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1.
Codas ; 33(5): e20200058, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34524350

RESUMO

PURPOSE: Verifying the association between clinical-functional vulnerability and vocal and auditory self-perception in seniors presenting a history of leprosy. METHODS: Cross-sectional study encompassing 117 elderly people from an old leprosy colony in southeastern Brazil. The research analyzed sociodemographic information and the following protocols: Clinical-Functional Vulnerability Index-20 (IVCF-20), Hearing Handicap Inventory for the Elderly Screening Version (HHIE-S), Screening for Vocal Change in the Elderly (RAVI) and Vocal Handicap Index 10 (IDV-10). For data analysis, the ordinal logistic regression model of proportional odds was used. RESULTS: 37.6% of the elderly were classified as robust, 35.0% at risk of fragility and 27.4% as frail. Vocal alteration (RAVI), vocal handicap (IDV-10) and restriction to auditory participation (HHIE-S) were observed in 65.8%, 24.8% and 48.7% respectively, in the studied population. In the multivariate analysis, it was found the oldest group (OR = 1.11; CI: 1.05-1.16) and those with vocal handicap (OR = 4.11; 95% CI: 1.77-9.56) were more likely to be classified as at risk of fragility or already fragile. The simultaneous presence of vocal handicap and restriction of auditory participation (46.9%) was larger among frail elderly people. CONCLUSION: The increasing age of the elderly and the presence of vocal handicap is associated with greater clinical-functional vulnerability. The high prevalence of both voice and hearing disorders reinforces the need for the speech therapist to be included in public policies, directed towards caring for people with a history of leprosy.


Assuntos
Audição , Hanseníase , Idoso , Brasil , Estudos Transversais , Humanos , Hanseníase/complicações , Autoimagem , Inquéritos e Questionários
2.
Front Immunol ; 12: 662307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354699

RESUMO

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.


Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto Jovem
3.
Front Immunol ; 12: 632482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276644

RESUMO

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson's disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.


Assuntos
Actinobacteria/imunologia , Epitopos/imunologia , Firmicutes/imunologia , Doença de Parkinson/microbiologia , Actinobacteria/classificação , Actinobacteria/genética , Actinobacteria/metabolismo , Idoso , Biomarcadores , Vias Biossintéticas , Citocinas/sangue , Fezes/microbiologia , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/metabolismo , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/imunologia
4.
Am J Trop Med Hyg ; 105(1): 31-36, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232909

RESUMO

Leprosy is an infectious disease caused by Mycobacterium leprae. China was once one of the countries with severe leprosy epidemics, but its incidence has remained low in recent years. Despite this, there has been no decrease in its incidence more recently, and it is still a public health problem which needs to be controlled. In this study, we analyzed the epidemiological characteristics and trends in the detection rate of new cases of leprosy in China between 2004 and 2016. There were 4,519 cases of leprosy in 28 provinces, municipalities, and autonomous regions between 2004 and 2016, and the total incidence was 0.02815 (per 100,000 individuals) and 21 deaths. The overall incidence of leprosy showed an inverted "V" distribution (i.e., an increase followed by a decrease). Yunnan, Sichuan, Guangdong, Guizhou, and Guangxi were the top five regions with the highest incidence rates, and they accounted for 68.7% of the total cases. There were more male patients than female patients, and peasants accounted for 71.7% of the leprosy cases. The patients with leprosy in China were mainly concentrated in the age-group 15-44 years, as this group accounted for 57.2% of the total cases. The purpose of this study is to explore the epidemiology of leprosy in China. This analysis will be useful for future monitoring of leprosy and establishment of public health measures in China, in keeping with the "Programme for the Elimination of Leprosy in China 2011-2020."


Assuntos
Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Estudos Retrospectivos , Adulto Jovem
5.
Int J Infect Dis ; 110: 111-113, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34271204

RESUMO

Leprosy is currently uncommon in Europe: the diagnosed cases are almost all imported from endemic areas. We report on an autochthonous case of borderline lepromatous leprosy in a 71-year-old Portuguese woman. The case was complicated by a reversal reaction and then by erythema nodosum leprosum. A literature review identified 18 reported cases of European autochthonous leprosy since 2000; all but one were observed in Mediterranean countries. Therefore, active clusters of leprosy persist in Europe, particularly in Spain, Greece, Portugal, and Italy.


Assuntos
Eritema Nodoso , Hipersensibilidade , Hanseníase Virchowiana , Hanseníase Multibacilar , Hanseníase , Idoso , Europa (Continente) , Feminino , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico
6.
PLoS Negl Trop Dis ; 15(6): e0009495, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34125854

RESUMO

BACKGROUND: This study evaluates implementation strategies for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzes immunoepidemiological aspects and follow-up of individuals living in a presumptively nonendemic area in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Quasi-experimental study based on LSQ throughout Jardinópolis town by community health agents, theoretical-practical trainings for primary care teams, dermatoneurological examination, anti-PGL-I serology, RLEP-PCR, and spatial epidemiology. A Leprosy Group (LG, n = 64) and Non-Leprosy Group (NLG, n = 415) were established. Overall, 3,241 LSQs were distributed; 1,054 (32.5%) LSQ were positive for signs/symptoms (LSQ+). Among LSQ+ respondents, Q2-Tingling (pricking)? (11.8%); Q4-Spots on the skin? (11.7%); Q7-Pain in the nerves? (11.6%); Q1-Numbness in your hands and/or feet? (10.7%) and Q8-Swelling of hands and feet? (8.5%) were most frequently reported symptoms. We evaluated 479 (14.8%) individuals and diagnosed 64 new cases, a general new case detection rate (NCDR) of 13.4%; 60 were among 300 LSQ+ (NCDR-20%), while 4 were among 179 LSQ negative (NCDR-2.23%). In LG, Q7(65%), Q2(60%), Q1(45%), Q4(40%) and Q8(25%) were most frequent. All 2x2 crossings of these 5 questions showed a relative risk for leprosy ranging from 3 to 5.8 compared with NLG. All patients were multibacillary and presented hypochromatic macules with loss of sensation. LG anti-PGL-I titers were higher than NLG, while 8.9% were positive for RLEP-PCR. The leprosy cases and anti-PGL-I spatial mappings demonstrated the disease spread across the town. CONCLUSIONS/SIGNIFICANCE: Implementation actions, primarily LSQ administration focused on neurological symptoms, indicate hidden endemic leprosy in a nonendemic Brazilian state.


Assuntos
Agentes Comunitários de Saúde/educação , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Mycobacterium leprae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Prevalência , Inquéritos e Questionários
7.
Nat Immunol ; 22(7): 839-850, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34168371

RESUMO

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.


Assuntos
Hanseníase Virchowiana/imunologia , Hanseníase Tuberculoide/imunologia , Mycobacterium leprae/imunologia , Pele/imunologia , Adolescente , Adulto , Idoso , Feminino , Fibroblastos/imunologia , Fibroblastos/microbiologia , Fibroblastos/patologia , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Queratinócitos/patologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Hanseníase Tuberculoide/genética , Hanseníase Tuberculoide/microbiologia , Hanseníase Tuberculoide/patologia , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , RNA-Seq , Análise de Célula Única , Pele/microbiologia , Pele/patologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Linfócitos T/patologia , Transcriptoma
8.
PLoS Negl Trop Dis ; 15(5): e0009382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939710

RESUMO

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Adulto Jovem
9.
J Pak Med Assoc ; 71(3): 838-842, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057932

RESUMO

OBJECTIVE: To determine the occurrence and characteristics of the two types of lepra reactions in new leprosy cases at initial diagnosis. Methods: The retrospective descriptive study was conducted at the Marie Adelaide Leprosy Centre, Karachi, and comprised all new leprosy cases registered from January 1, 2016, to June 30, 2018. Data was collected from the medical record database using a predesigned proforma. RESULTS: Of the 50 cases, 2(4%) were children and 48 (96%) were adults, with overall age ranging from 12 to 85 years. There were 41(82%) males and 9(18%) females.. Of the total, 30(60%) cases presented with type 1 reaction and 20(40%) with type 2. Further, 30(60%) cases were classified as borderline lepromatous. Among them, 17(57%) had type 2 reaction. Inflamed plaques were the main feature in 27(90%) cases of type 1. Crops of painful, erythematous nodules were seen in 19(95%) cases of type 2. Conclusion: Lepra reactions were found to be a presenting feature in a significant number of new leprosy cases at initial diagnosis.


