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1.
BJOG ; 124(12): 1867-1873, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28294509

RESUMO

OBJECTIVE: To evaluate the reliability of a four-level triage scale for obstetrics and gynaecology emergencies and to explore the factors associated with an optimal triage. DESIGN: Thirty clinical vignettes presenting the most frequent indications for obstetrics and gynaecology emergency consultations were evaluated twice using a computerised simulator. SETTING: The study was performed at the emergency unit of obstetrics and gynaecology at the Geneva University Hospitals. SAMPLE: The vignettes were submitted to nurses and midwives. METHODS: We assessed inter- and intra-rater reliability and agreement using a two-way mixed-effects intra-class correlation (ICC). We also performed a generalised linear mixed model to evaluate factors associated triage correctness. MAIN OUTCOME MEASURES: Triage acuity. RESULTS: We obtained a total of 1191 evaluations. Inter-rater reliability was good (ICC 0.748; 95% CI 0.633-0.858) and intra-rater reliability was almost perfect (ICC 0.812; 95% CI 0.726-0.889). We observed a wide variability: the mean number of questions varied from 6.9 to 18.9 across individuals and from 8.4 to 16.9 across vignettes. Triage acuity was underestimated in 12.4% of cases and overestimated in 9.3%. Undertriage occurred less frequently for gynaecology compared with obstetric vignettes [odds ratio (OR) 0.45; 95% CI 0.23-0.91; P = 0.035] and decreased with the number of questions asked (OR 0.94; 95% CI 0.88-0.99; P = 0.047). Certification in obstetrics and gynaecology emergencies was an independent factor for the avoidance of undertriage (OR 0.35; 95% CI 0.17-0.70; P = 0.003). CONCLUSION: The four-level triage scale is a valid and reliable tool for the integrated emergency management of obstetrics and gynaecology patients. TWEETABLE ABSTRACT: The Swiss Emergency Triage Scale is a valid and reliable tool for obstetrics and gynaecology emergency triage.


Assuntos
Serviços Médicos de Emergência/métodos , Ginecologia/métodos , Obstetrícia/métodos , Avaliação de Processos em Cuidados de Saúde , Triagem/métodos , Adulto , Simulação por Computador , Serviços Médicos de Emergência/normas , Serviço Hospitalar de Emergência/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Ginecologia/normas , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Tocologia/métodos , Tocologia/normas , Variações Dependentes do Observador , Obstetrícia/normas , Gravidade do Paciente , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Triagem/normas
2.
Diabetes Metab ; 38(4): 370-2, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22559928

RESUMO

AIM: Hypothermia is a recognized complication of severe hypoglycaemia, but its prevalence and characteristics are poorly studied. For this reason, this study aimed to evaluate hypothermia in severely hypoglycaemic patients. METHODS: A retrospective chart review was performed including all patients discharged between 2007 and 2010 from the Emergency Department of the Geneva University Hospital with a diagnosis of severe hypoglycaemia. RESULTS: Hypothermia was identified in 30 (23.4%) out of 128 patients with severe hypoglycaemia. Its incidence was not affected by age, type of diabetes, season or time of day (day/night). Using linear regression, the lowest recorded temperature was associated with the Glasgow coma scale (GCS) score (r2 = 13.8%, P < 0.0001) and inversely associated with the leukocyte count (r2 = 13.1%, P = 0.001). CONCLUSION: Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. The associations between hypothermia and the GCS score and the leukocyte count suggest that it is a marker of hypoglycaemia severity and/or duration. Hypothermia may represent an important compensatory mechanism in severe hypoglycaemia, reflecting a decrease in energy demand during glucose deprivation.


Assuntos
Hipoglicemia/diagnóstico , Hipoglicemiantes/efeitos adversos , Hipotermia/etiologia , Adulto , Medicina de Emergência , Feminino , Escala de Coma de Glasgow , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/complicações , Hipoglicemiantes/administração & dosagem , Hipotermia/sangue , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
J Thromb Haemost ; 10(3): 347-51, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22212132

RESUMO

BACKGROUND: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. OBJECTIVES: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. PATIENTS/METHODS: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. RESULTS: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42-1.11). However, when PE suspicion was based on new-onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26-0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97-6.07). CONCLUSIONS: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new-onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.


