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1.
J Dtsch Dermatol Ges ; 22(6): 803-809, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38769083

RESUMEN

BACKGROUND: The chronic inflammatory skin disease hidradenitis suppurativa (HS) leads to severe pain and reduced quality of life. Nonetheless, it often takes years until a correct diagnosis is made. In this analysis, disease-related experiences and pathways of patients with HS were investigated and compared with the physicians' perspective. METHODS: Public posts on forums and social media as well as results of a survey conducted among dermatologists and their patients on the actual medical care reality of HS in Germany were analysed. Furthermore, claims data from German health insurance companies were evaluated. RESULTS: Patients with HS suffer from a 43.3% reduction in working ability. Dermatology (26.5%) was the most frequently consulted specialty, with HS diagnosed predominantly in the inpatient setting (43.8%). Abscesses were described as the most frequent alternative diagnosis in HS patients (53.2%). Patient-reported changes of physicians in dermatology (34.1%) and surgery (42.4%) occurred predominantly within the specialty. Dermatology received most referrals from general practitioners (67.1%), but only 12.1% from surgeons. CONCLUSION: There is an urgent need to reduce the delay in diagnosis and the prolonged burden of disease in patients with HS. Therefore, awareness of the disease, its detection and treatment which goes beyond dermatology should be promoted, if possible as part of medical studies.


Asunto(s)
Diagnóstico Tardío , Hidradenitis Supurativa , Medios de Comunicación Sociales , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/terapia , Hidradenitis Supurativa/epidemiología , Humanos , Diagnóstico Tardío/estadística & datos numéricos , Alemania/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Derivación y Consulta/estadística & datos numéricos , Dermatología/estadística & datos numéricos
2.
Z Gastroenterol ; 61(8): 1009-1017, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35878605

RESUMEN

BACKGROUND: Healthcare workers (HCWs) are at a high risk of SARS-CoV-2 infection due to exposure to potentially infectious material, especially during aerosol-generating procedures (AGP). We aimed to investigate risk factors for SARS-CoV-2 infection among HCWs in medical disciplines with AGP. METHODS: A nationwide questionnaire-based study in private practices and hospital settings was conducted between 12/16/2020 and 01/24/2021. Data on SARS-CoV-2 infections among HCWs and potential risk factors of infection were investigated. RESULTS: 2070 healthcare facilities with 25113 employees were included in the study. The overall infection rate among HCWs was 4.7%. Multivariate analysis showed that regions with higher incidence rates had a significantly increased risk of infection. Furthermore, hospital setting and HCWs in gastrointestinal endoscopy (GIE) had more than double the risk of infection (OR 2.63; 95% CI 2.50-2.82, p<0.01 and OR 2.35; 95% CI 2.25-2.50, p<0.01). For medical facilities who treated confirmed SARS-CoV-2 cases, there was a tendency towards higher risk of infection (OR 1.39; 95% CI 1.11-1.63, p=0.068). CONCLUSION: Both factors within and outside medical facilities appear to be associated with an increased risk of infection among HCWs. Therefore, GIE and healthcare delivery setting were related to increased infection rates. Regions with higher SARS-CoV-2 incidence rates were also significantly associated with increased risk of infection.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Aerosoles y Gotitas Respiratorias , Factores de Riesgo , Personal de Salud
3.
BMC Infect Dis ; 21(1): 798, 2021 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-34376187

