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Skeletal #Muscles Do Not Undergo Apoptosis During Either #Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis

https://www.frontiersin.org/articles/10.3389/fphys.2018.01887/full

Muscle memory discovery ends 'use it or lose it' dogma

Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defined volume of cytoplasm, so when a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly. This phenomenon is known as the “myonuclear domain hypothesis.”

Recently, two independent models, one from rodents and the other from insects, have demonstrated that nuclei are not lost from skeletal muscle fibers when they undergo either atrophy or programmed cell death. These and other data argue against the current interpretation of the myonuclear domain hypothesis and suggest that once a nucleus has been acquired by a muscle fiber it persists.

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Injuries Associated With #Standing Electric #Scooter Use

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2722574

Twenty-seven patients were younger than 18 years (10.8%). Ten riders (4.4%) were documented as having worn a helmet, and 12 patients (4.8%) had either a blood alcohol level greater than 0.05% or were perceived to be intoxicated by a physician. Frequent injuries included fractures (79 [31.7%]), head injury (100 [40.2%]), and contusions, sprains, and lacerations without fracture or head injury (69 [27.7%]). The majority of patients (234 [94.0%]) were discharged home from the emergency department; of the 15 admitted patients, 2 had severe injuries and were admitted to the intensive care unit. Among 193 observed electric scooter riders in the local community in September 2018, 182 (94.3%) were not wearing a helmet.

Conclusions and Relevance Injuries associated with standing electric scooter use are a new phenomenon and vary in severity. In this study, helmet use was low and a significant subset of injuries occurred in patients younger than 18 years, the minimum age permitted by private scooter company regulations. These findings may inform public policy regarding standing electric scooter use.

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Human #Papillomavirus #Vaccination Before 13 and 15 Years of Age: Analysis of National Immunization Survey Teen Data

https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiy682/5265326

Human papillomavirus (HPV) vaccination is suboptimally used in the United States. Vaccination before the 13th birthday is recommended by the Advisory Committee on Immunization Practices and vaccination before the 15th birthday requires only 2 doses. We estimated the proportion of adolescents up to date for HPV vaccine using provider-verified vaccination data from the 2016 National Immunization Survey-Teen.

Only 16% of US adolescents completed HPV vaccination before turning 13, and 35% completed HPV vaccination before turning 15. With sexual activity initiation increasing throughout adolescence and higher immunogenicity for younger vaccinees, vaccination before the 13th birthday can provide better protection against HPV-related cancers.

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Effect of Intensive vs Standard Blood #Pressure Control on Probable #Dementia

https://jamanetwork.com/journals/jama/fullarticle/2723256

Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).

The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio HR, 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).

Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.

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External Validation of the #MEESSI Acute Heart #Failure Risk Score: A Cohort Study

https://annals.org/aim/article-abstract/2723394/external-validation-meessi-acute-heart-failure-risk-score-cohort-study

The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain.

The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 28.5% in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients.

External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations.

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#β-Blocker Therapy and Risk of Chronic Obstructive #Pulmonary Disease – A Danish Nationwide Study of 1·3 Million Individuals

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30004-5/fulltext

Highlights
•
Users of β-blockers had an overall 19·7% lower risk of COPD hospitalization compared to users of any other antihypertensive drug during follow-up.
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Users of β-blockers had an overall 44% lower risk of death from COPD compared to users of any other antihypertensive drug.
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Results from this study advocates changes in the present hesitation of treatment with β-blockers in patients at risk of or with concomitant COPD.

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Clinical Features of Non-obese, Apparently Healthy Japanese Men with Reduced #Adipose Tissue #Insulin Sensitivity

https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.2018-02190/5298594?redirectedFrom=fulltext

Adipose tissue insulin resistance is observed in obese subjects and is considered an early metabolic defect preceding insulin resistance in muscle and liver. While Asians readily develop metabolic disease without obesity, the clinical features of non-obese, apparently healthy Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated.

Based on the median ATIS value, subjects were divided into low- and high-FFA suppression groups. The low-FFA suppression group had moderate fat accumulation in abdominal subcutaneous adipose tissue and liver. Compared with the high-FFA group, they also had a lower fitness level, decreased insulin clearance, impaired insulin sensitivity in muscle, moderately elevated triglycerides, and lowered high-density lipoprotein cholesterol levels. All these factors were significantly correlated with ATIS. Hepatic insulin sensitivity was comparable between the two groups.

Conclusions
In non-obese, apparently healthy Japanese men, reduced ATIS was associated with moderate fat accumulation in subcutaneous fat and liver, lower insulin clearance, muscle insulin resistance, and moderate lipidemia. These data suggest that reduced ATIS may occur early in the development of metabolic syndrome, even in non-obese, apparently healthy men.

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Effect of #breakfast on #weight and energy intake: systematic review and meta-analysis of randomised controlled trials

https://www.bmj.com/content/364/bmj.l42

Meta-analysis of the results found a small difference in weight favouring participants who skipped breakfast (mean difference 0.44 kg, 95% confidence interval 0.07 to 0.82), but there was some inconsistency across trial results (I2=43%). Participants assigned to breakfast had a higher total daily energy intake than those assigned to skip breakfast (mean difference 259.79 kcal/day, 78.87 to 440.71; 1 kcal=4.18 kJ), despite substantial inconsistency across trial results (I2=80%). All of the included trials were at high or unclear risk of bias in at least one domain and had only short term follow-ups (mean period seven weeks for weight, two weeks for energy intake). As the quality of the included studies was mostly low, the findings should be interpreted with caution.

Conclusion This study suggests that the addition of breakfast might not be a good strategy for weight loss, regardless of established breakfast habit. Caution is needed when recommending breakfast for weight loss in adults, as it could have the opposite effect. Further randomised controlled trials of high quality are needed to examine the role of breakfast eating in the approach to weight management

The author of an accompanying opinion piece — a regular breakfast eater — concludes, "No harm can be done in trying out your own personal experiments in skipping breakfast."

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Cost‐effectiveness of combination disease‐modifying antirheumatics vs. tumour necrosis factor inhibitors in active #rheumatoid arthritis: TACIT trial

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23830

205 participants were recruited, 104 in the #cDMARDs arm, 101 in the TNFis arm. cDMARD arm participants with poor response at 6 months were offered TNFis; 46 (44%) switched. Relevant cost and outcome data were available for 93% of participants at 6 month follow‐up and 91‐92% at 12 month follow‐up. The cDMARDs arm had significantly lower total costs from all perspectives (6 month H&SC adjusted mean difference ‐£3615 (95% confidence interval ‐£4104 to ‐£3182); 12 month H&SC adjusted mean difference ‐£1930 (95% confidence interval ‐£2599 to ‐£1301)). The HAQ showed benefit to the cDMARDs arm at 12 months (‐0.16; 95% CI‐0.32 to ‐0.01); other outcomes/follow‐ups showed no differences.

Conclusion
Starting treatment with cDMARDs, rather than TNFis, achieves similar outcomes at significantly lower costs. Patients with active rheumatoid arthritis and meeting NICE criteria for expensive biologics can cost‐effectively be treated with combinations of intensive synthetic disease modifying drugs.

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Effects of Age and Sex of on Response to #Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary #Biliary Cholangitis

https://www.cghjournal.org/article/S1542-3565(19)30001-1/fulltext

Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival.

Younger patients (45 years or younger) had increased serum levels of transaminase than older patients (older than 45 years). Patients older than 45 years at time of treatment initiation had increased odds of a biochemical response to UDCA therapy, based on GLOBE score, compared to younger patients. The greatest odds of response to UDCA were observed in patients older than 65 years (odds ratio compared to younger patients 45 years or younger, 5.48; 95% CI, 3.92–7.67; P<.0001). Risk of liver transplant or death (compared to a general population matched for age, sex, and birth year) decreased significantly with advancing age: hazard ratio for patients 35 years or younger, 14.59 (95% CI, 9.66–22.02) vs hazard ratio for patients older than 65 years, 1.39 (95% CI, 1.23–1.57) (P<.0001). On multivariable analysis, sex was not independently associated with response or transplant-free survival.

Conclusion
In longitudinal analysis of 4355 adults in the Global PBC Study, we associated patient age, but not sex, with response to UDCA treatment and transplant-free survival. Younger age at time of PBC diagnosis is associated with increased risk of treatment failure, liver transplant, and death.

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Association of #Antibiotic Treatment With Outcomes in Patients Hospitalized for an #Asthma Exacerbation Treated With Systemic Corticosteroids

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2721036

Although professional society guidelines discourage use of empirical antibiotics in the treatment of asthma exacerbation, high antibiotic prescribing rates have been recorded in the United States and elsewhere

Compared with patients not treated with antibiotics, treated patients were older (median [IQR] age, 48 [36-61] vs 45 [32-57] years), more likely to be white (48.6% vs 40.9%) and smokers (6.6% vs 5.3%), and had a higher number of comorbidities (eg, congestive heart failure, 6.2% vs 5.8%). Those treated with antibiotics had a significantly longer hospital stay (median [IQR], 4 [3-5] vs 3 [2-4] days) and a similar rate of treatment failure (5.4% vs 5.8%). In propensity score–matched analysis, receipt of antibiotics was associated with a 29% longer hospital stay (length of stay ratio, 1.29; 95% CI, 1.27-1.31) and higher cost of hospitalization (median [IQR] cost, $4776 [$3219-$7373] vs $3641 [$2346-$5942]) but with no difference in the risk of treatment failure (propensity score–matched OR, 0.95; 95% CI, 0.82-1.11). Multivariable adjustment, propensity score weighting, and instrumental variable analysis as well as several sensitivity analyses yielded similar results.

Conclusions and Relevance Antibiotic therapy may be associated with a longer hospital length of stay, higher hospital cost, and similar risk of treatment failure. These results highlight the need to reduce inappropriate antibiotic prescribing among patients hospitalized for asthma

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Efficacy and safety of #statin therapy in #older people: a meta-analysis of individual participant data from 28 randomised controlled trials

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext

Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.
Interpretation

Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials

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#Fruit and #Vegetable Intake and Mortality in Adults undergoing Maintenance #Hemodialysis

https://cjasn.asnjournals.org/content/early/2019/01/30/CJN.08580718

Compared with the lowest tertile of servings per week (0–5.5, median 2), the adjusted hazard ratios for the middle (5.6–10, median 8) and highest (>10, median 17) tertiles were 0.90 (95% CI, 0.81 to 1.00) and 0.80 (95% CI, 0.71 to 0.91) for all-cause mortality, 0.88 (95% CI, 0.76 to 1.02) and 0.77 (95% CI, 0.66 to 0.91) for noncardiovascular mortality and 0.95 (95% CI, 0.81 to 1.11) and 0.84 (95% CI, 0.70 to 1.00) for cardiovascular mortality, respectively.

Conclusions Fruit and vegetable intake in the hemodialysis population is low and a higher consumption is associated with lower all-cause and noncardiovascular death.

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Association between suicidal #ideation and #suicide: meta-analyses of odds ratios, sensitivity, specificity and positive predictive value

https://www.cambridge.org/core/journals/bjpsych-open/article/association-between-suicidal-ideation-and-suicide-metaanalyses-of-odds-ratios-sensitivity-specificity-and-positive-predictive-value/D8A8A76A4AC052EEAF34E7EF44E20013

The expression of suicidal ideation is considered to be an important warning sign for suicide. However, the predictive properties of suicidal ideation as a test of later suicide are unclear.

The pooled sensitivity of suicidal ideation for later suicide was 41% (95% CI 35–48) and the pooled specificity was 86% (95% CI 76–92), with high between-study heterogeneity. Studies of suicidal ideation expressed by current and former psychiatric patients had a significantly higher pooled sensitivity (46% v. 22%) and lower pooled specificity (81% v. 96%) than studies conducted in non-psychiatric settings. The PPV among non-psychiatric cohorts (0.3%, 95% CI 0.1%–0.5%) was significantly lower (Q-value = 35.6, P < 0.001) than among psychiatric samples (3.9%, 95% CI 2.2–6.6).

Conclusions
Estimates of the extent of the association between suicidal ideation and later suicide are limited by unexplained between-study heterogeneity. The utility of suicidal ideation as a test for later suicide is limited by a modest sensitivity and low PPV.

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Computer simulations suggest that #prostate enlargement due to benign prostatic #hyperplasia mechanically impedes prostate cancer growth

https://www.pnas.org/content/116/4/1152

Prostate cancer and benign prostatic hyperplasia are common genitourinary diseases in aging men. Both pathologies may coexist and share numerous similarities, which have suggested several connections or some interplay between them.

The mechanical stress fields that originate as tumors enlarge have been shown to slow down their dynamics. Benign prostatic hyperplasia contributes to these mechanical stress fields, hence further restraining prostate cancer growth. We derived a tissue-scale, patient-specific mechanically coupled mathematical model to qualitatively investigate the mechanical interaction of prostate cancer and benign prostatic hyperplasia.

