Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): study protocol for a pilot randomised controlled trial.

BACKGROUND: Intensive care unit (ICU) survivors often suffer from cognitive, physical and mental impairments, known as post-intensive care syndrome (PICS). ICU follow-up clinics may improve aftercare of these patients. There is a lack of evidence whether or which concept of an ICU follow-up clinic is effective. Within the PINA study, a concept for an ICU follow-up clinic was developed and will be tested in a pilot randomised controlled trial (RCT), primarily to evaluate the feasibility and additionally the potential efficacy. METHODS/DESIGN: Design: Pilot RCT with intervention and control (usual care) arms plus mixed-methods process evaluation. PARTICIPANTS: 100 ICU patients (50 per arm) of three ICUs in a university hospital (Regensburg, Germany), ≥ 18 years with an ICU stay of > 5 days, a sequential organ failure assessment (SOFA) score > 5 during the ICU stay and a life expectancy of more than 6 months. INTERVENTION: The intervention will contain three components: information, consultation and networking. Information will be available in form of an intensive care guide for patients and next of kin at the ICU and phone support during follow-up. For consultation, patients will visit the ICU follow-up clinic at least once during the first 6 months after discharge from ICU. During these visits, patients will be screened for symptoms of PICS and, if required, referred to specialists for further treatment. The networking part (e.g. special referral letter from the ICU follow-up clinic) aims to provide a network of outpatient care providers for former ICU patients. Feasibility Outcomes: Qualitative and quantitative evaluation will be used to explore reasons for non-participation and the intervention´s acceptability to patients and caregivers. Efficacy Outcomes: Health-related quality of life (HRQOL) will be assessed as primary outcome by the physical component score (PCS) of the Short-Form 12 Questionnaire (SF-12). Secondary outcomes encompass further patient-reported outcomes. All outcomes are assessed at 6 months after discharge from ICU. DISCUSSION: The PINA study will determine feasibility and potential efficacy of a complex intervention in a pilot RCT to enhance follow-up care of ICU survivors. The pilot study is an important step for further studies in the field of ICU aftercare and especially for the implementation of a pragmatic multi-centre RCT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04186468 . Submitted 2 December 2019.

Outcome assessment in dermatology clinical trials and cochrane reviews: call for a dermatology-specific outcome taxonomy.

BACKGROUND: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision-making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology-specific reporting strategy that uses precise and consistent outcome definitions. OBJECTIVES: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. METHODS: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology-specific outcome taxonomy. RESULTS: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology-specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non-comparable outcome measurement instruments, metrics and reporting. CONCLUSIONS: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology-specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence.

12-year changes in cardiovascular risk factors in people with major depressive or bipolar disorder: a prospective cohort analysis in Germany.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder are associated with certain cardiovascular risk factors (CVRFs), but it is unclear whether they are associated with unfavourable changes of clinically manifest CVRFs over time. METHODS: We used baseline and 12-year follow-up (n = 1887) data from the German Health Interview and Examination Survey 1998. Multivariable linear regression models assessed associations between lifetime CIDI-diagnosed mood disorders at baseline and continuous risk factor-related outcomes (blood pressure, HbA1c, LDL-C, HDL-C, triglycerides, BMI) at follow-up. RESULTS: We did not find consistent deterioration of CVRFs in persons with compared to persons without MDD. Analyses pointed to severity of mood disorder as an important correlate of long-term changes of comorbid hypertension: while a history of mild MDD was not associated with changes in CVRFs, moderate MDD was associated with lower blood pressure [systolic: ß = - 7.5 (CI - 13.2; - 1.9); diastolic: ß = - 4.5 (CI - 7.8; - 1.3)] and a history of bipolar disorder was associated with higher systolic blood pressure at follow-up (ß = 14.6; CI 4.9-24.4). Further, severe MDD was weakly associated with a higher BMI at follow-up [ß = 1.2 (CI 0.0; 2.4)]. These outcomes were not mediated by use of psychotropic medication and remained statistically significant after adjusting for the use of antihypertensive medication. CONCLUSION: Since most investigated parameters showed no associations, participants with a lifetime history of MDD in this cohort did not carry a specific risk for a worsening of pre-existing clinically manifest CVRFs. Our findings extend evidence of MDD severity and bipolar disorder as important correlates of long-term changes of arterial hypertension and obesity.

Biometry of the corpus callosum assessed by 3D ultrasound and its correlation to neurodevelopmental outcome in very low birth weight infants.

OBJECTIVE: Several studies have shown a relation between the size of corpus callosum (CC) and outcome in preterm infants. Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. To establish reference values for biometry of the CC in very low birth weight infants and to correlate these measurements to neurodevelopmental outcome at 5 years of age. STUDY DESIGN: Forty-three preterm infants with a gestational age <32 weeks were included. Transfontanellar 3D-US measurements were obtained at nine different timepoints. RESULTS: 3D-US-based reference values for size, length, circumference and surface area of the CC could be established. Measurements at term-equivalent age showed a correlation to neurodevelopment outcome. CONCLUSION: Reliable biometric data of the CC can be established in preterm infants by 3D-US and correlate with neurodevelopmental outcome.

Differences in attentional functioning between preterm and full-term children underline the importance of new neuropsychological detection techniques.

AIM: The aim of this study was to investigate specific attentional components in preterm born children who had not yet started school. METHODS: Between January and December 2011, we assessed 52 preterm and 52 full-term children aged between five years five months and six years two months, of comparable age and gender, at the Medical University of Vienna. Different attentional components were evaluated through selected subtests of the Test of Attentional Performance and the German version of the Wechsler Intelligence Scale for Children. Each child's behaviour was also evaluated using parental ratings and descriptive item-based evaluation during neuropsychological assessment. RESULTS: Children born preterm showed poor attentional performance in sustained attention, focused attention and distractibility, as well as reductions in processing speed in divided attention and flexibility tasks. Children born preterm also showed decreased volitional attention compared with automatic attention. No problems were detected in alertness or inhibition. In addition, a higher rate of aborted tests, decreased motivation and poorer parental ratings were detected among the preterm population compared with full-term born children. CONCLUSION: Our results highlighted differences in attentional functioning between preterm and full-term children, indicating the importance of new neuropsychological techniques for the detection of specific attentional disorders.

[Patient-centredness in health services research]. / Patientenorientierung in der Versorgungsforschung.

This paper provides a sketch of key research areas within health services research focusing on patient-centredness. The evaluation of patient-reported outcomes (PROs) is increasingly required for evaluating interventions in clinical trials and in routine health care. Often, however, it is un-clear which PROs are best suited for a particular research question. One of the most commonly used PRO is the construct of quality of life (QoL), which has become an established outcome in clinical trials and is also named as a health goal in the German Social Code of Law. The concept of patient empowerment implies that autonomy and room for manoeuver of the individual patient should be strengthened. However, it is un-clear how the concept is best operationalised. One prerequisite for patient empowerment in routine health care is the development and implementation of evidence-based patient information. Another prominent research area focuses on the role of self-help and patient organisations in health services. Topics of interest are aims and activities of self-help organisations, potentials and challenges of integrating self-help into professional health services, effects of organised self-help support on patients and barriers of use.

Regional cortical development in very low birth weight infants with normal neurodevelopmental outcome assessed by 3D-ultrasound.

OBJECTIVE: Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. STUDY DESIGN: This prospective study aimed to determine whether 3D-US is appropriate to assess cortical development of the premature brain, and compare it to previously established reference values assessed by magnetic resonance imaging (MRI). Preterm infants with a gestational age (GA) of <32 weeks were examined by serial 3D-US scans. RESULT: Data of 30 patients with normal neurological development at the age of 5 years were included in the analysis. Cortical development was graded according to a five-point scoring system, and data were stratified into 6 age groups. Cortical developmental scores were established for various brain regions. In the frontal and frontoparietal regions, 3D-US reference values differed from published MRI reference values, but were consistent with the published data in all other regions. CONCLUSION: 3D-US reference values facilitate routine diagnostics and enable the evaluation of cortical development in preterm infants.

Novel energy resolving x-ray pinhole camera on Alcator C-Mod.

A new energy resolving x-ray pinhole camera has been recently installed on Alcator C-Mod. This diagnostic is capable of 1D or 2D imaging with a spatial resolution of ≈1 cm, an energy resolution of ≈1 keV in the range of 3.5-15 keV and a maximum time resolution of 5 ms. A novel use of a Pilatus 2 hybrid-pixel x-ray detector [P. Kraft et al., J. Synchrotron Rad. 16, 368 (2009)] is employed in which the lower energy threshold of individual pixels is adjusted, allowing regions of a single detector to be sensitive to different x-ray energy ranges. Development of this new detector calibration technique was done as a collaboration between PPPL and Dectris Ltd. The calibration procedure is described, and the energy resolution of the detector is characterized. Initial data from this installation on Alcator C-Mod is presented. This diagnostic provides line-integrated measurements of impurity emission which can be used to determine impurity concentrations as well as the electron energy distribution.

Reference values and early determinants of intra-abdominal fat mass in primary school children.

BACKGROUND: Intra-abdominal fat (IAF) is a valuable predictor of cardiovascular morbidity. However, neither reference values nor determinants are known in children. METHODS: IAF was assessed as sonographically measured intra-abdominal depth in 1,046 children [median age 7.6 years, interquartile range (IQR) 7.2-7.9; 54% boys] of the URMEL-ICE study. RESULTS: The intraclass correlation coefficient for intraobserver agreement was 0.93. The median IAF showed a significant gender difference (boys: 54.6 mm, IQR 50.1-59.3, vs. girls: 51.7 mm, IQR 46.3-56.4; p < 0.001). Age- and gender-specific centiles were generated. IAF showed a positive correlation to systolic blood pressure [regression coefficient (ß) = 0.24 mm Hg/mm; p < 0.001] and a negative correlation to HDL cholesterol (ß = -0.01 mmol/l/mm; p < 0.001). IAF showed a positive association with increased paternal and maternal BMI (ß = 0.28 mm/kg/m(2) and 0.27 mm/kg/m(2); p < 0.001), increased weight gain in the first 2 years of life (ß = 3.04 mm; p < 0.001), and maternal smoking during pregnancy (ß = 2.4 mm; p = 0.001). Increased parental education was negatively associated with IAF (maternal: ß = -0.65 mm/degree; p = 0.004, and paternal: ß = -0.61 mm/degree; p = 0.002). CONCLUSION: Sonography was a reliable tool to estimate IAF. Factors influencing IAF included rapid infant weight gain, smoking during pregnancy, and parental BMI and education. Since IAF showed an association with cardiovascular risk factors even in prepubertal children, it might become a valuable predictor of cardiovascular vulnerability.

