Counterfeit drugs in India: significance and impact on pharmacovigilance

Counterfeit drugs have emerged as a major global problem. This issue has been brought to the centre of the Indian media due to the death of 15 women attending a sterilization camp in Chhattisgarh. India’s pharmaceutical industry exports drugs worth 15 billion dollars, which means a high prevalence of counterfeiting in India’s drug industry has global repercussions. However, accurate figures on the extent of counterfeit drugs in India are not available. The scientific literature as well as media reports often quotes figures of 10-35%, though studies done by the Indian Government dispute this. Counterfeit drug numbers have been known to be under represented by Governments due to fear of undermining their economy and health systems. On the other hand, rival companies in other countries may have an incentive to over hype India’s counterfeit problem to dent India’s growing status as the leading global supplier of generic medicines. Lack of clear definitions and differences between laws of countries further complicate reporting. A high prevalence of counterfeit drugs has a large impact on both health and economic indicators. Additionally, counterfeit drugs provide significant challenges to Pharmacovigilance programmes. Hence, here we discuss the significance of use of counterfeit drugs in India and challenges faced by Pharmacovigilance due to the extensive use of counterfeit drugs

Maternal and perinatal outcome in instrumental vaginal deliveries over 5 years: a retrospective study

Background: Due to fear of trauma and less skill, use of instrumental vaginal delivery (IVD) is decreasing every year and incidence of caesarean section is increasing. Caesarean section is a major surgery associated with increased morbidity and mortality. This study evaluates the incidence of instrumental vaginal delivery and associated maternal and perinatal outcome. Methods: This observational retrospective study was carried out in full term antenatal patients in labour with vertex presentation who had undergone operative vaginal deliveries during the study period from January 2017 to December 2021 at G.C.S. Hospital. Data were obtained from the hospital records and analysed which included the age, parity, incidence, indication, the APGAR scores of the babies and complications in the patient. Results: Incidence of instrumental deliveries was found to be 1.98%. Most common indications for IVD were prolonged second stage of labour followed by foetal distress and post-dated pregnancy. Most common maternal complication was perineal tears and most common perinatal complication was neonatal intensive care unit (NICU) admission. Conclusions: The decision to proceed with an operative vaginal delivery when a spontaneous vaginal delivery is not possible must be based upon maternal and foetal factors. Most common maternal complications were perineal tears, cervical tears, episiotomy extension, vaginal laceration and atonic postpartum hemorrhage (PPH). Most common neonatal complications were NICU admission most commonly for neonatal hyperbilirubinemia.

Priprava i karakterizacija čvrstih disperzija etorikoksiba s polietilenglikolom 4000 i polivinilpirolidonom K30

The objective of the present investigation was to study the influence of polyethylene glycol 4000 (PEG) and polyvinylpyrrolidone K30 (PVP) on in vitro dissolution of etoricoxib from solid dispersions. The preliminary studies were carried out using physical mixture of drug and carriers. The solid dispersions were prepared using the solvent evaporation method. A 32 factorial design was adopted in the solvent evaporation method using the concentration of PEG and PVP as independent variables. Full and reduced models were evolved for dependant variables, such as the percentage of drug release in 10 min (Q10), percentage of drug release in 30 min (Q30), percentage of drug release in 45 min (Q45) and percent dissolution efficiency (DE). The reduced models were validated using two check points. Q10 > 65%, Q30 > 75%, Q45 > 85% and DE > 80% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependant variables. PEG was found to be more effective in increasing the drug dissolution compared to PVP. Wettability study was carried out for pure drug and optimized batch. FT-IR spectroscopy, microscopic study, differential scanning calorimetry and X-ray diffraction study were carried out in order to characterize drug in the solid dispersions. Improved dissolution was attributed to decreased crystallinity of the drug, improved wetting and solubilizing effects of carriers such as PEG and PVP from the solid dispersion of etoricoxib. In conclusion, dissolution of etoricoxib can be modulated using appropriate levels of hydrophilic carriers.U radu je proučavan utjecaj polietilenglikola 4000 (PEG) i polivinilpirolidona K30 (PVP) na in vitro oslobađanje etorikoksiba iz čvrstih disperzija. Preliminarni pokusi provedeni su sa smjesom ljekovite tvari i polimernih nosača. Čvrste disperzije pripravljene su metodom uparavanja otapala. Za ovu metodu razvijen je 32 faktorijalni dizajn koristeći koncentraciju PEG i PVP kao nezavisne varijable. Za zavisne varijable razvijeni su potpuni i reducirani modeli, kao što su postotak oslobođene ljekovite tvari u 10 (Q10), 30 (Q30) ili 45 minuta (Q45) i postotak učinkovitosti oslobađanja (DE). Reducirani modeli su validirani pomoću dviju kontrolnih točaka. Q10 > 65%, Q30 > 80%, Q45 > 85% i DE > 80% su upotrebljeni kao ograničenja za izbor optimirane serije. Prikazane su konturne linije za pojedine zavisne varijable. Oslobađanje lijeka bilo je učinkovitije iz pripravaka s PEG-om. Vlaženje je proučavano za čistu ljekovitu supstanciju i omptimiranu seriju. Za karakterizaciju ljekovite tvari u čvrstim disperzijama korištene su FT-IR spektroskopija, mikroskopske studije, diferencijalna pretražna kalorimetrija i difrakcija rentgenskim zrakama. Povećano oslobađanje posljedica je smanjene kristaliničnosti ljekovite tvari, pojačanog vlaženja i solubilizacijskog učinka polimernih nosača u disperzijama. Može se zaključiti da se oslobađanje etorikoksiba može modulirati promjenom količine hidrofilnih nosača

