Nicotine receptor partial agonists for smoking cessation.

BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007. OBJECTIVES: To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO.  SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs). MAIN RESULTS: We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I2 = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I2 = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I2 = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I2 = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I2 = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I2 = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I2 = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I2 = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I2 = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I2 = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I2 = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I2 = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I2 = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I2 = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I2 = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I2 not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I2 not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit. AUTHORS' CONCLUSIONS: Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.

Higher Meat Intake Is Associated with Higher Inflammatory Markers, Mostly Due to Adiposity: Results from UK Biobank.

BACKGROUND: High meat consumption might play a role in promoting low-grade systemic inflammation, but evidence is limited. OBJECTIVES: We examined cross-sectional associations of habitual meat consumption with serum C-reactive protein (CRP) and total white blood cell count (WBCC) in British adults. METHODS: We included 403,886 men and women (aged 38-73 y) participating in the UK Biobank who provided information on meat intake (via touchscreen questionnaire) and a nonfasting blood sample at recruitment (2006-2010). For a subset of participants (∼5%), an additional blood sample was collected (median 4.4 y later). We used multivariable linear regression models to estimate associations of meat intake (total meat, unprocessed red meat, processed meat, and poultry) with logCRP and logWBCC. RESULTS: The difference in the serum CRP (mg/L) for each 50-g/d higher intake for total meat was 11.6% (95% CI: 11.1, 12.0%), for processed meat was 38.3% (95% CI: 36.0, 40.7%), for unprocessed red meat was 14.4% (95% CI: 13.6, 15.1%), and for poultry was 12.8% (95% CI: 12.0, 13.5%). The difference in the WBCC (×10-9L) for each 50 g/d higher intake of total meat was 1.5% (95% CI: 1.4, 1.6%), for processed meat was 6.5% (95% CI: 6.1, 6.9%), for unprocessed red meat was 1.6% (95% CI: 1.4, 1.7%), and for poultry was 1.6% (95% CI: 1.4, 1.7%). All associations were attenuated after adjustment for adiposity; by 67% with BMI (in kg/m2) and by 58% with waist circumference for total meat and CRP, and by 53% and 47%, respectively, for WBCC, although associations remained statistically significant. Findings of sensitivity analyses in 15,420 participants were similar prospectively, except there were no associations between unprocessed red meat and WBCC. CONCLUSIONS: Higher meat consumption, particularly of processed meat, was positively associated with inflammatory markers in these British adults; however, the magnitudes of associations are small and predominantly due to higher adiposity.

Young People's Response to Parental Neurological Disorder: A Structured Review.

INTRODUCTION: A significant paucity of literature exists relating to the impact on children of parental neurological disorder, with the exception of multiple sclerosis. The wider literature in this field (parental cancer, depression, alcoholism, HIV/AIDS) exhibits the many potential challenges young people might experience during serious parental illness. Given this, a literature review of parental neurological disorder is long overdue. METHODS: This review is structured around the World Health Organisation (WHO) classification of neurological disorders. The WHO identifies 10 common neurological disorders; dementia, epilepsy, headache, multiple sclerosis, neuroinfections, neurological disorders associated with malnutrition, pain associated with neurological disorders, Parkinson's disease, stroke, and traumatic brain injury. A comprehensive search of the MEDLINE database was performed using key terms for each of the 10 conditions. Results for each condition were divided in to "negative", "positive and/or neutral" and "other" child responses. RESULTS: The search yielded a total of 6247 titles, of which 184 underwent a full-text assessment. Sixty-five met all eligibility criteria and were thus included in the review. A number of negative issues emerged across parental conditions including the prevalence of child mood disorders, parent-child role reversal, children's need for information on the parental condition, the importance of family cohesion, the negative effect of parental psychopathology and differences between male and female children. A limited number of positive outcomes were evident in a minority of parental conditions. Outcomes measured and methodologies employed were highly heterogeneous. CONCLUSION: Children generally respond negatively to parental neurological disorder. Responses varied between neurological disorders, suggesting the need for parental disease-specific guidance and clinical management where required.