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The Nuffield Department of Primary Care Health Sciences at the University of Oxford and the Royal College of General Practitioners (RCGP) have joined forces with clinical system supplier EMIS Health to urgently recruit as many GP practices as possible for COVID-19 research.
Interventions for preventing weight gain after smoking cessation
Background: Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting. Objectives: To systematically review the effects of: (1) interventions targeting post-cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post-cessation weight gain (referred to as 'Part 2'). Search methods: Part 1 - We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020. Part 2 - We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e-cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists. Selection criteria: Part 1 - trials of interventions that targeted post-cessation weight gain and had measured weight at any follow-up point or smoking cessation, or both, six or more months after quit day. Part 2 - trials included in the selected parent Cochrane reviews reporting weight change at any time point. Data collection and analysis: Screening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow-up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta-analysis using the inverse variance method for weight, and Mantel-Haenszel method for smoking. Main results: Part 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk. An intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) −3.70 kg, 95% confidence interval (CI) −4.82 to −2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD −1.30 kg, 95% CI −3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study found that no-one completed the VLCD intervention or achieved abstinence. Interventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I2 = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I2 = 26%). Some pharmacological interventions tested for limiting post-cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low-certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD −1.11 kg, 95% CI −1.93 to −0.29; 3 studies, 121 participants; I2 = 0%), but no evidence in the longer-term 12 months (MD −0.44 kg, 95% CI −2.34 to 1.46; 4 studies, 530 participants; I2 = 41%). There was low to very low-certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD −0.21 kg, 95% CI −2.28 to 1.86; 2 studies, 61 participants; I2 = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I2 = 0%). Part 2: We include 83 completed studies, 27 of which are new to this update. There was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD −0.25 kg, 95% CI −0.78 to 0.29; 4 studies, 404 participants; I2 = 0%). However, weight was reduced at 12 months (MD −2.07 kg, 95% CI −3.78 to −0.36; 3 studies, 182 participants; I2 = 0%). Both bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD −1.01 kg, 95% CI −1.35 to −0.67; 10 studies, 1098 participants; I2 = 3%); (fluoxetine MD −1.01 kg, 95% CI −1.49 to −0.53; 2 studies, 144 participants; I2 = 38%; low- and very low-certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD −0.26 kg, 95% CI −1.31 to 0.78; 7 studies, 471 participants; I2 = 0%). No studies of fluoxetine provided data at 12 months. There was moderate-certainty that NRT reduced weight at end of treatment (MD −0.52 kg, 95% CI −0.99 to −0.05; 21 studies, 2784 participants; I2 = 81%) and moderate-certainty that the effect may be similar at 12 months (MD −0.37 kg, 95% CI −0.86 to 0.11; 17 studies, 1463 participants; I2 = 0%), although the estimates are too imprecise to assess long-term benefit. There was mixed evidence of the effect of varenicline on weight, with high-certainty evidence that weight change was very modestly lower at the end of treatment (MD −0.23 kg, 95% CI −0.53 to 0.06; 14 studies, 2566 participants; I2 = 32%); a low-certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI −0.58 to 2.69; 3 studies, 237 participants; I2 = 0%). Authors' conclusions: Overall, there is no intervention for which there is moderate certainty of a clinically useful effect on long-term weight gain. There is also no moderate- or high-certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.
Risk of poor outcomes in patients who are obese following total shoulder arthroplasty and reverse total shoulder arthroplasty: a systematic review and meta-analysis
Background: A systematic review was performed to investigate the impact of obesity on outcomes following total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). Methods: Electronic databases and the grey literature were searched for studies that evaluated the influence of obesity (body mass index ≥ 30 kg/m2) on TSA and RTSA outcomes. A total of 15 studies were identified, with 10 studies reporting on predetermined outcomes considered in the TSA and RTSA population. Unadjusted data were pooled in a statistical meta-analysis where appropriate (Review Manager [RevMan], version 5.3) or summarized in narrative form. Effect sizes were expressed as odds ratios (ORs) for categorical data and weighted mean differences (WMDs) for continuous data. Results: The findings suggested that patients who were obese were at increased odds of a dislocation (OR, 2.49; 95% confidence interval [CI], 2.32-2.66), fracture (OR, 1.92; 95% CI, 1.77-2.08), and revision (OR, 1.49; 95% CI, 1.40-1.58) following TSA or RTSA. Conversely, obesity had no influence on the odds of an unscheduled return to the operating theater (OR, 0.83; 95% CI, 0.43-1.61). Postoperative forward flexion in patients who were obese differed from that in patients who were not obese (WMD, –9.8°; 95% CI, –17.53° to –2.07°); however, no differences in other functional measures including abduction (WMD, –0.78; 95% CI, –7.27 to 5.71) and external rotation (WMD, –1.41; 95% CI, –5.11 to 2.29) were found. Although patients who were obese reported significantly higher levels of pain (WMD, 1.13; 95% CI, 0.21 to 2.06), the difference was not clinically relevant. Conclusions: Surgeons should consider advising patients who are obese of the greater risk of dislocation, fracture, and revision when considering elective TSA or RTSA. Findings are limited by confounding variables but further our understanding of additional risks associated with pre-existing obesity, which will promote better-informed decisions prior to proceeding with surgery.
