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BACKGROUND: The use and advantages of point-of-care tests (POCTs) for C-reactive protein (CRP) in general practice, especially for upper respiratory tract infections (uRTIs), have been studied extensively. However, there is limited knowledge about test indications, prerequisites, and integration of these tests into everyday practice. AIM: This study aims to investigate the attitudes and experiences of general practitioners (GPs) in Germany regarding the use of semi-quantitative CRP-POCTs. The study places special emphasis on implementation in routine care, including testing procedures, feasibility, opportunities and barriers for specific consultation scenarios, as well as test indications and their impact on GP-patient communication. DESIGN & SETTING: Qualitative interview study with 10 GPs (May/2023 to Aug/2023) METHOD: Ten German GPs who participated in an observational study on CRP-POCT use in general practices were interviewed using semi-structured interviews. Audio recordings were transcribed and content analysis was performed. RESULTS: Interviewed GPs stated that CRP-POCTs offer several advantages for various treatment cases. They improve diagnostic confidence and certainty of GPs' therapeutic decisions, and offer a broad spectrum of indications and application scenarios. Additionally, they have a positive impact on GP-patient communication, and their ease of use enables rapid implementation into existing workflows. On the other hand, CRP-POCT increase the time required for test performance and patient consultation. CONCLUSION: Due to the numerous benefits of semi-quantitative CRP-POCTs, interviewed GPs have a favourable attitude towards their regular integration into everyday practice. Implementation barriers include increased time and personnel expenses for testing and inadequate reimbursement by German statutory health insurance.
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BACKGROUND: Point-of-care tests (POCTs) for C-reactive protein can support clinical decision-making of general practitioners (GPs) but are not widely used in German general practices. AIM: To investigate the utilization of semi-quantitative CRP-POCTs in routine primary care. DESIGN & SETTING: Prospective observational study in 49 general practices in Germany (Nov/2022 to Apr/2023). METHOD: GPs were provided with CRP-POCTs and collected data for each CRP-POCT use using standardized data collection sheets. RESULTS: Data from 1,740 CRP-POCT uses were recorded. GPs employed CRP-POCTs mainly for patients with respiratory tract infections (RTIs, 70.9% of all cases) and to a lesser extent for gastrointestinal infections (GIs, 10.3%). In RTIs, CRP-POCTs were frequently used to distinguish between bacterial and viral aetiology (60.8%) and to guide decisions on antibiotic prescribing (62.8%). In GIs, CRP-POCTs were mainly used to rule out severe disease progressions (53.2%) and for decisions on further diagnostic procedures (45.6%). In RTIs, CRP-POCTs influenced antibiotic prescribing in 77.5 % of the cases (32.3% in favour vs. 45.2% waiver). In GIs, CRP levels mainly affected decisions on further diagnostic procedures. GPs reported that CRP-POCTs were helpful in 88.6% of all cases. CONCLUSIONS: When available, German GPs predominantly use semi-quantitative CRP-POCTs to guide decisions on antibiotic prescribing in patients with RTI. CRP-POCT use improves clinical decision-making and increases the GPs' clinical confidence.
