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1.
Clin Exp Rheumatol ; 42(4): 895-904, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38683207

RESUMEN

OBJECTIVES: Giant cell arteritis (GCA) is one of the most common forms of vasculitis. There is an abundance of studies which are conducted in a randomised controlled trial setting but limited with respect to cohort size and follow-up time. GeVas is the first large-scale registry for vasculitides in German-speaking countries that enables to evaluate this rare disease. Herein we focus on the subgroup of GCA patients including follow-up data up to one year. METHODS: GeVas is a prospective, web-based, multicentre registry for the documentation of organ manifestations, outcomes, and therapy regimens in vasculitides. Recruitment started in June 2019. By April 2023, 15 centres were initiated and have started to enrol patients. RESULTS: After 4 years, 195 GCA-patients were included in the registry, of which 64% were female and 36% were male. The average age was 76 years at the time of recruitment (IQR=69-82). Seventy-nine percent were included in the registry because of a newly diagnosed GCA and 21% because of a relapse. At the first assessment most of the patients (89%) described general symptoms. Thirty-one percent stated ocular symptoms. Cranial symptoms were documented in 78% of the cases. All patients were documented with immunosuppressive treatment at start, of whom 95% received prednisolone, 16% cyclophosphamide, 20% methotrexate, and 48% tocilizumab. After three months 62% and after one year 91% of the patients achieved remission. CONCLUSIONS: Regarding demographics, clinical manifestations and diagnostics, our study showed a similar composition compared to other studies. However, our data differed in terms of treatment regimens.


Asunto(s)
Arteritis de Células Gigantes , Inmunosupresores , Sistema de Registros , Humanos , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/epidemiología , Arteritis de Células Gigantes/diagnóstico , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Estudios Prospectivos , Inmunosupresores/uso terapéutico , Alemania/epidemiología , Resultado del Tratamiento , Factores de Tiempo , Recurrencia
2.
Clin Exp Rheumatol ; 42(4): 852-858, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38607682

RESUMEN

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Sistema de Registros , Humanos , Femenino , Persona de Mediana Edad , Masculino , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Anciano , Estudios Prospectivos , Alemania/epidemiología , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/inmunología , Granulomatosis con Poliangitis/terapia , Recurrencia , Poliangitis Microscópica/epidemiología , Poliangitis Microscópica/tratamiento farmacológico , Poliangitis Microscópica/diagnóstico , Poliangitis Microscópica/terapia , Poliangitis Microscópica/inmunología , Síndrome de Churg-Strauss/epidemiología , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/inmunología , Progresión de la Enfermedad , Factores de Tiempo , Rituximab/uso terapéutico
3.
Rheumatol Int ; 43(4): 695-703, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36229671

RESUMEN

Patient-reported outcomes (PRO) represent a cornerstone in the management of patients with rheumatoid arthritis (RA). However, PRO are currently recorded mainly on paper and only during on-site appointments. Electronic PRO (ePRO) enable continuous remote monitoring and could improve shared decision-making (SDM) and implementation of a treat-to-target (T2T) approach. This study aims to investigate patient and physician experiences, perceived drawbacks and benefits of using an ePRO web-app (ABATON RA) to digitally support SDM and T2T. A qualitative study embedded in a multicenter randomized controlled trial (RCT) consisting of interviews with RA patients and physicians that were subsequently analyzed using deductive-inductive qualitative content analysis. Between August 2021 and May 2022, interviews with ten RA patients and five physicians were completed. Three key themes emerged in the analysis: (i) App user experiences; (ii) perceived drawbacks of app-supported rheumatology care; and (iii) perceived benefits of app-supported rheumatology care. Continuous ePRO collection and a high level of standardization strained some RA patients. Certain ePRO seemed outdated and were hard to understand. Patients and physicians appreciated having an improved overview of disease activity, capturing disease flares and continuous remote monitoring. Paper- and time-saving were associated with using ePRO. Physicians feared to become too focused on ePRO data, stressed the lack of ePRO monitoring reimbursement and app interoperability. For RA patients and physicians, benefits seemed to outweigh observed drawbacks of the digitally supported SDM using ePRO. The software was easy to use and could lead to a better understanding of the individual disease course, resource allocation and treatment of rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide , Reumatología , Humanos , Investigación Cualitativa , Medición de Resultados Informados por el Paciente , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico
4.
Z Gerontol Geriatr ; 56(2): 139-145, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35312810