RESUMEN

OBJECTIVES: The gold standard for diagnosing an infection with SARS-CoV-2 is detection of viral RNA by nucleic acid amplification techniques. Test capacities, however, are limited. Therefore, numerous easy-to-use rapid antigen tests based on lateral flow technology have been developed. Manufacturer-reported performance data seem convincing, but real-world data are missing. METHODS: We retrospectively analysed all prospectively collected antigen tests results performed between 23.06.2020 and 26.11.2020, generated by non-laboratory personnel at the point-of-care from oro- or nasopharyngeal swab samples at the University Hospital Augsburg and compared them to concomitantly (within 24 h.) generated results from molecular tests. RESULTS: For a total of 3630 antigen tests, 3110 NAAT results were available. Overall, sensitivity, specificity, NPV and PPV of antigen testing were 59.4%, 99.0%, 98.7% and 64.8%, respectively. Sensitivity and PPV were lower in asymptomatic patients (47.6% and 44.4%, respectively) and only slightly higher in patients with clinical symptoms (66.7% and 85.0%, respectively). Some samples with very low Ct-values (minimum Ct 13) were not detected by antigen testing. 31 false positive results occurred. ROC curve analysis showed that reducing the COI cut-off from 1, as suggested by the manufacturer, to 0.9 is optimal, albeit with an AUC of only 0.66. CONCLUSION: In real life, performance of lateral-flow-based antigen tests are well below the manufacturer's specifications, irrespective of patient's symptoms. Their use for detection of individual patients infected with SARS-CoV2 should be discouraged. This does not preclude their usefulness in large-scale screening programs to reduce transmission events on a population-wide scale.


Asunto(s)
COVID-19 , Humanos , Técnicas de Amplificación de Ácido Nucleico , ARN Viral , Estudios Retrospectivos , SARS-CoV-2 , Sensibilidad y Especificidad
4.
Z Gastroenterol ; 59(12): 1278-1287, 2021 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-34687033

RESUMEN

BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.


Asunto(s)
COVID-19 , Prueba de COVID-19 , Endoscopía Gastrointestinal , Alemania/epidemiología , Humanos , SARS-CoV-2
5.
J Clin Microbiol ; 57(1)2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30404944

RESUMEN

Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species. The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens. A multiplexed immunoassay for the quantification of HRP2, P. vivax LDH, and all-malaria LDH (pan LDH) was developed to accurately measure circulating antigen concentration and antigen distribution in a population with endemic malaria. The assay also measures C-reactive protein (CRP) levels as an indicator of inflammation. Validation was conducted with clinical specimens from 397 asymptomatic donors from Myanmar and Uganda, confirmed by PCR for infection, and from participants in induced blood-stage malaria challenge studies. The assay lower limits of detection for HRP2, pan LDH, P. vivax LDH, and CRP were 0.2 pg/ml, 9.3 pg/ml, 1.5 pg/ml, and 26.6 ng/ml, respectively. At thresholds for HRP2, pan LDH, and P. vivax LDH of 2.3 pg/ml, 47.8 pg/ml, and 75.1 pg/ml, respectively, and a specificity ≥98.5%, the sensitivities for ultrasensitive PCR-confirmed infections were 93.4%, 84.9%, and 48.9%, respectively. Plasmodium LDH (pLDH) concentration, in contrast to that of HRP2, correlated closely with parasite density. CRP levels were moderately higher in P. falciparum infections with confirmed antigenemia versus those in clinical specimens with no antigen. The 4-plex array is a sensitive tool for quantifying diagnostic antigens in malaria infections and supporting the evaluation of new ultrasensitive RDTs.


Asunto(s)
Antígenos de Protozoos/sangre , Infecciones Asintomáticas , Proteína C-Reactiva/análisis , Inmunoensayo/métodos , Malaria/sangre , Malaria/diagnóstico , Adulto , Infecciones Asintomáticas/epidemiología , Niño , Preescolar , Pruebas Diagnósticas de Rutina , Enfermedades Endémicas , Humanos , Lactante , L-Lactato Deshidrogenasa/sangre , Malaria/epidemiología , Mianmar/epidemiología , Plasmodium/inmunología , Proteínas Protozoarias/sangre , Sensibilidad y Especificidad , Uganda/epidemiología
6.
Malar J ; 18(1): 33, 2019 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-30717748

RESUMEN

Following publication of the original article [1], the authors flagged an error concerning a reference to a product in the Methods section.

