Neuromonitoring in neonatal intensive care units-an important need towards individualized neuroprotective care.

Neuromonitoring has been widely accepted as an important part in neonatal care. Amplitude-integrated EEG (aEEG) and near-infrared spectroscopy (NIRS) are often mentioned in this context, though being only a part of the fully array of methods and examinations that could be considered neuromonitoring. Within the broad array of medical conditions that could be encountered in a neonatal patient, it is important to be aware of the indications for neuromonitoring and especially which neuromonitoring technique to use best for the individual condition. aEEG is now a widely accepted neuromonitor in neonatology with its value in hypoxic events and seizures only rarely questioned. Other methods like NIRS still have to prove themselves in the future. The SafeBoosC-III trial showed that it still remains difficult for some of these methods to prove their value for the improvement of outcome. Bute future developments such as multimodal neuromonitoring with data integration and artificial intelligence analysis could improve the value of these methods.

A Complex Intervention to Prevent Medication-Related Hospital Admissions.

BACKGROUND: Children are often treated off-label and are at a disadvantage in pharmacotherapy. The aim of this study was to implement and evaluate a quality assurance measure (PaedPharm) for pediatric pharmacotherapy whose purpose is to reduce medication-related hospitalizations among children and adolescents. METHODS: PaedPharm consisted of the digital pediatric drug information system PaedAMIS, pediatric pharmaceutical quality circles (PaedZirk), and an adverse drug event (ADE) reporting system (PaedReport). The intervention was implemented in a cluster-randomized trial (DRKS 00013924) in 12 regions, with a pediatric and adolescent medicine clinic in each and a total of 152 surrounding private practitioners, in 6 sequences over 8 quarters. In addition to the proportion of ADE-related hospital admissions (primary endpoint), comprehensive process evaluation included other endpoints such as coverage, user acceptance, and relevance to practice. RESULTS: 41 829 inpatient admissions were recorded, of which 5101 were patients of physicians who participated in our study. 4.1% of admissions were ADE-related under control conditions, and 3.1% under intervention conditions (95% CI: [2.3; 5.9] and [1.8; 4.5], respectively). A model-based comparison yielded an intervention effect of 0.73 (population-based odds ratio; [0.39; 1.37]; p = 0.33). PaedAMIS achieved moderate user acceptance and PaedZirk achieved high user acceptance. CONCLUSION: The introduction of PaedPharm was associated with a decrease in medication-related hospitalizations that did not reach statistical significance. The process evaluation revealed broad acceptance of the intervention in outpatient pediatrics and adolescent medicine.

Real-world treatment of German patients with recurrent and advanced endometrial cancer with a post-platinum treatment: a retrospective claims data analysis.

PURPOSE: Endometrial cancer (EC) is the sixth most common malignancy among females worldwide. Due to limited therapeutic options, treatment of advanced or recurrent disease is associated with poor outcomes. The aim of this study was to describe the real-world treatment of patients with advanced or recurrent EC who received a systemic treatment following platinum-based chemotherapy. METHODS: This retrospective cohort study was based on anonymized German claims data covering the period between January 1, 2010, and June 30, 2020. Patients with EC who started an anticancer treatment following platinum-based chemotherapy were observed for a minimum follow-up of 12 months. Available claims data were used to describe patient characteristics, subsequent treatment lines, healthcare resource utilization, and overall survival (OS) of patients. RESULTS: Out of 713 patients with advanced or recurrent EC and who had received a platinum-based treatment, 201 (mean age: 68.9 years) with a post-platinum-based treatment were identified and observed. The median OS in this population was 335.0 days. Of the 201 patients, 79 patients (39.3%) received a second line of treatment (LOT), and 21 patients (10.4%) had 3 or more treatment lines. In the LOTs following platinum-based chemotherapy, more than 70 different treatment regimens were observed. The hospitalization rate was generally high, with 5.2 hospitalizations per patient-year in the follow-up period. CONCLUSION: The wide variety of therapeutic regimens applied in patients in Germany who progressed after platinum-based therapy confirms the lack of therapeutic strategy for these patients, and the poor prognosis highlights the urgent need for new treatment strategies.

Impact of disease progression on health-related quality of life of advanced ovarian cancer patients - Pooled analysis from the PRIMA trial.

OBJECTIVE: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL.

Costs of Public Health Screening of Children for Presymptomatic Type 1 Diabetes in Bavaria, Germany.

OBJECTIVE: We sought to evaluate costs associated with public health screening for presymptomatic type 1 diabetes in 90,632 children as part of the Fr1da study in Bavaria and in forecasts for standard care. RESEARCH DESIGN AND METHODS: We report on resource use and direct costs for screening-related procedures in the Fr1da study coordination center and laboratory and in participating pediatric practices and local diabetes clinics. Data were obtained from Fr1da study documents, an online survey among pediatricians, and interviews and records of Fr1da staff members. Data were analyzed with tree models that mimic procedures during the screening process. Cost estimates are presented as they were observed in the Fr1da study and as they can be expected in standard care for various scenarios. RESULTS: The costs per child screened in the Fr1da study were €28.17 (95% CI 19.96; 39.63) and the costs per child diagnosed with presymptomatic type 1 diabetes were €9,117 (6,460; 12,827). Assuming a prevalence of presymptomatic type 1 diabetes of 0.31%, as in the Fr1da study, the estimated costs in standard care in Germany would be €21.73 (16.76; 28.19) per screened child and €7,035 (5,426; 9,124) per diagnosed child. Of the projected screening costs, €12.25 would be the costs in the medical practice, €9.34 for coordination and laboratory, and €0.14 for local diabetes clinics. CONCLUSIONS: This study provides information for the planning and implementation of screening tests for presymptomatic type 1 diabetes in the general public and for the analysis of the cost-effectiveness of targeted prevention strategies.

Simulation Modeling for the Economic Evaluation of Population-Based Dietary Policies: A Systematic Scoping Review.

Simulation modeling can be useful to estimate the long-term health and economic impacts of population-based dietary policies. We conducted a systematic scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guideline to map and critically appraise economic evaluations of population-based dietary policies using simulation models. We searched Medline, Embase, and EconLit for studies published in English after 2005. Modeling studies were mapped based on model type, dietary policy, and nutritional target, and modeled risk factor-outcome pathways were analyzed. We included 56 studies comprising 136 model applications evaluating dietary policies in 21 countries. The policies most often assessed were reformulation (34/136), taxation (27/136), and labeling (20/136); the most common targets were salt/sodium (60/136), sugar-sweetened beverages (31/136), and fruit and vegetables (15/136). Model types included Markov-type (35/56), microsimulation (11/56), and comparative risk assessment (7/56) models. Overall, the key diet-related risk factors and health outcomes were modeled, but only 1 study included overall diet quality as a risk factor. Information about validation was only reported in 19 of 56 studies and few studies (14/56) analyzed the equity impacts of policies. Commonly included cost components were health sector (52/56) and public sector implementation costs (35/56), as opposed to private sector (18/56), lost productivity (11/56), and informal care costs (3/56). Most dietary policies (103/136) were evaluated as cost-saving independent of the applied costing perspective. An analysis of the main limitations reported by authors revealed that model validity, uncertainty of dietary effect estimates, and long-term intervention assumptions necessitate a careful interpretation of results. In conclusion, simulation modeling is widely applied in the economic evaluation of population-based dietary policies but rarely takes dietary complexity and the equity dimensions of policies into account. To increase relevance for policymakers and support diet-related disease prevention, economic effects beyond the health sector should be considered, and transparent conduct and reporting of model validation should be improved.

Utility Decrements Associated With Diabetes and Related Complications: Estimates From a Population-Based Study in Germany.

OBJECTIVES: Health utility decrement estimates for diabetes and complications are needed for parametrization of simulation models that aim to assess the cost-utility of diabetes prevention and care strategies. This study estimates health utility decrements associated with diabetes and cardiovascular and microvascular complications from a population-based German study. METHODS: Data were obtained from the population based cross-sectional KORA (Cooperative Health Research in the Augsburg Region) health questionnaire 2016 and comprised n = 1072 individuals with type 2 diabetes and n = 7879 individuals without diabetes. Health utility was assessed through the EQ-5D-5L. We used linear regression models with interaction terms between type 2 diabetes and different cardiovascular and microvascular complications while adjusting for demographic and socio-economic factors and other comorbidities. RESULTS: Type 2 diabetes (ß = -0.028, standard error [SE] = 0.014), stroke (ß = -0.070, SE = 0.010), cardiac arrhythmia (ß = -0.031, SE = 0.006), heart failure (ß = -0.073, SE = 0.009), coronary heart disease (ß = -0.028, SE = 0.010), myocardial infarction (ß = -0.020, SE = 0.011, estimates of main effect), and neuropathy (ß = -0.067, SE = 0.020), diabetic foot (ß = -0.042, SE = 0.030), nephropathy (ß = -0.032, SE = 0.025), and blindness (ß = -0.094, SE = 0.056, estimates of interaction terms) were negatively associated with health utility. The interaction term for diabetes x stroke (ß = -0.052, SE = 0.021) showed that the utility decrement for stroke is significantly larger in people with type 2 diabetes than in people without diabetes. CONCLUSIONS: Diabetes, cardiovascular, and microvascular conditions are associated with significant health utility decrements. Utility decrements for some conditions differ between people with and without type 2 diabetes. These results are of high relevance for the parametrization of decision analytic simulation models and applied health economic evaluations in the field of prevention and management of type 2 diabetes in Germany.

