Trends in child marriage, sexual violence, early sexual intercourse and the challenges for policy interventions to meet the sustainable development goals.

INTRODUCTION: Child marriage remains a prevalent issue in low- and middle-income countries (LMIC) despite global declines. Girls are disproportionately affected, facing health risks, limited education, and restricted decision-making power. We aim to provide insights for child marriage prevalence across LMIC from 1990 to 2020, with a focus on sexual violence and early sexual intercourse for public health policy interventions. METHODS: This study used World Bank datasets to assess progress in addressing child marriage in LMIC countries. Statistical analyses, including trend analysis and compound annual growth rate (CAGR), were conducted to evaluate indicators of first marriage, sexual violence, and sexual intercourse. Countries with sufficient data were categorized based on prevalence rates and trends, and detailed analysis focused on significant indicators. RESULTS: While significant reductions were observed in the prevalence of child marriage before the age of 15 and 18 and early sexual intercourse in most countries, few countries show increasing trends, and others could not demonstrate statistical trends due to data limitations, such as scarcity of data for boys. Overall, many countries showed a decline in sexual violence and early sexual intercourse before the age of 15, but some exhibited increasing trends. For instance, Zambia and Senegal showed a decreasing trend of sexual violence, while Nigeria exhibited an increasing trend. Notably, Uganda, Cameroon, and Sierra Leone for women, and Namibia, Zambia, and Kenya for men, experienced substantial decline in early sexual intercourse. CONCLUSION: There is a decline in child marriage, sexual violence, and early sexual intercourse in most countries independent from the income group. Only a few countries show slight increasing trends. The improvements confirm that policies that address education, employment, and deep-rooted gender inequality at the societal level seem to be effective and help reach the SDG. However, better data are needed to enhance the understanding of the development of child marriage in these countries to improve the effectiveness of policy intervention. Therefore, we recommend that policymakers not only include existing evidence that continues progress but also increase and improve the monitoring of relevant indicators.

Child marriage remains a prevalent issue despite global declines, particularly affecting girls who suffer from health risks, lower education, and restricted decision-making power. However, little is known about boys in this context. This study aims to examine We aim to provide insights for child marriage prevalence across LMIC from 1990 to 2020, with a focus on sexual violence and early sexual intercourse for public health policy interventions. To achieve this, we assessed progress in addressing child marriage in LMIC countries using World Bank datasets. Through statistical analyses, including trend analysis and linear regression, we evaluated various indicators. Countries with sufficient data were categorized based on prevalence and trends. The results revealed significant reductions in all indicators, few countries show increasing trends, and others could not demonstrate statistical trends due to data limitations, such as scarcity of data for boys. The Central African Republic experienced an increase in child marriage prevalence. Overall, many countries showed a decline in sexual violence and intercourse before the age of 15, but some exhibited increasing trends. For instance, Zambia and Senegal showed a decreasing trend of sexual violence, while Nigeria exhibits an increasing trend. Notably, Uganda, Cameroon, and Sierra Leone experienced substantial declines in early sexual intercourse for women, and Namibia, Zambia, and Kenya for men. There is a decline in child marriage, sexual violence, and early sexual intercourse in most countries independent of the income group. Only a few countries show slight increasing trends. The improvements confirm that policies that address education, employment, and deep-rooted gender inequality at societal level seem to be effective and help reach the SDG. However, better data are needed to enhance the understanding of the development of child marriage in these countries to improve the effectiveness of policy intervention. Therefore, we recommend that policymakers not only include existing evidence that continues progress but also increase and improve the monitoring of relevant indicators.

Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response.

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope.

Low-dose versus conventional-dose prednisolone for nephrotic syndrome relapses: a randomized controlled non-inferiority trial.