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INTRODUCTION: During the COVID-19 pandemic general practitioners (GP) practice teams were temporally confronted with major challenges which were accompanied by changes in practice organization and service provision. So far, little has been known about the views of patients who visited the GP practice for other than COVID-related reasons with regard to provision and use of GP services, the adjustments in the practice and the work of the practice team members. METHODS: The patient survey is a sub-study of the mixed-methods study VeCo-Praxis (GP healthcare for patients not suffering from COVID during the Corona pandemic) of the research practice network RESPoNsE (Research Practice Network East), which was conducted in the federal states of Berlin, Brandenburg and Thuringia. The questionnaire-based survey was carried out among patients who visited their GP practice in November 2022. The topics covered in the survey were developed by two focus groups consisting of 13 members of the RESPoNsE patient advisory board. The questionnaire was developed and piloted in a participatory approach with the RESPoNsE Patient Advisory Board. The results were analyzed descriptively using SPSS and discussed with the advisory board. RESULTS: 1,405 questionnaires from 37 practices were analyzed. 97% of respondents felt that the treatment they received at their GP practice during the COVID-19 pandemic was good. For the vast majority, appointments and acute consultations, prescriptions, laboratory tests, discussions of diagnostic results, routine follow-up check-ups and health checks were available to a sufficient extent. From the patients' perspective, the practices have successfully adapted to the challenges caused by COVID-19. Overall, the patients' trust in and their appreciation of the work of the practice staff have increased since the pandemic. Patients stated that GP practices should continue hygiene procedures, such as wearing a mask or keeping physical distance, in the future. DISCUSSION: Despite multiple reports of a significant decline in both provision and utilization of standard care in GP practices during the pandemic, our survey showed that the majority of patients felt that they received adequate GP care and were highly satisfied. The results should be interpreted against the background of possible selection bias. CONCLUSION: In this survey, GP patients were predominantly appreciative of GP care during the COVID-19 pandemic. The patients' assessment of the provision and use of GP services during the pandemic complements the corresponding perspective of GPs and medical practice assistants.
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COVID-19 , Pandemias , Atenção Primária à Saúde , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Alemanha , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Inquéritos e Questionários , Medicina Geral/estatística & dados numéricos , Adulto Jovem , Grupos Focais , Pesquisas sobre Atenção à SaúdeAssuntos
Assistência Ambulatorial , Cuidados Paliativos , Alemanha , Humanos , Cuidados Paliativos/estatística & dados numéricos , Assistência Ambulatorial/estatística & dados numéricos , Masculino , Feminino , Programas Nacionais de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Medicina/estatística & dados numéricosRESUMO
INTRODUCTION: The delegation of tasks and responsibilities from general practitioners (GPs) to medical practice assistants (MPAs) can contribute to ensuring primary care in Germany. The aim of the study was to collect and analyze attitudes and procedures of GPs and MPAs regarding the delegation of physician-related tasks and activities. METHODOLOGY: A self-designed, piloted questionnaire was sent to all GPs listed within the regional Associations of Statutory Health Insurance Physicians (KV) in Thuringia, Berlin, and Brandenburg (n=5,516) and their MPAs. Participants were asked to indicate which physician-related activities were already delegated and on which occasions further delegations could be considered. RESULTS: 890 GPs (response rate: 16.1%) and 566 MPAs participated in the written survey. The participants were predominantly female and most of them worked in urban areas. Numerous activities, such as medical history taking, triage, Disease Management Program (DMP) controls, vaccinations and home visits, have already been delegated. The willingness to delegate further tasks (e. g., follow-up prescriptions and referrals, independent takeover of simple consultations, assessing the necessity of physician consultation) was high. CONCLUSION: The survey showed a high level of willingness of both occupational groups to delegate physician-related activities to MFAs. An expansion seems possible under certain conditions. Many activities have already been delegated to MPAs in primary care practices. Our survey provides suggestions regarding further tasks suitable for delegation, some of which go beyond the delegation agreement valid in Germany.
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Clínicos Gerais , Humanos , Feminino , Masculino , Berlim , Alemanha , Inquéritos e Questionários , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: The main framework conditions for palliative care are set at the regional level. The scope of the forms of care used (outpatient, inpatient, general, specialized) varies widely. What is the quality of outcomes achieved by the palliative care provided on a federal states level? What are the associated costs of care? METHOD: Retrospective observational study using BARMER claims data from 145,372 individuals who died between 2016 and 2019 and had palliative care in the last year of life. Regional comparison with regard to the following outcomes: proportion of palliative care patients who died in the hospital, potentially burdensome care in the last 30 days of life (ambulance calls, [intensive care] hospitalizations, chemotherapy, feeding tubes, parenteral nutrition), total cost of care (last three months), cost of palliative care (last year), and cost-effectiveness ratios. Calculation of patient/resident characteristic adjusted rates, costs, and ratios. RESULTS: Federal states vary significantly with respect to the outcomes (also adjusted) of palliative care. Palliative care costs vary widely, most strongly for specialized outpatient palliative care (SAPV). Across all indicators and the cost-effectiveness ratio of total cost of care to at-home deaths, Westphalia-Lippe shows favorable results. CONCLUSION: Regions with better quality and more favorable cost (ratios) can provide guidance for other regions. The extent to which the new federal SAPV agreement can incorporate the empirical findings should be reviewed. Patient-relevant outcome parameters should be given greater weight than parameters aiming at structures of care.
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Cuidados Paliativos , Assistência Terminal , Humanos , Alemanha/epidemiologia , Assistência Ambulatorial , Hospitalização , Estudos RetrospectivosRESUMO
INTRODUCTION: The coronavirus pandemic did not only result in changes in the provision and utilization of health care services in general practice but also in an increased workload for physicians and medical practice assistants. The VeCo practice study retrospectively explores the experiences of both professional groups two years after the start of the pandemic. METHODS: In March and April 2022, general practitioners and medical practice assistants in the three German federal states of Berlin, Brandenburg and Thuringia were asked to complete a paper-based questionnaire. RESULTS: 657 general practitioners and 762 medical practice assistants completed the questionnaire. Both professional groups agreed to statements indicating a reduction in regular health care provisions. Nevertheless, 74% of the physicians and 82.9% of the medical practice assistants considered the health care provided to their patients during the pandemic as good. This was only possible through considerable additional effort and stress. While more than half of both groups reported that work was still enjoyable, three quarters of both groups stated that the challenges arising from the pandemic outstripped their capacity. Both groups would like to receive more recognition from society (medical practice assistants 93.2%, general practitioners 85.3%) and from their patients (87.7% and 69.9%, respectively). DISCUSSION: General practitioners and medical practice assistants reduced regular health care provision but were still able to maintain a good quality of care for their patients during the pandemic. It became clear that more appreciation and adequate financial compensation are necessary to ensure long-term sustainability of GP care. CONCLUSION: The subjective view of general practitioners and medical practice assistants on their health care provision shows that appreciation and adequate financial renumeration, particularly when working under most difficult conditions, are necessary to increase the attractiveness of a career in general practice, for both physicians and medical practice assistants.
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COVID-19 , Medicina Geral , Clínicos Gerais , Humanos , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Alemanha , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Pragmatic randomized controlled trials are able to make an essential contribution to the further development of evidence-based treatment recommendations for primary care patients. However, drug trials are regulated by specific guidelines and have not yet become a routine task in GP practices. Within the scope of a multi-center, double-blind, randomized controlled trial on treating urinary tract infections in women with and without antibiotics (REGATTA), the feasibility of pharmaceutical studies in GP practices was evaluated by means of a questionnaire sent out to participating physicians and practice nurses. METHODS: Using a self-designed, non-validated questionnaire, the perspectives, attitudes and experiences of participating physicians and practice nurses were assessed anonymously. In this way, we identified both hindering and beneficial factors affecting the conduct of drug trials in German GP practices. RESULTS: 39 physicians and 48 practice nurses participated in the survey. 95 % of the physicians and 88 % of the practice nurses indicated that the implementation of drug trials with all their regulatory requirements is, in principle, possible in GP practices. In particular, the high amount of time and documentation necessary were identified as barriers. The implementation can be facilitated by formulating a research question that is relevant to practice and patients and by support from the study center. CONCLUSION: Although participation in a drug trial is an additional burden in everyday practice, it is considered feasible and worthwhile by the GPs and practice nurses involved. Due to an assumed selection bias, the predominantly positive experiences of the respondents may be overestimated and transferable only to a limited extent.
