Can crowdsourced data help to optimize atopic dermatitis treatment? Comparing web search data and environmental data in Germany.

BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic skin diseases worldwide, showing various manifestations and having a severe impact on quality of life. As previous studies demonstrated, internet search analysis can help identify public interest in diseases and possible influencing factors on search behavior. OBJECTIVE: To identify AD-related topics of interest in Germany using internet search volume. METHODS: Google Ads Keyword Planner was used to identify AD-related search terms including their search volume in Germany on a national level as well as in 16 selected cities from January 2016 to December 2019. Identified keywords were qualitatively analyzed, and temporal trends as well as the influence of seasonal and environmental factors on search volume were assessed. RESULTS: Overall, 1222 AD-related search terms with a search volume of 8 842 360 searches were identified. An increase from 2016 to 2019 and seasonal peaks from January to April of each year were observed. Nationwide, the search volume correlated with mean monthly temperature and sun duration. With increasing temperature and sun duration, a significant decrease in search queries was observed. The most populated cities showed the lowest number of searches per 100 000 inhabitants (Berlin, Hamburg, and Munich). In the eight categories formed (comorbidities, general, influential factors, localization, stage of life, symptoms/severity, therapy/information, and questions on AD), the highest proportion of search queries were assigned to the category "therapy/information" in most cities. In this category, a focus on the topics of "alternative medicine" and "home remedies" could be observed. CONCLUSION: The overall high and increasing search volume indicates a high interest in AD-related topics, especially regarding treatment and disease education. Information provided by internet search volume analyses can optimize AD therapy and patient-centered care by providing insight into patient needs and predicting potential climatic trigger factors.

Happiness in dermatology: a holistic evaluation of the mental burden of skin diseases.

BACKGROUND: According to the World Health Organization, mental health is a state of well-being and not merely the absence of disease. However, studies exploring subjective well-being in patients with skin diseases are very rare. OBJECTIVES: To assess subjective well-being, i.e. 'happiness', in patients with different skin diseases and to compare them to other patient groups and healthy controls. METHODS: A cross-sectional study was conducted from 12/2017 to 04/2019. Patients receiving in- or outpatient care for psoriasis, atopic eczema, nummular eczema, mastocytosis, skin cancer (malignant melanoma and keratinocyte carcinoma), human immunodeficiency virus (HIV) or chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) were recruited at two hospitals in Bavaria, Germany. Healthy individuals living in or near Munich served as a control group. All participants filled in a questionnaire assessing happiness, measured as positive affect (PA), negative affect and satisfaction with life (SWL; together representing subjective well-being) and a heuristic evaluation of one's own happiness. RESULTS: Data from 229 dermatologic patients (53.3 ± 18.5 years, 48% women), 49 patients with inflammatory bowel diseases (48.9 ± 18.7 years, 43% women), 49 patients with HIV (46 ± 10.1 years, 10% women) and 106 healthy controls (38.4 ± 13.4 years, 49% women) were analysed. Compared to the controls, dermatologic patients reported lower heuristic happiness (P = 0.023) and PA (P = 0.001) but higher SWL (P = 0.043). Patients with psoriasis and atopic eczema reported the lowest happiness, as they reported significantly lower PA (P = 0.032 and P < 0.001) and heuristic happiness (P = 0.002 and P = 0.015) than the control group. Patients with skin cancer reported higher SWL than the control group (P = 0.003). Dermatologic patients reported lower happiness than patients with HIV but reported greater happiness than patients with IBD. CONCLUSIONS: Dermatologic patients experience lower levels of happiness, especially PA, compared to healthy controls. As PA is linked to desirable health outcomes, targeting PA could be a promising holistic approach for the treatment of skin diseases.

[Non-drug treatment of rheumatoid arthritis : An analysis of claims data and a survey of insured persons (Project PROCLAIR)]. / Nichtmedikamentöse Versorgung der rheumatoiden Arthritis : Eine Analyse von Abrechnungsdaten und einer Versichertenbefragung (Projekt PROCLAIR).

