Identifying the need for specialized palliative care in adult cancer patients - development and validation of a screening procedure based on proxy assessment by physicians and filter questions.

BACKGROUND: One challenge in caring for cancer patients with incurable disease is the adequate identification of those in need for specialized palliative care (SPC). The study's aim was to validate an easy to use phenomenological screening tool. METHODS: The German tool is based on the National Comprehensive Cancer Network (NCCN) Palliative Care guidelines and contains ten items in five domains that focus e.g. on diagnosis, functional status, complications, comorbidities, and palliative care relevant problems such as symptom management, distress, and support of family and team members. Sum score ranges from 0 to 14 (no need to great need). Assessment to identify SPC needs was done in university hospital wards between 1 and 08/2017 by health care professionals on admission of the patient if the disease was incurable and expected prognosis < 12 months. The Integrated Palliative Outcome Scale (IPOS, staff version), an outcome assessment instrument for palliative care that consists of ten items, served as external criterion; in sub samples inter-rater/test-retest were performed. RESULTS: Data from 208 patients with incurable disease and life expectancy < 12 months (54.8% female; average age 63.5 years, range 21-96) were assessed using the tool. The tool has good convergent validity; the correlation between the sum scores of IPOS and our tool showed a significant and substantial effect. The sum score was independent of the patient's age, gender and primary diagnosis. Patients who already were in contact with SPC had significantly higher screening scores than patients without. With a cut point of ≥ 5, 80.8% of the screened patients were in need for SPC. Cronbach's alpha was α = .600. Rater agreement (inter-rater, test-retest) varied between single items. Correlation coefficients showed significant substantial effects. CONCLUSIONS: This is the first validation of a screening procedure in German language identifying SPC needs of adult patients with advanced cancer and the first using filter questions as a pre-screening. Proxy assessment of SPC needs by physicians in cancer care settings is feasible and the suggested tool presents a valid instrument to trigger a PC consultation. TRIAL REGISTRATION: The study was not registered.

Public spirometry for primary prevention of COPD.

BACKGROUND: The most effective action for primary prevention of chronic obstructive lung disease is smoking cessation early enough. In secondary prevention, smokers with airway obstruction were more likely to quit smoking. The aim of this study was to evaluate the impact of a public spirometry on smoking habits in terms of primary prevention. METHODS: Spirometry with its medical analysis was offered to visitors of a local public event called 'Lange Nacht der Wissenschaften' ('Long night of sciences'). The impact of results on smoking habits was evaluated in all smokers with an anonymized questionnaire afterwards. RESULTS: Two hundred fifty-seven people with the median age of 30 years (interquartile range 22-46) were examined. Out of 44 current smokers (17.1%), only two individuals showed a prebronchodilator FEV1/forced vital capacity-value <0.7. Fourteen smokers stated to have an increased motivation to quit smoking whereas 28 smokers declared that their motivation to quit smoking was independent of spirometry result. These smokers were significantly younger (median age 28 vs. 40 years, P = 0.025) without differences in spirometry results or smoking habits. CONCLUSION: In an unselected population with a high amount of younger adults, normal spirometry did not show a short-term benefit for primary prevention of chronic obstructive lung disease in terms of increasing motivation to quit smoking.

Confocal laser endomicroscopy for diagnosing lung cancer in vivo.

Confocal laser endomicroscopy is a novel endoscopic technique that may allow imaging of living cells in lung tissue in vivo. We assessed the potential of this technique for the detection of histology during screening bronchoscopy for lung cancer. 32 patients with suspected malignancies underwent bronchoscopy with endomicroscopy using acriflavine hydrochloride. Standardised areas and localised lesions were analysed by in vivo confocal imaging during bronchoscopy and biopsies were taken. Confocal images were graded and correlated prospectively with conventional histology from biopsies. Acriflavine hydrochloride yielded high-quality confocal images and strongly labelled airway epithelial cells. No side-effects were noted. 75,522 confocal images from 56 different locations were compared prospectively with histological data from biopsy specimens. Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and subcellular structures. Neoplastic changes could be predicted with high accuracy (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%). Confocal laser endomicroscopy with acriflavine is a novel diagnostic tool for the analysis of living cells during bronchoscopy and permits virtual histology of neoplastic changes in the airways with high accuracy. This technique may enable the rapid diagnosis of neoplasia during ongoing endoscopy in patients with suspected lung cancer.

