RCT Evidence Research Articles

What is the RCT evidence for community first responders attending people who have had an out-of-hospital cardiac arrest?

What is the RCT evidence for community first responders attending people who have had an out-of-hospital cardiac arrest?

Labor Market Integration of Low-Educated Refugees: RCT Evidence from an Ambitious Integration Program in Sweden

This paper evaluates an ambitious and newly designed program for increased integration in Sweden. The purpose of the program is to help newly arrived, low-educated refugees into employment. The program includes four main components: (1) intensive initial language training, (2) work practice under close supervision, (3) job search assistance, and (4) extended cooperation between the local public sector and firms. An important feature of the program is that the demand side of the labor market, represented by the largest real estate company in Gothenburg, is involved in designing the program. Our evaluation is based on a randomized controlled trial, where potential participants in one of the first waves were randomly assigned to treatment and control groups. The paper presents results from the first two years after randomization. Using inference based on Fisher’s exact test, we show that the program has positive effects on employment: around 30% of the individuals in the treatment group are employed each month during the first year following the end of the program, compared to an average of approximately 15% in the control group.

Breaking Down Menstrual Barriers in Bangladesh; Cluster RCT Evidence on School Attendance and Psychosocial Outcomes of Adolescent Girls

Girls’ poor ability to manage menstrual health (MH) imposes barriers to education and general wellbeing, especially in low- and middle-income countries. This paper presents the results of the Ritu trial, a 2-year clustered randomized controlled trial, examining the effect of a multi-faceted menstrual health intervention in Bangladesh. We randomized 148 schools from one rural district, into one of three groups; i) receiving a school program (sanitation facilities, MH education and support); ii) a school program and a targeted household program (parental MH education); iii) or the control group. The primary beneficiaries are schoolgirls in grades 6 until 8, age 11-15. We measure short- to medium-term impacts on school attendance, a set of psychosocial outcomes, and menstrual health outcomes. We use three sources of school attendance data: information from administrative records; self-reported survey responses and data from spot-checks where someone from the research team would appear unannounced and on randomly selected dates at school to record attendance. We find significant treatment effects in both treatment arms. The Ritu trial significantly improved menstrual health outcomes. Moreover, it significantly reduced school absence rates and reduced the likelihood of dropping out of school before grade 8. The program also improved psychosocial wellbeing and empowerment during menses, but this did not translate into substantial improvement of general wellbeing and empowerment. We find little evidence that the additional household program generated larger effects than the school program alone – which is important for programming purposes given the substantial additional costs of the household intervention. Our findings show the school program was considerably more cost-effective than the combined program, both when measured in ‘additional years of schooling’ and ‘learning-adjusted years of schooling’. Even though MH programs are becoming more prevalent, supporting quantitative evidence on their impact is very limited. We show a positive impact of a menstrual health program on school attendance and other psychosocial outcomes of adolescent girls.

Does RCT evidence show that education and training of healthcare workers help prevent or minimize workplace aggression directed toward them?

Does RCT evidence show that education and training of healthcare workers help prevent or minimize workplace aggression directed toward them?

Does RCT evidence show that printed educational materials for healthcare professionals alter healthcare professionals' practice and/or patient outcomes?

Does RCT evidence show that printed educational materials for healthcare professionals alter healthcare professionals' practice and/or patient outcomes?

Does RCT evidence show that cash transfers or income-generating interventions improve access to food in low- and middle-income countries?

Does RCT evidence show that cash transfers or income-generating interventions improve access to food in low- and middle-income countries?

What are the effects of adding bupropion or fluoxetine to other treatments compared with using other treatments alone for people trying to quit smoking?

Limited RCT evidence suggests that adding bupropion or fluoxetine to nicotine replacement therapies (NRTs) or varenicline may have little effect on smoking cessation rates, adverse events, and other outcomes.

DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism

BackgroundThe interaction between genetic, epigenetic and environmental factors plays an important role in the aetiology of hypertension. GWAS and observational studies link the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) with hypertension, while riboflavin, the MTHFR cofactor, has been shown to reduce blood pressure and global DNA methylation in homozygous (TT genotype) individuals. It is currently unclear whether riboflavin modulates DNA methylation of other hypertension-related genes. ObjectivesTo compare DNA methylation of hypertension-related genes in adults stratified by MTHFR genotype and effect of riboflavin intervention in adults with the variant MTHFR 677TT genotype. MethodPyrosequencing was carried out for hypertension-related genes (ACE, AGTR1, GCK, GNA12, IGF2, MMP9 and NOS3) in blood samples from participants in previous trials (CC, n = 40; TT, n = 40). The effect of intervention with riboflavin (1.6 mg/d for16 weeks) or placebo on DNA methylation was investigated in adults with the variant MTHFR 677TT genotype (n = 80). ResultsIndividuals with the MTHFR 677TT v CC genotype had significantly higher average DNA methylation at NOS3 (+1.66%, P = 0.044). In response to riboflavin supplementation in TT individuals, there was an increase in average DNA methylation at IGF2 (+1.09%, P = 0.019) and a decrease at ACE (−0.44%, P = 0.021) in females only. Specific CpG sites were hypomethylated in GNA12 and hypermethylated in AGTR1. ConclusionThis study provides the first RCT evidence that riboflavin alters DNA methylation of hypertension-related genes in adults with the MTHFR 677TT genotype, providing some insight into mechanisms linking hypertension with the genotype-specific response of BP to riboflavin.

Review of Relative effectiveness assessments (REAs) of pharmaceuticals at the European network for health technology assessment (EUnetHTA): A first step towards a consolidated European perspective on comparative effectiveness & safety?

ObjectivesREAs from Joint Action (JA1−3) were reviewed and compared versus Health Technology Assessments (HTA) in France, Germany, UK, Italy. MethodsEUnetHTA REAs published until end of 2019 were identified. Leveraging information derived from the HTA bodies’ website key process (population; timing; national HTA bodies involved) and content characteristics (evidence base; comparative therapy, endpoints, subgroups) were determined and compared against national appraisals. ResultsAll twelve pharmaceutical EUnetHTA assessment finalized until end of 2019 were included with Ustekinumab being the most recent (October 2019) and Pazopanib the first assessment (September 2012). In all but three assessments EUnetHTA’s assessment did not cover the full EMA indication. Since JA3 time intervals between EMA approval and EUnetHTA assessment were < 80 days. Number of (co-)authoring HTA bodies ranged between 2 (in 6 REAs) and > 10 (Pazopanib). EUnetHTA did consider non – RCT evidence in 7 procedures; take a rather inclusive approach regarding appropriate comparative treatments; approach endpoints less restrictively than e.g. the German IQWiG/GBA; not apply a predetermined set of subgroups analyses. In seven REAs, national appraisal showed inhomogeneities across the 4 countries. National appraisals for Sotagliflozin and Ustekinumab were not yet available. ConclusionsA joint European HTA assessment has the potential to address the challenge of heterogeneity across the various national European HTA bodies and to determine joint European clinical development data standards that are aligned with regulatory requirements.

Ultrasound guidance for pediatric vein cannulation: an emergency nurse quality improvement initiative and registry

