Parental provisioning drives brain size in birds.

Large brains support numerous cognitive adaptations and therefore may appear to be highly beneficial. Nonetheless, the high energetic costs of brain tissue may have prevented the evolution of large brains in many species. This problem may also have a developmental dimension: juveniles, with their immature and therefore poorly performing brains, would face a major energetic hurdle if they were to pay for the construction of their own brain, especially in larger-brained species. Here, we explore the possible role of parental provisioning for the development and evolution of adult brain size in birds. A comparative analysis of 1,176 bird species shows that various measures of parental provisioning (precocial vs. altricial state at hatching, relative egg mass, time spent provisioning the young) strongly predict relative brain size across species. The parental provisioning hypothesis also provides an explanation for the well-documented but so far unexplained pattern that altricial birds have larger brains than precocial ones. We therefore conclude that the evolution of parental provisioning allowed species to overcome the seemingly insurmountable energetic constraint on growing large brains, which in turn enabled bird species to increase survival and population stability. Because including adult eco- and socio-cognitive predictors only marginally improved the explanatory value of our models, these findings also suggest that the traditionally assessed cognitive abilities largely support successful parental provisioning. Our results therefore indicate that the cognitive adaptations underlying successful parental provisioning also provide the behavioral flexibility facilitating reproductive success and survival.

Does the implementation of an incentive scheme increase adherence to diabetes guidelines? A retrospective cohort study of managed care enrollees.

BACKGROUND: A novel incentive scheme based on a joint agreement of a large Swiss health insurance with 56 physician networks was implemented in 2018. This study evaluated the effect of its implementation on adherence to evidence-based guidelines among patients with diabetes in managed care models. METHODS: We performed a retrospective cohort study, using health care claims data from patients with diabetes enrolled in a managed care plan (2016-2019). Guideline adherence was assessed by four evidence-based performance measures and four hierarchically constructed adherence levels. Generalized multilevel models were used to examine the effect of the incentive scheme on guideline adherence. RESULTS: A total of 6'273 patients with diabetes were included in this study. The raw descriptive statistics showed minor improvements in guideline adherence after the implementation. After adjusting for underlying patient characteristics and potential differences between physician networks, the likelihood of receiving a test was moderately but consistently higher after the implementation of the incentive scheme for most performance measures, ranging from 18% (albuminuria: OR, 1.18; 95%-CI, 1.05-1.33) to 58% (HDL cholesterol: OR, 1.58; 95%-CI, 1.40-1.78). Full adherence was more likely after implementation of the incentive scheme (OR, 1.37; 95%-CI, 1.20-1.55), whereas level 1 significantly decreased (OR, 0.74; 95%-CI, 0.65 - 0.85). The proportions of the other adherence levels were stable. CONCLUSION: Incentive schemes including transparency of the achieved performance may be able to improve guideline adherence in patients with diabetes and are promising to increase quality of care in this patient population.

Evidence-based indicators for the measurement of quality of primary care using health insurance claims data in Switzerland: update of the SQUIPRICA working group.

BACKGROUND: The level of quality of care of ambulatory services in Switzerland is almost completely unknown. Since health insurance claims are the only nationwide applicable and available data source for this purpose, a set of 24 quality indicators (QI) for the measurement of quality of primary care has been previously developed and implemented. The present paper reports on an evidence-based update and extension of the initial QI set. METHODS: Established pragmatic 6-step process based on informal consensus and potential QI extracted from international medical practice guidelines and pre-existing QI for primary care. Experts rated potential QI based on strength of evidence, relevance for Swiss public health, and controllability in the Swiss primary care context. Feasibility of a preliminary set of potential new QI was tested using claims data of persons with basic mandatory health insurance at one of the largest Swiss health insurers. This test built the basis for expert consensus on the final set of new QI. Additionally, two diabetes indicators included in the previous QI set were re-evaluated. RESULTS: Of 23 potential new indicators, 19 of them were selected for feasibility testing. The expert group consented a final set of 9 additional QI covering the domains general aspects/efficiency (2 QI), diagnostic measures (1 QI), geriatric care (2 QI), osteoarthritis (1 QI), and drug safety (3 QI). Two pre-existing diabetes indicators were updated. CONCLUSIONS: Additional QI relating to overuse and intersectoral care aspects extend the options of measuring quality of primary care in Switzerland based on claims data and complement the initial QI set.

