Long-term health consequences among individuals with SARS-CoV-2 infection compared to individuals without infection: results of the population-based cohort study CoMoLo Follow-up.

BACKGROUND: Most of the previous studies on health sequelae of COVID-19 are uncontrolled cohorts and include a relatively short follow-up. This population-based multi-center cohort study examined health consequences among individuals about 1 to 1.5 years after SARS-CoV-2 infection compared with non-infected. METHODS: The study population consisted of adults (≥ 18 years) from four municipalities particularly affected by the COVID-19 pandemic in the year 2020 who completed a detailed follow-up questionnaire on health-related topics. Exposure was the SARS-CoV-2 infection status (based on IgG antibodies, PCR test, or physician-diagnosis of COVID-19) at baseline (May to December 2020). Outcomes assessed at follow-up (October 2021 to January 2022; mean: 452 days) included recurrent or persistent health complaints, incident diseases, health-related quality of life (PROMIS-29), subjective health, and subjective memory impairment. Logistic and linear regression models were adjusted for baseline sociodemographic and lifestyle characteristics (age, sex, municipality, education, smoking, body mass index), pre-existing health conditions (chronic disease/health problem, health-related activity limitation, depressive/anxiety disorder), and follow-up time. RESULTS: Among 4817 participants, 350 had a SARS-CoV-2 infection at baseline and 4467 had no infection at baseline or during follow-up. Those with an infection statistically significantly more often reported 7 out of 18 recurrent or persistent health complaints at follow-up: smell/taste disorders (12.8% vs. 3.4%, OR 4.11), shortness of breath (23.0% vs. 9.5%, 3.46), pain when breathing (4.7% vs. 1.9%, 2.36), fatigue (36.9% vs. 26.1%, 1.76), weakness in legs (12.8% vs. 7.8%, 1.93), myalgia/joint pain (21.9% vs. 15.1%, 1.53) and cough (30.8% vs. 24.8%, 1.34) and 3 out of 6 groups of incident diseases: liver/kidney (2.7% vs. 0.9%, 3.70), lung (3.2% vs. 1.1%, 3.50) and cardiovascular/metabolic (6.5% vs. 4.0%, 1.68) diseases. Those with an infection were significantly more likely to report poor subjective health (19.3% vs. 13.0%, 1.91), memory impairment (25.7% vs. 14.3%, 2.27), and worse mean scores on fatigue and physical function domains of PROMIS-29 than non-infected. CONCLUSION: Even after more than one year, individuals with SARS-CoV-2 infection showed an increased risk of various health complaints, functional limitations, and worse subjective well-being, pointing toward profound health consequences of SARS-CoV-2 infection relevant for public health.

[Seroprevalence of SARS-CoV-2 among children and adolescents in Germany-an overview]. / SARS-CoV-2-Seroprävalenz bei Kindern und Jugendlichen in Deutschland ­ ein Überblick.

BACKGROUND: SARS-CoV­2 serologic studies complement and expand findings from confirmed COVID-19 cases through identification of undetected cases. OBJECTIVES: This article summarizes previous results on SARS-CoV­2 prevalence from seroepidemiological studies in Germany focusing on children and adolescents and complements the already existing overview on seroprevalence in adults from general population samples and especially blood donors in Germany. METHODS: The results are based on an ongoing systematic search in study registries, in literature databases, of preprint publications, and of media reports of seroepidemiological studies in Germany and their results. RESULTS: As of 17 September 2021, we are aware of 16 German seroepidemiological studies focusing on children and adolescents. Results are available for nine of these studies. For almost all settings studied, SARS-CoV­2 seroprevalence was well below 1% for preschool and elementary school children in the first COVID-19 wave and below 2% for adolescents. As the pandemic progressed, higher seroprevalences of up to 8% were found in elementary school children. DISCUSSION: Results of SARS-CoV­2 antibody studies in children and adolescents in Germany are scarce so far and are based on non-representative samples at local or regional level. In future studies, it is necessary on the one hand to estimate which proportion of children and adolescents has already either had an infection or has been vaccinated. On the other hand, it is important to investigate physical and mental health impairments that occur after an infection.