Methylene blue-aided in vivo staining of central airways during flexible bronchoscopy.

BACKGROUND: The early diagnosis of malignant and premalignant changes of the bronchial mucosa remains a major challenge during bronchoscopy. Intravital staining techniques are not new. Previous small case series suggested that analysis of the bronchial mucosal surface using chromoendoscopy allows a prediction between neoplastic and nonneoplastic lesions. OBJECTIVES: The aim of the present study was to evaluate chromobronchoscopy as a method to identify malignant and premalignant lesions in the central airways in a prospective manner. METHODS: In 26 patients we performed chromoendoscopy with 0.1% methylene blue during ongoing flexible white light bronchoscopy. Circumscribed lesions in central airways were further analyzed by biopsies and histopathologic examination. RESULTS: In the majority of cases neither flat nor polypoid lesions in the central airways were stained by methylene blue. In particular, exophytic growth of lung cancer did not show any specific pattern in chromobronchoscopy. However, a specific dye staining was detected in one case where exophytic growth of metastatic colorectal cancer was present in the right upper lobe. In two other cases, a circumscribed staining was noted in unsuspicious mucosa. But histology revealed inflammation only. CONCLUSIONS: In contrast to previous studies, the present findings clearly indicate that chromobronchoscopy is not useful for early detection of malignant or premalignant lesions of the central airways.

Fluorescein-aided confocal laser endomicroscopy of the lung.

BACKGROUND: There are only few reports about confocal laser endomicroscopy (CLE) for pulmonary imaging. In these studies, in contrast to gastrointestinal endoscopy, CLE was performed without fluorescein. OBJECTIVES: The aim of the present study was to evaluate the value of fluorescein usage for CLE of the lung. METHODS: Fluorescein-aided CLE was performed in 15 consecutively recruited patients and in 4 young healthy volunteers with a miniprobe during flexible bronchoscopy. Before and after intravenous administration of fluorescein, central airways and alveolar structures were evaluated. RESULTS: Fluorescein administration did not permit imaging of epithelial cells in the central airways. In the lung periphery, alveolar walls and partially macrophages could be seen in native imaging, as expected. After administration of fluorescein, alveoli were almost filled with foam in areas with normal lung tissue. The origin of this foam was shown to be artificial. Furthermore, in patients with pathologies of the lung parenchyma, dark neoplastic and inflammatory cells adjacent to the alveolar walls were identified. No relevant side effects of fluorescein administration could be observed. CONCLUSIONS: Fluorescein-aided CLE of the lung appeared to be safe and well tolerated. While the lack of staining of cells in the central airways was a major limitation, it permitted analysis of the lung interstitium and alveolar space and thus emerges as a new approach for the in vivo analysis of interstitial lung diseases.

Adherence to continuous positive airway pressure therapy for obstructive sleep apnea: impact of patient education after a longer treatment period.

BACKGROUND: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA) but it is often cumbersome so that adherence to CPAP therapy is limited. OBJECTIVES: We evaluated adherence to CPAP therapy after an additional educative intervention in OSA patients after a longer treatment period. METHODS: A short patient information program covering many aspects of symptoms, consequences and treatment of OSA was created, and standardized information sessions were developed to be given by an experienced sleep physician to >6,000 participants of patient support group meetings throughout Germany. They also received a booklet containing the essential information of the lectures. Of the 526 randomly selected members of these support groups receiving the anonymized questionnaire by mail, 475 CPAP patients sent the questionnaire back. Of these CPAP patients, 243 participated in a lecture und and had received a booklet (information group) and 232 CPAP patients had not attended a lecture (control group). RESULTS: In the information group, a significantly higher daily usage of CPAP devices (6.9 +/- 0.9 h/day) was reported compared with the control group (5.7 +/- 1.3 h/day; p < 0.001). Furthermore, the score in the Epworth Sleepiness Scale (ESS) was found to be significantly lower in the information group (median ESS = 6, interquartile range, IQR, 4-8 vs. median = 11, IQR 8-13; p < 0.001). CONCLUSIONS: Patients who attended our short information program showed a higher daily usage and a lower subjective daytime sleepiness. These results suggest that patients on CPAP therapy may benefit from education even after a longer treatment period.

