Search

Background Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. Objectives To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. Methods The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). Results HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). Conclusions Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

Non-invasive caries treatment is a major focus in modern dentistry. The present study was designed to evaluate the effectiveness of monomeric self-assembling peptide P11-4 (SAP P11-4) in combination with fluoride varnish or polymeric self-assembling peptide matrix (SAPM) in treatment of non-cavitated occlusal caries. Ninety children and adolescents were included in this randomized, gold-standard-controlled clinical trial. Test Group 1 received SAP P11-4 and twice fluoride varnish at baseline and Day 180, Test Group 2 received SAP P11-4 on baseline and twice weekly SAPM (home-application), and Control Group received fluoride varnish on baseline and Day 180. Caries progression was measured by laser fluorescence, Nyvad Caries Activity, ICDAS-II-codes, and investigator assessments. Laser fluorescence changes demonstrated superior results for Test Group 1 and 2, as values decreased compared to an increase for the Control Group (p 11-4, applied either in combination with fluoride varnish or twice weekly SAPM, was a superior treatment for early caries compared to fluoride varnish alone.

Purpose For surgical treatment of inguinal hernia, large-pore, lightweight mesh has been shown to offer advantages over small-pore, heavyweight options in terms of chronic post-operative inguinal pain, but without the disadvantage of having to deal with an increased recurrence rate. Limited data are available for the mesh plug repair technique. Therefore, the primary aim of this study is to compare large-pore, lightweight mesh versus small-pore, heavyweight mesh for mesh plug repair with regard to chronic pain and recurrences in elective primary unilateral hernias. In addition, we report our experience in repairing recurrent hernias. Methods Using a modified version of the questionnaire from the Danish Hernia Registry, two groups were surveyed: elective primary unilateral hernias and recurrent unilateral hernias. In both groups small-pore, heavyweight mesh (HWM) and lightweight, large-pore mesh (LWM) were compared with respect to chronic pain and recurrences. Propensity score matching (PS) was carried out on a pool of 1,782 patients. Effect sizes were assessed by using Cohen's d and Cramer's V. Results If the questionnaire item ‘lump/swelling’ is considered as a surrogate for recurrence (clinically verified in our study), the results in primary hernias after HWM show a 6.0% recurrence rate and 7.3% after LWM (p = 0.487) with a mean follow up of 31,3 months in HWM and 29,2 months in LWM respectively. The questionnaire item ‘pain impacting on work/leisure activities’ was answered with Yes in 11.5% following HWM and in 10.5% following LWM (p = 0.665). After the evaluation of the overall surgical results, we did not find differences. Comparing primary and recurrent hernia repair we found below small effect size differences with respect to the items of the questionnaire. Conclusions The use of LWM in repairing elective unilateral primary hernias by the mesh plug technique does not result in less chronic pain and more recurrences when compared with HWM. Recurrent hernias repaired by the mesh plug technique may have same outcomes like in primary hernia repair when considering the magnitude of effect sizes.

IntroductionThe quality of healthcare in childhood and adolescence is of key importance, in order to foster a healthy development and to avoid chronic health problems. Yet, data for Germany regarding the quality of healthcare for this patient group are lacking. The QualiPäd research project aims to estimate the quality of outpatient healthcare for children and adolescents in Germany, focusing on common psychiatric and physical disorders.Methods and analysisQuality indicators for seven common physical and mental childhood and adolescent clinical conditions (attention deficit/hyperactivity disorder, asthma, atopic dermatitis, depression, otitis media, conduct disorder/oppositional defiant disorder, tonsillitis) will be developed and ratified by experts, using the RAND/UCLA Appropriateness Method.Initially, 1400 medical records of children and adolescents with one of the aforementioned clinical conditions will then be randomly drawn from 40 outpatient practices in the German federal state of Hessen. The records will then be assessed regarding their adherence to the respective quality indicators. Based on this, the percentage of appropriate and inappropriate (eg, wasteful) healthcare of all clinical conditions (primary endpoint) will be estimated. Additionally, possible factors influencing the quality of care (eg, patient characteristics, type of condition, type of practice) will be identified using generalised estimation equation models.Ethics and disseminationThis study will show for which of the studied clinical conditions and/or patients improvement of quality of care is necessary within the German health system. Also, the quality indicators designed for the study can afterwards be implemented in regular care and thus enable regular reporting of the outpatient care of this target group. The authors plan to disseminate their findings through international, peer-reviewed scientific publications, and through presentations at national and international paediatric and child psychiatric conferences.Trial registration numberDRKS00022408., publishedVersion

Aktives Ruckentraining kann Ruckenbeschwerden wirksam reduzieren, es ist jedoch unklar, welche Wirkmechanismen fur diesen Ruckgang verantwortlich sind. Welche Bedeutung haben Trainingsumfang, muskulare Leistungssteigerung, Alter und Geschlecht fur die Wirksamkeit eines multimodalen Ruckentrainings? Im Rahmen einer Multicenterstudie (39 Standorte) uber 24 Monate durchliefen 1395 Menschen (Durchschnittsalter 46,9 [standard deviation (SD) ± 12,3] Jahre, 65 % Frauen) mit Ruckenbeschwerden ein multimodales Ruckentrainingsprogramm. Zu Beginn des Programms sowie nach 6, 12, 18 und 24 Monaten wurden Ruckenbeschwerden und physische Leistungsfahigkeit in Kraft, Mobilitat und bilateralen Kraftverhaltnissen der wirbelsaulenstabilisierenden Muskulatur gemessen. Die Teilnehmer trainierten im Durchschnitt 41,0 (SD ± 17,8) Trainingseinheiten a 60 min und steigerten sich im Vergleich zu den alters- und geschlechtsspezifischen Referenzwerten von Menschen ohne Ruckenbeschwerden in der Kraft um 28,1 %-Punkte, in der Mobilitat um 14,7 %-Punkte und im Kraftverhaltnis um 6,5 %-Punkte. Die Ruckenbeschwerden reduzierten sich um 37,5 %. Der Ruckgang der Ruckenbeschwerden wurde zu 70 % durch den Trainingsumfang und zu 30 % durch die physischen Leistungssteigerungen erklart. Das Geschlecht hatte keine und das Alter nur eine marginale Auswirkung auf den Trainingseffekt. Physische Leistungssteigerungen wirken sich positiv auf die Reduzierung der Ruckenbeschwerden aus. Die Anzahl der Trainingseinheiten ist fur den Ruckgang der Ruckenbeschwerden jedoch von deutlich hoherer Relevanz.