[Erratum to: Application of medicines and nutritional supplements in childhood and adolescence in Germany]. / Erratum zu: Anwendung von Arznei- und Nahrungsergänzungsmitteln im Kindes- und Jugendalter in Deutschland.

In KiGGS Wave 2, data from 3­ to 17-year-olds were collected from a total of 3462 persons using a standardized interview on the current use of AM/NEM in the last seven days. For trends analysis, data from 14,679 study participants in the same age group from the KiGGS baseline study were used.In KiGGS Wave 2, 36.4% (95% CI 34.1-38.8) of the 3­ to 17-year-olds had used at least one AM/NEM in the last seven days. The prevalence was highest at 46.5% in 14- to 17-year-olds and significantly different between girls and boys (56.4% vs. 37.3%). Only among girls were there significant differences by migrant background with a higher prevalence of use among girls without a migrant background.Most frequently, the preparations used were for treatment of the respiratory tract (girls: 14.5%, boys: 15.1%), followed by "Varia" (girls: 8.7%, boys: 9.3%) and preparations for the treatment of the musculoskeletal system (girls: 9.0%, boys: 5.9%). There was a significant decrease in the overall prevalence of medicine use compared to the KiGGS baseline study (46.4% vs. 36.4%). This decrease was mainly due to lower prevalences of use in the ATC main groups "N Nervous System" (7.5% vs. 5.4%), "J Systemic Anti-infectives" (2.5% vs. 1.4%) and "H Systemic Hormones, excl. Sexual Hormones and Insulins" (2.0% vs. 1.1%).The results describe key points in the use of AM/NEM, including self-medication for children and adolescents in Germany. They illustrate the use behaviour and represent a valuable supplement to prescription data.

[Application of medicines and nutritional supplements in childhood and adolescence in Germany : Results from KiGGS Wave 2]. / Anwendung von Arznei- und Nahrungsergänzungsmitteln im Kindes- und Jugendalter in Deutschland : Ergebnisse aus KiGGS Welle 2.

In KiGGS Wave 2, data from 3­ to 17-year-olds were collected from a total of 3462 persons using a standardized interview on the current use of AM/NEM in the last seven days. For trends analysis, data from 14,679 study participants in the same age group from the KiGGS baseline study were used.In KiGGS Wave 2, 36.4% (95% CI 34.1-38.8) of the 3­ to 17-year-olds had used at least one AM/NEM in the last seven days. The prevalence was highest at 46.5% in 14- to 17-year-olds and significantly different between girls and boys (56.4% vs. 37.3%). Only among girls were there significant differences by migrant background with a higher prevalence of use among girls without a migrant background.Most frequently, the preparations used were for treatment of the respiratory tract (girls: 14.2%, boys: 14.9%), followed by "Varia" (girls: 8.7%, boys: 9.3%) and preparations for the treatment of the musculoskeletal system (girls: 8.9%, boys: 5.8%). There was a significant decrease in the overall prevalence of medicine use compared to the KiGGS baseline study (46.4% vs. 36.4%). This decrease was mainly due to lower prevalences of use in the ATC main groups "N Nervous System" (7.5% vs. 5.4%), "J Systemic Anti-infectives" (2.5% vs. 1.4%) and "H Systemic Hormones, excl. Sexual Hormones and Insulins" (2.0% vs. 1.1%).The results describe key points in the use of AM/NEM, including self-medication for children and adolescents in Germany. They illustrate the use behaviour and represent a valuable supplement to prescription data.

[Headache, abdominal and back pain in children and adolescents in Germany : Results from KiGGS Wave 2 and trends]. / Kopf­, Bauch- und Rückenschmerzen bei Kindern und Jugendlichen in Deutschland : Ergebnisse aus KiGGS Welle 2 und Trends.

