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Background: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. Objective: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. Methods: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. Results: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). Conclusion: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN. [ABSTRACT FROM AUTHOR]

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a one-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent preexisting comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis. [ABSTRACT FROM AUTHOR]

Recurrent hyperkalaemia management and use of renin-angiotensin-aldosterone system inhibitors: a European multi-national targeted chart review. [Extracted from the article]

A novel approach for sequence-specific labeling of DNA using a newly designed fluorescent cofactor for the DNA methyltransferase from Thermus aquaticus (M.taql) is presented. The new cofactor is used to sequence-specifically label plasmid DNA in a M-Taql-catalyzed reaction.

The 2.0 Å crystal structure of the N6-adenine DNA methyltransferase M•TaqI in complex with specific DNA and a nonreactive cofactor analog reveals a previously unrecognized stabilization of the extrahelical target base. To catalyze the transfer of the methyl group from the cofactor S-adenosyl-l-methionine to the 6-amino group of adenine within the double-stranded DNA sequence 5′-TCGA-3′, the target nucleoside is rotated out of the DNA helix. Stabilization of the extrahelical conformation is achieved by DNA compression perpendicular to the DNA helix axis at the target base pair position and relocation of the partner base thymine in an interstrand π-stacked position, where it would sterically overlap with an innerhelical target adenine. The extrahelical target adenine is specifically recognized in the active site, and the 6-amino group of adenine donates two hydrogen bonds to Asn 105 and Pro 106, which both belong to the conserved catalytic motif IV of N6-adenine DNA methyltransferases. These hydrogen bonds appear to increase the partial negative charge of the N6 atom of adenine and activate it for direct nucleophilic attack on the methyl group of the cofactor. [ABSTRACT FROM AUTHOR]

Background:  Patients at increased risk of inadequate immune response to COVID-19 vaccinations due to their underlying disease or therapy are potentially vulnerable to severe COVID-19 courses. The aim is to assess the population size, clinical courses and hospitalization costs of these patients in Germany., Methods:  This retrospective cohort study is based on extrapolations of a representative sample of statutory health insurance (SHI) claims data from 2020. Clinical COVID-19 courses, hospitalization costs and durations are compared between the insured group at increased risk for inadequate immune response to COVID-19 vaccinations (risk group) and the insured group without this risk., Results:  There are approximately 1.82 million SHI-insured individuals in the risk group, of whom an estimated 240 000 insured individuals do not develop a humoral immune response after 3 COVID-19 vaccinations. The risk group shows higher proportions with COVID-19 (relative risk [RR] 1.21; 95 % confidence interval [95 % CI] 1.20-1.23), hospitalizations for COVID-19 (RR 3.40; 95 % CI 3.33-3.48), hospitalizations for COVID-19 with intensive care treatment (RR 1.36; 95 % CI 1.30-1.42), and mortality (RR 5.14; 95 % CI 4.97-5.33) compared with the group without risk. In addition, hospitalizations in the risk group are on average 18 % longer (15.36 days vs. 13.00 days) and 19 % more expensive (12 371 € vs. 10 410 €). Expected hospitalization costs in the risk group are four times greater than in the group without risk (4115 € vs. 1017 €)., Conclusions:  The risk group is vulnerable to COVID-19 and requires additional resources in the German hospital sector. This results in a need for further protective measures. Further studies are needed to evaluate the impact of different viral variants, active and passive immunizations, and therapies on clinical COVID-19 courses and their costs., Competing Interests: D.H. ist Angestellter der WIG2 GmbH. M.P. ist Angestellter der ZEG GmbH. Die WIG2 GmbH und die ZEG GmbH sind Auftragnehmer der AstraZeneca GmbH. P.L.D., V.L. und F. J. sind Angestellte der AstraZeneca GmbH. F.J. besitzt Aktien der CureVac N.V. C–M.W. hat Honorare, Reise- und Forschungsunterstützung von der AstraZeneca GmbH, BioNTech SE, Gilead Sciences GmbH, GlaxoSmithKline GmbH & Co. KG und der Moderna Germany GmbH erhalten., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

This observational study assessed the impact on the fracture incidence of osteoporosis medications in postmenopausal women in Germany. Continued treatment with osteoporosis medications was associated with reductions of fracture rates in a real-world setting., Purpose: The efficacy of osteoporosis medications has been demonstrated in clinical trials, but a lack of evidence exists of their real-world effectiveness. This real-world study assessed the treatment patterns and impact on the fracture incidence of osteoporosis medications in postmenopausal women in Germany., Methods: This cohort study used data from the WIG2 benchmark database, a German anonymised healthcare claims database. All women ≥ 50 years of age with ≥ 1 prescription for osteoporosis medication between 1 January 2013 and 31 December 2017 were included. The primary outcome was treatment effectiveness, evaluated as the change in fracture incidence after initiating treatment. Fracture types included all fractures, clinical vertebral, hip and wrist/forearm. Fracture incidence was assessed during the early-treatment period (0-3 months) and the on-treatment period (4-12, 13-24, 25-36 and 37-48 months)., Results: Baseline covariates and treatment patterns were determined for 41,861 patients. The median duration of therapy was longer with denosumab (587 days) than with intravenous ibandronate (451 days), intravenous zoledronate (389 days) or oral bisphosphonates (258 days). The baseline incidence rate of all fractures was higher in patients receiving denosumab than in those receiving other treatments (87.6, 78.2, 56.6 and 66.0 per 1000 person-years for denosumab, oral bisphosphonates, intravenous ibandronate and intravenous zoledronate, respectively). Rates of all fractures declined with continued denosumab (by 38%, 50%, 56% and 67% at 12, 24, 36 and 48 months, respectively) and oral bisphosphonates (by 39%, 44%, 49% and 42%, respectively) treatment., Conclusion: Continued treatment with osteoporosis medications was associated with reductions of fracture rates in a real-world setting., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

How to outwit a methyltransferase: Methyltransferases (Mtases) catalyze the transfer of the activated methyl group from the cofactor S-adenosyl-L-methionine (1) to acceptors R within a large variety of biomolecules. Through the use of the cofactor analogue 2 a whole nucleoside was coupled to DNA in a Mtase-catalyzed reaction., (© 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)