8.
Eur J Haematol ; 100(3): 294-303, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29240263

RESUMEN

BACKGROUND: Medicines that exert oxidative pressure on red blood cells (RBC) can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Due to X-chromosome inactivation, females heterozygous for G6PD with 1 allele encoding a G6PD-deficient protein and the other a normal protein produce 2 RBC populations each expressing exclusively 1 allele. The G6PD mosaic is not captured with routine G6PD tests. METHODS: An open-source software tool for G6PD cytofluorometric data interpretation is described. The tool interprets data in terms of % bright RBC, or cells with normal G6PD activity in specimens collected from 2 geographically and ethnically distinct populations, an African American cohort (USA) and a Karen and Burman ethnic cohort (Thailand) comprising 242 specimens including 89 heterozygous females. RESULTS: The tool allowed comparison of data across 2 laboratories and both populations. Hemizygous normal or deficient males and homozygous normal or deficient females cluster at narrow % bright cells with mean values of 96%, or 6% (males) and 97%, or 2% (females), respectively. Heterozygous females show a distribution of 10-85% bright cells and a mean of 50%. The distributions are associated with the severity of the G6PD mutation. CONCLUSIONS: Consistent cytofluorometric G6PD analysis facilitates interlaboratory comparison of cellular G6PD profiles and contributes to understanding primaquine-associated hemolytic risk.


Asunto(s)
Antimaláricos/efectos adversos , Eritrocitos/efectos de los fármacos , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/genética , Mosaicismo , Mutación , Primaquina/efectos adversos , Negro o Afroamericano , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Contraindicaciones de los Medicamentos , Eritrocitos/enzimología , Eritrocitos/patología , Femenino , Citometría de Flujo/métodos , Regulación de la Expresión Génica , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/enzimología , Deficiencia de Glucosafosfato Deshidrogenasa/etnología , Deficiencia de Glucosafosfato Deshidrogenasa/patología , Hemicigoto , Heterocigoto , Humanos , Masculino , Índice de Severidad de la Enfermedad , Programas Informáticos , Tailandia , Estados Unidos
9.
Malar J ; 17(1): 118, 2018 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-29549888

RESUMEN

BACKGROUND: As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100-200 parasites/µL (p/µL) and 800-1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test's performance against recombinant HRP2 and native cultured parasites. RESULTS: The uRDT detected dilutions of P. falciparum recombinant GST-W2 and FliS-W2, as well as cultured W2 and ITG, diluted in whole blood down to 10-40 pg/mL HRP2, depending on the protein tested. uRDT specificity was 100% against 123 archived frozen whole blood samples. Rapid test cross-reactivity with HRP3 was investigated using pfhrp2 gene deletion strains D10 and Dd2, pfhrp3 gene deletion strain HB3, and controls pfhrp2 and pfhrp3 double deletion strain 3BD5 and pfhrp2 and pfhrp3 competent strain ITG. The commercial Standard Diagnostics, Inc. BIOLINE Malaria Ag P.f RDT (SD-RDT) and uRDT detected pfhrp2 positive strains down to 49 and 3.13 p/µL, respectively. The pfhrp2 deletion strains were detected down to 98 p/µL by both tests. CONCLUSION: The performance of the uRDT was variable depending on the protein, but overall showed a greater than 10-fold improvement over the SD-RDT. The uRDT also exhibited excellent specificity and showed the same cross-reactivity with HRP3 as the SD-RDT. Together, the results support the uRDT as a more sensitive HRP2 test that could be a potentially effective tool in elimination campaigns. Further clinical evaluations for this purpose are merited.