BACKGROUND: Pain not only causes suffering in children and adolescents, but also leads to school absenteeism, medication intake, medical treatment, and an increased risk of recurrent pain in adulthood. OBJECTIVES: Based on data from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014-2017), the 3­month prevalence of recurrent headache, abdominal and back pain in girls and boys is reported, and is compared with the prevalence from the KiGGS baseline survey (2003-2006). The consequences of recurrent headache were also explored. MATERIALS AND METHODS: Data from >11,000 participants (KiGGS Wave 2) and from >12,000 (KiGGS baseline) participants aged between 3 and 17 years were analyzed. For 3­ to 10-year-olds, parents/guardians answered the questions, while 11- to 17-year-olds provided information themselves. RESULTS: In 3­ to 10-year-olds, recurrent abdominal pain was most prevalent, affecting one third of girls and one quarter of boys. Headache was the most frequent type of pain in 11- to 17-year-olds, affecting almost every second girl and about every third boy. The 3­month prevalence of recurrent headache, abdominal and back pain has increased in girls and boys, especially in the age groups 7 to 10 years and 11 to 13 years. Among recurrent headache sufferers, adolescents take medication almost twice as often as children. CONCLUSIONS: Headache, abdominal, and back pain are still and with increasing prevalence very common symptoms in children and adolescents in Germany. Their prevention requires a holistic view of children's health in the psychosocial living environment, and healthcare context.

[Secondary prevention of coronary heart disease in women and men in Germany from 1997-1999 and from 2008-2011-Trend analysis with two national health population surveys]. / Medikamentöse Sekundärprävention bei Frauen und Männern mit koronarer Herzkrankheit in Deutschland zwischen 1997­1999 und 2008­2011 ­ Trendanalyse mit Daten zweier bundesweiter Gesundheitssurveys.

BACKGROUND: The benefit of medicines in the secondary prevention of coronary heart disease (CHD) has been demonstrated in women and men. However, gender-specific differences have been observed in the prescription of these medicines. Information on trends in prevalence use in women and men from population-based studies are still lacking. METHODS: Data of people aged 40-79 years with CHD from the national health interview and examination surveys for adults in Germany from 1997-1999 (GNHIES98, n = 411) and from 2008-2011 (DEGS1, n = 440) were analyzed. Trend analyses via multivariable regression models, taking into account relevant covariables, were used to calculate the prevalence of medicine use in secondary prevention of CHD between GNHIES98 and DEGS1. The following groups were considered: antiplatelet, statins, beta-receptor blockers, agents acting on the renin-angiotensin system (RAS blocker), calcium-channel blockers, and nitrate. RESULTS: In one decade, the prevalence had increased for antiplatelet (24.0% vs. 59.6%), statins (18.5% vs. 56.2%), beta-receptor blockers (24.7% vs. 65.5%), and RAS blockers (31.6% vs. 69.0%). The prevalence of calcium-channel blockers (33.3% vs. 20.5%) and nitrate (40.6% vs. 10.1%) had decreased. In GNHIES98, men were more likely to use RAS blockers. Significant gender differences were found in DEGS1 only for angiotensin-converting-enzyme (ACE) inhibitors. CONCLUSION: This study showed an improvement in the use of drugs for the secondary prevention of CHD in both sexes.

Resting Heart Rate Percentiles and Associated Factors in Children and Adolescents.

OBJECTIVES: To present population-based resting heart rate (RHR) percentiles and associated factors in children and adolescents. STUDY DESIGN: Standardized RHR measurements with an oscillometric device were obtained from 3- to 17-year-olds who participated in the German Health Interview and Examination Survey for Children and Adolescents (n = 11 986). Age- and sex-specific RHR percentiles were derived using flexible age-dependent modeling. Linear regression was used to test associations of RHR and associated factors. RESULTS: RHR decreased with age and mean RHR was on average 3.0 beats per minute (bpm) higher in girls than in boys (P < .01). The 95th RHR-KiGGS-percentile (P95) in boys and girls are up to 10 bpm lower than P95 based on pooled heterogeneous international studies and more similar to percentiles based on population data from NHANES (higher or lower by ≤5 bpm, depending on age). Factors independently associated with RHR in both sexes were age, SBP and height in children aged 3-10 years; and age, systolic blood pressure, and high aerobic fitness in adolescents aged 11-17 years. In girls, we further found an association between RHR and underweight (OR 3.3 and 4.7 for underweight girls aged 3-10 and 11-17, respectively, compared with normal weight girls). Associations between RHR and aerobic fitness, physical activity, and media use were stronger in boys than in girls. CONCLUSION: This study provides population-based RHR percentiles and evidence for sex-dependent associations of cardiovascular risk factors with RHR in children and adolescents, many of which are lifestyle related.