Long-Term Effect of Weight Regain Following Behavioral Weight Management Programs on Cardiometabolic Disease Incidence and Risk: Systematic Review and Meta-Analysis
Background: Behavioral weight management programs (BWMPs) enhance weight loss in the short term, but longer term cardiometabolic effects are uncertain as weight is commonly regained. We assessed the impact of weight regain after BWMPs on cardiovascular risk factors, diabetes, and cardiovascular disease. Methods: Trial registries, 11 databases, and forward-citation searching (latest search, December 19) were used to identify articles published in English, from any geographical region. Randomized trials of BWMPs in adults with overweight/obesity reporting cardiometabolic outcomes at ≥12 months at and after program end were included. Differences between more intensive interventions and comparator groups were synthesized using mixed-effects, meta-regression, and time-to-event models to assess the impact of weight regain on cardiovascular disease incidence and risk. Results: One hundred twenty-four trials reporting on ≥1 cardiometabolic outcomes with a median follow-up of 28 (range, 11-360) months after program end were included. Median baseline participant body mass index was 33 kg/m2; median age was 51 years. Eight and 15 study arms (7889 and 4202 participants, respectively) examined the incidence of cardiovascular disease and type 2 diabetes, respectively, with imprecise evidence of a lower incidence for at least 5 years. Weight regain in BWMPs relative to comparators reduced these differences. One and 5 years after program end, total cholesterol/HDL (high-density lipoprotein) ratio was 1.5 points lower at both times (82 studies; 19 003 participants), systolic blood pressure was 1.5 mm mercury and 0.4 mm lower (84 studies; 30 836 participants), and HbA1c (%) 0.38 lower at both times (94 studies; 28 083 participants). Of the included studies, 22% were judged at high risk of bias; removing these did not meaningfully change results. Conclusions: Despite weight regain, BWMPs reduce cardiometabolic risk factors with effects lasting at least 5 years after program end and dwindling with weight regain. Evidence that they reduce the incidence of cardiovascular disease or diabetes is less certain. Few studies followed participants for ≥5 years. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018105744.
The effect of individual-level smoking cessation interventions on socioeconomic inequalities in tobacco smoking
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To investigate differences in the effectiveness of individual-level smoking cessation interventions by socioeconomic indicators, to estimate the potential that an intervention might increase or decrease health inequalities due to tobacco use.
Biomarkers of potential harm in people switching from smoking tobacco to exclusive e-cigarette use, dual use or abstinence: secondary analysis of Cochrane systematic review of trials of e-cigarettes for smoking cessation
Aims: This study aims to compare biomarkers of potential harm between people switching from smoking combustible cigarettes (CC) completely to electronic cigarettes (EC), continuing to smoke CC, using both EC and CC (dual users) and using neither (abstainers), based on behaviour during EC intervention studies. Design: Secondary analysis following systematic review, incorporating inverse variance random-effects meta-analysis and effect direction plots. Setting: This study was conducted in Greece, Italy, Poland, the United Kingdom and the United States. Participants: A total of 1299 adults smoking CC (nine studies) and provided EC. Measurements: Measurements were conducted using carbon monoxide (CO) and 26 other biomarkers. Findings: In pooled analyses, exhaled CO (eCO) was lower in EC versus EC + CC [mean difference (MD) = −4.40 parts per million (p.p.m.), 95% confidence interval (CI) = −12.04 to 3.24, two studies] and CC (MD = −9.57 p.p.m., 95% CI = −17.30 to −1.83, three studies). eCO was lower in dual users versus CC only (MD = −1.91 p.p.m., 95% CI = −3.38 to −0.45, two studies). Magnitude rather than direction of effect drove substantial statistical heterogeneity. Effect direction plots were used for other biomarkers. Comparing EC with CC, 12 of 13 biomarkers were significantly lower in EC users, with no difference for the 13th. Comparing EC with dual users, 12 of the 25 biomarkers were lower for EC, and five were lower for dual use. For the remaining eight measures, single studies did not detect statistically significant differences, or the multiple studies contributing to the outcome had inconsistent results. Only one study provided data comparing dual use with CC; of the 13 biomarkers measured, 12 were significantly lower in the dual use group, with no statistically significant difference detected for the 13th. Only one study provided data on abstainers. Conclusions: Switching from smoking to vaping or dual use appears to reduce levels of biomarkers of potential harm significantly.
