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Primary care physicians are increasingly incorporating screening tools for substance use disorders (SUDs) and referral to treatment into their practice. Despite efforts to provide access to treatment, patients with SUDs remain at an increased risk of mortality, both from overdose and from general medical conditions. Advance care planning (ACP) is recommended for patients with chronic, progressive medical conditions such as malignancies or heart failure. Though SUDs are widely acknowledged to be chronic diseases associated with an increased risk of mortality, there has been little discussion on ACP in this population. ACP is a discussion regarding future care, often including selection of a surrogate decision-maker and completion of an advanced directive. ACP has been associated with better quality of end-of-life and care more consistent with patient preferences. Studies in other vulnerable populations have shown that marginalized and high-risk individuals may be less likely to receive ACP. Similarly, patients with SUDs may employ different decision-makers than that defined by law (i.e., friend vs. family member), increasing the importance of discussing patient values and social structure. Physicians should routinely conduct ACP conversations with patients with SUDs, especially those with chronic, progressive medical conditions and/or severe, uncontrolled substance use disorders.
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Planejamento Antecipado de Cuidados/normas , Relações Médico-Paciente , Transtornos Relacionados ao Uso de Substâncias/terapia , Tomada de Decisão Clínica , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Medição de Risco , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Background: Prior studies have shown that outcomes of hematopoietic stem cell transplantation (HSCT) in human immunodeficiency virus (HIV)-positive patients have been similar to outcomes in HIV-negative patients since effective implementation of highly active antiretroviral therapy by 1998, but they are limited by small sample size or noninclusion of recent data. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 1998 to 2012 for HSCT, using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code 41.0. HIV-positive patients were identified by the presence of ICD-9-CM diagnostic codes 042, 043, 044, V08, and 079.53. The primary outcome was in-hospital mortality rate, and the secondary outcome the in-hospital complication rate of HSCT. Outcomes were assessed by means of univariate, multivariate regression and matched-pair analysis. Results: A total of 39517 patients who underwent HSCT were identified. Among these, 108 patients had HIV infection. There were no differences in in-hospital mortality rates or rates of intubation, sepsis, bacteremia, or graft-vs-host disease between HIV-positive and HIV-negative patients after allogeneic or autologous HSCT. In allogeneic HSCT, HIV-positive patients had a significantly higher incidence of nontuberculous mycobacterial and cytomegalovirus infection than HIV-negative patients. Conclusion: Although HIV-positive patients may have a higher risk of certain opportunistic infections, they are not at higher risk of serious in-hospital complications of HSCT. Allogeneic and autologous HSCT can be safely performed in HIV-positive patients.
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Infecções por HIV/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mortalidade Hospitalar , Adulto , Infecções por Citomegalovirus/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Infecções Oportunistas/epidemiologia , Fatores de Risco , Transplante Autólogo , Transplante Homólogo/efeitos adversos , Estados Unidos/epidemiologiaRESUMO
Legionella endocarditis is extremely uncommon, and embolic phenomena have never been reported. We report the first case of Legionella micdadei prosthetic valve endocarditis complicated by brain abscess. A 57-y-old immunocompromised woman with a history of mitral valve replacement developed confusion and left-sided weakness. Brain magnetic resonance imaging showed a 3-cm peripheral-enhancing mass. Transoesophageal echocardiography suggested a perivalvular abscess. Blood cultures and valve cultures were negative. She was diagnosed with 16S rRNA polymerase chain reaction and silver stain, and was discharged with levofloxacin after a redo mitral valve replacement. Twelve cases of Legionella endocarditis were reviewed. Only one case had a native valve, and her endocarditis occurred after pneumonia. All cases were cured. The duration of antibiotic therapy was variable. Legionella species should be considered in the differential diagnosis of culture-negative endocarditis in both immunocompetent and immunocompromised patients. Molecular techniques and silver impregnation stains are useful, especially when cultures using buffered charcoal-yeast extract agar are negative.