Different information needs in subgroups of people with diabetes mellitus: a latent class analysis.

BACKGROUND: Current evidence suggests that the information needs of people with diabetes mellitus differ across patient groups. With a view to being able to provide individualized information, this study aims to identify (i) the diabetes-related information needs of people with diabetes mellitus; (ii) different subgroups of people with specific information needs; and (iii) associated characteristics of the identified subgroups, such as sociodemographic characteristics, diabetes-related comorbidities, and well-being. METHODS: This cross-sectional study was based on data from 837 respondents with diabetes mellitus who participated in the population-based KORA (Cooperative Health Research in the Augsburg Region) Health Survey 2016 in Southern Germany (KORA GEFU 4 study) (45.6% female, mean age 71.1 years, 92.8% Type 2 diabetes). Diabetes-related information needs were assessed with a questionnaire asking about patients' information needs concerning 11 diabetes-related topics, e.g. 'long-term complications' and 'treatment/therapy'. Subgroups of people with different information needs and associated characteristics were identified using latent class analysis. RESULTS: We identified the following four classes of people with different information needs: 'high needs on all topics', 'low needs on all topics', 'moderate needs with a focus on complications and diabetes in everyday life', and 'advanced needs with a focus on social and legal aspects and diabetes research'. The classes differed significantly in age, years of education, type of diabetes, diabetes duration, diabetes-related comorbidities, smoking behaviour, diabetes education, current level of information, and time preference. CONCLUSIONS: Knowledge about different patient subgroups can be useful for tailored information campaigns or physician-patient interactions. Further research is needed to analyse health care needs in these groups, changes in information needs over the course of the disease, and prospective health outcomes.

Association between unrealistic comparative optimism and self-management in individuals with type 2 diabetes: Results from a cross-sectional, population-based study.

BACKGROUND AND AIMS: Unrealistic comparative optimism (UO), as the erroneous judgement of personal risks to be lower than the risks of others, could help explain differences in diabetes self-management. The present study tested the hypothesis that individuals with type 2 diabetes who underestimate their comparative heart attack risk, have a lower adherence regarding recommended self-management. METHODS: We used data from individuals with type 2 diabetes participating in the German KORA (Cooperative Health Research in the Region of Augsburg) GEFU 4 (self-administered health questionnaire 2016) study. UO was estimated by comparing participants' subjective comparative risk for having a heart attack within the next 5-years (ie, "higher than others," "average," "lower than others"), with their objective comparative 10-year cardiovascular disease risk based on the Framingham equations. We estimated binary logistic and linear regression models to analyze which characteristics were associated with UO and to test the association between UO and participants' self-management behaviors (ie, regular self-monitoring of body weight, blood sugar, and blood pressure, regular foot care, keeping a diabetes diary, and having a diet plan), and their sum score, respectively. All models were adjusted for socio-demographic and disease-related variables. RESULTS: The studied sample included n = 633 individuals with type 2 diabetes (mean age 70.7 years, 45% women). Smokers and males were more likely to show UO than nonsmokers and females. Furthermore, a higher blood pressure and a higher body mass index were associated with a higher likelihood of UO regarding heart attack risk. However, UO was not significantly associated with patient self-management. CONCLUSIONS: Unfavorable health behavior and risk factors are associated with UO. However, our results suggest that UO with regard to perceived heart attack risk may not be a relevant factor for patient self-management in those with type 2 diabetes.

Associations between self-management behavior and sociodemographic and disease-related characteristics in elderly people with type 2 diabetes - New results from the population-based KORA studies in Germany.

