Outbreak of severe community-acquired bacterial infections among children in North Rhine-Westphalia (Germany), October to December 2022.

PURPOSE: In late 2022, a surge of severe S. pyogenes infections was reported in several European countries. This study assessed hospitalizations and disease severity of community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in North Rhine-Westphalia (NRW), Germany, during the last quarter of 2022 compared to long-term incidences. METHODS: Hospital cases due to bacterial infections between October and December 2022 were collected in a multicenter study (MC) from 59/62 (95%) children's hospitals in NRW and combined with surveillance data (2016-2023) from the national reference laboratories for streptococci, N. meningitidis, and H. influenzae. Overall and pathogen-specific incidence rates (IR) from January 2016 to March 2023 were estimated via capture-recapture analyses. Expected annual deaths from the studied pathogens were calculated from national death cause statistics. RESULTS: In the MC study, 153 cases with high overall disease severity were reported with pneumonia being most common (59%, n = 91). IRs of bacterial infections declined at the beginning of the COVID-19 pandemic and massively surged to unprecedented levels in late 2022 and early 2023 (overall hospitalizations 3.5-fold), with S. pyogenes and S. pneumoniae as main drivers (18-fold and threefold). Observed deaths during the study period exceeded the expected number for the entire year in NRW by far (7 vs. 0.9). DISCUSSION: The unprecedented peak of bacterial infections and deaths in late 2022 and early 2023 was caused mainly by S. pyogenes and S. pneumoniae. Improved precautionary measures are needed to attenuate future outbreaks.

Sclerosing Cholangitis in Pediatric Inflammatory Bowel Disease: Early Diagnosis and Management Affect Clinical Outcome.

OBJECTIVE: To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). STUDY DESIGN: Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. RESULTS: Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years were followed up for a mean of 6.8 ± 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 ± 6.1 months vs 9.3 ± 19.4 months; P = .03), did not develop liver-related complications during follow-up. CONCLUSIONS: Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.

The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE-an avoidable health risk: the SAFE randomised trial.

BACKGROUND: Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement. METHODS: In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order. RESULTS: 39-53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation. CONCLUSIONS: Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard. Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS-German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018-Retrospectively registered). Trial protocol can be accessed online.

Multicenter Analysis of Acquired Undescended Testis and Its Impact on the Timing of Orchidopexy.

OBJECTIVE: To assess whether late orchidopexy for undescended testis represents delayed treatment of primary undescended testis or later-occurring acquired undescended testis. STUDY DESIGN: We examined boys undergoing orchidopexy for cryptorchidism regarding age at surgery and entity of undescended testis. We characterized differences between primary undescended testis and acquired undescended testis and evaluated the knowledge regarding the diagnosis and management of acquired undescended testis among practicing physicians. We conducted an observational study using a mixed-method multicenter cross-sectional design. A total of 310 consecutive boys undergoing orchidopexy for undescended testis at 6 pediatric medical centers in Germany between April 2016 and June 2018 were investigated regarding testicular position at birth and age at surgery. In addition, a survey on acquired undescended testis management was carried out in 1017 multidisciplinary physicians and final-year medical students. RESULTS: Only 13% of all patients were operated on in their first year of life. Among patients with known previous testicular position (67%), primary undescended testis (n = 103) and acquired undescended testis (n = 104) were equally frequent. More than one-half (56%) of orchidopexies performed after the first year of life were due to acquired undescended testis. Remarkably, only 15% of physicians considered acquired undescended testis as an indication for late surgery. CONCLUSIONS: Acquired undescended testis is more common than previously perceived and accounts for a significant proportion of "late" orchidopexies in patients with undescended testis. Acquired undescended testis needs to be better recognized in clinical practice and screening should continue in older children with previously descended testes. TRIAL REGISTRATION: German Clinical Trials Registry: DRKS00015903.

Time to shape up - assessment and reporting standards for data quality in clinical research using echocardiographic imaging techniques require improvement.

