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OBJECTIVE: The objective of this study was to assess the perceived risk of breast cancer (BC) and adoption of risk reduction behaviours among female first-degree relatives (FDRs) of BC patients attending care at the Uganda Cancer Institute (UCI). METHODS: A cross-sectional study was performed using a questionnaire to collect data between March to October 2019. Adult female FDRs of patients attending care at UCI were recruited consecutively. Breast cancer perceived risk was assessed using a verbal measure; 'My chances of getting BC are great' on a Likert scale with 5 response alternatives. Chi square tests and modified Poisson regression using generalised estimating equations model were used to determine associations and examine factors associated with perceived risk of BC. RESULTS: We enrolled 296 FDRs from 186 female BC patients. Few participants 118/296 (40%) had high perceived risk of BC. Majority 165/296 (56%), had ever practiced breast self-examination. At the multivariable modified Poisson GEE model, women aged 36-45 years were more likely to perceive themselves to be at high risk of developing BC compared to women aged 18-25 years (adjusted prevalence ratio: 1.174; 95% confidence interval [95%CI] = 1.05-2.88; p value = 0.030) after adjusting for age, religion, educational level and residence. CONCLUSION: Few FDRs of BC patients perceived themselves to be at high risk of developing BC and do not seek risk reduction measures including screening and early diagnosis approaches. Breast cancer health education especially targeting younger women should emphasize the increased risk of BC in FDRs.
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Neoplasias da Mama , Adulto , Humanos , Feminino , Adolescente , Adulto Jovem , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico , Estudos Transversais , Uganda/epidemiologia , Comportamento de Redução do Risco , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde , Fatores de RiscoRESUMO
Introduction: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the rapid adoption of telehealth to provide HIV care and treatment. However, limited information exists about the feasibility, acceptability, and efficacy of telehealth interventions at different points of the HIV care continuum. Methods: A systematic search was conducted of Ovid MEDLINE, PsycINFO, and CINAHL databases to synthesize evidence regarding the feasibility, acceptability, and efficacy of videoconferencing and video-based interventions for HIV testing and treatment in adult populations. Seventeen articles published through July 2021 were included in the review. We used descriptive methods to analyze data, and findings were reported using frequencies and percentages. Results: Findings show that videoconferencing and video-based interventions are generally feasible and acceptable. Videoconferencing is effective in improving adherence to HIV treatment and in promoting HIV testing. In addition, video-based interventions were effective in promoting HIV testing, treatment initiation, and adherence to medication. Both modalities enhanced linkage and retention in treatment for HIV-positive patients. Conclusions: Video-based and videoconferencing interventions are beneficial in HIV testing and treatment. However, the scarcity of primary studies employing these telehealth modalities means that there is a need for more research in these areas. Also, reviewed studies suffered from several limitations, including reliance on subjective measures, lack of standardized ways of evaluating acceptability and feasibility, use of small sample sizes, and short follow-up durations. In addition, there was less representation of studies from resource-limited settings disproportionately affected by HIV and AIDS. Thus, future research should focus on addressing these challenges.
