Risk of complications and poorer postoperative outcomes in obese and diabetic patients following upper limb arthroplasty: a systematic review and meta-analysis

The impact of obesity and diabetes mellitus on patient outcomes following upper limb arthroplasty is contentious. With increasing demand for joint arthroplasty, risk factors that predispose patients to greater complications and poorer outcomes must be thoroughly investigated. The objective of this review was to synthesise the best available evidence investigating the influence of obesity or diabetes mellitus on complications and/or poorer postoperative outcomes following total shoulder (TSA), reverse total shoulder (RTSA) and total elbow arthroplasty (TEA). Electronic databases (PubMed, CINAHL, and Embase) and grey literature were searched for studies that evaluated the influence of obesity (Body Mass Index [BMI] ≥ 30 kg/m²) or diabetes mellitus on arthroplasty outcomes. Two independent reviewers assessed the methodological validity of eligible studies and data was pooled in statistical meta-analysis where appropriate (RevMan 5.3; Cochrane Collaboration). The review was prospectively registered on PROSPERO (CRD42016053299). Twenty-one studies (20 cohort studies and one case-control) were included. The majority of studies considered TSA and/or RTSA populations, while four studies evaluated TEA patients. Obesity was found to significantly increase operative duration, with obese TSA/RTSA patients experiencing operations 10.00 minutes longer (95% CI [6.31, 13.69]) than patients with a BMI in the normal range, which increased to 12.48 minutes (95% CI [8.40, 16.55]) in patients with a BMI ≥ 35.0. Furthermore, obese and morbidly obese patients had 3.92 (95% CI 3.59, 4.28) to 5.46 (95% [CI 4.91, 6.07]) times greater odds of venous thromboembolism compared to their non-obese counterparts. Similarly, odds of infection increased with increasing BMI, from 2.37 (95% CI [1.65, 3.41]) times in obese, to greater than five times (95% CI [4.70, 5.39]) in morbidly obese. Obesity also increased the odds of revision (OR 1.52; 95% CI [1.43, 1.61]), dislocation (OR = 2.51; 95% CI [2.35, 2.69]) and fracture (OR = 1.94; 95% CI [1.79, 2.10]) in TSA, RTSA and TEA patients, however had no influence on the odds of urinary tract infection (OR = 0.88; 95% CI [0.48, 1.61], length of stay (MD = 0.15; 95% CI [-0.28, 0.58]), unscheduled return to theatre (OR = 0.74; 95% CI [0.44, 1.24]) or mortality (OR = 1.79; 95% CI [0.79, 4.03]). Nonetheless, morbid obesity made a small, yet significant, difference on mean length of stay (MD = 0.28; 95% CI [0.14, 0.43]). Evidence examining the effect of obesity on blood transfusion was inconclusive, while minimal evidence was available on pneumonia and quality of life. Diabetic TSA, RTSA and TEA patients had 2.93 (95% CI [1.97, 4.35]) times greater odds of mortality as an inpatient. Furthermore, diabetes mellitus was found to significantly affect odds of blood transfusion (OR = 1.49; 95% CI [1.41, 1.57]) and pneumonia (OR = 1.38; 95% CI [1.14, 1.67]), however had no effect on the odds of pulmonary embolism (OR = 1.17; 95% CI [0.94, 1.44]). The evidence for greater risk of blood transfusion in diabetic patients is a concern given the higher odds of further complications observed in transfused patients. There was also limited evidence on unscheduled return to theatre and urinary tract infection. No evidence was found examining the impact of diabetes mellitus on operative duration, dislocation, fracture, pain, function, quality of life, and revision. Inferences are limited for a number of the outcomes due to methodological shortcomings and confounders. Operative duration was inconsistently defined, and prophylactic regimes for infection and venous thromboembolism were not standardised and varied, across the included studies. The literature suggests that patient factors such as age and gender influence outcomes including revision, infection and fracture, and that surgical factors may impact the incidence of dislocation. A major limitation of studies investigating diabetes mellitus was that they reported data grouped by diabetes mellitus diagnosis without reporting the criteria used for diagnosis, or the level of glycaemic control at time of surgery. A further inherent limitation is the low level of evidence of observational study designs commonly used in orthopaedic research. Surgeons are advised to consider the additional risks associated with obesity and diabetes mellitus when determining optimal treatment options for upper limb arthroplasty patients.Thesis (M.Clin.Sc.) -- University of Adelaide, School of Public Health, 201

