Delayed Manifestation of Transurethral Syndrome as a Complication of Transurethral Prostatic Resection

Metabolic encephalopathy as a part of ‘transurethral syndrome’ is an immediate complication following transurethral resection of prostate. It occurs during or few hours after the surgery. However, delayed manifestation of this complication is rare. It is also possible that pretreatment with diuretics can exaggerate this problem by predisposing the patient to electrolyte abnormalities. Here we present a report of such a patient who manifested with neurological complications six days after the prostate surger

Determination of salmeterol xinafoate and its degradation products according to ICH guidelines with use of UPLC technique

The objective of reducing analysis time and maintaining good efficiency, there has been substantial focus on high-speed chromatographic separations. Recently, commercially available ultra performance liquid chromatography (UPLC) has proven to be one of the most promising developments in the area of fast chromatographic separations. In this work, a new isocratic reverse phase chromatographic stability indicating assay method was developed using UPLC for salmeterol xinafoate bulk drug. A novel stability-indicating UPLC assay method was developed and validated for salmeterol xinafoate and its degradation products. An isocratic UPLC method was developed to separate the drug from the degradation products, using an Acquity UPLC BEH C18 (50 mm x 2.1 mm column). Mixture of methanol: 0.06 % and pH 3.4 ammonium acetate (65:35) was used as mobile phase. The flow rate was kept 0.6 mL/min and the detection was carried out at 228 nm. The linearity of the proposed method was investigated in the range of 10-50 μg/mL (r2 = 0.999) for salmeterol xinafoate. The method detection limit was 0.5 μg/mL and the method quantification limit was 1 μg/mL. The percentage recovery of salmeterol xinafoate was ranged from 97.2 to 99.5 %. The %RSD values for intra-day precision study were <1.0 % and for inter-day study were < 2.0 %, confirming that the method was sufficiently precise. The validation studies were carried out fulfilling International Conference on Harmonisation (ICH) requirements. The procedure was found to be specific, linear, precise (including intra and inter day precision), accurate and robust.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Economic implications of ddPCR and NGS-based noninvasive prenatal testing for fetal aneuploidy screening

Noninvasive prenatal testing (NIPT) heralds a transformative era in prenatal care, revolutionizing fetal health assessment. The recent adoption of aneuploidy screening signifies a significant advancement in prenatal genetic care in India. The current study aimed to assess the cost-effectiveness of ddPCR-based NIPT for detecting chromosome aneuploidies, comparing it with the next-generation sequencing (NGS) platform. This study adopts a laboratory-based observational approach to investigate the cost implications of NIPT for trisomies 13, 18, and 21 using ddPCR and NGS technologies. A meticulously designed cost analysis methodology was employed, adhering to established standards. The yearly capital and operational costs of NIPT were calculated with precision, focusing on the specific methods associated with ddPCR and NGS. The calculated annual capital and operating costs for NIPT using the ddPCR were $16,411 and$246,540 while those using the NGS platform were $91,440 and$250,560, respectively. The total cost of NIPT using ddPCR for 2,400 tests was $262,951, with an estimated cost per test of$110. In contrast, the total cost of NIPT using the NGS platform for 600 tests was $342,000, resulting in an estimated cost per test of$570. The ddPCR is five times more cost-effective. Moreover, it exhibits a fourfold reduction in time expenditure, attributable to streamlined procedures and does not require a complex bioinformatics analysis compared to the NGS. Moreover, this preliminary outcome on cost analysis for NIPT using ddPCR, as opposed to the NGS platform, can be extended to the health technology assessment (HTA) perspective for prenatal screening programs

Increasing the accessibility, acceptability and use of the IUD in Gujarat, India

The USAID-funded FRONTIERS Program of the Population Council, in collaboration with the Department of Health & Family Welfare, Government of Gujarat, and the Center for Operations Research and Training, Vadodara, conducted an operations research study in India to test the hypothesis that by improving the demand for the IUD and simultaneously strengthening the technical competencies and counseling skills of the providers, use of the IUD use would increase. The findings show that demand-generation activities and provision of good-quality IUD services, together with a supportive programmatic environment, when carried out simultaneously showed increased acceptance of the IUD. The intervention could be easily integrated into the existing system. A sustained and coherent IEC campaign is required to remove myths; the IEC and counseling aids developed for the study have been well accepted by healthcare providers, clients, and national and state government officials

Determination of salmeterol xinafoate and its degradation products according to ICH guidelines with use of UPLC technique

