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Neuroscience and Biobehavioral Reviews Aug 2021Dementia is one of the greatest global challenges for public health; however, the relationship between anticholinergic drugs and dementia remains unclear. The aim of the... (Meta-Analysis)
Meta-Analysis Review
Dementia is one of the greatest global challenges for public health; however, the relationship between anticholinergic drugs and dementia remains unclear. The aim of the present study was to perform a systematic review and meta-analysis of the predictive roles of anticholinergic drugs in dementia risk. After pooling fourteen longitudinal and case-control studies with a total of 1,564,181 subjects, anticholinergic drug use was associated with an increased risk of all-cause dementia and Alzheimer's disease. Both low and high anticholinergic drug burdens were associated with dementia. Moreover, there was a dose-dependent relationship between anticholinergic drugs and risk of dementia. With respect to the categories of anticholinergic drugs, antiparkinson, urological drugs, and antidepressants increased the risk for dementia; however, cardiovascular and gastrointestinal drugs played potentially protective roles. These findings underscore the importance of anticholinergic drugs as a potential modifiable risk factor for dementia and provide treatment priorities to optimize dementia prevention.
Topics: Alzheimer Disease; Cholinergic Antagonists; Dementia; Humans; Pharmaceutical Preparations; Risk Factors
PubMed: 33933505
DOI: 10.1016/j.neubiorev.2021.04.031 -
Expert Opinion on Drug Safety Oct 2018Currently, five pharmacotherapeutic options are available to treat Alzheimer's disease: memantine; the three cholinesterase inhibitors donepezil, galantamine, and... (Meta-Analysis)
Meta-Analysis Review
Currently, five pharmacotherapeutic options are available to treat Alzheimer's disease: memantine; the three cholinesterase inhibitors donepezil, galantamine, and rivastigmine; and combination treatments with memantine and one cholinesterase inhibitor. Selection of the best course of treatment is based upon the evidence gathered by systematic reviews and meta-analyses of randomized controlled trials. Areas covered: This article provides a risk-benefit analysis of these treatments using evidence from meta-analyses on their safety and their efficacy. Expert opinion: Memantine improves cognitive functions and behavioral disturbances more efficiently than the placebo, both as monotherapy and in combination with donepezil. Although memantine monotherapy and combination therapy are associated with a few individual adverse events such as somnolence, it is well-tolerated and its safety (all-cause discontinuation) is comparable or superior to that of the placebo (agitation). Pooled cholinesterase inhibitors are superior to the placebo in the improvement of cognitive functions, but not behavioral disturbances and they are not well-tolerated, as evaluated by the high discontinuation rate. Donepezil (10 mg/day) and oral rivastigmine and galantamine monotherapies carry the risk for some adverse events including gastrointestinal symptoms. Therefore, we consider that combined treatment with memantine and donepezil is the most useful treatment for Alzheimer's disease.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Donepezil; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Indans; Memantine; Piperidines; Randomized Controlled Trials as Topic
PubMed: 30222469
DOI: 10.1080/14740338.2018.1524870 -
Orphanet Journal of Rare Diseases Feb 2019Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired...
OBJECTIVES
Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs.
METHODS
Systematic literature review.
RESULTS
Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium.
CONCLUSIONS
CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.
Topics: Cholinesterase Inhibitors; Humans; Mutation; Myasthenic Syndromes, Congenital; Neuromuscular Agents; Proteins
PubMed: 30808424
DOI: 10.1186/s13023-019-1025-5 -
The Turkish Journal of Gastroenterology... Dec 2017Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use... (Review)
Review
Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.
Topics: Drug-Related Side Effects and Adverse Reactions; Esophagus; Gastroesophageal Reflux; Humans; Risk Factors
PubMed: 29199166
DOI: 10.5152/tjg.2017.11 -
Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735 -
Advances in Therapy Sep 2022Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.
METHODS
This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).
RESULTS
The NMA was informed by five trials reporting FEV at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).
CONCLUSION
The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Benzyl Alcohols; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Drug Combinations; Fluticasone; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines
PubMed: 35849317
DOI: 10.1007/s12325-022-02231-0 -
JAMA Jun 2021The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.
OBJECTIVE
To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.
DATA SOURCES
MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.
STUDY SELECTION
Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.