This study aimed to investigate factors affecting (1) women’s media use regarding health-related behaviors during pregnancy and lactation, (2) women’s preferences for media format, and (3) the content of media-based interventions on lifestyle-related risk factors during pregnancy and lactation. A cross-sectional observational multi-center study of pregnant and lactating women and women of childbearing age was carried out in 14 randomly selected obstetric and gynecologic care settings in the 12 most populated cities in Baden-Wuerttemberg, South-West Germany. Data from 219 surveyed women showed that older women, pregnant women, and lactating women have a higher probability of using media during pregnancy and lactation, respectively. The majority of women preferred a combination of analog and digital media-based interventions in gynecological (46.9%) and obstetric (47.1%) care settings and at home (73.0%). Women would like to see information brochures and flyers on health-related behaviors during pregnancy and lactation for use in gynecological and obstetric care settings, and for media use at home, they would like to have books. The probability of preferring the favored media formats in gynecological and obstetric care settings and at home were associated with pregnancy status, relationship status, socioeconomic status (SES), ethnicity, and health insurance status. About 80% of the surveyed women preferred media content regarding recommendations for a healthy lifestyle and healthy behavior during pregnancy and lactation. All of the independent variables were associated with the probability of preferring a specific media content. The SES was found to play a major role in the probability of preferring a specific media content, followed by pregnancy status, ethnicity, and health insurance status. The results from our study provide a basis for tailored preventive interventions in gynecological and obstetric care settings and for use at home. The results imply that a woman can be reached before conception, during pregnancy, or during lactation with preventive measures tailored to their requirements, however, acceptance may vary across personal attributes, such as SES, ethnicity, and others.

Background Exercise is considered an effective intervention to relieve chronic back pain. However, it is still unknown whether specific exercise patterns vary in terms of their efficiency and effectiveness. Aim To investigate the differential health and economic effects of intensity, specificity and degree of subjective perceived physical exertion across five exercise patterns (endurance, gymnastics, fitness, back gymnastics, multimodal back exercise) in adults with back pain. Design Longitudinal observational cohort study over a period of 24 months. Setting Various non-therapeutic exercise facilities (e.g. outdoor, fitness centers, health insurance programs, sports clubs) across one federal state of Germany (Baden-Wuerttemberg). Population Adults with back pain (N.=2,542, Mean =46.9 years, 66% females, graded chronic back pain [GCPS] 1=40.5%, GCPS 2=27.3%, GCPS 3=20.7%, GCPS 4=11.5%). Methods Self-reported back pain (functional restrictions and pain = back pain function score, [BPFS]) and characteristics of exercising behavior (frequency, duration, type, physical exertion) were assessed at baseline and at 6, 12, 18 and 24 months. Direct medical costs for back disorders (international classification of diseases, dorsopathies: M40-M54) were compiled from health insurance records. Results Moderate- to high-intensity exercise patterns were effective in reducing back pain, particularly at lower levels of subjective perceived physical exertion. At these intensity levels, multimodal back exercise (i.e. exercising the spine-stabilizing muscles specifically, ergonomic training) was 14.5 times more effective than non-back specific fitness exercise in reducing BPFS. The beneficial effects of both exercise types increased with the initial severity of back pain. However, only multimodal back exercise (moderate- to high-intensity/high back specificity) was associated with a significant decrease in direct medical costs for back pain. Conclusions Targeted exercise of the spine-stabilizing musculature at moderate to high intensities without maximum perceived exertion is effective and efficient in reducing back pain. Clinical rehabilitation impact The combination of high-intensity and high-specificity exercises yielded a significant reduction in medical costs. However, the intensities in terms of muscular load in endurance training and gymnastics may not be sufficient to reduce back pain effectively.

To compare the cost-effectiveness of a multimodal back exercise programme for non-specific back pain with that of standard treatment. Medical costs were measured in euros (EUR) and effectiveness was measured using Graded Chronic Pain Status (GCPS). A controlled multicentre study (39 sites) with a 6-month intervention phase and follow-up at 6, 12 and 18 months. The study included 1,829 participants in an intervention group and 495 individuals in a control group. The multimodal back exercise programme comprises 36 exercise sessions for optimizing the spine stabilizing muscles and everyday motor func-tions. The patients were given a home training programme at the end of the intervention programme. The back exercise programme resulted in a significant reduction, of 0.4, in back pain grade on the GCPS after 2 years, compared with standard treat-ment, and reduced medical costs by 763 EUR. The exercise programme was therapeutically effective for GCPS back pain grades 1–4 and produced cost savings in the case of grade 4 GCPS. The multimodal back exercise programme was therapeutically effective for back pain (grades 1–2) and pain-related functional impairment (grades 3–4). It resulted in reduced costs for chronic back pain causing high pain-induced functional impairment (grade 4). The therapeutic and economic effects of the programme increase with the grade of back pain.

Objectives: The aim of this study was to test the relationship between a newly developed sugar index and caries experience in 4th- and 6th-graders. Materials and Methods: A total of 1,019 fourth-graders and 925 sixth-graders from 2 regions in Northern Germany participated in the study. Caries experience was recorded by applying the ICDAS criteria. Tooth-brushing habits and other independent variables were examined psychometrically. Structured questions were formulated that were related to specific everyday eating situations, especially between main meals, which proved to be relevant for a higher caries risk. To compare mean caries scores, nonparametric tests were applied. The Pearson coefficient was calculated in order to verify the correlation between the sugar index and the caries experience. The influence of various independent variables on caries experience was assessed by stepwise backward logistic regression analysis. Results: With regard to the primary teeth of the 4th-graders, significant correlations with values > 0.1 were found for all ICDAS outcome variables. With regard to the permanent teeth of the 6th-graders, the only significant correlations with the sugar index were for the ICDAS outcome variables D3–6MFT and D3–6FS. Conclusion: The results of our study show that not only the correlation between the sugar index and caries experience was stronger for 4th-graders than for 6th-graders, but also more distinctly visible differences were observed when comparing extreme groups. This indicates that protective factors, such as fluoridation and the preventive sealing of fissures, help level out the differences in caries occurrence in older children when compared to younger children.

Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2–4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CLPIP): no RRT CLPIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CLPIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CLPIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m2 significantly increased CLPIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p

Background This study investigated the effects of three different risk displays used in a cardiovascular risk calculator on patients’ motivation for shared decision-making (SDM). We compared a newly developed time-to-event (TTE) display with two established absolute risk displays (i.e. emoticons and bar charts). The accessibility, that is, how understandable, helpful, and trustworthy patients found each display, was also investigated. Methods We analysed a sample of 353 patients recruited in general practices. After giving consent, patients were introduced to one of three fictional vignettes with low, medium or high cardiovascular risk. All three risk displays were shown in a randomized order. Patients were asked to rate each display with regard to motivation for SDM and accessibility. Two-factorial repeated measures analyses of variance were conducted to compare the displays and investigate possible interactions with age. Results Regarding motivation for SDM, the TTE elicited the highest motivation, followed by the emoticons and bar chart (p

Background For children and adolescents with mental health problems, there is a lack of data as to whether the type of residential area (urban vs. rural) influences healthcare costs for affected individuals. The aim of this study was therefore to explore potential urban vs. rural healthcare cost differences in children and adolescents with conduct disorder (CD), one of the most frequent and cost-intensive child and adolescent psychiatric disorders. Additionally, we aimed to compare healthcare costs of youths with CD, and of youths without this diagnosis. Methods We analysed data from a German health insurance company, extracting all youths with a CD diagnosis in 2011 (CD group; N = 6337), and an age- and sex-matched group without this diagnosis (control group). For both groups, annual costs per person for outpatient and inpatient healthcare were aggregated, stratified by area of residence (urban vs. rural). Results While mean annual overall costs in the CD group did not differ significantly between urban and rural areas of residence (2785 EUR vs. 3557 EUR, p = 0.253), inpatient treatment costs were significantly higher in rural areas (2166 EUR (60.9% of overall costs) vs. 1199 EUR (43.1% of overall costs), p

Background In order to investigate correlations between specific parameters and dental caries, it is useful to record incipient and dentine lesions. Aim The aim of this study was to evaluate the effect of a selective intensified preventive program (SIP) on oral health of fourth graders using ICDAS. Design A cohort study was performed. ICDAS and DMFT index were recorded. Prevention and social factors were collected with psychometric questionnaires. The test group and the control group were parallelized using sociodemographic variables. Results The participants in the fluoride varnish program in the test region showed a significantly lower caries experience than pupils in the control region. The bivariate analysis revealed that a migrant background had a negative impact on oral health whereas fissure sealants, use of fluoridated table salt, use of fluoride tablets, early start of toothbrushing and high social status exerted a positive influence on dental health. Stepwise backward logistic regression analysis confirmed that fissure sealants, a high social status and an early start of toothbrushing had a significant positive impact on dental health. Conclusion The results of our study suggest that a SIP impedes the primary occurrence of incipient lesions and the transition from incipient to advanced lesions.

