Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Are cervical vertebrae suitable for age estimation?

BACKGROUND: The ability of cervical vertebrae (CV) staging to contribute in forensic age estimation is being discussed controversially. The large variability of CV geometries in the end stage of development might be the reason for not reaching a performance competitive to hand or third molar methods. Here we study the geometry of adult CV and demonstrate that the description of their "typical" appearance is often not met. MATERIALS AND METHODS: Lateral cephalograms from clinical routine of 320 subjects aged 20 years or above (median 24 years, 52% female) were evaluated. The criteria for the end stage of CV development (Hassel-Farman, Baccetti) were examined by assessing them in terms of metric measurements: (1) rectangular shape of C3/C4, (2) at least one of the height-width ratios of C3/C4 > 1 (both not <1), (3) significant concavities at the inferior margin of C2, C3 and C4. Metric data of the adults were also compared to those of 100 children aged 8-10 years (50% female). RESULTS: Adult CV often violated the criteria of rectangular shape (44% C3, 36% C4), of height-width ratio (16% C3, 35% C4) and inferior concavity (10% C2, 10% C3, 19% C4). All of the criteria for adult CV were fulfilled in only 24% of the subjects (95%CI 19-28%). The variability of measures of the CV shapes was large; e.g., the 95% reference ranges for the height-width ratios were 0.81-1.19 (C3) and 0.77-1.14 (C4). There was a material overlap of ranges of CV measures of adults and children. CONCLUSION: While hand bones and teeth have well-defined appearances in the end stage of development, adult CV have a large biological variance of shapes; it is hard to define their "typical" appearance. Moreover, measures of CV geometry do not strictly separate adults from children. These facts might reason the limited usefulness of CV in age estimation.

[Assessment of subjective physical well-being in heart failure : Validation of the FEW16 questionnaire]. / Erfassung des subjektiven körperlichen Wohlbefindens bei Herzinsuffizienz : Validierung des FEW16-Fragebogens.

INTRODUCTION: Improvement in the quality of life (QoL) is a major goal of therapy for heart failure (HF) patients. Physical well-being as an important component of QoL has not yet been sufficiently covered by disease-specific assessment instruments. The aim of the study was to validate the questionnaire for assessing subjective physical well-being (FEW16) in HF patients with preserved ejection fraction (HFpEF) from the exercise training in diastolic heart failure (Ex-DHF­P) trial. METHOD: A total of 64 HFpEF patients (65 years, 56 % female) were randomized to usual routine treatment with (n = 44) or without training (n = 20). At baseline and 3 months, patients were clinically evaluated and assessed using appropriate questionnaires on the QoL (SF36), physical well-being (FEW16) and depression (PHQ-D). RESULTS: The FEW16 showed good values for Cronbachs' alpha coefficients (0.85-0.93). The cross-validity with SF36 and PHQ-D was highly significant but more so for psychological aspects. At baseline, the FEW16 score correlated with age, the subscale resilience with age and the 6 min walking distance test. At follow-up, the total and resilience scores had improved in the training group. In contrast to the SF36, the FEW16 did not detect differences between the groups in Ex-DHF­P. DISCUSSION: The FEW16 questionnaire showed good internal consistency and correlation with SF36, its total score and resilience had improved after training; however, it did not reflect different changes between the study groups. The FEW16 is therefore more suited to assess general/mental well-being than the subjective physical well-being.

Reverse epidemiology in different stages of heart failure.

BACKGROUND: In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may 'start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages. METHODS: We pooled data from four cohort studies from the German Competence Network HF. Employing ACC/AHA-criteria, patients were allocated to stage A (n=218), B (n=1324), C1 (i.e., New York Heart Association [NYHA] classes I & II; n=1134), and C2+D (NYHA III & IV; n=639). RESULTS: With increasing HF severity median age increased (63/67/67/70 years), whereas the proportion of females (56/52/37/35%), median BMI (26.1/28.8/27.7/26.6 kg/m(2)), TC (212/204/191/172 mg/dl), and SBP (140/148/130/120 mmHg) decreased (P<0.001 for trend for all). In the total cohort, higher levels of all RF were associated with better survival, even after extensive adjustment for multiple confounders. If analyses were stratified, however, a higher RF burden predicted better survival only in clinically symptomatic patients: hazard ratio (HR) per +2 kg/m(2) BMI 0.91 (95% confidence interval 0.88; 0.95); per +10 mg/dl TC 0.93 (0.92; 0.95); per +5 mmHg SBP 0.94 (0.92; 0.95). CONCLUSION: In this well-characterized sample of patients representing the entire HF continuum, reverse associations were only consistently observed in symptomatic HF stages. Our data indicate that the phenomenon of a "reverse epidemiology" in HF is subject to significant selection bias in less advanced disease.

Impact of the ß1-adrenoceptor Arg389Gly polymorphism on heart-rate responses to bisoprolol and carvedilol in heart-failure patients.

This pharmacogenetic substudy of the prospective, double-blind, randomized CIBIS-ELD trial determined the impact of the ß1-adrenoceptor Arg189Gly polymorphism on heart-rate responses to bisoprolol or carvedilol in elderly patients with heart failure (421 with sinus rhythm, 107 with atrial fibrillation). Patients were randomized 1:1 to bisoprolol or carvedilol with a fortnightly dose-doubling scheme and guideline target doses. Patients with sinus rhythm responded essentially identically to bisoprolol and carvedilol, independent of genotype. Atrial fibrillation patients homozygous for Arg389 had a much smaller response to carvedilol than carriers of at least one Gly389 allele (mean difference 12 bpm, P < 0.00001). Carvedilol up to 2 × 12.5 mg did not reduce heart rate in Arg389Arg homozygotes at all. Interestingly, the immediate response to carvedilol did not differ between genotypes. The Arg389Gly polymorphism has a major impact on the heart-rate response to carvedilol (but not bisoprolol) in patients with heart failure plus atrial fibrillation.

Gender-specific predictors of early mortality after coronary artery bypass graft surgery.

BACKGROUND: Female gender is a risk factor for early mortality after coronary artery bypass graft surgery (CABG). Yet, the causes for this excess mortality in women have not been fully explained. OBJECTIVES: To analyse gender differences in early mortality (30 days post surgery) after CABG and to identify variables explaining the association between female gender and excess mortality, taking into account preoperative clinical and psychosocial, surgical and postoperative risk factors. METHODS: A total of 1,559 consecutive patients admitted to the German Heart Institute Berlin (2005-2008) for CABG were included in this prospective study. A comprehensive set of prespecified preoperative, surgical and postoperative risk factors were examined for their ability to explain the gender difference in early mortality. RESULTS: Early mortality after CABG was higher in women than in men (6.9 vs. 2.4 %, HR 2.91, 95 % CI 1.70-4.96, P < 0.001). Women were older than men (+4.7 years, P < 0.001), had lower self-assessed preoperative physical functioning (-16 points on a scale from 0 to 100, P < 0.001), and had higher rates of postoperative low cardiac output syndromes (6.6 vs. 3.3 %, P = 0.01), respiratory insufficiency (9.4 vs. 5.3 %, P = 0.006) and resuscitation (5.2 vs. 1.8 %, P = 0.001). The combination of these factors explained 71 % of the gender difference in early mortality; age and physical functioning alone accounted for 61 %. Adjusting for these variables, HR for female gender was 1.36 (95 % CI 0.77-2.41, P = 0.29). CONCLUSIONS: Age, physical function and postoperative complications are key mediators of the overmortality of women after aortocoronary bypass surgery. Self-assessed physical functioning should be more seriously considered in preoperative risk assessment particularly in women.

Implementation of pharmacotherapy guidelines in heart failure: experience from the German Competence Network Heart Failure.

