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AIM: The aim of the study was to explore practitioners' experiences and perspectives on continence training, in order to understand its relevance to practice and how take-up of, and engagement with, such training may be improved. DESIGN: 27 qualitative interviews were conducted with nursing, medical and allied health practitioners in three hospitals. METHODS: We analysed data thematically, both manually and with the aid of NVivo software. The research adheres to the consolidated criteria for reporting qualitative research checklist. RESULTS: Practitioners asserted the likely benefits of evidence-based continence training, including more judicious use of products, reduction in associated infection, better patient skin care and more facilitative communication with patients. Practitioners also identified preferred methods of continence training, according to their role and workload. To ensure better take-up of, and engagement with, continence training, it must be authorized as essential and provided in ways that reflect professional preferences and pragmatic resource considerations.
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Comunicação , Hospitais , Humanos , Pesquisa QualitativaRESUMO
CASE PRESENTATION: A 34-year-old man presented to Queen Elizabeth Central Hospital in Blantyre, Malawi with multiple enlarged right cervical lymph nodes. He had no associated constitutional symptoms. Fine-needle aspirate (FNA) of one of the lymph nodes was negative for acid-fast bacilli (AFB) by smear microscopy. The FNA specimen was not sent for histological examination. Mycobacterial culture and Xpert MTB/RIF were not available at the time. He tested positive for HIV but CD4 T-cell count was not requested at the time of HIV diagnosis, and he did not start antiretroviral therapy (ART) pending confirmation of the cause of lymphadenopathy. Excision biopsy of the lymph nodes was planned; however, the patient was lost to follow-up before the procedure was performed.
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Infecções por HIV , Mycobacterium tuberculosis , Adulto , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Mycobacterium tuberculosis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Bladder and bowel control difficulties affect 20% and 10% of the UK population, respectively, touch all age groups and are particularly prevalent in the older (65+ years) population. However, the quality of continence care is often poor, compromising patient health and well-being, increasing the risk of infection, and is a predisposing factor to nursing and residential home placement. OBJECTIVE: To identify factors that help or hinder good continence care for patients aged 65 years and over in hospital medical ward settings. Medical care, not surgical, was our exclusive focus. METHODS: We conducted 27 qualitative interviews with nursing, medical and allied health practitioners in three hospitals. We used a purposive sample and analysed data thematically, both manually and with the aid of NVivo software. RESULTS: Interviews revealed perspectives on practice promoting or inhibiting good quality continence care, as well as suggestions for improvements. Good continence care was said to be advanced through person-centred care, robust assessment and monitoring, and a proactive approach to encouraging patient independence. Barriers to quality care centred on lack of oversight, automatic use of incontinence products and staffing pressures. Suggested improvements centred on participatory care, open communication and care planning with a higher bladder and bowel health profile. In order to drive such improvements, hospital-based practitioners indicate a need and desire for regular continence care training. CONCLUSIONS: Findings help explain the persistence of barriers to providing good quality care for patients aged 65 years and over with incontinence. Resolute continence promotion, in hospitals and throughout the National Health Service, would reduce reliance on products and the accompanying risks of patient dependency and catheter-associated gram-negative bacteraemia. Robust assessment and care planning, open communication and regular continence care training would assist such promotion and also help mitigate resource limitations by developing safer, time-efficient continence care.
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Medicina Estatal , Incontinência Urinária , Idoso , Comunicação , Hospitais , Humanos , Pesquisa Qualitativa , Incontinência Urinária/epidemiologia , Incontinência Urinária/terapiaRESUMO
BACKGROUND: Non-communicable diseases (NCDs) such as diabetes and hypertension have become a prominent public health concern in Malawi, where health care services for NCDs are generally restricted to urban centres and district hospitals, while the vast majority of Malawians live in rural settings. Whether similar quality of diabetes care can be delivered at health centres compared to hospitals is not known. METHODS: We implemented a pilot project of decentralized diabetes care at eight health centres in four districts in Malawi. We described differences between district hospitals and rural health centres in terms of patient characteristics, diabetes complications, cardiovascular risk factors, and aspects of the quality of care and used multivariate logistic regression to explore factors associated with adequate diabetes and blood pressure control. RESULTS: By March 2019, 1339 patients with diabetes were registered of whom 286 (21%) received care at peripheral health centres. The median duration of care of patients in the diabetes clinics during the study period was 8.8 months. Overall, HIV testing coverage was 93.6%, blood pressure was recorded in 92.4%; 68.5% underwent foot examination of whom 35.0% had diabetic complications; 30.1% underwent fundoscopy of whom 15.6% had signs of diabetic retinopathy. No significant differences in coverage of testing for diabetes complications were observed between health facility types. Neither did we find significant differences in retention in care (72.1 vs. 77.6%; p=0.06), adequate diabetes control (35.0% vs. 37.8%; p=0.41) and adequate blood pressure control (51.3% vs. 49.8%; p=0.66) between hospitals and health centres. In multivariate analysis, male sex was associated with adequate diabetes control, while lower age and normal body mass index were associated with adequate blood pressure control; health facility type was not associated with either. CONCLUSION: Quality of care did not appear to differ between hospitals and health centres, but was insufficient at both levels.
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Diabetes Mellitus , Instituições de Assistência Ambulatorial , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Hospitais , Humanos , Malaui/epidemiologia , Masculino , Projetos Piloto , Atenção Primária à SaúdeRESUMO
Background: Mortality from bacterial meningitis, predominately caused by Streptococcus pneumoniae, exceeds 50% in sub-Saharan African countries with high HIV prevalence. Underlying causes of high mortality are poorly understood. We examined the host and pathogen proteome in the CSF of adults with proven pneumococcal meningitis (PM), testing if there was an association between differentially expressed proteins and outcome. Materials/Methods: CSF proteomes were analyzed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analyzed against mortality. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and neutrophil opsonophagocytic killing of S. pneumoniae. Results: CSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). Three hundred sixty individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential S. pneumoniae protein Elongation Factor Tu (EF-Tu) was significantly increased in CSF of non-survivors [False Discovery Rate (q) <0.001]. Expression of EF-Tu was negatively co-correlated against expression of Neutrophil defensin (r 0.4 p p < 0.002), but not against complement proteins C3 or Factor H. In vitro, addition of EF-Tu protein impaired S. pneumoniae neutrophil killing in CSF. Conclusions: Excessive S. pneumoniae EF-Tu protein in CSF was associated with reduced survival in meningitis in a high HIV prevalence population. We show EF-Tu may inhibit neutrophil mediated killing of S. pneumoniae in CSF. Further mechanistic work is required to better understand how S. pneumoniae avoids essential innate immune responses during PM through production of excess EF-Tu.
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Meningite Pneumocócica , Adulto , Feminino , Humanos , Imunidade Inata , Masculino , Fator Tu de Elongação de Peptídeos/metabolismo , Streptococcus pneumoniae/metabolismoRESUMO
BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in HIV-infected adults living in resource-limited countries. Comprehensive data on the aetiology are lacking but are needed to improve outcomes. METHODS: HIV-infected adults with severe (haemoglobin ≤70g/l) or very severe anaemia (haemoglobin ≤ 50 g/l) were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Fifteen potential causes and associations with anaemia severity and mortality were explored. RESULTS: 199 patients were enrolled: 42.2% had very severe anaemia and 45.7% were on ART. More than two potential causes for anaemia were present in 94% of the patients including iron deficiency (55.3%), underweight (BMI<20: 49.7%), TB infection (41.2%) and unsuppressed HIV infection (viral load >1000 copies/ml) (73.9%). EBV/CMV co-infection (16.5%) was associated with very severe anaemia (OR 2.8 95% CI 1.1-6.9). Overall mortality was high (53%; 100/199) with a median time to death of 17.5 days (IQR 6-55) days. Death was associated with folate deficiency (HR 2.2; 95% CI 1.2-3.8) and end stage renal disease (HR 3.2; 95% CI 1.6-6.2). CONCLUSION: Mortality among severely anaemic HIV-infected adults is strikingly high. Clinicians should be aware of the urgent need for a multifactorial approach including starting or optimising HIV treatment, considering TB treatment, nutritional support and optimising renal management.
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Anemia Ferropriva/etiologia , Infecções por HIV/complicações , Infecções por Herpesviridae/complicações , Desnutrição/complicações , Mortalidade , Tuberculose/complicações , Adulto , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por Herpesviridae/epidemiologia , Humanos , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Tuberculose/epidemiologiaRESUMO
INTRODUCTION: Iron deficiency is a treatable cause of severe anaemia in low-and-middle-income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-infection. METHODS: Severely anaemic (haemoglobin ≤70g/l) HIV-infected adults were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of blood markers (including hepcidin, mean corpuscular volume, mean cellular haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor (sTfR), sTfR index, sTfR-ratio) to detect BM-ID was evaluated by ROC area under the curve (AUCROC). RESULTS: Seventy-three patients were enrolled and 35 (48.0%) had BM-ID. Although hepcidin and MCV performed best (AUCROC of 0.593 and 0.545 respectively) all markers performed poorly in identifying BM-ID (ROC<0.6). The AUCROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) and in women 0.490 (sensitivity 60%, specificity 61%). CONCLUSION: BM-ID deficiency was common in severely anaemic HIV-infected patients. It is an important and potential treatable contributor to severe anaemia but lack of definitive biomarkers makes it difficult to accurately assess iron status in these patients. Further investigation of the potential of hepcidin is needed, including exploration of the differences in hepcidin results between males and females.
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Anemia Ferropriva/diagnóstico , Infecções por HIV/complicações , Hepcidinas/sangue , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Biomarcadores/sangue , Células da Medula Óssea/metabolismo , Feminino , Ferritinas/sangue , Humanos , Ferro/sangue , Malaui , Masculino , Receptores da Transferrina/sangue , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cardiovascular disease (CVD) risk among people living with HIV is elevated due to persistent inflammation, hypertension and diabetes comorbidity, lifestyle factors and exposure to antiretroviral therapy (ART). Data from Africa on how CVD risk affects morbidity and mortality among ART patients are lacking. We explored the effect of CVD risk factors and the Framingham Risk Score (FRS) on medium-term ART outcomes. METHODS: A prospective cohort study of standardized ART outcomes (Dead, Alive on ART, stopped ART, Defaulted and Transferred out) was conducted from July 2014-December 2016 among patients on ART at a rural and an urban HIV clinic in Zomba district, Malawi. The primary outcome was Dead. Active defaulter tracing was not done and patients who transferred out and defaulted were excluded from the analysis. At enrolment, hypertension, diabetes and dyslipidemia were diagnosed, lifestyle data collected and the FRS was determined. Cox-regression analysis was used to determine independent risk factors for the outcome Dead. RESULTS: Of 933 patients enrolled, median age was 42 years (IQR: 35-50), 72% were female, 24% had hypertension, 4% had diabetes and 15.8% had elevated total cholesterol. The median follow up time was 2.4 years. Twenty (2.1%) patients died, 50 (5.4%) defaulted, 63 (6.8%) transferred out and 800 (85.7%) were alive on ART care (81.7% urban vs. 89.9% rural). In multivariable survival analysis, male gender (aHR = 3.28; 95%CI: 1.33-8.07, p = 0.01) and total/HDL cholesterol ratio (aHR = 5.77, 95%CI: 1.21-27.32; p = 0.03) were significantly associated with mortality. There was no significant association between mortality and hypertension, body mass index, central obesity, diabetes, FRS, physical inactivity, smoking at enrolment, ART regimen and WHO disease stage. CONCLUSIONS: Medium-term all-cause mortality among ART patients was associated with male gender and elevated total/HDL cholesterol ratio.
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Antirretrovirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/epidemiologia , Doenças Metabólicas/epidemiologia , Adulto , Causas de Morte , Comorbidade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricosRESUMO
Background: Human immunodeficiency virus (HIV) programmes can be leveraged to manage the growing burden of non-communicable diseases (NCDs). Methods: In October 2015, a model of integrated HIV-NCD care was developed at a large HIV clinic in southeast Malawi. Blood pressure was measured in adults at every visit and random blood glucose was determined every 2 y. Uncomplicated antiretroviral therapy (ART)-only care was provided by nurses, integrated HIV-NCD management was provided by clinical officers. Waiting times were assessed using the electronic medical record system. The team met monthly to identify bottlenecks. Results: All (n=6036) adult HIV patients were screened and 765 were diagnosed with hypertension (prevalence 12.7% [95% confidence interval {CI} 11.9-13.5). A total of 2979 adult HIV patients were screened and 25 were diagnosed with diabetes mellitus (prevalence 0.8% [95% CI 0.6-1.2]). The mean duration of ART visits by clinical officers increased from 80.5 to 90 min during the first quarter following HIV-NCD integration but returned to 75 min the following quarter. The mean number of patients seen per day by clinical officers increased from 6 to 11 and for nurses decreased from 92 to 82 in that time period. The robust vertical HIV system made the design of integrated tools demanding. Challenges of integrated HIV-NCD care were related to patient flow, waiting times, NCD drug availability, data collection, clinic workload and the timing of diabetes and hypertension screening. Conclusions: Integrated HIV-NCD services provision was feasible in our clinic.
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Instituições de Assistência Ambulatorial/organização & administração , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Infecções por HIV/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Adulto , Glicemia , Pressão Sanguínea , Diabetes Mellitus/terapia , Eficiência Organizacional , Registros Eletrônicos de Saúde , Feminino , Infecções por HIV/tratamento farmacológico , Estilo de Vida Saudável , Humanos , Hipertensão/terapia , Malaui/epidemiologia , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Prevalência , Fatores de TempoRESUMO
OBJECTIVE: We explored if HIV infection is associated with impaired T-Helper 17 responses against Streptococcus pneumoniae in the lung. METHODS: We recruited 30 HIV-uninfected healthy controls, 23 asymptomatic HIV-infected adults not on ART, and 40 asymptomatic HIV-infected adults on ART (Median time 3.5yrs), in whom we collected bronchoalveolar lavage fluid. We measured alveolar CD4+ T cell immune responses following stimulation with pneumococcal cell culture supernatant using flow cytometry-based intracellular cytokine staining. RESULTS: We found that the proportion of alveolar CD4+ T cells producing IL-17A following stimulation with pneumococcal cell culture supernatant (CCS) was similar between HIV-uninfected controls and ART-naïve HIV-infected adults (0.10% vs. 0.14%; p = 0.9273). In contrast, the proportion and relative absolute counts of CD4+ T cells producing IL-17A in response to pneumococcal CCS were higher in ART-treated HIV-infected adults compared HIV-uninfected controls (0.22% vs. 0.10%, p = 0.0166; 5420 vs. 1902 cells/100 ml BAL fluid; p = 0.0519). The increase in relative absolute numbers of IL-17A-producing alveolar CD4+ T cells in ART-treated individuals was not correlated with the peripheral blood CD4+ T cell count (r=-0.1876, p = 0.1785). CONCLUSION: Alveolar Th17 responses against S. pneumoniae are preserved in HIV-infected adults. This suggests that there are other alternative mechanisms that are altered in HIV-infected individuals that render them more susceptible to pneumococcal pneumonia.
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Infecções por HIV/tratamento farmacológico , Interleucina-17/imunologia , Pulmão/imunologia , Pneumonia Pneumocócica/imunologia , Células Th17/imunologia , Adulto , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/virologia , Meios de Cultura/farmacologia , Feminino , Infecções por HIV/microbiologia , HIV-1/efeitos dos fármacos , Humanos , Interferon gama/imunologia , Lamivudina/uso terapêutico , Pulmão/citologia , Pulmão/microbiologia , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Nevirapina/uso terapêutico , Estavudina/uso terapêutico , Streptococcus pneumoniae , Células Th17/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia , Adulto JovemRESUMO
Disruption of lung cytokine networks during chronic HIV infection is incompletely restored in individuals on antiretroviral therapy.
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BACKGROUND: Mortality from acute bacterial meningitis (ABM) in sub-Saharan African adults and adolescents exceeds 50%. We tested if Goal Directed Therapy (GDT) was feasible for adults and adolescents with clinically suspected ABM in Malawi. MATERIALS AND METHODS: Sequential patient cohorts of adults and adolescents with clinically suspected ABM were recruited in the emergency department of a teaching hospital in Malawi using a before/after design. Routine care was monitored in year one (P1). In year two (P2), nurses delivered protocolised GDT (rapid antibiotics, airway support, oxygenation, seizure control and fluid resuscitation) to a second cohort. The primary endpoint was composite mean number of clinical goals attained. Secondary endpoints were individual goals attained and death or disability from proven or probable ABM at day 40. RESULTS: 563 patients with suspected ABM were enrolled in the study; 273 were monitored in P1; 290 patients with suspected ABM received GDT in P2. 61% were male, median age 33 years and 90% were HIV co-infected. ABM was proven or probable in 132 (23%) patients. GDT attained more clinical goals compared to routine care: composite mean number of goals in P1 was 0·55 vs. 1·57 in P2 GDT (p<0·001); Death or disability by day 40 from proven or probable ABM occurred in 29/57 (51%) in P1 and 38/60 (63%) in P2 (p = 0·19). CONCLUSION: Nurse-led GDT in a resource-constrained setting was associated with improved delivery of protocolised care. Outcome was unaffected. TRIAL REGISTRATION: www.isrctn.com ISRCTN96218197.
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Antibacterianos/uso terapêutico , Meningites Bacterianas/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , África Subsaariana , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments.
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Infecções por HIV/complicações , Acidente Vascular Cerebral/virologia , Vasculite/complicações , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/virologia , Malaui , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Vasculite/diagnóstico , Vasculite/virologia , Carga ViralRESUMO
AIMS: To describe the incidence and progression of retinopathy in people with diabetes in Southern Malawi over 5 years. To document visual loss in a setting where laser treatment is not available. METHODS: Subjects from a cohort sampled from a hospital-based, primary-care diabetes clinic in 2007 were traced in 2012. Laser treatment was not available. Modified Wisconsin grading of retinopathy was performed using slit lamp biomicroscopy by a single ophthalmologist in 2007 and using four-field mydriatic fundus photographs at an accredited reading centre in 2012. Visual acuity was measured by Snellen chart in 2007 and by 'Early Treatment of Diabetic Retinopathy Study' chart in 2012. HbA1c, blood pressure, HIV status, urine albumin-creatinine ratio, haemoglobin and lipids were measured. RESULTS: Of 281 subjects recruited in 2007, 135 (48%) were traced and assessed, 15 were confirmed dead. At follow-up (median 5.3 years) ≥2 step retinopathy progression was observed in 48 subjects (36.4%; 95% CI 28.2-44.6). Incidence of sight threatening diabetic retinopathy for those with level 10 (no retinopathy) and level 20 (background) retinopathy at baseline, was 19.4% (11.3-27.4) and 81.3% (62.1-100), respectively. In multivariate analysis 2 step progression was associated with HbA1c (OR 1.2495%CI 1.04-1.48), and haemoglobin level (0.77, 0.62-0.98). 25 subjects (18.8%) lost ≥5 letters, 7 (5.3%) lost ≥15 letters. CONCLUSIONS: Progression to sight threatening diabetic retinopathy from no retinopathy and background retinopathy was approximately 5 and 3 times that reported in recent European studies, respectively. Incidence of visual loss was high in a location where treatment was not available.
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Retinopatia Diabética/epidemiologia , Hemoglobinas Glicadas/metabolismo , Hemoglobinas/metabolismo , Idoso , Estudos de Coortes , Retinopatia Diabética/metabolismo , Retinopatia Diabética/mortalidade , Progressão da Doença , Feminino , Humanos , Incidência , Malaui/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Variable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC and CES-1) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2, using a two-stage strategy to improve information during the absorption phase. In contrast to recent studies in South Africa and Uganda, SNPs in SLCO1B1 did not explain variability in AUC0-∞ of rifampin. No pharmacokinetic associations were identified with AADAC or CES-1 SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampin exposure may vary between African populations. SLCO1B1 and other novel candidate genes, as well as nongenetic sources of interindividual variability, should be further explored in geographically diverse, adequately powered cohorts.
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Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/farmacocinética , Antituberculosos/farmacologia , Antituberculosos/farmacocinética , Rifampina/farmacologia , Rifampina/farmacocinética , Tuberculose Pulmonar/genética , Adulto , Hidrolases de Éster Carboxílico/genética , Genótipo , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Malaui , Polimorfismo de Nucleotídeo Único/genética , África do Sul , UgandaRESUMO
BACKGROUND: The epidemic of non-communicable diseases (NCDs) in low and middle income countries (LMICs) is widely recognised as the next major challenge to global health. However, in many LMICs, infectious diseases are still prevalent resulting in a "double burden" of disease. With increased life expectancy and longevity with HIV, older adults may particularly be at risk of this double burden. Here we describe the relative contributions of infections and NCDs to hospital admissions and mortality, according to age, in Malawi's largest hospital. METHODS: Primary diagnosis on discharge/death, mortality rates, and HIV status were recorded prospectively on consecutive adult medical in-patients over 2 years using an electronic medical records system. Diagnoses were classified as infections or NCDs and analysed according to age and gender. FINDINGS: 10,191 records were analysed. Overall, infectious diseases, particularly those associated with HIV, were the leading cause of admission. However, in adults ≥55 years, NCDs were the commonest diagnoses. In adults <55 years 71% of deaths were due to infections whereas in adults ≥55 years 56% of deaths were due to NCDs. INTERPRETATION: Infectious diseases are still the leading cause of adult admission to a central hospital in Malawi but in adults aged ≥55 years NCDs are the most frequent diagnoses. HIV was an underlying factor in the majority of adults with infections and was also present in 53% of those with NCDs. These findings highlight the need for further health sector shifts to address the double burden of infectious and NCDs, particularly in the ageing population.
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Doenças Transmissíveis/epidemiologia , Infecções por HIV/epidemiologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Adulto , Envelhecimento , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/mortalidade , Registros Eletrônicos de Saúde , Infecções por HIV/mortalidade , Humanos , Expectativa de Vida , Malaui/epidemiologia , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Background: Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. Methods: We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. Results: ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71-.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%-50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. Conclusions: MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation.
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Técnicas de Apoio para a Decisão , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/mortalidade , Adulto , Ensaios Clínicos como Assunto , Países em Desenvolvimento , Feminino , Infecções por HIV/epidemiologia , Humanos , Malaui/epidemiologia , Masculino , Meningites Bacterianas/patologia , Nomogramas , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
The Malawian health sector has a strong tradition of systematic data collection for monitoring and evaluation of large-scale services. A highly successful adapted Directly Observed Treatment, Short course "DOTS" framework, based on patient registers and paper-based mastercards was introduced to facilitate the management and monitoring of the scale up of antiretroviral therapy. Subsequently, a simple, touch-screen based electronic medical record system (EMRs) was effectively introduced at high burden ART sites. Based on this model, in 2010, a diabetes specific EMRs was introduced in the diabetes clinic at Queen Elizabeth Central Hospital. In this paper we report on the first 3 years experience with the diabetes EMRs. We highlight the strengths and weaknesses of the diabetes EMRs and present data on glycaemic control recorded in the system.