Background&#x0D; Between 10 and 25 percent of pediatric patients present to the emergency department (ED) with difficult to cannulate veins. Recent RCT evidence suggests that in pediatric patients assessed at being a predicted difficult IV start (by DIVA score of 3 or more), ultrasound guided catheter placement decreased the number of IV attempts, decreased time to successful IV placement, and improved first pass success, patient satisfaction, and catheter dwell time. Our QI project examines the specific learnings around ultrasound guided peripheral IV in pediatric patients and suggests opportunity for non-pediatric specialist hospitals to consider with the overall aim of minimizing IV attempts on all pediatric patients within our EDs.&#x0D; Building on a RCT led by Dr Curtis in pediatrics patients conducted at the Stollery from 2012-2014, a standardized ultrasound guided nurse performed procedure was implemented in 2016 at the University of Alberta and Stollery EDs, and expanded to the Royal Alexandra ED in 2017 and the Misericordia ED in 2019. Using the same education package and QI study methodology as previously reported in adult patients this study focused specifically on pediatric patients.&#x0D; Methods &#x0D; A quality improvement (QI) registry was utilized to track complications and success of pediatric patients at all sites. The aim was to assess for program success, and improve education, training, and procedural success as required. Staff who had achieved independent practice voluntarily completed a tracking form whenever an ultrasound procedure occurred. Completed forms were assessed on a continual basis for any opportunities for improvement. Qualitative feedback was also obtained from informal interviews, a focus group, and a survey of the trained nurses. Feedback was thematically analyzed and grouped into themes for reporting.&#x0D; Results &#x0D; There were no reported pediatric UGIV placed at the MCH and RAH during the study period. At the Stollery 126 cases were reported. Immediate insertion complications were noted in three cases as ‘pain or swelling at site’, and ‘unable to advance catheter’. In the first and second years of data collection the average number of traditional IV attempts prior to UGIV attempt decreased from 3.9 to 2.8; first ultrasound pass success increased from 65% to 86%; overall ultrasound success improved from 85% to 97.6% respectively. Increasing nurse skill was significant with a linear increase of first pass and overall success seen with increasing number of ultrasound starts: From 6-20 starts (54% first pass 64% overall success) through to &gt;150 starts (97% first pass and 100% overall). QI staff feedback included ensure adequate pediatric specific supplies such as longer length small gauge catheters, and a procedural focus of patient, provider, and assistant set up. Location of IV placement was noted to change in a number of cases from hand and A/C to forearm.&#x0D; Advice and Lessons Learned &#x0D; &#x0D; The key for staff to transition to procedural competance was to ensure initial and ongoing oportunities to place many ultrasound guided IVs (i.e. when time allows in all patients with non-optimal IV placement locations or with non-easy predicted tradititional IV starts)&#x0D; Further work is required at non specilaist hospitals with trained staff to increase ultrasound guided use in pedatric patients&#x0D; At all particapting sites work continues on unit level QI to minimize the number of IV attempts on all pedatric patients as well as work towards a cohort of available staff that are comforable and competent with ultrasound that can provide 24/7 unit coverage. (with limited numbers of trained staff there is increase burden on these staff to assist others while also completing their own nursing assignment.&#x0D;

Levels of evidence supporting drug, device, and other recommendations in the American Heart Association/American College of Cardiology guidelines

We abstracted recommendation statements from current ACC/AHA guideline documents (2008-2019). Two reviewers independently characterized each statement into categories based on its primary topic: pharmaceutical, device, non-invasive or minimally invasive therapeutic procedure, surgery, diagnostic invasive procedure or non-invasive imaging, laboratory, care strategies, health services or policy, history/physical examination, lifestyle or counseling. We determined the number and proportion of recommendations in each category characterized as level of evidence (LOE) A (supported by multiple RCTs), B (supported by a single RCT or observational data), and C (supported by expert opinion or limited data). Of 2934 recommendations from 29 clinical guideline documents, 784 (26.7%) were primarily about pharmaceuticals, 503 (17.1%) diagnostic invasive procedure or non-invasive imaging, 366 (12.5%) devices, 349 (11.9%) care strategies, 274 (9.3%) surgery, 216 (7.4%) therapeutic procedures, 162 (5.5%) lifestyle interventions or counseling, 160 (5.5%) health services, care delivery, or policy, 83 (2.8%) laboratory, and 37 (1.3%) elements of the history and physical. Across all recommendations, 257 (8.8%) were characterized as LOE A, with considerable variability by topic. 25.9% of lifestyle/counseling recommendations, 16.9% of lab recommendations, and 14.7% of drug recommendations were classified as LOE A, but <8% of recommendations in all other categories, including 5.5% of device recommendations, 6.0% of therapeutic procedure recommendations, 2.6% of surgery recommendations, and 5.0% of health services or policy recommendations. Less than 10% of current ACC/AHA guideline recommendations are supported by high quality evidence from RCTs, with substantial variability by topic and multiple areas with very few recommendations supported by high-quality evidence. Development and implementation of inexpensive methods for generating a higher volume of RCT evidence to support clinical practice are needed, especially in areas where there are not strong incentives to conduct RCTs.

Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype

DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p < 0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (−1.2%, p < 0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype.

Translating Surgical Transfusion Evidence into Practice: A Multicenter Prospective Observational Study

Background: Randomized controlled trials have confirmed the safety of a restrictive red-cell tranfusion threshold (8 g/dL) versus a liberal threshold in cardiac and orthopedic surgeries. We aim to examine whether these findings can be replicated with observational data and generalized to broader specialties and a lower threshold. Methods: This is a prospective observational study conducted in three region-representative hospitals in China. Inpatients aged ≥18 years undergoing surgeries from six red cell-consumptive specialties (2015–2016) were defined as the base population. Three criteria were used to derive an analytic population: no significant intraoperative bleeding (<500 mL); hemoglobin at 7–10g/dL; and stratified by specialties (CCV and nonCCV group). Propensity-score matching was used to minimize confounding effect when necessary. Findings: Of 36 607 patients, 3930 (10·7%) received transfusion. The transfusion rate significantly increased with the intraoperative bleeding and decreased with the hemoglobin (p trend <0·0001). After applying the three criteria and propensity-score matching, transfusion was unrelated with death (OR [95% CI]: CCV, 1·51 [0·25–9·23]; nonCCV, 1·41 [0·44–4·46]), composite complication (CCV, 1·36 [0·63–2·95]; nonCCV, 1·61 [0·98–2·66]), but was related with infection in nonCCV (2·15 [1·12–4·12]). Patient outcomes showed no significant differences after transfusions at hemoglobin of 7–8g/dL vs. 8–10g/dL. Interpretation: We have replicated the findings of transfusion RCTs in six specialties and a lower threshold. Tailoring both the design and analysis is crucial for using observational data to generalize RCT evidence into wide surgical transfusion practice. Funding Statement: The National Health and Family Planning Commission of China (no. 201402017). Declaration of Interests: Authors have nothing to disclose. Ethics Approval Statement: The need for written informed consent was waived by the institutional review board of Peking Union Medical College Hospital (the leading research site of MSCP; date: July 26th, 2013; no. S-574) considering that the project was a quality improvement endeavor and individual information was analyzed anonymously.

Does RCT evidence indicate that manualized Alcoholics Anonymous (AA) or other 12-step programs offer benefit over alternative interventions for people with alcohol use disorder?

Manualized Alcoholics Anonymous or other 12‐step programs are effective in terms of abstinence and may be at least as effective as other well‐established treatments for other outcomes. High‐certainty evidence shows that, for people with alcohol use disorder, manualized Alcoholics Anonymous (AA) or other 12‐step facilitation (TSF) programs compared with alternative interventions (both for five hours/week, five days a week, for three to six months) lead to more people being completely abstinent at 12 months (on average, 367 vs 304 per 1000 people), and this benefit seems to persist for at least 36 months. Very low‐certainty evidence suggests that the percentage of days abstinent may be higher with AA/TSF programs than with an alternative clinical intervention at 24 and 36 months (approx. 13% and 7%, respectively); it is unclear why similar benefit was not observed at 12 months. Low‐ to moderate‐certainty evidence suggests little to no difference in the period of abstinence at six months, in alcohol‐related consequences (physical, social, or psychological) at any time point, or in the number of drinks per drinking day at 12 and 24 months but probably favors AA/TSF at 36 months (by one drink). Results for the Addiction Severity Index may be better with AA/TSF programs than with an alternative clinical intervention at 6‐ and 12‐month follow‐up.

How effective is exercise as an adjunct to smoking cessation support for promoting smoking cessation in adults?

Low‐certainty evidence does not support the addition of exercise programs (typically in the form of group‐based cardiovascular‐type exercise supplemented by a home‐based exercise program) to smoking cessation support (typically in the form of a multisession cognitive‐behavioral smoking cessation program) for increasing smoking abstinence rates at six months or later (on average, 104 vs 97 per 1000 people). Very low‐certainty evidence also found little or no difference in relapse rates among people who had recently stopped smoking (on average, 140 vs 144 per 1000 people). RCT evidence is mixed but generally does not show benefit of an additional exercise program for rates of depression, anxiety, or cigarette withdrawal symptoms or cravings among people receiving smoking cessation support compared with people receiving smoking cessation support alone.