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Abscesso Encefálico/diagnóstico , Endocardite Bacteriana/diagnóstico , Legionella/isolamento & purificação , Legionelose/diagnóstico , Infecções Relacionadas à Prótese/diagnóstico , Adulto , Idoso , Antibacterianos/administração & dosagem , Técnicas Bacteriológicas , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Abscesso Encefálico/microbiologia , Abscesso Encefálico/patologia , Ecocardiografia , Endocardite Bacteriana/complicações , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/patologia , Endocárdio/diagnóstico por imagem , Endocárdio/patologia , Feminino , Humanos , Legionella/classificação , Legionelose/complicações , Legionelose/microbiologia , Legionelose/patologia , Levofloxacino , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ofloxacino/administração & dosagem , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/patologia , RadiografiaRESUMO
We evaluated the War on Worms in the Western Visayas (WOW-V) school-based mass treatment strategy in Capiz, the Philippines by assessing potential determinants of program acceptance among parents, teachers, and local health and education officials involved. Written surveys were distributed to parents and teachers assessing knowledge, attitudes and practices regarding soil-transmitted helminth (STH) infections. Associations between data were examined using the Fisher's exact test (alpha = 0.05). Descriptive statistics and t-tests were employed to analyze teacher survey results. Local health and education officials participated in key-informant interviews (KIs) to evaluate their attitudes and practices regarding WOW-V; data was qualitatively analyzed and grouped. A strong association was observed between parental consent during the first two rounds of treatment and willingness to do so again. Most parents gave consent for their child to receive treatment at least once and demonstrated a high level of knowledge regarding STH infections. The majority of teachers had positive attitudes toward their role in the program. Many identified lack of training and a fear of side effects as barriers to higher coverage. Lack of funding, program monitoring difficulties and insufficient parental education were identified by local officials as barriers. Proper planning and design is important to achieve high initial consent for program acceptance. The results correlate with studies showing relationships between health education and treatment acceptance. The implementation of health education and monitoring measures has the potential to greatly improve both treatment coverage and program infrastructure.
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Antinematódeos/uso terapêutico , Helmintíase/tratamento farmacológico , Enteropatias Parasitárias/tratamento farmacológico , Mebendazol/uso terapêutico , Pais/psicologia , Serviços de Saúde Escolar/organização & administração , Adolescente , Adulto , Criança , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Helmintíase/diagnóstico , Helmintíase/etiologia , Helmintíase/transmissão , Humanos , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/etiologia , Enteropatias Parasitárias/transmissão , Masculino , Pessoa de Meia-Idade , Filipinas/epidemiologia , Avaliação de Programas e Projetos de Saúde , Fatores SocioeconômicosRESUMO
PURPOSE: To characterize an unusual presentation of infectious posterior uveitis using multimodal imaging, and discuss the clinical decision-making involved in diagnosis and treatment. METHODS: Wide-field fundus photography, swept-source optical coherence tomography (OCT), swept-source OCT angiography, fluorescein angiography, and indocyanine green angiography. RESULTS: This patient presented with cyclical fevers and blurry vision. Fundus examination revealed bilateral optic disc edema, macular intraretinal white spots and many scattered yellow-white chorioretinal lesions. Multimodal imaging characteristics suggested that many of these lesions represent choroidal granulomas. Extensive systemic workup was only notable for borderline elevated Bartonella henselae IgG titers (1:128), however convalescent IgG titers were elevated at 38 days (1:512) supporting the diagnosis of Bartonella chorioretinitis. CONCLUSION: Ocular manifestations of Bartonella henselae infection are varied and may include choroidal granulomas. Multimodal imaging characteristics may help identify etiologies of infectious uveitis. Convalescent titers are important when evaluating patients with suspected Bartonellosis, especially patients with atypical presentations.
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Doença da Arranhadura de Gato , Uveíte Posterior , Humanos , Doença da Arranhadura de Gato/complicações , Doença da Arranhadura de Gato/diagnóstico , Uveíte Posterior/diagnóstico , Uveíte Posterior/etiologia , Imagem MultimodalRESUMO
Tenofovir disoproxil fumarate (TDF) is used worldwide to treat and prevent Human Immunodeficiency Virus (HIV) infection. Fanconi syndrome is a complication of TDF use and is characterized by inadequate reabsorption of glucose, phosphate and protein in the proximal tubule of the kidney which may eventually lead to osteomalacia manifested by symptoms of pain, muscular weakness and difficulty ambulating. We present a patient with severe osteomalacia due to progressive and unrecognized Fanconi's syndrome, who responded rapidly to TDF withdrawal, oral phosphate repletion and calcitriol. With the widespread use of TDF-containing antiviral regimens, it is critically important that physicians adhere to screening recommendations to detect early Fanconi syndrome, and recognize symptoms of osteomalacia as a serious complication.