BACKGROUND: Only small amounts of data are available on the prescription frequency of physical therapies (PT) for patients with rheumatoid arthritis (RA). OBJECTIVE: The aim of the study was to evaluate prescription frequencies of PT considering functional status and sociodemographic factors. MATERIAL AND METHODS: A total of 98,963 adults diagnosed with RA in 2013 were identified in claims data from the BARMER health insurance. A questionnaire was sent to a representative sample of 6193 people requesting information on the disease status. Of these 2535 persons were included who agreed to the linking of the questionnaire and claims data and who confirmed a diagnosis of RA. From the routine claims data the prescription of PT and occupational therapy as well as the medical discipline of the prescribing physician were analyzed. Multivariable logistic regression was conducted to determine which variables (age, sex, M05/M06 diagnosis, residential area, income, functional status and rheumatological care) were associated with the use of PT. RESULTS: In 2015 a total of 47% of the study population received PT (35% physiotherapy, 15% thermotherapy, 15% manual therapy, 2% electrotherapy and 6% massage) and 3% occupational therapy. Of the PT prescriptions 37% were issued by general practitioners, 27% by orthopedists and 18% by rheumatologists. Women and persons living in the eastern states of Germany and patients with high functional impairment were prescribed PT more often. Income, educational status, seropositivity and rheumatological care did not have any influence on the frequency of prescription of PT. CONCLUSION: There are deficits in the outpatient prescription of PT but without indications of an undersupply of population groups due to low socioeconomic status. In contrast to the prescription of disease-modifying antirheumatic drug (DMARD) treatment, PT is predominantly prescribed by general practitioners.

Neuromodulation of orexin neurons reduces diet-induced adiposity.

BACKGROUND/OBJECTIVES: Low levels of orexin are associated with obesity and reduced physical activity in humans and animals. SUBJECTS/METHODS: Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated orexin neurons in mouse lateral hypothalamus (LH) to measure effects on spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic injection of AAV vectors into caudal lateral LH of heterozygous orexin-Cre or C57/B6J mice. In one set of studies, excitation of orexin neurons was examined (virus: AAV2-EF1a-DIO-hM3Dq-mCherry), and test sessions began 3-4 h after light cycle onset. In a study examining the inhibition of orexin neurons (virus: AAV2-hSyn-DIO-hM4Di-mCherry), testing began 15 min prior to dark cycle onset. Clozapine n-oxide (CNO; 1 or 5 mg/kg) or saline was injected intraperitoneally and time spent moving in open field chambers was recorded for 2 h. Follow-up studies in separate mouse cohorts quantified SPA in parallel with changes in energy expenditure (EE) and chow intake using indirect calorimetry chambers (SableSystem™). Following acclimation, testing sessions (saline and/or CNO) took place over the course of ~1 week, with injections administered every day. Changes in SPA, EE, chow intake, fecal boli, and body composition (EchoMRI™) were measured. Additional mice cohorts were fed a high-fat diet (HFD) and injected with CNO daily up to 10 days to assess the potential for orexin activation to prevent diet-induced obesity. RESULTS: Activation of orexin resulted in increases in SPA in male and female mice, and was accompanied by increases in energy expenditure without changes in overall chow intake. When orexin activation occurred in the context of high fat diet, weight gain and adiposity were significantly attenuated. SPA was decreased when DREADDs were used to inhibit orexin activity. CONCLUSION: These results demonstrate that orexin neurons play a critical role in mediating physical activity and suggest a novel therapeutic target for treating obesity.

Unusual spinal tuberculosis in an Avar Age skeleton (Csongrád-Felgyo, Ürmös-tanya, Hungary): A morphological and biomolecular study.