Asunto(s)
Antígenos de Protozoos/sangre , Malaria Falciparum/diagnóstico , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/sangre , Antígenos de Protozoos/química , Antígenos de Protozoos/metabolismo , Humanos , Malaria Falciparum/sangre , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Proteínas Recombinantes , Sensibilidad y Especificidad , Pruebas Serológicas/métodos
11.
J Virol ; 87(19): 10855-73, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23903848

RESUMEN

The HIV-1 envelope glycoprotein (Env) mediates viral entry into host cells and is the sole target of neutralizing antibodies. Much of the sequence diversity in the HIV-1 genome is concentrated within Env, particularly within its gp120 surface subunit. While dramatic functional diversity exists among HIV-1 Env isolates-observable even in the context of monomeric gp120 proteins as differences in antigenicity and immunogenicity-we have little understanding of the structural features that distinguish Env isolates and lead to isolate-specific functional differences, as crystal structures of truncated gp120 "core" proteins from diverse isolates reveal a high level of structural conservation. Because gp120 proteins are used as prospective vaccine immunogens, it is critical to understand the structural factors that influence their reactivity with antibodies. Here, we studied four full-length, glycosylated gp120 monomers from diverse HIV-1 isolates by using small-angle X-ray scattering (SAXS) to probe the overall subunit morphology and hydrogen/deuterium-exchange with mass spectrometry (HDX-MS) to characterize the local structural order of each gp120. We observed that while the overall subunit architecture was similar among isolates by SAXS, dramatic isolate-specific differences in the conformational stability of gp120 were evident by HDX-MS. These differences persisted even with the CD4 receptor bound. Furthermore, surface plasmon resonance (SPR) and enzyme-linked immunosorbance assays (ELISAs) showed that disorder was associated with poorer recognition by antibodies targeting conserved conformational epitopes. These data provide additional insight into the structural determinants of gp120 antigenicity and suggest that conformational dynamics should be considered in the selection and design of optimized Env immunogens.


Asunto(s)
Antígenos Virales/inmunología , Epítopos/inmunología , Anticuerpos Anti-VIH/inmunología , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/inmunología , Vacunas contra el SIDA , Anticuerpos Neutralizantes , Antígenos Virales/metabolismo , Antígenos CD4/metabolismo , Medición de Intercambio de Deuterio , Diseño de Fármacos , Glicosilación , Proteína gp120 de Envoltorio del VIH/metabolismo , Humanos , Conformación Proteica , Dispersión del Ángulo Pequeño , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Resonancia por Plasmón de Superficie
12.
J Community Health ; 39(3): 487-93, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24173529

RESUMEN

The present study sought to examine: (1) the prevalence and correlates of biologically confirmed Hepatitis C (HCV) and (2) the prevalence and correlates of prior HCV diagnosis and an unmet need for HCV treatment, among a community residing sample of drug users. The current study used a subset of HCV tested participants from the larger NEURO-HIV Epidemiologic Study from Baltimore, Maryland (M(age) = 34.81, SD = 9.25; 46% female). All participants were tested for HCV at baseline. Self-report was used to assess awareness of an HCV diagnosis and participation in treatment. Of the 782 participants tested for HCV, 19% reported having received an HCV diagnosis in the past while 48% tested positive for HCV. Only 6% reported having received treatment for any form of hepatitis. Of those who tested HCV positive, 63% reported never being diagnosed, and only 13% received any treatment for HCV. We found that only 35% of those who reported a prior HCV diagnosis received any treatment. The findings regarding lack of HCV awareness and diagnosis were considerable as expected. These deficits suggest that there are numerous gaps in patients' knowledge and beliefs regarding HCV that may interfere at multiple steps along the path from diagnosis to treatment. This study clearly demonstrates that a critical need exists to improve public knowledge of HCV risk factors, the need for testing, and the availability of effective treatment.


Asunto(s)
Consumidores de Drogas , Conocimientos, Actitudes y Práctica en Salud , Hepatitis C/epidemiología , Adulto , Actitud Frente a la Salud , Baltimore/epidemiología , Femenino , Accesibilidad a los Servicios de Salud , Hepatitis C/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Autoinforme
13.
J Infect Dis ; 207(8): 1242-52, 2013 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-22891286

RESUMEN

BACKGROUND: Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA-SE, administered in combination with existing first-line chemotherapeutics rifampicin and isoniazid. METHODS: We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone. RESULTS: This combined approach induced robust and durable pluripotent antigen-specific T helper-1-type immune responses, decreased bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis-induced lung pathology, compared with chemotherapy alone. CONCLUSIONS: These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.