BACKGROUND: Reduction of steroid exposure in relapses of steroid-sensitive nephrotic syndrome (SSNS) is under-researched. METHODS: In this randomized controlled non-inferiority trial, 1-12-year-old children with relapse of SSNS were randomized to receive prednisolone 1 mg/kg/day (low dose) or 2 mg/kg/day (standard dose) until disease remission or day 15, whichever was earlier. Therapy was switched to 2 mg/kg/day in children in low-dose group not in remission by day 15. Primary outcome was days to remission, and secondary outcome being pattern of subsequent relapse(s) over 1 year. Estimating time to remission of 8 ± 2.5 days with standard-dose therapy, non-inferiority margin of 2 days, 90% power, and α-0.05, 60 patients were randomized. RESULTS: Of the 60 children (30 in each group) enrolled, 4 (one in low-dose group) failed remission by day 15. Time to remission was comparable between low-dose and standard-dose groups [9.0 ± 2.2 vs. 8.6 ± 2.2 days; mean difference (95% CI) 0.4 (- 0.79 to 1.59) days; p = 0.49], thus establishing non-inferiority of low dose. Median time to subsequent relapse was 86 (IQR 74.8, 97.2) and 150 (IQR 59.0, 240.9) days, in low- versus standard-dose groups, respectively (log rank p = 0.39). In follow-up, proportion of children having relapses, frequency of relapses, proportion with frequent relapse/steroid dependent (FR/SD), and cumulative corticosteroid dose taken were comparable between groups. CONCLUSIONS: This study shows that time to achieve remission after treatment of a relapse with low-dose prednisolone is non-inferior to that after treatment with conventional dose in children with SSNS. The proportion of children achieving remission, further course, and pattern of relapses was comparable between both groups.

Safety and efficacy of same-day discharge following elective percutaneous coronary intervention, including evaluation of next day troponin T levels.

BACKGROUND: As patients are increasingly undergoing elective percutaneous coronary intervention (PCI) with same-day discharge (SDD), and as post-PCI troponin T (TnT) elevations are associated with increased rates of death/myocardial infarction (MI) following elective PCI, we examined late outcomes with respect to post-PCI TnT elevations in patients undergoing SDD. METHODS AND RESULTS: We studied 303 patients (mean age 62±9years, 89% male) who underwent elective-PCI between October 2007 and September 2012, of whom 149 had SDD and 154 stayed overnight (ON) who were age-and sex-matched. Eligibility for SDD excluded patients with: multi-vessel PCI, proximal LAD lesions, chronic total occlusions, side branch occlusions, or access site complications. Femoral access rates were 72% and 96% among SDD and ON patients respectively. Post-PCI, SDD patients left at 4.40[4.13-5.30]hours, and ON patients left at 23.44[21.50-25.41]hours (p<0.001). Overall 8.45% met the 2012 universal MI definition. No patients were re-hospitalised within 48hours. At 30-days, unplanned cardiac re-hospitalisation rates were 3.4% and 0.7% among SDD and ON patients (p=0.118); the only event was MI in an SDD patient. At 16[9-32] months, rates of death, MI, target vessel revascularisation, stroke, were 1.3%,1.3%,2.7% and 1% respectively; the composite rate was 6%(6.1% SDD; 6% ON; p=0.965). Late death/MI rates among patients with, and without, post-PCI TnT levels≥5xURL were 3.4% and 2.8% respectively (p=0.588). CONCLUSION: SDD following elective PCI among low risk patients appears to be safe and ≥5 fold post-PCI TnT elevations did not appear to confer incremental short and long term risk. A larger cohort is required to confirm this observation.

Cardiovascular disease and lung cancer.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related death. While survival rates have improved with advancements in cancer therapeutics, additional health challenges have surfaced. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with lung cancer. CVD and lung cancer share many risk factors, such as smoking, hypertension, diabetes, advanced age, and obesity. Optimal management of this patient population requires a full understanding of the potential cardiovascular (CV) complications of lung cancer treatment. This review outlines the common shared risk factors, the spectrum of cardiotoxicities associated with lung cancer therapeutics, and prevention and management of short- and long-term CVD in patients with non-small cell (NSCLC) and small cell (SCLC) lung cancer. Due to the medical complexity of these patients, multidisciplinary collaborative care among oncologists, cardiologists, primary care physicians, and other providers is essential.