Fragestellung: Zum Screening von Autismus-Spektrum-Störungen (ASS) stehen verschiedene Fragebogenverfahren zur Verfügung. Leider zeigen neuere Studien, dass diese Verfahren zwar tatsächlich in der Lage sind, betroffene Personen mit ASS zu identifizieren, aber bezüglich der differentialdiagnostischen Abgrenzung zu anderen komplexen Störungsbildern (z. B. Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung [ADHS], emotionale Störungen, Persönlichkeitsstörungen), insbesondere bei Personen ohne deutliche kognitive Beeinträchtigung, Probleme aufweisen (niedrige Spezifität). Methodik: In der vorliegenden Studie wurde an einer großen Inanspruchnahme-Stichprobe aus 309 Patienten (153 mit ASS, 156 mit sonstigen psychischen Störungen, IQ > 70) geprüft, inwiefern ausgewählte Items des ADI-R im Screening-Prozess von hochfunktionalen ASS eingesetzt werden können. Ergebnisse: Bei einem Cut-off von 5 zeigte sich eine hohe Sensitivität (0.93), bei einem Cut-off von 6 eine gute Spezifität (0.74). Dieses Ergebnis blieb für verschiedene Untergruppen (Einteilung nach Diagnose/Alter/IQ/Geschlecht) stabil. Schlussfolgerung: Insgesamt hat sich gezeigt, dass acht Interviewfragen des ADI-R dazu dienen können, Kinder und Jugendliche mit hochfunktionaler ASS von solchen mit anderen psychischen Störungen zu unterscheiden. Die Kombination aus früh beginnenden, ausgeprägten Auffälligkeiten im sozialen Kontakt mit stereotypen oder zwanghaft-ritualisierten Verhalten oder Interessen kann anhand weniger Fragen zu Screening-Zwecken ermittelt werden. Jedoch ist im weiteren Verlauf eine ausführliche und spezifische weitere kinder- und jugendpsychiatrische Diagnostik notwendig.

The aim of the present study was to evaluate the influence of various risk factors on dental caries increment in deciduous teeth of preschool children over 2.5 years. A longitudinal study was carried out in kindergartens in two German counties in Northern Hesse. At baseline examination in 2006–2007, the mean age of the children was 3.5 years. Caries experience was recorded according to WHO standards. Information about feeding practices during early childhood and preventive measures were collected by a structured questionnaire for each child. Three hundred ninety-five (69.8 %) of the 566 children showed no caries increment. A caries increase of 1 to 10 dmf-teeth was exhibited by 171 children (30.2 %). The mean dmf-t increment amounted to 0.75. The bivariate analysis revealed that the consumption of sugary food and beverages had a negative impact on oral health. Early start of toothbrushing, use of fluoridated children’s toothpaste, and frequent toothbrushing exerted a positive influence on dental health. Stepwise backward logistic regression analysis confirmed that a high social status has a significant positive impact on dental health (p = 0.028), whereas the consumption of sugary food and beverages was significantly associated with a higher dental caries increment (p = 0.004). Obviously, it is not possible to limit the caries increment in children of low socioeconomic status as successfully as in children of high socioeconomic status. There must be a stronger focus on families of low socioeconomic status when preventive measures are performed on groups or individuals.

Die Effektivität des Elterntrainings „Stepping Stones/Triple P” als ergänzende Behandlung von Kindern mit einer Autismus-Spektrum-Störung (ASS) wurde untersucht. Die Eltern von 13 Kindern mit ASS (neun Jungen, vier Mädchen) zwischen vier und zwölf Jahren (M=6.7 Jahre, SD=2.61) nahmen an der Studie teil. Das Training fand über einen Zeitraum von 14 Wochen mit acht Gruppensitzungen à zwei Stunden statt. Die Eltern wurden zum Prä- und Postzeitpunkt, sowie sechs Monate später bezüglich komorbider Verhaltensauffälligkeiten und dem Erziehungsverhalten befragt. Außerdem wurden die autistische Kernsymptomatik sowie die elterliche Belastung zum Prä- und Postzeitpunkt erhoben. Ein Teil der Eltern wurde zusätzlich als Eigenwarteliste-Kontrollgruppe erfasst. Durch das Elterntraining konnten die komorbiden Verhaltensauffälligkeiten der Kinder reduziert werden (d=.65), außerdem verbesserten sich die Erziehungsfertigkeiten (d=.97). Keine Veränderungen ergaben sich hinsichtlich der elterlichen Belastung und der autistischen Kernsymptomatik. Insgesamt zeigt sich das Elterntraining nach „Stepping Stones/Triple P” als sinnvolle begleitende Intervention in der Behandlung von Kindern mit einer ASS.

Background Integrated Management of Childhood Illness (IMCI) is regarded as a standard public health approach to lowering child mortality in developing countries. However, little is known about how health workers adhere to the guidelines at the national level in sub-Saharan African countries. Methods Data from the Service Provision Assessment surveys of Namibia (NA) (survey year: 2009), Kenya (KE) (2010), Tanzania (TZ) (2006) and Uganda (UG) (2007) were analysed for adherence to the IMCI guidelines by health workers. Potential influencing factors included the survey country, patient’s age, the different levels of the national health system, the training level of the health care provider (physician, non-physician clinician, nurse-midwife, auxiliary staff), and the status of re-training in IMCI. Results In total, 6856 children (NA: 1495; KE: 1890; TZ: 2469; UG: 1002 / male 51.2–53.5%) aged 2–73 months (2–24 months, 65.3%; median NA: 19 months; KE: 18 months; TZ: 16 months; UG: 15 months) were clinically assessed by 2006 health workers during the surveys. Less than 33% of the workers carried out assessment of all three IMCI danger signs, namely inability to eat/drink, vomiting everything, and febrile convulsions (NA: 11%; KE: 11%; TZ: 14%; UG: 31%) while the rate for assessing all three of the IMCI main symptoms of cough/difficult breathing, diarrhoea, and fever was < 60% (NA: 48%; KE: 34%; TZ: 50%; UG: 57%). Physical examination rates for fever (temperature) (NA: 97%; KE: 87%; TZ: 73%; UG: 90%), pneumonia (respiration rate/auscultation) (NA: 43%; KE: 24%; TZ: 25%; UG: 20%) and diarrhoea (dehydration status) (NA: 29%; KE: 19%; TZ: 20%; UG: 39%) varied widely and were highest when assessing children with the actual diagnosis of pneumonia and diarrhoea. Adherence rates tended to be higher in children ≤ 24 months, at hospitals, among higher-qualified staff (physician/non-physician clinician) and among those with recent IMCI re-training. Conclusion Despite nationwide training in IMCI the adherence rates for assessment and physical examination remained low in all four countries. IMCI training should continue to be provided to all health staff, particularly nurses, midwives, and auxiliary staff, with periodic re-training and an emphasis to equally target children of all age groups.