Assuntos
Hanseníase , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Grupos Étnicos , Feminino , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Retrospectivos , Adulto Jovem
10.
Front Immunol ; 12: 661135, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017337

RESUMO

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67-198.21, p = 5.3447 × 10-7), SJS-TEN (OR = 36.00, 95% CI = 3.19-405.89, p = 2.1657 × 10-3), and DRESS (OR = 40.50, 95% CI = 6.38-257.03, p = 1.0784 × 10-5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67-149.52, p = 2.8068 × 10-7) and Taiwanese (OR = 31.50, 95% CI = 4.80-206.56, p = 2.5519 × 10-3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.


Assuntos
Alelos , Dapsona/efeitos adversos , Antígenos HLA-B/genética , Polimorfismo Genético , Pele/efeitos dos fármacos , Pele/patologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Criança , Pré-Escolar , Sistema Enzimático do Citocromo P-450/genética , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Antígenos HLA-B/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Estudos Prospectivos , Adulto Jovem
11.
Rev Bras Enferm ; 74(1): e20200649, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33886930

RESUMO

OBJECTIVES: to analyze activity limitations in patients with leprosy and their association to cognition and neuropsychiatric symptoms. METHODS: this cross-sectional design study included sixty patients with multibacillary leprosy assisted at a reference center. Participants were divided according to their physical disability and submitted to instruments assessing daily activities (basic and instrumental), cognitive functions, and neuropsychiatric symptoms. The order of the instruments was random to avoid any interference of test sequence on the results. RESULTS: fifty-five percent of the participants presented physical disabilities. All patients were independent in performing basic activities but sixty-six percent presented difficulties in performing instrumental activities. Cognitive decline and neuropsychiatric symptoms were seen in advanced stages of the disease, but they were more associated to patient age than to leprosy. CONCLUSIONS: leprosy patients presented physical disabilities and difficulties in performing instrumental daily activities. Cognitive decline and neuropsychiatric symptoms were more associated to aging than to leprosy itself.


Assuntos
Atividades Cotidianas , Sintomas Comportamentais/epidemiologia , Transtornos Cognitivos/epidemiologia , Cognição/fisiologia , Hanseníase/complicações , Transtornos Mentais/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
12.
J Pediatr Urol ; 17(4): 536.e1-536.e7, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33827777

RESUMO

INTRODUCTION: Early orchidopexy has been linked to improved long term outcomes of fertility and reduced malignancy rates. However, the optimal age of intervention has been subject to change over the years. OBJECTIVE: This study aims to study males aged 6 months or less who undergo laparoscopic assisted orchidopexy for intraabdominal testes to establish the safety, efficacy, and benefit in the defined age group. STUDY DESIGN: We prospectively assessed 19 boys at or below 6 months of age, who had laparoscopic assisted orchidopexy for intraabdominal undescended testes at Salmaniya Medical Complex in Bahrain between January 2014 and December 2018. We examined: demographics, laterality, testicular locations, testicular volumes, operative time, complications, and durations of hospitalization and follow-up. Ultrasound-derived testicular volumes were assessed before and after orchidopexy. They were calculated using the Hansen formula (Testicular volume = 0.52 × length [L] × width [W]2 [1]. They were then compared with reference ranges from a Dutch cohort study of 769 healthy boys. Successful outcomes were correct intrascrotal position with minimal complications and normal testicular volumes. RESULTS: A total of 19 males were operated at a mean age of 5.6 months and followed for a mean of 2.35 years. Of these, 7 had left-sided and 12 had right-sided cryptorchidism. Testicular locations were noted intra-operatively; 10 were above the internal ring, 5 near the iliac vessels, and 4 close to the kidney. The mean operative time was 59.58 minutes. Only 2 minor complications occurred and no cases of testicular atrophy. None of the patients required hospital-stay beyond 24 hours. The success rate was 89.46% in achieving correct scrotal position. Testicular volumes were normal before and after orchidopexy. They significantly increased after orchidopexy (P ≤ 0.05). The testicular growth rate after 24 months was slightly higher than normal. DISCUSSION: In line with previous studies we were 89.46% successful in re-positioning testes [2]. In contrast to studies intervening at older ages which associated intra-abdominal testes with greater risks of complications, we found few minor complications and no testicular atrophy [3,4]. Testicular volumes in the affected testes were normal, contrary to decreased volumes found by other researchers [5]. Limitations of this study are the small number of patients and short follow-up which limits assessment of long-term outcomes. CONCLUSION: Early orchiopexy is safe and effective. Laparoscopic assisted orchidopexy at an early age was beneficial and resulted in normal testicular volumes before and after surgery.


Assuntos
Criptorquidismo , Laparoscopia , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Criptorquidismo/cirurgia , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Orquidopexia , Estudos Retrospectivos , Testículo/cirurgia , Resultado do Tratamento
13.
J Manag Care Spec Pharm ; 27(4): 455-468, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33769850

RESUMO

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/economia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos , Adulto Jovem
14.
BMC Infect Dis ; 21(1): 282, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740912

RESUMO

BACKGROUND: Brazil has a high leprosy burden and poor treatment outcomes (TOs), manifesting in high relapse rates. Pernambuco, an impoverished Brazilian state suffering notable geographical health inequalities, has 'hyperendemic' leprosy. Although current literature identifies barriers and facilitators influencing leprosy treatment compliance, inadequate investigation exists on other factors influencing TOs, including carers' roles and psycho-dermatological impact. This qualitative study explores experiences and perceptions of leprosy patients and their carers in Pernambuco, Brazil; to identify location-specific factors influencing TOs, and consequently inform future management. METHODS: 27, semi-structured, in-depth interviews were conducted with 14 patients and 13 carers. Participants were recruited using maximum variation and snowball sampling from three clinics in Petrolina, Pernambuco. Transcripts and field notes from both participant groups were separately analysed using conventional thematic and deviant case analysis. The University of Birmingham Internal Research Ethics Committee and Instituto Lauro de Souza Lima provided ethical approval. RESULTS: Two homologous sets of four, primary, interdependent themes influencing leprosy TOs emerged: 'personal factors'; 'external factors'; 'clinical factors'; and 'the healthcare professional (HCP)-patient-carer relationship'. Poor participant knowledge and lack of symptomatic relief caused patients to distrust treatment. However, because participants thought HCP-led interventions were vital for optimal TOs, patients were effectively persuaded to adhere to pharmaceutical treatments. High standard patient and population education facilitated treatment engagement by encouraging evidence-based medicine belief, and dispelling health myths and stigma. Healthcare, on occasions, was perceived as disorganised, particularly in resource-scarce rural areas, and for those with mental health needs. Participants additionally experienced incorrect/delayed diagnoses and poor contact tracing. Leprosy's negative socio-economic impact on employment - together with stigma, dependency and changing relationships - caused altered senses of identity, negatively impacting TOs. Better dialogue between patients, HCPs and carers facilitated individualised patient support. CONCLUSION: This study highlights the importance of: effective evidence-based leprosy education; communication between HCPs, patients and carers; state-funded support; and healthcare resource distribution. These findings, if prioritised on governmental scales, provide the valuable insight needed to inform location-specific management strategies, and consequently improve TOs. Future research should evaluate the effectiveness of these implementations. Failure to address these findings will hinder regional elimination efforts.


Assuntos
Cuidadores/psicologia , Pessoal de Saúde/psicologia , Hanseníase/terapia , Pacientes/psicologia , Adulto , Idoso , Brasil , Feminino , Humanos , Entrevistas como Assunto , Conhecimento , Hanseníase/diagnóstico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Percepção , Retratamento , Adulto Jovem
15.
Neurol India ; 69(1): 140-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642286

RESUMO

Background: Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored. Objective: We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)]. Results: Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P < 0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%. Conclusion: These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity.


Assuntos
Hemossiderina , Vasculite , Idoso , Biópsia , Ferrocianetos , Humanos , Nervos Periféricos , Vasculite/diagnóstico
16.
PLoS Negl Trop Dis ; 15(3): e0009214, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33690671

RESUMO

BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Aldeídos , Antioxidantes , Carga Bacteriana , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae , Estresse Oxidativo , Carbonilação Proteica , Pele/metabolismo , Pele/patologia
17.
PLoS Negl Trop Dis ; 15(3): e0009201, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33725010

RESUMO

BACKGROUND: This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability. CONCLUSIONS/SIGNIFICANCE: A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy.


Assuntos
Erradicação de Doenças , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Tempo , Adulto Jovem
18.
Front Immunol ; 12: 647385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777045

RESUMO

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Senescência Celular/imunologia , Memória Imunológica , Imunossenescência/imunologia , Hanseníase/imunologia , Mycobacterium leprae , Dermatopatias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Antígenos CD/genética , Estudos de Casos e Controles , Citomegalovirus/imunologia , Feminino , Expressão Gênica , Humanos , Imunoglobulina G/sangue , Hanseníase/sangue , Hanseníase/microbiologia , Hanseníase/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Pele/imunologia , Pele/patologia , Dermatopatias/sangue , Dermatopatias/microbiologia , Dermatopatias/patologia , Adulto Jovem
19.
Medicine (Baltimore) ; 100(5): e23839, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592840

RESUMO

ABSTRACT: Non-tuberculous mycobacteria (NTM) comprise mycobacteria, with the exceptions of Mycobacterium (M.) leprae and the M. tuberculosis complex. Septic arthritis caused by NTM is so rare that there is no standardized treatment.Between April and September 2012, 27 patients were infected with M. massiliense in a single clinic following injection of steroid in the knee joint. Clinical data of 9 patients who received arthroscopic treatment in Seoul Hospital of Soonchunhyang University were analyzed retrospectively.Arthroscopic irrigation and debridement were performed average 2.6 times (1-3 times). As 6 out of 9 cases (67%) had joint contracture of the knee joint, arthroscopic adhesiolysis, and brisement were performed. After surgical procedures, Hospital for Special Surgery and Lysholm knee score showed improvement compared before the surgery, but a radiographic result evaluated by Kellgren-Lawrence revealed that 6 cases got deteriorated to stage 4 in the 4-year follow-up.NTM septic arthritis had a higher recurrence and a higher contracture incidence than septic arthritis caused by tuberculous mycobacteria or other bacteria. Treatment was possible with repeated arthroscopic debridement and intravenous antibiotics.


Assuntos
Artrite Infecciosa/cirurgia , Artroscopia/métodos , Injeções Intra-Articulares/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/cirurgia , Mycobacterium abscessus , Idoso , Artrite Infecciosa/induzido quimicamente , Artrite Infecciosa/microbiologia , Surtos de Doenças , Feminino , Humanos , Articulação do Joelho/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/induzido quimicamente , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
20.
Int J Infect Dis ; 105: 261-266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33592342

RESUMO

BACKGROUND: Evidence suggests that biological mechanisms involved in helminth infections and vitamin deficiencies increase susceptibility to other infections. The aim of this study was to investigate the associations of helminth co-infection and select micronutrient deficiencies with leprosy using a case-control design. METHODS: From 2016 to 2018, individuals aged ≥3 years were recruited at clinics in and around Governador Valadares, Minas Gerais, Brazil in three groups: cases of leprosy, household contacts and community-matched (non-contact) controls. Helminths were diagnosed through stool Kato Katz examination and serum reactivity to anti-soluble adult worm antigen preparation IgG4. Serum ferritin, 25-OH vitamin D and retinol concentrations were measured. Multi-variate logistic regression was conducted to identify associations with active leprosy. RESULTS: Seventy-nine cases of leprosy, 96 household contacts and 81 non-contact controls were recruited; 48.1% of participants were male with a median age of 40 years. Helminths were found in 7.1% of participants on Kato Katz test, all but one of which were Schistosoma mansoni, and 32.3% of participants were positive for S. mansoni serology. On multi-variate analysis, cases were more likely to be infected with helminths (diagnosed by stool) than household contacts [adjusted odds ratio (aOR) 8.69, 95% confidence interval (CI) 1.50-50.51]. Vitamin D deficiency was common, and was more likely in cases compared with non-contact controls (aOR 4.66, 95% CI 1.42,-15.33). Iron deficiency was not associated with leprosy, and vitamin A deficiency was not detected. CONCLUSION: These associations suggest that the immune consequences of schistosomiasis and vitamin D deficiency may increase the risk of active leprosy. Comorbid conditions of poverty deserve further study as addressing co-infections and nutritional deficiencies could be incorporated into programmes to improve leprosy control.


Assuntos
Coinfecção/complicações , Helmintos/fisiologia , Hanseníase/complicações , Mycobacterium leprae/fisiologia , Deficiência de Vitamina D/complicações , Adolescente , Adulto , Idoso , Animais , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Fezes/parasitologia , Feminino , Humanos , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
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