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INTRODUCTION: Medical schools increasingly require students to complete scholarly projects. Scholarly project programs that are required and longitudinal require considerable resources to implement. It is necessary to understand medical students' perspectives on the impact of such programs. Students at the University of Pittsburgh School of Medicine participate in a required, longitudinal research program (LRP) throughout all years of medical school training. Authors studied students' perceptions of this program. METHODS: Fourth-year medical students submit a written report in which they reflect on their experience with the LRP. Qualitative analysis of students' written reflections was performed on 120 reports submitted 2012-2017. Content analysis was performed using an inductive approach in which investigators coded information and searched for emerging themes. RESULTS: Four themes were identified. First, students described engaging in many steps of the research process, with many participating in projects from conception to completion. Second, students reported the LRP provided opportunities for leadership and independence, and many found this to be meaningful. Third, students developed appreciation for the difficulty of the research process through challenges encountered and practiced problem solving. Fourth, students acquired skills useful across multiple career paths, including critical appraisal of scientific literature, teamwork, and communication. DISCUSSION: Through participation in a required, longitudinal research program, medical students reported gaining valuable skills in leadership, problem solving, critical thinking, and communication. Students found that the longitudinal nature of the program enabled meaningful research experiences. These educational impacts may be worth the effort of implementing and maintaining longitudinal research experiences for medical students. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01319-6.
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OBJECTIVES: In the Philippines, morbidity control of soil-transmitted helminth (STH) infections is done through mass drug administration (MDA) of anthelmintics to school-age children (SAC). In 2013, the Philippines was devastated by the deadliest cyclone ever recorded, Typhoon Haiyan. The study aimed to understand the impact of Typhoon Haiyan on the MDA of anthelmintics to SAC in the provinces of Capiz and Iloilo in the Philippines from the perspectives of local health and education officials. METHODS: The study was conducted in the municipalities of Panay and Pilar in Capiz and the municipalities of Estancia and Sara in Iloilo, areas that were devastated by Typhoon Haiyan. Qualitative, semi-structured key informant interviews were conducted with 16 total participants, which included officials of the Department of Health, Department of Education, and concerned local government units. All interviews were transcribed verbatim and coded in an open, iterative manner. Codes were reviewed to identify patterns and themes. RESULTS: Participants described the following themes: (1) their perception that the typhoon had no effect on the MDA program or on resources necessary to complete the program; (2) the program's simple design allowed for 1-time administration to a pre-assembled population; (3) the program allowed a sense of community cohesiveness; (4) the program served as a vehicle for altruism, particularly regarding helping needy children, in this time of calamity. CONCLUSIONS: Our informants perceived that the MDA program in Region VI was not affected by Typhoon Haiyan. They attributed the resilience to the program's simple procedure, attitudes of altruism, program importance, and community cohesiveness. Despite Typhoon Haiyan's mass destruction of infrastructure and livelihood leading to incredible challenges, mobilization of the community allowed for the continuation and successful implementation of the MDA program. The experience of Region VI may serve as a model for other low- and middle-income countries prone to natural disasters.
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Tempestades Ciclônicas , Helmintíase , Administração Massiva de Medicamentos , Solo , Animais , Criança , Helmintíase/prevenção & controle , Helmintíase/transmissão , Helmintos/isolamento & purificação , Humanos , Filipinas , Solo/parasitologiaRESUMO
Candida rugosa is a rare cause of candidaemia, but important to recognize because of frequent azole-resistance and its association with catheters and total parenteral nutrition. Recommended therapy is an echinocandin or amphotericin, and catheter discontinuation. Fluconazole might be substituted based on susceptibility testing and a clinical response to initial therapy.
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Candida/isolamento & purificação , Candidíase/microbiologia , Fungemia/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Cateteres de Demora/microbiologia , Doença de Crohn , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: To determine whether family medicine program directors (PDs) experienced moral distress due to obstacles to Hepatitis C virus (HCV) treatment, and to explore whether they found those obstacles to be unethical. DESIGN: An omnibus survey by the Council of Academic Family Medicine's Educational Research Alliance was administered to 452 and completed by 273 US-based PDs. The survey gauged attitudes and opinions regarding ethical dilemmas in patient access to HCV treatment. RESULTS: Most of the respondents were male. Sixty-four percent of respondents believed that treatment should be an option for all patients regardless of cost. Forty-one percent believed that it was unethical to deny treatment based on past or current substance use, and 38% believed treatment should be offered to patients who were substance abusers. Moral distress was reported by 61% (score >3) of participants when they were unable to offer treatment to patients due to the patient's failure to meet eligibility criteria. In addition, PDs reporting moderate-to-high levels of moral distress were also likely to report the following opinions: 1) treatment should be offered regardless of cost, 2) it is unethical to deny treatment based on past behavior, 3) substance abusers should be offered treatment, 4) it is unethical for medicine to be prohibitively expensive, and 5) Medicaid policy that limits treatment will worsen racial and ethnic disparities. CONCLUSIONS: Currently, important ethical dilemmas exist in the access and delivery of HCV therapy. Although a diversity of opinions is noted, a significant proportion of PDs are concerned about patients' inability to avail equitable care and experience distress. In some cases, this moral distress is in response to, and in conflict with, current guidelines.
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Medicina de Família e Comunidade/ética , Acessibilidade aos Serviços de Saúde/economia , Hepatite C/tratamento farmacológico , Princípios Morais , Diretores Médicos/psicologia , Antivirais/economia , Antivirais/uso terapêutico , Custos de Medicamentos/ética , Medicina de Família e Comunidade/organização & administração , Medicina de Família e Comunidade/normas , Feminino , Acessibilidade aos Serviços de Saúde/ética , Acessibilidade aos Serviços de Saúde/normas , Hepatite C/economia , Hepatite C/etiologia , Humanos , Cobertura do Seguro/economia , Cobertura do Seguro/ética , Cobertura do Seguro/normas , Masculino , Medicaid/economia , Medicaid/normas , Estresse Ocupacional/psicologia , Diretores Médicos/ética , Diretores Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Transtornos Relacionados ao Uso de Substâncias/complicações , Inquéritos e Questionários/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: In June 2000, the hospital-acquired Clostridium difficile (CD) infection rate in our hospital (University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, PA) increased to 10.4 infections per 1000 hospital discharges (HDs); the annual rate increased from 2.7 infections per 1000 HDs to 7.2 infections per 1000 HDs and was accompanied by an increase in the frequency of severe outcomes. Forty-seven (51%) of 92 HA CD isolates in 2001 were identified as the "epidemic BI strain." A comprehensive CD infection control "bundle" was implemented to control the outbreak of CD infection. METHODS: The CD infection control bundle consisted of education, increased and early case finding, expanded infection-control measures, development of a CD infection management team, and antimicrobial management. Process measures, antimicrobial usage, and hospital-acquired CD infection rates were analyzed, and CD isolates were typed. RESULTS: The rates of compliance with hand hygiene and isolation were 75% and 68%, respectively. The CD management team evaluated a mean of 31 patients per month (11% were evaluated for moderate or severe disease). Use of antimicrobial therapy associated with increased CD infection risk decreased by 41% during the period 2003-2005 (P<.001). The aggregate rate of CD infection during the period 2001-2006 decreased to 4.8 infections per 1000 HDs (odds ratio, 2.2; 95% confidence interval, 1.4-3.1; P<.001) and by 2006, was 3.0 infections per 1000 HDs, a rate reduction of 71% (odds ratio, 3.5; 95% confidence interval, 2.3-5.4; P<.001). During the period 2000-2001, the proportion of severe CD cases peaked at 9.4% (37 of 393 CD infections were severe); the rate decreased to 3.1% in 2002 and further decreased to 1.0% in 2006--a 78% overall reduction (odds ratio, 20.3; 95% confidence interval, 2.8-148.2; P<.001). In 2005, 13% of CD isolates were type BI (20% were hospital acquired), which represented a significant reduction from 2001 (P<.001). CONCLUSIONS: The outbreak of CD infection with the BI strain in our hospital was controlled after implementing a CD infection control "bundle." Early identification, coupled with appropriate control measures, reduces the rate of CD infection and the frequency of adverse events.
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Clostridioides difficile/isolamento & purificação , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Enterocolite Pseudomembranosa/epidemiologia , Controle de Infecções/métodos , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Clostridioides difficile/classificação , Infecção Hospitalar/tratamento farmacológico , Educação , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/microbiologia , Desinfecção das Mãos , Hospitais Universitários , Humanos , Epidemiologia Molecular , Isolamento de Pacientes , PennsylvaniaRESUMO
Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.