RESUMEN

BACKGROUND AND OBJECTIVE: Demographic change confers significance to healthcare management of chronic diseases like psoriasis. There are few studies on the care of older people with psoriasis, particularly for the nursing home setting. It was investigated whether the number of psoriasis patients with specialist contact changes before vs. after nursing home admission. MATERIAL AND METHODS: We analyzed claims data of a German health insurance company including a cohort of newly admitted nursing home residents aged 65 years and older between 2011 and 2014, who received a diagnosis of psoriasis 1 year before nursing home admission. Outpatient care was compared between the years before vs. after nursing home admission. We conducted a multivariate regression analysis for identifying predictors for dermatological care. RESULTS: The study cohort included 718 insured persons (Ø83 years). Proportion of patients who had contact to a dermatologist significantly decreased after nursing home entry (44.6% before vs. 40.1% after nursing home entry). Strongest predictors for dermatological care after entry were a previously existing dermatological contact (odds ratio, OR 3.87, 95% confidence interval, CI 2.70-5.54) and prescription for topical steroids (OR 1.61, 95% CI 1.14-2.28). CONCLUSION: The analysis of health insurance data showed a pertinent decrease in the use of outpatient dermatological care after institutionalization. The evaluation of the adequacy of care is difficult due to the used database without clinical information. As long as no further investigations of this vulnerable patient group are available, the care of psoriasis patients of old age should be closely monitored. Dermatological knowledge of the skin in old age is an essential prerequisite for this.


Asunto(s)
Casas de Salud , Psoriasis , Humanos , Anciano , Estudios Retrospectivos , Hospitalización , Seguro de Salud , Psoriasis/diagnóstico , Psoriasis/epidemiología , Psoriasis/terapia
5.
Healthcare (Basel) ; 10(9)2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36141342

RESUMEN

Psoriasis (PS) is a chronic inflammatory skin disease, and it increasingly appears also in the elderly population. There is a rising interest in drug therapy for PS, especially for people receiving care in nursing homes (NH). Which PS-related drugs are prescribed in the time before nursing home admission (NHA), and to what extent does the supply of drugs change after NHA? Which specialties prescribe PS-related drugs? Statutory health insurance data were examined for people with PS, aged ≥ 65 years, who were newly admitted to a NH in the period 2011-2014 and observed for one year before and after NHA. Changes in prescription prevalence (pre-post comparison) were examined for significant differences. Prescriptions of PS-relevant drugs were measured by defined daily dose and stratified according to the prescribing specialist group. The analysis included 718 insured persons with PS (76.2% female, mean age 83.3 years). Systemic therapeutics played a minor role (pre: 2.6% vs. post: 2.1%) in drug therapy. Topical steroids had a high share of about 40% in the pre-post comparison. Overall, the proportion of people with PS who received treatment remained at a comparable level before and after NHA. A structured assessment of the skin is crucial, specifically in people with cognitive impairment.

6.
Dermatology ; 238(4): 753-761, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35176747

RESUMEN

BACKGROUND: To date, there have been no large studies describing real-world treatment of chronic prurigo (CPG) and pruritus (CPR) in Germany. OBJECTIVE: To determine the healthcare utilization, treatment patterns, and costs associated with CPG and CPR in Germany. METHODS: Retrospective analysis using anonymized claims data (German DAK-Gesundheit), based on a 40% sample of all insured adults of the DAK-Gesundheit on December 31, 2010 (N = 2,006,003). RESULTS: Patients with CPR (prevalence 2.2%) most commonly visited general medicine/general practitioners (GPs, 80.1%), followed by gynecologists (66.1%) and dermatologists (51.1%). Patients with CPG (prevalence 0.2%) most commonly visited dermatologists (85.7%), GPs (78.1%), and ophthalmologists (47.2%). Of adult patients, 44% received at least one drug prescription. Two thirds of patients with a drug prescription received ≥1 topical drug (66.2%), and 54.3% ≥1 systemic drug (total costs of approximately EUR 550,000 and 2,500,000, respectively). Of patients with CPG, 33.8% received ≥1 systemic and 45.1% ≥1 topical drug prescription (costs of approximately EUR 360,000 vs. 105,000). Of patients with CPR, 23.5% received ≥1 systemic and 28.6% ≥1 topical drug prescription (costs of approximately EUR 2,000,000 vs. 500,000). Of patients with CPG, 5.8% received ≥1 phototherapy application vs. 1.2% of patients with CPR. CONCLUSIONS: These findings reflect the reality of care and can form a basis for the identification of overuse, underuse, and misuse in order to design CPG and CPR healthcare more effectively and efficiently.


