Process Evaluation of a Medical Student-Delivered Smoking Prevention Program for Secondary Schools: Protocol for the Education Against Tobacco Cluster Randomized Trial.

BACKGROUND: Most smokers start smoking during their early adolescence under the impression that smoking entails positive attributes. Given the addictive nature of cigarettes, however, many of them might end up as long-term smokers and suffering from tobacco-related diseases. To prevent tobacco use among adolescents, the large international medical students' network Education Against Tobacco (EAT) educates more than 40,000 secondary school students per year in the classroom setting, using evidence-based self-developed apps and strategies. OBJECTIVE: This study aimed to evaluate the long-term effectiveness of the school-based EAT intervention in reducing smoking prevalence among seventh-grade students in Germany. Additionally, we aimed to improve the intervention by drawing conclusions from our process evaluation. METHODS: We conduct a cluster-randomized controlled trial with measurements at baseline and 9, 16, and 24 months postintervention via paper-and-pencil questionnaires administered by teachers. The study groups consist of randomized schools receiving the 2016 EAT curriculum and control schools with comparable baseline data (no intervention). The primary outcome is the difference of change in smoking prevalence between the intervention and control groups at the 24-month follow-up. Secondary outcomes are between-group differences of changes in smoking-related attitudes and the number of new smokers, quitters, and never-smokers. RESULTS: A total of 11,268 students of both sexes, with an average age of 12.32 years, in seventh grade of 144 secondary schools in Germany were included at baseline. The prevalence of cigarette smoking in our sample was 2.6%. The process evaluation surveys were filled out by 324 medical student volunteers, 63 medical student supervisors, 4896 students, and 141 teachers. CONCLUSIONS: The EAT cluster randomized trial is the largest school-based tobacco-prevention study in Germany conducted to date. Its results will provide important insights with regards to the effectiveness of medical student-delivered smoking prevention programs at school. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13508.

Differences in twenty-four-hour profiles of blue-light exposure between day and night shifts in female medical staff.

Light is the strongest zeitgeber currently known for the synchronization of the human circadian timing system. Especially shift workers are exposed to altered daily light profiles. Our objective is the characterization of differences in blue-light exposures between day and night shift taking into consideration modifying factors such as chronotype. We describe 24-hour blue-light profiles as measured with ambient light data loggers (LightWatcher) during up to three consecutive days with either day or night shifts in 100 female hospital staff including 511 observations. Linear mixed models were applied to analyze light profiles and to select time-windows for the analysis of associations between shift work, individual factors, and log mean light exposures as well as the duration of darkness per day. Blue-light profiles reflected different daily activities and were mainly influenced by work time. Except for evening (7-9 p.m.), all time windows showed large differences in blue-light exposures between day and night shifts. Night work reduced the duration of darkness per day by almost 4 h (ß^ = -3:48 hh:mm, 95% CI (-4:27; -3.09)). Late chronotypes had higher light exposures in the morning and evening compared to women with intermediate chronotype (e.g. morning ß^ = 0.50 log(mW/m2/nm), 95% CI (0.08; 0.93)). Women with children had slightly higher light exposures in the afternoon than women without children (ß^ = 0.48, 95% CI (-0.10; 1,06)). Time windows for the description of light should be chosen carefully with regard to timing of shifts. Our results are helpful for future studies to capture relevant light exposure differences and potential collinearities with individual factors. Improvement of well-being of shift workers with altered light profiles may therefore require consideration of both - light at the workplace and outside working hours.

Reverse Remodelling of the Atria After Treatment of Obstructive Sleep Apnoea with Continuous Positive Airway Pressure: Evidence from Electro-mechanical and Endocrine Markers.

BACKGROUND: Recent studies have suggested a strong association between obstructive sleep apnoea (OSA) and atrial fibrillation (AF). However, the impact of continuous positive airway pressure (CPAP) therapy on reverse atrial remodelling in patients with OSA is poorly understood. We aimed to determine the impact of CPAP therapy on total atrial conduction time measured by PA tissue Doppler imaging (TDI) interval in patients without history of AF. METHODS AND RESULTS: Thirty-five patients with first diagnosed OSA (group 1) and 20 reference patients without OSA (group 2) were prospectively enrolled. Group 1 was divided into 25 patients with starting CPAP therapy (intervention group) and 10 patients without CPAP therapy (control group). PA-TDI interval, measured by tissue Doppler imaging, and B-type natriuretic-peptide (BNP) were determined at baseline and repeated after 30 days in group 1. Patients with OSA had a significantly longer PA-TDI interval (131.4±16.0 ms vs. 120.1±6.4 ms, p<0.001) compared to reference patients. PA-TDI interval shortened significantly after 30 days of CPAP therapy (131±17.1 ms vs. 124.6±15.7 ms, p<0.001), whereas no significant change was found in the control group (132.6±13.6 ms vs. 133.2±13.1 ms, p=0.31) and BNP-levels decreased significantly (39.1±50.7 pg/ml vs. 28.2±42.4 pg/ml, p<0.01), while BNP-levels remained unaffected after 30 days in control group (31.5±20 pg/ml vs. 34.4±20.5 pg/ml, p=0.41). CONCLUSIONS: Change in PA-TDI interval, as an indirect surrogate marker of atrial remodelling, suggests reverse atrial remodelling in patients with OSA and treated by CPAP. This effect may ensue from decreased atrial pressure or volume overload, as indicated by significantly reduced BNP levels. These observations suggest that the substrate pre-disposing to AF may be reversible and moreover can be measured by PA-TDI interval and BNP.

Endothelin receptor-antagonists suppress lipopolysaccharide-induced cytokine release from alveolar macrophages of non-smokers, smokers and COPD subjects.

Smoking-induced COPD is characterized by chronic airway inflammation, which becomes enhanced by bacterial infections resulting in accelerated disease progression called exacerbation. Alveolar macrophages (AM) release endothelin-1 (ET-1), IL-6, CCL-2 and MMP-9, all of which are linked to COPD pathogenesis and exacerbation. ET-1 signals via ETA- and ETB-receptors (ETAR, ETBR). This is blocked by endothelin receptor antagonists (ERAs), like bosentan, which targets both receptors, ETAR-selective ambrisentan and ETBR-specific BQ788. Therefore, ERAs could have anti-inflammatory potential, which might be useful in COPD and other inflammatory lung diseases. We hypothesized that ERAs suppress cytokine release from AM of smokers and COPD subjects induced by lipopolysaccharide (LPS), the most important immunogen of gram-negative bacteria. AM were isolated from the broncho-alveolar lavage (BAL) of n=29 subjects (11 non-smokers, 10 current smokers without COPD, 8 smokers with COPD), cultivated and stimulated with LPS in the presence or absence of ERAs. Cytokines were measured by ELISA. Endothelin receptor expression was investigated by RT-PCR and western blot. AM expressed ETAR and ETBR mRNA, but only ETBR protein was detected. LPS and ET-1 both induced IL-6, CCL-2 and MMP-9. LPS-induced IL-6 release was increased in COPD versus non-smokers and smokers. Bosentan, ambrisentan and BQ788 all partially reduced all cytokines without differences between cohorts. Specific ETBR inhibition was most effective. LPS induced ET-1, which was exclusively blocked by BQ788. In conclusion, LPS induces ET-1 release in AM, which in turn leads to CCL-2, IL-6 and MMP-9 expression rendering AM sensitive for ERAs. ERAs could have anti-inflammatory potential in smoking-induced COPD.

Impact of lung diseases on morbidity and mortality after transcatheter aortic valve implantation: insights from spirometry and body plethysmography.

BACKGROUND: The study aims to determine the impact of different lung diseases on morbidity and mortality after transcatheter aortic valve implantation (TAVI). METHODS: Transcatheter aortic valve implantation was performed transfemoral or transaxillary with CoreValve prosthesis or Edwards SAPIEN prosthesis in patients with symptomatic severe aortic valve stenosis and high surgical risk. Examinations comprised spirometry, body plethysmography echocardiography, and x-ray before TAVI. The primary study end point was death from any cause after TAVI. RESULTS: During follow-up of 750 ± 538 days, 63 of 212 patients died. Logistic European System for Cardiac Operative Risk Evaluation (hazard risk [HR] 1.032, P < .001), aortic mean gradient (HR 0.96, P < .001), chronic obstructive pulmonary disease (COPD; each degree of COPD: HR 1.436, P = .001), restrictive ventilatory disease (HR 2.252, P = .002), oxygen dependency (HR 3.291, P = .004), and noninvasive ventilation (HR 3.799, P = .005) were independent predictors of long-term mortality. Restrictive ventilatory disease was associated with lower left ventricular ejection fraction, higher B-type natriuretic peptide levels, and pulmonary edema. CONCLUSION: In patients undergoing TAVI, lung diseases are an independent predictor of all-cause mortality. In particular, oxygen dependency patients and patients with severe COPD and noninvasive ventilation indicate a dismal prognosis. Transcatheter aortic valve implantation seems to have a dubious prognostic benefit in these patients.