The paleopathological analysis of a well-preserved young adult female skeleton from the AD 7-8th century (Avar Age) in Hungary revealed multiple lytic lesions in all of the thoracic and lumbar vertebral bodies. The lesions were characterized by smooth marginal zones and space-occupying mass appearance. The considerable loss of spongy bone in the thoracolumbar vertebrae resulted in angular deformity and fusion, characteristic of the healing stage of TB. Osteolytic lesions were also observed on the vertebral processes, ribs and sternum. On the endocranial surface, abnormal blood vessel impressions were revealed, indicating some kind of meningitis. The X-ray and CT analysis of the affected bones detected abnormal structures and cystic zones of destruction. The lesions were however not always bordered by areas of increased density, which is typical in cystic TB. Vertebral remains were also subjected to biomolecular analysis in two different laboratories, which attested the presence of Mycobacterium tuberculosis complex (MTBC) DNA and supported the paleopathological diagnosis of TB. Spoligotyping analysis confirmed the presence of MTBC DNA and more specifically an infection caused by bacteria belonging to the M. tuberculosis lineage. This case study provides new data for the paleoepidemiology of TB in this geographical area and historical period, and draws attention to the great variability of TB lesions in the human skeleton.

[Diagnostic spectrum, treatment indication and symptom duration in initial referrals to the rheumatologist]. / Diagnosespektrum, Behandlungsindikation und Symptomdauer von Erstzuweisungen zum Rheumatologen.

There is evidence that early initiation of therapy in inflammatory rheumatic diseases, in particular rheumatoid arthritis (RA), has a positive effect on disease course.To investigate referral procedures, 198 German rheumatologists reported over a 3-month period and for each patient seen for the first time on: patient characteristics, specialization of the referring physician, symptom duration, time interval between making the appointment and the first visit, diagnoses and relevant drug history. Multivariate logistic regression analyses were performed to investigate the odds ratios for a first consultation within 3 months after symptom onset.The 17,908 newly referred adult patients were 54 years old on average and 72% were women. Inflammatory rheumatic disease was diagnosed in 53%. Mean disease duration was 30 ± 57 months (median 7.3 months). There was no apparent association between patient age, education, disease severity or specialisation of the referring physician; however, there was a clear association with waiting times to first consultation.A higher number of early arthritis clinics could significantly shorten the time to first rheumatological consultation. Therefore, more efforts need to be made to fast-track referrals from primary care physicians to rheumatologists as well as to optimise rheumatologists' appointment regulations for new patients. However, these efforts can only succeed with a significant increase in the number of rheumatologists, while ensuring a firm economic basis.

Environmental gamma dosimetry with OSL of alpha-Al(2)O(3):C for in situ sediment measurements.

The physical properties of alpha-Al(2)O(3):C are very similar to that of quartz, which make it an attractive dosimetric material for geological and archaeological dating applications. Storage experiments in an ultra-low-radiation underground environment (UDO at PTB) and gamma-ray spectrometry show that the optically stimulated luminescence (OSL) signal of this material does neither suffer from a significant inherent background caused by traces of radionuclides (<6 microGy a(-1)) nor from fading. After having performed a simple calibration procedure, gamma dosimetry based on alpha-Al(2)O(3):C detectors, which were exposed in a brick block and a lead castle for different periods of time, provided concordant results with dose values derived from independent gamma-ray spectrometric measurements using high-purity germanium and NaI:Tl detectors. These investigations indirectly confirm both the absence of a significant inherent background and fading of the detector material. Small doses of a few micro gray accumulated in short exposure times to environmental radiation can be accurately measured, even when doses (i.e. transport dose) much larger than the actual environmental dose have to be subtracted. It is shown that the OSL signal caused by small transport doses can be easily and reproducibly reset even under difficult field conditions by illuminating the dosemeters with the blue light from Luxeon LEDs. Summarised, alpha-Al(2)O(3):C appears to be the material of choice for dosimetric dating applications of quartz or related materials, when analysed by using OSL.