Asunto(s)
Prurigo , Adulto , Atención a la Salud , Alemania/epidemiología , Humanos , Aceptación de la Atención de Salud , Prurigo/terapia , Prurito/tratamiento farmacológico , Estudios Retrospectivos
7.
Int Wound J ; 19(1): 76-85, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33949101

RESUMEN

Patients with chronic leg ulcer, pressure ulcer, or diabetic foot ulcer suffer from significant disease burden. With a view to improving healthcare provision sustainably, a predictive model of time to closure (time-to-event analysis) based on claims data was developed. To identify potential predictors of wound closure, clinical information absent from statutory health insurance (SHI) data was modelled. In patients with leg ulcers, age of the patient (hazard ratios [HR] 0.99), increasing number of comorbidities (HR 0.94), inpatient stays (HR 0.74), and treatment by a specialised wound care professional (HR 1.18) were significant predictors of time to closure (adjusted model). In almost all models, the number of inpatient stays and of comorbidities predicted a lower probability of healing. In addition, the age and the sex of the patient were found to be significant predictors in some models (leg ulcer: HR 0.99; pressure ulcer: HR 0.99). Increasing number of comorbidities and inpatient stays were predictors for closure time in all models. Since these predictors may give an indication of wound severity, further clinical information should be considered in future models, as also indicated by the moderate values of the c-statistics. This requires future data linkage between SHI and primary studies (eg, registers).


Asunto(s)
Pie Diabético , Úlcera de la Pierna , Análisis de Datos , Pie Diabético/epidemiología , Pie Diabético/terapia , Alemania/epidemiología , Humanos , Úlcera de la Pierna/epidemiología , Úlcera de la Pierna/terapia , Cicatrización de Heridas
8.
Clin Epidemiol ; 13: 593-602, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34321929

RESUMEN

BACKGROUND: Information on the prevalence of atopic dermatitis (AD) varies greatly, and so far, only a few studies describe the healthcare of patients with AD in Germany. OBJECTIVE: The aim of the study is to describe the prevalence and medications of people with AD in Germany. METHODS: Health insurance data for the year 2019 were examined. Prevalence rates, the severity of disease, comorbidities and pharmaceutical supply were analyzed. Insured persons with AD were identified with at least one outpatient or inpatient International Classification Code of Diseases (L20). RESULTS: In 2019, 4.21% [95% CI 4.21-4.22%] of insured persons had AD (3.6 million). Women were affected slightly more frequently than men (4.74% [95% CI 4.73-4.74%] and 3.64% [95% CI 3.64-3.65%]). Adolescents and children under the age of 15 had the highest prevalence of AD compared to other age groups (9.44% [95% CI 9.42-9.46%]). Majority of the insured persons with AD were affected by a mild to moderate form of the disease. The most common co-morbidity was infections of the skin (RR 5.00 [95% CI 4.97-5.02%]). Some patients were treated by a dermatologist, while others by a general practitioner, 39.10% and 36.74%, respectively. Of the anti-inflammatory drugs, systemic glucocorticosteroids preparations were used most frequently and were most frequently prescribed by the general practitioner. With a total of 42,841 prescriptions (1.53%), methotrexate (third-line treatment option) was prescribed more frequently than ciclosporin with 19,628 prescriptions (0.70%) or azathioprine with 25,696 prescriptions (0.92%). Ciclosporin (first-line treatment option) was prescribed much more frequently by a dermatologist (44.00% versus 14.32% by general practitioner). The biological dupilumab was prescribed 30,801 times (1,10%) and was also primarily prescribed by a dermatologist (66.67%). CONCLUSION: The present results reveal that a specialist treats approximately one-third of the patients with AD and that there is still a drug undersupply in some cases, especially concerning innovative drugs.