AIMS: Self-management behavior (SMB) is an important aspect in the management of diabetes. This study aimed to identify sociodemographic and disease-related factors associated with good SMB in people with type 2 diabetes (T2D). METHODS: We used data from 479 people with T2D aged 65 or older from the population-based KORA (Cooperative Health Research in the Area of Augsburg) Health Survey 2016 in Southern Germany. We estimated Poisson and logistic regression models testing the cross-sectional relationship between individual or disease-related characteristics and an established SMB sum index comprising six SMB dimensions stratified according to insulin treatment status. RESULTS: Mean age in the sample was 75 and mean diabetes duration was 13 years. The overall level of SMB was low. Higher SMB index scores were associated with higher age, treatment with insulin, participation in a diabetes education program, and, for people with insulin treatment, with a BMI below 30 kg/m2. Single item analyses generally supported these findings. CONCLUSIONS: SMB in people with T2D needs to be improved with efficient interventions. Targeting obese individuals and those at an early stage of the disease with low-barrier, regular education or self-management programs may be a preferred strategy.

Vedolizumab quantitation using high-resolution accurate mass-mass spectrometry middle-up protein subunit: method validation.

Background While quantitation methods for small-molecule and tryptic peptide bottom-up mass spectrometry (MS) have been well defined, quantitation methods for top-down or middle-up MS approaches have not been as well defined. Therapeutic monoclonal antibodies (t-mAbs) are a group of proteins that can be used to both demonstrate the advantages of top-down or middle-up detection methods over classic tryptic peptide bottom-up along with the growing need for robust quantitation strategies/software for these top-down or middle-up methods. Bottom-up proteolytic digest methods for the t-mAbs tend to suffer from challenges such as limited peptide selection due to potential interference from the polyclonal immunoglobulin background, complicated workflows, and inadequate sensitivity and specificity without laborious purification steps, and therefore have prompted the search for new detection and quantitation methods. Time-of-flight along with Orbitrap MS have recently evolved from the research and/or pharmaceutical setting into the clinical laboratory. With their superior mass measurement accuracy, resolution and scanning speeds, these are ideal platforms for top-down or middle-up characterization and quantitation. Methods We demonstrate a validated, robust, middle-up protein subunit detection and quantitation method for the IgG1 t-mAb, vedolizumab (VEDO), which takes advantage of the high resolution of the Orbitrap MS detection and quantitation software to increase specificity. Results Validated performance characteristics met pre-defined acceptance criteria with simple workflows and rapid turnaround times: characteristics necessary for implementation into a high-volume clinical MS laboratory. Conclusions While the extraction method can easily be used with other IgG1 t-mAbs, the detection and quantitation method may become an option for measurement of other proteins.

Change in Physical Activity after Diagnosis of Diabetes or Hypertension: Results from an Observational Population-Based Cohort Study.

Background: Chronic diseases like diabetes mellitus or hypertension are a major public health challenge. Irregular physical activity (PA) is one of the most important modifiable risk factors for chronic conditions and their complications. However, engaging in regular PA is a challenge for many individuals. The literature suggests that a diagnosis of a disease might serve as a promising point in time to change health behavior. This study investigates whether a diagnosis of diabetes or hypertension is associated with changes in PA. Methods: Analyses are based on 4261 participants of the population-based KORA S4 study (1999-2001) and its subsequent 7-and 14-year follow-ups. Information on PA and incident diagnoses of diabetes or hypertension was assessed via standardized interviews. Change in PA was regressed upon diagnosis with diabetes or hypertension, using logistic regression models. Models were stratified into active and inactive individuals at baseline to avoid ceiling and floor effects or regression to the mean. Results: Active participants at baseline showed higher odds (OR = 2.16 [1.20;3.89]) for becoming inactive after a diabetes diagnosis than those without a diabetes diagnosis. No other significant association was observed. Discussion: As PA is important for the management of diabetes or hypertension, ways to increase or maintain PA levels in newly-diagnosed patients are important. Communication strategies might be crucial, and practitioners and health insurance companies could play a key role in raising awareness.

Status quo bias and health behavior: findings from a cross-sectional study.

BACKGROUND: Status quo bias (SQB) has often been referred to as an important tool for improving public health. However, very few studies were able to link SQB with health behavior. METHODS: Analysis were based on data from the population-based KORA S4 study (1999-2001, n = 2309). We operationalized SQB through two questions. The first asked whether participants switched their health insurance for financial benefits since this was enabled in 1996. Those who did were assigned a 'very low SQB' (n = 213). Participants who did not switch were asked a second hypothetical question regarding switching costs. We assigned 'low SQB' to those who indicated low switching costs (n = 1035), 'high SQB' to those who indicated high switching costs (n = 588), and 'very high SQB' to those who indicated infinite switching costs (n = 473). We tested the association between SQB and physical activity, diet, smoking, alcohol consumption, the sum of health behaviors, and body mass index (BMI) using logistic, Poisson and ordinary least square regression models, respectively. Models were adjusted for age, sex, education, income, satisfaction with current health insurance and morbidity. RESULTS: SQB was associated with a higher rate of physical inactivity [OR = 1.22, 95% CI (1.11; 1.35)], a higher sum of unhealthy lifestyle factors [IRR = 1.05, 95% CI (1.01; 1.10)] and a higher BMI [ß = 0.30, 95% CI (0.08; 0.51)]. CONCLUSION: A high SQB was associated with unfavorable health behavior and higher BMI. Targeting SQB might be a promising strategy for promoting healthy behavior.

