Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
Front Genet ; 13: 1041462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406113

RESUMO

Background: The Sickle Pan-African Research Consortium (SPARCO) and Sickle Africa Data Coordinating Center (SADaCC) were set up with funding from the US National Institute of Health (NIH) for physicians, scientists, patients, support groups, and statisticians to collaborate to reduce the high disease burden and alleviate the impact of Sickle Cell Disease (SCD) in Africa. For 5 years, SPARCO and SADaCC have been collecting basic clinical and demographic data from Nigeria, Tanzania, and Ghana. The resulting database will support analyses to estimate significant clinical events and provide directions for targeting interventions and assessing their impacts. Method: The Nigerian study sited at Centre of Excellence for Sickle Cell Disease Research and Training (CESRTA), University of Abuja, adopted REDCap for online database management. The case report form (CRF) was adapted from 1,400 data elements adopted by SPARCO sites. It captures 215 data elements of interest across sub-sites, i.e., demographic, social, diagnostic, clinical, laboratory, imaging, and others. These were harmonized using the SADaCC data dictionary. REDCap was installed on University of Abuja cloud server at https://www.redcap.uniabuja.edu.ng. Data collected at the sites are sent to CESRTA for collation, cleaning and uploading to the database. Results: 7,767 people living with sickle cell disease were enrolled at 25 health institutions across the six zones in Nigeria with 5,295 having had at least one follow-up visit with their clinical data updated. They range from 44 to 1,180 from 3 centers from South East, 4 from South, 5 from South West, 8 from North Central, 4 in North West and 3 in the North East. North West has registered 1,383 patients, representing 17.8%; North East, 359 (4.6%); North Central, 2,947 (37.9%); South West, 1,609 (20.7%); South, 442 (5.7%) and South East, 1,027 patients (13.2%). Conclusion: The database is being used to support studies including analysis of clinical phenotypes of SCD in Nigeria, and evaluation of Hydroxyurea use in SCD. Reports undergoing review in journals have relied on the ease of data access in REDCap. The database is regularly updated by batch and individual record uploads while we are utilizing REDCap's in-built functions to generate simple statistic.

2.
Afr J Emerg Med ; 11(1): 46-52, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33437593

RESUMO

INTRODUCTION: South Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation. METHODS: We conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability. RESULTS: We included 1010 EU presentations and assessed 80/1010 (7.9%) as ADR-related, including 20/239 (8.4%) presentations among HIV-positive attendees. Among HIV-positive EU attendees with ADRs 17/20 (85%) were admitted, versus 22/60 (37%) of HIV-negative/unknown EU attendees. Only 5/21 (24%) ADRs in HIV-positive EU attendees were preventable, versus 24/63 (38%) in HIV-negative/unknown EU attendees. On multivariate analysis, only increasing drug count was associated with ADR-related EU presentation (adjusted odds ratio 1.10 per additional drug, 95% confidence interval 1.03 to 1.18), adjusted for age, sex, HIV status, comorbidity, and hospital. CONCLUSIONS: ADRs caused a significant proportion of EU presentations, similar to findings from other resource-limited settings. The spectrum of ADR manifestations in our EUs reflects South Africa's colliding epidemics of infectious and non-communicable diseases. ADRs among HIV-positive EU attendees were more severe and less likely to be preventable.