New Perspective on Pathophysiology and Management of Functional Mitral Regurgitation.

Functional mitral regurgitation (FMR) occurs as a result of global or segmental left ventricular (LV) dysfunction or left atrial dilatation, leading to mitral annular dilatation, papillary muscle displacement, mitral valve (MV) leaflet tethering, and leaflet remodeling. The prevalence of FMR continues to rise in the United States. Even mild FMR is associated with adverse clinical outcomes. Echocardiography is the primary imaging modality used to assess the type and severity of mitral regurgitation. FMR treatment depends on the etiology. Evidence-based pharmacologic and cardiac resynchronization therapies for underlying LV dysfunction remain the mainstay of treatment. Patients who remain symptomatic despite optimal medical therapy can be considered for surgical or percutaneous MV intervention. This article reviews the pathophysiology, imaging evaluation, and therapeutic options of FMR, highlighting the most recent developments in a rapidly evolving field.

Role of Sensitization and Awareness Program on Knowledge, Attitude, Views, and Practice of Self-Medication Among MBBS Students in a Medical College of Bihar.

Aims Self-medication is an essential component of self-care; however, its use has significantly increased. Its practice has many risks such as wrong diagnosis, adverse drug reactions, antimicrobial resistance, etc. Being future doctors, self-medication has a special impact on MBBS students. Henceforth, the present study was undertaken to sensitize MBBS students in a medical college in Bihar and to analyze its role in different aspects of self-medication. Methods and material This was a cross-sectional, questionnaire-based study. The questionnaire was circulated to MBBS students of all the phases. After collecting the responses, scoring and grading was done and then a sensitization and awareness program was conducted through different modes and medium. After three months the same questionnaire was distributed, and their response was again collected. Statistical analysis used With an expected 40% prevalence, the minimum sample size needed to attain a power of 95% and an alpha value of 0.05 was calculated to be 201. Statistical Package for Social Sciences version 16 was used for data analysis. The chi-square test was used to see the association in responses obtained, before and after sensitization. A P-value with ≤0.05 was considered statistically significant. Results The questionnaires were circulated among 439 students. On comparing the grades, we found that phase III students comparatively had better knowledge regarding different aspects of self-medication. On analyzing different aspects of self-medication, we found that there was a significant improvement in many aspects post-sensitization. Conclusions MBBS students are future doctors, hence they should be more educated about the pros and cons of self-medication. This study showed that the perception of participants improved after our educational activities. We hope that after becoming aware, these young budding doctors will spread awareness, which, in turn, will benefit society. Additionally, we hope that this study will have an impact on students from different medical colleges and even healthcare providers, promoting responsible self-medication practices when necessary.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.

Ethnopharmacology, phytochemistry, agrotechnology, and conservation of Inula racemosa Hook f. - A critically endangered medicinal plant of the western Himalaya.

ETHNOPHARMACOLOGICAL RELEVANCE: Inula racemosa Hook. f., is a critically endangered perennial herb distributed throughout the Himalaya; commercially useful in pharmaceutical products mainly because of its expectorant, antispasmodic, hypotensive, anti-inflammatory, carminative, thermogenic, digestive, cardiotonic, acrid, alexipharmic, anodyne, aphrodisiac, febrifuge, and antiseptic properties. The roots including rhizomes of the plant were used in the treatment of various ailments like chest pain, liver dysfunction, dyspnoea, and cardiovascular diseases by the ethenic Himalayan residents. AIM OF THE REVIEW: Even though there are plentiful studies involving I. racemosa for pharmacological properties, but there is gap or few records available on production technologies and patents. The purpose of review is to provide large unmanageable information in systematic form for researchers, health care contributors, and policy makers so that they efficiently integrate the existing information and provide balanced decision making. MATERIALS AND METHODS: Relevant data search was completed through systematic searches using various scientific databases including e-resources viz., Scopus, Google Scholar, Science Direct, ACS, Springer Link, Taylor and Francis, Scifinder, PubMed, PubChem, Web of Science, LibGen, Wiley, and China National Knowledge Infrastructure (CNKI). The list of literature cited in this review are dated from 1959 to 2021. RESULTS: Till date variety of ethnobotanical and pharmacological properties of essential oil including crude extract of I. racemosa have been documented. The shortlisted records revealed that the herb has a potential to treat stomach ulcer, respiratory tract infections including chronic obstructive pulmonary disease (COPD). Alantolactone and isoalloalantolactone were reported as the major bioactive constituents along with few fatty acids, phytosterols, and glycosides characterized by GC, GC/MS, HPLC, HPTLC and qNMR techniques. CONCLUSIONS: Based on a detailed literature survey on the plant, evidences were found fascinating for biological, traditional, and pharmacological effects, whilst there are no genomic resources available for this medicinal herb. Thus, molecular studies are critical for unravelling the production process of bioactive metabolites inside herb, which will underlay a path for improving these metabolites at commercial scale. Moreover, the association and role of particular phytoconstituent in its biological properties still needs to be validated. In addition, there are no reports on measures on its conservation and mechanism of toxicity research, which also needs more attention. We hope this review can provide a basis for further studies concerning the protected and efficient utilization of I. racemosa.

