of other psychoactive substances, it was necessary to reach the preparation level in the Prochaska algorithm to achieve a success rate greater than 50% (significant interaction: p = 0.02). Conclusion: The psychological preparation of the smoker plays a critical role. The management of smoking cessation must be personalized, especially for consumers of other psychoactive substances and/or smokers with a history of depression. [ABSTRACT FROM AUTHOR]

Background: The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment. Methodology: The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible. Results: Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6–96.1%) and 83,2% (95%CI 66–92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68–81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66–82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75–90%) versus 68% (95%CI 54–79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4–92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1–66%), OR: 3.14 (95%CI 1.1–8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66–85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49–73%) versus 82% (95%CI 70–89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates. Conclusions: Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications. [ABSTRACT FROM AUTHOR]

Introduction: Use of online social networks for smoking cessation has been associated with abstinence. Little is known about the mechanisms through which the formation of social ties in an online network may influence smoking behavior. Using dynamic social network analysis, we investigated how temporal changes of an individual’s number of social network ties are prospectively related to abstinence in an online social network for cessation. In a network where quitting is normative and is the focus of communications among members, we predicted that an increasing number of ties would be positively associated with abstinence. Method: Participants were N = 2,657 adult smokers recruited to a randomized cessation treatment trial following enrollment on BecomeAnEX.org, a longstanding Internet cessation program with a large and mature online social network. At 3-months post-randomization, 30-day point prevalence abstinence was assessed and website engagement metrics were extracted. The social network was constructed with clickstream data to capture the flow of information among members. Two network centrality metrics were calculated at weekly intervals over 3 months: 1) in-degree, defined as the number of members whose posts a participant read; and 2) out-degree-aware, defined as the number of members who read a participant’s post and commented, which was subsequently viewed by the participant. Three groups of users were identified based on social network engagement patterns: non-users (N = 1,362), passive users (N = 812), and active users (N = 483). Logistic regression modeled 3-month abstinence by group as a function of baseline variables, website utilization, and network centrality metrics. Results: Abstinence rates varied by group (non-users = 7.7%, passive users = 10.7%, active users = 20.7%). Significant baseline predictors of abstinence were age, nicotine dependence, confidence to quit, and smoking temptations in social situations among passive users (ps < .05); age and confidence to quit among active users. Among centrality metrics, positive associations with abstinence were observed for in-degree increases from Week 2 to Week 12 among passive and active users, and for out-degree-aware increases from Week 2 to Week 12 among active users (ps < .05). Conclusions: This study is the first to demonstrate that increased tie formation among members of an online social network for smoking cessation is prospectively associated with abstinence. It also highlights the value of using individuals’ activities in online social networks to predict their offline health behaviors. [ABSTRACT FROM AUTHOR]

Background: This is the first meta-analysis to compare the treatment effects and safety of administering donepezil alone versus a combination of memantine and donepezil to treat patients with moderate to severe Alzheimer Disease, particularly regarding cognitive functions, behavioral and psychological symptoms in dementia (BPSD), and global functions. Methods: PubMed, Medline, Embase, PsycINFO, and Cochrane databases were used to search for English and non-English articles for inclusion in the meta-analysis to evaluate the effect size and incidence of adverse drug reactions of different treatments. Results: Compared with patients who received donepezil alone, those who received donepezil in combination with memantine exhibited limited improvements in cognitive functions (g = 0.378, p < .001), BPSD (g = −0.878, p < .001) and global functions (g = −0.585, p = .004). Gradual titration of memantine plus a fixed dose and gradual titration of donepezil as well as a fixed dose and gradual titration of memantine resulted in limited improvements in cognitive functions(g = 0.371, p = .005), BPSD(g = −0.913, p = .001), and global functions(g = −0.371, p = .001). Conclusion: Both in the 24th week and at the final evaluation point, the combination of donepezil and memantine led to greater improvement in cognitive functions, BPSD, and global functions than did donepezil alone in patients with moderate to severe Alzheimer Disease. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. Methods and findings: We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. Conclusions: Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008. [ABSTRACT FROM AUTHOR]

