Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria.

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14-18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact.

Clinical outcome of rural in-hospital-stroke patients after interhospital transfer for endovascular therapy within a telemedical stroke network in Germany: a registry-based observational study.

OBJECTIVES: Little is known about in-hospital-stroke (IHS) patients with large vessel occlusion and subsequent transfer to referral centres for endovascular therapy (EVT). However, this subgroup is highly relevant given the substantial amount of IHS, the ongoing trend towards greater use of EVT and lack of EVT possibilities in rural hospitals. The study objective is to explore the clinical outcomes of this vulnerable patient group, given that both IHS and interhospital transfer are associated with worse clinical outcomes due to a higher proportion of pre-existing conditions and substantial time delays during transfer. DESIGN AND SETTING: Prospectively collected data of patients receiving EVT after interhospital transfer from 14 rural hospitals of the Telemedical Stroke Network in Southeast Bavaria (TEMPiS) between February 2018 and July 2020 was analysed. PARTICIPANTS: 49 IHS and 274 out-of-hospital-stroke (OHS) patients were included. OUTCOME MEASURES: Baseline characteristics, treatment times and outcomes were compared between IHS and OHS. The primary endpoint was a 3-month modified Rankin Scale (mRS). RESULTS: In IHS patients, atrial fibrillation (55.3% vs 35.9%, p=0.012), diabetes (36.2% vs 21.1%, p=0.024) and use of oral anticoagulants (44.7% vs 20.8%, p<0.001) were more frequent. Stroke severity was similar in both groups. Treatment times from symptom onset to first brain imaging, therapy decision or EVT were shorter for IHS patients. IHS patients displayed worse clinical outcomes: 59.2% of IHS patients died within 3 months compared with 28.5% of OHS patients (p<0.001). They were less likely to achieve moderate outcomes (mRS 0-3) 3 months after stroke (20.4% vs 39.8%, p=0.010). After controlling for possible confounding variables, IHS was associated with worse clinical outcomes (adjusted OR 3.04 (95% CI 1.57 to 6.04), p<0.001). CONCLUSIONS: The mortality of IHS patients after interhospital transfer and EVT was high and functional outcomes were worse compared with those of OHS patients. Further research is needed to ascertain whether IHS patients benefit from this therapeutic approach. A more careful selection of IHS patients for transfer and means to enable faster treatment should be considered. TRIAL REGISTRATION NUMBER: NCT04270513; Post-results.

Challenges in Palliative Care Nursing at a University Hospital: A Qualitative Interview Study.

We examined the perception of palliative care nurses regarding challenges, coping strategies, resources, and needs when working in a university hospital in Austria. A qualitative descriptive design was applied, using semistructured interviews with 8 female and 2 male nurses. All interviews were recorded as digital audio and transcribed verbatim. We used thematic analysis and MAXQDA. In our analysis, 6 themes emerged: Four themes related to challenges: ( a ) lack of a supporting structural framework, ( b ) conflict in interdisciplinary work, ( c ) conflict with caregivers, and ( d ) dealing with death in a highly specialized university environment. One theme related to ( e ) individual solutions and coping strategies, and 1 theme comprised ( f ) needs and suggestions for improvements. Taking care of the family of a dying person, handling threatening situation, and working with inexperienced physicians were among the most important challenges reported by nurses. A supportive team, professional counseling, and training related to communication skills and to culturally specific needs of families are perceived to be necessary to provide high-quality palliative care. Addressing the needs of nurses can substantially improve their working condition and has an impact not only on the nurses themselves but also on the quality of patient care.

Association Between Use of a Flying Intervention Team vs Patient Interhospital Transfer and Time to Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke in Nonurban Germany.

Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. Exposures: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. Main Outcomes and Measures: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). Results: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P < .001). There was no significant difference in modified Rankin Scale score after 3 months between patients in the flying team (n = 59) and transfer (n = 57) groups who received EVT (median [IQR] score, 3 [2-6] vs 3 [2-5]; adjusted common odds ratio for less disability, 1.91 [95% CI, 0.96-3.88]; P = .07). Conclusions and Relevance: In a nonurban stroke network in Germany, deployment of a flying intervention team to local stroke centers, compared with patient interhospital transfer to referral centers, was significantly associated with shorter time to EVT for patients with acute ischemic stroke. The findings may support consideration of a flying intervention team for some stroke systems of care, although further research is needed to confirm long-term clinical outcomes and to understand applicability to other geographic settings.

100 years of inherited metabolic disorders in Austria-A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021.

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the "Registry for Inherited Metabolic Disorders" started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000-113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months-100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the "Registry for Inherited Metabolic Disorders" is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.

Sex-Specific Differences in Mortality of Patients with a History of Bariatric Surgery: a Nation-Wide Population-Based Study.

PURPOSE: Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. MATERIALS AND METHODS: The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). RESULTS: In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p < 0.001(Chi-squared)). Moreover, the 30-day mortality was 0.19% and sixfold higher in men compared to women (0.48 vs. 0.08%; p < 0.001). CV (82%) and PSY (55%) were the most common comorbidities in deceased patients with no sex-specific differences. Diabetes (38%) was more common in men (43 vs. 33%; p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). CONCLUSION: After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women.

Project "Backtoclinic I": An overview on the state of care of adult PKU patients in Austria.

BACKGROUND: High rates of lost to follow-up (LTFU) adult patients are a major concern in the long-term management of phenylketonuria (PKU). To address this issue, we designed the project "Backtoclinic" with the purpose of identifying LTFU adult PKU patients in Austria as a first step to reestablish appropriate treatment. SUBJECTS AND METHODS: Individuals born between 1966 and 1999 and diagnosed with PKU through the National Austrian Newborn Screening Program (NANSP) were identified using the NANSP's database. Follow-up data were collected in the Austrian metabolic centers (Medical University of Vienna, Graz, Innsbruck and Salzburg). Patients with no contact to any of these centers within the previous two years were classified as LTFU. Epidemiological characteristics of the whole study population as well as of LTFU- and currently in follow-up patients were analyzed. RESULTS: Between 1966 and 1999, 281 individuals were diagnosed with PKU through the NANSP. Two patients died in their first year of life and were excluded from the analysis. Of the remaining 279 patients (mean age ± SD: 36.7 ± 9.1 y, 42.7% females), 177 (63.4%) are currently LTFU. The rate of LTFU patients is higher in men than in women (68.1% vs 57.5%), and markedly increases with age in both sexes. The gender gap is greatest in young adults (52.6% vs. 25.0% in the age range 20.0-24.9 y) and declines with age (94.4% vs. 80.0% in the age range > 45.0 y). CONCLUSIONS: We found an alarming rate of 63.4% of LTFU adult PKU patients in Austria, and observed a gender gap in the PKU state of care. Our findings illustrate the urgent need for the metabolic community to identify LTFU adult PKU patients and to develop strategies to reestablish appropriate treatment for men and women with PKU.

Long-term experience with triheptanoin in 12 Austrian patients with long-chain fatty acid oxidation disorders.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare inborn errors of metabolism with autosomal recessive inheritance that may cause life-threatening events. Treatment with triheptanoin, a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect, seems beneficial, but clinical experience is limited. We report our long-term experience in an Austrian cohort of LC-FAOD patients. METHODS: We retrospectively assessed clinical outcome and total hospitalization days per year before and after start with triheptanoin by reviewing medical records of 12 Austrian LC-FAOD patients RESULTS: For 12 Austrian LC-FAOD patients at three metabolic centers, triheptanoin was started shortly after birth in 3/12, and between 7.34 and 353.3 (median 44.5; mean 81.1) months of age in 9/12 patients. For 11 pediatric patients, mean duration of triheptanoin intake was 5.3 (median 3.9, range 1.2-15.7) years, 10/11 pediatric patients have an ongoing intake of triheptanoin. One patient quit therapy due to reported side effects. Total hospitalization days per year compared to before triheptanoin treatment decreased by 82.3% from 27.1 (range 11-65) days per year to 4.8 (range 0-13) days per year, and hospitalization days in the one year pre- compared to the one year post-triheptanoin decreased by 69.8% from 27.1 (range 4-75) days to 8.2 (range 0-25) days. All patients are in good clinical condition, show normal psychomotor development and no impairment in daily life activities. CONCLUSION: In this retrospective observational study in an Austrian LC-FAOD cohort, triheptanoin data show improvement in disease course. Triheptanoin appears to be a safe and beneficial treatment option in LC-FAOD. For further clarification, additional prospective randomized controlled trials are needed.

Combined Metabolomic Analysis of Plasma and Urine Reveals AHBA, Tryptophan and Serotonin Metabolism as Potential Risk Factors in Gestational Diabetes Mellitus (GDM).

Gestational diabetes mellitus during pregnancy has severe implications for the health of the mother and the fetus. Therefore, early prediction and an understanding of the physiology are an important part of prenatal care. Metabolite profiling is a long established method for the analysis and prediction of metabolic diseases. Here, we applied untargeted and targeted metabolomic protocols to analyze plasma and urine samples of pregnant women with and without GDM. Univariate and multivariate statistical analyses of metabolomic profiles revealed markers such as 2-hydroxybutanoic acid (AHBA), 3-hydroxybutanoic acid (BHBA), amino acids valine and alanine, the glucose-alanine-cycle, but also plant-derived compounds like sitosterin as different between control and GDM patients. PLS-DA and VIP analysis revealed tryptophan as a strong variable separating control and GDM. As tryptophan is biotransformed to serotonin we hypothesized whether serotonin metabolism might also be altered in GDM. To test this hypothesis we applied a method for the analysis of serotonin, metabolic intermediates and dopamine in urine by stable isotope dilution direct infusion electrospray ionization mass spectrometry (SID-MS). Indeed, serotonin and related metabolites differ significantly between control and GDM patients confirming the involvement of serotonin metabolism in GDM. Clustered correlation coefficient visualization of metabolite correlation networks revealed the different metabolic signatures between control and GDM patients. Eventually, the combination of selected blood plasma and urine sample metabolites improved the AUC prediction accuracy to 0.99. The detected GDM candidate biomarkers and the related systemic metabolic signatures are discussed in their pathophysiological context. Further studies with larger cohorts are necessary to underpin these observations.

Effect of fetal and infant malnutrition on metabolism in older age.

BACKGROUND: While malnutrition is an important concern in the developing world, Western countries are experiencing a pandemic of obesity and metabolic diseases. OBJECTIVE: This work reviews the current state of knowledge of the effects of malnutrition during early life on metabolism in older age. METHODS: The impact of early-life determinants on diabetes and related metabolic diseases in later life is elucidated by three different methodological approaches. First, results from animal studies in dietary manipulation models are reviewed. Second, findings from epidemiological studies that often use natural experiments to determine the effects of famines on the health status of the population are discussed. Finally, the relation between maternal or childhood malnutrition and diabetes in adulthood is explored in a big-data study using the entire population of a country across a century. RESULTS: We present overwhelming evidence that the maternal or early childhood nutritional status negatively affects both the short- and long-term health status and development of the offspring, thereby providing starting points to formulate intervention and prevention strategies. In particular, it was found that in the case of early-life exposure to famine, the risk of the offspring to develop type 2 diabetes in older age is up to 125% higher than without famine exposure. CONCLUSION: Due to its inherent complexity, an understanding of the long-term effects of maternal and childhood malnutrition on metabolism in older age necessitates interdisciplinary and big-data approaches. Only then can we hope to prevent chronic diseases at their earliest beginning.