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
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.
Knee instability as the primary cause of failure following Total Knee Arthroplasty (TKA): A systematic review on the patient, surgical and implant characteristics of revised TKA patients
Background The aim of this review was to systematically assess the current evidence available regarding knee instability after TKA to identify time to failure between primary and revision TKA. In addition, we considered the patient, surgical and implant characteristics of primary TKA patients revised for knee instability, and investigated methods used for knee instability diagnosis. Methods A systematic search of six databases and the unpublished literature was performed. Studies referring to instability in post-operative primary TKA patients, reporting on revision TKA due to instability, and published or available between 2005 to 30-Mar-2015 were eligible for inclusion. Quantitative data for continuous variables were pooled in statistical meta-analyses. Results A total of 1841 unique studies were identified, 42 of which met the selection criteria and a total of 22 studies included in the review. Time to failure between primary and revision TKA was 44.7 months (95% CI [33.8, 55.7]), and the weighted mean age at time of revision surgery was 67.6 years (95% CI [65.38, 69.75]). A gender distribution was identified, with approximately 16.4% more females revised for instability, however this was unable to be corrected for the baseline population. The majority of studies used a combination of radiographic and clinical testing to diagnose knee instability. Conclusion Research on knee instability following primary TKA reported early failure and subsequent revision knee surgery. The need for revision due to instability was frequently reported in a younger patient cohort and most commonly in female TKA patients. Early revision at a younger age highlights the severe implications of an unstable knee.
Mid-term migration of a cementless, porous acetabular cup: A 5 year Radiostereometric analysis
Purpose 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
Arthroscopic Chondral Debridement Using Radiofrequency Ablation for Patellofemoral Compartment Pathology
The purpose of this Technical Note is to introduce a surgical technique using a fluid pressure pump, mid-lateral portal, and radiofrequency ablation for visualization, assessment, and subsequent, accurate/adequate removal of patellofemoral articular lesions for the treatment of patellofemoral compartment pathology. With the patient in the supine position, and an inflated thigh tourniquet, standard lateral and medial portals are made. The medial-femoral compartment, notch, lateral-femoral compartment, and patellofemoral compartments are assessed. If pathology is seen within the patellofemoral compartment, a mid-lateral portal is made if chondral pathology cannot be addressed thoroughly. Addressing chondral pathology to achieve chondral stability is then performed using a combination of the radiofrequency ablator and chondrotome. This technique provides greater visibility and access to accurately and thoroughly smooth chondral pathology.
The Use of Scoring Systems in Knee Arthroplasty: A Systematic Review of the Literature
Background The primary purpose of this systematic review was to clarify and quantify scoring system utilization in knee arthroplasty literature. In addition, the study considered the frequency and relationship of score use in articles published across a range of orthopedic journals, and the influence of study design, level of evidence, primary research topic, and study country of origin on the scoring system used. Methods A systematic search of 8 electronic databases was performed to identify publications of clinical studies involving knee arthroplasty, in which a scoring system was used to assess patient outcomes. Results Of the 1994 unique publications identified, 438 met the selection criteria. Identified articles reported a total of 86 scoring systems, 5 of which were reported in greater than 10.0% of included studies. The 1989 Knee Society Score was markedly the most utilized scoring system (58.7%). Use of the Knee Society Score was significantly associated with orthopedic journal impact factor (IF; P =.001), with greater use observed in journals of lower IF. Use of the Western Ontario and McMaster Universities Osteoarthritis Index escalated with increasing IF; however, no statistically significant association was observed. A preference for scoring systems developed in the country of residence of the first author was also identified. Conclusions A large number of scoring systems are used to assess knee arthroplasty patients; however, 5 scores are consistently reported. By identifying and quantifying scoring system use, this review hopes to stimulate regularity in score usage to allow for improvements in comparability of clinician and patient-reported outcome measures in the knee arthroplasty literature.
