Safety of a condom uterine balloon tamponade (ESM-UBT) device for uncontrolled primary postpartum hemorrhage among facilities in Kenya and Sierra Leone

Background: Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone. Methods: Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study. Three expert maternal health investigator physicians analyzed each complication/adverse event and developed consensus on whether there was a potential causal relationship associated with use of the ESM-UBT device. Adverse events/complications specifically investigated included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis. Results: Of the 201 women treated with an ESM-UBT device in Kenya and Sierra Leone, 189 (94.0%) survived. Six-week or longer follow-up was recorded in 156 of the 189 (82.5%). A causal relationship between use of an ESM-UBT device and one death, three perineal injuries and one case of mild endometritis could not be completely excluded. Three experts found a potential association between these injuries and an ESM-UBT device highly unlikely. Conclusion: The ESM-UBT device appears safe for use in women with uncontrolled PPH. Trial registration Trial registration was not completed as data was collected as a quality assurance measure for the ESM-UBT kit

Latency Antigen α-Crystallin Based Vaccination Imparts a Robust Protection against TB by Modulating the Dynamics of Pulmonary Cytokines

BACKGROUND: Efficient control of tuberculosis (TB) requires development of strategies that can enhance efficacy of the existing vaccine Mycobacterium bovis Bacille Calmette Guerin (BCG). To date only a few studies have explored the potential of latency-associated antigens to augment the immunogenicity of BCG. METHODS/PRINCIPAL FINDINGS: We evaluated the protective efficacy of a heterologous prime boost approach based on recombinant BCG and DNA vaccines targeting α-crystallin, a prominent latency antigen. We show that "rBCG prime-DNA boost" strategy (R/D) confers a markedly superior protection along with reduced pathology in comparison to BCG vaccination in guinea pigs (565 fold and 45 fold reduced CFU in lungs and spleen, respectively, in comparison to BCG vaccination). In addition, R/D regimen also confers enhanced protection in mice. Our results in guinea pig model show a distinct association of enhanced protection with an increased level of interleukin (IL)12 and a simultaneous increase in immuno-regulatory cytokines such as transforming growth factor (TGF)β and IL10 in lungs. The T cell effector functions, which could not be measured in guinea pigs due to technical limitations, were characterized in mice by multi-parameter flow cytometry. We show that R/D regimen elicits a heightened multi-functional CD4 Th1 cell response leading to enhanced protection. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based R/D regimen over BCG. Our observations from guinea pig studies indicate a crucial role of IL12, IL10 and TGFβ in vaccine-induced protection. Further, characterization of T cell responses in mice demonstrates that protection against TB is predictable by the frequency of CD4 T cells simultaneously producing interferon (IFN)γ, tumor necrosis factor (TNF)α and IL2. We anticipate that this study will not only contribute toward the development of a superior alternative to BCG, but will also stimulate designing of TB vaccines based on latency antigens

Safety and Immunogenicity of DNA and MVA HIV-1 Subtype C Vaccine Prime-Boost Regimens: A Phase I Randomised Trial in HIV-Uninfected Indian Volunteers

STUDY DESIGN: A randomized, double-blind, placebo controlled phase I trial. METHODS: The trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos. RESULTS: Both vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-γ ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-γ ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1(st) and 2(nd) MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination. CONCLUSIONS: Although DNA priming resulted in enhancement of immune responses after 1(st) MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting. TRIAL REGISTRATION: Clinical Trial Registry CTRI/2009/091/00005

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The Influence of Experience and Sequence of Conflicting Emotions on Ad Attitudes

Two experiments suggest that when participants evaluate an ad, they prefer improving ad emotions, because attitudes are based on an assessment of whether the emotions deviate positively or negatively from previous levels of emotions. In contrast, when emotions are experienced, positive emotions facilitate coping with later negativity, and an ad with declining (vs. improving) emotions results in more favorable attitudes. This beneficial effect of experienced positive emotions in reducing the impact of subsequent negative emotions is reversed when the positive emotions are allowed to dissipate over a time delay between the experiences of the two emotions. (c) 2007 by JOURNAL OF CONSUMER RESEARCH, Inc..