Antidepressants for smoking cessation

Background The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short‐term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. Objectives To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long‐term tobacco smoking cessation in people who smoke cigarettes. Search methods We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022. Selection criteria We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow‐up from efficacy analyses. We included trials with any follow‐up length for our analyses of harms. Data collection and analysis We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow‐up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all‐cause mortality, and trial dropouts due to treatment. We carried out meta‐analyses where appropriate. Main results We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high‐certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate‐certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low‐certainty evidence). There was moderate‐certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high‐certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single‐form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. Authors' conclusions There is high‐certainty evidence that bupropion can aid long‐term smoking cessation. However, bupropion may increase SAEs (moderate‐certainty evidence when compared to placebo/no pharmacological treatment). There is high‐certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single‐form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability

Mid-term migration of a cementless, porous acetabular cup; A 5 year Radiostereometric Analysis

© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyPurpose The aim of the study was to determine the 5 year migratory and wear patterns, adverse events and clinical outcomes of a cementless, porous acetabular cup. Methods RSA imaging of a cohort of 11 patients was retrospective analysed at 5 years post Total Hip Arthroplasty (THA). Changes in pain, function and symptoms of the hip at 5 years post-THA were compared to preoperative and 2 year postoperative assessments on the Harris Hip Score (HHS) and Hip dysfunction and Osteoarthritis Outcome Score (HOOS). Results The majority of cup migration occurred up to 6 months and stabilised thereafter (6 months to 5 years, p = 0.091–0.866, Wilcoxon Signed Rank test). The direction of rotation around the 3 axes was evenly distributed among the cups between anterior-posterior rotation, internal-external rotation and increased-decreased inclination. The majority of the cups translated proximally, at an average migration of 0.36 mm (±95%CI 0.17) at 5-years post-THA. Following initial bedding in, up to 6 months, there was no detectable polyethylene wear between 6 months and 5 years. At 5 years postoperatively, a statistically significant difference was observed across all HOOS subscales in comparison to preoperative values, with higher means reported at 5 years (p < 0.001). The total mean HHS displayed a statistically significant improvement, increasing from ‘poor’ preoperatively to ‘good’ at 5 years post-THA. Conclusion Following initial migration between discharge and 6 months, the cementless porous acetabular cup demonstrated a tendency for stabilisation from 6 months up to 5 years post-THA, suggesting good mid-term fixation. Additionally, improvements in clinical outcome measures of pain, function and quality-of-life remained high following THA at 5 years post-surgery

Weight regain and mental health outcomes following behavioural weight management programmes: a systematic review with meta-analyses

Behavioural weight management programmes (BWMPs) lead to weight loss but subsequent weight regain may harm mental health outcomes. We searched for randomised trials of BWMPs in adults with overweight/obesity with follow-up ≥12 months from baseline that measured weight change both at and after programme-end. We included only studies reporting mental health at or after programme-end. We meta-analysed changes in various mental health outcomes using a random-effects model by nature of the comparator group and by time since programme end. Subgroup analysis explored heterogeneity. We used mixed models and meta-regression to analyse the association between change in weight and change in depression and/or anxiety over time, with higher scores indicating greater depression and/or anxiety. We included 47 studies. When comparing BWMPs (diet and/or exercise) to control, most estimates included the possibility of no difference, but pooled estimates for psychological wellbeing, self-esteem and mental-health composite scores at programme-end, anxiety at 1–6 months, and depression at 7–12 months after programme-end suggested improvements in intervention arms relative to control, with 95% CIs excluding no difference. Pooled estimates found no evidence that BWMPs harmed mental health at programme end or beyond. Mental health composite scores at programme-end favoured diet and exercise interventions over diet alone, with 95% CIs excluding no difference. All other measures and timepoints included the possibility of no difference or could not be meta-analysed due to high heterogeneity or a paucity of data. Mixed models and meta-regression of the association between change in depression and/or anxiety scores over time, and change in weight, were inconclusive. Despite weight regain after BWMPs, our meta-analyses found no evidence of mental health harm and some evidence that BWMPs may improve some dimensions of mental health at and after programme-end

Improved clinical outcome measures of knee pain and function with concurrent resolution of subchondral Bone Marrow Edema Lesion and joint effusion in an osteoarthritic patient following Pentosan Polysulphate Sodium treatment: a case report