Does hospital volume affect outcomes after abdominal cancer surgery: an analysis of Swiss health insurance claims data.

BACKGROUND: Medical treatment quality has been shown to be better in high volume than in low volume hospitals. However, this relationship has not yet been confirmed in abdominal cancer in Switzerland and is relevant for referral of patients and healthcare planning. Thus, the present study investigates the association between hospital volumes for surgical resections of colon, gastric, rectal, and pancreatic carcinomas and outcomes. METHODS: This retrospective analysis is based on anonymized claims data of patients with mandatory health insurance at Helsana Group, a leading health insurance in Switzerland. Outcome parameters were length of hospital stay, mortality and cost during the inpatient stay as well as at 1-year follow-up. Hospital volume information was derived from the Quality Indicators dataset provided by the Swiss Federal Office of Public Health. The impact of hospital volume on the different treatment outcomes was statistically tested using generalized estimating equations (GEE) models, taking into account the non-independence of observations from the same hospital. RESULTS: The studies included 2'859 resections in patients aged 18 years and older who were hospitalized for abdominal cancer surgery between 2014 and 2018. Colon resections were the most common procedures (n = 1'690), followed by rectal resections (n = 709). For rectal, colon and pancreatic resections, an increase in the mean number of interventions per hospital and a reduction of low volume hospitals could be observed. For the relationship between hospital volume and outcomes, we did not observe a clear dose-response relationship, as no significantly better outcomes were observed in the higher-volume category than in the lower-volume category. Even though a positive "routine effect" cannot be excluded, our results suggest that even hospitals with low volumes are able to achieve comparable treatment outcomes to larger hospitals. CONCLUSION: In summary, this study increases transparency on the relationship between hospital volume and treatment success. It shows that simple measures such as defining a minimum number of procedures only might not lead to the intended effects if other factors such as infrastructure, the operating team or aggregation level of the available data are not taken into account.

Life history, cognition and the evolution of complex foraging niches.

Animal species that live in complex foraging niches have, in general, improved access to energy-rich and seasonally stable food sources. Because human food procurement is uniquely complex, we ask here which conditions may have allowed species to evolve into such complex foraging niches, and also how niche complexity is related to relative brain size. To do so, we divided niche complexity into a knowledge-learning and a motor-learning dimension. Using a sample of 78 primate and 65 carnivoran species, we found that two life-history features are consistently correlated with complex niches: slow, conservative development or provisioning of offspring over extended periods of time. Both act to buffer low energy yields during periods of learning, and may thus act as limiting factors for the evolution of complex niches. Our results further showed that the knowledge and motor dimensions of niche complexity were correlated with pace of development in primates only, and with the length of provisioning in only carnivorans. Accordingly, in primates, but not carnivorans, living in a complex foraging niche requires enhanced cognitive abilities, i.e., a large brain. The patterns in these two groups of mammals show that selection favors evolution into complex niches (in either the knowledge or motor dimension) in species that either develop more slowly or provision their young for an extended period of time. These findings help to explain how humans constructed by far the most complex niche: our ancestors managed to combine slow development (as in other primates) with systematic provisioning of immatures and even adults (as in carnivorans). This study also provides strong support for the importance of ecological factors in brain size evolution.

Impact of intraoperative fluid administration on outcome in patients undergoing robotic-assisted laparoscopic prostatectomy--a retrospective analysis.

BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) gained much popularity during the last decade. Although the influence of intraoperative fluid management on patients' outcome has been largely discussed in general, its impact on perioperative complications and length of hospitalization in patients undergoing RALP has not been examined so far. We hypothesized that a more restrictive fluid management might lead to a shortened length of hospitalization and a decreased rate of complications in our patients. METHODS: Retrospective analysis of data of 182 patients undergoing RALP at an University Hospital (first series of RALP performed at the center). RESULTS: The amount of fluid administered was initially normalized for body mass index of the patient and the duration of the operation and additionally corrected for age and the interaction of these variables. The application of crystalloids (multiple linear regression model, estimate = -0.044, p = 0.734) had no effect on the length of hospitalization, whereas a negative effect was found for colloids (estimate = -8.317, p = 0.021). Additionally, a significant interaction term between age and the amount of colloid applied (estimate = 0.129, p = 0.028) was calculated. Evaluation of the influence of intraoperative fluid administration using multiple logistic regression models corrected for body mass index, duration of the surgery and additionally for age revealed a negative effect of crystalloids on the incidence of an anastomotic leak between bladder and urethra (estimate = -23.860, p = 0.017), with a significant interaction term between age and the amount of crystalloids (estimate = 0.396, p = 0.0134). Colloids had no significant effect on this particular complication (estimate = 1.887, p = 0.524). Intraoperative blood loss did not alter the incidence of an anastomotic leak (estimate = 0.001, p = 0.086), nor did it affect the length of hospitalization (estimate = 0.0001, p = 0.351). CONCLUSIONS: In accordance to the findings of our study, we suggest that a standardized, more restrictive fluid management might be beneficial in patients undergoing RALP. In older patients this measure would be able to shorten the length of hospitalization and to decrease the incidence of anastomosis leakage as a major complication.

Real-world treatment patterns and medical costs of prostate cancer patients in Switzerland - A claims data analysis.

BACKGROUND: Prostate cancer (PC) is the most prevalent cancer in men in Switzerland. However, evidence on the real-world health care use of PC patients is scarce. The aim of this study is to describe health care utilization, treatment patterns, and medical costs in PC patients over a period of five years (2014-2018). METHOD: We used routinely collected longitudinal individual-level claims data from a major provider of mandatory health insurance in Switzerland. Due to the lack of diagnostic coding in the claims data, we identified treated PC patients based on the treatments received. We described health care utilization and treatment pathways for patients with localized and metastatic PC. Costs were calculated from a health care system perspective. RESULTS: A total of 5591 PC patients met the inclusion criteria. Between 2014 and 2018, 1741 patients had outpatient radiotherapy for localized or metastatic PC and 1579 patients underwent radical prostatectomy. 3502 patients had an androgen deprivation therapy (ADT). 9.5% of these patients had a combination therapy with docetaxel, and 11.0% had a combination with abiraterone acetate. Docetaxel was the most commonly used chemotherapy (first-line; n = 413, 78.4% of all patients in chemotherapy). Total medical costs of PC in Switzerland were estimated at CHF 347 m (95% CI 323-372) in 2018. CONCLUSION: Most PC patients in this study were identified based on the use of ADT. Medical costs of PC in Switzerland amounted to 0.45% of total health care spending in 2018. Treatment of metastatic PC accounted for about two thirds of spending.

The economics of brain size evolution in vertebrates.

Across the animal kingdom, we see remarkable variation in brain size. This variation has even increased over evolutionary time. Traditionally, studies aiming to explain brain size evolution have looked at the fitness benefits of increased brain size in relation to its increased cognitive performance in the social and/or ecological domain. However, brains are among the most energetically expensive tissues in the body and also require an uninterrupted energy supply. If not compensated, these energetic demands inevitably lead to a reduction in energy allocation to other vital functions. In this review, we summarize how an increasing number of studies show that to fully comprehend brain size evolution and the large variation in brain size across lineages, it is important to look at the economics of brains, including the different pathways through which the high energetic costs of brains can be offset. We further show how numerous studies converge on the conclusion that cognitive abilities can only drive brain size evolution in vertebrate lineages where they result in an improved energy balance through favourable ecological preconditions. Cognitive benefits that do not directly improve the organism's energy balance can only be selectively favoured when they produce such large improvements in reproduction or survival that they outweigh the negative energetic effects of the large brain.