The aim of this study was to evaluate the in-vivo performance of the VistaProof fluorescence-based camera (VP) on occlusal surfaces. The study was approved by the ethics committee and informed consent was given by the participants. The study included 306 unrestored permanent teeth of 26 patients. The occlusal surfaces of the teeth were examined visually using International Caries Detection and Assessment System (ICDAS) criteria. Then, digital images of the surfaces were made using the VP. The actual depth of the lesions was assessed using radiographs and/or clinically by opening the lesion when appropriate. Correlation between all methods was assessed using Spearman's rank correlation coefficient (r s ). Sensitivity (SE) and specificity (SP) were calculated at D1-(enamel lesions) and D3-(dentine caries) diagnostic threshold and area under the ROC curve (AUC) were assessed. Significant positive correlation was found between ICDAS, VP measurements and the reference standard (r s 0.46–0.71, p

Biomed research international 2013, 349530 (2013). doi:10.1155/2013/349530, Published by Hindawi, New York [u.a.]

Introduction: Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. Methods: We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Results: Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. Discussion: In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.

A selective intensified prevention (SIP) was introduced at individual schools in deprived areas in Marburg County (Germany) in 1995. The outcome of the program was evaluated in sixth graders (mean age: 12.06 years) in comparison to a control region.Caries experience was recorded by applying International Caries Detection and Assessment System (ICDAS) II criteria. Tooth brushing habits and other independent variables were examined psychometrically. To compare the mean caries scores, non parametric tests were applied. The influence of various independent variables on caries experience was assessed by stepwise backward logistic regression analysis. The matching criteria age, gender, ethnicity and maternal education were used to parallelize the samples.ICDAS scores of 2-6 were detected uniformly more often in the control region than in the test group. Combining ICDAS scores 3-6, children from the control region (mean D(3-6)MFT: 1.73) showed roughly double the caries experience compared to the test group (mean D(3-6)MFT: 0.88, p 0.005). The D(5,6)MFT score of the test group amounted to 0.50, and the corresponding value of the reference group was 0.77 (p = 0.043). Multivariate analysis disclosed fissure sealants, early start of tooth brushing and topical fluoride application to be associated with the prevention of dental caries. High frequency of sugar intake was associated with the presence of dentine lesions.The results of our study confirm the positive effect of SIP on the dental health of 12-year-old pupils living in deprived areas.On the basis of ICDAS II, targeted preventive measures can be applied in children with increased caries risk. Frequent applications of fluoride varnish inhibit the progression of initial lesions in this group.

Selective intensified prevention (SIP) was introduced by the Dental Public Health Service in Marburg County in 1995. SIP is offered at individual schools in underprivileged districts including enhanced health education and oral hygiene instructions as well as fluoride varnish applications four times per year. The aim of this study was to evaluate the effect of the programme in 12-year-old children in comparison to a control region. The intervention group consisted of children attending schools in socially deprived areas in the county of Marburg-Biedenkopf who had participated in the preventive programme for 6 years. Control group subjects were recruited from schools in socially deprived areas in the county of Osnabruck with no school-based topical fluoridation programme. Caries experience was recorded using the criteria of the International Caries Detection and Assessment System (ICDAS II). Other variables such as oral hygiene behaviour, knowledge of dental health and dental fear were examined psychometrically. The statistical evaluation was performed by SPSS 17.0. To compare the mean caries scores of various subgroups, non-parametric tests were performed. In Marburg 236 children were examined, and 689 were participating in the control region. The samples were parallelized by constructing matched pairs with children from the control region. After matching the data of 210 children in each region, a total of 420 were involved in the statistical evaluation. Combining ICDAS scores 3 to 6 children from the control region (mean D3–6MFT: 1.73) showed roughly double the caries experience compared to the test group (mean D3–6MFT: 0.88, p

The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured, standardized assessment designed for use in diagnostic evaluation of individuals with suspected autism spectrum disorder (ASD). The ADOS has been effective in categorizing children who definitely have autism or not, but has lower specificity and sometimes sensitivity for distinguishing children with milder ASDs. Revised ADOS algorithms have been recently developed. The goals of this study were to analyze the predictive validity of different ADOS algorithms for module 3, in particular for high-functioning autism spectrum disorder. The participants were 252 children and adolescents aged between four and 16 years, with a full-scale IQ above 70 (126 with a diagnosis of ASD, 126 with a heterogeneous non-spectrum diagnosis). As a main finding, sensitivity was substantially higher for the newly developed ‘revised algorithm’, both for autism versus non-spectrum, as well as for the broader ASD versus non-spectrum, using the higher cut-off. The strength of the original algorithm lies in its positive predictive power, while the revised algorithm shows weaknesses in specificity for non-autism ASD. As the ADOS is valid and reliable even for higher functioning ASD, the findings of the present study have been used to make recommendations regarding the best use of ADOS algorithms in a high-functioning sample.

Carious lesions can occur at different sites on the occlusal surfaces of teeth and may differ in appearance and severity. This study aimed to evaluate how scoring several lesions on occlusal surfaces, as opposed to only one representative lesion, affects estimates of reproducibility and accuracy of fluorescence-based devices. Thirty-six permanent teeth with 2-3 investigation sites (n = 82) were examined by two examiners using the laser fluorescence device DIAGNOdent pen (LF) and the fluorescence camera VistaProof (FC). Lesion depth was then assessed histologically in serial sections of the teeth. Intra-class-correlation coefficients (ICC) and areas under the ROC-curves were calculated for all investigation sites and for one randomly selected site per tooth. Comparing the reproducibility and the performance for the whole sample and the independent sites showed only a small effect or no effect. Measuring multiple sites on teeth with fluorescence devices only moderately influences performance compared to one site being investigated.

Obwohl sich Eltern autistischer Kinder bereits in den ersten Lebensjahren Sorgen über die Entwicklung ihres Kindes machen, wird die Diagnose, insbesondere die des Asperger-Syndroms (AS), auch heute noch relativ spät gestellt. Vorhandene Studienergebnisse zu Frühsymptomen beziehen sich zumeist auf den frühkindlichen Autismus und zu ersten Symptomen bei AS liegen bisher nur wenige Studien vor. In der vorliegenden Untersuchung wird der Frage nachgegangen, welche spezifischen Frühsymptome beim AS auftreten, die eine frühe Diagnosestellung und differentialdiagnostische Unterscheidung zwischen AS und AHDS ermöglichen. Die Eltern von 117 Kindern im Alter von fünf bis 18 Jahren (74 mit Diagnose AS, 43 mit ADHS) wurden retrospektiv hinsichtlich früher Auffälligkeiten in der Entwicklung ihrer Kinder befragt. Es wurden zehn früh auftretende Symptome bei AS ermittelt, die eine gute Differenzierung zwischen den Diagnosen ermöglichen: Früh beginnende Kontakt- und Kommunikationsprobleme in Kombination mit im Entwicklungsverlauf zunehmenden stereotypen Verhaltensweisen stellen Symptome dar, die einer weiteren, differenzierten Diagnostik bedürfen.