Criteria used for diagnosis of adhesive capsulitis of the shoulder: A scoping review protocol
Review objective: The objective of this scoping review is to locate and summarize the current criteria used in the diagnosis of adhesive capsulitis of the shoulder in recent academic literature. Furthermore, we aim to explore differences, if any, in the criteria used across treating professions, study country of origin and study level of evidence.
Surgical site infection in overweight and obese Total Knee Arthroplasty patients
Purpose: 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.
Blood Loss in Total Knee Arthroplasty
Patients undergoing total knee arthroplasty (TKA) have expected blood loss during and after surgery. The morbidity associated with blood loss and the burden of blood transfusions in adult arthroplasty necessitates preoperative optimization as routine practice. Current literature remains inconclusive on which TKA surgical instrumentation techniques are effective in minimizing perioperative blood loss, and consequently lower transfusion rates. The primary objective of this retrospective review, of a prospective randomized cohort study, was to compare surgical and patient factors, and their influence on blood loss and transfusions rates, between one type of patient-specific instrumentation (PSI), navigated computer-assisted surgery (CAS), and conventional TKA surgical techniques. A cohort of 128 matched patients (38 PSI, 44 CAS, 46 conventional surgeries) were compared. Preoperative factors analyzed included; age, gender, body mass index, preoperative hemoglobin (Hb) (g/L), international normalized ratio, use of anticoagulants and comorbid bleeding diathesis. Maximal Hb drop and transfusion requirements were compared on day 1 to 3. Perioperative factors collected included: surgical time, tourniquet time, drain output, in situ drain time, order of tibia or femoral cut, and intraoperative loss from suction. The three groups did not differ on the preoperative patient demographics examined. The difference between preoperative Hb and the lowest postoperative Hb readings did not differ between study groups (p = 0.39). There are no statistically significant differences in blood loss when comparing PSI versus CAS versus conventional TKA. Although emerging evidence on PSI is encouraging, the PSI technique for TKA does not result in reduced blood loss. The study was registered with ClinicalTrials.gov: NCT01145157.
The influence of diabetes mellitus and obesity on upper limb arthroplasty outcomes: A systematic review protocol
Review question/objective: The objective of this review is to locate and synthesize the best available evidence investigating the impact of selected comorbidities on upper limb arthroplasty outcomes. The review question is: Are patients with diabetes mellitus or obesity at an increased risk of complications and/or poorer postoperative outcomes following total shoulder, reverse total shoulder and total elbow arthroplasty?
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 January 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); and 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 6 months or longer (RR = 3.81; 95% CI = 1.45–10.05; 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 = 0.80–2.56; 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.
The impact of weight loss interventions on disordered eating symptoms in people with overweight and obesity: a systematic review & meta-analysis
Background: It is unclear whether weight loss interventions worsen disordered eating in people living with overweight/obesity. We aimed to systematically evaluate the association between weight loss interventions and disordered eating. Methods: Six databases were searched from inception until September 2024. Trials of weight loss interventions in people with overweight/obesity were included if they reported a validated score for disordered eating on either the Eating Disorder Examination Interview or the Eating Disorder Examination Questionnaire pre- and post-intervention. Interventions included behavioural weight loss programmes (BWL) and pharmacotherapy licenced for weight loss, with or without concurrent psychological support, provided for at least 4 weeks. Pooled standardised mean differences (SMD) in scores of disordered eating were calculated using random effects meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool and the Newcastle–Ottawa scale for randomised and single-arm trials, respectively (PROSPERO ID: CRD42023404792). Findings: Thirty-eight studies with 66 eligible arms (61 interventions: 29 BWL, 11 BWL + pharmacotherapy, 20 BWL + psychological intervention, 1 pharmacotherapy + psychological intervention) and 3364 participants in total were included. The mean weight change was −4.7 kg (95% CI: −5.7, −3.7). Compared with baseline, disordered eating scores improved by −1.47 SMD units (95% CI: −1.67, −1.27, p < 0.001, I2 = 94%) at intervention completion (median of 4 months). Seven randomised trials that directly compared a weight loss intervention to no/minimal intervention reported an improvement of −0.49 SMD units (95% CI, −0.93, −0.04, p = 0.0035, I2 = 73%). Sub-group analyses showed: (a) disordered eating scores improved more in people with an eating disorder at baseline compared with people without high scores, (b) no clear evidence that the association depended upon intervention type, and (c) disordered eating scores improved more in trials rated at low overall RoB. Interpretation: Despite heterogeneity in effect size, weight loss interventions consistently improved disordered eating scores. These findings provide reassurance that weight loss interventions might not worsen disordered eating and may improve it. Funding: Novo Nordisk UK Research Foundation Doctoral Fellowship in Clinical Diabetes.