AIM: To evaluate the implementation of current pharmacotherapy guidelines of heart failure and to identify factors associated with high pharmacotherapy guideline adherence in heart failure patients. METHODS AND RESULTS: We pooled data from seven studies performed in the context of the German Competence Network Heart Failure selecting patients with chronic systolic heart failure and left ventricular ejection fraction (LVEF) <45% (n = 2,682). The quality of pharmacotherapy was evaluated by calculating the guideline adherence indicator (GAI), which considers three (GAI-3) or five (GAI-5) of the recommended heart failure substance classes and accounts for respective contraindications. GAI-3 was categorized as perfect (GAI = 100%: 71% of the cohort), medium (GAI = 50-99%: 22%), and poor adherence (GAI <50%: 7%). In ordinal regression, the following factors were positively associated with perfect adherence: history of revascularization (odds ratio 1.59, 95% confidence interval 1.27-1.98), prior ICD implantation (2.29, 1.76-2.98), and LV ejection fraction <30% (1.45, 1.19-1.76), whereas age (per 10 years; 0.82, 0.77-0.89), NYHA III/IV (0.15, 0.12-0.18), unknown duration of heart failure (0.69, 0.53-0.89), and antidepressant medication (0.61, 0.42-0.88) were negatively associated with perfect adherence. Better GAI-3 at baseline predicted favorable changes of LV ejection fraction and end-diastolic diameter after 1 year. One-year mortality risk was closely related to GAI-3 in both groups of NYHA functional class I/II (excellent vs. poor GAI-3: 7.2 vs. 14.5%, log rank = 0.004) and class III/IV (13.5 vs. 21.5%, log rank = 0.005). CONCLUSIONS: This large pooled analysis showed that a high level of guideline adherence is achievable in the context of clinical studies. Those receiving and tolerating optimal pharmacotherapy experience a better prognosis. Nevertheless, the implementation of heart failure medication needs further improvement in female and elderly patients, especially those in NYHA functional class >II and patients with LVEF ≥30%.

Association of glucose metabolism with diastolic function along the diabetic continuum.

AIMS/HYPOTHESIS: Hyperglycaemia and insulin resistance have been linked to diastolic dysfunction experimentally. We investigated the association between glucose metabolism and diastolic function along the whole spectrum of glucose metabolism states. METHODS: In the observational Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST-CHF) study, patients with risk factors for heart failure were included. We analysed data including comprehensive echocardiography from a subgroup of patients classified by OGTT and history as normal (n = 343), prediabetic (n = 229) and non-insulin treated (n = 335) or insulin-treated (n = 178) type 2 diabetic. RESULTS: While ejection fraction did not differ, markers of diastolic function significantly worsened across groups. Prediabetes represented an intermediate between normal glucose metabolism and diabetes with regard to echocardiography changes. Prevalence and severity of diastolic dysfunction increased significantly (p < 0.001) along the diabetic continuum. Glucose metabolism status was significantly associated with prevalence of diastolic dysfunction on multivariate logistic regression analysis. In the whole cohort, HbA(1c) correlated with early diastolic mitral inflow velocity (E):early diastolic tissue Doppler velocity at mitral annulus (e') ratio (E:e') (r = 0.20, p < 0.001). HbA(1c) was significantly associated with E:e' on multivariate analysis. Similarly, glucose metabolism status was significantly associated with E:e' on multivariate analysis. The distance walked in 6 min decreased along the diabetic spectrum and was significantly correlated with E:e' and grade of diastolic dysfunction. CONCLUSIONS/INTERPRETATION: Glucose metabolism is associated with diastolic dysfunction across the whole spectrum. Our data extend previous observations into the prediabetic and normal range, and may be relevant to preventive approaches, as no effective treatment has been identified for diastolic heart failure once established.

[Changes in treatment of squamous cell carcinoma over time. A process analysis]. / Adaptierte Behandlungsmodalitäten bei Patienten mit Plattenepithelkarzinomen im Wandel der Zeit. Eine Prozessanalyse.

BACKGROUND: The incidence of squamous cell carcinoma is rapidly increasing and requires process-optimized treatment dependent on the course of the patient's individual disease. Patient-based data on squamous cell carcinoma were used to analyze the treatment modalities before DRGs were introduced, after their introduction and after discussion about process-optimization in context of clinical pathways. PATIENTS AND METHODS: From the recorded data in the department of dermatology, all squamous cell carcinoma cases were identified and evaluated. In addition to patient characteristics, parameters describing the process, for example, length of stay in hospital, pre- and post-interventional days, were collected. RESULTS: Between 1998-2002, 2004-2006 and January to June 2007, 658 patients were treated for squamous cell carcinoma. In contrast to the times before DRGs, the treatment process has been significantly optimized, reducing the pre- and post-operative days and thus the duration of stay. Analysis of clinical pathways as part of the continuous improvement process was hardly able to detect further improvement. However, the weekly distribution of the admitted patients has been improved. CONCLUSIONS: Patients with squamous cell carcinoma requiring surgical excision benefit from an optimized process, just as do impatient facilities. However, optimized treatment modalities carry hardly any potential of improvement by the invention of clinical pathways.