Our simulations show that a history of benign prostatic hyperplasia creates mechanical stress fields in the prostate that impede prostatic tumor growth and limit its invasiveness. The technology presented herein may assist physicians in the clinical management of benign prostate hyperplasia and prostate cancer by predicting pathological outcomes on a tissue-scale, patient-specific basis

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The neuroactive potential of the human #gut #microbiota in quality of life and depression

https://www.nature.com/articles/s41564-018-0337-x

The relationship between gut microbial metabolism and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota–gut–brain communication has mostly been explored in animal models, with human research lagging behind.

Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants.

Using a module-based analytical framework, we assembled a catalogue of neuroactive potential of sequenced gut prokaryotes. Gut–brain module analysis of faecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression.

Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.

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Compounded Topical Pain #Creams to Treat Localized Chronic #Pain: A Randomized Controlled Trial

https://annals.org/aim/article-abstract/2724041/compounded-topical-pain-creams-treat-localized-chronic-pain-randomized-controlled

Pain creams compounded for neuropathic pain (ketamine, gabapentin, clonidine, and lidocaine), nociceptive pain (ketoprofen, baclofen, cyclobenzaprine, and lidocaine), or mixed pain (ketamine, gabapentin, diclofenac, baclofen, cyclobenzaprine, and lidocaine), or placebo.

For the primary outcome, no differences were found in the mean reduction in average pain scores between the treatment and control groups for patients with neuropathic pain (−0.1 points [95% CI, −0.8 to 0.5 points]), nociceptive pain (−0.3 points [CI, −0.9 to 0.2 points]), or mixed pain (−0.3 points [CI, −0.9 to 0.2 points]), or for all patients (−0.3 points [CI, −0.6 to 0.1 points]). At 1 month, 72 participants (36%) in the treatment groups and 54 (28%) in the control group had a positive outcome (risk difference, 8% [CI, −1% to 17%]).

Compounded pain creams were not better than placebo creams, and their higher costs compared with approved compounds should curtail routine use.

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Comparing #Automated Office Blood #Pressure Readings With Other Methods of Blood Pressure Measurement for Identifying Patients With Possible Hypertension

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2723074

Automated office blood pressure (AOBP) measurement involves recording several blood pressure (BP) readings using a fully automated oscillometric sphygmomanometer with the patient resting alone in a quiet place

Data were compiled from 31 articles comprising 9279 participants (4736 men and 4543 women). In samples with systolic AOBP of 130 mm Hg or more, routine office and research systolic BP readings were substantially higher than AOBP readings, with a pooled mean difference of 14.5 mm Hg (95% CI, 11.8-17.2 mm Hg; n = 9; I2 = 94.3%; P < .001) for routine office systolic BP readings and 7.0 mm Hg (95% CI, 4.9-9.1 mm Hg; n = 9; I2 = 85.7%; P < .001) for research systolic BP readings. Systolic awake ambulatory BP and AOBP readings were similar, with a pooled mean difference of 0.3 mm Hg (95% CI, −1.1 to 1.7 mm Hg; n = 19; I2 = 90%; P < .001).

Conclusions and Relevance Automated office blood pressure readings, only when recorded properly with the patient sitting alone in a quiet place, are more accurate than office BP readings in routine clinical practice and are similar to awake ambulatory BP readings, with mean AOBP being devoid of any white coat effect. There has been some reluctance among physicians to adopt this technique because of uncertainty about its advantages compared with more traditional methods of recording BP during an office visit. Based on the evidence, AOBP should now be the preferred method for recording BP in routine clinical practice.

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Clinical Practice Guideline: #Tonsillectomy in Children (Update)

https://journals.sagepub.com/doi/full/10.1177/0194599818801757

The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should recommend watchful waiting for recurrent throat infection if there have been <7 episodes in the past year, <5 episodes per year in the past 2 years, or <3 episodes per year in the past 3 years. (2) Clinicians should administer a single intraoperative dose of intravenous dexamethasone to children undergoing tonsillectomy. (3) Clinicians should recommend ibuprofen, acetaminophen, or both for pain control after tonsillectomy.

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A Randomized Trial of #E-Cigarettes versus #Nicotine-Replacement Therapy

https://www.nejm.org/doi/full/10.1056/NEJMoa1808779?query=featured_home

A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.

CONCLUSIONS
E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support.