3.
Clin Infect Dis ; 73(9): e3377-e3383, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32845997

RESUMO

BACKGROUND: Liver injury is a common complication of anti-tuberculosis therapy. N-acetylcysteine (NAC) used in patients with paracetamol toxicity with limited evidence of benefit in liver injury due to other causes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy of intravenous NAC in hospitalized adult patients with anti-tuberculosis drug-induced liver injury (AT-DILI). The primary endpoint was time for serum alanine aminotransferase (ALT) to fall below 100 U/L. Secondary endpoints included length of hospital stay, in-hospital mortality, and adverse events. RESULTS: Fifty-three participants were randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female, 89 (87%) were HIV positive. Median (IQR) serum ALT and bilirubin at presentation were 462 (266-790) U/L and 56 (25-100) µmol/L, respectively. Median time to ALT <100 U/L was 7.5 (6-11) days in the NAC arm and 8 (5-13) days in the placebo arm. Median time to hospital discharge was shorter in the NAC arm (9 [6-15] days) than in the placebo arm (18 [10-25] days) (HR, 1.73; 95% CI, 1.13-2.65). Mortality was 14% overall and did not differ by study arm. The study infusion was stopped early due to an adverse reaction in 5 participants receiving NAC (nausea and vomiting [3], anaphylaxis [1], pain at drip site [1]). CONCLUSIONS: NAC did not shorten time to ALT <100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay. NAC should be considered in management of AT-DILI. CLINICAL TRIALS REGISTRATION: South African National Clinical Trials Registry (SANCTR: DOH-27-0414-4719).


Assuntos
Acetilcisteína , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen , Acetilcisteína/efeitos adversos , Administração Intravenosa , Adulto , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos
4.
BMC Pediatr ; 20(1): 3, 2020 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901244

RESUMO

BACKGROUND: The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children's hospitals. METHODS: We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs. RESULTS: Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug). CONCLUSIONS: Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , África do Sul/epidemiologia
5.
S Afr J Infect Dis ; 34(1): 118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-34485456

RESUMO

BACKGROUND: Antibiotic resistance (ABR) is a global health crisis. We conducted a cross-sectional survey to describe South African patients' (n = 782) ABR knowledge, attitudes and perceptions (KAP), differences in KAP between public (n = 379, 48%) and private (n = 403, 52%) practice respondents and associations between attitudes, perceptions and knowledge scores. METHODS: Knowledge scores (15 questions) were placed into low (0% - 53%) and high (> 54%) categories (below and above overall mean). Comparisons were conducted using chi-squared and t-tests. RESULTS: Of all respondents, 72% believed it was the human body that becomes resistant to antibiotics, 66% stated that antibiotics are good for treating viruses and 25% of patients believed that people should be given antibiotics on demand. Mean knowledge scores were lower in public sector respondents (public 45%, s.d. 15%; private 60%, s.d. 30%; p ≤ 0.001). Public practice patients with high knowledge scores were more likely to report both negative KAP (antibiotic prescriptions justify doctors' visits, scientists will discover new antibiotics) and protective KAP (finishing a course of antibiotics, antibiotics do not treat all illnesses). Private practice patients with high knowledge scores were marginally less likely to report negative KAP (wanting antibiotics after long illnesses or when very sick) and more likely to report protective KAP (antibiotics have side effects and are a strong treatment). CONCLUSION: Our study shows differences in KAP by practice type and that greater knowledge increases the likelihood of protective attitudes, perceptions and behaviours.

6.
Clin Infect Dis ; 68(9): 1522-1529, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30165431

RESUMO

BACKGROUND: Bedaquiline is used as a substitute for second-line injectable (SLI) intolerance in the treatment of multidrug-resistant (MDR) tuberculosis, but the efficacy and safety of this strategy is unknown. METHODS: In this retrospective cohort study adults receiving bedaquiline substitution for MDR tuberculosis therapy, plus a matched control group who did not receive bedaquiline, were identified from the electronic tuberculosis register in the Western Cape Province, South Africa. The primary outcome measure was the proportion of patients with death, loss to follow-up, or failure to achieve sustained culture conversion at 12 months of treatment. RESULTS: Data from 162 patients who received bedaquiline substitution and 168 controls were analyzed; 70.6% were infected with human immunodeficiency virus. Unfavorable outcomes occurred in 35 of 146 (23.9%) patients in the bedaquiline group versus 51 of 141 (36.2%) in the control group (relative risk, 0.66; 95% confidence interval, .46 -.95). The number of patients with culture reversion was lower in those receiving bedaquiline (1 patient; 0.8%) than in controls (12 patients; 10.3%; P = .001). Delayed initiation of bedaquiline was independently associated with failure to achieve sustained culture conversion (adjusted odds ratio for every 30-day delay, 1.5; 95% confidence interval, 1.1-1.9). Mortality rates were similar at 12 months (11 deaths in each group; P = .97). CONCLUSIONS: Substituting bedaquiline for SLIs in MDR tuberculosis treatment resulted in improved outcomes at 12 months compared with patients who continued taking SLIs, supporting the use of bedaquiline for MDR tuberculosis treatment in programmatic settings.


Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Coinfecção , Etambutol/uso terapêutico , Etionamida/uso terapêutico , Feminino , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Isoniazida/uso terapêutico , Isoxazóis/uso terapêutico , Levofloxacino/uso terapêutico , Masculino , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Oxazolidinonas/uso terapêutico , Pirazinamida/uso terapêutico , Estudos Retrospectivos , África do Sul , Análise de Sobrevida , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/patologia
7.
J Acquir Immune Defic Syndr ; 80(3): 325-329, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531296

RESUMO

BACKGROUND: Most adults with virological failure on second-line antiretroviral therapy (ART) in resource-limited settings have no major protease inhibitor (PI) resistance mutations. Therefore, empiric switches to third-line ART would waste resources. Genotypic antiretroviral resistance testing (GART) is expensive and has limited availability. A clinical prediction rule (CPR) for PI resistance could rationalize access to GART. SETTING: A private sector ART cohort, South Africa. METHODS: We identified adults with virologic failure on ritonavir-boosted lopinavir/atazanavir-based ART and GART. We constructed a multivariate logistic regression model including age, sex, PI duration, short-term adherence (using pharmacy claims), concomitant CYP3A4-inducing drugs, and viral load at time of GART. We selected variables for the CPR using a stepwise approach and internally validated the model by bootstrapping. RESULTS: 148/339 (44%) patients had PI resistance (defined as ≥ 1 major resistance mutation to current PI). The median age was 42 years (interquartile range 36-48), 212 (63%) were females, 308 (91%) were on lopinavir/ritonavir, and median PI duration was 2.6 years (interquartile range 1.6-4.7). Variables associated with PI resistance and included in the CPR were age {adjusted odds ratio (aOR) 1.96 (95% confidence interval [CI]: 1.42 to 2.70) for 10-year increase}, PI duration (aOR 1.14 [95% CI: 1.03 to 1.26] per year), and adherence (aOR 1.22 [95% CI: 1.12 to 1.33] per 10% increase). The CPR model had a c-statistic of 0.738 (95% CI: 0.686 to 0.791). CONCLUSIONS: Older patients with high adherence and prolonged PI exposure are most likely to benefit from GART to guide selection of a third-line ART regimen. Our CPR to select patients for GART requires external validation before implementation.


Assuntos
Sulfato de Atazanavir/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Lopinavir/farmacologia , Adulto , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação
8.
South Afr J HIV Med ; 19(1): 851, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30167340

RESUMO

BACKGROUND: The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill HIV-infected patients recommends that treatment for Pneumocystis jirovecii pneumonia (PJP) should be considered without giving clear guidance on selecting patients for empiric PJP therapy. PJP is a common cause of hospitalisation in HIV-infected patients in resource-poor settings where diagnostic facilities are limited. METHODS: We developed clinical prediction rules for PJP in a prospective cohort of HIV-infected inpatients with WHO danger signs and cough of any duration. The reference standard for PJP was > 1000 copies/mL of P. jirovecii DNA on real-time sputum polymerase chain reaction (PCR). Four potentially predictive variables were selected for regression models: dyspnoea, chest X-ray, haemoglobin and oxygen saturation. Respiratory rate was explored as a replacement for oxygen saturation as pulse oximetry is not always available in resource-poor settings. RESULTS: We enrolled 500 participants. After imputation for missing values, there were 56 PJP outcome events. Dyspnoea was not independently associated with PJP. Oxygen saturation and respiratory rate were inversely correlated. Two clinical prediction rules were developed: chest X-ray possible/likely PJP, haemoglobin ≥ 9 g/dL and either oxygen saturation < 94% or respiratory rate. The area under the receiver operating characteristic curve of the clinical prediction rule models was 0.761 (95% CI 0.683-0.840) for the respiratory rate model and 0.797 (95% CI 0.725-0.868) for the oxygen saturation model. Both models had zero probability for PJP for scores of zero, and positive likelihood ratios exceeded 10 for high scores. CONCLUSION: We developed simple clinical prediction rules for PJP, which, if externally validated, could assist decision-making in the WHO seriously ill algorithm.