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Fármacos Anti-HIV/efeitos adversos , Antituberculosos/uso terapêutico , Ginecomastia/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Coinfecção/tratamento farmacológico , Ginecomastia/diagnóstico , Infecções por HIV/complicações , Humanos , Masculino , Inibidores da Transcriptase Reversa/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy. METHODS: A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3âml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60âml/min per 1.73âm. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD. RESULTS: Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6-98) weeks. For every 10-year increase in age and 10âml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratioâ=â1.70, 95% confidence interval (CI) 1.36-2.13] and 57% (adjusted odds ratioâ=â1.57, 95% CI 1.38-1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratioâ=â1.90, 95% CI: 1.10-3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratioâ=â3.96, 95% CI: 1.06-14.74). CONCLUSION: About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Tenofovir/uso terapêutico , Adulto , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , África do Sul/epidemiologiaRESUMO
In a pilot study, the feasibility of immune whey protein concentrate (40%; immune WPC-40) to aid the prevention of relapse of Clostridium difficile diarrhoea was evaluated. Immune WPC-40 was made from milk after immunization of Holstein-Frisian cows with C. difficile-inactivated toxins and killed whole-cell C. difficile. Immune WPC-40 contained a high concentration of specific sIgA antibodies, and was effective in neutralizing the cytotoxic effect of C. difficile toxins in cell assays in vitro. Immune WPC-40 conferred protection from otherwise lethal C. difficile-associated caecitis in hamsters. To obtain preliminary data in humans, 16 patients (10 male; median 57 years) with toxin- and culture-confirmed C. difficile diarrhoea were enrolled in an uncontrolled cohort study. Nine had a history of relapsing C. difficile diarrhoea. After completion of standard antibiotic treatment, the patients received immune WPC-40 TID for 2 weeks; it was well tolerated and no treatment-related adverse effects were observed. In all but one case, C. difficile toxins had disappeared from the faeces upon completion of treatment. During a follow-up period of median 333 days (range 35 days to 1 year), none of the patients had suffered another episode of C. difficile diarrhoea. These preliminary data suggest that immune whey protein concentrate-40 may be of help in the prevention of relapse of C. difficile diarrhoea.
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Anticorpos Antibacterianos/uso terapêutico , Clostridioides difficile/imunologia , Infecções por Clostridium/prevenção & controle , Diarreia/prevenção & controle , Animais , Bovinos , Estudos de Coortes , Cricetinae , Diarreia/imunologia , Humanos , Projetos Piloto , Estudos ProspectivosRESUMO
The impact of drug-drug interactions (DDIs) between interferon-free direct acting antiviral (DAA) regimens and antiretrovirals (ART) among HIV/HCV co-infected individuals in clinical practice settings is unknown. A single-center, retrospective chart review of co-infected patients was conducted from June 2014 to February 2015. Significant interactions between simeprevir (SMV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D regimen) with ART were identified based on available literature. SMV had the largest number of DDIs and was further investigated to determine the feasibility of ART switch to allow for DAA use. Of 127 subjects, 23% had advanced liver disease; 86% of those with known HCV genotype were HCV genotype 1. An ART switch allowing use of SMV, LDV, and 3D regimen was recommended in 97/127 (76%), 81/127 (64%), and 91/127 (72%) patients, respectively. Subjects on PI/r regimens had limited options for ART switch, with 40% of these patients unable to be switched to an ART regimen that avoided the use of a PI. In conclusion, the majority of HIV/HCV co-infected patients will be recommended to switch ART prior to use of interferon-free, DAA regimens, and an ART switch may not be feasible for more than a third of patients on a boosted PI. DDIs between ART and DAAs represent an additional barrier to treatment efficacy in clinical practice settings that are unaccounted for in clinical trials.
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Antivirais/uso terapêutico , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Inibidores de Proteases/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antivirais/farmacologia , Coinfecção/tratamento farmacológico , Feminino , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Ritonavir/uso terapêuticoRESUMO
During 2000, four cases of fatal Lassa fever were imported from Africa to Europe. In two patients, consecutive serum samples were available for monitoring of virus load and cytokine levels in addition to standard laboratory data. Both patients had non-specific early clinical symptoms including high fever. Patient 1 developed multi-organ failure and died of hemorrhagic shock on day 15 of illness, while patient 2 died of respiratory failure due to aspiration without hemorrhage on day 16. Ribavirin was administered to both patients beginning only on day 11. High serum aspartate aminotransferase and lactate dehydrogenase (LDH) levels were remarkable in both patients. Patient 1 had an initial virus load of 10(6) S RNA copies/ml as measured by real-time RT-PCR. Viremia increased steadily and reached a plateau of approximately 10(8)-10(9) copies/ml 4 days before death, while IFN-gamma and TNF-alpha rose to extremely high levels only shortly before death. In contrast, in patient 2 the virus load decreased from 10(7) to 10(6) copies/ml during the late stage of illness which was paralleled by a decrease in the IFN-gamma and TNF-alpha levels. The IL-10 level increased when specific IgM and IgG appeared. These data suggest that a high virus load and high levels of pro-inflammatory cytokines in the late stage of Lassa fever play an important role in the pathogenesis of hemorrhage, multi-organ failure, and shock in Lassa fever.