Electronic cigarettes for smoking cessation
Background: Electronic cigarettes (ECs) are handheld electronic vaping devices that produce an aerosol by heating an e-liquid. 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 safety, tolerability, and effectiveness of using EC to help people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments, and no treatment. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 February 2024 and the Cochrane Tobacco Addiction Group's Specialized Register to 1 February 2023, reference-checked, and contacted study authors. Selection criteria: We included trials randomizing people who smoke to an EC or control condition. We included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report an eligible outcome. Data collection and analysis: We followed standard Cochrane methods for screening and data extraction. We used the risk of bias tool (RoB 1) and GRADE to assess the certainty of evidence. Critical outcomes were abstinence from smoking after at least six months, adverse events (AEs), and serious adverse events (SAEs). Important outcomes were biomarkers, toxicants/carcinogens, and longer-term EC use. 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 pairwise and network meta-analyses (NMA). Main results: We included 90 completed studies (two new to this update), representing 29,044 participants, of which 49 were randomized controlled trials (RCTs). Of the included studies, we rated 10 (all but one contributing to our main comparisons) at low risk of bias overall, 61 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. Nicotine EC results in increased quit rates compared to nicotine replacement therapy (NRT) (high-certainty evidence) (RR 1.59, 95% CI 1.30 to 1.93; I2 = 0%; 7 studies, 2544 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6 more). The rate of occurrence of AEs is probably similar between groups (moderate-certainty evidence (limited by imprecision)) (RR 1.03, 95% CI 0.91 to 1.17; I2 = 0%; 5 studies, 2052 participants). SAEs were rare, and there is insufficient evidence to determine whether rates differ between groups due to very serious imprecision (RR 1.20, 95% CI 0.90 to 1.60; I2 = 32%; 6 studies, 2761 participants; low-certainty evidence). Nicotine EC probably results in increased quit rates compared to non-nicotine EC (moderate-certainty evidence, limited by imprecision) (RR 1.46, 95% CI 1.09 to 1.96; I2 = 4%; 6 studies, 1613 participants). In absolute terms, this might lead to an additional three quitters per 100 (95% CI 1 to 7 more). There is probably little to no difference in the rate of AEs between these groups (moderate-certainty evidence) (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 5 studies, 840 participants). There is insufficient evidence to determine whether rates of SAEs differ between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I2 = 0%; 9 studies, 1412 participants; low-certainty evidence). Compared to behavioural support only/no support, quit rates may be higher for participants randomized to nicotine EC (low-certainty evidence due to issues with risk of bias) (RR 1.96, 95% CI 1.66 to 2.32; I2 = 0%; 11 studies, 6819 participants). In absolute terms, this represents an additional four quitters per 100 (95% CI 3 to 5 more). There was some evidence that (non-serious) AEs may be more common in people randomized to nicotine EC (RR 1.18, 95% CI 1.10 to 1.27; I2 = 6%; low-certainty evidence; 6 studies, 2351 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 0.93, 95% CI 0.68 to 1.28; I2 = 0%; 12 studies, 4561 participants; very low-certainty evidence). Results from the NMA were consistent with those from pairwise meta-analyses for all critical outcomes. There was inconsistency in the AE network, which was explained by a single outlying study contributing the only direct evidence for one of the nodes. 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 both 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 or no treatment also suggests benefit, but is less certain due to risk of bias inherent in the study design. Confidence intervals were, for the most part, wide for data on AEs, SAEs, and other safety markers, with no evidence for a difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT, but low-certainty evidence for increased AEs compared with behavioural support/no support. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longer, larger studies are needed to fully evaluate EC safety. Our included studies tested regulated nicotine-containing EC; illicit products and/or products containing other active substances (e.g. tetrahydrocannabinol (THC)) may have different harm profiles. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this 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.
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.