Lung volumes and mean apnea duration in obstructive sleep apnea.

Former studies suggested that lung volumes might play a role in pathomechanisms of obstructive sleep apnea (OSA). Mean apnea duration (MAD) is a rarely investigated parameter in OSA but is possibly a surrogate of arousal threshold. The aim of this study was to evaluate the influence of lung volumes to MAD in OSA. In 69 patients with obstructive sleep apnea (51 male und 18 female, BMI 34.2+/-6.0 kg/m(2), age 53.6+/-9.7 years, AHI 43.1+/-21.1/h) we performed a polysomnography and pulmonary function testing in daytime. There was a significant correlation between MAD and residual volume (RV) (r=0.51; p<0.001), which was the highest correlation we found. In linear regression analysis RV remained the only independent variable with significant influence on MAD (p<0.001). We could show that RV seems to play a role in the mechanisms of apnea termination in terms of MAD. MAD reflects the time until a specific negative intrathoracic pressure is reached to induce an arousal. In this process dependency on RV could explain our results. Despite some limitations these results provide some new aspects in understanding pathophysiology of OSA.

Long-term improvement of insulin sensitivity during CPAP therapy in the obstructive sleep apnoea syndrome.

BACKGROUND: We recently demonstrated that continuous positive airway pressure (CPAP) therapy rapidly improves insulin sensitivity within 2 days in non-diabetic patients with obstructive sleep apnea syndrome. In these very patients we investigated whether this improvement of insulin sensitivity is maintained during long-term CPAP therapy. MATERIAL/METHODS: After a mean of 2.9 years (963+/-98 days) of CPAP treatment, these patients were reevaluated and hyperinsulinemic euglycemic clamp studies were performed in those with regular and effective CPAP treatment. RESULTS: From the initial 31 patients 16 could be reevaluated. 4 patients did not use their devices regularly (CPAP usage <2.5 h/night), 2 patients had insufficient CPAP treatment (AHI > or =10/h). One patient had developed type 2 diabetes mellitus. In the remaining 9 patients who used their devices regularly and effective (mean CPAP usage 5.2+/-1.6 h/night, mean AHI 3.3+/-2.6/h), mean insulin sensitivity index (ISI) was significantly higher than the baseline ISI established 2.9 years before (10.6+/-7.0 vs. 6.3+/-5.6 micromol/kg x min; p=0.008). At baseline 7 out of 9 patients had an impaired fasting glucose, after 2.9 years of treatment 3 out of 9 patients still had an impaired fasting glucose. The mean body mass index (BMI) had remained unchanged (31.4+/-7.8 vs. 31.4+/-7.6 kg/m2; mean individual difference -0.02+/-1.9 kg/m2). CONCLUSIONS: OSA is a risk factor for impaired insulin sensitivity. CPAP treatment, when used regularly and with effective pressure, may improve insulin sensitivity over long time.

The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes.

BACKGROUND: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. OBJECTIVES: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. METHODS: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 +/- 21.3; body mass index (BMI) 37.3 +/- 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 +/- 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. RESULTS: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 +/- 2.94 vs. 2.74 +/- 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 +/- 0.6%; not significant). Fasting leptin levels showed no significant changes. CONCLUSIONS: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.

Serum hyaluronate correlates with histological progression in alcoholic liver disease.

