Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: A Systematic Review and GRADE Compliant Bootstrapped Meta-Analysis of Randomized Clinical Trials.

Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.

Impact of alkaline earth metal doping on the structural, electronic, and optical properties of all inorganic lead-free CsSnX3(X = I, Br) perovskites: a first-principles study.

Recently, researchers have focused on developing more stable, Pb-free perovskites with improved processing efficiency and notable light harvesting ability. In this regard, Sn-based (Sn-b) perovskites have gained considerable interest in developing eco-friendly perovskite solar cells (PSCs). However, the oxidation of Sn2+to Sn4+deteriorates the performance of Sn-b PSCs. Nevertheless, this issue could be mitigated by doping alkaline earth (AE) metal. Herein, we have studied the significance of AE doping on CsSnX3(X = Br, I) perovskites using density functional theory based calculations. The structural, electronic, and optical properties of CsAEySn1-yX3(y= 0, 0.25; AE = Be, Mg, Ca, Sr) compounds were systematically investigated to explore potential candidate materials for photovoltaic applications. Formation energy calculations suggested that the synthesis of other AE-doped compounds is energetically favorable except for the Be-doped compounds. The band gaps of the materials were calculated to be in the range of 0.12-1.02 eV using the generalized gradient approximation. Furthermore, the AE doping considerably lowers the exciton binding energy while remarkably enhancing the optical absorption of CsSnX3, which is beneficial for solar cells. However, in the case of Be and Mg doping, an indirect band gap is predicted. Our theoretical findings demonstrate the potential of executing AE-doped perovskites as absorber material in PSCs, which could deliver better performance than pristine CsSnX3PSCs.

The Spectrum of Pathogenic Yeast Infection in a Tertiary Care Hospital in Assam, India.

CONTEXT: In view of the growing incidence of pathogenic yeast infection all over the world, this study was undertaken to understand its etiology and epidemiology in Assam. AIMS: To characterize and study the antifungal susceptibility pattern of the pathogenic yeasts from the clinical samples. SETTINGS AND DESIGN: The study was a hospital-based cross-sectional study. METHODS AND MATERIAL:  150 patients were enrolled in the study and from which clinical samples were collected. A total of 83 samples showing the growth of yeast in culture were included in the study. The yeasts were identified by conventional and BioMerieux ID 32C and VITEK 2TM. Antifungal susceptibility test was done by disk diffusion method as per Clinical and Laboratory Standards Institute (CLSI), M44-A2. STATISTICAL ANALYSIS USED:  Data was analyzed using statistical software Epi-Info 7.1.2.0 (2013; CDC, Atlanta, USA). For comparison of categorical data, the Chi-square test or Fisher exact test was used. A value of p less than 0.05 was considered statistically significant. RESULTS:  The most affected population was the age group of ≤10 years (32.5%) with male preponderance (67.5%). Yeasts were mostly isolated bloodstream infections (49.3%). The major risk factor was prolonged antibiotic intake. Predominant yeast isolates were Candida albicans (43.4%) followed by Candida tropicalis (19.3%). Emerging yeasts like Kodaemea ohmeri (4.8%), Pichia anomala (2.4%), and Candida auris (1.2%) were also isolated. Amphotericin B was effective against all yeast isolates. All the isolates of Candida krusei were resistant to all the azoles. CONCLUSIONS:  The study reflects that there is a growing incidence of emerging yeast infections and efforts are to be made for their identification and antifungal susceptibility testing for the initiation of appropriate therapy.

Efficacy of COVID-19 vaccines: a systematic review and network meta-analysis of phase 3 randomized controlled trials.

Several vaccines have been approved for the prevention of COVID-19. However, no head-to-head trials comparing their clinical efficacy have been performed. This network meta-analysis aims to identify those, among the competing existing vaccines, conferring the maximum protection against COVID-19. A literature search was done in Medline (via PubMed), Embase and Cochrane Library databases for phase 3 randomized controlled trials evaluating the efficacy of different COVID-19 vaccines. Search results were screened and eligible studies were included to perform a network meta-analysis in software 'R' version 4.1.2 using a random effect model. Cochrane's 'Risk of Bias tool (RoB2)' was used for quality assessment. Raw data from the included studies was used for network meta-analysis. Assessment of inconsistency was not possible as no study compared two or more vaccines directly. A forest plot for indirect comparison of various COVID-19 vaccines was obtained. Rankogram and 'P' scores were obtained to rank the vaccines based on the indirect evidence of their comparative efficacy. A total of 17 randomized controlled trials evaluating the efficacy of 16 COVID-19 vaccines, were included in the network meta-analysis. A total of 361,386 participants was included in this network meta-analysis. Overall risk of bias among included studies was of 'some concern'. All the COVID-19 vaccines had a statistically significant reduction of risk for contracting symptomatic SARS-CoV-2 in comparison to the placebo, however, the maximum protection (RR 0.05) was with BNT126b2. The indirect comparison also revealed BNT126b2 vaccine confers the highest protection against symptomatic SARS-CoV-2 infection in comparison to all others included, with a 'P' score of 0.9771 followed by mRNA-1273, rAD26 & rAD5 and NVX-CoV2373. The evidence generated from this network meta-analysis indicates the good efficacy of all the included vaccines in preventing symptomatic COVID-19 as compared to placebo. The BNT126b2 vaccine was found to provide the highest protection against symptomatic SARS-CoV-2 among all included followed by mRNA-1273, rAD26 & rAD5, NVX-CoV2373 and others.

A Systematic Review and Meta-analysis of Efficacy and Safety of Dexmedetomidine Combined With Intrathecal Bupivacaine Compared to Placebo.

BACKGROUND:  Dexmedetomidine has been approved as a sedative agent in critical patients. It is also frequently used as an adjuvant with local anesthetic in spinal anesthesia. However, its use as an adjuvant has not been approved due to the paucity of data. The present systematic review and meta-analysis were undertaken to synthesize evidence for efficacy and safety when dexmedetomidine is combined with bupivacaine in spinal anesthesia. METHODS: A literature search was done using PubMed, Google Scholar, Embase, and Cochrane Library. Search results were screened and eligible studies were included to perform a systematic review and meta-analysis using the software 'Review Manager (RevMan) version 5.4.1' using a random effect model. Cochrane's' Risk of Bias tool (RoB2)' was used for quality assessment. Mean and standard deviation was used to calculate the standardized mean difference and its forest plot for efficacy measures. For the adverse event, a number of events were used to determine the risk ratio and its forest plot using RevMan software. Publication bias is visualized using a funnel plot. RESULTS:  A total of 21 randomized control trials evaluating the efficacy and safety of intrathecal dexmedetomidine were included in the meta-analysis. A total of 1382 participants was included in this meta-analysis. The effect estimates for efficacy parameters, i.e. duration of the sensory block having SMD 2.33; CI, 1.83-2.83, motor block with SMD 1.83, CI 1.21, 2.46, and analgesia SMD 2.81; CI, 2.11-3.51. The risk ratio for adverse effects, i.e. nausea/vomiting, bradycardia, hypotension was not significant whereas it was significant for the incidence of shivering with RR 0.38; CI 0.23-0.97. The overall risk of bias among included studies was either of 'some concern' or 'high risk.' CONCLUSIONS:  Intrathecal dexmedetomidine when combined with bupivacaine was found to significantly increase the three efficacy parameters, i.e. duration of sensory block, motor block, and analgesia. It also appears to be safe with no increased risk of bradycardia or hypotension. It is also associated with decreased postoperative shivering.

A Narrative Review of Antiviral Drugs Used for COVID-19 Pharmacotherapy.