Advanced echocardiography techniques such as speckle tracking imaging are sensitive diagnostic tools frequently used in various clinical and scientific scenarios. Importantly, imperfect reproducibility and dependence of post-processing algorithms on echocardiographic image quality are potential methodological limitations. Therefore, meticulous assessment of data quality and detailed reporting of study methodology, sample specifics, technical peculiarities and measurement conditions are crucial. Unfortunately, despite the recognized importance of this, there is still no broadly accepted standard for assessing the quality of echocardiographic images in clinical research reports. This article quintessentially highlights important shortcomings of data quality assessment and methodological study design, commonly occurring in clinical research reports using advanced echocardiography techniques. Finally, suggestions are made as to how researchers, scientific communities and biomedical journals can contribute to the ever-lasting process of improving the quality of clinical research in cardiovascular imaging.

Common Indications and The Diagnostic Yield of Esophagogastroduodenoscopy in Children with Gastrointestinal Distress.

BACKGROUND: The number of inconspicuous results of esophagogastroduodenoscopies (EGDs) in childhood appears to be disturbingly high. The aim of this study was to analyze the diagnostic yield of EGD and to determine its relevance of specific clinical indications. METHODS: We performed a retrospective analysis of 380 consecutive pediatric patients who underwent diagnostic EGD in two German level I pediatric gastroenterology departments in 2015 and 2016. RESULTS: 44% of the 380 patients were male and 17% were younger than 5 years old. 55% of all EGDs (n=210) did not yield a pathological result. 27% (n=104) of all EGDs were performed due to nonspecific symptoms (epigastralgia, nausea). Strikingly, in this group, 88% (n=91) showed normal results and in only 12% a diagnosis was made: reflux esophagitis (n=5), Helicobacter pylori (HP) gastritis (n=6) or hemorrhagic gastritis (n=1). Fewer inconspicuous EGDs were performed in patients with dysphagia (68%) or heartburn and reflux (61%). 59 patients were examined due to serologically elevated celiac antibodies. Here, the diagnosis could be confirmed histopathologically in 78% (n=46). Of the 37 patients with abdominal pain and a previously positive non-invasive HP test, EGD served to establish the diagnosis of HP gastritis in 84%. CONCLUSIONS: The diagnostic yield for EGDs is increased in patients with more specific symptoms (i. e. dysphagia, heartburn, HP, celiac disease). Consequently, as an invasive procedure, EGD warrants a strict indication.

Shortcomings in the management of undescended testis: guideline intention vs reality and the underlying causes - insights from the biggest German cohort.

OBJECTIVES: To assess the implementation of the current guideline and identify potential underlying causes for late surgery in children with undescended testis (UDT) in Germany. UDT is the most common surgical issue in paediatric urology and to avoid malignant degeneration and subfertility current guidelines recommend orchidopexy during the first year of life; however, this seems not to be implemented in practice. PATIENTS AND METHODS: In all, 5 547 patients with cryptorchidism at 16 hospitals nationwide were studied regarding age at orchidopexy between 2003 and 2016. Multivariate analysis was performed to identify factors influencing timing of surgery. Additionally, a survey on knowledge of UDT management was conducted amongst physicians treating boys and final-year medical students. RESULTS: Between 2003 and 2008 only 4% of boys with UDT underwent surgery before the age of 1 year. After the guideline update from 2009, this figure was 5% from 2010 to 2012, and 8% from 2013 to 2016. The presence of a specialised department for paediatric surgery, as well as a high UDT case-to-year ratio positively influenced the timing of orchidopexy. The survey revealed discipline-specific differences in the levels of knowledge about UDT management. One-third of respondents did not know the guideline recommendations and 61% felt insufficiently informed. International comparisons revealed significant differences in the age at surgery of boys with UDT, with Germany and Great Britain ranging in the middle of the field. CONCLUSIONS: Currently, only a small proportion of boys with UDT are operated upon during their first year of life. The level of knowledge in attending physicians remains in need of improvement. This should be actively addressed, i.e. by campaigns and educational programmes. Further studies are needed to investigate the underlying causes of late orchidopexy in UDT.

Novel functional advanced echocardiography for the assessment of myocardial mechanics in children with neurocardiogenic syncope - a blinded prospective speckle tracking head-up tilt-table challenge study.

BACKGROUND: Data on left ventricular (LV) function in patients with neurocardiogenic syncope (NS) is conflicting in adults and lacking in children. The aim of this study was to analyze LV myocardial performance in children with NS at rest and during head-up tilt-table (HUTT) testing. METHODS: This is the first study to combine HUTT and speckle-tracking echocardiography (STE) in children with NS. 43 consecutive normotensive pediatric patients with NS (mean age 13.9 ± 2.6 years, 51% female) and 41 sex- and age-matched healthy controls were included in the study. The study groups consisted of 21 patients with a positive HUTT reaction (HUTT+) and 22 with a negative HUTT reaction (HUTT-). STE was used to analyze peak systolic LV myocardial strain and strain rate. RESULTS: Conventional echocardiographic parameters were similar in all analyzed groups. When compared to healthy controls, children with NS had depressed levels of circumferential strain rate (p = 0.032) and significantly depressed longitudinal strain rate (p <  0.001) at rest. Interestingly, during HUTT testing LV global strain and strain rate were similar in both groups. LV strain rate was lowest in HUTT+ followed by HUTT- and control subjects both at rest and during HUTT. CONCLUSIONS: Resting LV longitudinal strain rate is attenuated in children with NS, especially in those with a positive HUTT response. This is further evidence that NS patients feature altered cardiac mechanics rendering them prone to vasovagal perturbations that can ultimately result in collapse. TRIAL REGISTRATION: Witten/Herdecke University ethics committee clinical study number: UWH-73-2014.

The influence of real-time blood glucose levels on left ventricular myocardial strain and strain rate in pediatric patients with type 1 diabetes mellitus - a speckle tracking echocardiography study.

BACKGROUND: Echocardiographic myocardial performance parameters such as strain and strain rate are increasingly used to assess systolic and diastolic function in patients with diabetes mellitus and several other clinical and scientific scenarios. While long-term metabolic marks such as HbA1C are inherently assessed in diabetic patients, the actual blood glucose level at the very moment of the echocardiographic study has not yet been taken into account for the assessment of cardiac mechanics. The aim of this study was to investigate the influence of real-time blood glucose levels on left ventricular (LV) myocardial strain and strain rate in pediatric patients with type 1 diabetes mellitus (T1DM). METHODS: We performed speckle tracking echocardiography on 39 normotensive pediatric patients with uncomplicated type 1 diabetes mellitus (mean age 11.5 ± 3.5 years, 40 % female) and 44 sex- and age-matched healthy controls (mean age 11.4 ± 2.9 years, 45 % female). T1DM patients were sub-categorized according to their blood sugar levels (with a cutoff of 150 mg/dL) at the moment of the echocardiographic exam. Investigators were blinded to the participants' study group status. RESULTS: Interestingly, diabetic patients with higher blood sugar levels demonstrated significantly increased LV circumferential strain (p = 0.003) and strain rate (p = 0.005) as well as global longitudinal strain rate (p = 0.002) in comparison to T1DM patients with lower blood sugar levels or healthy controls. CONCLUSIONS: For the investigation of myocardial performance with sensitive methods such as speckle tracking echocardiography in diabetic study populations real-time blood sugar levels should be taken into account. Further studies are needed to verify these findings in large-scale patient cohorts and serial intra-individual measurements in different metabolic states.

Operative management of cryptorchidism: guidelines and reality--a 10-year observational analysis of 3587 cases.