9.
Acta Derm Venereol ; 101(10): adv00566, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34263331

RESUMEN

Psoriatic arthritis is a frequent manifestation of psoriasis, and has a high level of impact on physical func-tioning, work ability and quality of life. However, there have been few studies of the epidemiology, development of and risk factors for concomitant psoriatic arthritis in patients with psoriasis. This study analysed data from a German public health insurance database of > 2 million individuals. Factors influencing the development of psoriatic arthritis were determined by descriptively analysing comorbidities and Cox regression modelling. The prevalences of psoriasis and psoriatic arthritis were 2.63% and 0.29% in adults (18+ years) and, respectively, 0.30% and 0.01% in children (0-17 years). The proportion of adult patients with incident psoriasis who developed concomitant psoriatic arthritis within five years after diagnosis of psoriasis (mean 2.3 years) was 2.6%. Cardiovascular diseases are the most frequent comorbidity in patients with psoriasis with or without concomitant psoriatic arthritis. Depression and neurosis/stress disorder were identified as indicators for the development of psoriatic arthritis.


Asunto(s)
Artritis Psoriásica , Psoriasis , Adulto , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Niño , Comorbilidad , Humanos , Seguro de Salud , Psoriasis/diagnóstico , Psoriasis/epidemiología , Calidad de Vida , Factores de Riesgo
11.
Clin Epidemiol ; 13: 373-382, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34079380

RESUMEN

BACKGROUND: Most epidemiological data on vitiligo refer to selected environments or focus on the prevalence of comorbidity unrelated to the population. OBJECTIVE: Aim of the study was to gain robust representative prevalence data on vitiligo and on associated dermatologic comorbidity in the German adult population. METHODS: A dual population-based approach was applied with 1) primary data obtained between 2004 and 2014 from dermatological exams in the general working population; 2) claims data from a large German statutory health insurance, reference year 2010. RESULTS: In the working cohort (N = 121,783; 57% male; mean age 43 years), the prevalence of vitiligo was 0.77% (0.84% in men; 0.67% in women). In the claims data (N = 1,619,678; 38% male; mean age 46 years), prevalence was 0.17% (0.14% in men; 0.18% in women). In the working cohort, vitiligo was significantly more common in people with fair skin type, ephelides and port-wine stains and less common in people with acne and solar lentigines. In the claims data, vitiligo was associated with a variety of skin conditions, eg, atopic dermatitis, psoriasis and alopecia areata. CONCLUSION: The resulting discrepancy of claims vs primary data between 0.17% and 0.77% indicates the most probable spectrum of vitiligo prevalence in Germany. It is more frequently observed in clinical exams than recorded in claims data, indicating a marked proportion of people seeking no medical help. Such nonattendance may result from the fact that many treatment options do not provide satisfying benefits to the patients.

12.
J Dtsch Dermatol Ges ; 19(7): 1013-1019, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33938627

RESUMEN

BACKGROUND: To date, robust epidemiological metrics as well as data on comorbidity in pediatric urticaria are lacking. They form the basis for the design of efficient healthcare. METHODS: Retrospective study to analyze epidemiological data in pediatric urticaria. The analysis is based on routine data of a health insurance company operating throughout Germany (DAK-Gesundheit). Insured people under 18 years of age who received at least one confirmed outpatient or inpatient urticaria diagnosis according to the ICD-10 classification in the years 2010 to 2015 were included in the analysis and compared to children without a corresponding diagnosis. RESULTS: Of 2.3 million insured individuals, 313,581 (13.5 %) were under 18 years of age (153,214 female). Urticaria was diagnosed in 1.7 % of the 313,581 patients. The prevalence of urticaria decreased with age from 3.0 % in the 0-3-year age group to 1.0 % in the 14-18-year age group. Boys and girls were almost equally affected in all age groups. Atopic diseases as comorbidity occurred more frequently in children with urticaria than in the control group (16.0 % vs. 8.0 %). Autoimmune diseases, mental health problems, and obesity also occurred more frequently in children with urticaria than in the control group. CONCLUSIONS: The increased prevalence of specific comorbidities in children with urticaria suggests an increased need for screening. Multimodal treatment strategies need to be developed and interdisciplinary collaboration promoted.


Asunto(s)
Urticaria , Adolescente , Niño , Comorbilidad , Atención a la Salud , Femenino , Humanos , Masculino , Prevalencia , Estudios Retrospectivos , Urticaria/diagnóstico , Urticaria/epidemiología
14.
J Dtsch Dermatol Ges ; 19(3): 389-398, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33491912

RESUMEN

BACKGROUND: Regarding skin cancer screening, patients in Germany have the choice between a direct screening by dermatologists or an initial screening by general practitioners followed by dermatological screening if further examination is required. The aim of this study is to evaluate whether screening by general practitioners is associated with risk selection in subsequent dermatological screenings. PATIENTS AND METHODS: We conducted a retrospective observational study based on claims data from a German health insurance company (Barmer GEK). Patient pathways in skin cancer screenings between 2008 and 2016 were analyzed, and differences between the two groups were tested at 95 % confidence intervals. RESULTS: A total of 495,000 initial and 111,000 secondary examinations by dermatologists were analyzed. The proportion of subsequent excisions was lower in initial screenings by dermatologists. To diagnose one person with non-melanoma skin cancer or melanoma, five or 23 to 42 excisions were necessary, depending on the type of excision considered. The number of examinations to identify one patient ranged from 25 to 53 for non-melanoma skin cancer and 42 to 165 for melanoma. For melanoma, the number of excisions and screenings to diagnose skin cancer was lower in secondary examinations. CONCLUSIONS: The results indicate a risk selection through initial examinations by general practitioners. However, there are other aspects that should be taken into account when comparing the two pathways.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Análisis de Datos , Detección Precoz del Cáncer , Humanos , Tamizaje Masivo , Melanoma/diagnóstico , Melanoma/epidemiología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología
15.
J Dtsch Dermatol Ges ; 17(12): 1239-1249, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31885171

RESUMEN

BACKGROUND AND OBJECTIVES: The aim of the present study was to determine the prevalence and incidence of skin cancer. PATIENTS AND METHODS: We calculated prevalence and incidence for cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) in 2012 in Germany, using claims data of 2.1 million insured persons. In order to allow statements concerning differences between subgroups, we calculated 95 % confidence intervals. Finally, we standardized prevalence and incidence with regard to the German population. RESULTS: The prevalence and incidence of CM amounted to 0.12 % and 0.04 % and increased with age. For NMSC these measures were 0.65 % and 0.15 %. Of the prevalent and incident patients, 88.9 % and 87.4 % (CM) and 99.4 % and 98.8 % (NMSC) respectively were at early stages. A projection on the whole population resulted in 75,419 persons affected by CM and 376,004 persons affected by NMSC, including 24,075 (CM) and 84,618 (NMSC) incident patients. CONCLUSIONS: In this study, we defined epidemiological measures according to the number of patients affected by skin cancer and having a medical consultation indicating a need for treatment. These results can serve in future research as a data basis for analysis of health service demand in skin cancer patients and the associated costs.


Asunto(s)
Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Prevalencia , Distribución por Sexo , Melanoma Cutáneo Maligno
17.
Mol Immunol ; 114: 30-40, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31336247

RESUMEN

Heterozygous gain-of-function (GOF) mutations in the cytokine-regulated transcription factor STAT1 (signal transducer and activator of transcription 1) lead to chronic mucocutaneous candidiasis (CMC). However, the molecular basis of these pathogenic missense mutations is largely unknown. In this study, we characterized in more detail the CMC-associated GOF substitution mutation of arginine-to-tryptophan at position 274 (R274W) and, in addition, the adjacent glutamine-to-alanine mutation at position 275 (Q275A). Both mutants displayed elevated tyrosine phosphorylation levels, prolonged nuclear accumulation, and increased transcriptional responses to interferon-γ (IFNγ) stimulation. No difference was observed between wild-type (WT) and mutant STAT1 in DNA sequence-specificity or dissociation kinetics from high-affinity DNA-binding elements known as gamma-activated sites (GAS). Furthermore, all variants exhibited similar cooperative DNA binding. Unexpectedly, in vitro dephosphorylation rates using the recombinant STAT1-inactivating Tc45 phosphatase in both the absence and presence of double-stranded GAS elements were similar in all STAT1 variants. Likewise, the rate of tyrosine phosphorylation by Janus kinase 2 (JAK2) was unaltered as compared to the WT molecule, excluding that the phenotype of these mutants is caused by either defective Tc45-catalyzed dephosphorylation or JAK2-induced hyper-activation. Interestingly, within 10 min of IFNγ exposure, the majority of R274W and Q275A molecules had entered the nucleus, whereas the wild-type protein remained predominantly cytosolic. Thus, the exchange of critical residues located at the binding interface in the antiparallel dimer conformer led to a premature accumulation of phospho-STAT1 in the nuclear compartment. In summary, our data show that the hyper-activity of the GOF mutations results, at least in part, from the premature nuclear import of the tyrosine-phosphorylated molecules and not from alterations in their phosphorylation or dephosphorylation rates.