Use of Prescribed Drugs to Treat Chronic Diseases during Pregnancy in Outpatient Care in Switzerland between 2014 and 2018: Descriptive Analysis of Swiss Health Care Claims Data.

Evidence on the use of drugs during pregnancy in Switzerland is lacking. We aimed to evaluate the utilisation of drugs to treat chronic diseases during pregnancy in Switzerland. We identified all pregnancies (excluding abortions) in Swiss Helsana claims data (2014-2018). In those, we identified all claims for drugs to treat a chronic disease, which typically affects women of childbearing age. Potentially teratogenic/fetotoxic drugs were evaluated during specific risk periods. Results were demographically weighted relative to the Swiss population. We identified claims for ≥1 drug of interest during 22% of 369,371 weighted pregnancies. Levothyroxine was most frequently claimed (6.6%). Antihypertensives were claimed during 5.3% (3.9% nifedipine in T3). Renin-Angiotensin-Aldosterone System (RAAS) inhibitors were dispensed to 0.3/10,000 pregnancies during trimester 2 (T2) or trimester 3 (T3). Insulin was claimed during 3.5% of pregnancies, most frequently in T3 (3.3%). Exposure to psychotropic drugs was 3.8% (mostly Selective serotonin reuptake inhibitors (SSRIs)) and to drugs for obstructive airway diseases 3.6%. Traditional immunosuppressants (excluding corticosteroids) were claimed during 0.5% (mainly azathioprine and hydroxychloroquine), biologic immunosuppressants (Tumour necrosis factor-alpha (TNF-alpha) inhibitors and interleukin inhibitors) during 0.2%, and drugs to treat multiple sclerosis during 0.09% of pregnancies. Antiretrovirals were claimed during 0.15% of pregnancies. Patterns of drug claims were in line with treatment recommendations, but relatively rare events of in utero exposure to teratogenic drugs may have had severe implications for those involved.

Use of valproate in pregnancy and in women of childbearing age between 2014 and 2018 in Switzerland: a retrospective analysis of Swiss healthcare claims data.

AIMS OF THE STUDY: The prevalence of the use of valproate during pregnancy and by women of childbearing age in Switzerland is not known. We aimed to study the use of antiseizure drugs by these women in Switzerland, with a particular focus on valproate. METHODS: We conducted a retrospective descriptive study using the healthcare claims database of the Swiss health insurance Helsana (2014–18). We established two separate study populations: (1) a cohort of pregnancies leading to a delivery, and (2) all women of childbearing age (15–45 years) who were insured with Helsana for at least one year during the study period. We identified the dispensation of valproate, lamotrigine, carbamazepine, levetiracetam, topiramate, pregabalin, gabapentin, phenobarbital, and phenytoin (1) between delivery and three months prior to the estimated date of the last menstrual period, and (2) by calendar year. We quantified exposure prevalence of each antiseizure drug as the number of women with ≥1 prescription fill per 10,000 (1) pregnancies, and (2) women by calendar year. Results were weighted for the demographic distribution of the Helsana population relative to the Swiss population. RESULTS: We identified a weighted pregnancy population of 387,418 pregnancies, with a mean maternal age at delivery of 31.9 years (standard deviation 5.1). Lamotrigine was the most frequently dispensed antiseizure drug during pregnancy (20/10,000), followed by levetiracetam (11/10,000), and pregabalin (3.8/10,000). Valproate was dispensed to 1.9/10,000 women during pregnancy and to 1.3/10,000 women within 90 days prior to the last menstrual period but not during pregnancy. The weighted study population of women aged 15–45 years consisted of 2,781,151 women, of whom 74,080 (270/10,000) were exposed to ≥1 of the evaluated antiseizure drugs. Pregabalin was the most frequently dispensed antiseizure drug (64/10,000), followed by lamotrigine (46/10,000), topiramate (32/10,000), and valproate (25/10,000). The use of valproate decreased from 28/10,000 women in 2014 to 21/10,000 women in 2018. CONCLUSIONS: The prevalence of exposure to valproate during pregnancy was comparable to Denmark and lower than in other European countries. Despite decreasing exposure prevalence, the use of valproate in women of childbearing age in Switzerland seems higher than the actual clinical need.