Asunto(s)
Antígenos Bacterianos/inmunología , Antituberculosos/farmacología , Mycobacterium tuberculosis/inmunología , Rifampin/farmacología , Vacunas contra la Tuberculosis/uso terapéutico , Tuberculosis Pulmonar/terapia , Adyuvantes Inmunológicos/administración & dosificación , Animales , Antígenos Bacterianos/administración & dosificación , Antituberculosos/inmunología , Proteínas Bacterianas/inmunología , Quimioterapia Adyuvante/métodos , Modelos Animales de Enfermedad , Femenino , Isoniazida/administración & dosificación , Isoniazida/farmacología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Macaca fascicularis/inmunología , Macaca fascicularis/microbiología , Ratones , Ratones Endogámicos C57BL , Mycobacterium tuberculosis/patogenicidad , Rifampin/administración & dosificación , Prevención Secundaria , Análisis de Supervivencia , Factores de Tiempo , Vacunas contra la Tuberculosis/inmunología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/inmunología , Vacunación
14.
J Pers Med ; 14(4)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38673036

RESUMEN

BACKGROUND: With a rising number of multiple sclerosis (MS) cases and increasing pressure on health systems, digital companion apps like Brisa, designed specifically for people with MS, can play an important role in the patient journey. These apps enable the collection of real-time longitudinal data that are critical to our understanding of the pathophysiology and progression of MS. METHODS: This retrospective, descriptive analysis consists of data from Brisa users who registered between 6 August 2021 and 8 September 2022. Of the unique users, 37.7% (n = 1593) fulfilled the inclusion criteria including information about medication and demographics and tracked one or more symptoms and/or patient-reported outcomes. Users were classified as moderate-efficacy treatment users, high-efficacy treatment users and ocrelizumab users, and the reporting frequency and scores of symptoms and patient-reported outcomes were analyzed. RESULTS: The largest cohort of Brisa users (405) reported treatment with ocrelizumab and were mostly diagnosed 2-5 years before the survey. The most reported MS symptoms were similar between OUs (ocrelizumab users), HETUs (high-efficacy treatment users) and METUs (moderate-efficacy treatment users). OUs on average reported symptoms and answered questionnaires more frequently. Baseline scores between HETUs and OUs were similar, whereas baseline scores of METUs were slightly lower in comparison. In a further analysis of OUs, disability scores increased with age; users aged 26-45 years had higher pain scores than 18-25-year-olds. No significant differences were found in quality of life, bowel control and vision between age groups. CONCLUSION: These findings show that the characteristics of the Brisa cohort are similar to the results of other studies and registries and can provide a representative overview of everyday disease management. Thereby, these results can bridge the gap between clinical research and real patient experience, but they also raise new questions, such as how often the hard-and-early therapy approach is already used and whether baseline characteristics and reasons for choosing a particular treatment contribute to the different outcomes over time. Answering these questions requires further research and analysis.