Asunto(s)
Mutación con Ganancia de Función/genética , Mutación Missense/genética , Dominios Proteicos/genética , Factor de Transcripción STAT1/genética , Candidiasis Mucocutánea Crónica/genética , Línea Celular Tumoral , Núcleo Celular/genética , Células Cultivadas , Citocinas/genética , Células HeLa , Heterocigoto , Humanos , Interferón gamma/genética , Fosforilación/genética , Unión Proteica/genética , Transducción de Señal/genética , Transcripción Genética/genética
18.
Ann Thorac Surg ; 108(6): 1783-1792, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31254507

RESUMEN

BACKGROUND: The major drawback of isolated annuloplasty in secondary mitral regurgitation (MR) is the reoccurrence of MR. We prospectively compared the results of isolated annuloplasty vs annuloplasty with simultaneous standardized subannular repair. METHODS: The study comprised 101 patients with secondary type IIIb MR. Of these, 51 underwent annuloplasty plus standardized subannular repair with realignment of both papillary muscles (subannular repair) and 50 underwent isolated annuloplasty. The primary study end point was the reoccurrence of MR >2 at the 1-year follow-up. Secondary end points were survival, freedom from major adverse cardiac events, and residual leaflet tethering. RESULTS: Baseline characteristics were comparable in both groups. There was no significant difference in in-hospital mortality (P = .3). Although postrepair MR was comparable between the subannular repair and isolated annuloplasty subgroups, the residual leaflet tethering (tenting area, 127.6 ± 35.8 mm2 vs 166.3 ± 47.3 mm2, P = .02; posterior mitral leaflet angle, 19.2 ± 4.7 degrees vs 24.8 ± 5.2 degrees, P = .001; anterior mitral leaflet angle, 25.4 ± 5.8 degrees vs 34.1 ± 4.0 degrees, P = .001; and tenting height, 5.9 ± 1.4 mm vs 9.2 ± 2.2 mm, P = .001) were significantly increased in the isolated annuloplasty group (P < .001). At the 1-year follow-up, we found a significant difference between the groups in the freedom from MR >2 of 98% (50 of 51) for subannular repair vs 86.7% (39 of 45) for isolated annuloplasty (P = .045) and mortality of 0% (0 of 51) for subannular repair vs 10% (5 of 50) for isolated annuloplasty (P = .025). CONCLUSIONS: In secondary MR with reduced leaflet motion, the combination of annuloplasty and standardized subannular repair is associated with a significantly reduced MR reoccurrence, decreased residual leaflet tenting, and significantly improved 1-year outcome compared with annuloplasty alone.


Asunto(s)
Anuloplastia de la Válvula Mitral/métodos , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Complicaciones Posoperatorias/epidemiología , Progresión de la Enfermedad , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/fisiopatología , Estudios Prospectivos , Función Ventricular Izquierda
19.
Z Evid Fortbild Qual Gesundhwes ; 140: 22-34, 2019 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-30876780