Time preference, outcome expectancy, and self-management in patients with type 2 diabetes.

BACKGROUND: Patient self-management is crucial to prevent complications and mortality in type 2 diabetes. From an economic perspective, time preference predicts short-sighted decision making and thus might help to explain non-adherence to self-anagement recommendations. However, recent studies on this association have shown mixed results. PURPOSE: In this study, we tested whether the combination of time preference and outcome expectancy can improve the predictions of self-management behavior. PATIENTS AND METHODS: Data from 665 patients with type 2 diabetes were obtained from the cross-sectional KORA (Cooperative Health Research in the Region of Augsburg) GEFU 4 study. Time preference and outcome expectancy were measured by one question each, which were answered on a 4-point Likert scale. Their association with six self-managing behaviors was tested in logistic and linear regression analyses. Likewise, we examined the association between self-management and the interaction of outcome expectancy and time preference. RESULTS: A high time preference was associated with a significantly lower sum of self-management behaviors (ß=-0.29, 95% CI [-0.54, -0.04]). Higher outcome expectancy was associated with a higher self-management score (ß=0.21, 95% CI [-0.03, 0.45]). The interaction model showed that low time preference was only associated with better self-management when combined with a high outcome expectancy (ß=0.05, 95% CI [-0.28, 0.39] vs ß=0.27, 95% CI [-0.09, 0.63]). CONCLUSION: Time preference and outcome expectancy are interrelated predictors of patient self-management and could be used to identify and to intervene on patients with a potentially poor self-management.

Direct healthcare costs associated with device assessed and self-reported physical activity: results from a cross-sectional population-based study.

BACKGROUND: Physical inactivity (PIA) is an important risk factor for many chronic conditions and therefore might increase healthcare utilization and costs. This study aimed to analyze the association of PIA using device assessed and self-reported physical activity (PA) data with direct healthcare costs. METHODS: Cross-sectional data was retrieved from the population based KORA FF4 study (Cooperative Health Research in the Region of Augsburg) that was conducted in southern Germany from 2013 to 2014 (n = 2279). Self-reported PA was assessed with two questions regarding sports related PA in summer and winter and categorized into "high activity", "moderate activity", "low activity" and "no activity". In a subsample (n = 477), PA was assessed with accelerometers and participants were categorized into activity quartiles ("very high", "high", "low" and "very low") according to their mean minutes per day spent in light intensity, or in moderate-vigorous PA (MVPA). Self-reported healthcare utilization was used to estimate direct healthcare costs. We regressed direct healthcare costs on PA using a two-part gamma regression, adjusted for age, sex and socio-demographic variables. Additional models, including and excluding potential additional confounders and effect mediators were used to check the robustness of the results. RESULTS: Annual direct healthcare costs of individuals who reported no sports PA did not differ from those who reported high sports PA [+€189, 95% CI: -188, 598]. In the subsample with accelerometer data, participants with very low MVPA had significantly higher annual costs than participants with very high MVPA [+€986, 95% CI: 15, 1982]. CONCLUSION: Device assessed but not self-reported PIA was associated with higher direct healthcare costs. The magnitude and significance of the association depended on the choice of covariates in the regression models. Larger studies with device assessed PA and longitudinal design are needed to be able to better quantify the impact of PIA on direct healthcare costs.

Applying the health action process approach to bicycle helmet use and evaluating a social marketing campaign.