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Medicina Geral , Médicos , Feminino , Alemanha , Humanos , Corpo Clínico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Comparative effectiveness of different types of palliative homecare is sparsely researched internationally-despite its potential to inform necessary decisions in palliative care infrastructure development. In Germany, specialized palliative homecare delivered by multi-professional teams has increased in recent years and factors beyond medical need seem to drive its involvement and affect the application of primary palliative care, delivered by general practitioners who are supported by nursing services. AIM: To compare effectiveness of primary palliative care and specialized palliative homecare in reducing potentially aggressive interventions at the end-of-life in cancer and non-cancer. DESIGN: Retrospective population-based study with claims data from 95,962 deceased adults in Germany in 2016 using multivariable regression analyses. SETTINGS/PARTICIPANTS: Patients having received primary palliative care or specialized palliative homecare (alone or in addition to primary palliative care), for at least 14 days before death, differentiating between cancer and non-cancer patients. RESULTS: Rates of potentially aggressive interventions in most indicators were higher in primary palliative care than in specialized palliative homecare (p < 0.01), in both cancer and non-cancer patients: death in hospital (odds ratio (OR) 4.541), hospital care (OR 2.720), intensive care treatment (OR 6.749), chemotherapy (OR 2.173), and application of a percutaneous endoscopic gastrostomy (OR 4.476), but not for parenteral nutrition (OR 0.477). CONCLUSION: Specialized palliative homecare is more strongly associated with reduction of potentially aggressive interventions than primary palliative care in the last days of life. Future research should identify elements of specialized palliative homecare applicable for more effective primary palliative care, too. German Clinical Trials Register (DRKS00014730).
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Serviços de Assistência Domiciliar , Neoplasias , Assistência Terminal , Adulto , Alemanha , Humanos , Neoplasias/terapia , Cuidados Paliativos , Estudos RetrospectivosRESUMO
BACKGROUND: Palliative care supply increased in Germany in recent years. But how many people use which forms of palliative care and how does this differ between regions? METHOD: Retrospective cohort study with claims data from insured persons who died in 2016: Based on services billed at least once in the last six months of life, we determined the use of primary palliative care (PPC), specialized palliative homecare (SPHC), as well as inpatient palliative and hospice care, using regional billing codes for PPC and SPHC services for the first time. RESULTS: Of the 95,962 deceased in the study population, 32.7% received palliative care nationwide, with variations from 26.4% in Bremen to 40.8% in Bavaria. PPC services were billed at 24.4% (16.9% in Brandenburg to 34.1% in Bavaria). SPHC services received 13.1% (6.3% in Rhineland-Palatinate to 18.9% in Brandenburg and 22.9% in Westphalia-Lippe with different SPHC practices). Inpatient palliative care was received by 8.1% (6.7% in Schleswig-Holstein/Hesse to 13.0% in Thuringia); 3.3% (1.6% in Bremen to 5.6% in Berlin) with hospice services. CONCLUSION: SPHC is used more frequently than previously reported, while PPC is declining. Utilization seems to be based less on objective needs than on region-specific framework conditions. Besides needs criteria, further development of palliative care should be oriented more towards outcomes and relevant framework conditions.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Berlim , Alemanha , Humanos , Cuidados Paliativos , Estudos RetrospectivosRESUMO
BACKGROUND: Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. METHOD: A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. RESULTS: Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0-6 months; SMD, - 0.1; 95% CI, - 0.24-0.04; I2 = 0%). Only two studies contributed to the meta-analysis for long term (12-18 months) outcomes yielding a small effect (SMD, - 0.23; 95% CI, - 0.38- -0.08; I2 = 0%). CONCLUSIONS: Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.