[Basic treatment of early rheumatoid arthritis. Abstaining from rheumatological care and preferring alternative medicine increase the risk of undertreatment]. / Basistherapie bei früher rheumatoider Arthritis. Verzicht auf rheumatologische Mitbetreuung und Präferenz für Alternativmedizin erhöhen das Risiko einer Unterversorgung.

The major challenge in the management of rheumatoid arthritis (RA) is the early initiation and long-term continuation of disease-modifying antirheumatic drug (DMARD) therapy. A total of 916 RA patients (ACR criteria, disease duration <2 years) were investigated in regard to frequency and reasons for DMARD discontinuation. All patients were under rheumatological care at the start of the observation and almost all were receiving DMARDs at study entry (95%). The proportion decreased to 87% within 3 years. Of the 171 patients without DMARD, 5% abstained due to (planned) pregnancy, 28% due to contraindications and/or severe adverse events and 54% due to remission. Only 12% were non-compliant. Multivariate regression analysis revealed non-specialised care (OR 4.6; 59% CI 3.2-6.7), RF seronegativity (OR 2.6; 95% CI 1.8-3.8), no patient education (OR 2.2; CI 95% 1.5-3.4), preference for alternative medicine (OR 8.2; 95% CI 4.0-16.8) and > or =10 years of education (OR 1.8; 95% CI 1.3-2.7) as independent risks for DMARD abstention. Age, sex, comorbidity or disease activity did not influence adherence to DMARD therapy. Since preference for alternative medicine was the strongest risk predictor, further investigations are needed to determine the characteristics of this preference regarding compliance with DMARD medication in RA. The positive influence of patient education on DMARD continuation emphasizes its importance.

[Transition clinic--it is not always a simple segue in rheumatology for adults]. / Transition-Clinic -- Der nicht immer einfache Ubergang in die Rheumatologie für Erwachsene.

Chronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children's and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into account. Paediatric and adult rheumatologists should establish close cooperation and implement specific transition programs to meet the special health care needs of these patients.

[Out-of-pocket medical spending for care in patients with recent onset rheumatoid arthritis]. / Was kostet die rheumatoide Arthritis den Erkrankten? "Out-of-Pocket"--Ausgaben im Frühstadium der Erkrankung.

We examined out-of-pocket medical expenditures (OoP) of 869 patients with recent onset rheumatoid arthritis (ACR criteria, disease duration <2 years) using data from a prospective observational cohort. Out-of-pocket costs were retrospectively assessed for a period of 6 months by a list of 14 cost domains. Of the patients, 82% had costs due to copayments for prescribed drugs and 56% for over-the-counter drugs. Within six months each patient spent an average of 47 (+/- 67) Euro as co-payment and 45 (+/- 96) Euro for over-the-counter drugs. A comparable sum was spent for complementary and alternative medicine (47+/-250 Euro), which was used by 14% of the patients. The mean total OoP expenditure caused by RA was 628 Euro p.a. (median 306, IQ 66-334 Euro). The median costs accounted for approximately 2% of the average disposable yearly income in Germany. Out-of-pocket spending increased with functional limitations, poor health condition and pain as well as with level of education. A multivariate logistical regression analysis showed that patients with these characteristics spent about twice as much as patients with mild disease or low educational level. The odds ratios for having more than 306 Euro OoP-costs p.a. were OR=2.6 (CI 1.7-4) for patients with severe vs. moderate functional disability (HAQ> or =1.5 vs <1.5), OR=2.4 (CI 1.4-4.4) for patients in poor vs. good health condition (NRS 7-10 vs 0-3), and OR=2.1 for patients with severe vs. mild pain (CI 1.4-3.3). The level of OoP spending also varied by employment status (OR=0.28; CI 0.1-0.6 for jobless vs employed patients). Despite almost universal insurance coverage in Germany, patients with rheumatoid arthritis were exposed to substantial OoP expenditures. As policymakers discuss cost sharing and design of benefit packages to contain health spending, it is important to consider the expenditures that persons with chronic conditions like rheumatoid arthritis already have.

Practice variation in the treatment of rheumatoid arthritis among German rheumatologists.

OBJECTIVE: To describe practice variation in the treatment of rheumatoid arthritis (RA) among German rheumatologists with regard to drug and non-drug therapy. METHODS: We used data of 7,326 patients with RA registered in a national German rheumatological database in 1998. In the database, every patient with an inflammatory rheumatic disease seen at one of the German Collaborative Arthritis Centres is registered once a year with a standard clinical data form and a patient questionnaire. We compared health care provided by 29 rheumatological outpatient units. For drug and non-drug treatment unit prescription rates, ranges and outliers were calculated. Logistic regression analysis was used for case mix adjustment and for the identification of practice patterns. RESULTS: We observed variation concerning the frequency of use of single disease modifying antirheumatic drugs (DMARD). The median of the prescription rates in the 29 units for methotrexate (MTX) was 55% in 1998 (1st quartile: 51%, 3rd quartile: 63%); sulfasalazine had a median of 15% (quartiles: 10%/19%), antimalarials a median of 8% (quartiles: 5%/21%). Combination DMARD therapy was used in 11% (quartiles: 6%/18%). Prescriptions of low dose steroids (< or = 7.5 mg) had a median of 45% (quartiles: 35%/55%), and nonsteroidal antiinflammatory drugs (NSAID) had a median prescription rate of 58% (quartiles: 50%/70%). High variation was also found concerning active physiotherapy (median: 41%; quartiles 34%/55%) and passive physical measures (median 14%, quartiles 9%/37%). Differences in case mix (age, sex, rheumatoid factor, disease duration, severity, disability) only explained a small proportion of the total variation. When the units were grouped according to the frequency of prescription of DMARD combination therapy, treatment patterns could be identified. Units with higher rates of DMARD combination therapy used more drugs for the prevention and treatment of osteoporosis, more active physiotherapy but fewer NSAID and fewer passive physical therapies. CONCLUSION: Variation in drug and non-drug treatment indicates significant differences in health care provision. Trends in the drug management of RA are adopted differentially by the members of the rheumatology community. The large variability in non-drug therapies may, apart from differences in availability, suggest a lack of agreement on therapeutic effectiveness.

Molecular evidence for different stages of tuberculosis in ancient bone samples from Hungary.

This paleomicrobiologic study was conducted on osseous tissue specimens from ancient Hungarian skeletal samples from the 7-8th and the 17th centuries AD with typical macromorphologic evidence of osseous tuberculosis (n = 3), morphologic alterations probably due to tuberculosis (n = 6), or with nontypical osseous changes of vertebral bodies suggestive of inflammatory reaction (n = 5). From these bone samples, DNA was extracted and amplified by polymerase chain reaction (PCR) by using various primer pairs recognizing DNA segments of different mycobacterial species. To confirm specificity of the analysis, the amplification products of several samples were subjected to restriction enzyme digestion and/or direct sequencing. Of the analyzed 14 cases, 8 were unambiguously positive for mycobacterial DNA of the Mycobacterium tuberculosis complex, as shown by the amplification of the IS6110 sequence. In 13 cases we found a PCR product with primers specific for the 65-kDa antigen gene, including 2 cases without genomic DNA. We conclude that the application of other mycobacterial DNA primers may reveal contamination of bones with atypical saprophytic mycobacteria. A positive result for typical mycobacteria was seen in 2 of 3 cases with typical morphologic signs of tuberculosis and amplifiable DNA, in 3 of 6 probable cases, but also in 3 of 6 cases with nontypical bone changes. This indicates that minor osseous reactions of the surface of vertebral bodies may be due-at least in several cases-to infections with bacteria of the M. tuberculosis complex. In these cases the disease may have proceeded rapidly, and the morphologic osseous changes may represent "early" stages of tuberculous infection of the vertebrae.