[Physical activity and prevention of Alzheimer's dementia: current evidence and feasibility of an interventional trial]. / Körperliche Aktivität und Prävention der Alzheimerdemenz: Ubersicht über die aktuelle Evidenz und Uberlegungen zur Machbarkeit einer Interventionsstudie.

There is accumulating evidence from animal and epidemiologic studies that physical exercise is neuroprotective in healthy animals and humans and can prevent cognitive decline in chronic neurodegenerative processes like Alzheimer's dementia. However, data from well-designed interventional, randomized non-pharmacologic trials is lacking in contrast to other areas of medicine like prevention of hypertension, diabetes or the antipsychotic-associated metabolic syndrome. The demonstration of a potential positive effect of physical exercise on preventing dementia using a controlled study design would represent a significant progress in the prevention of dementia and public health, especially as long as other treatments for dementia prevention are lacking.

Does the quality of dental images depend on patient's age and sex ?- Explanations from the forensic sciences.

The objective of this analysis was to investigate the dependency of image quality of dental panoramic radiographs on patient's age and sex, and to demonstrate that forensic science can explain these relationships. The image qualities of 100 dental panoramic radiographs obtained from 50 patients with two devices were assessed by ten independent observers of different specialisations. Image quality decreased with increasing age of the patients (P=0.003). One of the devices turned out to be superior to the other; however, this difference between the devices was present only in older patients but not in young ones (P=0.03). Image quality was higher in women than in men (P=0.01). The observed influences of age and sex are explained by results of forensic investigations concerning age-related changes of the dental pulp and sex differences of the skull geometry. Thus forensic science can elucidate effects relevant for everyday clinical practice. Studies on dental image quality must consider age and sex of the patients.

Biological activity of two botulinum toxin type A complexes (Dysport and Botox) in volunteers: a double-blind, randomized, dose-ranging study.

Despite extensive clinical experience and published data regarding botulinum toxin, questions remain about the clinical substitution of one botulinum toxin formulation for another. In the case of Dysport and Botox, dose-equivalence ratios ranging from 1:1 to 6:1 (Dysport:Botox) have been advocated. This dose-ranging, electroneurographic study investigated the dose equivalence, diffusion characteristics (spread) and safety of these two type-A toxins in 79 volunteers. Dysport and Botox caused significant and similar reductions in compound muscle action potential (CMAP) amplitude in the target muscle (extensor digitorum brevis, EDB) 2 weeks after injection, with effects persisting to the 12-week timepoint. For both products, the reduction in amplitude was increased with increasing doses and with increasing concentration. The effects of toxin on neighbouring muscles were much smaller and of a shorter duration than those on the target muscle, implying a modest spread of toxin. Unlike the target muscle, the effects were greater with the higher volume, suggesting this volume led to greater diffusion from the EDB. No adverse events were reported. Statistical modelling with CMAP amplitude data from the target muscle gave a bioequivalence of 1.57 units of Dysport:1 unit of Botox (95 % CI: 0.77-3.20 units). The data indicate that a dose-equivalence ratio of 3:1 was within the statistical error limits, but ratios over 3:1 are too high.

Critical evaluation of methods for determination of body fat content in children: back to basic parameters?

Considering the increasing prevalence of obesity among children and of obesity related disorders in the pediatric population, the reliable evaluation of body fat content in children is of critical importance in research and clinical medicine. In this study, we assessed the congruency of different estimates for body fat content in prepubertal children. We determined anthropometric parameters, such as BMI and skinfold thickness, and bioelectrical impedance in 676 prepubertal Caucasian children. We calculated body fat percentage (BF%) from these parameters applying 5 distinct algorithms and established raw centiles for these models. Expectedly, girls had significantly higher BF% regardless of the method applied. There were, however, significant variances in the calculated amount of BF% between the algorithms, with BIA based equations giving highest BF%, while skinfold based equations tended to provide lower BF% values. Direct comparison of the algorithms revealed a high degree of inconsistency and poor agreement in the assessment of body fat with variations of >10% BF%. Great differences in basic parameters, such as DeltaBMI (3.2 kg/m (2)) or Deltaskinfolds (1.75-fold), would be needed to reliably predict correct ranking of 10% difference in body fat with 95% probability. In summary, BF% strongly varies depending on both the method as well as the algorithm used. This questions the applicability of such field methods for the assessment of BF% for comparative analyses and the superiority of information over basic parameters such as BMI.