Background: Intellectual disability (ID) is relatively common in people with epilepsy, with prevalence estimated to be around 25%. Surprisingly, given this relatively high frequency, along with higher rates of refractory epilepsy than in those without ID, little is known about outcomes of different management approaches/clinical services treating epilepsy in adults with ID—we investigate this area. Materials & methods: We undertook a naturalistic observational cohort study measuring outcomes in n = 91 adults with ID over a 7-month period (recruited within the period March 2008 to April 2010). Participants were receiving treatment for refractory epilepsy (primarily) in one of two clinical service settings: community ID teams (CIDTs) or hospital Neurology services. Results: The pattern of comorbidities appeared important in predicting clinical service, with Neurologists managing the epilepsy of relatively more of those with neurological comorbidities whilst CIDTs managed the epilepsy of relatively more of those with psychiatric comorbidities. Epilepsy-related outcomes, as measured by the Glasgow Epilepsy Outcome Scale 35 (GEOS-35) and the Epilepsy and Learning Disabilities Quality of Life Scale (ELDQoL) did not differ significantly between Neurology services and CIDTs. Discussion: In the context of this study, the absence of evidence for differences in epilepsy-related outcomes amongst adults with ID and refractory epilepsy between mainstream neurology and specialist ID clinical services is considered. Determining the selection of the service managing the epilepsy of adults with an ID on the basis of the skill sets also required to treat associated comorbidities may hence be a reasonable heuristic. [ABSTRACT FROM AUTHOR]

Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression. An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity. [ABSTRACT FROM AUTHOR]

Background: Little is known about homeless patients in intensive care units (ICUs). Objectives: To compare clinical characteristics, treatments, and outcomes of homeless to non-homeless patients admitted to four ICUs in a large inner-city academic hospital. Methods: 63 randomly-selected homeless compared to 63 age-, sex-, and admitting-ICU-matched non-homeless patients. Results: Compared to matched non-homeless, homeless patients (average age 48±12 years, 90% male, 87% admitted by ambulance, 56% mechanically ventilated, average APACHE II 17) had similar comorbidities and illness severity except for increased alcohol (70% vs 17%,p<0.001) and illicit drug(46% vs 8%,p<0.001) use and less documented hypertension (16% vs 40%,p = 0.005) or prescription medications (48% vs 67%,p<0.05). Intensity of ICU interventions was similar except for higher thiamine (71% vs 21%,p<0.0001) and nicotine (38% vs 14%,p = 0.004) prescriptions. Homeless patients exhibited significantly lower Glasgow Coma Scores and significantly more bacterial respiratory cultures. Longer durations of antibiotics, vasopressors/inotropes, ventilation, ICU and hospital lengths of stay were not statistically different, but homeless patients had higher hospital mortality (29% vs 8%,p = 0.005). Review of all deaths disclosed that withdrawal of life-sustaining therapy occurred in similar clinical circumstances and proportions in both groups, regardless of family involvement. Using multivariable logistic regression, homelessness did not appear to be an independent predictor of hospital mortality. Conclusions: Homeless patients, admitted to ICU matched to non-homeless patients by age and sex (characteristics most commonly used by clinicians), have higher hospital mortality despite similar comorbidities and illness severity. Trends to longer durations of life supports may have contributed to the higher mortality. Additional research is required to validate this higher mortality and develop strategies to improve outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Analyzing the disease-related web searches of Internet users provides insight into the interests of the general population as well as the healthcare industry, which can be used to shape health care policies. Methods: We analyzed the searches related to neurological diseases and drugs used in neurology using the most popular search engines in the US, Google and Bing/Yahoo. Results: We found that the most frequently searched diseases were common diseases such as dementia or Attention Deficit/Hyperactivity Disorder (ADHD), as well as medium frequency diseases with high social impact such as Parkinson’s disease, MS and ALS. The most frequently searched CNS drugs were generic drugs used for pain, followed by sleep disorders, dementia, ADHD, stroke and Parkinson’s disease. Regarding the interests of the healthcare industry, ADHD, Alzheimer’s disease, MS, ALS, meningitis, and hypersomnia received the higher advertising bids for neurological diseases, while painkillers and drugs for neuropathic pain, drugs for dementia or insomnia, and triptans had the highest advertising bidding prices. Conclusions: Web searches reflect the interest of people and the healthcare industry, and are based either on the frequency or social impact of the disease. [ABSTRACT FROM AUTHOR]

