Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration

A phenytoin prodrug, 3-phosphoryloxymethyl phenytoin (ACC-9653; 1), has been developed with more favorable physicochemical properties than phenytoin for parenteral administration. The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy. Each patient (9 males, 1 female) received a single iv dose of undiluted 1 equivalent to their twice daily phenytoin dose (100-200 mg). An equivalent dose of im 1 was administered in the gluteus maximus muscle one week later. Serial blood samples were obtained after each dose. Phenytoin and 1 concentrations were measured using HPLC. Compartmental analysis using weighted nonlinear least squares, and noncompartmental pharmacokinetic analysis were performed on each patient's concentration-time data. Data following iv 1 in eight of ten patients were best described using a two-compartment model. Mean pharmacokinetic parameter estimates for iv 1 in these patients were central volume of distribution (Vdc) of 0.040 +/- 0.0084 L/kg and plasma disappearance half-life (t1/2 alpha) of 8.0 +/- 2.9 min ("conversion" t1/2). Overall mean clearance (CL) was 0.24 +/- 0.080 L/kg/h in the 10 patients. Mean pharmacokinetic parameter estimates for im 1 were a rate constant (ka) of 2.47 +/- 1.41 h-1 and an absolute bioavailability (F) of 100.5 +/- 20.3%. Mean observed tmax values for phenytoin were 0.57 +/- 0.26 and 1.46 +/- 0.76 h following iv and im 1, respectively. Model-independent estimates of clearance agreed well with the compartmental analyses. Steady-state predose phenytoin concentrations did not significantly vary from the comparable concentrations following iv 1 administration (p = 0.22).(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors Influencing the Sex Ratio at Birth in India: A New Analysis based on Births Occurring between 2005 and 2016

Previous research on sex ratio at birth (SRB) in India has largely relied on macro‐analysis of census data that do not contain the breadth of factors needed to explain patterns in SRB. Additionally, no previous research has examined the differentiation of factors associated with SRB across birth orders, a key determinant in societies affected by son preference. This study aims to fill these gaps using micro‐data related to 553,461 births occurring between 2005 and 2016 collected as part of the 2015–2016 National Family Health Survey. Analyses used multivariable logistic regressions stratified by birth order to examine associations with SRB at the national level. The SRB at birth order 1 was outside the biological normal limit, and generally increased with birth order. First births in households with wealth in the middle and richest quintiles, with mothers who desired a higher ideal number of sons than daughters, and in lower fertility communities had a higher probability of being male. Most SRB correlates were visible at birth orders 3 or higher. Programs and policies designed to address India's male‐skewed SRB must consider the diverse factors that influence SRB, particularly for higher order births.     

Menstrual hygiene management and its determinants among adolescent girls in low-income urban areas of Delhi,India: a community-based study

ObjectivesMenstrual hygiene management (MHM) in developing countries is linked to human rights, social justice, and the education and empowerment of young girls. The objective of this study was to assess menstrual hygiene practices and their determinants among adolescent girls, including school dropouts, and the effects of pad distribution programs in urban resettlement areas of Delhi, India.Methods A cross-sectional study was conducted from March 2019 to February 2020 in urban resettlement colonies and 2 villages of Delhi among 1,130 adolescent girls aged 10 to 19 years, who were interviewed face to face.Results In total, 954 participants (84.4%) used only disposable sanitary pads, 150 (13.3%) used both sanitary pads and cloths, and 26 (2.3%) used only cloths (n=1,130). Most school-going girls utilized the scheme for pad distribution, but only two-thirds of the girls who were out of school utilized the scheme. In the adjusted analysis, girls with lower educational status, those who had dropped out of school, and those from the Muslim religious community were more likely to use cloths for MHM.Conclusion More than 4 out of 5 adolescent girls in Delhi in low-income neighborhoods preferred sanitary pads for MHM. The government free pad scheme reached near-universal utilization among school-going girls (97%), but the subsidized pad scheme for girls who did not attend school was insufficiently utilized (75%).     

Nanomagnet-facilitated pharmaco-compatibility for cancer diagnostics: Underlying risks and the emergence of ultrasmall nanomagnets

Cancer therapy is a fast-emerging biomedical paradigm that elevates the diagnostic and therapeutic potential of a nanovector for identification, monitoring, targeting, and post-treatment response analysis. Nanovectors of superparamagnetic iron oxide nanoparticles (SPION) are of tremendous significance in cancer therapy because of their inherited high surface area, high reactivity, biocompatibility, superior contrast, and magnetic and photo-inducibility properties. In addition to a brief introduction, we summarize various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches. Post-synthesis particulate and surface alterations in terms of pharmaco-affinity, liquid accessibility, and biocompatibility to facilitate cancer therapy are highlighted. SPION parameters including particle contrast, core-fusions, surface area, reactivity, photosensitivity, photodynamics, and photothermal properties, which facilitate diverse cancer diagnostics, are discussed. We also elaborate on the concept of magnetism to selectively focus chemotherapeutics on tumors, cell sorting, purification of bioentities, and elimination of toxins. Finally, while addressing the toxicity of nanomaterials, the advent of ultrasmall nanomagnets as a healthier alternative with superior properties and compatible cellular interactions is reviewed. In summary, these discussions spotlight the versatility and integration of multi-tasking nanomagnets and ultrasmall nanomagnets for diverse cancer theragnostics.     

Reasons for delay in cataract surgery in patients with advanced cataracts during the COVID-19 pandemic

Purpose:To analyze the reasons for delay in cataract surgery in patients with advanced cataracts during the COVID-19 pandemic.Methods:This was a prospective, cross-sectional, multicenter questionnaire study which included patients with mature cataract, nuclear sclerotic cataract grade IV, and cataracts with best corrected visual acuity (BCVA) <5/60, during the COVID-19 pandemic from December 2020 to April 2021. Reasons for delay in presentation to the hospital were analyzed.Results:One thousand four hundred seventy two patients were recruited with advanced cataracts. Absence of ophthalmic care nearby (44.2%), lack of awareness regarding elective surgeries (42.6%), lack of public transportation (37%), fear of contracting COVID-19 (23.4%), and waiting for outreach camps (20.4%) were found to be the reasons behind the delay in cataract surgery. 53.7% of the patients had worsening of defective vision and 55.3% of them had difficulty in carrying out activities of family living. 30.8% of the patients faced difficulty in commuting and 8.4% of the patients suffered a fall during this pandemic due to worsening of the visual acuity.Conclusion:The lockdown imposed during the pandemic has created a significant backlog of patients who are progressing to advanced cataracts due to lack of ophthalmic care nearby, lack of awareness regarding elective surgeries, lack of public transportation, and no outreach camps. Proactive measures to deal with this backlog are of utmost need to prevent blindness due to cataract.     

Fragmented ECG as a Risk Marker in Cardiovascular Diseases

Various noninvasive tests for risk stratification of sudden cardiac death (SCD) were studied, mostly in the context of structural heart disease such as coronary artery disease (CAD), cardiomyopathy and heart failure but have low positive predictive value for SCD. Fragmented QRS complexes (fQRS) on a 12-lead ECG is a marker of depolarization abnormality. fQRS include presence of various morphologies of the QRS wave with or without a Q wave and includes the presence of an additional R wave (R’) or notching in the nadir of the R’ (fragmentation) in two contiguous leads, corresponding to a major coronary artery territory. fQRS represents conduction delay from inhomogeneous activation of the ventricles due to myocardial scar. It has a high predictive value for myocardial scar and mortality in patients CAD. fQRS also predicts arrhythmic events and mortality in patients with implantable cardioverter defibrillator. It also signifies poor prognosis in patients with nonischemic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. However, fQRS is a nonspecific finding and its diagnostic prognostic should only be interpreted in the presence of pertinent clinical evidence and type of myocardial involvement (structural vs. structurally normal heart).     

Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA

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