[Vocal efficiency parameters in children and adolescents: effect of physical development and singing activity]. / Stimmleistungsparameter bei Kindern und Jugendlichen: Einfluss der körperlichen Entwicklung und der sängerischen Aktivität.

The influence of physical development and singing activity on vocal efficiency in children and adolescents is well known from clinical experience. There is, however, no comparative study between singing and non-singing children which also considers the influence of age and gender. Therefore, standard values for evaluation in clinical practice are missing. We examined the following parameters in 164 healthy children and adolescents (90 boys, 74 girls; 11-16 years), 86 without singing activity (group A) and 78 members of children's and youth choirs (group B): frequency and dynamic range of voice and its borders with a voice range profile, mean fundamental frequency (normal and loud phonation), maximum voice intensity, and maximum duration of intonation. The statistical analysis was performed using three-way ANOVA. We found significantly higher ranges of frequency and intensity in singing children and adolescents (p<0.0001). The borders of the dynamic range and the upper border of the frequency range were significantly higher in group B (p<0.0001). The boys in group B used a higher mean fundamental frequency during loud phonation. There were no significant differences between groups in maximum voice intensity (p=0.051) but a tendency towards higher values in singing children. As an unexpected result, we found significantly higher values in maximum duration of intonation in group A (p<0.0001) independent of age and gender, which seems to be related to the methods used. Regular training of the singing voice results in positive effects on several voice parameters in children as well as adolescents. Our results can be used for estimating standard values in professional clinical and educational care of young singing voices and non-singing children. For this purpose, voice range profile is particularly suitable.

Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2.

A Thr789Ala variant in the von Willebrand Factor (vWF) gene is associated with increased vWF plasma concentrations and might therefore affect the risk of coronary heart disease (CHD) in the general population. Patients with type 2 diabetes have an increased risk for premature atherosclerosis and are characterized by alterations of the coagulation system. However, it is not known whether the Thr789Ala variant in the vWF gene contributes to the increased CHD risk in patients with type 2 diabetes. We therefore investigated the potential relationship between the Thr789Ala variant in the vWF gene and the occurrence of CHD in 356 patients with type 2 diabetes, either with (DM+/CHD+, n = 204) or without evidence for CHD (DM+/CHD-, n = 152). In addition, two control groups without type 2 diabetes, with (DM-/CHD+, n = 22) or without CHD (DM-/CHD-, n = 100), were investigated. Individuals with the vWF Thr789Ala variant have significantly higher von Willebrand factor plasma concentrations (p < 0.001). In addition, ristocetin co-factor was significantly increased in vWF Thr789Ala variant carriers (p < 0.05). Ristocetin co-factor levels and collagen binding capacity were also increased in individuals affected with either type 2 diabetes, CHD or both (DM+/CHD+, DM+/CHD-, DM-/CHD+) as compared to healthy controls (DM-/CHD-) (p < 0.001). However, we did not find an association between the vWF Thr789Ala variant and the occurrence of CHD in patient with type 2 diabetes (p = 0.34). In conclusion, although the Thr789Ala vWF gene variant is associated with increased plasma concentrations of vWF, ristocetin co factor levels and collagen binding capacity in patients with type 2 diabetes and CHD, a direct effect of this variant on the occurrence of CHD in patients with type 2 diabetes, could not be detected.

Knowing more by fewer measurements: about the (In)ability of bioelectric impedance to enhance obesity research in children.

The prevalence of obesity is increasing worldwide. The implications for human health can already be observed in children. Consequently, it is desirable to provide good quantitative descriptions of the relationship of body fat and health risks, such as hypertension. Bioelectric impedance analysis has been frequently praised to be useful for assessing body fat. Devices to analyse body composition based on this technique seem to be selling well, while the real gain in information they provide is unclear. Here we show in a cohort of 2,218 schoolchildren that the body mass index (which is more easily and less costly to determine) is a better predictor of hypertension than the data delivered by impedance analysis. Moreover, we demonstrate that the output of a random number generator is competitive with impedance measurement for this purpose. It is explained by simple arguments from physics why the formulas for the computation of body fat from bioelectric impedance obliterate rather than clarify the relationship of obesity and hypertension. As a consequence, we suggest questioning the opinion propagated by others that bioelectric impedance analysis is a useful tool in field studies on body fat in children. Measurements requiring more effort (compared to simpler methods) should be proved to add worthwhile information, otherwise they should be avoided.