Abstract TMP14: Contemporary Use of IV Alteplase in Acute Ischemic Stroke Beyond 4.5 Hours of Stroke Onset in Clinical Practice is Rare

Introduction: Two RCTs conducted from 2010-2018 showed benefit in ischemic stroke (IS) of IV tPA &gt;4.5 h from last known well (LKW) using advanced imaging selection. Many subjects were wakeup strokes treated &lt; 4.5 h of symptom discovery (SxD). We assessed the frequency of IV tPA &gt; 4.5 h in the national GWTG-Stroke clinical registry during the same period as the RCTs were performed. Methods: We analyzed all IS hospitalizations between 1/1/09 - 10/1/18 at fully participating GWTG-Stroke sites to identify 219,565 patients at 1919 sites who received IV tPA (no thrombectomy) and had valid LKW, SxD and treatment times recorded. Table shows significant covariates (standardized differences &gt;10%) Results: Treatment beyond 4.5 h from LKW was rare, occurring in 2.19% (n=4798) of all tPA cases, and 50% of those treated were still within 4.5 h from SxD. The distribution of time to treatment in minutes was similar when stroke onset was defined by LKW compared to SxD (median (IQR) 134 (100-174) vs. 125 (94-163)) (Fig). The use of IV tPA at &gt;4.5 h from LKW as a proportion of all tPA cases treated varied substantially across sites (median (IQR) 1.7% (0-3.1%)) but fewer than ~10% of sites had more than 5% of their tPA use occurring beyond 4.5 h. Compared to &lt; 4.5 h, patients treated &gt;4.5 h differed in age, AF, arrival mode/time, stroke severity and hospital region (Table). Conclusions: During the past decade and prior to published RCT evidence that extended window IV tPA was effective, US sites in GWTG-Stroke rarely treated patients beyond the guideline-approved window of 4.5 h. It will be important to monitor adoption of extended window thrombolysis in the US, and determine if additional RCT data are required to change practice.

An evaluation of rectal artesunate for the pre-hospital management of severe malaria

ABSTRACT Introduction Severe falciparum malaria stills accounts for around half a million childhood deaths per year in sub-Saharan Africa. Prompt treatment of sick children close to home starting with artesunate given rectally by appropriately trained people can be lifesaving. Areas covered Rectal artesunate (RAS) has been developed for use in the WHO approved strategy of pre-referral intervention. This review covers the formulation, pharmacokinetics, safety, efficacy, and implementation of this drug. There is little RCT evidence and the only RCT has been controversial. It is unlikely that there will be further randomized studies in the field. There is a concern that the administration of a single dose of artesunate without adequate follow up therapy may encourage the emergence of artemisinin resistance. Expert opinion Artesunate is an essential drug and RAS is a very useful, potentially lifesaving formulation designed to be quickly administered in remote areas to severely unwell children by non-medical personnel. However, its use needs to be monitored and onward referral for definitive antimalarial treatment ensured.

Comparative effectiveness of vitamin D supplementation via buccal spray versus oral supplements on 25(OH)D concentrations: a systematic review