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COVID-19 , Infecções por HIV , Telemedicina , Humanos , Adulto , Estudos de Viabilidade , COVID-19/diagnóstico , SARS-CoV-2 , Telemedicina/métodos , Teste de HIV , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: Involuntary childlessness is a global phenomenon that negatively impacts the couple, or the family involved. The experiences of women living with involuntary childlessness have not been well documented in the literature, specifically in the Ugandan context. The purpose of the study was to explore the experiences of women living with involuntary childlessness in Uganda. METHODS: A qualitative phenomenological approach was used. Fifteen in-depth interviews were conducted among women experiencing involuntary childlessness attending a National Referral Hospital. Purposive sampling was, and data saturation determined the actual sample size. Thematic analysis was used for data analysis. The results are presented in the form of text and narrative quotes from participants. RESULTS: Six themes emerged (i) Inadequate social support (ii) psychological torture (iii) continued grief (iv) marital instability (v) failure attributed to childlessness and (vi) financial constraints. Inadequate social support was in the form of having an unsupportive partner, altered social relation, and altered social status, while women experienced name-calling, emotional abuse, stigma, and blame under the psychological torture theme. Women experienced feelings of distress and grief, including anger, irritability, sadness, stress, and feelings of despair. Women with involuntary childlessness recounted experiencing unstable marriages characterized by infidelity, divorce, abandonment, and polygamous marriages. Some women coped positively, while others employed negative coping strategies such as social withdrawal and isolation. Women who their partners and families well supported coped positively. In contrast, those who did not receive as much support were stressed, sad, angry, and had lost hope of pregnancy. CONCLUSIONS: In this study, women with involuntary childlessness lacked social support amidst experiences of marital turmoil, psychological torture, feelings of distress and grief, unfulfilled motherhood expectations, and financial constraints while seeking treatment, therefore, there is a need to screen the women for psychological / mental illness symptoms and provide empathetic care and counseling. The prevalence of involuntary childlessness is not well documented in Uganda and a study can be done to determine its extent.
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Adaptação Psicológica , Infertilidade Feminina , Gravidez , Humanos , Feminino , Uganda , Infertilidade Feminina/psicologia , Emoções , Pesquisa QualitativaRESUMO
This study investigates the impacts of the first wave of the COVID-19 pandemic on smallholder farmers and their coping strategies in three contrasting Low- and Middle-Income Countries. The case studies include Brazil (South region), Madagascar (Atsimo Atsinanana region), and Tanzania (Morogoro/Eastern Tanzania). These countries were chosen because i) the economies are strongly influenced by the agricultural sector; ii) their national food security is strongly affected by smallholder production, and, iii) they represent a set of contrasting government responses to COVID-19 including the denial of the pandemic. Data were collected through semi-structured household interviews in all three countries in rural areas. COVID-19 induced effects were found in all three countries, including in Brazil and Tanzania where both national governments initially neglected the existence of COVID-19 and introduced few containment measures only. Here, mobility and trade restrictions of other countries impact also on agricultural trade and production in countries in which governments took less action to COVID-19 and also people remained home and practiced social distancing even if no official government policy was issued. The findings in all three countries suggest that the COVID-19 crisis had negatively affected smallholders' agricultural production, leading to a vicious cycle of low production, low incomes, and higher food insecurity. Results of this study raise the thorny issue of how best to balance containment of pandemic and future shocks against the well-being of the vulnerable rural population in lower- and middle-income countries; especially considering also the degree of global interconnected and the potential of polices to effect people beyond the national scale.
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BACKGROUND: HIV testing among men in sub-Saharan Africa is sub-optimal. Despite several strategies to improve access to underserved populations, evidence regarding engaging men in professional and formal occupations in HIV testing is limited. This study explored employed professional men's preferences for uptake of HIV self-testing, and linkage to HIV care, or prevention services. METHODS: This was an explorative-descriptive qualitative study where a sample of 33 men from six Ugandan urban centres. Participants were purposively selected guided by the International Standard Classification of Occupations to participate in in-depth interviews. The data were collected using an interview guide and the sample size was determined by data saturation. Eligibility criteria included fulltime formal employment for over a year at that organization. The data were analyzed manually using thematic content analysis. RESULTS: Three categories emerged: uptake of HIV self-tests, process of HIV self-testing and linkage to post-test services. The different modes of distribution of HIV self-test kits included secondary distribution, self-tests at typically male dominated spaces, delivery to workplaces and technology-based delivery. The process of HIV self-testing may be optimized by providing collection bins, and mHealth or mobile phone applications. Linkage to further care or prevention services may be enhanced using medical insurance providers, giving incentives and tele counselling. CONCLUSION: We recommend utilization of several channels for the uptake of HIV self-tests. These include distribution of test kits both to offices and men's leisure and recreation 'hot spots', Additionally, female partners, peers and established men's group including social media groups can play a role in improving the uptake of HIV self-testing. Mobile phones and digital technology can be applied in innovative ways for the return of test results and to strengthen linkage to care or prevention services. Partnership with medical insurers may be critical in engaging men in professional employment in HIV services.