PURPOSE: A number of research articles has been published evaluating safety and efficacy of drugs against COVID-19. This study was undertaken to collate and review the information regarding common proposed anti- viral drugs for easy reference. METHODS: The literature was search was done using terms like severe acute respiratory syndrome or SARS-CoV-2 or 2019-nCoV or SARS-CoV or COVID-19 in combination with drugs or treatment or pharmaco-therapy using PubMed and google scholar to identify relevant articles. RESULTS: Despite showing good early results, hydroxychloroquine and lopinavir-ritonavir has not shown clinical benefit in randomized controlled trials. However lopinavir in combination with other drugs specially interferon is being investigated. Remdesivir has shown positive effect in terms of clinical improvement and continued to being investigated alone or in combination with other drugs. Favipiravir has shown mixed results and more data from adequately powered study is needed to prove its efficacy. CONCLUSIONS: Many drugs which showed positive effect in initial studies could not replicate the same benefit in large randomized controlled trials. There is need to evaluate efficacy and safety of drugs based on high quality evidence before allowing it to be used in general population.

Pharmacokinetics-Based Optimization of Phototherapy in Neonates Undergoing Treatment for Hyperbilirubinemia.

Introduction: Neonatal jaundice results from combined effects of both increased production of bilirubin and decreased hepatic excretory capacity in neonates. Since its discovery, phototherapy is the most widespread treatment used in neonatal jaundice. In this work, we try to search for a relationship between exposure to phototherapy and decrease in serum bilirubin (linearity vs proportionality). Methods:The present research was non-randomized prospective study conducted in the Neonatal Intensive Care Unit (NICU), Department of Paediatrics, AIIMS, New Delhi, and the Department of Pharmacology, AIIMS, New Delhi, India. Subjects were recruited from neonates admitted in NICU AIIMS, which meets our selection criteria. Infants were given a low dose of either phototherapy continuously or phototherapy for the first six hours and a double dose of phototherapy for the next six hours. Samples were collected before the beginning of the study (0 hours) and then at six and 12 hours. Bilirubin concentration was measured using HPLC and (LC-MS/MS). Results and conclusion:The percentage of reduction during the 6-12-hour interval was compared with that during the 0-6-hour interval if all experimental conditions were kept unchanged. A relationship curve between percentage of reduction and irradiance was created based on the percentage of reduction in serum bilirubin during the 0-6-hour and 0-12-hour intervals. The present study suggests that the relationship between efficacy, as measured by percentage of reduction in serum bilirubin, and irradiance is unlikely to be linear. Collected data are insufficient to clearly distinguish between proportionality and saturation point, considering that the results may be possible with both of these hypotheses.

Animal health perceptions and challenges among smallholder farmers around Kaziranga National Park, Assam, India: A study using participatory epidemiological techniques.

Improvements to smallholder farming are essential to improvements in rural prosperity. Small farmers in the Kaziranga region of Assam operate mixed farming enterprises in a resource limited environment, which is subject to seasonal flooding. Participatory techniques, were used to elucidate the animal health challenges experienced in this landscape in order to inform and guide future animal health education and interventions. The flooding is essential for agricultural activities, but is a source of major losses and disruption. Farmers experience significant losses to their crops due to raiding by wild species such as elephants; predation of livestock by wild carnivores is also of concern. Access to veterinary services and medicines is limited by both financial and geographic constraints. Interviewees discussed nutritional and management issues such as poor availability of fodder and grazing land, while meeting attendees preferred to concentrate discussions on animal health issues. Livestock keepers were adept and consistent at describing disease syndromes. The key challenges identified by farmers were: foot-and-mouth disease; Newcastle disease; haemorrhagic septicaemia; chronic fasciolosis; diarrhoea; bloating diseases; goat pox; and sarcoptic mange. Improvements in the efficiency of farming in this region is a prerequisite for the local achievement of United Nations Sustainable development goals. There exist clear opportunities to increase productivity and prosperity among farmers in this region through a combination of vaccination programmes and planned animal management schemes, driven by a programme of participatory farmer education.

Colostrum provision and care of calves among smallholder farmers in the Kaziranga region of Assam, India.

Smallholder cattle farming in Assamese villages is sub-optimal in terms of calf survivability, growth, age at first service, and milk yield. Proper understanding of the local situation is essential to formulate appropriate, locally driven, livestock keeper education to sustainably improve animal health, welfare and productivity. In-depth interviewing and direct observation were used to understand the farming strategies, husbandry practices and challenges to health and productivity in a cluster of typical villages in the Kaziranga region of Assam, India, where resource use is balanced between the needs of humans and livestock, with competition from wild species. Knowledge of the importance of colostrum consumption by calves is poor. Timely consumption of sufficient colostrum (locally called "phehu") by calves was clearly sub-optimal in the majority of households. The reasons behind this are nuanced, but the practice of collecting colostrum from newly calved cows to make confectionery for human consumption is an important contributory factor. Care of the umbilicus of the newborn is not routine practice in the locality. Local women are the key group assisting with young and sick animals, including cases of simple dystocia and retained foetal membranes. Cows are usually milked once daily, to attempt to balance the needs for milk of household with those of the calf, which can result in suboptimal nutrition for calves. There are clear opportunities to improve animal health and productivity through locally provided farmer education, particularly with reference to colostrum provision, and the engagement of women farmers in any such programme is key to success.

Spread and impact of goat pox ("sagolay bohonta") in a village smallholder community around Kaziranga National Park, Assam, India.

During September and October 2017, a highly fatal outbreak of a disease clinically indistinguishable from goat pox occurred in the villages around the Kaziranga National Park, Assam, India. This was investigated through clinical examination of affected animals, individual interviews with goat keepers and participatory village meetings. Laboratory confirmation was impractical due to the isolation and poverty of the affected community and unnecessary due to the specific nature of the clinical signs. Respondents reported not having encountered the disease previously, and it would appear that a naïve local population developed within an endemically affected region because of a trend to avoid purchasing animals from outside the village. Local grazing practices appear to have had a role in both the spread and control of the outbreak. Goats are an important form of savings and cash income to people in the locality, and the outbreak may result in considerable financial hardship for affected goat keepers. We provide a detailed description of the clinical disease and the spread of the outbreak in the locality. Awareness of the disease with reference to farming practices will provide opportunities for future disease control to enhance animal welfare and rural prosperity.

Efficacy, Safety and Treatment Satisfaction of Glimepiride vs Sitagliptin in Combination with Metformin in Type 2 Diabetes Mellitus.

INTRODUCTION: Metformin is a preferred drug for starting treatment in type 2 diabetes mellitus. But, eventually most of the patients need additional drug to control blood sugar level. The choice of drug depends upon several factors including patient specific criteria, economical factors and treatment satisfaction. AIM: The aim of the present study is to investigate the effects of adding sitagliptin or glimepiride on efficacy, safety and treatment satisfaction in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: It was a retrospective observational study on 50 patients each in sitagliptin and glimepiride group, who are receiving treatment for at least 12 weeks and are stable on respective treatment regimen. Glycated haemoglobin (HBA1c) was the primary measure of efficacy. Safety was assessed by checking weight gain/loss, hypoglycaemia episodes and other laboratory investigations. Patient satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire. RESULTS: The HbA1c level after 12-24 weeks of treatment was not found to be significant compared to each other or from baseline. Compared to baseline fasting plasma glucose & postprandial plasma glucose were lower in glimepiride group. Sitagliptin was associated with less episodes of hypoglycaemia. Weight gain was associated with glimepiride but it was non-significant (p=0.08). Overall treatment satisfaction score were better for sitagliptin but were not statistically significant. CONCLUSION: The efficacy of sitagliptin was comparable. Sitagliptin had superior adverse effect profile with less chances of hypoglycaemia and weight gain. Questionnaire scores were higher for sitagliptin indicating better treatment satisfaction compared to glimepiride.