AbstractVitamin D (vitD) deficiency is the most common nutritional deficiency worldwide. Most patients are treated with oral vitD capsules (either vitD2 or vitD3). A few studies have reported equal efficacy of buccal spray vitD. This is a new formulation that is absorbed via the oral mucosa into the systemic circulation, bypassing the gastrointestinal route. The main objective of this systematic review was to identify RCT evidence for the comparative effectiveness of buccal spray versus oral vitD on serum 25-hydroxyvitaminD [25-OHD] concentrations and any adverse effects of buccal spray vitD. We have published an a priori protocol using Joanna Briggs Institute (JBI) methodology (PROSPERO CRD42018118580). A three-step search strategy to identify RCTs was conducted, which reported serum 25-OHD concentrations from five databases from 2008–2018. Retrieved abstracts were screened; included papers imported into JBI SUMARI and assessed for study quality (GRADE) by two authors. Meta-analysis was planned. Three RCTs met our inclusion criteria. Due to heterogeneity of studies, meta-analysis was not possible. In a RCT crossover study, mean serum 25-OHD concentrations were significantly higher in patients with malabsorption syndrome (n = 20) on 1000IU buccal spray + 117.8%(10.46, 95%CI6.89,14.03ng/ml) vs.1000IU oral vitD3 + 36.02%(3.96, 95%CI2.37, 5.56ng/ml) at 30days (p &lt; 0.0001). Mean serum 25-OHD were also significantly higher in healthy adults (n = 20) on buccal spray + 42.99%(7.995, 95%CI6.86,9.13ng/ml)vs.oral vitD3 + 21.72%(4.06, 95%CI3.41,4.71ng/ml) at 30days (p &lt; 0.0001). In another RCT crossover study, ANCOVA revealed no significant difference in the mean and SD change from baseline total 25-OHD concentrations in adults (n = 22) on 3000IU buccal spray vs. 3000IU oral vitD3 + 44%,26.15 (SD17.85) vs. + 51%,30.38 (SD17.91)nmol/l, respectively;F = 1.044, adjusted r20.493,p = 0.313 at 4 weeks. In a RCT, 800IU buccal spray was equally effective as 750IU oral vitD3 in children with neurodisabilities(n = 24) at 3 months. Both groups had a significant increase in 25-OHD; 11.5 ng/ml(median8–19) to 26.5(13.6–39)ng/ml and 15.5ng/ml(8–20) to 34.5(22–49)ng/ml, respectively (z = 150;p &lt; 0.0001). The overall certainty of evidence was very low to moderate. No adverse effects were reported. The evidence from these studies suggests that 800IU-3000IU doses of buccal spray vitD3 given daily may be an effective alternative as oral vitD3 in obtaining short-term haematological responses in serum 25-OHD concentrations. Buccal spray vitD3 may be a useful alternative for patients with intestinal malabsorption or dysphagia. Future research should compare buccal spray VD3 to intramuscular injections and confirm these findings in well-designed trials.

How does real-time video counseling compare with telephone counseling for adults attempting to quit smoking?

Current RCT evidence comparing real‐time video counseling with telephone counseling is insufficient to guide a clinical choice between the two. Very low‐certainty evidence derived from two trials with 608 participants suggests that counseling delivered by real‐time video is no more likely to lead to people quitting smoking than counseling provided over the telephone. Real‐time video counseling also made little or no difference in the number of quit attempts, intervention adherence, or therapeutic alliance or satisfaction when measured by scores. Of note, satisfaction, when measured in a recommendation‐to‐family‐or‐friend test, was greater among people receiving video counseling than in those given telephone counseling (on average, 970 vs 919 per 1000 people would recommend video counseling). Numbers of withdrawals and adverse events were not reported.

Can relapse prevention interventions help adults who have quit smoking while hospitalized to maintain abstinence?

RCT evidence regarding interventions to prevent relapse among adults who have quit smoking while hospitalized is insufficient to allow conclusions. Relapse prevention interventions, such as post‐discharge telephone or in‐person counseling/buddy support and nicotine patch therapy, do not appear to improve abstinence rates on follow‐up after discharge among patients who achieve abstinence in the hospital. In both behavioral and drug intervention trials, both control and intervention groups received a brief in‐hospital intervention before discharge. Due to uncertainty regarding allocation concealment and blinding of participants and outcome assessors, as well as small numbers of trials and participants, the quality of these trials is uncertain. In addition, generalizability of trial results may be limited, as all included trial participants were 50 to 60 years of age, all participants in one trial were women, and two trials comprised solely patients with cardiovascular disease. For effects of relapse prevention in other populations, see CCA 2613 (for pregnant women), 2615 (for adults who quit smoking alone), and 2616 (for adults who quit smoking after receiving assistance).