Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden.

OBJECTIVE: Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum­containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. MATERIALS AND METHODS: A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). LIMITATIONS: Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment's cost effectiveness in different countries. CONCLUSIONS: This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Essential oil and nanocarrier-based formulations approaches for vaginal candidiasis.

An exclusive site for local drug delivery is the vagina, especially for vaginal infections. The fungus Candida albicans causes vaginal infection known as vulvovaginal candidiasis, a highly prevalent and recurrent gynaecological disease among women. Vaginal candidiasis affects over 75% of women at a certain point in their life and has a recurrence rate of 40-50%. Medicinal plants provide some very effective phytoconstituents which when delivered as nanosystems have enhanced therapeutic action and efficacy by alteration in their characteristics. Antifungal drugs are used to treat these conditions, alternative medicine is required for prophylaxis and improved prognosis. The current review focuses on the research carried out on various nanocarrier-based approaches and essential oil-based formulations for vaginal candidiasis.

The vagina is a part of a woman's body that can sometimes get sick from a fungus called Candida albicans. This sickness is called thrush, and it's very common. More than 75% of women will get it at some point, and it might come back again after it's gone. There are medicines that can help, but some plants can also be used to make powerful medicine that can heal the sickness from tiny particles called 'nanosized carriers'. Scientists are studying different ways to give the medicine to the sick area from these plants.

Studies of Phytochemicals, Antioxidant, and Antibacterial Activities of Pinus gerardiana and Pinus roxburghii Seed Extracts.

Pine seeds are considered as nonwood forest products (NWFP) with regularly increasing market's demand. They can be eaten in various ways such as roasted or raw. In addition, they are included in various traditional dishes like in cookies, sauces, candies, cakes, breads, and other bakery items and, moreover, for medicinal purposes. GC-MS study is performed to analyze the phytochemical compounds present in the seed extracts of Pinus roxburghii (Chir) and Pinus gerardiana (Chilgoza). In total, 25 compounds were identified each in Chir and Chilgoza. In Chir seeds, abundantly present compounds were 2,4-di-tert-butylphenol (16.6%), followed by ç-Terpinene (9.9%) and cyclohexanol, 4-ethenyl-4-methyl-3-(1-methylethenyl)-, (1à,3à,4á) (9.8%), whereas in Chilgoza seeds, the maximum amount of compound was 1-hexyl-1-nitrocyclohexane (17.3%), followed by phenol, 2,6-bis(1,1-dimethylethyl) (15.4%), and heptadecane, 2-methyl (8.4%). The total phenolic content of Chir seed sample was 1536 ± 4.35 (mg GAE/100 g), whereas in the Chilgoza seed extract was 642.66 ± 2.08 (mg GAE/100 g). The application of RP-HPLC-DAD system revealed that Chir and Chilgoza seeds have maximum quantity of catechin (15.77 ± 0.16 µg/mg and 17.49 ± 0.32 µg/mg, respectively). Both Chir and Chilgoza seed extracts exhibited significant antioxidant (radical scavenging) potential, through H2O2 (618.94 ± 21.45 µg/mL and 575.16 ± 19.88 µg/mL) and DPPH (552.60 ± 13.03 µg/mL and 429.15 ± 3.80 µg/mL) assays, respectively. Additionally, a well-known antibacterial potential was also found in both plants' dichloromethane extracts, with 64 to 256 µg/mL of minimum inhibitory concentrations. As a whole, result shows the importance of both plants as a naturally occurring phytochemical source with significant antibacterial and antioxidant activity.

Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis.

Background: Overall survival (OS) is the most patient-relevant outcome in oncology; however, in early cancers, large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS between interventions. Use of early time-to-event outcomes as surrogates for OS can help facilitate faster approval of cancer therapies. In locally advanced head and neck squamous cell carcinoma (LA-HNSCC), event-free survival (EFS) was previously evaluated as a surrogate outcome (Michiels 2009) and demonstrated a strong correlation with OS. The current study aimed to further assess the correlation between EFS and OS in LA-HNSCC using an updated systematic literature review (SLR) focusing on patients receiving definitive chemoradiation therapy (CRT). Methods: An SLR was conducted on May 27, 2021 to identify randomized controlled trials assessing radiotherapy alone or CRT in the target population. Studies assessing CRT and reporting hazard ratios (HRs) or Kaplan-Meier data for OS and EFS were eligible for the analysis. CRT included any systemic treatments administered concurrently or sequentially with radiation therapy. Trial-level EFS/OS correlations were assessed using regression models, and the relationship strength was measured with Pearson correlation coefficient (R). Correlations were assessed across all CRT trials and in trial subsets assessing concurrent CRT, sequential CRT, RT+cisplatin, targeted therapies and intensity-modulated RT. Subgroup analysis was conducted among trials with similar EFS definitions (i.e. EFS including disease progression and/or death as events) and longer length of follow-up (i.e.≥ 5 years). Results: The SLR identified 149 trials of which 31 were included in the analysis. A strong correlation between EFS and OS was observed in the overall analysis of all CRT trials (R=0.85, 95% confidence interval: 0.72-0.93). Similar results were obtained in the sensitivity analyses of trials assessing concurrent CRT (R=0.88), sequential CRT (R=0.83), RT+cisplatin (R=0.82), targeted therapies (R=0.83) and intensity-modulated RT (R=0.86), as well as in trials with similar EFS definitions (R=0.87), with longer follow-up (R=0.81). Conclusion: EFS was strongly correlated with OS in this trial-level analysis. Future research using individual patient-level data can further investigate if EFS could be considered a suitable early clinical endpoint for evaluation of CRT regimens in LA-HNSCC patients receiving definitive CRT.

Gastric ulcer healing by chebulinic acid solid dispersion-loaded gastroretentive raft systems: preclinical evidence.

Background: Chebulinic acid (CA), a component in Terminalia chebula, exhibits antiulcer activity, but has poor aqueous solubility. Raft-forming systems incorporating solid dispersions (SDs) of CA, were developed to overcome its poor biopharmaceutical properties and to prolong the gastric residence time for maximum activity. Methods: SDs were formulated by a solvent evaporation method using Eudragit EPO. Raft formulations consisted of sodium alginate as a polymer. Results: Release of CA in the dissolution medium was 40%, whereas SDs showed 95.45% release. The CA raft system (20 mg/kg) showed curative efficacy in an alcohol-induced gastric ulcer model and increased protection when compared with omeprazole (10 mg/kg) and CA suspension (20 mg/kg). Conclusion: These studies demonstrated SD raft systems to be a promising approach for antiulcer therapy by CA.

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index < 0.7), nano-range (~357.4 ± 2% nm), transmittance (> 90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris.

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne.

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management.

Phytochemistry, Pharmacology, and Nutraceutical Profile of Carissa Species: An Updated Review.

Carissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania's subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3ß-hydroxyolean-11-en-28,13ß-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.

Impact of geographic access to primary care providers on pediatric behavioral health screening.

Behavioral Health (BH) screening is critical for early diagnosis and treatment of pediatric mental disorders. The objective of this study was to assess the impact of geographic access to primary care providers (PCP) on pediatric BH screening in children with different race/ethnicity. A retrospective cohort study was conducted using the 2013-2016 administrative claims data from a large pediatric Medicaid Managed Care Plan that have been linked to 2010 US Census data and the 2017 National Provider Identifier (NPI) Registry. Geographic access was defined as the actual travel distance to nearest PCP and the PCP density within 10-mile travel radius from each individual's residence. Stratified multivariate logistic regression was conducted to examine the association between the geographic access to PCP and the likelihood of receiving screening for behavioral disorders within each racial/ethnic group. BH screening rate was 12.6% among 402,655 children and adolescents who met the inclusion criteria. Multivariable analysis stratified by individual race/ethnicity revealed that Hispanic and Black children were more vulnerable to the geographic access barriers than their non-Hispanic White counterparts. The increase in travel distance to the nearest PCP was negatively associated with screening uptake only among Hispanics (10-20 miles vs. 0-10 miles: OR = 0.78, 95% CI [0.71-0.86]; 20-30 miles vs. 0-10 miles: OR = 0.35, 95% CI [0.23-0.54]). In a subgroup that had access to at least one PCP within 10 miles of travel distance, the variation in PCP density had a greater impact on the screening uptake among Hispanics and Blacks than that in non-Hispanic Whites.

Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential.

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers' phytochemicals and illustrates their potential role as drugs.

Association of Primary and Behavioral Health Integrated Care Upon Pediatric Mental Disorder Treatment.