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background At present, there are no registered products for the treatment of subchondral Bone Marrow Edema Lesion (BML) and associated knee pain. Patients who do not respond to current anti-inflammatory therapies are left with limited treatment options, and may resort to operative management with Total Knee Arthroplasty (TKA). We report the use of Pentosan Polysulphate Sodium (PPS) for the treatment of BMLs of the knee. Case presentation We report the case of a 70-year-old female with knee osteoarthritis presenting with a high level of knee pain, scoring 8 on the Numerical Rating Scale (NRS), and functional limitation demonstrating a poor Lysholm Knee Score of 37. MRI scans of the knee revealed subchondral BML in the medial femoral condyle and medial tibial plateau. The patient was administered a course of Pentosan Polysulphate Sodium (PPS) intramuscularly twice weekly, for 3 weeks. MRI scans 2 weeks post-treatment showed complete resolution of the bone marrow edema at the medial femoral condyle and medial tibial plateau with concomitant recovery from pain (NRS pain score of 0), and a 43% improvement of the Lysholm Knee Score. In addition, marked reduction in joint effusion was also demonstrated in the MRI scan post PPS therapy. Conclusion The MRI interpretations demonstrate improved clinical outcome measures ensuing therapeutic intervention with PPS, and warranting further investigation into the efficacy of PPS in the treatment of BML associated pain and dysfunction in the osteoarthritic population via randomized controlled trial, or equivalent rigorous methodological technique

Smoking cessation for improving mental health

Background: There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self‐medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health. Objectives: To examine the association between tobacco smoking cessation and change in mental health. Search Methods: We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously‐conducted non‐Cochrane review where searches were conducted from database inception to 13 April 2012. Selection Criteria: We included controlled before‐after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow‐up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later. Data Collection and Analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow‐up. Secondary outcomes included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders. We assessed the risk of bias for the primary outcomes using a modified ROBINS‐I tool. For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow‐up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta‐analyses we used a generic inverse variance random‐effects model and quantified statistical heterogeneity using I2. We conducted subgroup analyses to investigate any differences in associations between sub‐populations, i.e. unselected people with mental illness, people with physical chronic diseases. We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non‐randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose‐response gradient). Main Results: We included 102 studies representing over 169,500 participants. Sixty‐two of these were identified in the updated search for this review and 40 were included in the original version of the review. Sixty‐three studies provided data on change in mental health, 10 were included in meta‐analyses of incidence of mental health disorders, and 31 were synthesised narratively. For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD −0.28, 95% CI −0.43 to −0.13; 15 studies, 3141 participants; I2 = 69%; low‐certainty evidence); depression symptoms: (SMD −0.30, 95% CI −0.39 to −0.21; 34 studies, 7156 participants; I2 = 69%' very low‐certainty evidence); mixed anxiety and depression symptoms (SMD −0.31, 95% CI −0.40 to −0.22; 8 studies, 2829 participants; I2 = 0%; moderate certainty evidence). These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time‐varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate. For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD −0.19, 95% CI −0.34 to −0.04; 4 studies, 1792 participants; I2 = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I2 = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I2 = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I2 = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I2 = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I2 = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I2 = 87%). Authors' Conclusions: Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low‐ to moderate‐certainty evidence that smoking cessation is associated with small to moderate improvements in mental health. These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time‐varying confounding would strengthen the evidence in this area.</p

Surgical site infection in overweight and obese Total Knee Arthroplasty patients

© 2018 Prof. PK Surendran Memorial Education Foundation. Published by Elsevier, a division of RELX India, Pvt. Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyPurpose This aim of this study was to evaluate the rate of surgical site infection (SSI) in patients undergoing Total Knee Arthroplasty (TKA), to improve our understanding of the associations between infection rate and obesity. Methods Data was reviewed for 839 primary TKA procedures performed at a National Arthroplasty Centre over one year (April 2007–March 2008). SSI data was collected at 30 days and one year post-operatively. Patients were grouped guided by the WHO classifications of obesity; normal (BMI < 25.0), overweight (BMI 25.00–29.99), obese class I (BMI 30.00–34.99), obese class II (BMI 35.00–39.99), obese class III (BMI ≥ 40.00). Statistical significance was assessed by Fisher’s Exact Test. Results When grouped by BMI, 30.9% of patients were obese class I, 19.0% obese class II and 8.7% obese class III. Of the total cohort, 22 patients (2.6%) had superficial SSI and 13 (1.5%) had deep SSI. When comparing the obese class III cohort to all other cohorts (non-obese class III), the odds ratios for superficial SSI was 4.20 (95% CI [1.59, 11.09]; p = 0.009) and deep SSI was 6.97 (95% CI [2.22, 21.89]; p = 0.003). In the obese class III cohort, superficial SSI rate was higher in females (8.9%) than males (5.9%), yet deep SSI demonstrated the opposite, with a higher occurrence in males (11.8%) compared to females (5.4%). Conclusion This study suggests that obese class III TKA patients are at increased odds of superficial and deep SSI compared to other BMI cohorts. Interestingly, male obese class III patients demonstrated a higher rate of deep infection compared to their female counterparts. However, it must be noted that study findings are limited as confounders were unable to be accounted for in this retrospective study design