MAIN OUTCOMES AND MEASURES
Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.
RESULTS
Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).
CONCLUSIONS AND RELEVANCE
Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Quality of Life; Severity of Illness Index; Symptom Flare Up; Xerostomia
PubMed: 34009257
DOI: 10.1001/jama.2021.7872 -
The Cochrane Database of Systematic... May 2018Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.
OBJECTIVES
To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017.
SELECTION CRITERIA
Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews.
DATA COLLECTION AND ANALYSIS
Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model.
MAIN RESULTS
We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare.
AUTHORS' CONCLUSIONS
There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.
Topics: Administration, Cutaneous; Administration, Inhalation; Chewing Gum; Female; Humans; Male; Nicotine; Nicotinic Agonists; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Prevention; Tablets; Time Factors; Tobacco Use Cessation Devices
PubMed: 29852054
DOI: 10.1002/14651858.CD000146.pub5 -
Journal of the American Medical... Jan 2021To investigate the association between anticholinergic drug burden (ADB), measured with anticholinergic drug scales, and delirium and delirium severity. (Review)
Review
OBJECTIVES
To investigate the association between anticholinergic drug burden (ADB), measured with anticholinergic drug scales, and delirium and delirium severity.
DESIGN
Systematic review.
SETTING AND PARTICIPANTS
All available studies.
METHODS
A systematic literature search was performed in Medline, Embase, PsycINFO, Web of Science, CINAHL, Cochrane library, and Google Scholar. Studies evaluating the association between ADB (measured as a total score) and delirium or delirium severity, published in English, were eligible for inclusion.
RESULTS
Sixteen studies, including 148,756 persons, were included. Fifteen studies investigated delirium. ADB was measured with the Anticholinergic Risk Scale (ARS, n = 5), the Anticholinergic Cognitive Burden Scale (ACB, n = 6), the list of Chew (n = 1), the Anticholinergic Drug Scale (ADS, n = 5), a modified version of the ARS (n = 1), and a modified version of the ACB (n = 1). A high ADB, measured with the ARS, was associated with delirium (5/5). Also with the modified version of the ARS and ACB, an association was found between a high ADB and delirium during 3-month (1/1) and 1-year follow-up (1/1), respectively. When ADB was assessed with other scales, the results were inconclusive, with only 1 positive association for the ACB (1/6) and ADS (1/5) each. The possible association between ADB and delirium severity has also been investigated (ADS n = 2, Summers Drug Risk Number n = 1). One study found an association between a high ADB, measured with the ADS, and an increase in severity of delirium.
CONCLUSIONS AND IMPLICATIONS
ADB assessed with the ARS is consistently associated with delirium. The association found between the modified versions of the ARS and ACB and delirium needs confirmation. When ADB was assessed with other scales, the findings were inconclusive. The current findings suggest that the ARS might be a useful tool to identify patients at increased risk for delirium.
Topics: Cholinergic Antagonists; Delirium; Humans; Pharmaceutical Preparations
PubMed: 32703688
DOI: 10.1016/j.jamda.2020.04.019 -
The Cochrane Database of Systematic... Nov 2022Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce... (Review)
Review
BACKGROUND
Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review.
OBJECTIVES
To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2022, and reference-checked and contacted study authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials, in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants, or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses.
MAIN RESULTS
We included 78 completed studies, representing 22,052 participants, of which 40 were RCTs. Seventeen of the 78 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 50 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.63, 95% CI 1.30 to 2.04; I = 10%; 6 studies, 2378 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.02, 95% CI 0.88 to 1.19; I = 0%; 4 studies, 1702 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.12, 95% CI 0.82 to 1.52; I = 34%; 5 studies, 2411 participants). There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I = 0%; 8 studies, 1272 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.66, 95% CI 1.52 to 4.65; I = 0%; 7 studies, 3126 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.03, 95% CI 0.54 to 1.97; I = 38%; 9 studies, 1993 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit.
AUTHORS' CONCLUSIONS
There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
Topics: Humans; Smoking Cessation; Electronic Nicotine Delivery Systems; Tobacco Use Cessation Devices; Nicotinic Agonists; Systematic Reviews as Topic; Nicotine; Randomized Controlled Trials as Topic
PubMed: 36384212
DOI: 10.1002/14651858.CD010216.pub7