Background: Conventional pharmacotherapies and psychotherapies for major depression are associated with limited adherence to care and relatively low remission rates. Yoga may offer an alternative treatment option, but rigorous studies are few. This randomized controlled trial with blinded outcome assessors examined an 8-week hatha yoga intervention as mono-therapy for mild-to-moderate major depression. Methods: Investigators recruited 38 adults in San Francisco meeting criteria for major depression of mild-to-moderate severity, per structured psychiatric interview and scores of 14–28 on Beck Depression Inventory-II (BDI). At screening, individuals engaged in psychotherapy, antidepressant pharmacotherapy, herbal or nutraceutical mood therapies, or mind-body practices were excluded. Participants were 68% female, with mean age 43.4 years (SD = 14.8, range = 22–72), and mean BDI score 22.4 (SD = 4.5). Twenty participants were randomized to 90-minute hatha yoga practice groups twice weekly for 8 weeks. Eighteen participants were randomized to 90-minute attention control education groups twice weekly for 8 weeks. Certified yoga instructors delivered both interventions at a university clinic. Primary outcome was depression severity, measured by BDI scores every 2 weeks from baseline to 8 weeks. Secondary outcomes were self-efficacy and self-esteem, measured by scores on the General Self-Efficacy Scale (GSES) and Rosenberg Self-Esteem Scale (RSES) at baseline and at 8 weeks. Results: In intent-to-treat analysis, yoga participants exhibited significantly greater 8-week decline in BDI scores than controls (p-value = 0.034). In sub-analyses of participants completing final 8-week measures, yoga participants were more likely to achieve remission, defined per final BDI score ≤ 9 (p-value = 0.018). Effect size of yoga in reducing BDI scores was large, per Cohen’s d = -0.96 [95%CI, -1.81 to -0.12]. Intervention groups did not differ significantly in 8-week change scores for either the GSES or RSES. Conclusion: In adults with mild-to-moderate major depression, an 8-week hatha yoga intervention resulted in statistically and clinically significant reductions in depression severity. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objective: To assess state coverage and utilization of Medicaid smoking cessation medication benefits among fee-for-service enrollees who smoked cigarettes. Methods: We used the linked National Health Interview Survey (survey years 1995, 1997–2005) and the Medicaid Analytic eXtract files (1999–2008) to assess utilization of smoking cessation medication benefits among 5,982 cigarette smokers aged 18–64 years enrolled in Medicaid fee-for-service whose state Medicaid insurance covered at least one cessation medication. We excluded visits during pregnancy, and those covered by managed care or under dual enrollment (Medicaid and Medicare). Multivariate logistic regression was used to determine correlates of cessation medication benefit utilization among Medicaid fee-for-service enrollees, including measures of drug coverage (comprehensive cessation medication coverage, number of medications in state benefit, varenicline coverage), individual-level demographics at NHIS interview, age at Medicaid enrollment, and state-level cigarette excise taxes, statewide smoke-free laws, and per-capita tobacco control funding. Results: In 1999, the percent of smokers with ≥1 medication claims was 5.7% in the 30 states that covered at least one Food and Drug Administration (FDA)-approved cessation medication; this increased to 9.9% in 2008 in the 44 states that covered at least one FDA-approved medication (p<0.01). Cessation medication utilization was greater among older individuals (≥ 25 years), females, non-Hispanic whites, and those with higher educational attainment. Comprehensive coverage, the number of smoking cessation medications covered and varenicline coverage were all positively associated with utilization; cigarette excise tax and per-capita tobacco control funding were also positively associated with utilization. Conclusions: Utilization of medication benefits among fee-for-service Medicaid enrollees increased from 1999–2008 and varied by individual and state-level characteristics. Given that the Affordable Care Act bars state Medicaid programs from excluding any FDA-approved cessation medications from coverage as of January 2014, monitoring Medicaid cessation medication claims may be beneficial for informing efforts to increase utilization and maximize smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Suicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care. Methods: The ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors. Results: Suicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk. Conclusions: Reducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV. [ABSTRACT FROM AUTHOR]