BACKGROUND: Undescended testis (UDT) is the most common disorder in pediatric surgery and one of the most important risk factors for malignancy and subfertility. In 2009 local guidelines were modified and now recommend treatment to be completed by the age of 1. Aim of this study was to analyze age distribution at the time of orchidopexy, whether the procedure is performed according to guideline recommendations and to assess primary care pediatricians' attitude regarding their treatment approach. METHODS: We retrospectively analyzed 3587 patients with UDT regarding age at orchidopexy between 2003 and 2012 in 13 German hospitals. Furthermore, we conducted an anonymized nation-wide survey among primary care pediatricians regarding their attitude toward management of UDT. RESULTS: Before modification of the guideline 78% (n = 1245) of the boys with UDT were not operated according to guideline recommendations. After the modification that number rose to 95% (n = 1472). 42% of the orchidopexies were performed on patients aged 4 to 17 years. 46% of the primary care pediatricians were not aware of this discrepancy and 38% would only initiate operative management after the first year of life. In hospitals with pediatric surgery departments significantly more patients received orchidopexy in their first year of life (p < .001). CONCLUSION: The guideline for UDT in Germany has not yet been implemented sufficiently. Timing of orchidopexy must be optimized in order to improve long-term prognosis. Both primary care providers and parents should be educated regarding the advantages of early orchidopexy in UDT. Prospective studies are needed to elucidate the high rate of late orchidopexies.

Metal implant removal: benefits and drawbacks--a patient survey.

BACKGROUND: Hardware removals are among the most commonly performed surgical procedures worldwide. Current literature offers little data concerning postoperative patient satisfaction. The purpose of our study was to evaluate the patients' point of view on implant removal. METHODS: We surveyed patients of a German level one trauma center, who underwent hardware removal in 2009 and 2010, with regard to their personal experiences on implant removal. Exclusively, data obtained out of the survey were analyzed. RESULTS: In 332 patients surveyed, most hardware removals were performed at the ankle joint (21%) followed by the wrist (15%). The most frequent indication was a doctor's recommendation (68%), followed by pain (31%) and impaired function (31%). Patient reported complication rate of implant removal was 10%. Importantly, after implant removal because of pain or impaired function patients reported an improvement in function (72%) as well as decreased pain (96%). 96% of all responding patients and 66% of the patients who suffered from subsequent complications would opt for surgical implant removal again. CONCLUSION: In summary, despite the challenging and frequently troublesome nature of surgical hardware removal our data contradicts the widely held view that implant removal is often without a positive effect on the patients. These findings may influence the surgeons' attitude towards implant removal and their day-to-day routine in patient counseling.

Viewpoint: digital paediatrics-so close yet so far away.

Technology is driving a revolution in healthcare, but paediatric services have not fully harnessed the potential. Digital health solutions yet to achieve their promise in paediatrics include electronic health records, decision support systems, telemedicine and remote consultations, despite the accelerated uptake during the COVID-19 pandemic. There are also significant potential benefits in digitally enabled research, including systems to identify and recruit participants online or through health records, tools to extract data points from routine data sets rather than new data collection, and remote approaches to outcome measurement. Children and their families are increasingly becoming digital health citizens, able to manage their own health and use of health services through mobile apps and wearables such as fitness trackers. Ironically, one barrier to the uptake of these technologies is that the fast pace of change in this area means the evidence base behind many of these tools remains underdeveloped. Clinicians are often sceptical of innovations which appear largely driven by enthusiasts rather than science. Rigorous studies are needed to demonstrate safety and effectiveness. Regulators need to be agile and responsive. Implementation needs adequate resource and time, and needs to minimise risks and address concerns, such as worries over losing human contact. Digital health care needs to be embedded in medical education and training so that clinicians are trained in the use of innovations and can understand how to embed within services. In this way, digital paediatrics can deliver benefits to the profession, to services and to our patients.

Are Parents Informed Well Enough About Their Child's Long-term Risks Related to Undescended Testis?

Worldwide, recommendations for timely surgical repair of undescended testis (UDT) are not well translated into clinical practice, potentially due to suboptimal patient/parent education. We evaluated the frequency and content of information provided to affected parents of 310 consecutive cases of UDT undergoing orchidopexy. Parents were enquired regarding details of education provided by the attending clinician. 18% of parents were not provided with detailed information regarding any long-term consequences of untreated UDT. In the 79% who were educated, information about impaired fertility was frequent, while malignant degeneration, hypogonadism and testicular atrophy were poorly communicated. 49% of all parents searched for further information on the internet or through a second medical opinion. The frequency and level of detail of information regarding long-term complications provided to parents of children with UDT is suboptimal and needs to be improved.