Time trends in general practitioners' home visits for older patients: a retrospective cross-sectional study from Switzerland.

WHAT IS KNOWN ON THE SUBJECT, AND WHAT THE STUDY ADDS: The number of home visits by general practitioners (GPs) has decreased in recent years, in contrast to the increasing number of frail and older patients in western countries. Current data on GP home visit numbers and rates are lacking for Switzerland. Our study provides new data on GP home visit numbers and rates, and their associations with patient characteristics. AIM: Our study aimed at investigating the time trend of GP home visits to older patients from 2014 to 2018 in Switzerland, and associations between GP home visits and patient characteristics including healthcare utilisation and living situation. METHODS: Retrospective cross-sectional study of insurance claims data from 2014 to 2018 among patients aged ≥65 years (Nextrapolated = 2,095,102; Nraw = 339,301). We compared patient characteristics between patients with and without GP home visits using descriptive statistics. We performed logistic regression analyses to detect associations between patient characteristics and GP home visits, including subgroups of patients aged ≥80 and patients living in a nursing home. Regression models were adjusted for age and sex. RESULTS: The yearly GP home visit rate declined from 10.7% to 9.3% from 2014 to 2018 (p <0.0001). Among patients aged ≥80, the rate declined from 26.1% to 23.1% (p <0.0001), and among patients living in a nursing home from 68.7% to 65.8% (p <0.0001). Regression analyses revealed increased health care utilisation and a higher burden of morbidity and mortality in patients receiving GP home visits. CONCLUSION: There is an ongoing decline of GP home visits over the past years, with a potentially negative impact on the quality of care for older and frail patients.

Use of drugs to treat symptoms and acute conditions during pregnancy in outpatient care in Switzerland between 2014 and 2018: analysis of Swiss healthcare claims data.

BACKGROUND: Evidence on the use of drugs during pregnancy in Switzerland is lacking. OBJECTIVES: To evaluate utilisation of prescribed drugs during pregnancy in outpatient care in Switzerland, focusing on treatments for pain, infections, gastro-oesophageal reflux, nausea/vomiting, and constipation. METHODS: We conducted a descriptive study using the Swiss Helsana claims database (2014­2018). We established a cohort of pregnancies by identifying deliveries and estimating the date of the last menstrual period. We identified claims for the following drugs during pregnancy; analgesics (opioids, paracetamol, and nonsteroidal anti-inflammatory drugs [NSAIDs]), oral antibiotics, antacids, proton pump inhibitors (PPIs), anti-nausea drugs (propulsives and 5HT3-antagonists), and laxatives. Within these drug groups we quantified exposure prevalence to the most prescribed drugs (to >1% of pregnancies) during pregnancy as well as to specific potentially teratogenic or fetotoxic drugs during specific risk periods. Results were extrapolated relative to the demographic distribution of the Swiss population. RESULTS: We identified an extrapolated population of 369,371 pregnancies, with a weighted mean maternal age of 32.0 years (weighted standard deviation 5.1). Analgesics were claimed in 34.5% (95% confidence interval [CI] 33.9­35.0%) of pregnancies, most frequently paracetamol (30.3%, 29.8­30.8%), followed by NSAIDs (8.6%, 8.3­8.8%), and opioids (2.6%, 2.4­2.8%). NSAIDs were claimed in 1.3% (1.2­1.4%) of pregnancies after week 24, and opioids were claimed in 1.3% (1.2­1.4%) in trimester 3. Antibiotics were dispensed in 26.3% (25.8­26.8%) of pregnancies, most frequently amoxicillin (14.6%, 95% CI 14.2­14.9%). Claims for potentially teratogenic or fetotoxic antibiotics during risk periods were each recorded in <0.6% of pregnancies. PPIs were claimed in 16.0% (15.6­16.3%) and antacids in 10.6% (10.3­11.0%) of pregnancies, but several antacid products are not reimbursed and thus not present in insurance claims. Anti-nausea drugs were claimed in 16.4% (16.0­16.7%) of pregnancies, most frequently metoclopramide in 14.4% (14.0­14.7%). Ondansetron was mainly dispensed in trimester 1, 1.0% (0.9­1.1%). In total, 6.4% (6.2­6.7%) of pregnancies had a claim for laxatives, most frequently for macrogol (2.4%, 95% CI 2.2­2.5%). CONCLUSION: The observed pattern of claimed drugs during pregnancy is in line with existing treatment guidelines. Exposure to potentially teratogenic and fetotoxic drugs was small, but given the lack of recorded diagnosis, we cannot determine if their use was clinically indicated.

Comparing Two Imaging Methods for Follow-Up of Lung Cancer Treatment: A Randomized Pilot Study.

BACKGROUND: Scientific data on the image modality to be used in postcurative treatment surveillance of non-small cell lung cancer patients are scarce. This prospective randomized pilot trial compared the performance of integrated 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and contrast-enhanced computed tomography (CE-CT). METHODS: After termination of curative-intent treatment, patients were randomly assigned to the PET-CT or the CE-CT group. Imaging was performed every 6 months for 2 years. If suspicious radiologic findings were detected or patients became symptomatic, a diagnostic workup was initiated. Sensitivity, specificity, and positive predictive value for detecting cancer recurrence were calculated for both imaging procedures. RESULTS: The study enrolled 96 patients. In 14 of 50 patients (28%) in the PET-CT group and in 14 of 46 patients (30%) in the CE-CT group, a suspicious radiologic finding was confirmed as cancer recurrence after diagnostic workup. False-positive findings were detected in 11 patients (22%) of the PET-CT group and in 8 patients (17%) of the CE-CT group. The sensitivity, specificity, and positive predictive value for detecting cancer recurrence (95% confidence interval) were 0.88 (0.62 to 0.98), 0.62 (0.42 to 0.79), and 0.56 (0.35 to 0.76) for PET-CT and 0.93 (0.68 to 1.00), 0.72 (0.53 to 0.87), and 0.64 (0.41to 0.83) for CE-CT, respectively. CONCLUSIONS: The results of our study suggest that PET-CT is not superior to CE-CT in detecting cancer recurrence during 2 years after curative-intent treatment of non-small cell lung cancer.

Geographical Origin, Delayed Implantation, and Induced Ovulation Explain Reproductive Seasonality in the Carnivora.

Patterns of reproductive seasonality in the Carnivora are difficult to study comparatively, due to limited numbers of species for which information is available. Long-term databases of captive populations could overcome this difficulty. We apply a categorical description and a quantitative high-resolution measure (birth peak breadth, the number of days in which 80% of all births occur) based on daily observations in captivity to characterize the degree of reproductive seasonality in the Carnivora for 114 species with on average 1357 births per species. We find that the majority of species retained the birth seasonality displayed in the wild. Latitude of natural origin, delayed implantation, and induced ovulation were the main factors influencing reproductive seasonality. Most species were short-day breeders, but there was no evidence of an absolute photoperiodic signal for the timing of mating or conception. The length of the gestation period (corrected for body mass) generally decreased with birth seasonality but increased in species with delayed implantation. Birth seasons become shorter with increasing latitude of geographical origin, likely because the length of the favorable season declines with increasing latitude, exerting a strong selective pressure on fitting both the reproductive cycle and the interval offspring needs for growth following the termination of parental care into the short time window of optimal environmental conditions. Species with induced ovulation exhibit a less seasonal reproductive pattern, potentially because mates do not have to meet during a short time window of a fixed ovulation. Seasonal species of Carnivora shorten their gestation period so reproduction can occur during the short time window of optimal environmental conditions. Alternatively, other Carnivora species lengthen their gestation periods in order to bridge long winters. Interestingly, this occurs not by decelerating intrauterine growth but by delaying implantation.