RESUMEN

OBJECTIVE: There are still few epidemiological data on patients with chronic wounds (leg ulcers, diabetic foot ulcers and pressure ulcers). Statutory health insurance (SHI) data is increasingly being used for questions relating to healthcare science. When using this data, which is primarily collected for billing purposes, the methodological procedure for defining cases must be presented transparently. Here, it must be checked whether the target group can be validly defined using the coded diagnoses and, if necessary, further information from routine data. Therefore, the aim of this contribution is, on the one hand, to develop criteria with the help of which patients with a florid (active) chronic wound can be identified safely or as doubtful cases in routine data and, on the other hand, to determine the corresponding frequency estimates. METHODS: Initially, a literature research was carried out to identify parameters relevant to care in patients with chronic wounds. In the next step, these were divided into specific, less specific and non-specific criteria (visual validity) in a multi-stage consensus procedure with regard to the specificity for wound care. On this basis, three different case definitions are used to identify florid chronic wounds. Based on an SHI sample of insured persons, frequency estimates were made for various case definitions (safe and questionable cases). RESULTS: Of the 21 parameters identified in the literature, eight were classified as specific, six as less specific and eight as non-specific criteria for the identification of patients with chronic florid wounds. Using diagnostic coding alone for the target diseases, an administrative prevalence of chronic wounds of 1.13% was observed for the year 2010. If a case is defined using the less specific and/or the specific criteria, prevalence drops to 0.79%; if only the specific criteria are used, prevalence drops only marginally to 0.78%. These changes were observed in patients with leg ulcers and diabetic foot ulcers, but not in patients with pressure ulcers. Here, the lowest administrative prevalence (0.18%) can be seen when only looking at the diagnoses, but this increases slightly when taking wound-relevant treatments into account (specific and less specific criteria: 0.25%). CONCLUSION: It is possible to define patients with a chronic florid wound on the basis of wound-relevant treatments using SHI data and to make estimates of administrative prevalence. Depending on the question, the criteria for defining cases can be narrowed down or broadened. The comparison provides information on the internal validity of diagnostic coding. However, further studies are needed to verify external validity.


Asunto(s)
Pie Diabético , Programas Nacionales de Salud/estadística & datos numéricos , Úlcera por Presión , Heridas y Lesiones/diagnóstico , Enfermedad Crónica , Pie Diabético/diagnóstico , Alemania , Humanos , Seguro de Salud , Úlcera de la Pierna/diagnóstico , Úlcera por Presión/diagnóstico , Prevalencia , Heridas y Lesiones/clasificación
20.
Dtsch Arztebl Int ; 113(6): 92-8, 2016 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-26931625

RESUMEN

BACKGROUND: Nursing home residents often suffer from a multiplicity of medical conditions and take many different drugs. Many drugs are eliminated via the kidneys and thus require dose adjustment in patients with renal insufficiency. This is the first study to address the prevalence of renal insufficiency among nursing home residents in Germany, and the extent to which such persons take drugs that are contraindicated or incorrectly dosed because of renal insufficiency. METHODS: We carried out a cross-sectional study in nursing homes in the German regions of Bremen and Lower Saxony. Data were collected by nursing staff and given to us anonymously. Whenever the nursing home data did not include a current creatinine value, the patient's general practitioner was asked to supply this value. The estimated creatinine clearance (eCCr) was calculated with the Cockcroft-Gault formula. RESULTS: 852 residents of 21 nursing homes were included in the study; eCCr values were obtainable for 685 (80.4%) of them (average age, 83.3 years; 75.2% female). 48.2% of these patients (95% confidence interval [CI] 41.8-54.5) had moderate renal insufficiency (eCCr 59-30 mL/min), and 15.5% (95% CI 12.4-18.6) had severe renal insufficiency (eCCr <30 mL/min). 19.7% were regularly taking at least one medication that was contraindicated or incorrectly dosed in the light of renal insufficiency. Predictors for such inappropriate drug use were advanced age, female sex, arterial hypertension, and polypharmacy. The drugs that were most often inappropriately used were metformin, ramipril, and potassium chloride. CONCLUSION: Nursing home residents often suffer from renal insufficiency and should therefore have their creatinine levels measured regularly. A knowledge of the creatinine level is a prerequisite for the proper adjustment of drug doses (if necessary). A practical and compact summary of dose-adjustment recommendations for patients with renal insufficiency would be desirable but is not yet available.


Asunto(s)
Hogares para Ancianos/estadística & datos numéricos , Hipertensión/epidemiología , Prescripción Inadecuada/estadística & datos numéricos , Casas de Salud/estadística & datos numéricos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Alemania/epidemiología , Humanos , Masculino , Polifarmacia , Prevalencia , Pronóstico , Factores de Riesgo , Distribución por Sexo
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