ANXIOLYTIC ACTIVITY OF MARINE MACROALGAE SARGASSUM ILICIFOLIUM AND PADINA TETRASTOMATICA IN MICE

Objective: The present study was designed to investigate an anxiolytic effect of chloroform and ethanol extract of Sargassum ilicifolium (SI) and Padina tetrastomatica (PT) in mice.Methods: Acute toxicity study was done as per OECD 423 guidelines. Based on acute toxicity studies, doses of 200, 400 and 600 mg/kg of SI and PT extracts were selected, and the anxiolytic activity was assessed using Elevated plus maze (EPM) and light/dark exploration (L/DE) tests.Results: Diazepam (2 mg/kg), the ethanol extract of SI (400 mg/kg) as well as ethanol extract of PT (600 mg/kg) significantly increased time spent and entries into the open arm in EPM test. In L/DE test Diazepam, chloroform extract (600 mg/kg) and ethanol extract (400 mg/kg) of SI as well as chloroform extract (600 mg/kg) and ethanol extract (600 mg/kg) of PT significantly increased time spent in light box and transition between the boxes.Conclusion: in the present investigation, ethanol extract at 400 and chloroform extract at 600 mg/kg of Sargassum ilicifolium as well as ethanol extract at 400 and 600 mg/kg and chloroform extract at 600 mg/kg of Padina tetrastomatica exhibited an anxiolytic effect in the experimental model of anxiety. However, additional research will be necessary to investigate the mechanism underlying this anxiolytic activity. Keywords: Sargassum ilicifolium, Padina tetrastomatica, Brown algae, Anxiolytic activit

Benefits of lung-protective ventilation: Looking beyond the ICU

Background\ud Lung-protective ventilation with the use of low tidal volumes and positive end-expiratory pressure is considered best practice in the care of many critically ill patients. However, its role in anesthetized patients undergoing major surgery is not known.\ud \ud Methods\ud Objective: The aim of the study was to determine whether lung-protective ventilation improves outcomes in anesthetized patients undergoing major abdominal surgery.\ud \ud Design: The Intraoperative Protective Ventilation (IMPROVE) trial is a multicenter, open-label double-blind, parallel-group randomized control trial in seven French university hospitals.\ud \ud Setting: The IMPROVE study enrolled 400 adults at intermediate to high risk of pulmonary complications undergoing major abdominal surgeries between 31 January 2011 and 10 August 2012.\ud \ud Intervention: Patients were randomly assigned to receive volume-controlled ventilation in one of two strategies: nonprotective ventilation with a tidal volume of 10 to 12 ml/kg predicted body weight with no positive end-expiratory pressure and no scheduled recruitment maneuver, or lung-protective ventilation with a tidal volume of 6 to 8 ml/kg predicted body weight, a positive end-expiratory pressure of 6 to 8 cmH2O, and recruitment maneuvers every 30 minutes after intubation. Recruitment maneuvers were also standardized and applied as continuous positive airway pressure of 30 cmH2O for 30 seconds.\ud \ud Outcomes: The primary outcome was a composite of major pulmonary and extrapulmonary complications within the first 7 days after surgery. Major pulmonary complications were defined as pneumonia or the need for invasive or noninvasive ventilation for acute respiratory failure. Major extrapulmonary complications were defined as sepsis, severe sepsis, septic shock, and death. Secondary outcomes included components of primary outcome, surgical complications, and healthcare utilization endpoints such as the duration of stay in the ICU and hospital at the end of a 30-day follow-up period.\ud \ud Results\ud The two intervention groups had similar characteristics at baseline. In the intention-to-treat analysis, the primary outcome occurred in 21 of 200 patients (10.5%) assigned to lung-protective ventilation, as compared with 55 of 200 patients (27.5%) assigned to nonprotective ventilation (relative risk, 0.40; 95% confidence interval, 0.24 to 0.68; P = 0.001). Over the 7-day postoperative period, 10 patients (5.0%) assigned to lung-protective ventilation required noninvasive ventilation or intubation for acute respiratory failure, as compared with 34 patients (17.0%) assigned to nonprotective ventilation (relative risk, 0.29; 95% confidence interval, 0.14 to 0.61; P = 0.001). The length of the hospital stay was shorter among patients receiving lung-protective ventilation than among those receiving nonprotective ventilation (mean difference, −2.45 days; 95% confidence interval, 4.17 to −0.72; P = 0.006).\ud \ud Conclusions\ud As compared with a practice of nonprotective mechanical ventilation, the use of a lung-protective ventilation strategy in intermediate-risk and high-risk patients undergoing major abdominal surgery was associated with improved clinical outcomes and reduced healthcare utilization