15.
Ther Adv Neurol Disord ; 17: 17562864241237857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525488

RESUMEN

Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients with poor prognostic factors, it remains unclear whether this approach has been adopted by a broad range of MS providers in Germany yet. Objective: To assess the adoption of the early highly effective treatment (EHT) compared to the treat-to-target treatment approach with the option of escalating treatment efficacy over time in Germany based on real-world evidence data. Design: Patient-level pharmacy dispensing data from the Permea platform were analysed from 2020 to 2022. Methods: In total, 29,529 therapy beginners (>18 years) were included to analyse shifts in treatment approaches over time and switching behaviour. Medication classification adhered to the German Society of Neurology guidelines and designated fumarates, glatiramer acetate, teriflunomide and interferons as low-efficacy category 1 medications; cladribine and S1P-modulators as medium-efficacy category 2 medications; and alemtuzumab, natalizumab, ocrelizumab, ofatumumab and rituximab (off-label) as high-efficacy category 3 medications. Results: Our results show that 70.0% of patients redeemed their first prescription for category 1 medication, 16.3% for category 2 and 13.7% for category 3 medications. The proportion of prescriptions filled shifted from 2020 to 2022 with a decrease of 14.7% for category 1 drugs and an increase of 12.5% for category 3 drugs. 93.2% of patients stayed on their initially prescribed medication category. 3.2% of category 1 and 3.7% of category 2 therapy beginners escalated to category 3 medication. 3.4% of category 3 medication users de-escalated their treatment to category 1 or category 2. Conclusion: While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by German guidelines, MS providers increasingly adopt the EHT approach.

16.
Mult Scler Relat Disord ; 88: 105751, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38968925

RESUMEN

BACKGROUND: The hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data. METHODS: The analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ2-square and t-tests. RESULTS: 29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD. CONCLUSION: Between 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS.


Asunto(s)
Esclerosis Múltiple , Humanos , Alemania , Estados Unidos , Esclerosis Múltiple/terapia , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Masculino , Femenino , Persona de Mediana Edad , Factores Inmunológicos/uso terapéutico , Estudios Longitudinales , Adulto Joven
17.
J Virol ; 86(16): 8750-64, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22674993

RESUMEN

The gp120 subunit of the HIV Env glycoprotein is responsible for receptor interactions leading to viral entry and is a primary target for neutralizing antibodies. Most structural studies have focused on the heavily truncated, deglycosylated gp120 core, leaving fundamental aspects of the glycoprotein that are responsible for immune evasion and receptor-induced activation unresolved. Here we investigate full-length, glycosylated HIV gp120 in unliganded and CD4-bound forms by using small-angle X-ray scattering to visualize global structural reorganization and hydrogen/deuterium exchange to track changes in local conformational dynamics. The studies revealed unliganded full-length gp120 to be considerably more dynamic, particularly at the CD4 binding site, than suggested by previous studies of the subunit core alone. The large V1/V2 loops, previously unmapped, are positioned to mask the coreceptor binding site in an orientation that recapitulates that observed in the Env trimer. CD4 binding shifts V1/V2 to unmask the coreceptor binding site and triggers profound dynamic changes in gp120 spanning from the binding site to the gp41-interactive face of gp120. These findings provide further insights on the structural basis of Env antigenicity and immunogenicity and of allosteric effects upon receptor binding.


Asunto(s)
Antígenos CD4/química , Antígenos CD4/metabolismo , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/metabolismo , Glicoproteínas/química , Glicoproteínas/metabolismo , Modelos Moleculares , Simulación de Dinámica Molecular , Conformación Proteica , Dispersión del Ángulo Pequeño
18.
Malar J ; 12: 286, 2013 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-23961874

RESUMEN

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzyme deficiency. It is characterized by abnormally low levels of G6PD activity. Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when exposed to 8‒aminoquinoline-based drugs, such as primaquine. For this reason it is imperative to identify individuals with G6PD deficiency prior to administering these anti-malarial drugs. There is a need for the development and evaluation of point-of-care G6PD deficiency screening tests suitable for areas of the developing world where malarial treatments are frequently administered. The development and evaluation of new G6PD tests will be greatly assisted with the availability of specimen repositories. METHODS: Cryopreservation of erythrocytes was evaluated as a means to preserve G6PD activity. Blood specimens from 31 patients including ten specimens with normal G6PD activity, three with intermediate activity, and 18 with deficient activity were cryopreserved for up to six months. RESULTS: Good correlation in G6PD activity between fresh and cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining showed that intracellular G6PD activity distribution within the red blood cell populations is preserved during cryopreservation. Furthermore, the mosaic composition of red blood cells in heterozygous women is also preserved for six months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD deficiency also showed high concordance in G6PD status determination between cryopreserved specimens and fresh specimens. CONCLUSIONS: A methodology for establishing a specimen panel for evaluation of G6PD tests is described. The approach is similar to that used in several malaria research facilities for the cryopreservation of parasites in clinical specimens and axenic cultures. Specimens stored in this manner will aid both the development and evaluation of current and emerging G6PD tests. The availability of G6PD tests is a critical bottleneck to broader access to drugs that confer radical cure of Plasmodium vivax, a requirement for elimination of malaria.