The Ecology of Social Learning in Animals and its Link with Intelligence.

Classical ethology and behavioral ecology did not pay much attention to learning. However, studies of social learning in nature reviewed here reveal the near-ubiquity of reliance on social information for skill acquisition by developing birds and mammals. This conclusion strengthens the plausibility of the cultural intelligence hypothesis for the evolution of intelligence, which assumes that selection on social learning abilities automatically improves individual learning ability. Thus, intelligent species will generally be cultural species. Direct tests of the cultural intelligence hypothesis require good estimates of the amount and kind of social learning taking place in nature in a broad variety of species. These estimates are lacking so far. Here, we start the process of developing a functional classification of social learning, in the form of the social learning spectrum, which should help to predict the mechanisms of social learning involved. Once validated, the categories can be used to estimate the cognitive demands of social learning in the wild.

Significant improvement of olfactory performance in sleep apnea patients after three months of nasal CPAP therapy - Observational study and randomized trial.

OBJECTIVES: The olfactory function highly impacts quality of life (QoL). Continuous positive airway pressure is an effective treatment for obstructive sleep apnea (OSA) and is often applied by nasal masks (nCPAP). The influence of nCPAP on the olfactory performance of OSA patients is unknown. The aim of this study was to assess the sense of smell before initiation of nCPAP and after three months treatment, in moderate and severe OSA patients. METHODS: The sense of smell was assessed in 35 patients suffering from daytime sleepiness and moderate to severe OSA (apnea/hypopnea index ≥ 15/h), with the aid of a validated test battery (Sniffin' Sticks) before initiation of nCPAP therapy and after three months of treatment. Additionally, adherent subjects were included in a double-blind randomized three weeks CPAP-withdrawal trial (sub-therapeutic CPAP pressure). RESULTS: Twenty five of the 35 patients used the nCPAP therapy for more than four hours per night, and for more than 70% of nights (adherent group). The olfactory performance of these patients improved significantly (p = 0.007) after three months of nCPAP therapy. When considering the entire group of patients, olfaction also improved significantly (p = 0.001). In the randomized phase the sense of smell of six patients deteriorated under sub-therapeutic CPAP pressure (p = 0.046) whereas five patients in the maintenance CPAP group showed no significant difference (p = 0.501). CONCLUSIONS: Olfactory performance improved significantly after three months of nCPAP therapy in patients suffering from moderate and severe OSA. It seems that this effect of nCPAP is reversible under sub-therapeutic CPAP pressure. TRIAL REGISTRATION: ISRCTN11128866.

Shared microbiome in gums and the lung in an outpatient population.

OBJECTIVES: Whether periopathogenic bacteria occur in the lung and gums simultaneously and what impact periodontitis has is unknown. METHODS: In consecutive outpatients scheduled for bronchoscopies we performed a periodontal screening index. PCR to determine four periopathogens and seven less pathogenic species in both the periodontal pocket and bronchial protected specimen brush was used. Activated MMP8 in saliva and bronchial fluid was measured. RESULTS: Periopathogens were detectable in gums and in the bronchial protected specimen brush in 75 (80%) and 27 (30%) of the cases, respectively. The concentration of activated MMP 8 was above 40 ng/ml in the saliva and in the bronchial fluid sample in six and 31 subjects, respectively. Significant agreement between the periodontal and bronchial compartment was found in three out of the four periopathogens. Patients with periopathogens in the lung suffered from periodontitis more frequently (p = 0.01). In patients with periopathogens detectable in the lung the concentration of aMMP8 tends to be more frequently above 40 ng/ml in the bronchial fluid (p = 0.09). CONCLUSIONS: Agreement between periodontal and bronchial microbiome is more distinct for periopathogens than for less pathogenic species. Periodontitis itself represents a risk factor for pulmonary colonization with certain periopathogens. Pulmonary colonization with periopathogens seems to be associated with increased local inflammation.