[Bone metabolism in 53 children and adolescents with chronic inflammatory bowel disease]. / Knochenstoffwechsel bei 53 Kindern und Jugendlichen mit chronisch entzündlichen Darmerkrankungen.

BACKGROUND: Osteopathy is a common clinical feature of chronic inflammatory bowel disease (IBD) in children and young adults at the time of primary diagnosis. The aim of the following study was to address the question of prevalance of a decreased bone density or increased bone metabolism in children with IBD. PATIENTS: We examined 63 patients (mean age 13 years; 5 - 18 years): 36 Crohn's disease (MC) patients, 16 colitis ulcerosa (CU) patient and one patient with colitis indeterminata (CID). 10 children who had been referred to the gastroenterological outpatient department due to suspected IBD symptoms were later found not to suffer from IBD. These 10 patients therefore were included in the study as controls. RESULTS: 8 of 10 CU patients and 18 of 28 MC patients showed a pathological bone density and abnormalities in bone metabolism. Repetitive bone density measurement was performed in 18 patients. In MC patients a - 0.39 SDS decrease of bone mineral density was found, without a simultaneous deterioration of clinical stage and inspite of a decreased cumulative prednisolon dosage. However in CU patients a + 0.06 SDS increase of bone mineral density was detected. These patients had a lower cumulative prednisolon dosage and a stable clinical course. CONCLUSIONS: In conclusion, pediatric IBD patients often show abnormalities in bone metabolism and decreased bone density. There is a need for multicentre, prospective randomised control trials to further identify therapeutic tools on the basis of the multifactorial etiology of bone disease in pediatric IBD patients.

[Metoclopramide and dexamethasone in prevention of postoperative nausea and vomiting after inhalational anaesthesia]. / Metoclopramid und Dexamethason zur Prophylaxe von postoperativer Ubelkeit und Erbrechen nach balancierter Anästhesie.

OBJECTIVE: Because of its complex profile of action (binding to dopamine, serotonin and histamine receptors), low rate of adverse effects and low cost as a medicinal preparation, metoclopramide is an interesting substance for the prophylaxis of post-operative nausea and vomiting (PONV). As a single substance its antiemetic effects are slight at the usual dose, so the aim was to test the efficacy of a combination of metoclopramide and dexamethasone for the prevention of PONV on a group of patients with the same operative trauma. METHOD: All patients (n = 204) were recruited prospectively (January-October 2002) and were to undergo a lumbar disc operation. The anaesthetic was administered according to a standard procedure as a balanced anaesthetic with fentanyl and isoflurane in oxygen/air. 60 min before the end of the operation, all patients were given 10 mg of metoclopramide and 8 mg of dexamethasone intravenously. The Würzburg-Oulu-Score served as an instrument for comparison, because no placebo group has been included. 24 hours after the operation, all patients were asked to report on nausea and vomiting, stating the time and the degree of discomfort (quantification by means of an analogue numerical scale from 0-10). The influence of age, height, weight, duration of the anaesthetic, operating position and increased dexamethasone dose was analyzed in addition to the risk factors according to the score. The cost analysis was based on the purchase prices of the hospital dispensary. RESULTS: The expected PONV incidence was 35.8%; 10% nausea (average intensity 4.3) and 3% emesis (4.8) was reported for the 24-hour period. The rescue medication (dimenhydrinate) was requested 8 times. Nausea was mainly during the early part of the period (0-6 hours). Of 42 patients with a history of PONV, 71% had no symptoms. The Odds Ratios for female sex (2.9), non-smoker status (2.0) and post-operative opioid administration (1.9) correspond to the data given in the literature; it was not possible to determine the significance of a history of PONV as an independent risk factor. None of the other factors investigated had a significant influence on PONV. For the chosen combination of antiemetic drugs the number-needed-to-treat is 3.9 (95% CI: 3.3-4.7). The direct costs of the PONV prophylaxis are 0.65 euro per patient. CONCLUSIONS: The metoclopramide/dexamethasone combination proved to be effective and inexpensive, on the basis of these findings it is used prophylactically at our hospital if only one PONV risk factor exists.