Using joint models to study the association between CD4 count and the risk of death in TB/HIV data

BACKGROUND: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model. METHODS: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data. RESULTS: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84). CONCLUSIONS: In this paper we have shown that the “current value” association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes

Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol

Background A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa. Methods The study is designed as an open-label cluster randomized controlled trial. Sixteen clinic supervisors who oversee 40 primary health care (PHC) clinics in two rural districts of KwaZulu-Natal, South Africa will be randomized to either the control group (provision of standard government guidance for TB-HIV integration) or the intervention group (provision of standard government guidance with active enhancement of TB-HIV care integration through a quality improvement approach). The primary outcome is all-cause mortality among TB-HIV patients. Secondary outcomes include time to antiretroviral therapy (ART) initiation among TB-HIV co-infected patients, as well as TB and HIV treatment outcomes at 12 months. In addition, factors that may affect the intervention, such as conditions in the clinic and staff availability, will be closely monitored and documented. Discussion This study has the potential to address the gap between the establishment of TB-HIV care integration policies and guidelines and their implementation in the provision of integrated care in PHC clinics. If successful, an evidence-based intervention comprising change ideas, tools, and approaches for quality improvement could inform the future rapid scale up, implementation, and sustainability of improved TB-HIV integration across sub-Sahara Africa and other resource-constrained settings. Trial registration Clinicaltrials.gov, NCT02654613. Registered 01 June 2015

The clinical profile and outcome of children with West syndrome in KwaZulu-Natal Province, South Africa: A 10-year retrospective review

Background. West syndrome (WS) is a rare epileptic encephalopathy of infancy. There is currently no research on the incidence or prevalence of WS in Africa. Methods. We aimed to describe the outcome of children with WS at a quaternary-level hospital in KwaZulu-Natal, South Africa (SA). This was a retrospective chart review conducted on patients diagnosed with WS over a 10-year period. Eight children (males, n=7; African, n=6; Asian, n=2) identified with WS out of 2 206 admitted with epilepsy. The median age (range) at diagnosis was 7.5 (1 - 9) months. The average time between onset of epileptic spasms and diagnosis was 3.1 months. Results. Six patients had abnormal neuroimaging (atrophy (n=2); corpus callosum agenesis (n=2); tuberous sclerosis (n=1); focal dysplasia (n=1)). Drug management included sodium valproate (n=8), topiramate (n=7) and levetiracetam (n=3). Subsequent definitive treatment was intramuscular adrenocorticotrophic hormone (n=3), vigabatrin (n=2) and oral prednisone (n=4). Four (50%) patients had complete seizure remission (neuromigratory disorder (n=2); tuberous sclerosis (n=1); and idiopathic (n=1)) and 4 had partial remission (neonatal complications (n=3); idiopathic (n=1)). Discussion. Most of our patients had symptomatic WS, with 50% remission on treatment. Outcomes were poorer in our study when compared with those in published data. Conclusion. Further collaborative studies are still needed to evaluate the true impact and prevalence of WS in SA

The clinical profile and outcome of children with West syndrome in KwaZulu-Natal Province, South Africa: A 10-year retrospective review

Background. West syndrome (WS) is a rare epileptic encephalopathy of infancy. There is currently no research on the incidence or prevalence of WS in Africa. Methods. We aimed to describe the outcome of children with WS at a quaternary-level hospital in KwaZulu-Natal, South Africa (SA). This was a retrospective chart review conducted on patients diagnosed with WS over a 10-year period. Eight children (males, n=7; African, n=6; Asian, n=2) identified with WS out of 2 206 admitted with epilepsy. The median age (range) at diagnosis was 7.5 (1 - 9) months. The average time between onset of epileptic spasms and diagnosis was 3.1 months. Results. Six patients had abnormal neuroimaging (atrophy (n=2); corpus callosum agenesis (n=2); tuberous sclerosis (n=1); focal dysplasia (n=1)). Drug management included sodium valproate (n=8), topiramate (n=7) and levetiracetam (n=3). Subsequent definitive treatment was intramuscular adrenocorticotrophic hormone (n=3), vigabatrin (n=2) and oral prednisone (n=4). Four (50%) patients had complete seizure remission (neuromigratory disorder (n=2); tuberous sclerosis (n=1); and idiopathic (n=1)) and 4 had partial remission (neonatal complications (n=3); idiopathic (n=1)). Discussion. Most of our patients had symptomatic WS, with 50% remission on treatment. Outcomes were poorer in our study when compared with those in published data. Conclusion. Further collaborative studies are still needed to evaluate the true impact and prevalence of WS in SA

Open Access A Quality Improvement Intervention to Inform Scale-Up of Integrated HIV-TB Services: Lessons Learned From KwaZulu-Natal, South Africa

In South Africa, mortality rates among HIV-TB coinfected patients are among the highest in the world. The key to reducing mortality is integrating HIV-TB services, however, a generalizable implementation method and package of tested change ideas to guide the scale-up of integrated HIV-TB services are unavailable. We describe the implementation of a quality improvement (QI) intervention, health systems’ weaknesses, change ideas, and lessons learned in improving integrated HIV-TB services. / Methods: Between December 1, 2016, and December 31, 2018, 8 nurse supervisors overseeing 20 primary health care (PHC) clinics formed a learning collaborative to improve a set of HIV-TB process indicators. HIV-TB process indicators comprised: HIV testing services (HTS), TB screening among PHC clinic attendees, isoniazid preventive therapy (IPT) for eligible HIV patients, antiretroviral therapy (ART) for HIV-TB coinfected patients, and viral load (VL) testing at month 12. Routine HIV-TB process data were collected and analyzed. / Results: Key change interventions, generated by health care workers, included: patient-flow redesign, daily data quality checks; prior identification of patients eligible for IPT and VL testing. Between baseline and post-QI intervention, IPT initiation rates increased from 15.9% to 76.4% (P=.019), HTS increased from 84.8% to 94.5% (P=.110), TB screening increased from 76.2% to 85.2% (P=.040), and VL testing increased from 61.4% to 74.0% (P=.045). ART initiation decreased from 95.8% to 94.1% (P=.481). / Discussion: Although integrating HIV-TB services is standard guidance, existing process gaps to achieve integration can be closed using QI methods. QI interventions can rapidly improve the performance of processes, particularly if baseline performance is low. Improving data quality enhances the success of QI initiatives

Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis

HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (BST-2), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2

A cluster‐randomized controlled trial to improve the quality of integrated HIV‐tuberculosis services in primary healthcareclinics in South Africa

Introduction: Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub-optimally implemented. Quality improvement (QI) methods offer a low-cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV-TB care in rural South African primary healthcare (PHC) clinics. Methods: Sixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on-site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study-appointed data capturers from all study clinics. This study's outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing. Results: The QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02–1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02–2.72; p=0·044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups. Conclusions: QI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV-TB service delivery and increase the success of future QI scale-up activities

Co-enrollment in multiple HIV prevention trials — Experiences from the CAPRISA 004 Tenofovir gel trial

Background: In settings where multiple HIV prevention trials are conducted in close proximity, trial participants may attempt to enroll in more than one trial simultaneously. Co-enrollment impacts on participant's safety and validity of trial results. We describe our experience, remedial action taken, inter-organizational collaboration and lessons learnt following the identification of co-enrolled participants. Experiences: Between February and April 2008, we identified 185 of the 398 enrolled participants as ineligible. In violation of the study protocol exclusion criteria, there was simultaneous enrollment in another HIV prevention trial (ineligible co-enrolled, n = 135), and enrollment of women who had participated in a microbicide trial within the past 12 months (ineligible not co-enrolled, n = 50). Following a complete audit of all enrolled participants, ineligible participants were discontinued via study exit visits from trial follow-up. Custom-designed education program on co-enrollment impacting on participants' safety and validity of the trial results was implemented. Shared electronic database between research units was established to enable verification of each volunteer's trial participation and to prevent future co-enrollments. Lessons learnt: Interviews with ineligible enrolled women revealed that high-quality care, financial incentives, altruistic motives, preference for sex with gel, wanting to increase their likelihood of receiving active gel, perceived low risk of discovery and peer pressure are the reasons for their enrollment in the CAPRISA 004 trial. Conclusion: Instituting education programs based on the reasons reported by women for seeking enrollment in more than one trial and using a shared central database system to identify co-enrollments have effectively prevented further co-enrollments