Urinary tract infection in children with Nephrotic syndrome: One of the hurdles for primary care physician and pediatrician towards timely diagnosis and optimum management of the disease.

Background: Urinary tract infection (UTI) is a common infection in children with nephrotic syndrome (NS). Clinical experience suggests that childhood nephrotic syndrome is frequently diagnosed incorrectly and managed inadequately on the top of this existing UTI in the episode becomes an additive obstacle for the primary care physicians or pediatricians towards optimum management, leading to poor outcome. So, we have conducted this clinico- microbiological study of UTI in NS in children to provide the exact picture of UTI with NS so that the primary care providers can be helped in having high index of suspicion of this infection and knowing prevalent organisms and their antimicrobial sensitivity pattern. Aim: The aim of the study was to study clinical features and identify the responsible organisms with its drug sensitivity pattern with response to treatment in various types and stages of NS with UTI in children. Methods: This cross-sectional hospital based study was conducted on 50 children of 2-18 years of age with NS attending nephrology clinic or admitted to the Paediatric ward of AIIMS, Rishikesh. Demographic, clinical, and microbiological data were recorded and details were entered in a predesigned proforma sheet. Results: Out of 50 cases, 8 (16%) had a positive urine culture. Six (75%) out of them had first episode and two (25%) were frequent relapsers of NS. Fever, decreased urine output, and generalized edema were the presenting features. The most common bacteria responsible for UTI was Pseudomonas aeruginosa (in around 25% isolates). Escherichia coli and Citrobacter koseri were the most resistant organisms. Patients were treated with antibiotics according to sensitivity pattern which resulted in resolution of symptoms and repeat urine culture became sterile subsequently. Conclusion: About one-sixth of children with Nephrotic Syndrome had UTI. UTI should be ruled out in every case of NS in active phase to prevent long-term morbidity and mortality.

Current trends in production, morphology, and real-world environmental applications of biochar for the promotion of sustainability.

Biochar has sparked a lot of interest in recent years for various applications such as contaminant removal, carbon sequestration and soil amendment. However, laboratory scale studies dominates over the real-world applications. In this study, we first enumerated on the various ongoing uses of biochar along with adsorption mechanism; and then identified the most suitable source, and efficient method for biochar production; and finally proposed real-world practical applications of biochar as an additive to control diffuse micropollutant pollution along the highways and railway tracks; as well as the pollution through agricultural runoff. We demonstrated that directly or indirectly, biochar can definitely help to achieve all the 17 Sustainable Development Goals. The study on the practical use of biochar is an emerging area, because a lot of research needs are there to realise the full-potential of biochar with ways of attaining sustainable development goals towards waste, energy and pollution management.

Non-Pharmaceutical Interventions as Controls to mitigate the spread of epidemics: An analysis using a spatiotemporal PDE model and COVID-19 data.

