RESUMO
BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.
Assuntos
Acne Vulgar , Fármacos Dermatológicos , Acne Vulgar/tratamento farmacológico , Adapaleno , Peróxido de Benzoíla/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Géis , Humanos , Metanálise em Rede , Qualidade de Vida , Resultado do TratamentoRESUMO
Undoubtedly, comorbidities complicate long-term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would allow for a more considered and proactive approach to the long-term management of HIV. This review examines cross-sectional analyses of six European cohort studies (Athens Multicenter AIDS Cohort Study, Aquitaine Cohort, EuroSIDA Cohort study, French claims EGB, German InGef Cohort and the Italian Cohort of Individuals, Naïve for Antiretrovirals), which included individuals with HIV followed over a certain period of time. Based on these cohorts, we examined how comorbidities have changed over time; how they compromise HIV management; and how much of a financial burden they impart. These data also provided a framework to explore the major issues of ageing and HIV and the practical implications of managing such issues in real-life practice.
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Antirretrovirais/uso terapêutico , Comorbidade , Infecções por HIV/tratamento farmacológico , Gastos em Saúde , Envelhecimento , Estudos Transversais , Gerenciamento Clínico , Europa (Continente) , Feminino , Humanos , MasculinoRESUMO
In neonatal intensive care units (NICUs), 87.5% of alarms by the monitoring system are false alarms, often caused by the movements of the neonates. Such false alarms are not only stressful for the neonates as well as for their parents and caregivers, but may also lead to longer response times in real critical situations. The aim of this project was to reduce the rates of false alarms by employing machine learning algorithms (MLA), which intelligently analyze data stemming from standard physiological monitoring in combination with cerebral oximetry data (in-house built, OxyPrem). MATERIALS & METHODS: Four popular MLAs were selected to categorize the alarms as false or real: (i) decision tree (DT), (ii) 5-nearest neighbors (5-NN), (iii) naïve Bayes (NB) and (iv) support vector machine (SVM). We acquired and processed monitoring data (median duration (SD): 54.6 (± 6.9) min) of 14 preterm infants (gestational age: 26 6/7 (± 2 5/7) weeks). A hybrid method of filter and wrapper feature selection generated the candidate subset for training these four MLAs. RESULTS: A high specificity of >99% was achieved by all four approaches. DT showed the highest sensitivity (87%). The cerebral oximetry data improved the classification accuracy. DISCUSSION & CONCLUSION: Despite a (as yet) low amount of data for training, the four MLAs achieved an excellent specificity and a promising sensitivity. Presently, the current sensitivity is insufficient since, in the NICU, it is crucial that no real alarms are missed. This will most likely be improved by including more subjects and data in the training of the MLAs, which makes pursuing this approach worthwhile.
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Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal , Aprendizado de Máquina , Monitorização Fisiológica , Oximetria , Teorema de Bayes , Circulação Cerebrovascular , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Terapia Intensiva Neonatal/métodos , Monitorização Fisiológica/métodos , Oximetria/métodos , Oximetria/normasRESUMO
OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/imunologia , HIV-1/imunologia , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Modelos Estatísticos , Soroconversão , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. METHODS: We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. RESULTS: Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. CONCLUSIONS: This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Comprimidos/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Multiple surgical procedures in a single patient are relatively common and lead to dependent (clustered) data. This dependency needs to be accounted for in study design and data analysis. A systematic review was performed to assess how clustered data were handled in inguinal hernia trials. The impact of ignoring clustered data was estimated using simulations. METHODS: PubMed, Embase and the Cochrane Library were reviewed systematically for RCTs published between 2004 and 2013, including patients undergoing unilateral or bilateral inguinal hernia repair. Study characteristics determining the appropriateness of handling clustered data were extracted. Using simulations, various statistical methods accounting for clustered data were compared with an analysis ignoring clustering by assuming 100 hernias, with a varying percentage of patients having bilateral hernias. RESULTS: Of the 50 eligible trials including patients with bilateral hernias, 20 (40 per cent) did not provide information on how they dealt with clustered data and 18 (36 per cent) avoided clustering by assessing the outcome by patient and not by hernia. None of the remaining 12 trials (24 per cent) considered clustering in the design or analysis. In the simulations, ignoring clustering led to an increased type I error rate of up to 12 per cent and to a loss in power of up to 15 per cent, depending on whether the patient or the hernia was the randomization unit. CONCLUSION: Clustering was rarely considered in inguinal hernia trials. The simulations underline the importance of considering clustering as part of the statistical analysis to avoid false-positive and false-negative results, and hence inappropriate study conclusions.
Assuntos
Interpretação Estatística de Dados , Hérnia Inguinal/cirurgia , Herniorrafia , Avaliação de Resultados em Cuidados de Saúde/métodos , Análise por Conglomerados , Simulação por Computador , Humanos , Modelos Teóricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de PesquisaRESUMO
BACKGROUND: Carbetocin is a synthetic oxytocin-analogue, which should be administered as bolus according to manufacturer's recommendations. A higher speed of oxytocin administration leads to increased cardiovascular side-effects. It is unclear whether carbetocin administration as short infusion has the same efficacy on uterine tone compared with bolus administration and whether haemodynamic parameters differ. METHODS: In this randomized, double-blind, non-inferiority trial, women undergoing planned or unplanned Caesarean section (CS) under regional anaesthesia received a bolus and a short infusion, only one of which contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine tone two, three, five and 10 min after cord-clamping by manual palpation using a linear analogue scale from 0 to 100. We evaluated whether the lower limit of the 95% CI of the difference in maximum uterine tone within the first five min after cord-clamping did not include the pre-specified non-inferiority limit of -10. RESULTS: Between December 2014 and November 2015, 69 patients were randomized to receive carbetocin as bolus and 71 to receive it as short infusion. Maximal uterine tone was 89 in the bolus and 88 in the short infusion group (mean difference -1.3, 95% CI -5.7 to 3.1). Bp, calculated blood loss, use of additional uterotonics, and side-effects were comparable. CONCLUSIONS: Administration of carbetocin as short infusion does not compromise uterine tone and has similar cardiovascular side-effects as a slow i.v. bolus. In accordance with current recommendations for oxytocin, carbetocin can safely be administered as short -infusion during planned or unplanned CS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.
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Cesárea/métodos , Ocitócicos/administração & dosagem , Ocitócicos/uso terapêutico , Ocitocina/análogos & derivados , Adulto , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Injeções Intravenosas , Ocitócicos/efeitos adversos , Ocitocina/administração & dosagem , Ocitocina/efeitos adversos , Ocitocina/uso terapêutico , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Resultado do Tratamento , Contração Uterina/efeitos dos fármacosRESUMO
BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.
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Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Adulto , Algoritmos , Análise por Conglomerados , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Filogenia , Fatores de Risco , Suíça/epidemiologiaRESUMO
BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.
Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Suíça/epidemiologiaRESUMO
BACKGROUND: Patients with asthma who smoke have reduced lung function, increased exacerbation rates and increased steroid resistance compared to non-smoking asthmatics. In mice, cigarette smoke has been reported to have both pro- and anti-Th2 response effects. OBJECTIVE: We hypothesized that combining tobacco cigarette smoke (tCS) with allergen exposure increases inflammation, airway remodelling and lung function in mice. To test this hypothesis, we combined a severe triple allergen model with tCS exposure and investigated whether effects were due to Toll-like receptor 4 signalling and/or nicotine and also observed when nicotine-free cigarettes were used. METHODS: Mice were sensitized with ovalbumin, cockroach and house dust mite allergen in alum followed by intratracheal challenges with allergen twice a week for 6 weeks or additionally exposed to tCS during the allergen challenge period. Nicotine or nicotine-free herbal cigarette smoke was also applied to allergen challenged mice. RESULTS: tCS significantly reduced eosinophil numbers, IL-4 and IL-5 concentrations in the lung, total and allergen-specific IgE in serum, improved lung function and reduced collagen I levels. With the exception of collagen I all parameters reduced by tobacco cigarette smoke were also reduced in Toll-like receptor 4-deficient mice. Nicotine-free cigarette smoke also had significant anti-inflammatory effects on eosinophils, IL-4 and IL-5 concentrations in the lung and reduced airway hyperreactivity, albeit weaker than tobacco smoke. Applying nicotine alone also reduced Th2 cytokine levels and eosinophil numbers in the airways. CONCLUSION: Our experiments show that tCS exposure reduces allergen-induced Th2 response in the lung and associated collagen I production and development of airway hyperreactivity. With the exception on collagen I formation, these effects were not dependent on Toll-like receptor 4. The observed anti-Th2 effects of both nicotine and nicotine-free herbal cigarette smoke together suggests that tCS reduces the Th2 responses through nicotine and other products released by burning tobacco.
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Remodelação das Vias Aéreas , Alérgenos/imunologia , Asma/etiologia , Asma/fisiopatologia , Doenças Respiratórias/etiologia , Doenças Respiratórias/patologia , Fumar , Animais , Asma/diagnóstico , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunomodulação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nicotina/efeitos adversos , Testes de Função Respiratória , Doenças Respiratórias/fisiopatologia , Transdução de Sinais , Fumar/efeitos adversos , Baço/imunologia , Baço/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
OBJECTIVES: Tenofovir is associated with reduced renal function. It is not clear whether patients can be expected to fully recover their renal function if tenofovir is discontinued. METHODS: We calculated the estimated glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study remaining on tenofovir for at least 1 year after starting a first antiretroviral therapy regimen with tenofovir and either efavirenz or the ritonavir-boosted protease inhibitor lopinavir, atazanavir or darunavir. We estimated the difference in eGFR slope between those who discontinued tenofovir after 1 year and those who remained on tenofovir. RESULTS: A total of 1049 patients on tenofovir for at least 1 year were then followed for a median of 26 months, during which time 259 patients (25%) discontinued tenofovir. After 1 year on tenofovir, the difference in eGFR between those starting with efavirenz and those starting with lopinavir, atazanavir and darunavir was - 0.7 [95% confidence interval (CI) -2.3 to 0.8], -1.4 (95% CI -3.2 to 0.3) and 0.0 (95% CI -1.7 to 1.7) mL/min/1.73 m(2), respectively. The estimated linear rate of decline in eGFR on tenofovir was -1.1 (95% CI -1.5 to -0.8) mL/min/1.73 m(2) per year and its recovery after discontinuing tenofovir was 2.1 (95% CI 1.3 to 2.9) mL/min/1.73 m(2) per year. Patients starting tenofovir with either lopinavir or atazanavir appeared to have the same rates of decline and recovery as those starting tenofovir with efavirenz. CONCLUSIONS: If patients discontinue tenofovir, clinicians can expect renal function to recover more rapidly than it declined.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/fisiopatologia , Organofosfonatos/efeitos adversos , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Humanos , Masculino , Organofosfonatos/administração & dosagem , Estudos Prospectivos , Tenofovir , Suspensão de TratamentoRESUMO
AIM: To assess self-perceived health status and mental health outcomes of former extremely low-birth-weight (ELBW) infants at young adulthood compared with community norms and to analyse predictors of poor outcome. METHODS: Fifty-five ELBW adults, 18 men (33%), with median (range) gestational age of 28.7 (25.0-34.0) weeks and birth weight of 930 (680-990) grams, born in Switzerland, were included. They self-rated their health status and mental health at a mean (range) age of 23.3 (21.8-25.9) years. Health status was measured by the Medical Outcomes Study Short Form-36 questionnaire and mental health by the Brief Symptom Inventory. RESULTS: The mean scores for both outcome measures were in the normal range. However, the study group self-rated significantly higher physical health status and lower mental health status compared with the community norms, and scores for self-perceived mental health tended to be worse in the former. ELBW adults reported more problems in socio-emotional role functioning compared with the community norms. Female sex was associated with poorer and bronchopulmonary dysplasia with better mental health status. CONCLUSION: Health status and mental health of former ELBW adults were overall satisfying. However, the comparison with the community norms revealed differences, which may be important for parental and patient counselling and developing support strategies.
Assuntos
Nível de Saúde , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Saúde Mental , Autoimagem , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Avaliação de Resultados em Cuidados de Saúde , Autorrelato , Fatores Socioeconômicos , Suíça/epidemiologia , Adulto JovemRESUMO
AIM: The aim of this study was to test the hypothesis that singleton late preterm infants (34 0/7 to 36 6/7 weeks of gestation) compared with full-term infants have a higher incidence of short-term morbidity and stay longer in hospital. METHODS: In this retrospective, multicentre study, electronic data of children born at five hospitals in Switzerland were recorded. Short-term outcome of late preterm infants was compared with a control group of full-term infants (39 0/7 to 40 6/7 weeks of gestation). Multiple gestations, pregnancies complicated by foetal malformations, maternal consumption of illicit drugs and infants with incomplete documentation were excluded. The results were corrected for gender imbalance. RESULTS: Data from 530 late preterm and 1686 full-term infants were analysed. Compared with full-term infants, late preterm infants had a significant higher morbidity: respiratory distress (34.7% vs. 4.6%), hyperbilirubinaemia (47.7% vs. 3.4%), hypoglycaemia (14.3% vs. 0.6%), hypothermia (2.5% vs. 0.6%) and duration of hospitalization (mean, 9.9 days vs. 5.2 days). The risk to develop at least one complication was 7.6 (95% CI: 6.2-9.6) times higher among late preterm infants (70.8%) than among full-term infants (9.3%). CONCLUSION: Singleton late preterm infants show considerably higher rate of medical complications and prolonged hospital stay compared with matched full-term infants and therefore need more medical and financial resources.
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Idade Gestacional , Doenças do Prematuro/epidemiologia , Recém-Nascido Prematuro , Nascimento a Termo , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Morbidade , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologiaRESUMO
OBJECTIVES: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. METHODS: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. RESULTS: Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. CONCLUSIONS: As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.
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Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Teorema de Bayes , Contagem de Linfócito CD4 , Estudos de Coortes , Darunavir , Farmacorresistência Viral , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Terapia de Salvação , Resultado do Tratamento , Carga ViralRESUMO
Blood cultures are routinely taken in outpatients with fever and suspected bacterial infections. However, in the majority of cases, they are not informative and of limited value for clinical decision making. The aim of this study was therefore to investigate factors associated with positive blood cultures in outpatients presenting to an outpatient clinic and emergency room. This was a case-control study of all outpatients with positive blood cultures from January 1, 2006 to October 31, 2007 and matched control patients with negative blood cultures in the same time period. Microbiology results and medical charts were reviewed to determine factors associated with positive blood cultures. The presence of a systemic inflammation response syndrome (SIRS) (OR 2.7, 95% Cl 1.0-7.2) and increased C-reactive protein (CRP) (OR 1.1 per 10 mg/l, 95% Cl 1.0-1.2) were the most powerful predictive values for the development of positive blood cultures. In positive cases serum albumin was lower (35 mg/l versus 39 mg/l) than in controls. SIRS, increasing CRP and low albumin were associated with positive blood cultures in outpatients. With simple clinical assessment and few laboratory tests indicative of infection, it is possible to define a group at higher risk for bacteremia in outpatients.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/patologia , Sangue/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Albumina Sérica/análise , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto JovemRESUMO
BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.
Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por HIV/diagnóstico , Virologia/métodos , Adulto , Algoritmos , Feminino , HIV-1/classificação , HIV-1/genética , HIV-1/imunologia , Humanos , Imunoensaio , Masculino , RNA Viral/sangue , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cranial ultrasound (cUS) findings help doctors in the clinical management of preterm infants and in their discussion with parents regarding prediction of outcome. cUS is often used as outcome measure in clinical research studies. Accurate cUS performance and interpretation is therefore required. AIMS: The aims of this study were (i) to assess the interobserver variability in cUS interpretation, and (ii) to evaluate whether level of cUS expertise influences the interobserver variability. METHODS: Fifty-eight cUS image series of preterm infants born below 32 weeks of gestation collected within the Swiss Neonatal Network were sent to 27 observers for reviewing. Observers were grouped into radiologists, experienced neonatologists and less experienced neonatologists. Agreement between observers was calculated using Kappa statistics. RESULTS: When cystic periventricular leukomalacia, intraventricular haemorrhage and periventricular haemorrhagic infarction were combined to one outcome, agreement among all observers was moderate. When divided into subgroups, kappa for the combined outcome was 0.7 for experienced neonatologists, 0.67 for radiologists and 0.53 for inexperienced neonatologists. Marked difference in interobserver agreement between experienced neonatologists and radiologists could be found for haemorrhagic periventricular ifraction (HPI). CONCLUSIONS: Our results suggest that interobserver agreement for interpretation of cUS varies from poor to good varying with the type of abnormality and level of expertise, suggesting that widespread structured training should be made available to improve the performance and interpretation of cUS.
Assuntos
Encefalopatias/diagnóstico por imagem , Ecoencefalografia/métodos , Recém-Nascido Prematuro , Feminino , Humanos , Recém-Nascido , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SuíçaRESUMO
BACKGROUND: Premature infants are often stressed by the current retinopathy of prematurity (ROP) screening procedure. Additionally, only < 10 % of the screened infants will develop a ROP stadium requiring laser therapy. Therefore the present screening strategy is unsatisfactory. Furthermore, the current guidelines do not take into account postnatal factors. A new method considering postnatal factors is the weight, insulin-like growth factor, neonatal ROP (WINROP) algorithm. This approach is based on the early postnatal weight gain. The aim of this study was to assign the WINROP-algorithm to a preterm population in Switzerland and to analyze its ability for prediction. PATIENTS AND METHODS: In this retrospective study, all preterm infants with a gestational age (GA) < 32 weeks and/or a birth weight (BW) ≤ 1500 g taken care of in the Department of Neonatology at the University Hospital Zurich from January 2003 to December 2008 were included. The weekly postnatal weight gain was analyzed by means of the modified WINROP-algorithm. RESULTS: Altogether 376 preterm infants were analyzed. In 58 infants a "high-risk" alarm was released, thereof eight preterms developed a severe ROP and four of them needed laser therapy. CONCLUSIONS: The high predictive value of the WINROP-algorithm was confirmed in our population of Swiss preterms. This instrument has the potential to simplify the current ROP screening procedure. Accordingly, the amount of ophthalmoscopies could be reduced significantly.
Assuntos
Programas de Rastreamento/métodos , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia , Aumento de Peso , Comorbidade , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade , Suíça/epidemiologiaRESUMO
BACKGROUND: Our aim was to evaluate the clinical impact of routine amniotic fluid and neonatal surface swab microbiology at Caesarean section. MATERIALS AND METHODS: Microbiology data from 1 537 neonates delivered by Caesarean section were analysed in the light of clinical outcome. RESULTS: 1 340 (87%) neonates had non-pathogenic bacteria or negative culture results from both amniotic fluid and surface swab samples. Of the 197 (13%) neonates with pathogenic bacteria, 22 (1.4%) were diagnosed with infection, but only in 6 (0.4%) were the bacteria presumed to be responsible for the infection. Amniotic fluid and surface swab culture had sensitivities of 54% and 35%, and positive predictive values of 14% and 17%, respectively, for detecting a neonate at risk of infection. CONCLUSION: Amniotic fluid and neonatal surface swab microbiology at Caesarean section contributes little if anything to postnatal management and can be safely dropped from operative routine.