Assuntos
Fibrilação Atrial/epidemiologia , Embolia Pulmonar/epidemiologia , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Dor no Peito/epidemiologia , Distribuição de Qui-Quadrado , Dispneia/epidemiologia , Eletrocardiografia , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Análise Multivariada , Razão de Chances , Prevalência , Embolia Pulmonar/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X
4.
J Intern Med ; 271(5): 451-62, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22061093

RESUMO

OBJECTIVES: To explore the diagnostic accuracies of anti-apolipoproteinA-1 (anti-ApoA-1) IgG and anti-phosphorylcholine (anti-PC) IgM alone, expressed as a ratio (anti-ApoA-1 IgG/anti-PC IgM), and combined with the Thrombolysis In Myocardial Infarction (TIMI) score for non-ST-segment elevation myocardial infarction (NSTEMI) (NSTEMI-TIMI score) to create a new diagnostic algorithm - the Clinical Autoantibody Ratio (CABR) score - for the diagnosis of NSTEMI and subsequent cardiac troponin I (cTnI) elevation in patients with acute chest pain (ACP). METHODS: In this single-centre prospective study, 138 patients presented at the emergency department with ACP without ST-segment elevation myocardial infarction. Anti-ApoA-1 IgG and anti-PC IgM were assessed by enzyme-linked immunosorbent assay on admission. Post hoc determination of the CABR score cut-off was performed by receiver operating characteristics analyses. RESULTS: The adjudicated final diagnosis was NSTEMI in 17% (24/138) of patients. Both autoantibodies alone were found to be significant predictors of NSTEMI diagnosis, but the CABR score had the best diagnostic accuracy [area under the curve (AUC): 0.88; 95% confidence interval (CI): 0.82-0.95]. At the optimal cut-off of 3.3, the CABR score negative predictive value (NPV) was 97% (95% CI: 90-99). Logistic regression analysis showed that a CABR score >3.3 increased the risk of subsequent NSTEMI diagnosis 19-fold (odds ratio: 18.7; 95% CI: 5.2-67.3). For subsequent cTnI positivity, only anti-ApoA-1 IgG and CABR score displayed adequate predictive accuracies with AUCs of 0.80 (95% CI: 0.68-0.91) and 0.82 (95% CI: 0.70-0.94), respectively; the NPVs were 95% (95% CI: 90-98) and 99% (95% CI: 94-100), respectively. CONCLUSION: The CABR score, derived from adding the anti-ApoA-1 IgG/anti-PC IgM ratio to the NSTEMI-TIMI score, could be a useful measure to rule out NSTEMI in patients presenting with ACP at the emergency department without electrocardiographic changes.


Assuntos
Apolipoproteína A-I/imunologia , Autoanticorpos/sangue , Infarto do Miocárdio , Fosforilcolina/imunologia , Terapia Trombolítica/métodos , Idoso , Algoritmos , Área Sob a Curva , Intervalos de Confiança , Eletrocardiografia/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/imunologia , Razão de Chances , Valor Preditivo dos Testes
6.
Praxis (Bern 1994) ; 99(4): 235-40, 2010 Feb 17.
Artigo em Alemão | MEDLINE | ID: mdl-20166049

RESUMO

COPD is a progressive disease whom course is characterized by repeated exacerbations, with a negative impact on quality of life and health costs. Although a causal link between the identification of viruses in the upper respiratory tract and exacerbation is not definitively established, there is growing evidence that viruses are important triggers of exacerbations in more than 50 percent of cases. Yet, neither clinical presentation nor biological markers permit to discriminate between viral and non viral exacerbations.