Drug-induced liver injury: results from the hospital-based Berlin Case-Control Surveillance Study.

AIM: Drug-induced liver injury (DILI) is often responsible for acute liver failure, drug withdrawal, boxed warnings or drug non-approval. Therefore, we conducted a case-control study to determine the hepatotoxic risk of a wide range of drugs. METHODS: The Berlin Case-Control Surveillance Study FAKOS included all 51 Berlin hospitals in a hospital network. Between 2002 and 2011, 198 patients with acute idiopathic hepatitis, 377 inpatient controls and 708 outpatient controls were ascertained. Case patients were thoroughly validated using anamnestic, clinical, laboratory and histological data. Drug exposure was obtained in a face-to-face interview. A possible drug aetiology was assessed in individual patients by applying the updated Council for International Organizations of Medical Sciences (CIOMS) scale. Drug risks were further quantified [odds ratios (OR) with 95% confidence intervals (CI)] in a case-control design with unconditional logistic regression analysis. Drug intake in the last 28 days before index date was considered for the analysis. RESULTS: The study corroborated hepatotoxic risks for a number of drugs, including phenprocoumon (OR 3.3, 95% CI 1.5, 6.7), amiodarone (OR 5.5, 95% CI 1.3, 21.2), clozapine (OR 34.6, 95% CI 2.8, 824.9) and flupirtine (OR 40.2, 95% CI 5.5, 856.9). Increased risks were also suggested for less commonly reported substances such as angiotensin II receptor blockers, atypical antipsychotics and for biperiden, a drug never before reported to be hepatotoxic. CONCLUSIONS: Our study identified a large number of drugs as possible causes of hepatotoxicity. The observed risk for seldom reported substances highlights the need for further post-authorization safety studies not exclusively focusing on drugs already labelled as potentially hepatotoxic.

Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case-Control Surveillance Study.

PURPOSE: Treatment with metamizole (dipyrone) has steadily increased in Germany over the last decade. The consequences of this increase for metamizole-induced agranulocytosis (MIA) are unclear. The present study addressed this topic using data from the Berlin Case-Control Surveillance Study. METHODS: Adult patients (≥18 years of age) with acute nonchemotherapy-induced agranulocytosis were identified by active surveillance in all 51 Berlin hospitals between 2000 and 2010. Cases related to metamizole were ascertained applying the drug causality criteria of the World Health Organization. The incidence rate of MIA was calculated and standardised by age and sex based on the German standard population in 2010. RESULTS: Twenty-six MIA cases out of 88 (30 %) patients with validated agranulocytosis were ascertained. The incidence of MIA was 0.96 (95 % confidence interval (CI) 0.95-0.97) cases per million per year. The median age of MIA cases was 50 years (quartile (Q)1 31 years; Q3 68 years) and 19 (73 %) of them were women. In 17 (65 %) cases, neutrophil granulocytes dropped below the value of 0.1 × 10(9) cells/L with three patients suffering from sepsis. Headache and postoperative pain were the most frequent indications for metamizole in outpatients (n = 16) and inpatients (n = 10), respectively. The median treatment duration was 6 days (Q1 4 days; Q3 19 days). CONCLUSIONS: MIA persists as a severe condition in current pharmacotherapy. The continuous increase of metamizole applications should be critically assessed, especially in regard to indications in the outpatient setting and with respect to metamizole treatment duration.

Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany.