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Médicos de Atenção Primária , Transtornos de Estresse Pós-Traumáticos , Humanos , Intervenção Psicossocial , Psicoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
AIM: The paper quantifies discrepancies between date of payment and date of service provision when doing analyses in relation to date of death and also in relation to the end of a calendar year. In analyses of this type, time differences between service provision and payment can lead to both under- and overestimation of service use. We aim to capture these phenomena in claims data from different sectors (primary care, medication prescription, prescription of remedies and medical aids, hospital care). METHOD: We have used pre-structured claims data from a scientific data warehouse of a large German statutory health insurance covering people that died in 2016. We investigated the discrepancies in time between date of service provision and date of payment for different outpatient and inpatient services based on data from 2015 to 2017. An exact date (dd/mm/yyyy) was only available for data covering prescriptions of remedies and medical aids. Data covering medication prescriptions were only exact to the month of payment (mm/yyyy), whereas data covering outpatient physician care were only exact to the quarter of payment (q/yyyy). RESULTS: For both outpatient physician care and hospital care, less than 1% had a payment date after the date of death. The share is considerably higher (28-31%) for prescriptions of remedies and medical aids. The majority of payments occurred within 3 months after death (93% for prescriptions of remedies and medical aids, 67% for primary care services). Less than 1% of outpatient physician care and about 18% of remedies had been paid after the end of the calender year 2015. Here too, the majority of payments were made within the first 3 months of 2016 (100% of prescriptions of remedies and medical aids, 65% of primary care services). CONCLUSIONS: Discrepancies in time between date of service provision and date of payment pose a challenge and are a potential source of under-/overestimation of health service utilization when doing analyses in relation to date of death or the end of a calendar year. This needs to be taken into account when requesting the data, but also in preparing and analysing them. The primary recommendation is to ensure that services with a payment date after death are included explicitly.
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Assistência Ambulatorial , Prescrições de Medicamentos , Confiabilidade dos Dados , Análise de Dados , Alemanha , Humanos , Programas Nacionais de Saúde , Pacientes Ambulatoriais , Estados UnidosRESUMO
BACKGROUND: Since 2007, the German statutory health insurance covers Specialized Outpatient Palliative Care (SAPV). SAPV offers team-based home care for patients with advanced and progressive disease, complex symptoms and life expectancy limited to days, weeks or months. The introduction of SAPV is ruled by a directive (SAPV directive). Within this regulation, SAPV delivery models can and do differ regarding team structures, financing models, cooperation with other care professionals and processes of care. The research project SAVOIR is funded by G-BA's German Innovations Fund to evaluate the implementation of the SAPV directive. METHODS: The processes, content and quality of SAPV will be evaluated from the perspectives of patients, SAPV teams, general practitioners and other care givers and payers. The influence of different contracts, team and network structures and regional and geographic settings on processes and results including patient-reported outcomes will be analyzed in five subprojects: [1] structural characteristics of SAPV and their impact on patient care, [2] quality of care from the perspective of patients, [3] quality of care from the perspective of SAPV teams, hospices, ambulatory nursing services, nursing homes and other care givers, content and extent of care from [4] the perspective of General Practitioners and [5] from the perspective of payers. The evaluation will be based on different types of data: team and organizational structures, treatment data based on routine documentation with electronic medical record systems, prospective assessment of patient-reported outcomes in a sample of SAPV teams, qualitative interviews with other stakeholders like nursing and hospice services, a survey in general practitioners and a retrospective analysis of claims data of all SAPV patients, covered by the health insurance fund BARMER in 2016. DISCUSSION: Data analysis will allow identification of variables, associated with quality of SAPV. Based on these findings, the SAVOIR study group will develop recommendations for the Federal Joint Committee for a revision of the SAPV directive. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00013949 (retrospectively registered, 14.03.2018), DRKS00014726 (14.05.2018), DRKS00014730 (30.05.2018). Subproject 3 is an interview study with professional caregivers and therefore not registered in DRKS as a clinical study.