This study aimed to evaluate a laser fluorescence device (the DIAGNOdent) and a visual classification system (ICDAS-II) for occlusal caries diagnosis. It also aimed to determine whether fluorescence measurements taken at the tooth surface correlate with the fluorescence measurements taken within the body of the lesion. The occlusal surfaces of 100 extracted permanent teeth were examined using ICDAS-II and DIAGNOdent (LF-tooth). Serial sections were made and lesion depth was assessed histologically. DIAGNOdent readings were also taken from the sections (LF-section). There were significant positive strong correlations between ICDAS-II and histology (r(S) = 0.71) and LF-section and histology (r(S) = 0.70), and only moderate correlations between LF-tooth and histology (r(S) = 0.51) and LF-tooth and LF-section (r(S) = 0.60). Diagnostic accuracy for ICDAS-II was generally better than for LF-tooth. While the DIAGNOdent device provides an objective reading for detection and monitoring of carious lesions, using the cut-off ranges previously suggested leads to inferior performance.

Summary Background and objective: In our original study based on five monozygotic twin pairs and seven same-sex sib pairs, we previously showed that genetic factors contribute to body weight gain induced by the atypical antipsychotic clozapine. We aim to study this further by including patients treated with the atypical antipsychotics olanzapine or risperidone as well as opposite-sex sib pairs. Methods: Twin and sib pairs were identified by a telephone screening. Measured data on weight and other clinical variables were obtained cross-sectionally and retospectively from medical records. In seven monozygotic twin pairs and 12 sib pairs (total number of patients treated: n = 38, mean age 29·5 ± 9·5, range 13·7–54·3 years), the similarity in BMI (kg/m2) change under these atypical antipsychotics (atypical ΔBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total ΔBMI) was explored. Results: For total ΔBMI we found greater similarity in antipsychotic-induced BMI change in MZ twin pairs than in sib pairs (intrapair difference) with a heritability of h2 = 0·6, but not for atypical ΔBMI, possibly because of a genetically influenced weight plateau achieved under antipsychotic medication. Conclusion: The results of the present and our previous report suggest a contribution of genetic factors in antipsychotic-induced weight gain of 60–80%.

Background Although the diagnosis of restless legs syndrome (RLS) is largely based on the presence of the four essential criteria, no validated diagnostic questionnaire exists for use in epidemiological studies or clinical practice.

Histology is frequently used as a gold standard to validate caries detection devices. Poor assessment consistency could lead to apparent changes in diagnostic accuracy. In multi-center, multi-examiner studies electronic transfer of information would be convenient, provided there is no deteriation in quality. This study tested the hypothesis that examiner reproducibility in the assessment of caries lesion depth when viewing photographic images of histological sections on a computer monitor, is comparable with viewing the same sections under a microscope using two histological classification systems.166 investigation sites (96 teeth) were selected for visual examination (ICDAS-II) and sections made using a novel technique which reduced risk of section damage and allowed accurate allocation of section to each investigation site. Digital images of the sections were produced and four examiners viewed the sections under a microscope and on a separate occasion corresponding digital images on a computer monitor. Presence and extent of caries was scored according to two histological classification systems (Downer, ERK).The inter- and intra-examiner reproducibility for both histological classification systems and both examination techniques was substantial to almost perfect (weighted kappa=0.63-0.90). Comparing the kappa values between microscopy and viewing digital images, there was no effect or only a small effect between both examination techniques (effect size 0.00-0.28). There was also a strong relationship between the two viewing techniques (r(s)=0.748-0.844).Viewing digital images of tooth sections produces results comparable to viewing images directly under a microscope and therefore has potential benefits for multi-centre studies.

Carious lesions can occur at different sites on the occlusal surfaces of teeth and may differ in appearance and severity. This study aimed to evaluate how estimates of reproducibility and accuracy of ICDAS-II were affected when all lesions on occlusal surfaces, or only a representative lesion, were scored. 100 permanent teeth with 1–4 investigation sites on the occlusal surface were examined visually by four examiners. Serial sections of the teeth were assessed for lesion depth. Intra- and interexaminer reproducibility (weighted kappa values), sensitivity, and specificity were calculated for all investigation sites and for a randomly selected site per tooth. Comparing the kappa values for the whole sample and the independent sites, no effect or only a small effect was found. Comparing the areas under the ROC-curves no effect could be shown. Examining multiple sites on teeth leads to results comparable to when a single independent site is chosen per tooth.

Aripiprazole is a fairly new atypical antipsychotic substance. It acts as a partial D2- and 5-HT1A-agonist and as a 5-HT2A-antagonist. To date, there are few data concerning the dose-serum concentration relationship in children and adolescent psychiatric patients. Also, there are only few data on the influence of age, sex, body mass index, smoking behavior, and comedication on aripiprazole serum concentrations. In 33 consecutively admitted patients of a child and adolescent psychiatric hospital [age (mean +/- standard deviation) 18.7 +/- 1.7 years (range, 13.5-21.6 years)], 117 steady-state serum concentrations (repeated samples from individuals) of aripiprazole and its metabolite dehydroaripiprazole were assessed using high-performance liquid chromatography. The aripiprazole (mean +/- standard deviation) daily dose was 12.9 +/- 6.4 mg (range, 5-30 mg); the aripiprazole serum concentration was 142.0 +/- 122.7 ng/mL (range, 40.0-648.3 ng/mL; interquartile range, 74.0-167.0 ng/mL). The mean dehydroaripiprazole serum concentration was 51.6 +/- 22.3 ng/mL (range, 30.0-111.6 ng/mL; interquartile range, 34.3-62.1 ng/mL). There was a positive correlation between oral dose and serum concentrations of aripiprazole (r = 0.548, P = 0.001) and dehydroaripiprazole (r = 0.740, P < 0.0005). Aripiprazole serum concentrations showed high inter- and intraindividual variability. Intraindividual variability was one- to 9.3-fold (dehydroaripiprazole: one- to 8.6-fold) and maximum interindividual variability 6.4-fold (dehydroaripiprazole: 6.8-fold). No significant influence was detected for age, sex, body mass index, comedication, and smoking on concentration-to-dose aripiprazole serum concentrations. Further studies are required to obtain data on the relationship between serum concentrations and resulting clinical effects.

Background and purpose: The cause of Tourette syndrome (TS) is not precisely known, although several lines of evidence point at an involvement of the immune system in its pathogenesis. Results: Here, we report the results of a pilot study investigating frequently analysed lymphocyte surface markers in 20 adult patients with TS (16 males; 37.3 ± 15.8 years) and 20 matched controls (16 males; 37.5 ± 15.3 years). Statistical analysis revealed significant differences for the investigated lymphocyte surface markers. The difference in CD69+/CD22+-B cells (23.0 ± 10.5% vs. 13.1 ± 6.1%; P = 0.001) and in CD95+/CD4+-T cells (41.5 ± 12.1% vs. 24.6 ± 10.0%; P = 0.0001) was still significant after Bonferroni–Holm correction. Conclusion: Our preliminary data indicate that TS may be associated with an increased peripheral immune activity.