Assuntos
Infecções Bacterianas/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Infecções Respiratórias/complicações , Viroses/diagnóstico , Doença Aguda , Infecções Bacterianas/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Humanos , Infecções Respiratórias/diagnóstico
7.
AIDS ; 14(14): 2145-51, 2000 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-11061656

RESUMO

OBJECTIVE AND METHODS: In 1998 we reported on a randomized comparison between stavudine plus didanosine plus placebo versus stavudine plus didanosine plus hydroxyurea (HU), in patients with a CD4 count of 200-500 x 10(6) cells/l. After 3 months, the HU group had a higher proportion of patients with viral load < 200 x 10 cells/l. At the end of the 3 months blinded period, patients in the placebo group had the option to add HU if their viral load remained > 200 x 10(6) cells/l. We report results after 24 months. RESULTS: Seventy-two patients were randomized to the HU arm, and a further 30 elected to add HU after 12 weeks. Twenty-four months after the start of the trial, only 25% of the 72 patients originally randomized to HU, and 20% of the 30 who added HU after week 12, were still taking it. The reasons for stopping HU were: lack of efficacy (45%), adverse events (37%) and patient or physician preference (18%). Side effects were more frequent in the didanosine/stavudine/HU group than in the didanosine/stavudine group: neuropathy (35 versus 15%, P< 0.02), fatigue (22 versus 7%, P< 0.01), and nausea or vomiting (26 versus 9%, P< 0.01). Of those who had discontinued HU, 73% were taking three drugs including a protease inhibitor. Patients who had started HU were compared with similar patients who had started protease inhibitors in the Swiss cohort. The probability of stopping HU was higher than the probability of stopping nelfinavir or indinavir, and similar to the probability of stopping ritonavir. CONCLUSION: HU increased the antiviral effect of stavudine plus didanosine. However, side effects were more frequent, and after 24 months the majority of patients had switched to protease inhibitor regimens.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Hidroxiureia/uso terapêutico , Estavudina/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Diarreia/induzido quimicamente , Didanosina/efeitos adversos , Quimioterapia Combinada , Inibidores Enzimáticos/efeitos adversos , Seguimentos , Humanos , Hidroxiureia/efeitos adversos , Náusea/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estavudina/efeitos adversos
9.
Am J Manag Care ; 6(20 Suppl): S1054-65; quiz 1066-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11484305

RESUMO

Low-molecular weight heparins (LMWHs) have become attractive alternatives to standard unfractionated heparin (UFH) for the treatment and prophylaxis of deep vein thrombosis (DVT), and for the management of acute coronary syndrome (ACS). The economic impact of the use of LMWHs has been studied in randomized controlled studies, in demonstration projects in managed care institutions, and in decision models. These studies provide valuable insight into the ways LMWHs can be economically attractive despite higher per unit costs compared with UFH. For the treatment of DVT, the cost benefit of using LMWHs results primarily from the cost shifting from inpatient to outpatient care, and might be limited by the eligibility of patients for outpatient management. In contrast, the attractiveness of LMWHs for ACS and DVT prophylaxis hinges on the increased effectiveness of LMWHs compared with standard UFH.


Assuntos
Antifibrinolíticos/economia , Heparina de Baixo Peso Molecular/economia , Programas de Assistência Gerenciada/economia , Trombose Venosa/economia , Antifibrinolíticos/uso terapêutico , Efeitos Psicossociais da Doença , Técnicas de Apoio para a Decisão , Custos de Medicamentos , Educação Médica Continuada , Educação Continuada em Farmácia , Heparina de Baixo Peso Molecular/uso terapêutico , Custos Hospitalares , Humanos , Estados Unidos , Trombose Venosa/tratamento farmacológico
10.
J Infect Dis ; 180(3): 850-3, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10438378

RESUMO

We have developed sensitive assays for viremia and cell-associated human immunodeficiency virus type 1 (HIV-1) RNA and DNA to assess the predictive value of virological parameters determined in blood for virus load in lymph nodes (LNs). Eighteen patients were included; 13 received stavudine/didanosine/hydroxyurea and 5 stavudine/didanosine, and all had viremia <500 copies/mL for >3 months. At the time of LN biopsy (median, 10 months), the median viremia was 2.09 log copies/mL (range, <0.70-3.34). Cell-associated HIV-1 RNA and DNA were detectable in blood and LNs of all patients. The median cell-associated RNA and DNA were 2.16 log copies/106 cells and 2.60 log copies/106 cells in blood versus 4.31 log RNA copies/106 cells and 3.26 log DNA copies/106 cells in LNs. Regression analysis shows that, in treated patients with sustained low viremia, cell-associated RNA and DNA in blood are better predictors of virus load in LNs than viremia.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Hidroxiureia/uso terapêutico , Linfonodos/virologia , RNA Viral/sangue , Estavudina/uso terapêutico , Carga Viral , Síndrome da Imunodeficiência Adquirida/imunologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Quimioterapia Combinada , Infecções por HIV/imunologia , Humanos , Linfonodos/imunologia , Linfonodos/patologia
11.
Clin Exp Immunol ; 115(3): 458-63, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10193418

RESUMO

The relationship between blood CD8+ T lymphocyte subsets, as defined by CD28 and CD38 expression, and plasma viraemia and CD4+ T cells in HIV-1 infection was investigated. In a cross-sectional study of 46 patients with either no or stable anti-retroviral treatment, there was a strong negative correlation between the percentage of CD8+CD28- and the percentage of CD4+ T cells (r = -0.75, P < 0.0001), and a positive correlation between absolute numbers of CD8+CD28+ and CD4+ T cells (r = 0.56, P < 0.0001). In contrast, the expression of CD38 by CD8+ T lymphocytes correlated primarily with plasma viraemia (e.g. the percentage of CD38+ in CD8bright cells, r = 0.76, P < 0.0001). In the 6 months following triple therapy initiation in 32 subjects, there was a close correlation between changes (delta) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. delta % CD8+CD28+ versus delta % CD4+, r = 0.37, P = 0.0002; delta % CD8+CD28- versus delta % CD4+, r = -0.66, P < 0.0001). A marked decline of the number of CD8+ T cells expressing CD38 was also observed. These results suggest the existence of a T cell homeostasis mechanism operating in blood with CD4+ and CD8+CD28+ cells on the one hand, and with CD8+CD28- cells on the other. In addition, the percentage of CD38+ cells in CD8+ cells, generally considered an independent prognostic factor, could merely reflect plasma viral load.


Assuntos
Antígenos CD , Antígenos de Diferenciação/metabolismo , Antígenos CD28/metabolismo , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1 , NAD+ Nucleosidase/metabolismo , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Fármacos Anti-HIV/uso terapêutico , Biomarcadores , Linfócitos T CD4-Positivos/imunologia , Estudos de Coortes , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Homeostase , Humanos , Glicoproteínas de Membrana , Prognóstico , Suíça , Subpopulações de Linfócitos T/imunologia , Viremia/imunologia
12.
Ann Pharmacother ; 32(9): 892-5, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9762377

RESUMO

OBJECTIVE: To report a case of rhabdomyolysis related to rapid correction of hyponatremia attributable to compulsive drinking of water, possible complicated by clozapine use. CASE SUMMARY: A 42-year-old white man treated with clozapine for schizophrenia was admitted for a generalized seizure. Marked hyponatremia due to psychogenic polydipsia was present. He developed a marked elevation of creatine kinase concentrations after correction of hyponatremia with hyperosmolar sodium solution, without clinical signs of rhabdomyolysis. DISCUSSION: Rhabdomyolysis associated with hyponatremia due to water intoxication has been reported in 17 patients to date. A possible explanation may lie within the framework of the calcium-sodium exchange across the skeletal muscle cell membrane. By increasing muscle cell permeability, clozapine treatment may possibly enhance the destruction of muscle cells. CONCLUSIONS: Hyponatremia due to water intoxication and concurrent use of clozapine should be considered in the differential diagnosis of rhabdomyolysis, especially in the severely psychiatrically disabled population.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Comportamento de Ingestão de Líquido , Hiponatremia/complicações , Rabdomiólise/etiologia , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Masculino , Rabdomiólise/induzido quimicamente , Esquizofrenia Paranoide/complicações , Esquizofrenia Paranoide/tratamento farmacológico , Esquizofrenia Paranoide/fisiopatologia , Psicologia do Esquizofrênico , Cloreto de Sódio/uso terapêutico
13.
Schweiz Med Wochenschr ; 128(31-32): 1171-4, 1998 Aug 04.
Artigo em Francês | MEDLINE | ID: mdl-9738275

RESUMO

We report a case of severe hypoglycaemia following co-trimoxazole therapy. An 88-year-old woman was admitted with urinary tract infection and treated with co-trimoxazole (960 mg bid). Seven days after initiation of the treatment she became comatose. Blood sugar was 1.3 mmol/l and C-peptide at the upper limit of normal range. Glucose infusion restored normal consciousness and no hypoglycaemia recurred after interruption of co-trimoxazole therapy. Advanced aged was the only risk factor identified. Other risk factors described in previous case reports are renal failure, poor nutritional state and high doses of co-trimoxazole.


Assuntos
Hipoglicemia/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/tratamento farmacológico , Idoso , Glicemia/metabolismo , Peptídeo C/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem
14.
AIDS ; 12(8): F71-7, 1998 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-9631134

RESUMO

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Hidroxiureia/uso terapêutico , Estavudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Estudos de Coortes , Didanosina/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Estavudina/administração & dosagem , Suíça , Viremia
15.
J Infect Dis ; 177(3): 783-5, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9498464

RESUMO

The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. Before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. After 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (+/-SE) increase of 73 (+/-21) CD4 and 296 (+/-70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log +/- 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameters.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Hepatite C/tratamento farmacológico , Viremia/tratamento farmacológico , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Hepatite C/sangue , Hepatite C/complicações , Humanos , Indinavir/uso terapêutico , Masculino , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico , Viremia/complicações
16.
Antivir Ther ; 3 Suppl 4: 65-7, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10723515

RESUMO

A total of 144 human immunodeficiency virus (HIV)-infected patients (mean CD4 cell count, 367 cells/mm3) were included in a double-blind placebo-controlled trial testing the efficacy on surrogate markers of HIV progression of the combination didanosine (2',3'-dideoxyinosine or DDI) plus stavudine (2',3'-didehydro-2',3'-dideoxythymidine or D4T) with or without hydroxyurea. The primary end point was a reduction of HIV RNA levels to below 200 copies/ml after 12 weeks of treatment. The results showed that the triple combination was associated with a more profound decrease in HIV RNA with an increased proportion of patients with viraemia < 200 copies/ml. This effect persisted for the majority of the patients after a 48 week follow-up. In contrast, the increase in CD4 cell counts was less in patients treated with hydroxyurea because of lymphopenia, and adverse events were more frequent in hydroxyurea-treated patients. In conclusion, the addition of hydroxyurea consistently improved the antiviral activity of the didanosine/stavudine combination over a 48 week follow-up. Increased toxicity and decreased effect on CD4 cell counts might inspire caution.


Assuntos
Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Hidroxiureia/uso terapêutico , Estavudina/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Didanosina/efeitos adversos , Sinergismo Farmacológico , Quimioterapia Combinada , Seguimentos , Humanos , Hidroxiureia/efeitos adversos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/efeitos adversos
17.
AIDS ; 11(12): F95-9, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9342060

RESUMO

OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Protease de HIV/genética , Ritonavir/uso terapêutico , Saquinavir/uso terapêutico , Síndrome da Imunodeficiência Adquirida/sangue , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos de Coortes , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Feminino , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Masculino , Mutação , Projetos Piloto , Ritonavir/efeitos adversos , Ritonavir/farmacocinética , Saquinavir/efeitos adversos , Saquinavir/farmacocinética , Viremia/tratamento farmacológico
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