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Assistência Ambulatorial/normas , Cuidados Paliativos/normas , Ensaios Clínicos como Assunto/métodos , Atenção à Saúde/normas , Medicina Geral/normas , Alemanha , Humanos , Estudos Multicêntricos como Assunto , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Estudos Prospectivos , Qualidade da Assistência à Saúde , Assistência Terminal/normasRESUMO
OBJECTIVE: For most patients with depression, GPs are the first and long-term medical providers. GP-centered health care (GPc-HC) programs target patients with chronic diseases. What are the effects of GPc-HC on primary care depression management? METHOD: An observational retrospective case-control study was conducted using health insurance claims data of patients with depressive disorder from July 2011 to December 2012. RESULTS: From 40,298 patients insured with the largest health plan in Central Germany participating in the GPc-HC program (intervention group, IG), we observed 4645 patients with depression over 18months: 72.2% women; 66.6years (mean); multiple conditions (morbidity-weight 2.50 (mean), 86%>1.0). We compared them with 4013 patients who did not participate (control group). In participants we found lower number of incomplete/non-specified depression diagnoses (4.46vs.4.82;MD-0.36; p<0.01); lower rate of patients consulting more than one GP-practice (49.1%vs.58.0%;PP-8.9;p<0.01); more GP-contacts (18.19vs.15.59;MD+2.60;p<0.01); more GP-initiated referrals to specialists (82.9%vs.79.3%;PP+3.6;p<0.05), more antidepressant pharmacotherapy prescribed by a GP (37.9%vs.35.4%;PP+2.5;p<0.05), more frequent guideline-concordant therapy duration (19.2%vs.13.1%;PP+6.1;p<0.01) and more patients receiving "GP-psychosomatic basic care" (38.2%vs.30.2%;PP+8.0;p<0.01). CONCLUSION: Depressive patients participating in a GPc-HC program may be more often diagnosed by a GP, receive symptom-monitoring and appropriate depression treatment.
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Depressão/terapia , Transtorno Depressivo/terapia , Clínicos Gerais/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Depressão/diagnóstico , Depressão/epidemiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/organização & administraçãoRESUMO
OBJECTIVES/HYPOTHESIS: To evaluate the selective glucocorticoid receptor agonist (SEGRA) compound A, a potential novel therapeutic for inner ear disorders, for ototoxic effects. STUDY DESIGN: Laboratory animal study. METHODS: Experimental guinea pigs were grouped as follows: Systemic application of compound A (1.5 mg/kg and 4.5 mg/kg; n = 6/group) and intratympanic application of compound A (1 mM and 10 mM; n = 6/group). Contralateral ears in topically treated animals served as controls. Hearing thresholds were determined by auditory brainstem response before and directly after the application of compound A, as well as on days 3, 7, 14, 21, and 28. At the end of the experiments, temporal bones were harvested for histological evaluation. RESULTS: Systemic administration of compound A (1.5 mg/kg and 4.5 mg/kg) did not cause hearing threshold shifts, whereas the intratympanic injection (1 mM and 10 mM) resulted in a hearing loss. Histological analysis of the middle and inner ears after topical compound A application showed alterations in the tympanic membranes, the auditory ossicles, and the round window membranes, whereas spiral ganglion cells and hair cells were not affected. CONCLUSION: SEGRAs such as compound A could provide novel therapeutic options for the treatment of inner ear disorders and reduce metabolic side effects. Whereas the intratympanic application of compound A resulted in a hearing loss, the systemic application of compound A merits evaluation for otoprotective effects in trauma models.
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Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Receptores de Glucocorticoides/antagonistas & inibidores , Membrana Timpânica/efeitos dos fármacos , Membrana Timpânica/patologia , Adenina/farmacologia , Administração Tópica , Animais , Limiar Auditivo/fisiologia , Biópsia por Agulha , Citratos/farmacologia , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Glucose/farmacologia , Cobaias , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Fosfatos/farmacologia , Distribuição Aleatória , Valores de ReferênciaRESUMO
Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1ß. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10-inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI.