OBJECTIVE: The objective of this study was to examine whether linkage with mental health (MH) treatment differed across 3 different integrated care arrangements (ICAs), following incident attention deficit hyperactive disorder (ADHD) and major depressive disorder (MDD) diagnoses given by primary care providers (PCPs) in the pediatric setting. METHODS: Using claims linking with multiple public data sources, we examined the treatment initiation among children receiving an incident diagnosis of ADHD or MDD from PCPs working in practices with various ICAs. ICAs were categorized as PCP practiced alone (non-co-located), PCP practiced with specialist outside the practice but co-located at the practice site (co-located), and employed specialists who were co-located (co-located and co-affiliated). RESULTS: A total of 4203 incident ADHD and 298 incident MDD cases diagnosed by PCPs were identified, of which 3123 (74%) with ADHD and 200 (67%) with MDD received treatment within 90 days since the diagnosis. Children diagnosed with ADHD by co-located and co-affiliated PCPs were twice as likely to receive treatment as those diagnosed by non-co-located PCPs (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.24-2.78). Of those treated, children diagnosed by co-located and co-affiliated PCPs were 2 times more likely to receive guideline recommended psychotherapy (OR = 2.15; 95% CI, 1.35-3.44). These patients were also more likely to be treated at the diagnosing site versus elsewhere. Similar beneficial effects were not observed in those first diagnosed by co-located but non-affiliated PCPs. CONCLUSIONS: Service co-location between co-affiliated PCPs and MH specialists was associated with significant higher ADHD treatment rate and the receipt of guideline-recommended psychotherapy.

Cost-effectiveness of pembrolizumab compared with chemotherapy in the US for women with previously treated deficient mismatch repair or high microsatellite instability unresectable or metastatic endometrial cancer.

AIMS: There is limited published evidence for the cost-effectiveness of treatments for unresectable or metastatic endometrial cancer (mEC). The objective of this analysis was to assess the cost-effectiveness of pembrolizumab versus chemotherapy for previously treated unresectable or mEC, in women whose tumors have deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). The analysis was carried out from a US healthcare payer perspective. MATERIALS AND METHODS: A lifetime partitioned survival model comprising three health states (progression-free, progressed disease and death) was constructed. Chemotherapy was represented by single-agent paclitaxel or doxorubicin. Overall survival, progression-free survival and time on treatment data for pembrolizumab were obtained from a Phase II clinical study that included women with previously treated dMMR/MSI-H unresectable or mEC (KEYNOTE-158, NCT02628067). Survival data for chemotherapy were obtained from a published Phase III study for previously treated advanced endometrial cancer. Costs included were drug acquisition and administration, health-state, end-of-life, and adverse event management. Costs were presented in 2019 US$. Outcomes were calculated as quality-adjusted life-years (QALYs), using EQ-5D data from KEYNOTE-158. Model results were tested extensively in deterministic and probabilistic sensitivity analyses. RESULTS: Results demonstrated that pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios (ICERs) of $58,165 and $57,668 per QALY gained, respectively. Pembrolizumab was associated with a large QALY and life-year gain per person versus chemotherapy over the model time horizon (deterministic 4.68 life year gain, 3.80 QALYs), with the majority of QALYs accrued in the progression-free health state. LIMITATIONS: The key limitation of the analysis was the lack of comparative effectiveness data for pembrolizumab versus chemotherapy. CONCLUSIONS: Pembrolizumab is a highly cost-effective treatment option when compared with chemotherapy for women with previously treated dMMR/MSI-H unresectable or mEC. Results were robust to the changes in parameters and assumptions explored.

Determination of Colistin B in Chicken Muscle and Egg Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Colistin, an imperative member of the polymyxin group, is a cationic peptide antibiotic. Itis also known as polymyxin E, but this peptide antibiotic has been forbidden for human consumption due to its high toxicity. Regrettably, this antibiotic is utilized as a feed additive and veterinary drug for animals. Due to the toxicity of colistin, the presence of its residue in the animal system represents a threat to human health regarding the consumption of meat, especially chicken. A novel method was proposed for quantifying colistin B in chicken muscles and eggs using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). In this method, extraction of colistin B from samples was achieved by mixing the sample with acidified methanol:water (1/1, v/v), followed by centrifugation and filtration by a membrane filter excluding solid-phase extraction (SPE) clean up, as well as evaporation steps. The analysis was conducted by optimized liquid chromatography-tandem mass spectrometry (LC-MS/MS), and method performance was assessed in terms of the limit of quantitation, specificity, selectivity, precision, linearity and recovery in coherence with the guidelines of SANTE and the Commission Decision 2002/657/EC. The result obtained from the study showed the limit of quantitation (LOQ) as 10 µg Kg-1 for muscles and 5 µg Kg-1 for eggs, with acceptable recoveries along with precision. The linearity was plotted in the range of 5-25 µg L-1 (solvent) for egg and 10-50 µg Kg-1 (matrix-matched) for muscles. The result of average recoveries showed the value of 70-94% (3.3-12% relative standard deviation (RSD)) for chicken muscles and 88-107% (2.5-18.6% RSD) for egg samples, which meets the criteria for acceptability of method according to both SANTE and 2002/657/EC guidelines. This proposed protocol provides a cost-effective solution for food testing labs by reducing the cost of the sample preparation by 60% along with the time required for SPE cleanup. Further, the optimized method was also tested on real samples collected from nearby provinces in Solan city, Himachal Pradesh, India, and three out of 20 muscles were found to have colistin B in the range of 50-560 µg Kg-1.

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment.

AIMS: The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC) of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability. BACKGROUND: QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in bioavailability would result in minimization of side effects. OBJECTIVE: The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential lymphatic uptake. METHODS: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables during optimization by Central Composite Design. RESULTS: The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of - 19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical, smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cycloheximide untreated rats' group of QF-NLC by 2.43 times as compared to cycloheximide treated group, confirmed lymphatic absorption of QF- NLC. CONCLUSION: The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.

Evaluating Time to In-Hospital Venous Thromboembolism in Obese Patients.

BACKGROUND: Currently, no consensus approach exists for optimal venous thromboembolism (VTE) prophylaxis in obese (BMI ≥30 kg/m2) patients. Time to development of in-hospital VTE is not well studied. OBJECTIVE: This study evaluates time to in-hospital VTE in obese patients. METHODS: A single-center, retrospective study evaluated obese patients that developed an in-hospital VTE. Patients were categorized into 3 BMI groups: 30 to 34.9 (group 1), 35 to 39.9 (group 2), and ≥40 (group 3) kg/m2. The primary end point compared time to VTE between the groups. RESULTS: A total of 246 patients were included, and time to VTE was similar between the groups, 8 (group 1) versus 8 (group 2) versus 9 days (group 3); P = .38. Secondary outcomes showed time to VTE was shorter in acute care versus ICU patients (7.5 vs 10 days; P = .01), nonsurgical versus surgical patients (6 vs 9 days; P = .004), and no prophylaxis versus mechanical plus pharmacologic prophylaxis (4.5 vs 9 days; P < .001). CONCLUSIONS: BMI category did not significantly impact time to in-hospital VTE. This study provides insight into the timing of in-hospital VTE in obese patients. The differences in prophylactic strategies highlight the importance of optimized prophylaxis.

Understanding of Colistin Usage in Food Animals and Available Detection Techniques: A Review.

Progress in the medical profession is determined by the achievements and effectiveness of new antibiotics in the treatment of microbial infections. However, the development of multiple-drug resistance in numerous bacteria, especially Gram-negative bacteria, has limited the treatment options. Due to this resistance, the resurgence of cyclic polypeptide drugs like colistin remains the only option. The drug, colistin, is a well-known growth inhibitor of Gram-negative bacteria like Acinetobacter baumanni, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Technological advancements have uncovered the role of the mcr-1(mobilized colistin resistance) gene, which is responsible for the development of resistance in Gram-negative bacteria, which make them distinct from other bacteria without this gene. Additionally, food animals have been determined to be the reservoir for colistin resistance microbes, from which they spread to other hosts. Due to the adverse effects of colistin, many developed countries have prohibited its usage in animal foods, but developing countries are still using colistin in animal food production, thereby imposing a major risk to the public health. Therefore, there is a need for implementation of sustainable measures in livestock farms to prevent microbial infection. This review highlights the negative effects (increased resistance) of colistin consumption and emphasizes the different approaches used for detecting colistin in animal-based foods as well as the challenges associated with its detection.

Bioassay guided fractionation of rhizome extract of Rheum emodi wall as bio-availability enhancer of antibiotics against bacterial and fungal pathogens.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum emodi Wall., is an important medicinal plant extensively used in Ayurvedic and Unani systems of traditional medicine. It is known to possess antioxidant, antibacterial, antifungal, anticancer, wound healing and immune enhancing activities. AIM OF THE STUDY: The aim of the current study was to investigate the antimicrobial activity and synergistic potential of different solvent fractions and phytocompounds of Rheum emodi rhizome against bacterial and fungal pathogens. MATERIAL AND METHODS: The antimicrobial and synergistic potential of the crude methanolic extract, different solvent fractions (n-hexane, chloroform, ethyl acetate, and residual aqueous) and isolated phytocompounds of the rhizome of Rheum emodi were assayed by broth microdilution method. The bioactive phytocompounds were isolated through silica TLC and quantified using HPTLC and HPLC. The bioactive phytocompounds were identified by LC-MS analysis. RESULTS: Phytochemical analysis of the sub-fractions showed that the TPC (417.94 ± 1.2 mg g-1 GAE) and TFC (187.40 ± 0.5 mg g-1 RE) were highest in residual aqueous extracts. The chloroform sub-fraction possessed the highest antimicrobial activity against bacterial (Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae) and fungal strains (Candida albicans MTCC 277 and ATCC 90028). The MIC of chloroform sub-fraction against S. aureus, K. pneumoniae, E. coli, C. albicans was 1.95, 3.91, 15.62 and 62.5 µg ml-1, respectively. TLC and LC-MS analysis of chloroform sub-fraction identified phytocompounds namely emodin D4 (m/z 274.262), rhein13c6 (m/z 290.176), chrysophanol dimethyl ether (m/z 282.291), and resveratrol (m/z 340.456). Quantification of emodin content showed that the chloroform sub-fraction (101.4543 µg mg-1, 194.8037 µg mg-1 measured through HPTLC and HPLC, respectively), and its TLC fraction (II) (75.18 µg mg-1, 232.384 µg mg-1 measured through HPTLC and HPLC, respectively) are rich in emodin. Furthermore, chloroform sub-fraction, its TLC fractions and emodin showed profound synergistic activity in combination with antibacterial and antifungal antibiotics and lowered the dosage of antibiotics by 4-257 folds. CONCLUSIONS: The bioassay guided fractionation of R. emodi rhizome methanolic extract identified phytocompounds (emodin, rhein13c6, chrysophanol dimethyl ether and resveratrol) that act as bioavailability enhancers of antibacterial and antifungal antibiotics, hence revealing their potential in treating multidrug resistance.

Patient-reported outcomes in light of supportive medications in treatment-naïve lung cancer patients.

PURPOSE: The impact of supportive medications on patient-reported outcomes (PROs) has not been systematically evaluated. We describe the supportive medications used by treatment-naïve lung cancer patients and assess their association with PROs from MD Anderson Symptom Inventory (MDASI). METHODS: Treatment-naïve lung cancer patients who completed PROs from MDASI at the initial visit to MD Anderson Cancer Center were included. Medications from the initial visit were abstracted from the electronic medical records system and categorized into therapeutic classes based on U.S. Pharmacopeia v7.0. A chi-square or Mann-Whitney U test was conducted as appropriate. RESULTS: Among 459 patients, ~ 50% took any analgesics and 25% were on opioids. One-third of patients with moderate-severe pain were not on any analgesics. Patients taking opioids had significantly worse median pain scores (6 vs. 0) compared with those not taking any analgesics (p < 0.0001). Higher proportion of patients with moderate-severe pain took opioids compared with those with mild pain (52% vs. 16%, p < 0.0001). Patients on opioids also reported significantly worse scores for five other cancer-specific core symptoms and all six symptoms rating interference with daily life. Only 15% of patients with higher composite score for depression-related symptoms were on antidepressants. However, patients taking antidepressants did not significantly differ in any individual MDASI symptom scores compared with those not on antidepressants (p = 0.4858). CONCLUSIONS: Our results suggest a need for better screening for pain and depression and optimization of pain management in treatment-naïve lung cancer patients since their poor functional status may result in suboptimal cancer therapy.

Reversibility of psychotropic medication induced weight gain among children and adolescents with bipolar disorders.

OBJECTIVE: To assess the reversibility of weight gain associated with psychotropic medications in children. METHODS: A retrospective cohort study was conducted using an ambulatory electronic medical records database. Individuals under 18 years of age were identified if they were initiating a new course of second generation/atypical antipsychotics (SGA) or mood stabilizers (MS) following a bipolar disorder diagnosis and subsequently discontinued treatment within 24 months of treatment initiation. RESULTS: Of the 297 children who had experienced positive BMI percentile increase (mean±SD: 8.71±11.94) during the treatment of SGA and/or MS, treatment discontinuation led to an average of 1.88 (±13.41) unit decrease in BMI percentile during a 12-month period since the treatment discontinuation. Repeated measure mixed model analysis showed that the reduction of BMI percentile after treatment discontinuation was neither associated with the treatment regimens patients previously received, nor associated with time since the treatment discontinuation. The three statistically significant predictors were baseline BMI percentile, BMI percentile gained during the treatment, and comorbid substance abuse disorder. CONCLUSION: Children with bipolar disorder were able to lose a fraction of weight gained during pharmacotherapy after the treatment discontinuation, however, their BMI percentile may not return to the prior treatment level within a year post-medication discontinuation.