Elevated Matrix Metalloproteinase Levels in Bronchi Infected with Periodontopathogenic Bacteria.

OBJECTIVES: To determine whether bronchial colonisations/infections with periodontopathogenic bacteria are associated with elevated inflammatory markers such as MMPs, interleukins and Tumor necrosis factor alpha in the bronchial fluid. METHODS: Periodontal status was assessed in consecutive outpatients planned for elective bronchoscopies, and PCR for periodontopathogenic bacteria was performed from a protected specimen brush sample taken from the bronchial mucosa. Additionally, MMPs, interleukins and Tumor necrosis factor alpha were measured in the bronchial fluid. RESULTS: Out of the four species assessed, one species was found in 13 of 91 (14%) patients, and two in 12 (13%), three in 13 (14%) and all four in 1 (1%) patient, respectively. In multiple linear regression models the presence of Treponema denticola showed a consistent pattern of positive effects in bronchial fluid (Bonferroni adjusted p-values) on the levels of MMP9 (p adj.: 0.028) and MMP12 (p adj.: 0.029). Active smoking was independently associated with increased levels of aMMP8 (p adj.: 0.005) and MMP9 (p adj.: 0.009). Levels of IL-1 ß, IL-8 and Tumor necrosis factor alpha measured in the bronchial fluid were not affected by the presence of periodontopathogenic bacteria. CONCLUSIONS: Bronchial colonisation/infection with Treponema denticola and smoking are independently associated with elevated MMPs (MMP9/MMP12 and MMP8/MMP9, respectively) in the bronchial fluid.

Late Post-Conditioning with Sevoflurane after Cardiac Surgery--Are Surrogate Markers Associated with Clinical Outcome?

INTRODUCTION: In a recent randomized controlled trial our group has demonstrated in 102 patients that late post-conditioning with sevoflurane performed in the intensive care unit after surgery involving extracorporeal circulation reduced damage to cardiomyocytes exposed to ischemia reperfusion injury. On the first post-operative day the sevoflurane patients presented with lower troponin T values when compared with those undergoing propofol sedation. In order to assess possible clinical relevant long-term implications in patients enrolled in this study, we performed the current retrospective analysis focusing on cardiac and non-cardiac events during the first 6 months after surgery. METHODS: All patients who had successfully completed the late post-conditioning trial were included into this follow-up. Our primary and secondary endpoints were the proportion of patients experiencing cardiac and non-cardiac events, respectively. Additionally, we were interested in assessing therapeutic interventions such as initiation or change of drug therapy, interventional treatment or surgery. RESULTS: Of 102 patients analyzed in the primary study 94 could be included in this follow-up. In the sevoflurane group (with 41 patients) 16 (39%) experienced one or several cardiac events within 6 months after cardiac surgery, in the propofol group (with 53 patients) 19 (36%, p=0.75). Four patients (9%) with sevoflurane vs. 7 (13%) with propofol sedation had non-cardiac events (p=0.61). While a similar percentage of patients suffered from cardiac and/or non-cardiac events, only 12 patients in the sevoflurane group compared to 20 propofol patients needed a therapeutic intervention (OR: 0.24, 95% CI: 0.04-1.43, p=0.12). A similar result was found for hospital admissions: 2 patients in the sevoflurane group had to be re-admitted to the hospital compared to 8 in the propofol group (OR 0.23, 95% CI: 0.04-1.29, p=0.10). CONCLUSIONS: Sevoflurane does not seem to provide protection with regard to the occurrence of cardiac and non-cardiac events in the 6-month period following cardiac surgery with the use of extracorporeal circulation. However, there was a clear trend towards fewer interventions (less need for treatment, fewer hospital admissions) associated with sevoflurane post-conditioning in patients experiencing any event. Such results might encourage launching large multicenter post-conditioning trials with clinical outcome defined as primary endpoint.