Aim: The aim of this study was to assess inter- and intra-examiner reproducibility and accuracy in the detection and assessment of occlusal caries in extracted human teeth using a newly developed visual method for caries diagnosis (International Caries Detection and Assessment System, ICDAS-II). Serial sectioning and microscopy were used as the ‘gold standard’. Methods: The occlusal surfaces of 100 teeth were examined by 4 dentists using the ICDAS-II graded scores 0–6. Thereafter the teeth were serially sectioned and assessed for depth of the lesion with two histological classification systems. Results: The weighted kappa values for inter- and intra-examiner reproducibility for the ICDAS-II examination were 0.62–0.83. There was a moderate relationship between the visual and both histological examinations (rs = 0.43–0.72). At the D1 diagnostic threshold (enamel and dentine lesions) specificity was 0.74–0.91 and sensitivity was 0.59–0.73. At the D3 diagnostic threshold (dentine lesions) specificity was 0.82–0.94 and sensitivity was 0.48–0.83 for the 4 examiners. Conclusion: The ICDAS-II system has demonstrated reproducibility and diagnostic accuracy for the detection of occlusal caries at varying stages of the disease process which are comparable to previously reported data using similar visual classification systems.

To assess the preventive measures which were associated with the striking caries decline observed in Marburg (Germany) between 1982 and 2002 and to investigate the relationship between caries prevalence and the type of educational level. 1,237 twelve-year-old children were examined in four different types of schools. D3MFT and the number of teeth with fissure sealants were registered. Information about preventive measures carried out in the past was collected by structured questionnaires. To compare the mean caries scores of various subgroups, Mann-Whitney U-tests and ANOVA were performed. Variables associated with caries were included in a binary logistic regression analysis. In 2002 the mean D3MFT score amounted to 0.78. In 80.7% of the pupils fissure sealants were observed, on average 3.5 teeth with sealants were recorded per child. There were significant differences between the mean D3MFT scores and the mean number of teeth with fissure sealants among the various school types. Use of fluoride supplements in the past, use of fluoridated table salt and fissure sealants were the factors in the binary logistic regression analysis which were significant in preventing caries.

To explore the association between eating disorders (EDs) prior to the use of clozapine/olanzapine (pre-clozapine/olanzapine EDs) and after initiation of these antipsychotics (post-clozapine/olanzapine EDs).Sixty-four consecutively admitted patients receiving clozapine/olanzapine were screened using the M-Composite International Diagnostic Interview (M-CIDI) to identify subjects with pre-clozapine/olanzapine EDs (DSM-IV criteria). We investigated post-clozapine/olanzapine EDs and binge eating behavior using the Questionnaire on Eating and Weight Patterns (QEWP) and used the Naranjo probability scale as objective causality assessment.Post-clozapine/olanzapine EDs were significantly more frequent in patients with pre-clozapine/olanzapine EDs (5 of 6) when compared to patients without pre-clozapine/olanzapine EDs (4 of 58) [chi(2) = 26.29; df = 1; p0.001] [odds ratio (OR) 67.5; 95% CI: 6.3-725.8]. According to the Naranjo probability scale, recurrence or deterioration of EDs in patients with prior EDs was definitely (n = 1) or probably (n = 4) related to the intake of clozapine/olanzapine.Clozapine/olanzapine may induce recurrence or deterioration of binge eating symptomatology or full-blown EDs in patients with prior EDs.

Background Sound teeth and incipient lesions require regular monitoring to detect possible progression of caries early on. Aim To evaluate the ability of the VistaProof (VP) fluorescence-based camera for monitoring occlusal surfaces. Design A total of 419 posterior teeth (205 primary molars, 145 permanent molars, and 69 premolars) of 35 patients were examined (average age: 9.1 years). The occlusal surfaces were classified visually according to the criteria of the International Caries Detection and Assessment System (ICDAS). VP measurements were performed at baseline (t1), and the examinations were repeated after six (t2) and twelve month (t3). Correlation between methods was calculated using Spearman's rank correlation coefficient (rs). Wilcoxon test was used to monitor whether VP identified changes as well as ICDAS (α = 0.05). Results Correlations between ICDAS and VP were significantly positive (rs: 0.66–0.73, P

Primary care physicians (PCPs) play a key role in the initial assessment and management of children and adolescents with mental health problems. However, it is unclear whether current medical education curricula sufficiently equip PCPs for this task. The aim of this study was to investigate, which child and adolescent psychiatry (CAP)-related skills and knowledge PCPs say they require in their daily practice. A questionnaire was generated, employing a modified two-step Delphi approach. Besides socio-demographic items, the questionnaire contained 17 CAP-related knowledge items and 13 CAP-related skills items, which had to be rated by importance in daily practice. The questionnaire was distributed to 348 office-based paediatricians and 500 general practitioners (GPs) in Germany. The overall return rate was 51.3% (435/848). Regarding CAP-related knowledge, both paediatricians and GPs rated somatoform disorders and obesity as highly important for daily practice. Moreover, paediatricians also deemed regulatory disorders during infancy (e.g. crying, sleep disorders) as important, while GPs assessed knowledge on paediatric depression as relevant. For paediatricians and GPs, the most relevant CAP-related skills were communicating with children and adolescents and their parents. Additionally, paediatricians rated differentiating between non-pathologic and clinically relevant behaviour problems very relevant, while GPs considered basic psychotherapeutic skills essential. The CAP-related knowledge and skills perceived relevant for doctors in primary care differ from the majority of current medical school CAP curricula, which cover mainly typical, epitomic CAP disorders and are predominantly knowledge-oriented. Therefore, medical education in CAP should be amended to reflect the needs of PCPs to improve healthcare for children and adolescents with mental health problems.

The management of white-spot lesions remains a challenge, especially during and after fixed orthodontic treatment. The aim of this in vitro study was to evaluate the efficacy of the newly introduced self-assembling peptide P11-4 (Curodont™) for regenerating demineralized tooth tissue on smooth surfaces. Another aim was to evaluate whether the DIAGNOdent (DD) and VistaProof (VP) fluorescence systems are suitable for differentiating between demineralized and remineralized enamel. A total of 40 sound samples (buccal surfaces) of extracted human posterior teeth were artificially demineralized. The samples were examined visually as well as via DD and VP. Curodont was applied to 30 samples which were then stored in a remineralizing agent (test group). In control group 1, Curodont was applied to 5 samples which were then stored in water. Control group 2 consisted of 5 samples stored in the remineralizing agent only. Sample surfaces were examined visually and by means of DD and VP after 1 week (t1), 8 weeks (t2), and 12 weeks (t3). All fluorescence measurements were taken twice. Sample surfaces were viewed using a scanning electron microscope (SEM). Statistical analysis was conducted using the IBM SPSS® Statistics and MedCalc® programs. The fluorescence measurements’ reproducibility was calculated using the intraclass correlation coefficient (ICC). A χ2 test was applied to detect any significant differences between the fluorescence measurements of the test and control groups at each examination. Receiver operating characteristic (ROC) curves of DD and VP were constructed and areas under the ROC curve (AUC) were compared (α = 0.05) between the two fluorescence devices. Reproducibility of DD was moderate at t3, while the ICC values were high for all other measurements. Significant differences between the fluorescence measurements at t2 and t3 between the test and control groups (p