Background: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far. Objective: To compare CPM to methylprednisolone (MP) in SPMS. Methods: Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area—MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model. Results: Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31–1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14–4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17–0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected. Conclusion: Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability. Trial Registration: Clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Tobacco consumption is a risk factor for chronic diseases and worldwide around six million people die from long-term exposure to first- or second-hand smoke annually. One effective approach to tobacco control is smoking cessation counseling by primary care physicians. However, research suggests that smoking cessation counseling is not sufficiently implemented in primary care. In order to understand and address the discrepancy between evidence and practice, an overview of counseling practices is needed. Therefore, the aim of this systematic literature review is to assess the frequency of smoking cessation counseling in primary care. Self-reported counseling behavior by physicians is categorized according to the 5A’s strategy (ask, advise, assess, assist, arrange). An electronic database search was performed in Embase, Medline, PsycINFO, CINAHL and the Cochrane Library and overall, 3491 records were identified. After duplicates were removed, the title and abstracts of 2468 articles were screened for eligibility according to inclusion/exclusion criteria. The remaining 97 full-text articles reporting smoking cessation counseling by primary care physicians were assessed for eligibility. Eligible studies were those that measured physicians’ self-reported smoking cessation counseling activities via questionnaire. Thirty-five articles were included in the final review (1 intervention and 34 cross-sectional studies). On average, behavior corresponding to the 5A’s was reported by 65% of physicians for “Ask”, 63% for “Advise”, 36% for “Assess”, 44% for “Assist”, and 22% of physicians for “Arrange”, although the measurement and reporting of each of these counseling practices varied across studies. Overall, the results indicate that the first strategies (ask, advise) were more frequently reported than the subsequent strategies (assess, assist, arrange). Moreover, there was considerable variation in the items used to assess counseling behaviour and developing a standardized instrument to assess the counseling strategies implemented in primary care would help to identify and address current gaps in practice. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver transplantation is a potential cure for liver damage from Wilson’s disease but the course of neuropsychiatric manifestations after transplantation remains undetermined. Material and methods: In this study, data on all patients who’d received a liver transplant for Wilson’s disease at the Shiraz Organ Transplantation Center between December 2000 and March 2014 were reviewed and compared to data on a control group who’d received a liver transplant over the same period but due to other causes. Results: Out of 2198 patients who’d received a liver transplant in the period; 107 patients were diagnosed with Wilson’s disease (21 with fulminant hepatic failure); age of patient ranged from 5 to 59 years; 56.07% of patients in this series had some type of neuropsychiatric manifestation before transplantation, of which 66.67% showed improvement after the procedure. 18 patients had aggravation of neuropsychiatric symptoms after transplantation. These neuropsychiatric symptoms were mostly for anxiety, tremor and depression but there were four cases of new onset dysarthria, rigidity and ataxia in various combinations. Survival rates of 1-month, 1-year, and 5-years for patients with Wilson’s disease were 88%, 86%, 82%, respectively, evaluations were not statistically different from that of the control group. Conclusions: Liver transplantation showed good long-term results in patients with Wilson’s disease, even in those presenting fulminant hepatic failure. Neuropsychiatric manifestations normally show improvement after transplantation but in some cases new onset of manifestations occurred after successful liver transplantation. [ABSTRACT FROM AUTHOR]

Network meta-analysis (NMA) expands the scope of a conventional pairwise meta-analysis to simultaneously compare multiple treatments, which has an inherent appeal for clinicians, patients, and policy decision makers. Two recent reports have shown that the impact of excluding a treatment on NMAs can be substantial. However, no one has assessed the impact of excluding a trial from NMAs, which is important because many NMAs selectively include trials in the analysis. This article empirically examines the impact of trial exclusion using both the arm-based (AB) and contrast-based (CB) approaches, by reanalyzing 20 published NMAs involving 725 randomized controlled trials and 449,325 patients. For the population-averaged absolute risk estimates using the AB approach, the average fold changes across all networks ranged from 1.004 (with standard deviation 0.004) to 1.072 (with standard deviation 0.184); while the maximal fold changes ranged from 1.032 to 2.349. In 12 out of 20 NMAs, a 1.20-fold or larger change is observed in at least one of the population-averaged absolute risk estimates. In addition, while excluding a trial can substantially change the estimated relative effects (e.g., log odds ratios), there is no systematic difference in terms of changes between the two approaches. Changes in treatment rankings are observed in 7 networks and changes in inconsistency are observed in 3 networks. We do not observe correlations between changes in treatment effects, treatment rankings and inconsistency. Finally, we recommend rigorous inclusion and exclusion criteria, logical study selection process, and reasonable network geometry to ensure robustness and generalizability of the results of NMAs. [ABSTRACT FROM AUTHOR]

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder’s theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed. [ABSTRACT FROM AUTHOR]

Background and objective: Relative effectiveness of smoking cessation medications—varenicline, bupropion and nicotine replacement therapy (NRT)—remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters. Methods: In a national smoking cessation program in Taiwan (2012–2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity. Results: Participants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19–1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24–1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14–1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01–1.65), men (OR = 1.31, CI: 1.18–1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24–1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04–1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch. Conclusions: In smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: There is wide variability in the amount of weight gained when quitting smoking, but little is known about key predictors of weight gain. We examined the impact of body mass index (BMI) category and sociodemographic variables on post-cessation weight gain. Materials and Methods: We utilized National Health and Nutrition Examination Survey data from five consecutive cycles of data collection from 2003–2004 to 2011–2012 to estimate post-cessation weight gain by BMI category among recent quitters (n = 654). We analyzed data on their “current weight” and their “past year weight”. We also compared the recent quitters with current smokers, in order to estimate the amount of weight that could be attributed to quitting smoking. Results: Recent quitters gained 1.4 kg (95% CI: 0.8 to 2.0), while current smokers had a non-significant weight change (-0.01 kg (95% CI: -0.3 to 0.2). Weight gain was significant for those in the normal weight (3.1 kg, 95% CI: 2.3 to 3.9) and overweight BMI categories (2.2 kg, 95% CI: 1.1 to 3.2). Conclusions: BMI category is a key factor in the extent of post-cessation weight gain, with normal and overweight recent quitters gaining significant amounts of weight. [ABSTRACT FROM AUTHOR]

Objective: to develop and validate the Drug Derived Complexity Index (DDCI), a predictive model derived from drug prescriptions able to stratify the general population according to the risk of death, unplanned hospital admission, and readmission, and to compare the new predictive index with the Charlson Comorbidity Index (CCI). Design: Population-based cohort study, using a record-linkage analysis of prescription databases, hospital discharge records, and the civil registry. The predictive model was developed based on prescription patterns indicative of chronic diseases, using a random sample of 50% of the population. Multivariate Cox proportional hazards regression was used to assess weights of different prescription patterns and drug classes. The predictive properties of the DDCI were confirmed in the validation cohort, represented by the other half of the population. The performance of DDCI was compared to the CCI in terms of calibration, discrimination and reclassification. Setting: 6 local health authorities with 2.0 million citizens aged 40 years or above. Results: One year and overall mortality rates, unplanned hospitalization rates and hospital readmission rates progressively increased with increasing DDCI score. In the overall population, the model including age, gender and DDCI showed a high performance. DDCI predicted 1-year mortality, overall mortality and unplanned hospitalization with an accuracy of 0.851, 0.835, and 0.584, respectively. If compared to CCI, DDCI showed discrimination and reclassification properties very similar to the CCI, and improved prediction when used in combination with the CCI. Conclusions and Relevance: DDCI is a reliable prognostic index, able to stratify the entire population into homogeneous risk groups. DDCI can represent an useful tool for risk-adjustment, policy planning, and the identification of patients needing a focused approach in everyday practice. [ABSTRACT FROM AUTHOR]