Stereophotogrammetry can feasibly assess 'physiological' longitudinal three-dimensional head development of very preterm infants from birth to term.

Head development is a surrogate for brain development in infants and is related to neurocognitive outcome. There is only limited knowledge on early extra-uterine head shape and size assessment in very preterm infants. Here, 26 very preterm infants with a mean gestational age of 29.1 ± 2.2 weeks and a mean birth weight of 1273.8 ± 427.7 g underwent serial stereophotogrammetric 3D head imaging in weekly intervals from birth to term-equivalent age. The main outcome was the longitudinal assessment of the 'physiological' preterm head development with cephalometric size (head circumference, cranial volume) and shape parameters (cranial index, cranial vault asymmetry index) according to chronological and postmenstrual age (PMA). Potential clinical risk factors for the development of an abnormal low cranial index (dolichocephaly) were analysed. In serial measurements of 26 infants, the estimated head volume (95% confidence interval) increased from 244 (226-263) cm3 at 28 weeks PMA to 705 (688-721) cm3 at 40 weeks PMA. Moderate or severe dolichocephaly occurred in 21/26 infants (80.8%). Cranial index decreased over time (72.4%; 70.7-74 95% confidence interval). Brachycephaly and plagiocephaly were uncommon. No risk factors for severe dolichocephaly were identified. Our study shows that early detection of head shape and size anomalies utilizing 3D stereophotogrammetry is feasible and safe even in very preterm infants < 1500 g and/or < 32 weeks. 3D stereophotogrammetry could be used for timely identification of infants at risk for head shape anomalies. No specific risk factors for head shape anomalies were identified, especially not mode and duration of respiratory support.

Culture-Associated DNA Methylation Changes Impact on Cellular Function of Human Intestinal Organoids.

BACKGROUND & AIMS: Human intestinal epithelial organoids (IEOs) are a powerful tool to model major aspects of intestinal development, health, and diseases because patient-derived cultures retain many features found in vivo. A necessary aspect of the organoid model is the requirement to expand cultures in vitro through several rounds of passaging. This is of concern because the passaging of cells has been shown to affect cell morphology, ploidy, and function. METHODS: Here, we analyzed 173 human IEO lines derived from the small and large bowel and examined the effect of culture duration on DNA methylation (DNAm). Furthermore, we tested the potential impact of DNAm changes on gene expression and cellular function. RESULTS: Our analyses show a reproducible effect of culture duration on DNAm in a large discovery cohort as well as 2 publicly available validation cohorts generated in different laboratories. Although methylation changes were seen in only approximately 8% of tested cytosine-phosphate-guanine dinucleotides (CpGs) and global cellular function remained stable, a subset of methylation changes correlated with altered gene expression at baseline as well as in response to inflammatory cytokine exposure and withdrawal of Wnt agonists. Importantly, epigenetic changes were found to be enriched in genomic regions associated with colonic cancer and distant to the site of replication, indicating similarities to malignant transformation. CONCLUSIONS: Our study shows distinct culture-associated epigenetic changes in mucosa-derived human IEOs, some of which appear to impact gene transcriptomic and cellular function. These findings highlight the need for future studies in this area and the importance of considering passage number as a potentially confounding factor.

Guidance on the interpretation of faecal calprotectin levels in children.

BACKGROUND: Faecal calprotectin (FCP) is a powerful tool to predict inflammatory bowel disease (IBD) in patients with gastrointestinal symptoms. In the paediatric patient population, the reference value of < 50 µg/g and the influence of age on FCP levels result in a high number of redundant investigations and specialist referrals. We assessed paediatric FCP levels, their diagnostic value and corresponding referral pathways from primary and secondary care. METHODS: We analysed two cohorts from a precisely defined catchment area: one consisted of all FCPs measured in this area (n = 2788). The second cohort-a subset of the first cohort-consisted of FCP values and corresponding clinical data from children who were referred for possible IBD to our department (n = 373). RESULTS: In the first cohort, 47% of FCP levels were > 50 µg/g, 15% were ≥ 250 µg/g. Children < 1y had significantly (p < 0.001) higher FCP than older children. In the second cohort, 6.7% of children with an FCP of < 250 µg/g (or 8.6% with an FCP of < 600 µg/g) had IBD-all featured symptoms suggestive of IBD (e.g. bloody diarrhoea, nocturnal abdominal pain, weight loss) or abnormal blood tests. 76% of patients in whom raised FCP (> 50 µg/g) was the sole reason for being referred for suspected IBD did not have IBD. CONCLUSION: Children with an FCP < 600 µg/g and without matching symptoms suggestive of IBD are unlikely to have IBD. A higher FCP reference value may provide cost-effective improvement that could avoid redundant investigations and specialist referrals. A guideline for specialist referrals is proposed.

