Repurposing AZD5438 and Dabrafenib for Cisplatin-Induced AKI.

SIGNIFICANCE STATEMENT: To combat both untoward effects of nephrotoxicity and ototoxicity in cisplatin-treated patients, two potential therapeutic oral anticancer drugs AZD5438 and dabrafenib, a phase-2 clinical trial protein kinase CDK2 inhibitor and an US Food and Drug Administration-approved drug BRAF inhibitor, respectively, were tested in an established mouse AKI model. Both drugs have previously been shown to protect significantly against cisplatin-induced hearing loss in mice. Each drug ameliorated cisplatin-induced increases in the serum biomarkers BUN, creatinine, and neutrophil gelatinase-associated lipocalin. Drugs also improved renal histopathology and inflammation, mitigated cell death by pyroptosis and necroptosis, and significantly enhanced overall survival of cisplatin-treated mice. BACKGROUND: Cisplatin is an effective chemotherapy agent for a wide variety of solid tumors, but its use is dose-limited by serious side effects, including AKI and hearing loss. There are no US Food and Drug Administration-approved drugs to treat both side effects. Recently, two anticancer oral drugs, AZD5438 and dabrafenib, were identified as protective against cisplatin-induced hearing loss in mice. We hypothesize that similar cell stress and death pathways are activated in kidney and inner ear cells when exposed to cisplatin and tested whether these drugs alleviate cisplatin-induced AKI. METHODS: The HK-2 cell line and adult FVB mice were used to measure the protection from cisplatin-induced cell death and AKI by these drugs. Serum markers of kidney injury, BUN, creatinine, and neutrophil gelatinase-associated lipocalin as well as histology of kidneys were analyzed. The levels of markers of kidney cell death, including necroptosis and pyroptosis, pERK, and proliferating cell nuclear antigen, were also examined by Western blotting and immunofluorescence. In addition, CDK2 knockout (KO) mice were used to confirm AZD5438 protective effect is through CDK2 inhibition. RESULTS: The drugs reduced cisplatin-induced cell death in the HK-2 cell line and attenuated cisplatin-induced AKI in mice. The drugs reduced serum kidney injury markers, inhibited cell death, and reduced the levels of pERK and proliferating cell nuclear antigen, all of which correlated with prolonged animal survival. CDK2 KO mice were resistant to cisplatin-induced AKI, and AZD5438 conferred no additional protection in the KO mice. CONCLUSIONS: Cisplatin-induced damage to the inner ear and kidneys shares similar cellular beneficial responses to AZD5438 and dabrafenib, highlighting the potential therapeutic use of these agents to treat both cisplatin-mediated kidney damage and hearing loss.

Optimisation of multigrain seera from sorghum, green gram and finger millet: effect of ingredients on functional, structural and thermal properties.

Seera, is a traditional Indian fermented food, has high carbohydrate and reducing sugar content, however, lacks functional components like antioxidant properties. The present study aims to optimize and evaluate the multigrain seera with added values. The optimization of seera was made using mixture design, with green gram (X1, 15-30%), sorghum (X2, 15-25%) and finger millet (X3, 5-10%) as independent variables. The responses checked were total phenolic content (Y1), protein content (Y2) and overall acceptability (Y3). The optimum run with green gram (25.58%), sorghum (15%) and finger millet (9.41%) resulted in TPC (1.2 ± 0.12 mg GAE/g), protein content (11.40 ± 0.10 g) with overall acceptability (8.32 ± 0.30). The optimized multigrain seera depicted higher fibre (4.23 ± 0.08%), ash (1.90 ± 1.1%) and protein (11.40 ± 0.10%) than the control seera. The rheological properties of seera depicted shear thinning and elastic behaviour. Texture profile analysis showed that cohesiveness (0.415 ± 0.01) increased significantly (along with decreased springiness (0.251). Morphology of seera showed broken and deformed starch granules with few cracks due to fermentation phenomena that leads to superficial corrosion. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05854-5.

Fortification by design: A rational approach to designing vitamin D delivery systems for foods and beverages.

Over the past few decades, vitamin D deficiency has been recognized as a serious global public health challenge. The World Health Organization has recommended fortification of foods with vitamin D, but this is often challenging because of its low water solubility, poor chemical stability, and low bioavailability. Studies have shown that these challenges can be overcome by encapsulating vitamin D within well-designed delivery systems containing nanoscale or microscale particles. The characteristics of these particles, such as their composition, size, structure, interfacial properties, and charge, can be controlled to attain desired functionality for specific applications. Recently, there has been great interest in the design, production, and application of vitamin-D loaded delivery systems. Many of the delivery systems reported in the literature are unsuitable for widespread application due to the complexity and high costs of the processing operations required to fabricate them, or because they are incompatible with food matrices. In this article, the concept of "fortification by design" is introduced, which involves a systematic approach to the design, production, and testing of colloidal delivery systems for the encapsulation and fortification of oil-soluble vitamins, using vitamin D as a model. Initially, the challenges associated with the incorporation of vitamin D into foods and beverages are reviewed. The fortification by design concept is then described, which involves several steps: (i) selection of appropriate vitamin D form; (ii) selection of appropriate food matrix; (iii) identification of appropriate delivery system; (iv) identification of appropriate production method; (vii) establishment of appropriate testing procedures; and (viii) system optimization.

Prevalence of chronic pain in Pakistan - a national survey.

OBJECTIVE: To assess the prevalence of chronic pain, its physical and psychosocial impact on daily life, and the various therapies adopted to alleviate pain. METHODS: The cross-sectional population-based telephonic survey was conducted from May to July 2021 at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, and comprised patients of either gender aged at least 18 years suffering from chronic pain who visited the institutional laboratory collection centres. In the first phase, people who were suffering from chronic pain were screened, while in the second phase, data was collected using a detailed questionnaire exploring pain history, treatment and its effects. The data was compiled and analysed using Antlere's AI based software. RESULTS: Of the 4,801 patients contacted, 757(15.75%) were suffering from chronic pain. A total of 201(20%) subjects reported that their pain score was 5/10 on the numerical rating scale. Back pain was the major complaint (183, 18%) among the subjects. Of the total, 335(44.25%) were having active treatment, and 226 (67%) of them said the medication was effective. Overall, 706 (93%) patients had never visited a pain management specialist. Furthermore, 252 (33%) participants were diagnosed with depression, and 106 (14%) patients said that they were suicidal at some point in life. CONCLUSIONS: .The survey observed that a high percentage of unawareness existed on pain management among the Pakistani citizens.

Vitamin A fortification: Recent advances in encapsulation technologies.

Vitamin A is an essential micronutrient whose deficiency is still a major health concern in many regions of the world. It plays an essential role in human growth and development, immunity, and vision, but may also help prevent several other chronic diseases. The total amount of vitamin A in the human diet often falls below the recommended dietary allowance of approximately 900-1000 µ$ \umu $ g/day for a healthy adult. Moreover, a significant proportion of vitamin A may be degraded during food processing, storage, and distribution, thereby reducing its bioactivity. Finally, the vitamin A in some foods has a relatively low bioavailability, which further reduces its efficacy. The World Health Organization has recommended fortification of foods and beverages as a safe and cost-effective means of addressing vitamin A deficiency. However, there are several factors that must be overcome before effective fortified foods can be developed, including the low solubility, chemical stability, and bioavailability of this oil-soluble vitamin. Consequently, strategies are required to evenly disperse the vitamin throughout food matrices, to inhibit its chemical degradation, to avoid any adverse interactions with any other food components, to ensure the food is palatable, and to increase its bioavailability. In this review article, we discuss the chemical, physical, and nutritional attributes of vitamin A, its main dietary sources, the factors contributing to its current deficiency, and various strategies to address these deficiencies, including diet diversification, biofortification, and food fortification.

Measles surveillance in Kashmir: A mixed methods study.

Background: Measles surveillance serves as the means of monitoring program success. The quintessential purpose of measles surveillance is to identify gaps and garner effective public health responses to achieve measles elimination. Objectives: There were two key objectives: (i) to conduct an in-depth review of the existing measles surveillance system in Kashmir and highlight its strengths and weaknesses and (ii) to assess the pattern of measles-containing vaccine (MCV1) coverage and MCV2 coverage among under-5 years children and describe the health-seeking patterns of suspected cases of measles. Methods: The mixed methods study was conducted in the Kashmir valley from March 2018 to March 2019. An explorative qualitative design was followed using individual face-to-face interviews with thirty-two (n = 32) different stakeholders from the state, district, medical block, and primary health center (PHC) levels. To complement the qualitative study, a quantitative survey was done in two districts, Srinagar and Ganderbal, which consist of 5 and 4 medical blocks, respectively. Results: Among the suspected cases of measles, 52% had visited PHCs. Sixty-four suspected cases of measles (64) were immunized with two doses of MCV. None of the clinically suspected cases of measles were further investigated. In the qualitative analysis, five themes were generated viz, "measles surveillance description of Kashmir valley;" "factors affecting measles surveillance, perceptions, and experiences of stakeholders;" "barriers to measles surveillance;" "measles surveillance activities need to be intensified;" and "respondent recommendations for building an effective and sensitive measles surveillance system." Conclusion: The current measles surveillance system in Kashmir was not effectively functioning; case-based measles surveillance is not being done as per the WHO guidelines. There is a lack of planning, advocacy, awareness, and communication of measles surveillance among the stakeholders. The visible barriers in measles surveillance included lack of training, logistics, incentives, and monitoring by internal and external agencies.

Physicochemical, structural and functional properties of native and irradiated starch: a review.

The world population has crossed seven billion and such a huge population has increased the pressure and considerably affects our ability to feed ourselves. It has now emerged as a new challenge for policy makers, food scientists and other associated people to make food available to everyone. To achieve this, underutilized crops/plants that act as good sources of starch need to be explored. Starch in its native form have certain limitations in its functional properties to be used for different applications. Therefore, it becomes important to explore certain technologies which could be used for modification of properties of starch. During the last decades gamma irradiation has emerged as an efficient processing technique for the modification of starch when compared to the other available processes. This review, aims to summarize the effects of gamma irradiation on various properties of starch such as physicochemical and rheological properties, functional characteristics, thermal behaviour etc. so as to make the starch suitable for various applications in different industries including the food industry.

Resiquimod enhances mucosal and systemic immunity against avian infectious bronchitis virus vaccine in the chicken.

Adjuvant enhancing mucosal immune response is preferred in controlling many pathogens at the portal of entry. Earlier, we reported that a toll-like-receptor 7 (TLR7) agonist, resiquimod (R-848), stimulated the systemic immunity when adjuvanted with the inactivated Newcastle disease virus vaccine in the chicken. Here, we report the effect of R-848 when adjuvanted with live or inactivated avian infectious bronchitis virus (IBV) vaccines with special emphasis on mucosal immunity. Specific pathogen free (SPF) chicks (n = 60) were equally divided into six groups at two weeks of age and immunized with either inactivated or live IBV vaccine adjuvanted with or without R-848. Groups that received either PBS or R-848 served as control. A booster was given on 14 days post-immunization (dpi). R-848 enhanced the antigen specific humoral and cellular immune responses when co-administered with the vaccines as evidenced by an increase in the antibody titre in ELISA and stimulation index in lymphocyte transformation test (LTT) till 35 dpi and increased proportion of CD4+ and CD8+ T cells on 21 dpi in the flow cytometry. Interestingly, it potentiated the IgA responses in the tear and intestinal secretions when used with both live and inactivated IBV vaccines. The combination of IBV vaccine with R-848 significantly up-regulated the transforming growth factor beta 4 (TGFß4) transcripts in the peripheral blood mononuclear cells (PBMCs) than that of the respective vaccine per se. An enhanced secretory IgA response is likely due to the up-regulation of TGFß4, which is responsible for class switching to IgA. In conclusion, co-administration of R-848 with inactivated or live IBV vaccine enhanced the systemic as well as mucosal immune responses in the chicken.

Benign Paroxysmal Positional Vertigo After Joint Replacement Surgeries: Case Series.