AIMS: Drug-induced long QT syndrome (diLQTS) leading to Torsade de Pointes (TdP) is a potentially lethal condition, which has led to several post-marketing drug withdrawals in the past decade. The true incidence of diLQTS/TdP is largely unknown. One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies. To gain more insight into the incidence of diLQTS and TdP, the Berlin Pharmacovigilance Center (PVZ-FAKOS) has actively and prospectively identified patients who developed this particular type of drug-induced adverse event. Here, the basic characteristics of the affected patients are summarized and suspected drugs are discussed. Furthermore, an extrapolation of the Berlin incidence rates to the German Standard Population is presented. METHODS AND RESULTS: Using a Berlin-wide network of 51 collaborating hospitals (>180 clinical departments), adult patients presenting with long QT syndrome (LQTS/TdP) between 2008 and 2011 were identified by active surveillance of these hospitals. Drug exposures as well as other possible risk factors were obtained from the patient's files and in a face-to-face interview with the patient. One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process. The majority (66%) of these cases were female and 60% had developed LQTS/TdP in the outpatient setting. Thirty-five (60%) of 58 confirmed cases were assessed as drug-related based on a standardized causality assessment applying the criteria of the World Health Organization. Drugs assessed as related in more than two cases were metoclopramide, amiodarone, melperone, citalopram, and levomethadone. The age-standardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females. CONCLUSION: While European annual reporting rates based on spontaneous reports suggest an annual diLQTS/TdP incidence of 0.26 per million in Germany, we estimated a considerably higher incidence of diLQTS/TdP in an active surveillance approach. Further measures are warranted to better sensitize physicians against this potentially life-threatening drug-induced adverse event.

Primary prevention in general practice - views of German general practitioners: a mixed-methods study.

BACKGROUND: Policy efforts focus on a reorientation of health care systems towards primary prevention. To guide such efforts, we analyzed the role of primary prevention in general practice and general practitioners' (GPs) attitudes toward primary prevention. METHODS: Mixed-method study including a cross-sectional survey of all community-based GPs and focus groups in a sample of GPs who collaborated with the Institute of General Practice in Berlin, Germany in 2011. Of 1168 GPs 474 returned the mail survey. Fifteen GPs participated in focus group discussions. Survey and interview guidelines were developed and tested to assess and discuss beliefs, attitudes, and practices regarding primary prevention. RESULTS: Most respondents considered primary prevention within their realm of responsibility (70%). Primary prevention, especially physical activity, healthy eating, and smoking cessation, was part of the GPs' health care recommendations if they thought it was indicated. Still a quarter of survey respondents discussed reduction of alcohol consumption with their patients infrequently even when they thought it was indicated. Similarly 18% claimed that they discuss smoking cessation only sometimes. The focus groups revealed that GPs were concerned about the detrimental effects an uninvited health behavior suggestion could have on patients and were hesitant to take on the role of "health policing". GPs saw primary prevention as the responsibility of multiple actors in a network of societal and municipal institutions. CONCLUSIONS: The mixed-method study showed that primary prevention approaches such as lifestyle counseling is not well established in primary care. GPs used a selective approach to offer preventive advice based upon indication. GPs had a strong sense that a universal prevention approach carried the potential to destroy a good patient-physician relationship. Other approaches to public health may be warranted such as a multisectoral approach to population health. This type of restructuring of the health care sector may benefit patients who are unable to afford specific prevention programmes and who have competing demands that hinder their ability to focus on behavior change.

Off-label medicine use in children and adolescents: results of a population-based study in Germany.