We investigate the spatiotemporal dynamics and control of an epidemic using a partial differential equation (PDE) based Susceptible-Latent-Infected-Recovered (SLIR) model. We first validate the model using empirical COVID-19 data corresponding to a period of 45 days from the state of Ohio, United States. Upon optimizing the model parameters in the learning phase of the analysis using actual infection data from a period of the first 30 days, we then find that the model output closely tracks the actual data for the next 15 days. Next, we introduce a control input into the model to represent the Non-Pharmaceutical Intervention of social distancing. Implementing the control using two distinct schemes, we find that in both cases the control input is able to significantly mitigate the infection spread. In addition to opening a novel pathway towards the characterization, analysis and implementation of Non-Pharmaceutical Interventions across multiple geographical scales using Control frameworks, our results highlight the importance of first-principles based PDE models in understanding the spatiotemporal dynamics of epidemics triggered by novel pathogens.

Zinc Supplementation for Prevention of Febrile Seizures Recurrences in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have documented lower serum zinc levels in patients with febrile seizures in comparison to febrile patients without seizure. However, there is limited evidence comparing the effects of zinc supplementation with placebo on recurrence of febrile seizures in children. OBJECTIVES: To study the effects of zinc supplementation on recurrence rate of febrile seizures in children less than 60 months of age. DESIGN: Systematic review and meta-analysis of randomized and quasi-randomized controlled trials. DATA SOURCE AND SELECTION CRITERIA: We searched PubMed, EMBASE and CENTRAL databases for articles reporting randomized or quasi-randomized controlled trials comparing the effects of zinc supplementation with placebo on recurrence of febrile seizures in children aged less than 60 months. We performed a fixed effect meta-analysis to provide pooled odds ratio of febrile seizure recurrence. Quality of evidence was assessed using GRADE approach. PARTICIPANTS: Children aged less than 60 months. INTERVENTION: Zinc supplementation. OUTCOME MEASURES: Odds of febrile seizure recurrence. RESULTS: Four clinical trials with a total of 350 children were included in the review. There was no statistically significant difference between odds of febrile seizure recurrence during one year follow up, in children on zinc supplementation compared to those on placebo (OR 0.70; 95% CI 0.41 - 1.18, I2 = 0%). CONCLUSIONS: Available evidence is very low quality and thus inadequate to make practice recommendations.

Mucin-filled CBD, difficult to manage cholangitis.

Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the pancreas but occasionally can involve surrounding structures (1.9%-6.6%), like bile duct and duodenum, and are labelled as IPMN with invasion. Jaundice as a manifestation of IPMN is not common (4.5%). It can present as jaundice as a result of invasion of common bile duct (CBD) resulting in stricture formation or uncommonly as a result of fistulising to CBD with resultant obstruction of CBD by thick mucin secreted by this tumour. As only few cases (around 23) of mucin-filled CBD are reported in the literature. We are presenting our experience in dealing a rare case of obstructive jaundice caused by IPMN fistulising into CBD, highlighting the difficulties faced in managing such case, especially with regards to biliary drainage and what can be the optimum management in such cases.

Research gaps in transforming tuberculosis data to action for better health outcomes: A systematic literature review.

BACKGROUND: In their work to end the tuberculosis (TB) epidemic in lower- and middle-income countries, national TB programs need a tool to measure, monitor, and strengthen relevant capabilities to create a continuous transformation of data into action (D2A) to improve TB program results. However, there is a lack of scientific evidence to determine specific measurement dimensions of a D2A continuum that enables TB programs to identify the barriers and enablers of D2A and to guide the selection of interventions appropriate for the context and decision-making capabilities of various TB program actors. METHODS: A systematic review of peer-reviewed and grey literature was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 48 peer-reviewed publications were selected for data extraction and analysis. RESULTS: The findings show that selected publications discussed the health system level, stakeholders involved in decision making, decision type, data system, data sources, data use enablers and barriers, decision-making framework and steps, decision outcome/impact, and how that outcome was measured. The findings highlight barriers and enablers to data use and explain the relationship among data sources, decision type, and stakeholders. Seventeen D2A measurement dimensions were identified. CONCLUSIONS: Transforming data to action is a continuous process that recognizes that data use indicators vary by type of decisions, decision makers, and the health system level at which decisions are made. As a logical next step, the project team plans to develop and validate a D2A continuum toolkit that will include a measurement scale, implementation guide, and data collection and analysis Microsoft Excel workbook.

Cushing syndrome in an infant due to cortisol secreting adrenal pheochromocytoma: a rare association.

Adrenocortical tumors are the most common cause of endogenous Cushing syndrome in infancy and early childhood. Cushing syndrome resulting from ectopic adrenocorticotrophic hormone (ACTH) producing tumor has been infrequently reported in adults. Cortisol secreting pheochromocytoma is rarely reported in literature. We report an eleven month old child presenting to us as Cushing syndrome with hypertension due to left adrenal tumor. He was treated with antihypertensives and left adrenalectomy was done under perioperative glucocorticoid coverage. Diagnosis of pheochromocytoma was made only after histopathology. Despite the rare association of Cushing syndrome and pheochromocytoma, preoperative diagnosis of pheochromocytoma is required for appropriate perioperative medical and anaesthetic management to prevent life threatening complications.

Prospects of acne vaccines targeting secreted virulence factors of Cutibacterium acnes.

INTRODUCTION: Acne vulgaris afflicts many people, and despite the multitude of the anti-acne products on the market, there is still no effective treatment that can prevent and cure this disease. The severity of acne vulgaris is highly associated with the inflammatory response to Propionibacterium acnes (P. acnes) now referred to as Cutibacterium acnes (C. acnes), an opportunistic skin bacterium in the human skin microbiome. Areas covered: We here provide the prospects of creating acne vaccines targeting secreted virulence factors of C. acnes including secretory Christie-Atkins-Munch-Peterson (CAMP) factor. Neutralization of secreted virulence factors by either active or passive vaccination may have a lower risk of disturbing the microbial ecosystem in the human skin microbiome. Expert opinion: Major steps could be taken to start a public vaccination program at an early age to prevent the future occurrence of acne vulgaris. Future therapeutic monoclonal antibodies can be designed to specifically neutralize virulence factors of C. acnes including CAMP factors without disrupting the optimal balance of C. acnes in the human skin microbiome and lowering the risk of creating drug-resistant C. acnes. Targeting secreted virulence factors without disturbing the commensal relationship of host can be a novel gateway towards the therapeutic treatment of acne vulgaris.

Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial.

OBJECTIVE: Adequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of fentanyl for analgesia and sedation in neonates. METHODS: In this open-label randomised controlled trial, neonates requiring 24-48 hours of mechanical ventilation and fentanyl administration were recruited. In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain, Agitation and Sedation Scale for acute and ongoing pain, respectively) and incidence of adverse effects of fentanyl. RESULTS: 100 neonates were recruited, 53 in CI and 47 in IB group. In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p<0.001) was significantly higher and area under concentration-time curve (AUC0-24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour/L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens. CONCLUSION: CI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4-0.6 ng/mL produces adequate analgesia and sedation in neonates. TRIAL REGISTRATION NUMBER: CTRI/2014/11/005190.

Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives.

Cancer is a leading cause of disease burden throughout the world. Many cancers develop as a result of exposure to both lifestyle and environmental factors that are potentially modifiable. In the last few years, much of the scientific attention has drawn to the discovery of new and effective chemopreventive agents from natural sources. A multitude of phytoconstituents have been explored for their potential to prevent the occurrence of carcinogenesis both in vitro and in vivo by means of diverse cellular and molecular approaches. Key focus of this review is to highlight some significant and new information about different molecular aspects of chemopreventive ability of plant based phytochemicals in terms of their inhibitory potential on cancer growth. In addition, information regarding certain limiting factors such as whole animal physiology, tumour microenvironment and bioavailability of active components of phytoconstituents used in pre/clinical trials are further explored. This review would further assist the scientific community involved in designing efficacious chemopreventive approaches using these phytochemicals in treating cancer.