Benign paroxysmal positional vertigo (BPPV) is characterized by brief episodes of vertigo triggered by changes in head position caused by the displacement of otoliths from the utricle to the semicircular canals, particularly the posterior canal. This study explored the potential link between BPPV, the patient's preexisting conditions, and surgery-related factors including surgical positioning, duration of the procedure, exposure to vibratory forces, and anesthesia effects. This report presents two cases of BPPV following major joint replacement surgery. The first case involved a 65-year-old male with a history of diet-controlled diabetes who had undergone right-sided total hip replacement. The second case was that of a 60-year-old female with a history of osteoporosis managed with bisphosphonate therapy and left-sided knee replacement. Both patients developed vertigo symptoms one day postoperatively and were diagnosed with BPPV. In both cases, the Dix-Hallpike test confirmed the right-sided posterior canal BPPV diagnosis, and the patients were successfully treated using the Epley maneuver. Notably, there was no recurrence of vertigo at the four-week follow-up. These cases highlight the importance of considering BPPV in patients presenting with vertigo symptoms after joint replacement surgery, especially in the presence of comorbidities like diabetes and osteoporosis which possibly increase susceptibility to BPPV. This article presents two cases of benign paroxysmal positional vertigo (BPPV) following non-otologic surgery. It explores the pathophysiological mechanism underlying BPPV after such surgeries and also discusses the diagnosis and treatment approaches. This underscores the need for prompt diagnosis and treatment of BPPV to improve postoperative outcomes.

Colonoscopic cancer detection rate: a new performance measure - is it FIT for purpose?

Introduction: Gastrointestinal symptoms correlate poorly with cancer diagnosis. A faecal immunochemical test (FIT) result of ≥10 µg has high sensitivity and negative predictive value for colorectal cancer (CRC) detection. An FIT-based diagnostic pathway may lead to more effective resource utilisation. We aimed to use National Endoscopy Database (NED) data to create a new colonoscopy performance measure, cancer detection rate (CDR) to assess the appropriate identification of target populations for colonoscopy; then to use CDR to assess the impact of implementing an FIT-based referral pathway locally. Methods: NED data were analysed to compare local diagnostic colonoscopic CDR in 2019 (prepathway revision) and 2021 (postpathway revision), benchmarked against overall national CDR for the same time frames. Results: 1, 123, 624 NED diagnostic colonoscopies were analysed. Locally, there was a significant increase in CDR between 2019 and 2021, from 3.01% (2.45%-3.47%) to 4.32% (3.69%-4.95%), p=0.003. The CDR increase was due to both a 10% increase in the number of CRCs detected and a 25% reduction in the number of diagnostic colonoscopies performed. Nationally, there was a smaller, but significant, increase in CDR from 2.02% (1.99%-2.07%) to 2.33% (2.29%-2.37%), p<0.001. The rate of increase in CDR% between 2019 and 2021 was significantly different locally compared with nationally. Conclusion: Our study indicates that the introduction of a robustly vetted FIT-based algorithm to determine whether diagnostic colonoscopy is required, is effective in increasing the colonoscopic CDR. Moreover, CDR appears to be a meaningful performance metric that can be automatically calculated through NED, enabling monitoring of the quality of referral and vetting pathways.

Accuracy of procalcitonin for diagnosing sepsis in adult patients admitted to the emergency department: a systematic review and meta-analysis.

BACKGROUND: Differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS) is challenging. Biomarkers like procalcitonin (PCT) aid early risk assessment and guide antibiotic use. This study aims to ascertain PCT's accuracy as a sepsis biomarker among adult emergency department admissions. METHOD: The PRISMA guidelines were followed to search for relevant articles in five electronic databases between April 14th and August 4th, 2023: PubMed, Cochrane Library, ProQuest, EMBASEs, and ScienceDirect. Studies had to be published in English to avoid directly translating scientific terms. Besides, the inclusion criteria were based on the diagnosis of sepsis in adult patients admitted to an emergency department. QUADAS-2 tool provided by the Review Manager version 5.4.1 was utilized to assess the risk of bias in included studies. STATA (v. 16) software was used to perform the meta-analysis. RESULTS: Ten of 2457 studies were included. We sampled 2980 adult sepsis patients for the under-investigated role of PCT in ED sepsis diagnosis. PCT emerged as the primary early diagnostic biomarker with high levels (29.3 ± 85.3 ng/mL) in sepsis patients. Heterogeneity in outcomes, possibly due to bias in cohort and observational studies, was observed. CONCLUSION: PCT tests offer moderate accuracy in diagnosing sepsis and stand out for rapidly and precisely distinguishing between viral and bacterial inflammations.