BACKGROUND: Bicycle injuries are of concern in Canada. Since helmet use was mandated in 1996 in the province of British Columbia, Canada, use has increased and head injuries have decreased. Despite the law, many cyclists do not wear a helmet. Health action process approach (HAPA) model explains intention and behaviour with self-efficacy, risk perception, outcome expectancies and planning constructs. The present study examines the impact of a social marketing campaign on HAPA constructs in the context of bicycle helmet use. METHOD: A questionnaire was administered to identify factors determining helmet use. Intention to obey the law, and perceived risk of being caught if not obeying the law were included as additional constructs. Path analysis was used to extract the strongest influences on intention and behaviour. The social marketing campaign was evaluated through t-test comparisons after propensity score matching and generalised linear modelling (GLM) were applied to adjust for the same covariates. RESULTS: 400 cyclists aged 25-54 years completed the questionnaire. Self-efficacy and Intention were most predictive of intention to wear a helmet, which, moderated by planning, strongly predicted behaviour. Perceived risk and outcome expectancies had no significant impact on intention. GLM showed that exposure to the campaign was significantly associated with higher values in self-efficacy, intention and bicycle helmet use. CONCLUSION: Self-efficacy and planning are important points of action for promoting helmet use. Social marketing campaigns that remind people of appropriate preventive action have an impact on behaviour.

Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD patients.

BACKGROUND: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease. METHODS: Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort. The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles. The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities. RESULTS: Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD. AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT) compared with COPD patients without AATD. There were no significant differences between groups regarding indirect costs and HRQL. CONCLUSION: Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD. AT was not associated with lower costs or higher HRQL. TRIAL REGISTRATION: NCT01245933.

Biochemical Identification of Vitamin B12 Deficiency in a Medical Office.

BACKGROUND: A vitamin B12 deficiency can be an underlying cause or a deteriorating factor in several diseases. Nevertheless, early identification of such a deficiency remains a problem. Holotranscobalamin (HTC) is presently considered to be the gold standard. We tested the predictive power of other B12 parameters by comparing them with HTC. METHODS: The blood of 77 patients from a medical office was tested for HTC, total B12 (CLIA [chemiluminescent immunoassay] and MTP [microbiological test with microtitre plates]), MMA (methylmalonic acid), HCY (homocysteine), and MCV (mean cell volume). The parameters were correlated and sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), LR+ (positive likelihood ratio), and LR- (negative likelihood ratio) in comparison to HTC were determined. A ROC analysis was also performed. RESULTS: At a cutoff value of 35 pmol/L for HTC, the total B12 CLIA (cutoff 211 ng/L) qualified 53% of individuals as having a B12 deficiency. The total B12 MTP (cutoff 288 ng/L) classified 71% as having a B12 deficiency. Specificity was similar in both cases (CLIA, 93%; MTP, 95%). With a cutoff value of 10 µmol/L for homocysteine, the best negative prediction was achieved. MVA has a low sensitivity (41%) and a high specificity (90%). Based on the ROC analysis, which indicated superiority of the B12-MTP, the reference levels of B12-CLIA and B12-MTP were raised to 304 and 368 ng/L, respectively. Thus, a probable B12 deficiency was identified in 94% of cases with either method and with a comparable specificity. CONCLUSIONS: If total B12 is applied to identify B12 deficiency, the cutoff values should be elevated to 304 (B12-CLIA) and 368 ng/L (B12-MTP) to improve the predictive power. The negative-predictive power of HCY can be useful in daily routine. HTC has a broad grey area of uncertainty and MMA should only be applied as a confirmatory test.

The influence of a whole food vegan diet with Nori algae and wild mushrooms on selected blood parameters.

BACKGROUND: Vegan and vegetarian diets could overcome many diseases of civilization. This study examines whether a whole food vegan diet with Nori algae and wild mushrooms can provide a sufficient quantity of critical nutrients. METHODS: Five blood samples (Baseline to Time 5) were taken over eight months from 75 subjects (10 vegans without B12 supplementation who consumed Nori algae and wild mushrooms, 20 vegans with supplementation, 40 vegetarians, 5 meat-eaters). Blood was analyzed for blood cell counts, total vitamin B12, holotranscobalamin, homocysteine, methylmalonic acid, vitamin B6, folic acid, ferritin, TSH, zinc, creatinine, vitamin D2 and D3. RESULTS: In the vegan group without supplementation, all means were within the tolerance (holotranscobalamin, homocystein) or normal, except for elevated methylmalonic acid and diminished vitamin D. This group developed significantly higher vitamin D2 levels. The vegan group with B12 supplementation and the vegetarian group showed normal values for all parameters. CONCLUSIONS: Vegans following a whole food diet had a borderline supply of vitamin B12. Folic acid, vitamin B6, TSH, iron metabolism, and the blood count were in the normal range. Vegans taking dietary supplements demonstrated satisfactory overall results. An ingestion of sundried mushrooms can contribute to the supply of vitamin D.