BACKGROUND: Population-based self-reported data on off-label medicine use independent from health care provisions are lacking. The purpose of this study is to investigate off-label medicine use in children and adolescents in Germany in a non-clinical setting and to identify prevalence, determinants and spectrum of off-label medicine use. METHODS: Data were obtained from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) conducted by the Robert Koch Institute (2003-2006). 17,450 randomly selected children aged 0-17 years took part in the drug interviews. Of those, 8,899 took at least one medicine during the 7 days preceding the interview. Off-label medicine use was defined as the discrepancy between actual use and the intended use described in the summary of product characteristics. Off-label medicine use was stratified into off-label indication, off-label age, off-label over-dosing, and off-label under-dosing. RESULTS: The prevalence rate of off-label medicine use among those who used medicines amount of is 40.2%. The prevalence rate is significantly higher in boys (41.4%), in children aged 3 to 6 years (48.7%), without migration background (40.9%), with high social status (42.5%), living in small (42.0%) and medium sized cities (41.6%), and with a poor parents rated health status (41.7%). 12,667 preparations (attributable in respect to off-label use) were taken by 8,899 children. 30% of the medicines have been used off-label. Off-label medicine use was highest in preparations of the ATC-class "C00 Cardiovascular System". In all origins of medicine, all age groups and all ATC-classes under-dosing was the most frequent reason for off-label medicine use. CONCLUSIONS: There is a considerable level of self-reported off-label medicines use in the general paediatric population. Further investigations are needed to examine in how far off-label medicine use is based on lack of knowledge or on empiricism in paediatric pharmacotherapy. Attention also needs to be paid to under-dosing which potentially exposes drug users to risks of side effects without the benefit of a therapeutic effect. Clinical trials for licensing of paediatric medicines, education of health care professionals, but also of parents and carers are needed to ensure the rational use of medicines.

German GPs' willingness to expand roles of physician assistants: a regional survey of perceptions and informal practices influencing uptake of health reforms in primary health care.

BACKGROUND: Many countries with shortages in health personnel are introducing task shifting in primary health care. GPs' attitudes and practices strongly affect task shifting and the expansion of the roles of physician assistants (PAs). OBJECTIVE: To assess, in a German state with shortages of health personnel, the overall willingness of GPs to delegate home visit tasks to PAs and to elicit their perceptions of barriers to and benefits of such delegation and the current practice of informal delegation. METHODS: Postal self-administered anonymous survey of all practicing GPs in the rural state of Mecklenburg-Vorpommern. Main outcomes were GPs' willingness to delegate in home visit tasks to a properly trained PA, perceived barriers to and benefits of home visit delegation and current practice of informal delegation. Using multinomial logistic regression, associations were identified among outcome variables, and characteristics of the GPs and of their practices. RESULTS: Response rate was 47%. Responders (500) were comparable to all GPs in the state (1096); 48% of practitioners are willing to delegate home visits tasks to PAs. The main barrier to delegation was the related costs of PAs' training (34%), and the main benefit that it 'saves the GP's time' (67%). The 46% of practitioners who are informally delegating home visit tasks were significantly more likely be younger [odds ratio (OR) and 95% confidence interval (CI)] [OR = 0.96 (0.93-0.99)] and female [OR = 1.70 (1.12-2.58)]. CONCLUSION: The increasing proportion of women in family medicine might favor task shifting in General Practice.

Blood pressure and resting heart rate in 3-17-year-olds in Germany in 2003-2006 and 2014-2017.

To track blood pressure (BP) and resting heart rate (RHR) in children and adolescents is important due to its associations with cardiovascular outcomes in the adulthood. Therefore, the aim of this study was to examine BP and RHR over a decade among children and adolescents living in Germany using national examination data. Cross-sectional data from 3- to 17-year-old national survey participants (KiGGS 2003-06, n = 14,701; KiGGS 2014-17, n = 3509) including standardized oscillometric BP and RHR were used for age- and sex-standardized analysis. Measurement protocols were identical with the exception of the cuff selection rule, which was accounted for in the analyses. Different BP and RHR trends were observed according to age-groups. In 3- to 6-year-olds adjusted mean SBP and DBP were significantly higher in 2014-2017 compared to 2003-2006 (+2.4 and +1.9 mm Hg, respectively), while RHR was statistically significantly lower by -3.8 bpm. No significant changes in BP or in RHR were observed in 7- to 10-year-olds over time. In 11- to 13-year-olds as well as in 14- to 17-year-olds lower BP has been observed (SBP -2.4 and -3.2 mm Hg, respectively, and DBP -1.8 and -1.7 mm Hg), while RHR was significantly higher (+2.7 and +3.7 bpm). BP trends did not parallel RHR trends. The downward BP trend in adolescents seemed to follow decreasing adult BP trends in middle and high-income countries. The increase in BP in younger children needs confirmation from other studies as well as further investigation. In school-aged children and adolescents, the increased RHR trend may indicate decreased physical fitness.

