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Why do some hospitals perform better than others? A realist evaluation of the role of health workforce management in well-performing health care organisations; a study of 4 hospitals in Ghana
No full textNevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin
No full textBackground Rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment. Methods Eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)). Trial registration number: NCT00617643 (www.clinicaltrials.gov). Results Day 7 geometric mean nevirapine C(12) [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P < 0.01). Nevirapine C(12) on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng.h/mL versus 43 195 (35 607-57 035) ng.h/mL in the NVP400 arm (P < 0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng.h/mL versus the NVP400 arm 44 918 (36 264-62 769) ng.h/mL (P = 0.03). Conclusions In co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered
When the 'non-workable ideological best' becomes the enemy of the 'imperfect but workable good'
No full textThis brief paper addresses some of the difficulties inherent in international ideological approaches to solving the complex problems of health care financing and delivery in poor countries using Ghana as an example. It concludes with an appeal for problem solving approaches involving informed debate as to optimal ways forward to solve low income country health financing woes that are open minded about possible options rather than vested in particular positions
Persistence of Leishmania donovani antibodies in past visceral leishmaniasis cases in India
No full textAnti-Leishmania donovani antibodies persistence in past Visceral Leishmaniasis (VL) cases was retrospectively assessed by means of Direct Agglutination Test (DAT) and rK39 ELISA. Antibody titres remained high for an extended period of time in past VL. These results highlight the need to carefully elicit the history of patients with VL symptoms
Evaluation of the BD MGIT TBc Identification Test (TBc ID), a rapid chromatographic immunoassay for the detection of Mycobacterium tuberculosis complex from liquid culture
No full textThe BACTEC MGIT 960 system is increasingly used to culture Mycobacterium tuberculosis. We evaluated the performance of the new immunochromatographic assay BD MGIT TBc Identification Test (TBc ID) for the rapid identification of M. tuberculosis complex in clinical samples when performed directly from BACTEC MGIT 960 culture positive for acid-fast bacilli (AFB). Of 92 cultures evaluated, the sensitivity and specificity of the TBc ID test was 98.5% and 100%, respectively compared to sequencing of the 16S rRNA gene. One culture that was TBc ID test negative but that was identified as M. tuberculosis by 16S rRNA sequencing was confirmed to have a mutation in the mpt64 gene. The TBc ID test is an easy and sensitive method for the identification of M. tuberculosis complex in liquid culture medium, does not require a high level of skills, neither any additional specific equipment and gives results in 15min, which provide a good alternative for the rapid identification of M. tuberculosis complex in liquid medium
High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
No full textBACKGROUND: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. METHODS: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/mul], N=34 ], optimal [282 (200-415) cells/mul, N=64] and super-optimal [528 (416-878) cells/mul, N=30]. RESULTS: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P=0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P<0.001) and super-optimal responders (P<0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P=0.022]. CONCLUSION: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART
Visceral leishmaniasis in Muzaffarpur district, Bihar, India from 1990 to 2008
No full textBACKGROUND: Visceral Leishmaniasis (VL) is a vector-borne disease transmitted by Phlebotomus argentipes. To understand the VL seasonality, annual and monthly variations of VL incidence and its relationship to meteorological variables, the numbers of VL cases reported in Muzaffarpur district, Bihar, India from 1990 to 2008 were studied. METHODS: Annual VL incidence per 10,000 and the total number of annual VL cases reported at block Community Health Centres (CHC), Public Hospitals or Non-Governmental Organisations (NGO) and the number of VL cases per month from 2000 to 2008 as well as the monthly average of cases for 2000-08, 2000-04 and 2005-08 periods along with the monthly averages of temperature, rainfall and relative humidity were plotted. VL Standardised Incidence Ratios per block were computed for the periods of 1990-1993, 1994-1998, 1999-2004 and 2005-2008 and month wise from 2002 to 2008. A negative binomial regression model was used to evaluate the association between meteorological variables and the number of VL cases per month from 2000 to 2008. RESULTS: A total of 68,358 VL cases were reported in Muzaffarpur district from 1990 to 2008, ranging from 1,2481 in 1992 to 1,161 in 2001. The blocks with the highest number of cases shifted from East (1990-98) to West (1999-2008). Monthly averages of cases ranged from 149 to 309, highest peak in March-April and another one in July. Monthly VL incidence was associated positively to rainfall and negatively to relative humidity and the numbers of VL cases in the previous month. INTERPRETATION: The number of cases reported to the public health sector allowed the describing of the spatial distribution and temporal variations in the Muzaffarpur from 1990 to 2008. However, to assess the actual VL burden, as well as the efficacy of the control measures applied in the district, reporting from private practices and NGOs should be encouraged
Likely health outcomes for untreated acute febrile illness in the tropics in decision and economic models; a delphi survey
No full textBACKGROUND: Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses. Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death. However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion. Widely diverse opinions can lead to conflicting outcomes in models they inform. METHODS AND FINDINGS: A Delphi survey was conducted with malaria experts aiming to reach consensus on key parameters for public health and economic models, relating to the outcome of untreated febrile illnesses. Survey questions were stratified by malaria transmission intensity, patient age, and HIV prevalence. The impact of the variability in opinion on decision models is illustrated with a model previously used to assess the cost-effectiveness of malaria rapid diagnostic tests. Some consensus was reached around the probability that patients from higher transmission settings with untreated malaria would progress to severe disease (median 3%, inter-quartile range (IQR) 1-5%), and the probability that a non-malaria illness required antibiotics in areas of low HIV prevalence (median 20%). Children living in low transmission areas were considered to be at higher risk of progressing to severe malaria (median 30%, IQR 10-58%) than those from higher transmission areas (median 13%, IQR 7-30%). Estimates of the probability of dying from severe malaria were high in all settings (medians 60-73%). However, opinions varied widely for most parameters, and did not converge on resurveying. CONCLUSIONS: This study highlights the uncertainty around potential consequences of untreated malaria and bacterial illnesses. The lack of consensus on most parameters, the wide range of estimates, and the impact of variability in estimates on model outputs, demonstrate the importance of sensitivity analysis for decision models employing expert opinion. Results of such models should be interpreted cautiously. The diversity of expert opinion should be recognised when policy options are debated
Double ethical review of North-South collaborative clinical research: hidden paternalism or real partnership?
No full textDespite their universal character, the ethical principles governing clinical research need to be translated into procedures and practices, which will vary among countries and regions because of differences in local cultural norms and in the available resources. Double ethical review, by which a research protocol is submitted for ethical clearance both in the country or countries where the research takes place and in the country of the sponsor or funding agency, will then help ensure that all relevant perspectives are taken into account. In addition, a geographically and culturally close ethics committee can do a much better informed and comprehensive assessment of the respective skills of the clinical sites and of the sponsor. But the practical implementation of double ethical review can bring significant difficulties and delays, especially in multi-site and multi-country researches. Currently, most ethics committees do not proactively seek communication with others evaluating the same research protocol in different socio-economical and cultural contexts, so in practice there is no mutual learning process. Proactive communication would help to build collaborative partnership among ethical bodies, promoting common practices and resolving conflicting opinions