Impact of program characteristics on weight loss in adult behavioral weight management interventions: systematic review and component network meta-analysis

Objective: Behavioral weight management programs (BWMPs) for adults lead to greater weight loss at 12 months than minimal-intervention control treatments. However, there is considerable heterogeneity in the content of BWMPs and outcomes of treatment. This study assessed the contribution of individual components of BWMPs, using Bayesian component network meta-analysis. Methods: Randomized controlled trials of BWMPs in adults were identified (latest search: December 2019) and arms coded for presence or absence of 29 intervention components grouped by type, content, provider, mode of delivery, and intensity. Results: A total of 169 studies (41 judged at high risk of bias) were included in the main analysis. Six components had effect estimates indicating clinically significant benefit and credible intervals (CrIs) excluding no difference: change in diet (mean difference [MD] = −1.84 kg, 95% CrI: −2.91 to −0.80); offering partial (MD = −2.12 kg, 95% CrI: −3.39 to −0.89) or total meal replacements (MD = −2.63 kg, 95% CrI: −4.58 to −0.73); delivery by a psychologist/counselor (MD = −1.45 kg, 95% CrI: −2.81 to −0.06) or dietitian (MD = −1.31 kg, 95% CrI: −2.40 to −0.24); and home setting (MD = −1.05 kg, 95% CrI: −2.02 to −0.09). Conclusions: Future program development should consider including these components; other approaches continue to warrant evaluation of effectiveness

An exploration of flavours in studies of e‐cigarettes for smoking cessation: secondary analyses of a systematic review with meta‐analyses

Aims: To estimate associations between e-cigarette flavour and smoking cessation and study product use at 6 months or longer. Methods: Secondary analysis of data from a living systematic review, with meta-analyses and narrative synthesis, incorporating data up to Jan 2022. Included studies provided people who smoked combustible cigarettes with nicotine e-cigarettes for the purpose of smoking cessation, compared with no treatment or other stop smoking interventions. Measurements included smoking cessation and study product use at 6 months or longer reported as risk ratios (RR) with 95% confidence intervals (CI); flavour use at any time points. Results: We included 16 studies (n=10,336); 14 contributed to subgroup analyses and 10 provided participants with a choice of e-cigarette flavour. We judged nine, five and two studies at high, low, and unclear risk of bias, respectively. Subgroup analyses showed no clear associations between flavour and cessation or product use. In all but one analysis tests for subgroup differences resulted in I2 values between 0% and 35%. In the comparison between nicotine e-cigarettes and nicotine replacement therapy (NRT) (I2 =65.2% for subgroup differences), studies offering tobacco flavour e-cigarettes showed evidence of a greater proportion of participants still using at six-months or longer (RR=3.81; 95% CI=1.45 to 10.05; 3 studies; n=1181; I2 =84%), whereas there was little evidence for greater 6-month use when studies offered a choice of flavours (RR=1.44; 95% CI=0.80 to 2.56; 2 studies; n=454; I2 =82%). However, substantial statistical heterogeneity within subgroups makes interpretation of this result unclear. In the 10 studies where participants had a choice of flavours and this was tracked over time some switching between flavours occurred, but there were no clear patterns in flavour preferences. Conclusions: There does not appear to be a clear association between e-cigarette flavours and smoking cessation or longer-term e-cigarette use, possibly due to a paucity of data. There is evidence that people using e-cigarettes to quit smoking switch between e-cigarette flavours

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses

Background Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e‐cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. Objectives To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e‐cigarettes, when used to help people stop smoking tobacco. Search methods We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. Selection criteria We included randomised controlled trials (RCTs), cluster‐RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e‐cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co‐interventions (e.g. behavioural support) were eligible if the co‐intervention was provided equally to study arms. Data collection and analysis We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta‐analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta‐regression. We evaluated certainty using GRADE. Main results Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e‐cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high‐certainty evidence that nicotine e‐cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast‐acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high‐certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast‐acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate‐certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non‐nicotine/placebo e‐cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low‐certainty evidence), equating to one additional quitter (95% CrI ‐2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low‐certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non‐nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low‐certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e‐cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e‐cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). Authors' conclusions The most effective interventions were nicotine e‐cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high‐certainty evidence for the effectiveness of nicotine patch, fast‐acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non‐nicotine e‐cigarettes and tapering of nicotine dose (both low certainty). There was moderate‐certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head‐to‐head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation