Muscle Reference Values From Thoracic and Abdominal CT for Sarcopenia Assessment: The Framingham Heart Study.

BACKGROUND: Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking. OBJECTIVE: The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia. MATERIALS AND METHODS: This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application. RESULTS: The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex. CONCLUSIONS: This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.

Association of Sarcopenia With Toxicity-Related Discontinuation of Adjuvant Endocrine Therapy in Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

PURPOSE: Sarcopenia, an age-related decline in muscle mass and physical function, is associated with increased toxicity and worse outcomes in women with breast cancer (BC). Sarcopenia may contribute to toxicity-related early discontinuation of adjuvant endocrine  therapy (aET) in women with hormone receptor-positive (HR+) BC but remains poorly characterized. METHODS AND MATERIALS: This multicenter, retrospective cohort study included consecutive women with stage 0-II HR+ BC who received breast conserving therapy (lumpectomy and radiation therapy) and aET from 2011 to 2017 with a 5-year follow-up. Skeletal muscle index (SMI, cm2/m2) was analyzed using a deep learning model on routine cross-sectional radiation simulation imaging; sarcopenia was dichotomized according to previously validated reports. The primary endpoint was toxicity-related aET discontinuation; logistic regression analysis evaluated associations between SMI/sarcopenia and aET discontinuation. Cox regression analysis evaluated associations with time to aET toxicity, ipsilateral breast tumor recurrence (IBTR), and disease-free survival (DFS). RESULTS: A total of 305 women (median follow-up, 89 months) were included with a median age of 67 years and early-stage BC (12% stage 0, 65% stage I). A total of 60 (20%) women experienced toxicity-related aET discontinuation. Sarcopenia was associated with toxicity-related early discontinuation of aET (odds ratio, 2.18; P = .036) and shorter time to aET toxicity (hazard ratio [HR], 1.62; P = .031). SMI or sarcopenia were not independently associated with IBTR or DFS; toxicity-related aET discontinuation was associated with worse IBTR (HR, 9.47; P = .002) and worse DFS (HR, 4.53; P = .001). CONCLUSIONS: Among women with early-stage HR+ BC who receive adjuvant radiation therapy and hormone therapy, sarcopenia is associated with toxicity-related early discontinuation of aET. Further studies should validate these findings in women who did not receive adjuvant radiation therapy. These high-risk patients may be candidates for aggressive symptom management and/or alternative treatment strategies to improve outcomes.

Echolocation click parameters of short-finned pilot whales (Globicephala macrorhynchus) in the wild.

Short-finned pilot whales (Globicephala macrorhynchus) are large, deep-diving predators with diverse foraging strategies, but little is known about their echolocation. To quantify the source properties of short-finned pilot whale clicks, we made 15 deployments off the coast of Tenerife of a deep-water hydrophone array consisting of seven autonomous time-synced hydrophone recorders (SoundTraps), enabling acoustic localization and quantification of click source parameters. Of 8185 recorded pilot whale clicks, 47 were classified as being recorded on-axis, with a mean peak-to-peak source level (SL) of 181 ± 7 dB re 1 µPa, a centroid frequency of 40 ± 4 kHz, and a duration of 57 ± 23 µs. A fit to a piston model yielded an estimated half-power (-3 dB) beam width of 13.7° [95% confidence interval (CI) 13.2°-14.5°] and a mean directivity index (DI) of 22.6 dB (95% CI 22.5-22.9 dB). These measured SLs and DIs are surprisingly low for a deep-diving toothed whale, suggesting we sampled the short-finned pilot whales in a context with little need for operating a long-range biosonar. The substantial spectral overlap with beaked whale clicks emitted in similar deep-water habitats implies that pilot whale clicks may constitute a common source of false detections in beaked whale passive acoustic monitoring efforts.

Why whales are big but not bigger: Physiological drivers and ecological limits in the age of ocean giants.

The largest animals are marine filter feeders, but the underlying mechanism of their large size remains unexplained. We measured feeding performance and prey quality to demonstrate how whale gigantism is driven by the interplay of prey abundance and harvesting mechanisms that increase prey capture rates and energy intake. The foraging efficiency of toothed whales that feed on single prey is constrained by the abundance of large prey, whereas filter-feeding baleen whales seasonally exploit vast swarms of small prey at high efficiencies. Given temporally and spatially aggregated prey, filter feeding provides an evolutionary pathway to extremes in body size that are not available to lineages that must feed on one prey at a time. Maximum size in filter feeders is likely constrained by prey availability across space and time.

Propofol sedation in Drug Induced Sedation Endoscopy without an anaesthesiologist â€" a study of safety and feasibility.

BACKGROUND: Propofol sedation in Drug Induced Sedation Endoscopy (DISE) of the upper airway of patients with obstructive sleep apnea (OSA) without the presence of anesthesiologist has not been done before. Propofol sedation is normally administered by an anesthesiologist. This is the first study of this new method. METHODOLOGY: Based on the positive experience with Nurse-administered Propofol Sedation (NAPS) for endoscopic procedures in the departments of gastroenterology we wanted to test the set-up as method of propofol sedation for DISE procedures in our Otorhinolaryngology (ORL) department. The ORL specialists and staff nurses that carry out DISE procedures all underwent a formalized education in Nurse-administered Propofol Sedation before the study. We included 200 patients with severe snoring and / or obstructive sleep apnea. They were referred for DISE examination prior to possible targeted surgery based on the findings. RESULTS: In our study the aforementioned ORL team successfully cared out propofol sedation without the presence of an anesthesiologist. All examinations were carried out according to plan. There were no adverse events during the procedures or in the following observational period. CONCLUSIONS: The NAPS method of sedation for DISE seems safe and feasible when performed by trained staff in a hospital setting.

Cerebral blood flow, oxygen metabolism, and lactate during hypoxia in patients with obstructive sleep apnea.

Study Objectives: Obstructive sleep apnea (OSA) is associated with increased risk of stroke but the underlying mechanism is poorly understood. We suspect that the normal cerebrovascular response to hypoxia is disturbed in patients with OSA. Methods: Global cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and lactate concentration during hypoxia were measured in patients with OSA and matched controls. Twenty-eight patients (82.1% males, mean age 52.3 ± 10.0 years) with moderate-to-severe OSA assessed by partial polysomnography were examined and compared with 19 controls (73.7% males, mean age 51.8 ± 10.1 years). Patients and controls underwent magnetic resonance imaging (MRI) during 35 min of normoxia followed by 35 min inhaling hypoxic air (10%-12% O2). After 3 months of continuous positive airway pressure (CPAP) treatment, 22 patients were rescanned. Results: During hypoxia, CBF significantly increased with decreasing arterial blood oxygen concentration (4.53 mL (blood)/100 g/min per -1 mmol(O2)/L, p < 0.001) in the control group, but was unchanged (0.89 mL (blood)/100 g/min per -1 mmol(O2)/L, p = 0.289) in the patient group before CPAP treatment. The CBF response to hypoxia was significantly weaker in patients than in controls (p = 0.003). After 3 months of CPAP treatment the CBF response normalized, showing a significant increase during hypoxia (5.15 mL (blood)/100 g/min per -1 mmol(O2)/L, p < 0.001). There was no difference in CMRO2 or cerebral lactate concentration between patients and controls, and no effect of CPAP treatment. Conclusions: Patients with OSA exhibit reduced CBF in response to hypoxia. CPAP treatment normalized these patterns.

Management of obstructive sleep apnea in Europe.

OBJECTIVES: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. METHODS: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. RESULTS: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. CONCLUSIONS: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.

Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST).

BACKGROUND: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. METHODS: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. RESULTS: At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. CONCLUSIONS: Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Medico-legal implications of sleep apnoea syndrome: driving license regulations in Europe.

BACKGROUND: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region. METHODS: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK). RESULTS: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome. CONCLUSION: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

Smoking cessation in patients with respiratory diseases: a high priority, integral component of therapy.

Smoking cessation is the one of the most important ways to improve the prognosis of patients with respiratory disease. The Task Force on guidelines for smoking cessation in patients with respiratory diseases was convened to provide evidence-based recommendations on smoking cessation interventions in respiratory patients. Based on the currently available evidence and the consensus of an expert panel, the following key recommendations were made. 1) Patients with respiratory disease have a greater and more urgent need to stop smoking than the average smoker, so respiratory physicians must take a proactive and continuing role with all smokers in motivating them to stop and in providing treatment to aid smoking cessation. 2) Smoking cessation treatment should be integrated into the management of the patient's respiratory condition. 3) Therapies should include pharmacological treatment (i.e. nicotine replacement therapy, bupropion or varenicline) combined with behavioural support. 4) Respiratory physicians should receive training to ensure that they have the knowledge, attitudes and skills necessary to deliver these interventions or to refer to an appropriate specialist. 5) Although the cost of implementing these recommendations will partly be offset by a reduction in attendance for exacerbations, etc., a budget should be established to enable implementation. Research is needed to establish optimum treatment strategies specifically for respiratory patients.

Essential communication skills in individual smoking cessation.

When dealing with smokers it is important to realize that nicotine addiction plays a major role. Minimal clinic smoking cessation advice by a physician is a powerful motivation to quit and even short intervention (<3 minutes) is effective especially when repeated. There is a dose-response relationship between the number and duration of sessions and quit rate. The optimum programme contains 4-5 sessions of 10-15 minutes duration during the first six weeks after quit day. It is essential that smokers select a target quit day and stop smoking completely on that day as even a few cigarettes per day in the first weeks are strongly related to relapse. Administration of nicotine replacement products or bupropion may double success rates. The communication with smokers should be emphatic and adjusted to the level of change. Barriers to successful smoking cessation and structured interventions are described. The use of the five As to motivated smokers and the five Rs to smokers not ready to quit is recommended. Telephone and written material may supplement clinic visits in the follow-up period.

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.

BACKGROUND: Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. OBJECTIVE: To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. RESULTS: Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). CONCLUSION: Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.

[Compliance of patients with chronic obstructive lung disease receiving oxygen therapy at home]. / Behandlingskomplians hos patienter med kronisk obstruktiv lungesygdom i behandling med ilt i hjemmet.

Twenty-nine patients with severe chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy (LTOT) were prospectively studied for compliance with therapy. Seven patients (24%) used oxygen < 16 hours/day and their mean 24-hour pulse oximetry showed mild hypoxaemia. In addition, we found that eight patients (28%) were smokers. We suggest that the follow-up of these patients should focus on the daily duration of the use of oxygen and cessation of smoking to optimise the effect of this therapy.

Sociodemographic predictors of success in smoking intervention.

AIM: To examine the role of sociodemographic factors as predictors of sustained smoking cessation for the population who volunteer to participate in intervention programmes. METHOD: Data for the 3575 smokers who participated in the CEASE (collaborative European anti-smoking evaluation) trial, a European multicentred study that used transdermal nicotine patches as an adjunct to smoking cessation in the chest clinic, were analysed. The effects of age, sex, smoking habit, socioeconomic status (housing conditions, education, and employment), disease, smoking habits of relatives, and baseline markers of tobacco use on sustained smoking cessation (self-reported abstinence and expired carbon monoxide < 10 parts per million) were assessed using logistic regression modelling (odds ratio (OR), 95% confidence interval (CI)). RESULTS: 477/3575 smokers were sustained abstainers one year after the intervention (overall success rate 13.3%). In the univariable logistic regression models an effect of active treatment on smoking cessation was observed (OR 1.50, 95% CI 1.15 to 1.96), and additional effects on outcome were found for age (OR 1.02, 95% CI 1.01 to 1.03), sex (men v women: OR 1.38, 95% CI 1.14 to 1.68), housing conditions (OR 1.43, 95% CI 1.25 to 1.65), current respiratory (OR 0.79, 95% CI 0.67 to 0.92) or cardiac disease (OR 0.46, 95% CI 0.28 to 0.75), and markers of tobacco use (cigarettes per day: OR 0.79, 95% CI 0.69 to 0.90; expired carbon monoxide: OR 0.98, 95% CI 0.97 to 0.99). Education and employment did not have a significant effect on the outcome. The effect of the variables associated with success in smoking cessation persisted after adjustment for covariates. CONCLUSION: Age, sex, and housing conditions have a major effect on smoking cessation in European smokers participating in smoking cessation programmes.

Smoking cessation with four nicotine replacement regimes in a lung clinic.

Smoking cessation is a key intervention for prevention of several lung diseases. The aim of the present study was to compare the effect of smoking cessation with nicotine replacement in a lung clinic in a low resource set-up suitable for implementation in other lung clinics. This was an open, randomized trial with 4 different nicotine replacement regimes combined with minimal behavioural support in daily routine. A total of 446 smokers (>9 cigarettes x day(-1)) were allocated to a nurse-conducted smoking cessation programme with 4 treatment arms: a 5-mg nicotine patch ("placebo"), a 15-mg nicotine patch, nicotine inhaler, and a 15-mg nicotine patch plus nicotine inhaler. Recommended use of the nicotine products were 3 months with the possibility of continuing use up to 9 months on an individual basis. Individual follow-up studies were scheduled after 2 and 6 weeks, 3, 6, 9 and 12 months. The 12-month point prevalence was 6% (5-mg patch (placebo)), 16% (15-mg patch) (p<0.05), 9% (inhaler) and 11% (15-mg patch plus inhaler), respectively. To conclude, the set-up investigated in this study which included minimal behavioural support with nicotine patches should be evaluated in other lung clinics, as it doubled success rate when compared to a placebo with a 1-yr point prevalence of 16% and also the resources used are limited.

Adequacy of oxygenation in a group of Danish patients with COPD on long-term oxygen therapy.

The aim of this study was to assess the adequacy of oxygenation in patients with chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy (LTOT) in Copenhagen county. Twenty-six patients were enrolled and assessed prospectively by 24-h pulse oximetry. Patients comprised seven males and 19 females with a mean age of 69 +/- 5 yrs, arterial oxygen tension of 6.5 +/- 0.6 kPa, forced vital capacity of 1.47 L, forced expiratory volume in one second of 0.5 +/- 0.2 L (22 +/- 9% of predicted) and St. George's Respiratory Questionnaire total score of 61 +/- 14. The mean 24-h arterial oxygen saturation measured by pulse oximetry (Sp,O2) was within normal limits (94 +/- 1%), but mild hypoxaemia with a mean Sp,O2 of 89 +/- 4% and a total of 12 +/- 15 desaturation episodes per patient were observed, mostly during daily activities. Multiple regression analysis revealed no significant predictors for patient oxygenation. In summary, 24-h pulse oximetry showed adequate oxygenation in this group of COPD patients on LTOT, though mild hypoxaemia was present during some daily activities.

Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society.

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.