Carotid Intima-Media Thickness Percentiles in Adolescence and Young Adulthood and Their Association With Obesity and Hypertensive Blood Pressure in a Population Cohort.

BACKGROUND: This study aimed to derive carotid intima media thickness (CIMT) percentiles from a population-based sample of adolescents and young adults using improved technology, standardization and quality control, and to investigate the association of CIMT with hypertensive blood pressure (BP) and obesity. METHODS: Four thousand seven hundred nine 14- to 28-year-old participants of the German KiGGS cohort 11-year follow-up, which was based on a nationwide population sample, had B-mode ultrasound CIMT measurement with semi-automated edge-detection and automatic ECG-gated real-time quality control. CIMT percentiles were estimated from far wall CIMT during 2 to 6 heart cycles using the GAMLSS statistical model. Hypertensive BP, overweight, obesity, and a risk score from added Z scores of triglycerides, total/HDL (high-density lipoprotein)-cholesterol ratio, and glycated hemoglobin were based on standardized measurements at baseline and follow-up. RESULTS: CIMT differed by sex at all ages, furthermore by age and height in a nonlinear fashion. Percentiles were estimated simultaneously by age and height. Hypertensive BP and obesity were associated cross-sectionally and longitudinally with a higher risk of CIMT ≥75th percentile in log-binomial regression models adjusted for age, sex, height, current smoking, and cardiovascular risk score. For CIMT ≥90th percentile, the relative risk effect estimates were consistently >1 but often had large confidence intervals including 1, largest adjusted relative risk 3.37 (95% CI, 1.41-8.04) for the combination of hypertensive BP and obesity at follow-up. CONCLUSIONS: Based on state-of-the-art measurements and statistical techniques, these population-based CIMT percentiles by sex, age and height add unbiased evidence for the association of subclinical atherosclerosis with hypertensive BP and obesity in the young.

Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome.

BACKGROUND: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk. METHODS: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.7% White, 85.6% symptomatic), computational methods identified proteins interacting most significantly with 216 QT-prolonging drugs. All cases underwent sequencing of 31 candidate genes arising from this analysis or associating with congenital LQTS. Variants were filtered using a minor allele frequency <1% and classified for susceptibility for aLQTS. Gene-burden analyses were then performed comparing the primary cohort to control exomes (n=452) and an independent replication aLQTS exome sequencing cohort. RESULTS: In 25.5% of cases, at least one rare variant was identified: 22.2% of cases carried a rare variant in a gene associated with congenital LQTS, and in 4% of cases that variant was known to be pathogenic or likely pathogenic for congenital LQTS; 7.8% cases carried a cytochrome-P450 (CYP) gene variant. Of 12 identified CYP variants, 11 (92%) were in an enzyme known to metabolize at least one culprit drug to which the subject had been exposed. Drug-drug interactions that affected culprit drug metabolism were found in 19% of cases. More than one congenital LQTS variant, CYP gene variant, or drug interaction was present in 7.8% of cases. Gene-burden analyses of the primary cohort compared to control exomes (n=452), and an independent replication aLQTS exome sequencing cohort (n=67) and drug-tolerant controls (n=148) demonstrated an increased burden of rare (minor allele frequency<0.01) variants in CYP genes but not LQTS genes. CONCLUSIONS: Rare susceptibility variants in CYP genes are emerging as potentially important pharmacogenomic risk markers for aLQTS and could form part of personalized medicine approaches in the future.

Exercise and Carotid Properties in the Young-The KiGGS-2 Study.

