Achieving optimal cancer outcomes in East Africa through multidisciplinary partnership: a case study of the Kenyan National Retinoblastoma Strategy group.

BACKGROUND: Strategic, interdisciplinary partnerships are essential to addressing the complex drivers of health inequities that result in survival disparities worldwide. Take for example the aggressive early childhood eye cancer retinoblastoma, where survival reaches 97 % in resource-rich countries, but is as low 30 % in some resource-limited nations, where 92 % of the burden lies. This suggests a need for a multifaceted approach to achieve a tangible and sustainable increase in survival. METHODS: We assembled the history the Kenyan National Retinoblastoma Strategy (KNRbS), using information documented in NGO reports, grant applications, news articles, meeting agendas and summaries. We evaluated the KNRbS using the principles found in the guide for transboundary research partnerships developed by the Swiss Commission for Research Partnerships with Developing Countries. RESULTS: A nationally co-ordinated approach drawing input and expertise from multiple disciplines and sectors presented opportunities to optimise cure of children with retinoblastoma. Annual meetings were key to achieving the over 40 major outputs of the group's efforts, related to Awareness, Medical Care, Family Support and Resource Mobilization. Three features were found to be critical to the KNRbS success: multidisciplinarity, consistency and flexibility. CONCLUSION: The KNRbS has achieved a number of key outputs with limited financial investment. As a partnership, the KNRbS meets most of the criteria identified for success. Challenges remain in securing the long-term sustainability of its achievements. Elements of the Kenyan National Retinoblastoma Strategy may be useful to other developing countries struggling with limited survival of retinoblastoma and other cancers or rare diseases

Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.Wellcome Trust (Grant ID: 084716/Z/08/Z)This is the final version of the article. It first appeared from Cell Press/Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.02

Islet Transplantation with Alemtuzumab Induction and Calcineurin-Free Maintenance Immunosuppression Results in Improved Short-and Long-Term Outcomes

BACKGROUND: Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required in order to improve long term outcomes. MATERIALS AND METHODS: Three subjects with unstable type 1 DM underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for three months then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was >2 years. Comparison was with sixteen historical subjects transplanted under the Miami version of the Edmonton protocol. RESULTS: Insulin independence was achieved in 2/3 alemtuzumab and 14/16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin independence rates remained unchanged in the Alemtuzumab group, but decreased from 14/16 (88%) to 6/16 (38%) in the Historical group over two years. Insulin requirements increased in the Historical group while remaining stable in the Alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (NS). Further comparison of Alemtuzumab versus Historical groups, up to 24 months, demonstrated significantly better: Mixed Meal Stimulation Index (24 months 1.0±0.08 n=3 vs 0.5±0.06 pmol/mL n=6, p<0.01), Mixed Meal peak C-peptide (24 months 5.0±0.5 n=3 vs 3.1±0.3 nmol/mL n=6, p<0.05), HbA1c (24 months 5.4±0.15 n=3 vs 6.3±0.12pmol/mL n=10, p<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. CONCLUSIONS: Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short and long term outcomes. Further investigation is underway for validation

The Influence of Comminution and Posterior Ligamentous Complex Integrity on Treatment Decision Making in Thoracolumbar Burst Fractures Without Neurologic Deficit?

STUDY DESIGN A prospective study. OBJECTIVE to evaluate the impact of vertebral body comminution and Posterior Ligamentous Complex (PLC) integrity on the treatment recommendations of thoracolumbar fractures among an expert panel of 22 spine surgeons. METHODS A review of 183 prospectively collected thoracolumbar burst fracture computed tomography (CT) scans by an expert panel of 22 trauma spine surgeons to assess vertebral body comminution and PLC integrity. This study is a sub-study of a prospective observational study of thoracolumbar burst fractures (Spine TL A3/A4). Each expert was asked to grade the degree of comminution and certainty about the PLC disruption from 0 to 100, with 0 representing the intact vertebral body or intact PLC and 100 representing complete comminution or complete PLC disruption, respectively. RESULTS ≥45% comminution had a 74% chance of having surgery recommended, while <25% comminution had an 86.3% chance of non-surgical treatment. A comminution from 25 to 45% had a 57% chance of non-surgical management. ≥55% PLC injury certainity had a 97% chance of having surgery, and ≥45-55% PLC injury certainty had a 65%. <20% PLC injury had a 64% chance of having non-operative treatment. A 20 to 45% PLC injury certainity had a 56% chance of non-surgical management. There was fair inter-rater agreement on the degree of comminution (ICC .57 [95% CI 0.52-.63]) and the PLC integrity (ICC .42 [95% CI 0.37-.48]). CONCLUSION The study concludes that vetebral comminution and PLC integrity are major dterminant in decision making of thoracolumbar fractures without neurological deficit. However, more objective, reliable, and accurate methods of assessment of these variables are warranted

The FEED1 trial: protocol for a randomised controlled trial of full milk feeds versus intravenous fluids with gradual feeding for preterm infants (30–33 weeks gestational age)

Background In the UK, approximately 8% of live births are preterm (before 37 weeks gestation), more than 90% of whom are born between 30 and 36 weeks, forming the largest proportion of a neonatal units’ workload. Neonatologists are cautious in initiating full milk feeds for preterm infants due to fears of necrotising enterocolitis (NEC). There is now evidence to dispute this fear. Small studies have shown that feeding preterm infants full milk feeds enterally from birth could result in a shorter length of hospital stay, which is important to parents, clinicians and NHS services without increasing the risk of NEC. This trial aims to investigate whether full milk feeds initiated in the first 24 h after birth reduces the length of hospital stay in comparison to introduction of gradual milk feeding with IV fluids or parenteral nutrition. Methods FEED1 is a multi-centre, open, parallel group, randomised, controlled superiority trial of full milk feeds initiated on the day of birth versus gradual milk feeds for infants born at 30+0 to 32+6 (inclusive) weeks gestation. Recruitment will take place in around 40 UK neonatal units. Mothers will be randomised 1:1 to full milk feeds, starting at 60 ml/kg day, or gradual feeds, as per usual local practice. Mother’s expressed breast milk will always be the first choice of milk, though will likely be supplemented with formula or donor breast milk in the first few days. Feeding data will be collected until full milk feeds are achieved (≥ 140 ml/kg/day for 3 consecutive days). The primary outcome is length of infant hospital stay. Additional data will be collected 6 weeks post-discharge. Follow-up at 2 years (corrected gestational age) is planned. The sample size is 2088 infants to detect a between group difference in length of stay of 2 days. Accounting for multiple births, this requires 1700 women to be recruited. Primary analysis will compare the length of hospital stay between groups, adjusting for minimisation variables and accounting for multiple births. Discussion This trial will provide high-quality evidence on feeding practices for preterm infants. Full milk feeds from day of birth could result in infants being discharged sooner. Trial registration ISRCTN ISRCTN89654042. Prospectively registered on 23 September 2019: ISRCTN is a primary registry of the WHO ICTRP network, and all items from the WHO Trial Registration dataset are included