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Infecções por HIV , Autoteste , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Humanos , Masculino , Homens , Ocupações , Pesquisa QualitativaRESUMO
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease, patients with MS can present higher risk of infections. PURPOSE: This study aimed to investigate the prevalence of Candida spp. in the oral cavity of MS patients in relation to a control group METHODS: In total, 100 individuals were selected: 55 diagnosed with MS and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture media selecting for Candida. Following an incubation period of 48 h, colony-forming units (CFU mL-1) were counted and colonies were isolated for Candida species identification by multiplex PCR. The results were analysed by chi-squared and Mann-Whitney U statistical tests considering a significance level of 5%. RESULTS: Candida spp. were confirmed in the oral cavity of 50.09% patients in the MS group and 35.55% individuals in the control group. In individuals positive for the growth of Candida spp., the median values of Candida colonies were 220 CFU mL-1 for the MS group and 120 CFU mL-1 for the control group. However, no statistically significant differences were observed between groups for both prevalence and CFU mL-1 count. Of the Candida species identified, 73.91% were C. albicans, 21.73% C. glabrata, 2.17% C. tropicalis, and 2.17% C. krusei. CONCLUSIONS: The colonization of Candida spp. in the oral cavity of individuals with multiple sclerosis was higher than in the control group; however these findings were not proven to be statistically significant.
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Candida , Boca/microbiologia , Esclerose Múltipla , Candida/isolamento & purificação , Candida albicans , Candida glabrata , Candida tropicalis , Estudos de Casos e Controles , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/microbiologia , Pichia , SalivaRESUMO
The World Health Organization declared 2020 the Year of the Nurse and the Midwife well before the world was plunged into a pandemic response to SARS-CoV-2 (COVID-19). Worldwide, nurses are advancing critical research and policy efforts to achieve all 17 of the United Nations Sustainable Development Goals (SDGs). Nursing is best positioned to ask and answer how to achieve the SDGs over the next decade, and in this COVID-19 era. In this article, we summarize the state of the nursing and midwifery literature about the SDGs. Twenty-four publications met criteria for inclusion, with nearly half published in 2019. Findings emphasize a need for: (a) nursing curricula and training revisions to include SDG content and strengthen development of a future nursing workforce comprised of global citizens; (b) innovative and disruptive nursing research documenting advances toward achieving the SDG 2030 agenda; (c) nursing practice that operates within a SDG framework; and (d) responsive and proactive nursing policy development that foresees what is needed to achieve the SDGs. When the urgency of COVID-19 response subsides, the world will adjust to a new normal and nursing must be positioned to lead and contribute to micro- and macro-level efforts toward achieving the SDGs.
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Infecções por Coronavirus/epidemiologia , Enfermagem , Pneumonia Viral/epidemiologia , Desenvolvimento Sustentável , COVID-19 , Humanos , Liderança , Pesquisa em Enfermagem , PandemiasRESUMO
BACKGROUND: Worldwide, HIV remains a major public health challenge, especially in Sub-Saharan Africa. Literature indicates that men's involvement in HIV testing, care, and treatment services is lower compared to women, therefore novel approaches are required to engage men in the cascade of HIV care. This study aimed to explore men's perception on the provision of HIV testing services in venues where English Premier League football games are televised. METHODS: An exploratory qualitative study was conducted between February and May 2018. Six focus group discussions were conducted with 50 conveniently selected men aged 18 years and older using a pre-tested discussion guide. All focus group discussions were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: Overall, HIV testing at venues telecasting English Premier League football games was acceptable to men. There was a very strong preference for health workers providing testing and counseling services be external or unknown in the local community. Possible motivators for testing services provided in these settings include subsidizing or eliminating entrance fee to venues telecasting games, integrating testing and counseling with health promotion or screening for other diseases, use of local football games as mobilization tools and use of expert clients as role models. CONCLUSIONS: This study suggests that HIV testing services at venues where EPL football games are televised is generally acceptable to men. In implementing such services, consideration should be given to preferences for external or unknown health workers and the motivating factors contributing to the use of these services. Given that HIV testing is currently not conducted in these settings, further research should be conducted to evaluate the feasibility of this approach as a means of enhancing HIV testing among Ugandan men.