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Hidradenite Supurativa/imunologia , Hidradenite Supurativa/patologia , Mediadores da Inflamação/fisiologia , Interleucinas/deficiência , Adolescente , Adulto , Idoso , Animais , Peptídeos Catiônicos Antimicrobianos/deficiência , Peptídeos Catiônicos Antimicrobianos/fisiologia , Células Cultivadas , Doença Crônica , Citocinas/biossíntese , Citocinas/deficiência , Feminino , Hidradenite Supurativa/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucinas/genética , Interleucinas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Regulação para Cima/imunologia , Adulto Jovem , Interleucina 22RESUMO
PURPOSE: This study analyzes (1) the value of tyrosinase reverse-transcriptase polymerase chain reaction (RT-PCR) of aspirates obtained by ultrasound-guided fine-needle aspiration cytology (US-FNAC) of sentinel nodes (SNs) in patients with melanoma before sentinel lymph node biopsy (SLNB) and (2) the value of RT-PCR of blood samples of all SLNB patients. PATIENTS AND METHODS: Between 2001 and 2003, 127 patients with melanoma (median Breslow depth, 2.1 mm) underwent SLNB. FNAC was performed in all SNs of all patients pre- and post-SLNB. The aspirates were partly shock-frozen for RT-PCR and were partly used for standard cytology. Peripheral blood was collected at the time of SLNB and at every outpatient visit thereafter. RESULTS: Thirty-four (23%) of 120 SNs were positive for melanoma. SN involvement was predicted by US-FNAC with a sensitivity of 82% and a specificity of 72%. Additional tyrosinase RT-PCR revealed the same sensitivity of 82% and a specificity of 72%. At a median follow-up time of 40 months from first blood sample, peripheral-blood RT-PCR was a significant independent predictor of disease-free survival (DFS) and overall survival (OS; P < .001). CONCLUSION: US-FNAC is highly accurate and eliminates the need for SLNB in 16% of all SLNB patients. RT-PCR of the aspirate or excised SN does not improve sensitivity or specificity. RT-PCR of blood samples predicts DFS and OS.
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Biomarcadores Tumorais/genética , Biópsia por Agulha Fina , Linfonodos/enzimologia , Melanoma/genética , Monofenol Mono-Oxigenase/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Biópsia de Linfonodo Sentinela , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Masculino , Melanoma/sangue , Melanoma/diagnóstico por imagem , Melanoma/enzimologia , Melanoma/terapia , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/sangue , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Acne inversa is a chronic inflammatory skin disease featuring cutaneous and subcutaneous nodular inflammation, fistula formation and discharge of foul-smelling secretions. The disease can lead to functional impairment and psychological problems. There is inflammation of the terminal hair follicles in intertriginous regions, especially perianal, axillary and inguinal areas. Less often there is submammary, periumbilical, retroauricular or nuchal involvement. Without treatment the disease is chronic and progressive. The causes of acne inversa are multifactorial and pathogenesis is still not well understood. Besides a positive family history, obesity and cigarette smoking are trigger factors. Early diagnosis and therapy of acne inversa saves the patient years of suffering. The most effective treatment is undoubtedly the radical wide excision of the affected areas. Local measures such as radiotherapy, photodynamic therapy and cryotherapy have provided little benefit; the same is true for systemic antibiotic treatment or hormonal therapy with anti-androgens. TNF-alpha antagonists seem to have a promising influence on the disease. Further studies investigating the effect of these substances on acne inversa are warranted.
Assuntos
Acne Vulgar/diagnóstico , Acne Vulgar/cirurgia , Padrões de Prática Médica/tendências , Acne Vulgar/terapia , Alemanha , Humanos , Guias de Prática Clínica como AssuntoRESUMO
A substantial improvement in the performance of pyroelectric 0-3 composites of ceramic particles in a polymer matrix has been achieved by doping the polymer matrix material. Readily prepared and polarized films with various volume fractions of lead zirconate-titanate (PZT) particles in polyurethane have been doped in a solution of lithium perchlorate in acetone to increase the conductivity. With an appropriate conductivity, the dielectric permittivities of the ceramic particles and the polymer matrix become matched, resulting in an improvement of the pyroelectric coefficient from about 6 microC/(m(2)K) to about 50 microC/(m(2)K). The experimental results are explained by theoretical predictions.