Background: Carotid intima-media thickness (cIMT) and stiffness (cS) are predictive markers of early vascular aging and atherosclerotic risk. This study assessed, whether exercise has protective effects on carotid structure and function or on vascular risk in the young. Methods: Volume and change of exercise (recreational and organized sports participation) of German adolescents and young adults was assessed within the prospective population-study KiGGS at KiGGS-Wave-1 (2009-2012) and KiGGS-Wave-2 (2014-2017) using standardized self-reporting questionnaires. CIMT and cS were measured by real-time B-mode ultrasound sequences with semi-automated edge-detection and automatic electrocardiogram-gated quality control in 2,893 participants (14-28 years, 49.6% female). A cumulative index for atherosclerotic risk (CV-R) included z-scores of mean arterial pressure, triglycerides, total/HDL-cholesterol-ratio, body mass index, and HbA1c. Results: At KiGGS-Wave-2 cross-sectional CV-R but not cS and cIMT was lower in all exercise-groups compared to "no exercise" (B = -0.73, 95%-CI = -1.26 to 0.19, p = 0.008). Longitudinal volume of exercise was negatively associated with CV-R (B = -0.37, 95%-CI = -0.74 to 0.00, p = 0.048) but not with cS and cIMT. Cross-sectional relative risk of elevated CV-R but not cS and cIMT was lower in all exercise-groups compared to "no exercise" (RR = 0.80, 95%-CI = 0.66 to 0.98, p = 0.033). High exercise volumes were associated with lower relative risk of elevated CV-R (RR = 0.80, 95%-CI = 0.65-0.97, p = 0.021) and cS in tendency but not with cIMT. Conclusions: Increased levels of exercise are associated with a better cardiovascular risk profile in young individuals, but not with cS and cIMT. Our study confirms previous recommendations on exercise in this age group without demonstrating a clear benefit on surrogate markers of vascular health.

Utilisation of outpatient medical services in Germany - Results from GEDA 2019/2020-EHIS.

Outpatient health care provision plays an important role in the identification and treatment of health problems. Data are needed on the utilisation of health care services and their determinants to enable health policy decision-making and needs-based care provision. The analyses set out in this article are based on current data on the utilisation of outpatient health care services. The data stem from the German Health Update (GEDA 2019/2020-EHIS), a nationwide cross-sectional survey of the resident population in Germany that is undertaken as part of the health monitoring conducted at the Robert Koch Institute. Around 80% of the population aged 18 or over were treated at least once within twelve months by a general practitioner, 60% by a specialist, and 10% received psychiatric or psychotherapeutic treatment. Less than half of those eligible had had a stool test during the past two years, and just over half had had a colonoscopy in the past ten years. Around 80% of women and 70% of men had had their blood pressure checked within the last year, and 60% had had their blood cholesterol or blood sugar levels monitored. Over 50% reported that they had taken medically prescribed drugs in the past two weeks. In general, most of the indicators under study suggest that utilisation increases with age and that utilisation is higher among women than men, with the exception of psychiatric and psychotherapeutic services, among others.

Carotid IMT and Stiffness in the KiGGS 2 National Survey: Third-Generation Measurement, Quality Algorithms and Determinants of Completeness.

Carotid intima-media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Overall completeness was 98% for far wall cIMT and 89% for CS parameters. Plane-specific completeness varied from 92%-96% for far wall and from 64%-69% for near-wall cIMT. Obesity independently predicted unsuccessful cIMT and CS measurements with odds ratios of 12.67 (95% confidence interval: 5.50-29.19) and 7.30 (4.87-10.94) compared with non-overweight after adjustment for blood pressure, cholesterol, smoking, hazardous drinking, age, sex and sonographer. Inter- and intra-rater reliabilities of cIMT and CS parameters in a sample of 15 young adults were good or excellent. Third-generation cIMT and CS measurements in the young with semi-automatic edge-detection and automatic real-time quality control has been successfully standardized with high reliability and very high completeness in a national survey setting. This provides a strong methodological foundation for further validation of the predictive value of cIMT and CS for atherosclerotic risk in the young.