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Infecções por HIV/prevenção & controle , Promoção da Saúde/métodos , Programas de Rastreamento/psicologia , Homens/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Futebol , Adulto , Idoso , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Uganda , Adulto JovemRESUMO
BACKGROUND: Despite advancement in Prevention of Mother to Child Transmission (PMTCT) services, the rate of MTCT of HIV in sub-Saharan Africa is still high. This is partly due to low retention of HIV positive mothers in HIV care. We sought to determine the level of retention and the factors associated with retention among HIV positive pregnant and breastfeeding mothers following accreditation of an antiretroviral therapy (ART) clinic to offer full time ART services in one of the lower health facilities in rural Western Uganda. METHODS: This study was a mixed methods study conducted in 5 health centres in rural Western Uganda from 10th April to 10th May 2017. A total of 132 retained and non-retained HIV positive pregnant and breastfeeding mothers were recruited. A Mother was categorized as retained if she had not missed her ART appointments at antenatal or postnatal clinic for ≥3 consecutive months. Questionnaires were administered and four focus group discussions were held. We used descriptive statistics to understand characteristics of mothers and their levels of retention. Thematic analysis was used to analyze qualitative data. RESULTS: About a third (35.6%) of the mothers were aged 18-24 with a median age of 26 (IQR 23, minimum age of 16 and maximum age of 39). More than half, 73 (55.3%) of all mothers were in HIV care for 3-24 months and about 116(87.9%) of all mothers were retained in HIV care. This was an improvement from 53% reported in 2015. We found lack of formal education, lack of disclosure of HIV status to the spouse, perceived lack of confidentiality and self stigmatization as factors hindering retention. The desire to have an HIV free baby, fear of death and opportunistic infections, support from significant others and community groups were factors associated with retention. CONCLUSIONS: We observed improved retention in lower health centres and to achieve 100% retention, we recommend interventions such as sensitizing HIV positive mothers on disclosure of HIV status to spouse, maintaining confidentiality of client information at the clinic, support to girl child education and formation of community support groups. TRIAL REGISTRATION: This study was retrospectively registered with the Uganda National Council for Science and Technology (UNCST), registration receipt number 10961 on the 9th March, 2018.
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Aleitamento Materno/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães/psicologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Serviços de Saúde Rural/organização & administração , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Grupos Focais , Humanos , Lactente , Recém-Nascido , Mães/estatística & dados numéricos , Gravidez , Uganda , Adulto JovemRESUMO
We experimentally implement a compressive Raman technology (CRT) that incorporates chemometric analysis directly into the spectrometer hardware by means of a digital micromirror device (DMD). The DMD is a programmable optical filter on which optimized binary filters are displayed. The latter are generated with an algorithm based on the Cramer-Rao lower bound. We compared the developed CRT microspectrometer with two conventional state-of-the-art Raman hyperspectral imaging systems on samples mimicking microcalcifications relevant for breast cancer diagnosis. The CRT limit of detection significantly improves, when compared to the CCD based system, and CRT ultimately allows 100× and 10× faster acquisition speeds than the CCD- and EMCCD-based systems, respectively.
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Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Calcinose , Algoritmos , Feminino , Humanos , Análise Espectral RamanRESUMO
Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.
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Vírus BK/isolamento & purificação , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Infecções por Polyomavirus/virologia , Eliminação de Partículas Virais , Sangue/virologia , Humanos , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla/complicações , Natalizumab/efeitos adversos , Urina/virologiaRESUMO
BACKGROUND: Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children. METHODS: A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1. RESULTS: Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent's HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status. CONCLUSIONS: Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level.
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Atitude Frente a Saúde , Revelação/estatística & dados numéricos , Infecções por HIV/psicologia , Pais/psicologia , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Medo/psicologia , Feminino , Infecções por HIV/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Relações Pais-Filho , Pobreza , Prevalência , Pesquisa Qualitativa , Inquéritos e Questionários , Uganda/epidemiologia , População Urbana , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The bronchoscopic microsample (BMS) probe allows direct epithelial lining fluid (ELF) level measurement without saline lavage. We investigated whether cytokine levels in ELF from a BMS differed from those obtained by bronchoalveolar lavage (BAL) in stable and acute lung disease. METHODS: In a single-centre, prospective observational cohort study of 45 patients, a sequential BMS probe procedure and BAL were performed on patients with stable chronic obstructive lung disease, interstitial lung disease, acute lung injury (ALI), burns-related inhalational injury or controls. ELF samples were assayed for IL-1ß, IL-6, IL-8, TNF-α and G-CSF. RESULTS: Both bronchoscopic microsampling and BAL showed significantly higher cytokine levels in the ELF from patients with ALI and burns-related inhalational injury than from those with chronic stable lung disease. The BMS method detected cytokine levels approximately 20- to 80-fold higher than the corresponding BAL (uncorrected for dilution). The ratio of BMS and BAL cytokine levels was as follows: the ratio for IL-1ß [mean 55, 95% confidence interval (CI) 34-88] was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.015) and IL-8 (mean 13, 95% CI -5 to 36, p = 0.03). The ratio for G-CSF (mean 43, 95% CI 24-75) was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.008). CONCLUSIONS: The BMS probe safely collects ELF with higher equivalent inflammatory cytokine concentrations than via BAL from patients with both acute and chronic lung disease and can be an alternative to saline BAL. Variations in cytokine concentrations between BMS and BAL and sampling-site differences warrant further study.
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Lesão Pulmonar Aguda/metabolismo , Lavagem Broncoalveolar , Broncoscopia/métodos , Queimaduras por Inalação/metabolismo , Citocinas/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Manejo de Espécimes/métodos , Adulto JovemRESUMO
OBJECTIVES: Data from North European rheumatoid arthritis (RA) populations has suggested a particularly strong association of gene-environment interaction between smoking and HLA-DRB1 shared epitope (SE) with antibodies to citrullinated α-enolase (CEP-1) and vimentin (cVim) peptides. We investigated this further by examining anticitrullinated peptide/protein antibody (ACPA) fine specificity in a Korean cohort, where there are notable differences in the RA-associated HLA-DRB1 alleles. METHODS: Antibodies to fibrinogen (cFib), α-enolase (CEP-1) and vimentin (cVim) peptides and cyclic citrullinated peptide (CCP) were measured in 513 cases. The Mann-Whitney U test was used to compare antibody levels. Logistic regression generated ORs for RA in a case-control analysis with 1101 controls. Association of ACPA status and erosion in patients with RA was examined by logistic regression. RESULTS: Anti-CCP, CEP-1, cVim and fibrinogen peptides were found in 86.7%, 63.9%, 45.5% and 74.7%, respectively. The number of ACPA and their levels were associated with SE, with evidence of a gene-dosage effect. There was a particular association of smoking with levels of anti-CEP-1. However, a gene-environment interaction was associated with all the ACPA positive subgroups, albeit the highest OR was seen with the anti-CCP+/cVim+ subset. In the absence of SE, smoking only conferred risk for anti-CCP negative subsets. The presence of erosions was not associated with the number of positive ACPA or specificity. CONCLUSIONS: The SE governed the magnitude and diversity of the ACPA response, but its interaction with smoking did not exclusively segregate with any of the ACPA specificities studied here. Smoking was associated with RA by SE-dependent and independent effects.
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Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Citrulina/imunologia , Cadeias HLA-DRB1/imunologia , Fumar/imunologia , Adulto , Especificidade de Anticorpos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/etiologia , Artrite Reumatoide/genética , Estudos de Casos e Controles , Epitopos/imunologia , Medicina Baseada em Evidências/métodos , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Genótipo , Cadeias HLA-DRB1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Fosfopiruvato Hidratase/imunologia , Radiografia , Fumar/efeitos adversos , Fumar/genética , Vimentina/imunologiaRESUMO
BACKGROUND: Studies suggest that periodontitis may be a risk factor for rheumatoid arthritis (RA). The purpose of this study was to determine whether periodontitis is associated with autoantibodies characteristic of RA. METHODS: Serum samples were tested for anti-cyclic citrullinated peptide (CCP), anti-mutated citrullinated vimentin (MCV), anti-citrullinated α-enolase peptide-1 (CEP-1), anti-citrullinated vimentin (cit-vim), anti-citrullinated fibrinogen (cit-fib) and their uncitrullinated forms anti-CParg (negative control for anti-CCP), anti-arginine-containing α-enolase peptide-1 (REP-1), anti-vimentin and anti-fibrinogen antibodies in patients with and without periodontitis, none of whom had RA. RESULTS: Periodontitis, compared with non-periodontitis, was associated with a normal frequency of anti-CCP and anti-MCV (â¼1%) but a higher frequency of positive anti-CEP-1 (12% vs 3%; p=0.02) and its uncitrullinated form anti-REP-1 (16% vs 2%; p<0.001). Positive antibodies against uncitrullinated fibrinogen and CParg were also more common among those with periodontitis compared to non-periodontitis patients (26% vs 3%; p<0.001, and 9% vs 3%; p=0.06). After adjusting for confounders, patients with periodontitis had 43% (p=0.03), 71% (p=0.002) and 114% (p<0.001) higher anti-CEP-1, anti-REP-1 and anti-fibrinogen titres, compared with non-periodontitis. Non-smokers with periodontitis, compared with non-periodontitis, had significantly higher titres of anti-CEP-1 (103%, p<0.001), anti-REP-1 (91%, p=0.001), anti-vimentin (87%, p=0.002), and anti-fibrinogen (124%, p<0.001), independent of confounders, confirming that the autoantibody response in periodontitis was not due to smoking. CONCLUSIONS: We have shown that the antibody response in periodontitis is predominantly directed to the uncitrullinated peptides of the RA autoantigens examined in this study. We propose that this loss of tolerance could then lead to epitope spreading to citrullinated epitopes as the autoimmune response in periodontitis evolves into that of presymptomatic RA.
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Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Citrulina/imunologia , Periodontite/imunologia , Adulto , Artrite Reumatoide/etiologia , Autoantígenos/imunologia , Autoimunidade/imunologia , Biomarcadores Tumorais/imunologia , Proteínas de Ligação a DNA/imunologia , Feminino , Humanos , Tolerância Imunológica/imunologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Periodontite/complicações , Fosfopiruvato Hidratase/imunologia , Fumar/imunologia , Proteínas Supressoras de Tumor/imunologia , Vimentina/imunologiaRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. OBJECTIVES: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. METHODS: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). RESULTS: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. CONCLUSIONS: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy.
Assuntos
Artrite Reumatoide , Infecções por Bacteroidaceae/imunologia , Hidrolases/genética , Hidrolases/imunologia , Tolerância Imunológica/genética , Porphyromonas gingivalis/imunologia , Adulto , Sequência de Aminoácidos , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/microbiologia , Autoanticorpos/imunologia , Infecções por Bacteroidaceae/metabolismo , Infecções por Bacteroidaceae/microbiologia , Citrulina/metabolismo , Feminino , Humanos , Tolerância Imunológica/imunologia , Masculino , Espectrometria de Massas , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/imunologia , Peptídeos Cíclicos/metabolismo , Periodontite/genética , Periodontite/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/genética , Desiminases de Arginina em ProteínasRESUMO
OBJECTIVES: To evaluate the efficacy and safety of an oral phosphodiesterase 4 inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring symptoms and signs in a pilot study including exploratory investigation of effects of PDE4 inhibition on blood biomarkers of bone biology. METHODS: In this double-blind, placebo-controlled, single-centre, Phase II study, patients with symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID or placebo over 12 weeks. Bath Indices were monitored serially. Patients were followed for 4 weeks after stopping medication. Bone biomarkers were assessed at baseline and day 85. RESULTS: 38 subjects were randomised and 36 subjects completed the study. Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance. The clinical indices returned to baseline values by 4 weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3, osteoprotegrin, or osteocalcin. CONCLUSIONS: Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Talidomida/análogos & derivados , Proteínas Adaptadoras de Transdução de Sinal , Administração Oral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Marcadores Genéticos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Inibidores da Fosfodiesterase 4/efeitos adversos , Projetos Piloto , Ligante RANK/sangue , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Espondilite Anquilosante/patologia , Espondilite Anquilosante/fisiopatologia , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate serum levels of 25(OH) vitamin D in patients with idiopathic inflammatory myopathies (IIM) (polymyositis (PM), dermatomyosistis (DM), inclusion body myositis (IBM) and juvenile DM (JDM)) and to compare these with healthy controls. METHODS: Serum samples from 149 patients with IIM and 290 healthy controls matched for gender and the month of blood sampling were analysed for 25(OH) vitamin D. ORs for vitamin D classes with 95% CI were calculated using a matched (conditional) logistic regression model. Groups were compared by the Kruskal-Wallis test and p values <0.05 were considered significant. RESULTS: Patients with IIM had significantly lower serum levels of 25(OH) vitamin D than healthy controls (median 39 (10-168) nmol/l vs 68 (19-197) nmol/l; p=0.0001). There was no significant difference in vitamin D levels between the myositis subgroups. When vitamin D levels were subclassified into deficient (<50 nmol/l), insufficient (50-74 nmol/l) and normal (≥75 nmol/l), most of the patients with PM (68%), DM (65%) and IBM (53%) had deficient levels compared with only 60 (21%) healthy individuals. In patients with IIM the OR for deficient versus normal was 17.7 (95% CI 8.1 to 38.6) and the OR for insufficient versus normal was 2.4 (95% CI 1.2 to 4.7). CONCLUSIONS: Low serum levels of vitamin D were found in most patients with IIM and may confer a risk factor for developing adult myositis, similar to some other autoimmune diseases.
Assuntos
Miosite/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Idoso , Estudos Transversais , Dermatomiosite/sangue , Dermatomiosite/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite de Corpos de Inclusão/sangue , Miosite de Corpos de Inclusão/epidemiologia , Polimiosite/sangue , Polimiosite/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: Postpartum depression among mothers living with HIV is a significant public health problem due to its effects on engagement in care, HIV disease progression, and an increased risk of mother-to-child transmission of HIV. OBJECTIVE: The objective of this study was to determine the prevalence and factors associated with postpartum depression among mothers living with HIV. DESIGN: The study employed a cross-sectional quantitative research design. METHODS: In this cross-sectional survey, we consecutively recruited 290 participants among mothers attending postnatal, immunization, and family planning clinics at an urban clinic in Uganda. Using an interviewer-administered questionnaire, we collected data on socio-demographics, obstetric, and HIV-related characteristics. Postpartum depression was assessed using the Patient Health Questionnaire version 9. We classified participants with Patient Health Questionnaire version 9 scores of ⩾10 as having postpartum depression. We conducted logistic regression to examine the association between postpartum depression and independent variables. RESULTS: The prevalence of postpartum depression was 15.9%. After controlling for other variables, participants who reported poor male partner support were more likely to experience postpartum depression compared to those who had good partner support (adjusted odds ratio = 4.52, confidence interval = 2.31-8.84, p value < 0.001). CONCLUSION: Mothers living with HIV should be routinely assessed for the presence of depression and male partner support. Health care providers of HIV-infected women should design strategies to promote male partner support for better maternal, infant, and HIV treatment outcomes.
Assuntos
Depressão Pós-Parto , Infecções por HIV , Lactente , Gravidez , Humanos , Feminino , Masculino , Depressão Pós-Parto/epidemiologia , Mães , Prevalência , Uganda/epidemiologia , Estudos Transversais , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/epidemiologiaRESUMO
OBJECTIVE: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH). METHODS: Double-blind, randomized, placebo-controlled trial. RESULTS: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity). CONCLUSIONS: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.