Sleep-disordered breathing decreases after opioid withdrawal: results of a prospective controlled trial.

An increased cardiovascular event rate in elderly patients under opioid medications was recently reported. One reason for this increase could be the occurrence of nocturnal apnea and hypoxia, as a consequence of sleep-disordered breathing (SDB). Using a controlled study, we prospectively analyzed SDB using polysomnography in a total of 18 patients before and after opioid withdrawal (opioid withdrawal group [OG]) and 14 patients before and after comprehensive pain management (without any strong-acting opioids) who served as the control group (CG). To analyze the differences, unpaired/paired t tests and Mann-Whitney U tests/Wilcoxon rank tests were used. At baseline, the OG presented more nocturnal apneas/hypopneas than the CG with an apnea-hypopnea index (AHI) of 41.4 ± 27.8 vs 21.8 ± 15.9 (P = 0.018). After treatment, the AHI decreased significantly only in the withdrawal group (OG: 16.7 ± 8.9; CG: 20.1 ± 12.9) (P < 0.01). Before treatment, none of the CG but half of the OG patients showed central apnea, which disappeared afterwards. A mean O2 saturation during rapid eye movement sleep lower than 90% was found in 27.5% of the OG patients before opioid withdrawal and in none of the patients after withdrawal (P < 0.01). The AHI was not significantly affected by body mass index, age, or sex. Obviously, nocturnal apnea and O2 desaturation occurred more frequently, as was clinically expected in patients with opioid intake; these findings may explain the opioid-associated cardiovascular morbidity. Thus, SDB may be a risk at lower opioid doses than hitherto described, and particular caution should be exercised in patients with comorbidities that might make them vulnerable to the consequences of SDB.

Difficult intubation and outcome after out-of-hospital cardiac arrest: a registry-based analysis.

BACKGROUND: Airway management during resuscitation attempts is pivotal for treating hypoxia, and endotracheal intubation is the standard procedure. This German Resuscitation Registry analysis investigates the influence of airway management on primary outcomes after out-of-hospital cardiac arrest, in a physician-based emergency system. METHODS: A total of 8512 patients recorded in the German Resuscitation Registry (2007-2011) were analyzed. The Return of Spontaneous Circulation After Cardiac Arrest (RACA) score was used to compare observed return of spontaneous circulation (ROSC) rates with the ROSC predicted by the score and to analyze factors influencing the primary outcome. Patients were classified into three groups: difficult intubation, impossible intubation, and a control group with normal airways. RESULTS: The observed ROSC matched the predicted ROSC in the group with difficult airways. The impossible intubation group had lower ROSC rates (31.3% vs. 40.5%; P < 0.05). Impossible intubation was more frequent in men (OR 2.28; 95% CI, 1.43-3.63; P = 0.001), young patients (OR 2.18; 95% CI, 1.26-3.76; P = 0.005) and those with trauma (OR 2.22; 95% CI, 1.01-4.85; P = 0.046). Fewer impossible intubations were reported when the emergency physicians were anesthesiologists (OR 0.65; 95% CI, 0.44-0.96; P = 0.028). If a supraglottic airway device was not used in the impossible intubation group, the observed ROSC (18.0%; 95% CI, 7.4-28.6%) was poorer than predicted (38.2%) (P < 0.05). CONCLUSIONS: Outcomes after resuscitation attempts are poorer when endotracheal intubation is not possible. Predictive factors for impossible intubation are male gender, younger age, and trauma. Supraglottic airway devices should be used at an early stage whenever these negative factors are present.

[Improvement of cardiopulmonary exercise capacity in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der kardiopulmonalen Leistungsfähigkeit bei Patienten mit obstruktivem Schlafapnoesyndrom unter CPAP-Langzeittherapie.

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is regarded as a cardiovascular risk factor. Therefore, cardiopulmonary exercise capacity in patients with OSAS before and under treatment with continuous positive airway pressure (CPAP) was investigated. PATIENTS AND METHODS: Cardiopulmonary exercise capacity was investigated in 36 patients with untreated OSAS using spiroergometry. A follow-up after at least 6 months was performed in 17 of these patients being treated with CPAP and in eight CPAP-neglecting patients, who served as controls. RESULTS: Maximum oxygen uptake ( O(2max)) was significantly reduced in all 36 patients with untreated OSAS (17.68 +/- 6.1 ml/min/kg) compared with reference values (30.72 +/- 4.9 ml/min/kg; p < 0.001). After an average of 305.7 +/- 104.8 nights of CPAP therapy, O(2max) rose from 15.33 +/- 4.8 to 18.53 +/- 6.9 ml/min/kg, whereas O(2max) remained unchanged in controls. Further spirometric parameters of exercise capacity as well as arterial blood pressure were also significantly improved under CPAP therapy. CONCLUSION: Cardiopulmonary exercise capacity is markedly reduced in patients with OSAS. Long-term CPAP therapy leads to a significant improvement of reduced cardiopulmonary exercise capacity in these patients.

Short-term effects of oral theophylline in addition to CPAP in mild to moderate OSAS.

Theophylline is effective in the treatment of central apneas and periodic breathing. In obstructive sleep apnea syndrome (OSAS), results of pharmacological monotherapy with theophylline are inconsistent. The present study investigates whether additional theophylline in patients with OSAS and continuous positive airway pressure (CPAP) therapy might improve ventilation, lower effective CPAP pressure levels or affect sleep architecture. Patients with mild to moderate OSAS (mean apnea index [AI] 12.8+/-11.7) and CPAP therapy (Autoset system; n=16, all male) received either 900 mg of oral sustained-release theophylline (T) or placebo (P) on two separate nights, 3 days apart, using a randomized double-blind crossover study design. There was no change in AI (T: 0.7+/-1.4 vs. P: 0.7+/-0.6/h; P=0.3) or apnea-hypopnea index (AHI; T: 4.3+/-3.3 vs. P: 4.5+/-3.7/h; P=0.84) when theophylline was added to CPAP therapy. We observed no difference in mean CPAP pressure (T: 6.9+/-2.1 vs. P: 6.7+/-1.9 cm H2O; P=0.7) or 95% pressure percentiles (T: 9.7+/-2.7 vs. P: 9.3+/-2.1cm H2O; P=0.3) when nights with theophylline were compared to placebo nights. Theophylline reduced significantly total sleep time (T: 290.6+/-58.9 vs. P: 338.0+/-40.1 min; P=0.02) and thus sleep efficiency (SE; T: 70.5+/-14.9%, P: 82.0+/-70.5%; P=0.005). Rapid eye movement and slow wave sleep were not affected. Oral theophylline did not show any additional effects on ventilation parameters or pressures in patients with mild to moderate OSAS once CPAP therapy has been successfully installed. SE was reduced with theophylline with unchanged sleep architecture. The role of oral theophylline may be in patients with predominately central apneas not eligible for ventilation therapy or severe cases.

[Early polysomnographic detection of congestive heart failure caused by aortic valve stenosis]. / Polysomnographische Früherkennung einer kardialen Dekompensation infolge hochgradiger Aortenklappenstenose.

BACKGROUND: Obstructive sleep apnea (OSAS) is assumed to be an independent cardiovascular risk factor, whereas central sleep apnea with Cheyne-Stokes breathing occurs in congestive heart failure and has a prognostic value. CASE REPORT: The case of a 74-year-old man with long-term continuous positive airway pressure treatment due to OSAS is reported. In a routine polysomnography central apneas and Cheyne-Stokes breathing without any clinical signs of heart failure were seen. Further investigations revealed a newly diagnosed aortic valve stenosis with good left ventricular function. Clinical signs of congestive heart failure came up 2 weeks after first diagnosed Cheyne-Stokes breathing. CONCLUSION: Cheyne-Stokes breathing can be observed in acute heart failure before occurrence of any clinical signs of congestive heart failure and should always lead to further investigations. The current understanding of pathophysiological pathways in Cheyne-Stokes breathing is reviewed.