Stereophotogrammetric head shape assessment in neonates is feasible and can identify distinct differences between term-born and very preterm infants at term equivalent age.

The development of head shape and volume may reflect neurodevelopmental outcome and therefore is of paramount importance in neonatal care. Here, we compare head morphology in 25 very preterm infants with a birth weight of below 1500 g and / or a gestational age (GA) before 32 completed weeks to 25 term infants with a GA of 37-42 weeks at term equivalent age (TEA) and identify possible risk factors for non-synostotic head shape deformities. For three-dimensional head assessments, a portable stereophotogrammetric device was used. The most common and distinct head shape deformity in preterm infants was dolichocephaly. Severity of dolichocephaly correlated with GA and body weight at TEA but not with other factors such as neonatal morbidity, sex or total duration of respiratory support. Head circumference (HC) and cranial volume (CV) were not significantly different between the preterm and term infant group. Digitally measured HC and the CV significantly correlated even in infants with head shape deformities. Our study shows that stereophotogrammetric head assessment is feasible in all preterm and term infants and provides valuable information on volumetry and comprehensive head shape characteristics. In a small sample of preterm infants, body weight at TEA was identified as a specific risk factor for the development of dolichocephaly.

Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover.

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their "normal" drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their "regular" drinking level, considerably higher alcohol intake-irrespective of the absolute amount-may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.

Grape or grain but never the twain? A randomized controlled multiarm matched-triplet crossover trial of beer and wine.

Background: Alcohol-induced hangover constitutes a significant, yet understudied, global hazard and a large socio-economic burden. Old folk wisdoms such as "Beer before wine and you'll feel fine; wine before beer and you'll feel queer" exist in many languages. However, whether these concepts in fact reduce hangover severity is unclear. Objectives: The aim of this study was to investigate the influence of the combination and order of beer and wine consumption on hangover intensity. Methods: In this multiarm, parallel randomized controlled matched-triplet crossover open-label interventional trial, participants were matched into triplets and randomly assigned according to age, gender, body composition, alcohol drinking habits, and hangover frequency. Study group 1 consumed beer up to a breath alcohol concentration (BrAC) ≥0.05% and then wine to BrAC ≥0.11% (vice versa for study group 2). Control group subjects consumed either only beer or only wine. On a second intervention day (crossover) ≥1 wk later, study-group subjects were switched to the opposite drinking order. Control-group subjects who drank only beer on the first intervention received only wine on the second study day (and vice versa). Primary endpoint was hangover severity assessed by Acute Hangover Scale rating on the day following each intervention. Secondary endpoints were factors associated with hangover intensity. Results: Ninety participants aged 19-40 y (mean age 23.9), 50% female, were included (study group 1 n = 31, study group 2 n = 31, controls n = 28). Neither type nor order of consumed alcoholic beverages significantly affected hangover intensity (P > 0.05). Multivariate regression analyses revealed perceived drunkenness and vomiting as the strongest predictors for hangover intensity. Conclusions: Our findings dispel the traditional myths "Grape or grain but never the twain" and "Beer before wine and you'll feel fine; wine before beer and you'll feel queer" regarding moderate-to-severe alcohol intoxication, whereas subjective signs of progressive intoxication were confirmed as accurate predictors of hangover severity. This trial was prospectively registered at the Witten/Herdecke University Ethics Committee as 140/2016 and retrospectively registered at the German Clinical Trials Register as DRKS00015285.