When the International Caries Detection and Assessment System (ICDAS-II) was introduced, a two-number coding system that identifies restorations/sealants with the first digit and scores the caries lesions with a second digit was suggested. The aim of this study was, first, to assess the intra- and interexaminer reproducibility of this method applied by predoctoral dental students and, second, to evaluate the influence of an additional theoretical training session on the reproducibility values. Twenty-four third-year dental students at Philipps University of Marburg, Germany, were trained in a theoretical session by an experienced examiner. The students were randomly divided into two groups to examine extracted teeth. The assessments were repeated after three weeks. Prior to the second examinations, one group received an additional theoretical training session. For the restoration code, mean kappa values for intra- and interexaminer reproducibility were between 0.28 and 0.82. For the caries code, mean kappa values for intra- and interexaminer reproducibility were between 0.34 and 0.72. The mean kappa values of the two groups did not differ significantly, either on the first digit or on the caries code (p>0.05).

Background The Marburg Heart Score (MHS) aims to assist GPs in safely ruling out coronary heart disease (CHD) in patients presenting with chest pain, and to guide management decisions. Aim To investigate the diagnostic accuracy of the MHS in an independent sample and to evaluate the generalisability to new patients. Design and setting Cross-sectional diagnostic study with delayed-type reference standard in general practice in Hesse, Germany. Method Fifty-six German GPs recruited 844 males and females aged ≥35 years, presenting between July 2009 and February 2010 with chest pain. Baseline data included the items of the MHS. Data on the subsequent course of chest pain, investigations, hospitalisations, and medication were collected over 6 months and were reviewed by an independent expert panel. CHD was the reference condition. Measures of diagnostic accuracy included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, likelihood ratios, and predictive values. Results The AUC was 0.84 (95% confidence interval [CI] = 0.80 to 0.88). For a cut-off value of 3, the MHS showed a sensitivity of 89.1% (95% CI = 81.1% to 94.0%), a specificity of 63.5% (95% CI = 60.0% to 66.9%), a positive predictive value of 23.3% (95% CI = 19.2% to 28.0%), and a negative predictive value of 97.9% (95% CI = 96.2% to 98.9%). Conclusion Considering the diagnostic accuracy of the MHS, its generalisability, and ease of application, its use in clinical practice is recommended.

Aim. To use visual inspection (ICDAS-II), laser fluorescence (LF), fluorescence based camera (FC) and radiographic examination (BW) for detection of caries and for treatment decision. Methods. The occlusal sites of 84 extracted permanent teeth were examined using all methods and treatment decisions (preventive or operative care) were recorded based on each method independently. For validation of the findings, fissures were opened with rotating instruments and clinical depth was determined as gold standard. Correlations ( 𝑟 𝑠 ), sensitivity, specificity and AUC were calculated. McNemar test was used to show whether different methods led to significant changes in treatment decisions. Results. Highest correlation was found between ICDAS-II and FC ( 𝑟 𝑠 0.84), ICDAS-II and gold standard (0.82) and FC and gold standard (0.81). ICDAS-II provided the highest performance (AUC 1.0), followed by FC (0.95) and LF (0.88). The greatest difference was found for treatment planning of dentine lesions, where the use of FC (cut-offs according to the literature) had the greatest agreement between operative treatment and dentine lesions, followed by use of ICDAS-II. Conclusion. ICDAS-II may have high potential for detection and treatment planning, and other devices, especially the fluorescence camera, can add substantial information to the visual examination, enabling examiners plan treatment more accurately.

The aim of this study was firstly to assess inter- and intra- examiner reproducibility and accuracy in the detection of occlusal caries in extracted human teeth using the newly developed fluorescence-based camera VistaCam iX and secondly to compare the performance to the established fluorescence device VistaProof. The occlusal surfaces of 101 teeth were assessed. The distribution of the lesions were characterized first visually using ICDAS-II (consensus score). The investigation sites were assessed by two examiners with different levels of experience in cariology (one experienced dentist, one final-year dental student) by both fluorescence-based cameras VistaCam iX (FC1) and VistaProof (FC2). The teeth were hemisectioned and assessed for lesion depth. Intra-class-correlation coefficients for inter- and intra-examiner reproducibility were 0.88-0.97 (FC1) and 0.82-0.98 (FC2), respectively. There was significant positive correlation (r (s), p0.01) between all methods (ICDAS-II, fluorescence, and histological examinations: 0.63-0.89) and between FC1 and FC2 (r (s) 0.85-0.90), respectively. Areas under the ROC curves (AUC) were 0.87-0.92 (D(1) and D(3) diagnostic threshold, FC1) and 0.91-0.96 (FC2). There were no significant differences between the AUC of both fluorescence cameras (p values0.05). Both fluorescence cameras demonstrated high reproducibility and good performance for the detection of occlusal caries at various stages of the disease process. The novice and the experienced examiner were able to apply both systems for detection of lesions. The in vitro performance of both devices was comparable to each other, although there was a tendency of a better performance for the FC2. Thus, within the limitations of an in vitro study, measurements with the FC2 can be continued by the new fluorescence camera (FC1) and data formerly assessed can be compared without significant loss of information.

Background: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. Methods: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain ( n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). Results: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83–0.91) for the derivation cohort and 0.90 (95% CI 0.87–0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3–5 points; negative result ≤ 2 points), which had a sensitivity of 87.1% (95% CI 79.9%–94.2%) and a specificity of 80.8% (77.6%–83.9%). Interpretation: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Data concerning the effectiveness of naturalistic treatments (treatment-as-usual) in child and adolescent psychiatric (CAP) services are scarce. The purpose of this prospective observational study was to examine the effectiveness of CAP treatments in a naturalistic outpatient setting. Three hundred six patients (attention-deficit/hyperactivity disorder, ADHD, n=94; conduct disorder, CD, n=57; anxiety disorder, AD, n=53; depressive disorder, DD, n=38; other diagnostic categories, n=64), from nine child and adolescent psychiatric practices in Germany, were evaluated. Treatment effects were compared between patients who received frequent treatment and patients who only participated in diagnostics and short interventions. Since randomization was not feasible, propensity score analysis methods were used. Regarding the total sample, no significant treatment effects were found. However, a subgroup analysis of the four most frequent disorders (ADHD, CD, AD, DD) showed small to moderate treatment effects in patients with ADHD and AD. In CD and DD subgroups, no significant treatment effects could be found. “Real-world” CAP outpatient treatment seems to produce significant effects for ADHD and AD, but not for CD and DD. Compared to efficacy studies, our results show that naturalistic treatment might be better than expected.