Interplay of time-delayed feedback control and temporally correlated noise in excitable systems.

The interplay of time-delayed feedback and temporally correlated coloured noise in a single and two coupled excitable systems is studied in the framework of the FitzHugh-Nagumo (FHN) model. By using coloured noise instead of white noise, the noise correlation time is introduced as an additional time scale. We show that in a single FHN system the major time scale of oscillations is strongly influenced by the noise correlation time, which in turn affects the maxima of coherence with respect to the delay time. In two coupled FHN systems, coloured noise input to one subsystem influences coherence resonance and stochastic synchronization of both subsystems. Application of delayed feedback control to the coloured noise-driven subsystem is shown to change coherence and time scales of noise-induced oscillations in both systems, and to enhance or suppress stochastic synchronization under certain conditions.

Secular changes of anthropometric measures for the past 30 years in South-West Germany.

We investigated long-term changes in weight and skinfold thicknesses in German schoolchildren. In 2006, anthropometric measures were collected after a standardized protocol among 1079 children within the Ulm Research on Metabolism, Exercise and Lifestyle in children (URMEL-ICE) study. Data were compared with historical data (1975-1976). In URMEL-ICE, prevalence of overweight (IOTF criteria) was 16.5% (boys) and 17.3% (girls) and of obesity 3.5 and 3.6%, respectively. Compared with historical data the number of children above the 90th percentile(1975/76) increased statistically significantly for weight (approximately 150% both sexes), for subscapular (boys 288%, girls 206%) and triceps skinfold thickness (boys 460%, girls 413%). Statistically significant increases above the 50th percentile(1975/76) were found: weight 36 and 26%, subscapular 43 and 60% and triceps skinfold thickness 63 and 69% for boys and girls, respectively. Body fat among 6- to 9-year-old children increased dramatically within 30 years. Moreover, our data suggest substantial changes in body composition among normal-weight children towards an increased body fat mass.

Impact of gamma-irradiation on the antioxidative properties of sage, thyme, and oregano.

Ionizing radiation is known to stimulate the generation of oxygen radicals which destabilize organic molecules resulting in a decrease of the system's antioxidant potential. The Salmonella typhimurium (TA102) reverse mutation assay, co-incubated with t-BOOH and H(2)O(2), was used to assess the effects of gamma-irradiation (dose: 10kGy) on the antioxidant properties of sage, thyme, and oregano in chloroform and methanol extracts as well as in their mixture. In addition, measurements of the trolox equivalent antioxidative capacity (TEAC), total polyphenol content (TPC), and tocopherol equivalent (TE) were performed. For the methanol and mixed extracts, antioxidative properties in the S. typhimurium reverse mutation assay were only found when using an exogenous metabolic activation system. Generally, the greatest inhibition of mutagenicity was observed in the chloroform fractions of irradiated and of non-irradiated herbs. The relative antioxidant activities for the different herbs were as follows: TA102/t-BOOH, TEAC, TPC: thyme approximately oregano>sage. TA102/H(2)O(2): thyme approximately oregano approximately sage. TE: sage>thyme>oregano. For the majority of the investigated samples the impact of irradiation was insignificant. Therefore, gamma-irradiation at the doses tested seems to have little, if any, effect on the antioxidative capacity of the tested herbs.

Outcome of very-low-birth-weight infants at 1 and 2 years of age. The importance of early identification of neurodevelopmental deficits.

The developmental and neurologic outcome of very-low-birth-weight infants (n=76) at 1 and 2 years, corrected for postconceptional age, and variables predicting outcome were assessed. At 1 year 24% of tile children were neurologically normal and at 2 years 61%. Developmental status was evaluated by use of the Griffiths Developmental Scales. The rate of cognitively normal children remained constant (58% at 1 year and 59% at 2 years) indicating that developmental status at 1 year was predictive for the second year. This early period is important, therefore, for the identification of developmental deficits and for establishing early, adequate interventions.

Inhibition of secretin-stimulated exocrine pancreatic secretion by diazoxide in the rat.

Diazoxide, a known insulin inhibitor, inhibits the pancreatic exocrine response to secretin in unanesthetized rats and does not modify the CCK-PZ-stimulated secretion. These results suggest that insulin may have a role on the stimulation of exocrine pancreas through secretin.