The objective of reducing analysis time and maintaining good efficiency, there has been substantial focus on high-speed chromatographic separations. Recently, commercially available ultra performance liquid chromatography (UPLC) has proven to be one of the most promising developments in the area of fast chromatographic separations. In this work, a new isocratic reverse phase chromatographic stability indicating assay method was developed using UPLC for salmeterol xinafoate bulk drug. A novel stability-indicating UPLC assay method was developed and validated for salmeterol xinafoate and its degradation products. An isocratic UPLC method was developed to separate the drug from the degradation products, using an Acquity UPLC BEH C18 (50 mm x 2.1 mm column). Mixture of methanol: 0.06 % and pH 3.4 ammonium acetate (65:35) was used as mobile phase. The flow rate was kept 0.6 mL/min and the detection was carried out at 228 nm. The linearity of the proposed method was investigated in the range of 10-50 μg/mL (r2 = 0.999) for salmeterol xinafoate. The method detection limit was 0.5 μg/mL and the method quantification limit was 1 μg/mL. The percentage recovery of salmeterol xinafoate was ranged from 97.2 to 99.5 %. The %RSD values for intra-day precision study were <1.0 % and for inter-day study were < 2.0 %, confirming that the method was sufficiently precise. The validation studies were carried out fulfilling International Conference on Harmonisation (ICH) requirements. The procedure was found to be specific, linear, precise (including intra and inter day precision), accurate and robust.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Study of forced degradation behaviour of eprosartan mesylate and development of validated stability indicating assay method by UPLC

The present research work describes comprehensive stress testing of eprosartan mesylate (EM) according to ICH guideline Q1A (R2), and development of a stability-indicating reversed phase ultra performance liquid chromatographic (UPLC) assay. The drug was subjected to acid (0.5N HCl), neutral and alkaline (0.5 N NaOH) hydrolytic conditions at 80 °C, and to oxidative decomposition at room temperature. Photolysis was carried out by exposing the drug during the day time to sunlight (60,000-70,000 lux) for two days and oxidative study was performed with 0.5 mg/ml in 30 % hydrogen peroxide (H2O2 ) at room temperature for 25 hr. The solid drug was also subjected to 50 °C for 30 days in a hot air oven. Degradation of the drug was found to occur under alkaline, acidic and neutral hydrolytic conditions. Separation of the drug and the degradation products was successfully achieved on a BEH (bridged ethylene hybrid) C18 column (1.7 µm, 2.1 mm × 150 mm) with gradient elution of water-acetonitrile as mobile phase. The flow rate and detection wavelength were 0.1 ml/min and 232 nm, respectively. The method was validated and the response was found to be linear in the drug concentration range 5-25 µg/ml (r2 = 0.999). The %RSD in intra-day and inter-day precision studies was < 0.8 %. Recovery of the drug from a mixture of degradation products was between 98.3 and 99.8 %. The LOD and LOQ of developed method were obtained at 0.15 µg/ml and 0.45 µg/ml respectively. The method was specific to the drug, selective to degradation products, and robust. PDA purity test also confirmed the specificity of the method.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Systematic screening to integrate reproductive health services in India

This study, conducted in large public clinics and small health posts in the city of Vadodara, India, tested the effectiveness of a systematic screening technique in integrating reproductive health services at the provider level. The objective was to determine if women screened during clinic visits received more services, appointments, and referrals per visit than women who were not screened. Results show that in experimental group clinics the number of services per visit increased while control clinics experienced a slight decrease; the effect of systematic screening was smaller in health posts than in clinics. In experimental posts, services per visit increased by nine percent compared to a decrease of 16 percent among controls. The municipality of Vadodara will begin systematic screening in all clinics. Gujarat state, where Vadodara is located, also plans to adopt the intervention

A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crstallographic Fragment Screening of the Catalytic Core Domain

HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials. ALLINIs exhibit a multimodal mechanism of action by inducing aberrant IN multimerization during virion morphogenesis and by competing with IN for binding to its cognate cellular cofactor LEDGF/p75 during early steps of HIV-1 infection. However, quinoline-based ALLINIs impose a low genetic barrier for the evolution of resistant phenotypes, which highlights a need for discovery of second-generation inhibitors. Using crystallographic screening of a library of 971 fragments against the HIV-1 IN catalytic core domain (CCD) followed by a fragment expansion approach, we have identified thiophenecarboxylic acid derivatives that bind at the CCD-CCD dimer interface at the principal lens epithelium-derived growth factor (LEDGF)/p75 binding pocket. The most active derivative (5) inhibited LEDGF/p75-dependent HIV-1 IN activity in vitro with an IC50 of 72 μm and impaired HIV-1 infection of T cells at an EC50 of 36 μm. The identified lead compound, with a relatively small molecular weight (221 Da), provides an optimal building block for developing a new class of inhibitors. Furthermore, although structurally distinct thiophenecarboxylic acid derivatives target a similar pocket at the IN dimer interface as the quinoline-based ALLINIs, the lead compound, 5, inhibited IN mutants that confer resistance to quinoline-based compounds. Collectively, our findings provide a plausible path for structure-based development of second-generation ALLINIs

Consanguinity and reproductive health among Arabs

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic