Innovative approaches to clinical data management in resource limited settings using open-source technologies.

<p>Innovative Approaches to Clinical Data Management in Resource Limited Settings Using Open-Source Technologies</p

Decolonising education is reflexive, deliberate, and necessary

LSE’s Yossie Olaleye, Hope Kyarisiima, and Camilla Omollo reflect on the debates that took place at the Decolonising Education conference that took place at the University of Sussex on Monday 11th April

Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups.

BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease transmitted by sandflies and is fatal if left untreated. Phase II trials of new treatment regimens for VL are primarily carried out to evaluate safety and efficacy, while pharmacokinetic data are also important to inform future combination treatment regimens. The efficacy of VL treatments is evaluated at two time points, initial cure, when treatment is completed and definitive cure, commonly 6 months post end of treatment, to allow for slow response to treatment and detection of relapses. This paper investigates a generalization of the triangular design to impose a minimum sample size for pharmacokinetic or other analyses, and methods to estimate efficacy at extended follow-up accounting for the sequential design and changes in cure status during extended follow-up. METHODS: We provided R functions that generalize the triangular design to impose a minimum sample size before allowing stopping for efficacy. For estimation of efficacy at a second, extended, follow-up time, the performance of a shrinkage estimator (SHE), a probability tree estimator (PTE) and the maximum likelihood estimator (MLE) for estimation was assessed by simulation. RESULTS: The SHE and PTE are viable approaches to estimate an extended follow-up although the SHE performed better than the PTE: the bias and root mean square error were lower and coverage probabilities higher. CONCLUSIONS: Generalization of the triangular design is simple to implement for adaptations to meet requirements for pharmacokinetic analyses. Using the simple MLE approach to estimate efficacy at extended follow-up will lead to biased results, generally over-estimating treatment success. The SHE is recommended in trials of two or more treatments. The PTE is an acceptable alternative for one-arm trials or where use of the SHE is not possible due to computational complexity. TRIAL REGISTRATION: NCT01067443 , February 2010

Thermal Analysis of Polyamide-66/POSS nanocomposite fiber

Poly Hexamethylene Adipamide (PA-66) nanocomposite fibers were prepared by melt mixing PA-66 using two Polyhedral Oligomeric Silsesquioxane (POSS) as fillers: Octaphenyl Polyhedral Oligomeric Silsesquioxane (OPS) and Octa-Aminophenyl Polyhedral Oligomeric Silsesquioxane (OAPS). OPS and OAPS in PA-66 was varied between 1% wt. and 3% wt. PA-66 nanocomposite fibers with varying concentrations of POSS were then analyzed using TGA, DSC and then compared to that of neat PA-66. PA-66 was thermally stable up to 350°C with low molecular weight species burning off below 200°C. PA-66-OPS were also thermally stable up to 350°C with burn-off of low molecular weight species being below 240°C. PA-66-OAPS was found to be more thermally stable (up to 400°C) with low molecular weight species burning off below 200°C. The decomposition temperatures of the PA66/POSS nanocomposites increased as the POSS content was increased, an indicator that the thermal decay of the PA66/POSS nanocomposites was slowed down by incorporating POSS into the PA66 matrix. Addition of POSS to PA-66 also increased crystallization temperature but did not change the melting temperatures. OAPS exhibited better thermal behavior when added to PA-66 compared to OPS and therefore is recommended as a prospective nanomaterial for further studies

Definition and analysis of endpoints in clinical trials for visceral leishmaniasis:

Paper presented at Strathmore International Math Research Conference on July 23 - 27, 2012Paper presented at Strathmore International Mathematics Research Conference on July 23 - 27, 201

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Barriers to the Effective Regulation of the Building Construction Industry: An Empirical Analysis

This study investigates key barriers to the effective regulation of the building construction industry in Kenya, a case study of Kisii Town. It was guided by the Public Interest Theory of Regulation, which provided the underpinning elucidating why the building construction industry in Kenya needs regulation. The target population comprised 84 registered building contractors with a sample size of 66 selected using simple random sampling by application of random number table. As regards limitation, the study does not measure the extent of quality assurance within the construction industry, but rather delve on the key factors impeding its effective regulation. The research findings show that ineffective regulation of the construction industry in Kisii Town was prompted by the joint activities of building development contractors and limitations of the National Construction Authority (NCA) (the regulator). Regarding the activities of building contractors, identified barriers included failure to refer to key legislation that regulates the construction industry, failure to obtain statutory approvals of building development, and laxity to invite supervision of ongoing projects by planning authorities. Conversely, factors elucidating why NCA was not successfully regulating the construction industry included inadequate multi-sectoral coordination, inadequate surveillance, and limited sensitization of key stakeholders. Drawing from these findings, the study recommends regular monitoring and enhanced enforcement that would promote compliance and sensitization of contractors with applicable standards and regular inspections of ongoing projects. Also, establishing a coordinating committee to harmonize institutions that deal with development control. Keywords: Construction Industry, Kenya, Kisii Town, Regulatio

Conformity assessment to development plan implementation as a tool for development control in Kisii Town, Kenya

The objective of this study was to determine if the current land use development patterns in Kisii Town conformed to development zones in approved 1972 Kisii Town Physical Development Plan. Spatio-temporal analysis guided by Object Based Image Analysis (OBIA) was undertaken using QGIS software, integrating satellite image epochs of 2005, 2010 and 2017. Results showed that all approved development zones were not conformed to by ensuing land use development patterns, thus denoting nonconformity. The study also tested the hypothesis that there was no statistically significant difference between approved land use development patterns in the 1972 Kisii Town Physical Development Plan and ensuing land use development patterns in 2017. The test however found a significant difference between the two paired samples (M = 43.555, SD = 34.661) and (M = 36.344, SD = 34.047), t (9) = 4.03, p = 0.003. The null hypothesis was as a result rejected at 95% confidence level. The study concluded that because conformity to the development plan declined by a mean of 7.206, its objective as a tool for development control in Kisii Town was not attained. Recommendation was made that since the plan is outdated, a comprehensive plan covering the entire town should be prepared to provide a framework for development control. Additionally, there is need to adopt a strict enforcement and monitoring regime that ensures compliance with the plan.Keywords: Conformity, physical development plan, development control, Kisii Tow