The aim of this study was to assess inter- and intra-examiner reproducibility and accuracy in the detection and assessment of occlusal caries in extracted human teeth using the newly developed fluorescence based camera VistaProof. Serial sectioning and microscopy are considered the gold standard. The occlusal surfaces of 53 teeth (99 investigation sites) were examined by two examiners with different levels of experience in cariology (one experienced dentist, one final-year dental student) and the VistaProof. Thereafter, the teeth were serially sectioned and assessed for lesion depth. The intraclass correlation coefficients for inter- and intra-examiner reproducibility for the fluorescence-based examinations were 0.76–0.95. There was a significant correlation between the fluorescence and histological examinations for both examiners (r s = 0.47 and 0.55, P < 0.01). At the D1 diagnostic threshold (enamel and dentin lesions), sensitivity was 0.71–0.86 and specificity was between 0.32 and 0.76 at different cutoff values. At the D3 diagnostic threshold (dentin lesions), sensitivity was 0.04–0.91 and specificity was 0.56–0.99 for both examiners. When the areas under the receiver-operating characteristic curves were compared, there was no significant difference in the performance between the examiners (P = 0.52 at the D1 threshold, P = 0.81 at the D3 threshold). The VistaProof demonstrated high reproducibility and good diagnostic performance for the detection of occlusal caries at various stages of the disease process. Novice and experienced examiners were able to apply this system as a supportive device for caries diagnostic and monitoring purposes. Sensitivity and specificity values varied depending on the cutoff values.

Aim: To evaluate intra- and interexaminer reproducibility of ICDAS-II on occlusal caries diagnosis when different time intervals were allowed to elapse between examinations. A subsidiary aim was to determine whether collapsing the codes would influence this reproducibility. Methods: The occlusal surfaces of 50 permanent posterior teeth were investigated by 3 trained examiners using ICDAS-II at baseline, 1 day, 1 week and 4 weeks after baseline. Results: Weighted kappa values for intra- and interexaminer reproducibility were 0.76–0.93. Conclusion: The time span did not have a major impact on assessing intra- and interexaminer reproducibility. Collapsing ICDAS-II codes had no impact on examiner reproducibility.

Olanzapine (OLZ) is a widely used antipsychotic substance. Therapeutic drug monitoring (TDM) of OLZ is recommended but is based on known reference ranges derived from intraindividual and interindividual variability measurements. There have been few studies on the interindividual variability of OLZ serum concentrations in adolescents, and no data on intraindividual variability are available. This study explored the intraindividual variability of OLZ serum concentrations in 85 patients attending a child and adolescent psychiatric hospital (age at first assessment: mean +/- SD, 16.7 +/- 2.0; range, 10.3-20.6 years; 54 male, 31 female). A total of 577 steady-state OLZ serum concentrations (2 to 24 measurements per patient; mean, 6.8, and SD, +/-5.4) were measured, using high-performance liquid chromatography (HPLC). Intraindividual variability of dose-corrected OLZ serum concentrations was 1.04- to 10.7-fold. The intraindividual variabilities of the metabolites OLZ N-desmethyl (DMO) and OLZ 2-hydroxymethyl (2OH) were 1.08- to 83.2-fold and 1.0- to 47-fold, respectively. Intraindividual variability of OLZ (DMO; 2OH) serum concentration accounted for 47% (89.8%, 74.9%) of total variance. OLZ daily dose, number of co-medications, body mass index (BMI), age, and post-dose interval had a significant influence on the intraindividual variability of dose-corrected OLZ serum concentrations (all P0.001). The serum concentrations of OLZ and OLZ metabolites in adolescents show high intraindividual variability, potentially limiting the value of TDM. It is recommended that repeated serum concentration measurements are made in individuals treated with OLZ, in order to obtain a more precise estimate of the intraindividual variability of serum concentrations.

The aim of this study was to assess dose-related steady-state serum concentrations of olanzapine (OLZ) and its metabolites N-desmethyl OLZ (DMO) and 2-hydroxymethyl OLZ (2-OH-OLZ) (assessed by high-performance liquid chromatography) in 122 child and adolescent psychiatric patients (age 16.9 +/- 2.2, range, 10-21 years; 74 males, 48 females) with a variety of diagnoses: schizophrenia group (n = 80); nonschizophrenia group (n = 29); anorexia nervosa (AN) group (n = 13). Median OLZ serum concentrations were 32.7 (range, 1-118; all patients), 37.7 (2-115; schizophrenia group), and 18.7 (1-63, AN group) ng/mL. The median OLZ concentration-to-dose (C/D) ratio (n = 122) was 2.6, with 90% of the distribution between 0.8 and 5.5 (ng/mL)/(mg/d). OLZ concentration was significantly correlated with DMO (r = 0.567; P < 0.0005) but not with 2-OH-OLZ (r = 0.122; P = 0.188). Daily OLZ dose was correlated with OLZ concentration in all (r = 0.684; P < 0.0005), schizophrenic (r = 0.542; P < 0.0005), and AN (r = 0.805; P = 0.001) patients, respectively. Patients aged less than 16 years displayed similar C/D for OLZ (P = 0.58) but higher C/D for DMO (P = 0.003) than those 16 years or older. AN patients received lower median OLZ doses (7.5; 5-15 mg) than schizophrenic patients (12.5; 2.5-40 mg), even after correcting for body mass index (P = 0.02). OLZ dose did not differ (P = 0.088) between smokers and nonsmokers, but smokers showed lower C/D for OLZ than nonsmokers (P = 0.008). C/D for OLZ was 38% higher (P = 0.041) under comedication with selective serotonin reuptake inhibitors when compared with OLZ monotherapy. Multiple linear regression analysis revealed that 46% of the variation of OLZ concentration can be explained by dose, diagnosis, age, sex, smoking, and comedication. The data are compared with the literature, and the relevance of therapeutic antipsychotic drug monitoring in previously sparsely investigated subgroups, such as children and adolescents or patients with AN, is emphasized.

In a retrospective study in two different regions of Germany, 1,041 fifteen-year-old pupils were examined for dental fluorosis. The adolescents had taken part in different caries prevention programmes. There were 746 subjects in the study group and 295 subjects in the control group. For each participant, specific aspects of early development, diet and fluoride exposure in group prevention programmes and at home were determined by means of questionnaires. The Thylstrup-Fejerskov index was used to classify the fluorosis scores on the buccal surfaces of teeth 11, 12, 13, 14, 15 and 16 after compressed air drying of the teeth. Binary logistic stepwise regression analyses were conducted to identify associations between fluorosis and potential influence factors. A distinction was made between early and late developing tooth parts. The significance level was set at α = 0.05. Fluorosis prevalence in the regions studied was 7.1 and 11.3%, respectively. The difference was not statistically significant (p = 0.052; chi square). Binary logistic stepwise regression analysis revealed that ‘early start of toothbrushing’ was a statistically significant predictor of dental fluorosis in the early-mineralizing enamel (OR = 1.99, p = 0.027). For the late-mineralizing enamel no single independent variable was identified as a significant predictor of dental fluorosis.

Mit der vorliegenden Studie wurde die Wirkung einer zahnmedizinischen Intensivprophylaxe (SIP) auf die Zahngesundheit von Schulern im Vergleich zu einer Kontrollgruppe untersucht. Wahrend sich die Erstklassler bezuglich der Zahngesundheit kaum unterschieden, ergaben sich bei den mit SIP betreuten Viert- und Sechstklasslern signifikant niedrigere DMF-T-Werte. Bei den psychometrischen Variablen zeigten sich mit Ausnahme der Zahnbehandlungsangst kaum Unterschiede zwischen der Versuchs- und Kontrollgruppe.