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Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUC0–48) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC0–48 in a cohort of 30 patients was 14.2 (14) mg·hr/L. The incidence of severe chronic graft-versus-host disease (GVHD) (73% vs. 11%, p = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUC0–48 < 14 mg·hr/L group (54 days vs. 344 days, p = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%, p = 0.12) and overall survival (295 days vs. not reached, p = 0.2). CEPM AUC0–48, is associated with severe chronic GVHD and GRFS post-haplo-HCT in this exploratory study. There is scope for personalizing day + 4 PTCy dose based on day + 3 CEPM AUC0–8. [ABSTRACT FROM AUTHOR]

This paper explains mathematical framework of physical phenomenon happening in nature and social opinion dynamics. It is divided into two parts. The first part deals with design of the trajectory tracking algorithm for multiple mobile robots and in the second part rendezvous algorithm is described. Trajectory tracking algorithm is designed using leader-follower approach in which each follower robot tracks the reference trajectory generated by the leader. Rendezvous algorithm is designed by deriving consensus equation using algebraic graph theory. Condition for achieving rendezvous point is also derived. Simulation shows the effectiveness of proposed algorithm. [ABSTRACT FROM AUTHOR]

In the present study, out of the total 200 MNM participants, WHO and GOI criteria missed the MNM diagnosis in 34 (16.5%) and 33 women respectively. Thus, GOI MNM criteria need to be amended for reconsideration of dialysis during pregnancy as a direct MNM criteria (Squires [21]). The comparison and validation of this newly formulated GOI MNM criteria with the WHO MNM criteria have not yet been evaluated. [Extracted from the article]

Objectives: To ascertain the role of antibiotics in induction and maintenance of remission in ulcerative colitis (UC) Methods: We searched electronic databases for keywords ulcerative colitis or inflammatory bowel disease and antibiotics or antimicrobials. We performed a meta-analysis of randomized trials comparing antibiotics with control/placebo for clinical response, need for second line therapy, colectomy, and adverse effects. Subgroup analysis to clarify the mode of administration, number of antibiotics or the setting of use (acute severe UC or active non–severe UC) were also performed. Results: Thirteen trials with 785 patients were included. The pooled odds ratio of achieving clinical response with antibiotics was 1.74 (95% CI, 1.17-2.58). No differences were noted in relapse rates, need for second line therapy, colectomy or, adverse effects with the use of antibiotics. Subgroup analysis showed no differences with use of single or combination of antibiotics. Analysis of trials only in the setting of acute severe colitis did not demonstrate any benefit. Conclusion: The use of oral antibiotics in the setting of non-severe active UC could have some benefit in clinical response. The use of antibiotics is not of benefit in acute severe colitis, but oral antibiotics need to be evaluated in adult patients. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) was one of the earliest drugs to be recommended for tackling the COVID-19 threat leading to its widespread usage. We provide preliminary findings of the system, established in a tertiary care academic center for the administration of HCQ prophylaxis to healthcare workers (HCW) based on Indian Council of Medical Research (ICMR) advisory.Methods: A dedicated clinical pharmacology and internal medicine team screened for contraindications, administered informed consent, maintained compliance and monitored for adverse events.Results: Among the 194 HCWs screened for ruling out contraindications for prophylaxis, 9 were excluded and 185 were initiated on HCQ. A total of 55 adverse events were seen in 38 (20.5%) HCWs out of which 70.9%, 29.1% were mild and moderate & none were severe. Before the completion of therapy, a total of 23 participants discontinued. Change in QTc interval on day 2 was 5 (IQR: -3.75, 11) ms and the end of week 1 was 15 ms (IQR: 2, 18). Out of the 5 HCW who turned positive for COVID-19, 2 were on HCQ.Conclusion: HCQ prophylaxis was found to be safe and well tolerated in HCW when administered after appropriate screening and with monitoring for adverse events. [ABSTRACT FROM AUTHOR]

Background: Prevalence and impact of thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) minor allele frequencies in South Asian population is unclear. Methods: We searched PubMed and Embase with keywords-TPMT and NUDT15 combined with South Asian countries. We included studies reporting frequency of TPMT and NUDT15 polymorphisms. We estimated the pooled prevalence of TPMT and NUDT15 polymorphisms and their impact on pooled odds ratio of adverse events with thiopurines. Results: We included 26 studies in our analysis. The pooled prevalence of NUDT15 and TPMT polymorphisms was 16.5% (95% CI: 13.09–20.58) and 4.57% (95% CI: 3.66–5.68), respectively. In patients with adverse effects, the pooled prevalence of NUDT15 and TPMT polymorphism was 49.51% (95% C.I. 21.69–77.64) and 9.47% (95% C.I. 5.39–16.11), respectively. The odds ratio (OR) of adverse events with presence of TPMT polymorphisms was 3.65 (95% C.I., 1.43–9.28). The pooled OR for adverse events in presence of NUDT15 polymorphism was 12.63 (95% C.I., 3.68–43.26). Conclusion: NUDT15 were reported more frequently than the TPMT polymorphisms in South Asian population and were more frequently associated with adverse events. These findings may have implications for preemptive testing amongst South Asian population and immigrants prior to starting thiopurines. [ABSTRACT FROM AUTHOR]

There exist limited strategies to address the issue of topical medication without prescription (MWP) use. A survey with pre-coded questionnaires was conducted with 210 patients following up in the dermatology clinic of a tertiary care center. The knowledge and attitude scores were regressed against demographics and exploratory practice questions, and latent class analysis was carried out to check any particular set of characteristics associated with study subpopulations. Forty-seven (22%) participants were found using topical antimicrobial containing MWP. Participants with good knowledge score had 3.41 (95% C.I. = 1.68–7.33), 2.99 (1.37–6.73), and 2.49 (1.26–5.15) times association with opting of distance as the prime reason for availing topical MWP, habit of always reading the accompanying drug leaflet, and understanding that OTC topical medication may change the effect of the already prescribed drugs. Participants with good attitude score showed 2.76 (1.50–5.13) times association with limiting the use of steroid containing topical MWP. Latent class analysis identified one subset of participants having lesser knowledge and attitude scores and quoted financial reasons for the procurement of MWP; however, it was found to have greater income as compared to remaining participants. The strategy to identify the target patient audience so as to deliver patient education intervention programs, regarding safe and effective use of MWP was built. [ABSTRACT FROM AUTHOR]

Role of chemoprophylaxis for prevention of antitubercular therapy-related drug-induced liver injury (ATT-DILI) is uncertain. Electronic databases were searched for randomized trials reporting on chemoprophylaxis agents for prevention of ATT-DILI. We included studies evaluating the role of a drug in comparison to controls/placebo. The primary outcome was the occurrence of ATT-DILI. We performed a Bayesian random-effects network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrI) for those arms where at least two studies were available. Additional comparative studies for these arms were also identified. Fourteen studies were identified and seven included in the meta-analysis. The agents used for prevention of ATT-DILI were silymarin/silibinin (4 trials), N-acetylcysteine (NAC) (3 studies), herbal preparations (5 studies) and one study each for cholecalciferol and carnitine. Compared with controls/placebo, the odds of occurrence of hepatotoxicity with NAC was 7 * 10−17 (95% CrI: 2.8 * 10−53, 0.0053) and Silymarin was 0.68 (95% CrI: 0.084, 4.6). NAC had the highest probability of rank 1 (0.99) which was followed by Silymarin (0.004). N-acetyl cysteine, but not Silymarin/Silibinin, appears to be beneficial in prevention of ATT-DILI. However, the results were limited by the possible risk of bias in included studies, variable definitions of ATT-DILI and limited number and category of patients. [ABSTRACT FROM AUTHOR]

With the goal of improving the affordability of medicines, governments across the globe have instituted various forms of price controls. Since 2013, India has been regulating the prices of drugs included in its national list of essential medicines (NLEM). Here we evaluate the cost variations among available cardiovascular drugs and perform cost-analysis comparing essential and non-essential drugs. Data on listed prices of selected cardiovascular drugs – essential (NLEM) and non-essential (NNLEM) – were sourced from multiple drug information compendia. Price of medications was calculated in cost-per-defined-daily-dose (DDD)-units and NLEM vs. NNLEM drugs were compared. Regression analysis was used to explore the determinants of percentage cost variation (PCV) of drugs. The median-cost/DDD of essential medicines was lower as compared to non-essential ones for all therapeutic drug classes, with greatest difference observed for antianginals and least for heart failure medicines. There were substantial cost variations with values in excess of 1000% for six medicines, all being essential. The regression analysis failed to demonstrate a significant effect of essentiality on PCV (β = 0.19, P = 0.314). Our analyses demonstrate considerable cost variations for some essential cardiovascular medicines. Given the need for prolonged and often, lifelong-treatment, there is significant potential for cost savings based on chosen brand, highlighting the need for patient as well as prescriber education. [ABSTRACT FROM AUTHOR]

1. Terbinafine (TBF), a common antifungal agent, has been associated with rare incidences of hepatotoxicity. It is hypothesized that bioactivation of TBF to reactive intermediates and subsequent binding to critical cellular proteins may contribute to this toxicity. In the present study, we have characterized the bioactivation pathways of TBF extensively in human, mouse, monkey, dog and rat liver microsomes and hepatocytes. 2. A total of twenty glutathione conjugates of TBF were identified in hepatocytes; thirteen of these conjugates were also detected in liver microsomes. To the best of our knowledge, only two of these conjugates have been reported previously. The conjugates were categorized into three groups based on their mechanism of formation: (a) alkene/alkyne oxidation followed by glutathione conjugation, with or without N-demethylation, (b) arene oxidation followed by glutathione conjugation, with or without N-demethylation, and (c) N-dealkylation followed by glutathione conjugation of the allylic aldehyde, alcohol and acid intermediates. 3. Differences were observed across species in the contributions of these pathways toward overall metabolic turnover. We conclude that, in addition to the glutathione conjugates known to form by Michael addition to the allylic aldehyde, there are other pathways involving the formation of arene oxides and alkene/alkyne epoxides that may be relevant to the discussion of TBF-mediated idiosyncratic drug reactions. [ABSTRACT FROM AUTHOR]

Glorisa superba(GS) is a medicinal plant that has been traditionally used in the treatment of joint pain and rheumatoid arthritis (RA). The present study was carried out to investigate the antiarthritic activity ofGlorisa superbahydroalcoholic extract (GSHE) in an adjuvant-induced arthritis (AIA) rat model. Arthritis was induced by sub-plantar administration of complete Freund’s adjuvant (CFA) and GSHE (25, 50, or 100 mg/kg/day) was administered orally for 21 consecutive days. Joint diameter was measured on Days 0, 3, 7, 14, and 21. GSHE dose dependently attenuates the increased joint diameter and serum tumor necrosis factor (TNF)-α level following induction of arthritis by adjuvant. This attenuation was well substantiated with reduced mRNA expression of interleukin (IL)-1β, IL-6, TNF-α, and NF-κB. Additionally, GSHE inhibited phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway as there was decreased protein expression of MAPK (p-p38/p38 and p-ERK/ERK p-JNK/JNK ratio). Moreover, GSHE in a dose-dependent fashion normalized the redox status of ankle joint (GSH, malonaldialdehyde [MDA], and NO levels and superoxide dismutase [SOD] and catalase [CAT] activities) and displayed decreased inflammatory cell infiltration in histopathological findings. Taken together, these findings indicate that GSHE protects against AIA by modulating MAPK. [ABSTRACT FROM PUBLISHER]

A convenient method for the synthesis of thiazoles by treatment of α-bromoketones with thioamides (Hantzsch synthesis) in the absence of catalysts under microwave irradiation has been developed. The products were formed rapidly in excellent yields. An efficiency comparison of time, yield, and effort clearly proved the microwave technique to be superior. The structures of the newly synthesized compounds were characterized by spectroscopic data and elemental analyses. The synthesized compounds were tested for their biological activity. Depending on the substituents, some of the thiazoles exhibit very good antibacterial or antifungal activity. [ABSTRACT FROM AUTHOR]

This paper describes the finding of an experimental study to measure the detector paralysis factor and the use of this parameter in conjunction with detector dead time to better model detector dead-time response. The idealized one-parameter models, the paralyzable and nonparalyzable models, are inadequate to properly model the dead-time response of any real detector system. To address this deficiency, a more realistic two-parameter model is proposed that incorporates the paralysis factor of the detector in addition to the dead time. The revised two-parameter-based model is an extension of Lee and Gardner's two-dead-time model. A simple scheme is proposed to deduce these parameters from the recorded data based on the rise and drop of count rates from a decaying source. Measurements were made using 56Mn and 52V. The data collected in this study show that a high-purity germanium (HPGe) detector has a paralysis factor of ~50 to 77% and a dead time of 6 to 10 µS. Using the data collected by Lee and Gardner, the paralysis factor for a Geiger-Mueller (GM) counter is estimated to be ~5%. These results are consistent with the approximating assumption that GM counters are nonparalyzing and HPGe detectors are paralyzing. [ABSTRACT FROM AUTHOR]

Abstract The present study assessed whether applying enhanced recovery after surgery (ERAS) guidelines for cesarean delivery is feasible in the tertiary care setting with an add-on objective to identify barriers to successful implementation. The cross-sectional study included women undergoing elective CS and willing to participate. The study attempted to understand barriers to ERAS implementation through timely interviewing study participants. Sixty-two patients participated in the study. Antenatal and fetal complications were observed in 39(63%) and 32(51%) participants. The study observed that at least 80% of the proposed components could be applied to 71% of the study population. All 15 components could be applied to 7(11.2%) patients, and at least 50% could be applied to 58(94%) patients. The least applied component was minimizing starvation by taking clear liquids until 2 hrs before surgery in 26(42%) patients due to waiting hours outside the operation-theater (OT). When fitness-for-discharge was assessed against the percent components of ERAS implemented, the area under the curve (AUC) value was 0.75, with a specificity value of 95.65% and a positive predictive value of 94.12%. In the postoperative ERAS bundle, fitness-for-discharge on day-two was statistically associated with early and frequent breastfeeding (p = 0.000) and prevention of intra-op hypotension (p = 0.03). In conclusion, the primary barriers to implementing ERAS were resource limitations in the form of single functional OT and limited doctors. [ABSTRACT FROM AUTHOR]