Priprava kompleksa etorikoksiba s β-ciklodekstrinom metodom gnječenja i njihova karakterizacija

The binary system of etoricoxib with β-cyclodextrin (β-CD) was prepared by the kneading method. Drug-cyclodextrin interactions in solution were investigated by the phase solubility analysis. Differential scanning calorimetry, infrared spectroscopy, powder X-ray diffractometry and microscopic study were used to characterize the solid state of all binary systems, whereas their dissolution properties were evaluated according to the USP XXIII paddle method. The results indicate partial interaction of the drug with β-CD in the physical mixture and complete interaction in the kneaded complex. The dissolution of etoricoxib was notably increased as compared to pure drug as well as its physical mixture. The complex showed more than 75% drug released in 30 min.Metodom gnječenja pripravljen je binarni sustav etorikoksiba s β-ciklodekstrinom (β-CD). Tijekom 30 minuta iz kompleksa se oslobodilo više od 75% ljekovite tvari, što je značajno više u odnosu na fizičku smjesu etorikoksiba i β-CD ili na čistu ljekovitu tvar. Interakcije lijeka i ciklodekstrina u otopini ispitivane su analizom fazne topljivosti. Za karakterizaciju čvrstog stanja svih binarnih sustava korišteni su diferencijalna pretražna kalorimetrija, infracrvena spektroskopija, difrakcija rentgenskih zraka na praškastom uzorku i mikroskopija. Oslobađanje je praćeno metodom lopatice prema USP XXIII. Rezultati ukazuju na djelomičnu interakciju ljekovite tvari s β-CD u fizičkoj smjesi i potpunu interakciju u kompleksu

A study of feto-maternal outcome in case of premature rupture of membrane at a tertiary care center

Background: Premature rupture of membranes is the rupture of the fetal membranes in the absence of uterine contraction or before the onset of labor. When this occurs before 37 weeks of gestation, it is termed as preterm premature rupture of membranes. Management depends upon gestational age and the presence of complicating factors. An accurate assessment of gestational age and knowledge of the maternal, fetal and neonatal risks are essential to appropriate evaluation, counselling, and care of patients with PROM. The purpose of the study is timely diagnosis and appropriate management of the cases of PROM and PPROM to improve maternal and neonatal outcomes. Methods: A Prospective study was performed at the department of obstetrics and gynecology, at a tertiary care center from August 2020 to December 2021. A clinical data sheet was made for recording all information about the pregnant women after taking their consent. And their maternal and neonatal outcomes were recorded. Results: a total of 150 cases of PROM and PPROM were taken during our study out of which 53.33% belong to the younger age group, 43.33% were primi gravida, 66.66% belonged to the lower socioeconomic class, 25.33% had a previous history of abortion followed by dilatation and evacuation, rate of cesarean delivery was 34.66% and rate of NICU admission of neonates was 15.78% and 57.87% babies had low birth weight and rate of stillbirth was 1.97%. whereas 34.66% of cases had various complications related to PROM. Conclusions: Individualized management of PROM cases depending on the gestational age and risk of complications and antibiotic coverage is the best way to achieve a good fetomaternal outcome

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world’s highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%.Peer ReviewedPostprint (published version

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Characterization of Fatty Acids, Polysaccharides, Amino Acids, and Minerals in Marine Macroalga <i>Chaetomorpha crassa</i> and Evaluation of Their Potentials in Skin Cosmetics

Cosmetic industries are highly committed to finding natural sources of functional active constituents preferable to safer materials to meet consumers’ demands. Marine macroalgae have diversified bioactive constituents and possess potential benefits in beauty care products. Hence, the present study was carried out to characterize the biochemical profile of marine macroalga Chaetomorpha crassa by using different techniques for revealing its cosmetic potentials. In results, the FTIR study characterized the presence of different bioactive functional groups that are responsible for many skin-beneficial compounds whereas six and fifteen different important phycocompounds were found in GCMS analysis of ethanolic and methanolic extracts, respectively. In the saccharide profile of C. crassa, a total of eight different carbohydrate derivatives were determined by the HRLCMS Q-TOF technique, which showed wide varieties of cosmetic interest. In ICP AES analysis, Si was found to be highest whereas Cu was found to be lowest among other elements. A total of twenty-one amino acids were measured by the HRLCMS-QTOF technique, which revealed the highest amount of the amino acid, Aspartic acid (1207.45 nmol/mL) and tyrosine (106.77 nmol/mL) was found to be the lowest in amount among other amino acids. Their cosmetic potentials have been studied based on previous research studies. The incorporation of seaweed-based bioactive components in cosmetics has been extensively growing due to its skin health-promoting effects