Effectiveness of video role play with PowerPoint lecture on knowledge domain among medical students—An open label randomized control trial

BACKGROUND: Video is an effective teaching and learning tool as it is one of the few mediums that has been used effectually in all facades of medical education both with face-to-face teaching and at a distance. During a specified amount of space and time, video description can provide more details, converting complex concepts into simpler ones. The aim of the study is to assess the effectiveness of video role play (VRP) on knowledge domain among medical students.MATERIAL AND METHODS: The study was done as an open label randomized control trial among first-year medical students in a private medical college in a rural district in Tamil Nadu, where the subjects were randomized into two groups. The intervention group was given video role-play demonstration of the specified topic with a minute description. The control group was given PowerPoint lecture of the same topic. Baseline pretest and posttest score after two weeks was done to assess the effectiveness of video role play on knowledge domain among the students.RESULTS: The mean age of the population was 18.72 (0.71) years. The gender distribution showed that 70 (47.3%) were males and 78 (52.7%) were females. The result showed that Mean ± SD score of VRP posttest [9.36 ± 0.92] was significantly more in comparison with that of post score of PowerPoint [5.16 ± 1.98].CONCLUSION: This concludes that VRP can act more effectively in understanding a lecture than using PowerPoint method. It is an interesting and exciting teaching–learning method involving the active participation of the students and the faculty

Antistaphylococcal and neutrophil chemotactic injectable κ-carrageenan hydrogel for infectious wound healing

Staphylococcus aureus wound infection is a major concern due to the resistance of S. aureus to topical antibiotics and capacity to inhibit neutrophil migration at the infection site. To overcome these problems, we have developed 0.01% (v/v) octenidine dihydrochloride (Oct) and 0.5% (w/w) chitosan-treated serum (CTS) containing 1.5% (w/v) κ-carrageenan hydrogel (κC). Oct is an antiseptic agent, against which no resistance is reported so far, and CTS has neutrophilic attractant properties. The prepared Oct-CTS-κC hydrogel is injectable and biocompatible. Using in vitro experiments, we demonstrated CTS can induce the migration of polymorphonuclear neutrophils (PMNs) and fibroblasts that can facilitate tissue regeneration at a wound site. In vitro release studies revealed a sustained release of Oct and serum proteins from the Oct-CTS-κC hydrogel. Antibacterial properties of developed hydrogels were tested against S. aureus and its clinical isolates. Further, the in vivo antibacterial efficacy of the prepared hydrogel was evaluated in an S. aureus-infected Sprague-Dawley (SD) rat wound. Both in vitro and in vivo studies showed that the Oct-CTS-κC hydrogel inhibited S. aureus growth. Thus, the developed Oct-CTS-κC hydrogel can be potentially exploited for S. aureus-infected wound healing

Over-expression of superoxide dismutase obliterates the protective effect of BCG against tuberculosis by modulating innate and adaptive immune responses

An efficient global control of tuberculosis requires development of alternative vaccination strategies that can enhance the efficacy of existing BCG vaccine. In this study, we evaluated the protective efficacy of a recombinant BCG (rBCG) vaccine over-expressing iron-cofactored superoxide dismutase (SOD-A), one of the prominent oxidative stress response proteins of Mycobacterium tuberculosis. Contrary to our expectations, over-expression of SOD-A resulted in the abrogation of BCG's ability to confer protection in guinea pig as well as in murine model. Analysis of immune responses revealed that over-expression of SOD-A by rBCG has pleiotropic effects on innate and adaptive immune responses. Macrophages infected in vitro with rBCG exhibited a marked reduction in apoptosis and microbicidal potential. In addition, rBCG vaccination of mice resulted in a reduced IFNγ and increased IL10 production when compared with the BCG vaccination. Further, we show that rBCG vaccination failed to generate an effective multi-functional CD4 T cell response. Altogether, our findings suggest that over-expression of SOD-A in BCG enhances the immuno-suppressive properties of BCG, characterized by skewing of immune responses towards Th2 type, an inefficient multi-functional T cell response and reduced apoptosis and microbicidal potential of macrophages leading to abolishment of BCG's protective efficacy