9.
Int J Infect Dis ; 75: 67-73, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30125689

RESUMO

BACKGROUND: Tuberculosis is a major cause of mortality among HIV-infected inpatients, and the World Health Organization (WHO) recommends an algorithm to improve diagnosis. The urine lateral flow lipoarabinomannan (LAM) and sputum Xpert MTB/RIF tests are promising tools, but the optimal diagnostic algorithm is unclear. METHODS: This prospective cohort study enrolled HIV-positive inpatients with cough and WHO danger signs. The Xpert MTB/RIF test and mycobacterial culture were performed on sputum using sputum induction when necessary, and the LAM test was performed on stored urine. Tuberculosis was diagnosed by culture from any site. The diagnostic accuracy and costs of testing were determined for single and combined tests. RESULTS: Tuberculosis was confirmed in 169 of 332 patients (50.9%). The yield of LAM, Xpert MTB/RIF on spontaneous sputum (Xpert Spot), and Xpert MTB/RIF on spontaneous or induced sputum (Xpert SI) was 35.5%, 23.1%, and 90.5%, respectively. When LAM was placed before Xpert Spot and Xpert SI in an algorithm, the yield was 50.9% and 92.3%, respectively. Adding culture to Xpert MTB/RIF only increased the yield by 1.2% and 2.7%, respectively. Use of the LAM test reduced costs. CONCLUSIONS: Sputum induction is important to increase the yield of Xpert MTB/RIF for seriously ill patients with HIV and cough. LAM testing has little effect on yield when sputum induction is available, but reduces costs and may have other benefits.


Assuntos
Técnicas e Procedimentos Diagnósticos/economia , Infecções por HIV/complicações , Lipopolissacarídeos/urina , Escarro/química , Tuberculose/diagnóstico , Adulto , Algoritmos , Feminino , Humanos , Lipopolissacarídeos/economia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/fisiologia , Estudos Prospectivos , Escarro/microbiologia , Tuberculose/economia , Tuberculose/etiologia , Tuberculose/microbiologia
10.
AIDS Res Ther ; 15(1): 5, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29433509

RESUMO

BACKGROUND: Criteria for the 2007 WHO algorithm for diagnosing tuberculosis among HIV-infected seriously ill patients are the presence of one or more danger signs (respiratory rate > 30/min, heart rate > 120/min, temperature > 39 °C, and being unable to walk unaided) and cough ≥ 14 days. Determining predictors of poor outcomes among HIV-infected inpatients presenting with WHO danger signs could result in improved treatment and diagnostic algorithms. METHODS: We conducted a prospective cohort study of inpatients presenting with any duration of cough and WHO danger signs to two regional hospitals in Cape Town, South Africa. The primary outcome was all-cause mortality up to 56 days post-discharge, and the secondary outcome a composite of any one of: hospital admission for > 7 days, died in hospital, transfer to a tertiary level or tuberculosis hospital. We first assessed the WHO danger signs as predictors of poor outcomes, then assessed the added value of other variables selected a priori for their ability to predict mortality in common respiratory opportunistic infections (CD4 count, body mass index (BMI), being on antiretroviral therapy (ART), hypotension, and confusion) by comparing the receiver operating characteristic (ROC) area under the curve (AUC) of the two multivariate models. RESULTS: 484 participants were enrolled, median age 36, 66% women, 53% had tuberculosis confirmed on culture. The 56-day mortality was 13.2%. Inability to walk unaided, low BMI, low CD4 count, and being on ART were independently associated with poor outcomes. The multivariate model of the WHO danger signs showed a ROC AUC of 0.649 (95% CI 0.582-0.717) for predicting 56-day mortality, which improved to ROC AUC of 0.740 (95% CI 0.681-0.800; p = 0.004 for comparison between the two ROC AUCs) with the multivariate model including the a priori selected variables. Findings were similar in sub-analyses of participants with culture-positive tuberculosis and with cough duration ≥ 14 days. CONCLUSION: The study design prevented a rigorous evaluation of the prognostic value of the WHO danger signs. Our prognostic model could result in improved algorithms, but needs to be validated.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Pacientes Internados , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Algoritmos , Coinfecção , Feminino , Infecções por HIV/mortalidade , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença , Organização Mundial da Saúde , Adulto Jovem
11.
Clin Infect Dis ; 66(9): 1419-1426, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29126226

RESUMO

Background: The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill human immunodeficiency virus (HIV)-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients. Methods: We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defined danger signs. Culture-positive tuberculosis from any site was the reference standard. A priori selected variables were assessed for univariate associations with tuberculosis. The most predictive variables were assessed in a multivariate logistic regression model and used to establish a clinical prediction rule for diagnosing tuberculosis. Results: We enrolled 484 participants. The median age was 36 years, 65.5% were female, the median CD4 count was 89 cells/µL, and 35.3% were on antiretroviral therapy. Tuberculosis was diagnosed in 52.7% of participants. The c-statistic of our clinical prediction rule (variables: cough ≥14 days, unable to walk unaided, temperature >39°C, chest radiograph assessment, hemoglobin, and white cell count) was 0.811 (95% confidence interval, .802-.819). The classic tuberculosis symptoms (fever, night sweats, weight loss) added no discriminatory value in diagnosing tuberculosis. Xpert MTB/RIF assay sensitivity was 86.3% and specificity was 96.1%. Conclusions: Our clinical prediction rule had good diagnostic utility for tuberculosis among seriously ill HIV-infected inpatients. Xpert MTB/RIF assay, incorporated into the updated 2016 WHO algorithm, had high sensitivity and specificity in this population. Our findings could facilitate improved diagnosis of tuberculosis among seriously ill HIV-infected inpatients in resource-constrained settings.


Assuntos
Algoritmos , Infecções por HIV/microbiologia , Pacientes Internados/estatística & dados numéricos , Tuberculose Pulmonar/diagnóstico , Tuberculose/diagnóstico , Adulto , Contagem de Linfócito CD4 , Tosse/etiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Logísticos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Valor Preditivo dos Testes , Estudos Prospectivos , Radiografia Torácica , África do Sul , Tórax/diagnóstico por imagem , Organização Mundial da Saúde
12.
S Afr Med J ; 107(5): 405-410, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28492121

RESUMO

BACKGROUND: Education of medical students has been identified by the World Health Organization as an important aspect of antibiotic resistance (ABR) containment. Surveys from high-income countries consistently reveal that medical students recognise the importance of antibiotic prescribing knowledge, but feel inadequately prepared and require more education on how to make antibiotic choices. The attitudes and knowledge of South African (SA) medical students regarding ABR and antibiotic prescribing have never been evaluated. OBJECTIVE: To evaluate SA medical students' perceptions, attitudes and knowledge about antibiotic use and resistance, and the perceived quality of education relating to antibiotics and infection. METHODS: This was a cross-sectional survey of final-year students at three medical schools, using a 26-item self-administered questionnaire. The questionnaires recorded basic demographic information, perceptions about antibiotic use and ABR, sources, quality, and usefulness of current education about antibiotic use, and questions to evaluate knowledge. Hard-copy surveys were administered during whole-class lectures. RESULTS: A total of 289 of 567 (51%) students completed the survey. Ninety-two percent agreed that antibiotics are overused and 87% agreed that resistance is a significant problem in SA - higher proportions than those who thought that antibiotic overuse (63%) and resistance (61%) are problems in the hospitals where they had worked (p<0.001). Most reported that they would appreciate more education on appropriate use of antibiotics (95%). Only 33% felt confident to prescribe antibiotics, with similar proportions across institutions. Overall, prescribing confidence was associated with the use of antibiotic prescribing guidelines (p=0.003), familiarity with antibiotic stewardship (p=0.012), and more frequent contact with infectious diseases specialists (p<0.001). There was an overall mean correct score of 50% on the knowledge questionnaire, with significant differences between institutions. Students who used antibiotic prescribing guidelines and found their education more useful scored higher on knowledge questionnaires. CONCLUSION: There are low levels of confidence with regard to antibiotic prescribing among final-year medical students in SA, and most students would like more education in this area. Perceptions that ABR is less of a problem in their local setting may contribute to inappropriate prescribing behaviours. Differences exist between medical schools in knowledge about antibiotic use, with suboptimal scores across institutions. The introduction and use of antibiotic prescribing guidelines and greater contact with specialists in antibiotic prescribing may improve prescribing behaviours.

13.
Pediatr Infect Dis J ; 36(3): 250-255, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27870815

RESUMO

BACKGROUND: Existing clinical decision rules (CDRs) to diagnose group A streptococcal (GAS) pharyngitis have not been validated in sub-Saharan Africa. We developed a locally applicable CDR while evaluating existing CDRs for diagnosing GAS pharyngitis in South African children. METHODS: We conducted a prospective cohort study and enrolled 997 children 3-15 years of age presenting to primary care clinics with a complaint of sore throat, and whose parents provided consent. Main outcome measures were signs and symptoms of pharyngitis and a positive GAS culture from a throat swab. Bivariate and multivariate analyses were used to develop the CDR. In addition, the diagnostic effectiveness of 6 existing rules for predicting a positive culture in our cohort was assessed. RESULTS: A total of 206 of 982 children (21%) had a positive GAS culture. Tonsillar swelling, tonsillar exudates, tender or enlarged anterior cervical lymph nodes, absence of cough and absence of rhinorrhea were associated with positive cultures in bivariate and multivariate analyses. Four variables (tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough), when used in a cumulative score, showed 83.7% sensitivity and 32.2% specificity for GAS pharyngitis. Of existing rules tested, the rule by McIsaac et al had the highest positive predictive value (28%), but missed 49% of the culture-positive children who should have been treated. CONCLUSION: The new 4-variable CDR for GAS pharyngitis (ie, tonsillar swelling and one of tonsillar exudate, no rhinorrhea, no cough) outperformed existing rules for GAS pharyngitis diagnosis in children with symptomatic sore throat in Cape Town.


Assuntos
Faringite/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes , Criança , Sistemas de Apoio a Decisões Clínicas , Feminino , Humanos , Masculino , Faringite/microbiologia , Estudos Prospectivos , Índice de Gravidade de Doença , África do Sul , Infecções Estreptocócicas/microbiologia
14.
AIDS Res Ther ; 13: 40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27891161

RESUMO

BACKGROUND: Gynaecomastia is associated with exposure to antiretroviral therapy (ART), in particular efavirenz. There is limited data on clinical characteristics of patients with ART-associated gynaecomastia in resource-limited settings and little guidance on the optimal management of this adverse drug reaction (ADR). We describe the clinical characteristics, management and outcomes of gynaecomastia cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in South Africa. METHODS: We identified all gynaecomastia cases in adolescent boys and men on ART reported to the hotline between June 2013 and July 2014. We collected follow up data telephonically at monthly intervals to document clinical management and outcomes. RESULTS: We received 51 reports of gynaecomastia between June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the hotline. All patients were on efavirenz-based ART. Mean age was 34 years (standard deviation 12) and seven were adolescents. The median onset of gynaecomastia was 15 months after efavirenz initiation (interquartile range 6-42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%). Serum testosterone was quantified in 25 of 35 patients with follow up data, and was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in 29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). CONCLUSIONS: Gynaecomastia was a frequently reported ADR in our setting, occurring with prolonged efavirenz exposure. Testosterone was low in the minority of tested cases. Most clinicians elected to switch patients off efavirenz, and gynaecomastia improved in the majority.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Ginecomastia/epidemiologia , Linhas Diretas/estatística & dados numéricos , Adolescente , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Criança , Ciclopropanos , Ginecomastia/induzido quimicamente , Ginecomastia/diagnóstico , Ginecomastia/terapia , Infecções por HIV/tratamento farmacológico , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , África do Sul/epidemiologia , Testosterona/sangue , Resultado do Tratamento
15.
Pharmacoepidemiol Drug Saf ; 25(11): 1313-1319, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27464823

RESUMO

PURPOSE: Severe skin reactions may complicate combination antiretroviral therapy (cART). Nevirapine is known to be associated with severe skin reactions, but there are conflicting data on risk factors in African patients. We reviewed cases of severe skin reactions admitted to a tertiary hospital in Cape Town, South Africa. We identified associations with severe skin reactions in patients on cART. METHODS: We described severe skin reaction cases in patients taking cART admitted to Groote Schuur Hospital in Cape Town, South Africa, between 2006 and 2012. We included those patients who developed a severe skin reaction within 120 days of cART initiation in a case-control analysis. We identified control patients matched on date of cART initiation and primary care facility by linkage with the Western Cape electronic provincial HIV database. We conducted a conditional (fixed effects) logistic regression modelling. RESULTS: We identified 169 severe skin reactions in patients on cART. The most common presentations were Stevens Johnson syndrome/toxic epidermal necrolysis (49%) and drug hypersensitivity syndrome (36%). One hundred forty-one patients were female, of which 27 were pregnant. Median duration of hospitalization was 12 days (interquartile range 8 to 19) and six patients died. We included 91 cases and 361 matched controls in the analysis. Severe skin reaction was associated with nevirapine exposure, adjusted odds ratio of 7.6 (95%CI 3.7 to 15.7) and with pregnancy, adjusted odds ratio 3.7 (95%CI 1.3 to 10.8) compared with men. CONCLUSIONS: Severe skin reactions resulted in prolonged admission to hospital in this setting. We found that nevirapine use and pregnancy are independently associated with severe skin reaction. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Toxidermias/etiologia , Nevirapina/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Estudos de Casos e Controles , Toxidermias/epidemiologia , Toxidermias/fisiopatologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Logísticos , Masculino , Nevirapina/administração & dosagem , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , África do Sul , Síndrome de Stevens-Johnson/epidemiologia
16.
Int J Antimicrob Agents ; 48(2): 158-62, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27345268

RESUMO

Considering that most patients who experience virological failure (VF) on lopinavir-based antiretroviral therapy (ART) fail due to poor adherence rather than resistance, an objective adherence measure could limit costs by rationalising the use of genotype antiretroviral resistance testing (GART) in countries with access to third-line ART. A cross-sectional study was conducted in a resource-limited setting at two large clinics in Kwazulu-Natal, South Africa, in patients experiencing VF (HIV-RNA > 1000 copies/mL) on lopinavir-based ART who had undergone GART. Associations between major protease inhibitor (PI) resistance mutations and random plasma lopinavir concentrations were explored. A total of 134 patients, including 31 children, were included in the analysis. The prevalence of patients with major PI resistance mutations was 20.9% (n = 28). A random lopinavir concentration above the recommended minimum trough of 1 µg/mL [adjusted odds ratio (aOR) = 5.81, 95% confidence interval (CI) 2.04-16.50; P = 0.001] and male sex (aOR = 3.19, 95% CI 1.22-8.33; P = 0.018) were predictive of the presence of at least one major PI resistance mutation. Random lopinavir concentrations of <1 µg/mL had a negative predictive value of 91% for major PI resistance mutations. Random lopinavir concentrations are strongly associated with the presence of major PI resistance mutations. Access to costly GART in patients experiencing VF on second-line ART could be restricted to patients with lopinavir concentrations above the recommended minimum trough of 1 µg/mL or, in areas where GART is unavailable, could be used as a criterion to empirically switch to third-line ART.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Lopinavir/farmacologia , Adesão à Medicação , Plasma/química , Adolescente , Adulto , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Diagnóstico Diferencial , Feminino , Infecções por HIV/diagnóstico , Humanos , Lactente , Lopinavir/análise , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , África do Sul , Falha de Tratamento , Adulto Jovem
17.
Medicine (Baltimore) ; 95(19): e3437, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27175644

