Role of the SAFE pathway and the mitochondria in HDL cholesterol (and its constituent sphingosine-1-phosphate) induced cardioprotection

High density lipoprotein cholesterol (HDL) and its component sphingosine-1-phosphate (S1P) protect against myocardial infarction. Recently, the SAFE (survivor activating factor enhancement) pathway, involving tumour necrosis factor (TNF) and the transcription factor signal transducer and activator of transcription 3 (STAT-3), has been identified as a key signalling pathway in cardioprotection, although the end effector remains unclear

Setting priorities in health research using the model proposed by the World Health Organization: development of a quantitative methodology using tuberculosis in South Africa as a worked example

BackgroundSetting priorities is important in health research given the limited resources available for research. Various guidelines exist to assist in the priority setting process; however, priority setting still faces significant challenges such as the clear ranking of identified priorities. The World Health Organization (WHO) proposed a Disability Adjusted Life Year (DALY)-based model to rank priorities by research area (basic, health systems and biomedical) by dividing the DALYs into ‘unavertable with existing interventions’, ‘avertable with improved efficiency’ and ‘avertable with existing but non-cost-effective interventions’, respectively. However, the model has conceptual flaws and no clear methodology for its construction. Therefore, the aim of this paper was to amend the model to address these flaws, and develop a clear methodology by using tuberculosis in South Africa as a worked example.MethodsAn amended model was constructed to represent total DALYs as the product of DALYs per person and absolute burden of disease. These figures were calculated for all countries from WHO datasets. The lowest figures achieved by any country were assumed to represent ‘unavertable with existing interventions’ if extrapolated to South Africa. The ratio of ‘cost per patient treated’ (adjusted for purchasing power and outcome weighted) between South Africa and the best country was used to calculate the ‘avertable with improved efficiency section’. Finally, ‘avertable with existing but non-cost-effective interventions’ was calculated using Disease Control Priorities Project efficacy data, and the ratio between the best intervention and South Africa’s current intervention, irrespective of cost.ResultsThe amended model shows that South Africa has a tuberculosis burden of 1,009,837.3 DALYs; 0.009% of DALYs are unavertable with existing interventions and 96.3% of DALYs could be averted with improvements in efficiency. Of the remaining DALYs, a further 56.9% could be averted with existing but non-cost-effective interventions.ConclusionsThe amended model was successfully constructed using limited data sources. The generalizability of the data used is the main limitation of the model. More complex formulas are required to deal with such potential confounding variables; however, the results act as starting point for development of a more robust model.Electronic supplementary materialThe online version of this article (doi:10.1186/s12961-016-0081-8) contains supplementary material, which is available to authorized users

Health promotion via SMS improves hypertension knowledge for deaf South Africans

Abstract Background Signing Deaf South Africans have limited access to health information. As a result, their knowledge about health is limited. Cell phone usage in South Africa is high. This study aimed to assess whether a short message service (SMS)-based health promotion campaign could improve Deaf people’s knowledge of hypertension and healthy living. Additionally, the study aimed to assess the acceptability of using SMSs for health promotion targeting Deaf people. Methods A baseline questionnaire assessed participants’ knowledge about hypertension before an SMS-based information campaign was conducted. After the campaign, an exit questionnaire was conducted, containing the same questions as the baseline questionnaire with additional questions about general acceptability and communication preferences. Results were compared between baseline and exit, using McNemar’s test, paired t-test and Wilcoxon signed-rank test. Focus groups aimed to get further information on the impact and acceptability of SMSs. The focus groups were analysed using inductive thematic analysis. Results The campaign recruited 82 participants for the baseline survey, but due to significant loss-to-follow-up and exclusions only 41 participants were included in the analysis of the survey. The majority (60%) were men. Eighty percent were employed, while 98% had not finished high school. The campaign showed a statistically significant improvement in overall knowledge about hypertension and healthy living amongst participants. Six individual questions out of 19 also showed a statistically significant improvement. Despite this, participants in focus groups found the medical terminology difficult to understand. Several ways of improving SMS campaigns for the Deaf were identified. These included using using pictures, using ‘signed’ SMSs, combining SMSs with signed drama and linking SMS-campaigns to an interactive communication service that would enable the Deaf to pose questions for clarification. Focus groups suggested that participants who were hypertensive during the campaign adopted a healthier lifestyle. Conclusion SMSs were effective in improving Deaf people’s knowledge of hypertension and healthy living. However, SMS-campaigns should be cognizant of Deaf people’s unique needs and communication preference and explore how to accommodate these. Trial registration The research was registered with the Pan African Clinical Trial Registry on December 1, 2015. Identification number: PACTR201512001353476

Comparison of two text message (mHealth) campaigns for the Deaf: Contracted out v. conducted in-house

Cell phone-based health information (mobile health or mHealth) campaigns are an emerging technology. This evaluation focused on the aspect of cost of two health information campaigns, one on hypertension and one on pregnancy. Researchers could either contract out the technical components of the campaigns or attempt to run the campaigns themselves, in-house. The in-house campaigns cost an estimated ZAR13 548.72 v. the private provider quotes which ranged from ZAR27 542.97 to ZAR34 227.59. Running the campaigns in-house was more labour intensive and required more technical expertise, but had a reduced delivery failure rate (9.2% in-house v. 30.0% private provider). Running small to medium SMS (text message) campaigns for evaluative purposes proved advantageous over contracting out to private providers. Larger-scale evaluations and full-scale roll-out will require the services of private providers, but it is still essential that researchers actively engage with and monitor the technical aspects of these campaigns

Antenatal health promotion via short message service at a Midwife Obstetrics Unit in South Africa: a mixed methods study

Abstract Background Adequate antenatal care is important to both the health of a pregnant woman and her unborn baby. Given South Africa’s high rate of cellphone penetration, mobile health interventions have been touted as a potentially powerful means to disseminate health information. This study aimed to increase antenatal health knowledge and awareness by disseminating text messages about clinic procedures at antenatal visits, and how to be healthy during pregnancy. Methods Participants recruited were pregnant women attending a primary health care facility in Cape Town. A controlled clinical trial was carried out where the intervention group (n = 102) received text messages staggered according to the week of pregnancy at the time of recruitment. The control group (n = 104) received no text messages. These text messages contained antenatal health information, and were delivered in English, Xhosa or Afrikaans, according to the preference of each participant. A baseline knowledge questionnaire with nine questions was administered prior to the intervention. The same questionnaire was used with added health-related behaviour questions for the intervention group at exit. A modified intention-to-treat analysis was done. To compare the control and intervention group’s knowledge, Fisher’s exact tests and two-sample t-tests tests were carried out for binary and continuous outcomes, respectively. A focus group of seven participants from the intervention group was then conducted to gain more insight into how the text messages were perceived. Results There was substantial loss to follow-up during the study with only 57% of the participants retained at exit. No statistically significant difference was detected between the control and intervention group in any of the nine knowledge questions at exit (all p > 0.05). Responses from the focus group indicated that the text messages acted as a welcome reminder and a source of positive motivation, and were perceived as extended care from the health care provider. Conclusions While the intervention failed to improve antenatal health knowledge, evidence from self-reported behaviour and the focus group suggests that text messages have the potential to motivate change in health-seeking behaviour. One should be mindful of loss to follow-up when rolling out mobile health interventions in developing country settings. Trial registration Pan African Clinical Trials Registry PACTR201406000841188 . Registered 3 June 2014

Ethanolamine is a novel STAT-3 dependent cardioprotective agent

Ethanolamine is a biogenic amine found naturally in the body as part of membrane lipids and as a metabolite of the cardioprotective substances, sphingosine-1-phosphate (S1P) and anandamide. In the brain, ethanolamine, formed from the breakdown of anandamide protects against ischaemic apoptosis. However, the effects of ethanolamine in the heart are unknown. Signal transducer and activator of transcription 3 (STAT-3) is a critical prosurvival factor in ischaemia/reperfusion (I/R) injury. Therefore, we investigated whether ethanolamine protects the heart via activation of STAT-3. Isolated hearts from wildtype or cardiomyocyte specific STAT-3 knockout (K/O) mice were pre-treated with ethanolamine (Etn) (0.3 mmol/L) before I/R insult. In vivo rat hearts were subjected to 30 min ischaemia/2 h reperfusion in the presence or absence of 5 mg/kg S1P and/or the FAAH inhibitor, URB597. Infarct size was measured at the end of each protocol by triphenyltetrazolium chloride staining. Pre-treatment with ethanolamine decreased infarct size in isolated mouse or rat hearts subjected to I/R but this infarct sparing effect was lost in cardiomyocyte specific STAT-3 deficient mice. Pre-treatment with ethanolamine increased nuclear phosphorylated STAT-3 [control 0.75 ± 0.08 vs. Etn 1.50 ± 0.09 arbitrary units; P < 0.05]. Our findings suggest a novel cardioprotective role for ethanolamine against I/R injury via activation of STAT-3

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Additional file 2: of Setting priorities in health research using the model proposed by the World Health Organization: development of a quantitative methodology using tuberculosis in South Africa as a worked example

Disease burden estimates. (DOC 41 kb