BACKGROUND: Endotracheal intubation is an integral part of general anesthesia. The hemodynamic stress responses associated with it, though transient, are unpredictable and variable. In comparison with healthy individuals, those with comorbid health issues can have life-threatening complications with this sympathetic response. Hence, in this study, we compared the efficacy of intravenous low doses of dexmedetomidine, fentanyl, and magnesium sulfate (MgSO₄) in reduction of the hemodynamic response to endotracheal intubation. MATERIALS AND METHODS: This prospective randomized study compared three groups of dexmedetomidine (0.6 μg/kg) (Group D), fentanyl (2 μg/kg) (Group F), and MgSO₄ 30 mg/kg (Group M). A total of 105 American Society of Anesthesiologist's 1 and 2 patients were selected with 35 in each group. The hemodynamic variables recorded at baseline, during induction and intubation up to ten minutes were pulse rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure. The assessment of quantitative and qualitative data was done with the one-way ANOVAs, Student's t-test, and Chi-square test. Analysis of variance was done by post hoc tests. RESULTS: There were statistically significant differences that were observed with dexmedetomidine and fentanyl groups in respect to heart rate and blood pressure responses to laryngoscopy and intubation when compared to MgSO₄. A significant attenuation of response from baseline values was also noted with dexmedetomidine and fentanyl groups. CONCLUSION: Efficacy of low doses of both dexmedetomidine and fentanyl was equipotent in attenuating response in comparison with MgSO₄, and we conclude that dexmedetomidine can serve as an alternative to fentanyl.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO). MATERIALS AND METHODS: Seven groups of Sprague–Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment. RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone. CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis.

OBJECTIVES: Isotretinoin (ISO) is a retinoic acid-derived molecule which is very efficient in the treatment of acne vulgaris (AV). Little is known regarding alterating affects of systemic ISO on immune system. SUBJECTS AND METHODS: Thirty-two patients with moderate and severe AV with indications for systemic ISO treatment were recruited. The evaluation of peripheral blood lymphocyte subsets was made on treatment initiation and at the end of the therapy by flow cytometry. RESULTS: CD16/56+ natural killer (NK) cell levels were higher in patients with severe acne compared to moderate acne (P = 0.009). CD45RA+ (naive) cell levels decreased significantly after systemic ISO treatment; the mean percentage was 66.9 ± 6.5 which decreased to 63.9 ± 7.5 after treatment (P = 0.013). CD19+ cell levels were also significantly increased; mean percentage (%) and absolute cell counts were 8.0 ± 3.1 and 161.3 ± 7.36 cells/μl which increased to 10 ± 2.7 and 227.7 ± 108.7 cells/μl, at the end of treatment, respectively (P = 0.007, P = 0.011). CONCLUSIONS: NK cell count may be a parameter related to acne severity. Systemic ISO may have an inhibitory effect on naïve T cells. Finally, systemic ISO seems to stimulate mature B-cell proliferation.

INTRODUCTION: The adverse events of sutures used for the closure of surgical incisions influence clinical outcomes. Literature on the safety profile of the application of unidirectional barbed sutures in oral and maxillofacial surgery is scarce. Hence, focused materiovigilance was done to monitor and compare the adverse events of unidirectional barbed and poliglecaprone 25 nonbarbed sutures for intraoral incision closure. METHODS: In a prospective randomized comparative study, 64 patients requiring intraoral incision closure were randomized to receive either unidirectional barbed or poliglecaprone 25 nonbarbed sutures. Postoperatively, patients were monitored for any adverse events for 15 days. Causality association of adverse events with sutures was done using the European Commission directives on safety reporting of medical devices. RESULTS: Adverse events observed with unidirectional barbed suture were suture extrusion (n = 7; 21.875%) and suture discomfort (n = 3; 9.375%). While subjects who received poliglecaprone 25 suture experienced suture discomfort (n = 6; 18.75%) and knot unraveling (n = 2; 6.25%). The number of adverse events in both groups was statistically comparable (P = 0.78). Causality assessment of adverse events was probable for suture extrusion and discomfort with nonbarbed and barbed sutures, while it was possible for knot unraveling for nonbarbed sutures. CONCLUSION: Both types of study sutures were associated with minor severity adverse events when used for the closure of intraoral surgical incisions. Suture extrusion had a probable causal association with barbed suture. Knot unraveling was possibly associated with the nonbarbed suture. Both types of suture materials were equally safe in oral and maxillofacial intraoral surgical incision closure.

BACKGROUND: Imatinib mesylate is the cornerstone therapy in the management of chronic myeloid leukemia (CML). Monitoring of adverse drug reactions (ADRs) of imatinib in our patients is very important to ensure their safety. Aims and Objectives: The current study aims to monitor ADRs encountered in CML patients in the chronic phase with imatinib (400 mg/day). MATERIALS AND METHODS: This prospective, observational study was conducted from November 2011 to May 2015 on 310 patients presented to the Departments of Clinical Hematology and Pharmacology of SCB MCH, Cuttack, diagnosed with CML at chronic phase. Collected ADRs were entered in the ADR reporting form (PvPI) and were analyzed for causality and severity. RESULTS: Anemia was the most common hematological ADR, whereas hyperpigmentation and nausea were the most common nonhematological ADRs reported. Maximum ADRs were mild to moderate and required no change in the treatment course. CONCLUSION: The study revealed that imatinib mesylate, a well tolerated drug, has very few cases of severe ADRs in Indian patients at the chronic stable phase of CML.

Mycobacterium tuberculosis (MTB) requires a perpetual supply of iron for its sustenance. Iron scarcity and its limited availability in the host environment because of an encounter of various sites during the establishment of infection has led to the evolution of strategies for iron uptake, which includes biosynthesis of iron-chelating molecules called siderophores, Heme uptake pathways, recently discovered host iron transport protein receptors like glyceraldehyde-3-phosphate dehydrogenase and the development of machinery for proper storage of the acquired iron and its regulation. The components of the iron uptake machineries are viable targets in multidrug-resistant tuberculosis, some of which include the MmpL3 heme transfer protein, MbtA enzyme, and the ESX-3 system, while employment of approaches like the synthesis of siderophore drug conjugates, heme analogs, xenosiderophores as drug delivery agents, and the blockade of siderophore recycling are encouraged too. Thus, the mentioned discoveries stand as promising targets against various strains of MTB.

Traditional drug development is a tedious process with involvement of enormous cost and a high attrition rate. Outsourcing drug development services to contract research organizations (CROs) has become an important strategy for cost and risk reduction, capacity building, and data generation. The therapeutic and operational expertise of these CROs has allowed pharmaceutical industry to reduce in-house infrastructure as well as research capacity. Working with specialized CROs has not only increased the rate of success but also the speed of drug discovery process. Small firms with promising molecules but limited resources and large firms interested in diversifying their dimensions are utilizing the services of efficient CROs. Globally, approximately one-third of the drug development processes are now being outsourced and the data generated by the independent third party are well appreciated during regulatory submissions. In this article, we discuss the international and national trends, outsourcing services and models, key considerations while selecting CRO, and benefits and challenges of outsourcing. Further, we discuss how the technical expertise of competent CROs was utilized when traditional ways of conducting clinical trials were disrupted by the COVID-19 pandemic. Taken together, the increasing health-care demands, COVID-19 pandemic or any other such upcoming health crisis, and recent advances in advanced technologies (machine learning and artificial intelligence, etc.) are likely to fuel global CRO market in the coming years.

Belantamab mafodotin (BLMF) is an interesting therapeutic alternative for multiple myeloma (MM) patients pretreated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Scientific evidence on BLMF provides immature data about progression-free survival and overall survival by short follow-up of patients with poor prognoses. Cases with long follow-ups could provide additional information about BLMF. This case reports a patient with MM treated with BLMF who had received nine previous lines of therapy with a follow-up of 11 months. No complete response was obtained. However, no disease progression was observed and the patient was still alive at the end of this work. BLMF showed manageable adverse effects. Our patient presented advanced disease, good functional status at the beginning of BLMF treatment, and elevated levels of lactate dehydrogenase during BLMF therapy. The influence of these last two factors was not evaluated in clinical trials. This relationship should be assessed more deeply in future studies.