RESUMO

Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals' medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34-65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06-2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09-1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07-1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17-3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africa's high HIV and tuberculosis burden. Identification and management of these ADRs should be considered in HIV and tuberculosis care and treatment programs and should be emphasized in health care worker training programmes.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , África do Sul/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
18.
Drug Saf ; 39(2): 159-69, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26547719

RESUMO

INTRODUCTION: The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. METHODS: We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. RESULTS: We received 772 ADR reports, of which 87/772 (11.3%) were classified as certain, 176/772 (22.8%) as probable, 361/772 (46.8%) as possible, and 148/772 (19.2%) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6%), 87/624 (13.9%), and 77/624 (12.3%), respectively. The ADR was severe in 27.3% of rashes, 36.4% of kidney injury reports and 88.5% of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti-tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3%) improved, 9 (2.3%) had complete resolution, 32 (8.4%) remained unchanged, 6 (1.6%) deteriorated, 10 (2.6%) died and 72 (18.8%) had unknown outcome. Advice provided was followed in 93.2% of these cases. Of 223 ADRs with preventability data, 40 (17.9%) were preventable. CONCLUSION: Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority.


Assuntos
Injúria Renal Aguda/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Fármacos Anti-HIV/efeitos adversos , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Injúria Renal Aguda/etiologia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estudos Prospectivos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
19.
Br J Clin Pharmacol ; 80(4): 818-26, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25475751

RESUMO

AIMS: Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status. METHODS: We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was 'possible', 'probable' or 'certain' using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria. RESULTS: ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7). CONCLUSIONS: In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitais/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , África do Sul/epidemiologia , Adulto Jovem
20.
BMC Infect Dis ; 14: 664, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25472544

RESUMO

BACKGROUND: Most patients who experience virologic failure (VF) on second line antiretroviral therapy (ART) in low-middle income countries fail due to poor adherence rather than antiretroviral resistance. A simple adherence tool designed to detect VF would conserve resources by rationally limiting need for viral load (VL) testing and, in those countries with access to third line ART, the need for resistance testing. METHODS: We conducted an observational cohort study of patients who initiated second line ART at a clinic in Kwazulu-Natal, South Africa. Using clinical and pharmacy refill data extracted from the clinic's electronic database, we determined risk factors for VF. Three different methods of calculating short term pharmacy refill adherence were evaluated and compared with long term adherence since second line initiation. We also explored the ability of differing durations of short term pharmacy refill to predict VF on second line ART. RESULTS: We included 274 patients with a median follow up of 27 months on second line ART. VF ranged between 3% and 16% within each six month interval after initiating second line ART. 243 patients with at least one VL after 4 months on second line were analysed in the statistical analysis. Pharmacy refill adherence assessed over shorter periods (4 to 6 months) predicted virologic suppression as well as pharmacy refill assessed over longer periods. The risk of VF fell 73% with each 10% increase in adherence measured from pharmacy refills over a 4 month period. Low CD4 count at second line ART initiation was a significant independent risk factor for VF. CONCLUSION: Patients identified as poorly adherent by short term pharmacy refill are at risk for VF on second line ART. This pragmatic adherence tool could assist in identifying patients who require adherence interventions, and help rationalize use of VL monitoring and resistance testing among patients on second line ART.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adesão à Medicação , Adulto , Instituições de Assistência Ambulatorial , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Farmacorresistência Viral , Feminino , Humanos , Masculino , Fatores de Risco , África do Sul , Falha de Tratamento , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA