Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity

Thermodynamics of clay – Drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography

An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hydrochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes

Breast lesions and cancer: histopathology and molecular classification in a referral hospital in Ghana

Background: Histological diagnosis is crucial to the management of breast diseases. It determines the kind of disease, the treatment modalities, and the outcome of management. Our department receives breast biopsies from the northern sector of Ghana constituting over 50% of the Ghanaian population. This study aimed at elucidating the pattern of disease and associated traditional prognostic indices of breast cases in our department over a period of 9 years.Methods: Information on the demographic characteristics and the histological diagnoses made on all breast cases received and processed in the department were accessed and entered into an Excel spreadsheet. Slides were reviewed and IHC was done on suitable cases. Descriptive statistics were generated using IMB-SPSS version 23.Results: A total of 4276 breast cases were received by the department within the study period, with 97.6% being female. Age ranged (female/male) from 10 to 98/13 to 102 years, with mean ages of 38.2 years (SD ± 16.7) and 41.15 years (SD ± 21.6), respectively. Cases were evenly distributed in both left and right breasts and 4.3% were bilateral. Inflammatory conditions were seen in 7.5% of cases. The most diagnosed benign tumor was fibroadenoma (54%), followed by fibrocystic change (8.1%). Gynecomastia was diagnosed in 66.3% of males. Malignant cases were 38.6%, with invasive carcinoma NST being the most frequent (87.5%). Histological grades were I = 9.4%, II = 41.6%, and III = 49%. Molecular subtypes were luminal A (19.8%), luminal B (9.9%), Her2 (16%), and TNBC (54.3%).Conclusion: Our findings show an increase in breast cancer cases compared to previous studies in our center, suggesting increased awareness and improved diagnosis. However, this increase is consistent with most studies in sub-Saharan Africa

Antimycobacterial and cytotoxic activity of selected medicinal plant extracts

AbstractEthnopharmacological relevanceTuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants.Material and methodsThe microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis.ResultsResults of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8).ConclusionThe overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis

A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release

Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced ‘medium-sized’ EVs (CVB1i-mEVs). These mEVs (100–300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection

Mycobacterial species causing pulmonary tuberculosis At the korle bu teaching hospital, Accra,

Objective: Characterize mycobacterial species causing pulmonary tuberculosis (PTB) at the Korle-Bu Teaching Hospital in Ghana.Design: Sputum smear positive samples, two (2) from 70 patients diagnosed as having tuberculosis, after they had consented, were collected from the Korle-Bu Teaching Hospital Chest Clinic betweenJanuary and July 2003. Setting: Korle-Bu Teaching Hospital Chest Clinic, Accra. Results: Sixty-four mycobacterial isolates wereobtained and confirmed as members of Mycobacterium tuberculosis complex by colonial morphology and conventional biochemical assays. Fortyseven (73%) were M. tuberculosis, the human strain, 2 (3%) M. bovis, the bovine strain, 13 (20%) M. africanum I (West Africa type), and 2 (3%) M. africanum II (East Africa type). Conclusion: The results indicate that, there are various strains causing PTB at the Korle-BuTeaching Hospital and of great concern is M. bovis, which mostly causes extra-PTB in humans but found to cause PTB in this study. This calls for the need to conduct a nationwide survey using bothconventional and molecular techniques to characterize various mycobacterial species causing TB in Ghana. This will result in better understanding of the various strains circulating in the country andinform individual TB treatment regimen especially the inclusion or exclusion of pyrazinamide

Diagnosis of tuberculosis in Ghana: The role of laboratory training

Objectives: The laboratory is considered the cornerstone of tuberculosis (TB) control programme. International review of Ghana’s programme in the late nineties identified the laboratory services as the weakestcomponent. Sputum smear microscopy (SSM) being the main method of diagnosing pulmonary TB in Ghana, the training objectives were to: (i) strengthen the knowledge and skills of laboratory personnel on SSM(ii) impart necessary techniques in biosafety and (iii) introduce a Quality Assurance (QA) system in order to strengthen SSM services.Methods: Personnel were selected for training during a nationwide situation analysis of SSM centres in 2000/2001. Four training sessions on SSM/QA were held between 2001/2004.Results: A total of 80 personnel were trained: 10 regional TB coordinators and 70 laboratory personnel. The participants upon return to their respective regions also organized training within their districts. This approach resulted in another 100 district TB coordinators and 200 laboratory personnel being trained. Improvement in smear preparation, staining and reading ability of the participants were observed during the post-test and subsequent visit to their respective laboratories. The training has led to strengthening of TB laboratory services in the country and has contributed to increase in case detection from 10,745 in 2000 to 11,827 in2004 and 14,022 in 2008. It was observed during the post-training follow-up and quarterly supervision visits that morale of the personnel was high.Conclusion: Continuous training and re-training of laboratory personnel on SSM and QA at regular intervals do play an important role for effective and efficient TB control programme

Predictors of fetal anemia and cord blood malaria parasitemia among newborns of HIV-positive mothers

Background: Malaria and HIV infections during pregnancy can individually or jointly unleash or confound pregnancy outcomes. Two of the probable outcomes are fetal anemia and cord blood malaria parasitemia. We determined clinical and demographic factors associated with fetal anemia and cord blood malaria parasitemia in newborns of HIV-positive women from two districts in Ghana. Results: We enrolled 1,154 antenatal attendees (443 HIV-positive and 711 HIV-negative) of which 66% were prospectively followed up at delivery. Maternal malaria parasitemia, and anemia rates among HIV+ participants at enrolment were 20.3% and 78.7% respectively, and 12.8% and 51.6% among HIV- participants. Multivariate linear and logistic regression models were used to study associations. Prevalence of fetal anemia (cord hemoglobin level < 12.5 g/dL) and cord parasitemia (presence of P. falciparum in cord blood at delivery) were 57.3% and 24.4% respectively. Factors found to be associated with fetal anemia were maternal malaria parasitemia and maternal anemia. Infant cord hemoglobin status at delivery was positively and significantly associated with maternal hemoglobin and gestational age whilst female gender of infant was negatively associated with cord hemoglobin status. Maternal malaria parasitemia status at recruitment and female gender of infant were positively associated with infant cord malaria parasitemia status. Conclusions: Our data show that newborns of women infected with HIV and/or malaria are at increased risk of anemia and also cord blood malaria parasitemia. Prevention of malaria infection during pregnancy may reduce the incidence of both adverse perinatal outcomes. © 2013 Laar et al.; licensee BioMed Central Ltd

Use of a molecular bacterial load assay to distinguish between active TB and post-TB lung disease

Authors acknowledge financial support from the EDCTP2 programme supported by the European Union project (grant #: TMA2016SF-1463-REMODELTZ) and DELTAS Africa Initiative (Afrique One-ASPIRE /DEL-15-008). The Afrique One-ASPIRE is funded by a consortium of donors including the African Academy of Sciences, Alliance for Accelerating Excellence in Science in Africa, the New Partnership for Africa's Development Planning and Coordinating Agency, the Wellcome Trust (107753/A/15/Z), and the UK Government. PMM, SKH and SGM were also supported by NIH U01AI115594.Publisher PDFPeer reviewe