OBJECTIVES: Chronic alcohol consumption may lead to the development of liver cirrhosis. Serum concentrations of hyaluronate were suggested as a predictor in chronic liver disease, but its power to distinguish between severity of fibrosis and inflammation had not been assessed. In order to evaluate hyaluronate as a marker to detect early stages of alcoholic liver disease and to establish a possible correlation with hepatic histology, serum concentrations were measured by radioimmunoassay in 87 patients with biopsy-proven fatty liver, fatty liver and mild fibrosis, fatty liver and inflammation, severe fibrosis and inflammation, and cirrhosis, and in 12 non-alcoholic control subjects. In addition, serum hyaluronate was determined in 40 non-cirrhotic alcoholic patients with either a normal serum aspartate aminotransferase (AST) or an AST elevated at least two-fold. RESULTS: Serum hyaluronate increased significantly with advanced stages of alcoholic liver disease, while levels in patients with fatty liver were elevated only slightly without reaching significance. Hyaluronate correlated well with histological stage and was highly sensitive for detecting fibrosis in general and perivenular fibrosis as an indicator of progression to cirrhosis. Hyaluronate levels were not influenced by AST levels. CONCLUSION: Serum hyaluronate is a good predictor of the presence of even moderate hepatic fibrosis in alcoholic liver disease, justifying its clinical use to assess morphological alterations of the liver in alcoholics.

Auto-CPAP therapy for obstructive sleep apnea: induction of microarousals by automatic variations of CPAP pressure?

STUDY OBJECTIVES: To investigate the frequency of microarousals (MA) associated with pressure changes during auto-CPAP therapy (APAP) for obstructive sleep apnea (OSA). DESIGN: Patients with OSA were studied by polysomnography during APAP therapy (Somnosmart). The MA were classified on the basis of concomitant changes in APAP pressure. SETTING: Sleep laboratory of a university hospital PARTICIPANTS: 30 patients with moderate to severe OSA. MEASUREMENTS AND RESULTS: The mean AHI during APAP was 4.7+/-4.7, the mean arousal index was 14.5+/-6.6 per hour. During epochs with a pressure variation greater than 0.5 mbar, significantly more MA occurred (0.30+/-0.17 MA per epoch) than in epochs with constant treatment pressure (0.10+/-0.054 MA per epoch; p<0.001). There were more MA during pressure-increase epochs than during pressure-decrease epochs (0.42+/-0.24 vs. 0.16+/-0.12 MA per epoch; p<0.001). 82.5 percent of the MA were not preceded by a significant change in pressure (at least 0.5 mbar within 30 sec.), 10.6% were associated with a significant prior increase and 6.9% with a significant prior decrease in pressure. The percentage of MA preceded by a significant pressure variation varied between 2.3% and 61%, with a mean of 18.9%. CONCLUSIONS: The overall frequency of MA was low, and in most individuals the relative amount of "pressure-associated MA" was not significant. However in some individuals it cannot be excluded that some additional MA may have been induced by pressure variations. Should it prove possible to prevent such "pressure-associated MA" by optimizing the regulation of APAP pressure, the overall clinical effect of APAP treatment may be improved.

Insulin resistance, hyperleptinemia, and obstructive sleep apnea in Launois-Bensaude syndrome.

OBJECTIVE: Launois-Bensaude Syndrome (LBS) is a very rare cause of obesity, characterized by a symmetrical accumulation of a very large number of lipomata in different regions of the body, excluding the face, the forearms, and the shanks. Obesity is known to be closely associated with insulin resistance, hyperleptinemia, and obstructive sleep apnea (OSA). We were interested in studying whether these conditions are also present in patients with obesity due to LBS with a similar frequency as in patients with "simple" truncal obesity. RESEARCH METHODS AND PROCEDURES: We performed polysomnography and hyperinsulinemic euglycemic clamp studies and measured serum leptin in three patients with LBS and in six patients with "simple" truncal obesity, matched for sex and body mass index (LBS group, 36.39 kg/m(2); controls, 35.82 kg/m(2)). RESULTS: Polysomnography revealed severe OSA in one LBS patient with marked "horsecollar lipomata." In the other LBS patients, no OSA could be demonstrated. The leptin levels of the two groups were comparable (LBS group, 36.39 microg/liter; controls, 37.18 microg/liter) and the insulin responsiveness index was also comparable in the two groups (LBS group, 3.47 micromol/kg. minute; controls, 3.79 micromol/kg. minute). DISCUSSION: Patients with LBS demonstrated similar metabolic features in terms of insulin sensitivity and hyperleptinemia as patients with "simple" truncal obesity. LBS is not strictly associated with OSA.