Asunto(s)
Recolección de Muestras de Sangre/métodos , Criopreservación/métodos , Eritrocitos/citología , Eritrocitos/enzimología , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Glucosafosfato Deshidrogenasa/sangre , Análisis Químico de la Sangre , Pruebas de Enzimas , Eritrocitos/química , Eritrocitos/metabolismo , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Masculino
19.
Diagn Microbiol Infect Dis ; 106(4): 115974, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37224607

RESUMEN

OBJECTIVE: To evaluate the diagnostic accuracy of rapid VitaPCR™ (Credo) assay as screening test in emergency department (ED) patients prior to transfer or medical interventions. METHODS: In this prospective study 6642 oropharyngeal swabs from nonpreselected ED patients were tested for SARS-CoV-2 with (1) extraction-free VitaPCR and (2) extraction-based reference assays (Aptima®, cobas®, Xpert®Xpress). RESULTS: The median TAT of VitaPCR was 47 minutes (IQR: 38-59), while reference assays required 6.2 hours (IQR: 4.4-13.3). VitaPCR's sensitivity, specificity, PPV and NPV was 77.9%, 99.9%, 97.9%, and 98.9% in relation to Hologic Panther TMA; 78.3%, 99.8%, 96.4%, and 98.5% compared to Roche cobas6800 PCR; 71.2%, 99.2%, 94.9%, and 94.3% using Cepheid GeneXpert PCR as reference. CONCLUSION: High-sensitivity testing is needed to limit nosocomial spread and identify asymptomatic COVID-19 patients. However, time advantage of the VitaPCR must be weighed against its significantly lower sensitivity, especially when used in high-risk environments such as hospitals.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Estudios Prospectivos , Sensibilidad y Especificidad , Hospitales , Nasofaringe
20.
Ther Adv Musculoskelet Dis ; 15: 1759720X231187189, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37565049

RESUMEN

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which primarily affects the axial skeleton resulting in chronic back pain and stiffness. According to the guideline, the first-line treatment includes non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-pharmacological treatment. Second line treatment involves biological disease-modifying antirheumatic drugs (bDMARDs) such as tumour necrosis factor and interleukin-17 inhibitors. Objectives: The aim of this social media listening research project was to analyse switches of medication and the reasons thereof to gain valuable insights into real-life journeys of patients suffering from axSpA. Methods: Publicly available posts in German-speaking disease-specific forums were scanned for disease-specific keywords and commonly used drugs by axSpA patients on the Permea platform. Posts containing at least two key words were selected and switches between medications were manually labelled. A total of 287 scraped posts between 01 July 2010 and 04 Feb 2022 were analysed. Results: The largest group of described medication switches was initially using bDMARDs. Switches to a different bDMARD, termination of medication and switches to glucocorticoids were most frequently named. Patients on NSAIDs switched to glucocorticoids, a different NSAID or bDMARD, whereas patients on csDMARDs most frequently changed to bDMARDs. In all medication groups the main reason for switching was insufficient efficacy and side effects. Additionally, for the medication groups bDMARDs, csDMARDs and corticosteroids, pregnancy and lactation were given as a reason for switching, whereas patients in the NSAID group never mentioned pregnancy and breastfeeding as a reason for switching treatment. Conclusion: Our analysis shows medication switches based on real-life patient experiences shared with peers in a social listening setting. We also show medication switches differing from advised guidelines. Gathering real-life insights into patients' journey dealing with chronic diseases allows us to understand, and thereby improve patient care and treatment.

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