Comparative Analysis of Intravenous Opioids Versus Thoracic Epidural Anesthesia in Fractured Rib Pain Management: A Systematic Review and Meta-Analysis.

Rib fractures, common among trauma victims, lead to significant morbidity and mortality. Managing the associated pain is challenging, with IV opioids and thoracic epidural analgesia (TEA) being utilized. While epidural analgesia is often preferred for fractured rib pain, existing data encompasses both lumbar and thoracic approaches. This review aimed to compare TEA and IV opioids for persistent rib fracture pain. A comprehensive search across five databases yielded 987 articles, of which seven met the eligibility criteria. Outcomes were categorized into primary (pain reduction) and secondary (mortality, hospital/ICU stays, analgesia-related complications) endpoints. Analyzed with Review Manager (RevMan) Version 5.4.1 (2020; The Cochrane Collaboration, London, United Kingdom), the pooled data from two sources showed TEA significantly more effective in reducing pain than IV opioids (standardized mean difference (SMD): 2.23; 95%CI: 1.65-2.82; p < 0.00001). Similarly, TEA was associated with shorter ICU stays (SMD: 0.73; 95%CI: 0.33-1.13; p = 0.0004), while hospitalization duration showed no substantial difference (SMD: 0.82; 95%CI: -0.34-1.98). Mortality rates also did not significantly differ between TEA and IV opioids (risk ratio (RR): 1.20; 95%CI: 0.36-4.01; p = 0.77). Subgroup analysis revealed fewer pneumonia cases with TEA (RR: 2.06; 95%CI: 1.07-3.96; P = 0.03), with no notable disparities in other complications. While TEA's superiority in pain relief for rib fractures suggests it is the preferred analgesic, the recommendation's strength is tempered by the low methodological quality of supporting articles.

Burden of Goitre and Urinary Iodine Status among Primary School Children in Kashmir, India-Evidence from a Population-Based Iodine Deficiency Disorder Survey.

Introduction: Iodine deficiency is the leading cause of preventable brain damage, with 30% of the world's population suffering from iodine deficiency disorders (IDDs). The objectives of the study are to estimate the prevalence of goitre among schoolchildren in the age group of 6-12 years, to find out the proportion of households with adequately iodised salt, and to assess the dietary iodine intake by measuring urinary iodine levels in the urine samples of school-going children. Methods: A cross-sectional study was conducted in four pre-selected districts of the Kashmir division of Jammu and Kashmir in school-going children aged 6 to 12 years. Multi-stage 30 cluster sampling was used to select the study sample. For the selection of 30 clusters in each district, probability proportional to size (PPS) was employed. From each cluster, 90 children were selected. From a sub-sample of children in each district, 540 salt samples and 270 urine samples were also collected. Results: A total of 10,800 children aged 6-12 years were examined. Grade I goitre was present in 1382 (12.8%) and 116 (1.07%) which were having Grade II goitre. The weighted prevalence of goitre for four districts was 12.6%, lowest for district Ganderbal and highest for district Shopian. Half of the population in all the districts consumed salt with iodine levels of <15 ppm. Urinary iodine levels <99.9 mg/L were present in 15.7% indicating mild to moderate iodine deficiency. Conclusion: Though the present survey showed some decline in the total goitre rate (TGR) from a prevalence of 14.8% in 2017 to 12.6% in 2022, it continues to be a public health problem of mild to moderate intensity in Kashmir. The salt consumed at the household level was inadequately iodised. Hence, efforts in IDD elimination activities need to be scaled up further with emphasis on iodised salt quality control and intensive education at the community level.

Benign Paroxysmal Positional Vertigo (BPPV) After Concussion in Two Adolescent Players During a Rugby Game.

Benign paroxysmal positional vertigo (BPPV) is a medical condition where patients develop symptoms of vertigo, "room spinning," associated with nausea and vomiting. BPPV is believed to be caused by a disturbance in the inner ear vestibular system. Trauma has been recognized as one of the risk factors for this condition. BPPV can be easily diagnosed and treated by bedside maneuvers. Due to a lack of awareness among some treating clinicians, patients may have to wait for a long time before the correct management is offered. We share two cases of BPPV in 15- and 16-year-old male school students who developed posterior canal BPPV following a head injury during a rugby game. Both patients continue to have vertigo symptoms for several weeks before the final diagnosis. BPPV symptoms completely resolved following the Epley maneuver. Frontline clinicians need to diagnose and treat BPPV early to prevent the persistence of these debilitating symptoms. As far as we are aware, no previous study has published the occurrence of BPPV in young adolescent rugby players.

High flow nasal oxygen (HFNO) in the treatment of COVID-19 infection of adult patients from - An emergency perspective: A systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, which was first discovered in Wuhan, China. The disease has grown into a global pandemic causing mild to moderate symptoms in most people. The disease can also exhibit serious illnesses, especially for patients with other chronic diseases such as cardiovascular diseases, diabetes, chronic respiratory disease, or cancer. In such cases of severe illness, high flow nasal oxygen (HFNO) has been used to provide oxygenation to COVID-19 patients. However, the efficiency of HFNO remains uncertain, prompting the conduction of this systematic review to evaluate the effectiveness of the therapy. A thorough search for relevant and original articles was carried out on five electronic databases, including ScienceDirect, PubMed, Cochrane Library, Embase, and Google Scholar. No time limitation was placed during the search as it included all the articles related to COVID-19 from 2019 to 2022. The search strategy utilized in this systematic review yielded 504 articles, of which only 10 met the eligibility criteria and were included. Our meta-analysis reveals that HFNO success rate was higher than HFNO failure rates (0.52 (95% CI; 0.47, 0.56) and 0.48 (95% CI; 0.44, 0.53), respectively), however, the difference was statistically insignificant. HFNO was associated with a significant decrease in mortality and intubation rates (0.28 (95% CI; 0.19, 0.39) and 0.28 (95% CI; 0.18, 0.41), respectively). Our statistical analysis has shown that significantly lower ROX index (5.07 ± 1.66, p = 0.028) and PaO2/FiO2 (100 ± 27.51, p = 0.031) are associated with HFNO failure, while a significantly lower respiratory rate (RR) (23.17 ± 4.167, p = 0.006) is associated with HFNO success. No statistically significant difference was observed in SpO2/FiO2 ratio between the HFNO success and failure groups (154.23 ± 42.74 vs. 124.025 ± 28.50, p = 0.62, respectively). Based on the results from our meta-analysis, the success or failure of HFNO in treating COVID-19 adult patients remains uncertain. However, HFNO has been shown to be an effective treatment in reducing mortality and intubation rates. Therefore, HFNO can be recommended for COVID-19 patients but with close monitoring and should be carried out by experienced healthcare workers.

Teachers' perceptions of the impact of COVID-19 pandemic and virtual teaching on the physical and mental health of children in Kashmir: A qualitative study.

Background: Children inherently want to remain engrossed in the activities as easily as possible within their ecological environment and academic curricular ambit. Covid-19 adversely affected our physical, social, and mental conditions and children were no exception. Objectives: To understand the experiences of teachers who have been doing virtual teaching to children during COVID-19; To understand the impact of virtual teaching and COVID-19 on physical and mental health of children. Materials and Methods: The qualitative study was conducted in the Kashmir valley and school teachers teaching students from class Ist to class 8th were involved in the study. Participants were selected purposefully based on the inclusion criteria. One-to-one in-depth interviews were conducted with sixteen (16) school teachers, using a preformed interview guide. Data analysis was performed using the thematic analysis method. Results: Data analysis yielded four overarching themes and twelve subthemes viz:- 1) Attitudes towards online sessions among teachers (2) factors affecting the physical and mental health of children (3) Effectiveness of online classes for individual lines of children's mental development (4) External and internal factors impacting child development and pedagogy. Conclusion: The study result explicitly showed mental and physical health of children got considerably affected by online teaching during the Covid-19 pandemic. Online teaching especially to children is less yielding in terms of effective academic consequences. Nevertheless, blending online teaching with pedagogy can enhance certain multidimensional capabilities of the children.

Clinical assessment and risk stratification for prehospital use of methoxyflurane versus standard analgesia in adult patients with trauma pain.

Oligoanalgesia, the undertreatment of trauma-related pain using standard analgesics in prehospital and emergency departments, has been extensively documented as one of the major challenges affecting the effective treatment of trauma-related pain. When administered in low doses, methoxyflurane has been highlighted by numerous medical works of literature to provide an effective, nonopioid, nonnarcotic treatment alternative to standard analgesics for prehospital and emergency department use. Low-dose methoxyflurane has been associated with fast-pain relief in adult patients manifesting moderate-to-severe pain symptoms. This systematic review and meta-analysis aimed to assess the clinical implication of low-dose methoxyflurane use in prehospital and emergency departments in adult patients with moderate-to-severe trauma-related pain. Moreover, the review aimed at assessing the risk stratification associated with using low-dose methoxyflurane in prehospital and emergency departments. The systematic review and meta-analysis performed a comprehensive search for pertinent literature assessing the implications and risks of using low-dose methoxyflurane in adult patients exhibiting moderate-to-severe trauma-related pain in prehospital settings. A comparison between the use of low-dose methoxyflurane and standard-of-care analgesics, placebo, in prehospital settings was reported in four clinically conducted randomized controlled trials (RCTs). These RCTs included the STOP! trial, InMEDIATE, MEDIATA, and the PenASAP trials. A meta-analysis comparing the time taken to achieve first pain relief on initial treatment of patients with moderate-to-severe trauma-related pain favored the use of low-dose methoxyflurane to the standard-of-care analgesics (mean difference = -6.63, 95% confidence interval = -7.37, -5.09) on time taken to establish effective pain relief. Low-dose methoxyflurane has been associated with superior and faster pain relief in prehospital and emergency departments in adult patients exhibiting moderate-to-severe trauma-related pain compared to other standard analgesics.

The Utility of the Mini-Clinical Evaluation Exercise (Mini-CEX) in the Emergency Department: A Systematic Review and Meta-Analysis Evaluating the Readability, Feasibility, and Acceptability of Mini-CEX Utilization.

Assessment tools, such as the mini-clinical evaluation exercise (mini-CEX), have been developed to evaluate the competence of medical trainees during routine duties. However, their effectiveness in busy environments, such as the emergency department (ED), is poorly understood. This study assesses the feasibility, reliability, and acceptability of implementing the mini-CEX in the ED. PubMed, Google Scholar, ScienceDirect, Scopus, and Web of Science databases were scoured for observational and randomized trials related to our topic. Moreover, a manual search was also conducted to identify additional studies. After the literature search, data were extracted from studies that were eligible for inclusion by two independent reviewers. When applicable, meta-analyses were performed using the Comprehensive Meta-Analysis software. In addition, the methodological quality of studies was evaluated using the Newcastle-Ottawa Scale. Of the 2,105 articles gathered through database and manual searches, only four met the criteria for inclusion in the review. A combined analysis of three studies revealed that trainee-patient interactions averaged 16.05 minutes (95% CI = 14.21-17.88), and feedback was given in about 10.78 minutes (95% CI = 10.19-11.38). The completion rates for mini-CEX were high: 95.7% (95% CI = 87.6-98.6) for medical trainees and 95.8% (95% CI = 89.7-98.3) for assessors. Satisfaction with mini-CEX was notable, with 63.5% (95% CI = 51.5-74.1) of medical trainees and 75.7% (95% CI = 63.9-84.6) of assessors expressing contentment. Qualitative data from one study demonstrated that 70.6% of faculty members could allocate suitable time for mini-CEX during their clinical shifts. The mini-CEX is a feasible and acceptable assessment tool within the ED. Furthermore, there is evidence to suggest that it might be reliable.

Antihypertensive Interventions in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis Evaluating Clinical Outcomes Through an Emergency Medicine Paradigm.

High blood pressure (HBP) is usually prominent after the onset of acute ischemic stroke (AIS). Although previous studies have found that about half of patients with AIS have a background of hypertension, there is no clear etiology for HBP in AIS. The literature reveals discrepancies in the relationship between HBP and clinical outcomes of AIS, pointing toward the contested effect of blood pressure (BP) reduction clinical outcomes. Thus, the potential benefits and hazards of HBP treatment were explored in the context of clinical outcomes after AIS. An electronic database and a manual search were carried out to identify all the articles related to this topic and published between 2000 and January 2023. The Review Manager software was also used to perform the meta-analysis and quality appraisal. In analyses related to patients not treated with reperfusion therapies, mortality, and dependency outcomes were categorized as short-term (<3 months) or long-term (≥3 months). Our search strategy yielded 2459 articles, of which only 15 met the inclusion criteria. The results of our meta-analysis demonstrate that in patients not treated with reperfusion therapies, BP lowering had no significant impact on either short-term or long-term mortality (risk ratio (RR): 1.18; 95% confidence interval (CI): 0.81-1.73; p = 0.39, and RR: 1.04; 95% CI: 0.77-1.40; p = 0.81, respectively) and dependency (RR: 1.12; 95% CI: 0.97-1.30; p = 0.11, and RR: 0.98; 95% CI: 0.90-1.07; p = 0.61, respectively). Furthermore, BP lowering prior to reperfusion showed no significant effect on mortality (RR: 0.7; 95% CI: 0.23-2.26; p = 0.58), but it did significantly reduce the risk of dependency (RR: 0.89; 95% CI: 0.85-0.94; p < 0.00001). When the dataset was restricted to patients who had successful reperfusion, intensive BP lowering (target systolic BP <120 mmHg) was found to increase the risk of dependency (RR: 1.23; 95% CI: 1.09-1.39; p = 0.0009). In addition, BP reduction had an insignificant effect on the risk of recurrent strokes and combined vascular events (RR: 1.00; 95% CI: 0.54-1.84; p = 1.00, and RR: 0.99; 95% CI: 0.70-1.41; p = 0.95, respectively). Lowering BP in patients not treated with reperfusion therapies is not beneficial in reducing the risk of either short or long-term mortality and dependency. However, BPR before reperfusion reduces the risk of dependency, while aggressive BPR (target systolic blood pressure (SBP) <120 mmHg) after successful reperfusion increases the risk of dependency. Therefore, we recommend BPR as early as possible for patients undergoing reperfusion therapies but suggest against aggressive BPR in patients who have undergone successful reperfusion.

Vitamin C fortification: need and recent trends in encapsulation technologies.

The multifaceted role of vitamin C in human health intrudes several biochemical functions that are but not limited to antioxidant activity, homoeostasis, amino acid synthesis, collagen synthesis, osteogenesis, neurotransmitter production and several yet to be explored functions. In absence of an innate biosynthetic pathway, humans are obligated to attain vitamin C from dietary sources to maintain its optimal serum level (28 µmol/L). However, a significant amount of naturally occurring vitamin C may deteriorate due to food processing, storage and distribution before reaching to the human gastrointestinal tract, thus limiting or mitigating its disease combating activity. Literature acknowledges the growing prevalence of vitamin C deficiency across the globe irrespective of geographic, economic and population variations. Several tools have been tested to address vitamin C deficiency, which are primarily diet diversification, biofortification, supplementation and food fortification. These strategies inherit their own advantages and limitations. Opportunely, nanotechnology promises an array of delivery systems providing encapsulation, protection and delivery of susceptible compounds against environmental factors. Lack of clear understanding of the suitability of the delivery system for vitamin C encapsulation and fortification; growing prevalence of its deficiency, it is a need of the hour to develop and design vitamin C fortified food ensuring homogeneous distribution, improved stability and enhanced bioavailability. This article is intended to review the importance of vitamin C in human health, its recommended daily allowance, its dietary sources, factors donating to its stability and degradation. The emphasis also given to review the strategies adopted to address vitamin c deficiency, delivery systems adopted for vitamin C encapsulation and fortification.