The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

RELATIVE BIOAVAILABILITY OF OMEPRAZOLE CAPSULES AFTER ORAL DOSING

ABSTRACT Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of stomach. Pharmacokinetics and relative bioavailability of generic products of omeprazole were compared with innovator product, Losec. Twelve healthy adult volunteers participated in the study which was conducted according to a randomized, open-label single dose Latin square cross over design. The preparations were compared using area under the plasma concentration -time curve (AUC), peak plasma concentration (C max ), and time to reach peak plasma concentration (t max ). The two generic capsules proved to be bioequivalent with brand-name omeprazole with regard to the pharmacokinetic parameters C max , AUC 0-t , AUC 0-inf and t max . Moreover the parametric confidence intervals (90%) for the ratio of the C max , AUC 0-8 and AUC 0-∞ values lie between 0.8-1.2. The test formulations were found bioequivalent to the reference formulation by the one-way ANOVA test procedure. On the basis of these results, the 3 formulations were considered to be bioequivalent. Two subjects demonstrated increase in AUCs and high C max after administration of either product which may attribute to the ethnic disposition of omeprazole in these subjects

Formulation development and evaluation of metformin chewing gum with bitter taste masking

Background: Medicated gums are intended to be chewed and act either locally, absorbed via the buccal mucosa or swallowed with saliva. We prepared the metformin gum to overcome its side effects including vomiting, diarrhea, and abdomen discomfort. Furthermore, it could be useful for those who have swallowing problems. Materials and Methods: Metformin hydrochloride (250 mg) with suitable sweeteners was mixed manually for 5 min. This mixture was spray dried, freeze dried, or directly mixed with chewing gum base. Glycerin, xylitol, and menthol were added and the produced paste was kept in the freezer for 2 h to be stable. As the metformin shows bitter taste, we tried to mask this unpleasant taste with using different methods explained. The releasing pattern was evaluated by using a mechanical chewing machine. The best formulation with the optimized releasing pattern, suitable physicochemical properties and pleasant taste were selected. Content uniformity, releasing percent, and other physicochemical properties were identified as well. Taste, flavor, and appearance characteristics were evaluated by using a self-made questionnaire based on the hedonic test method. Results: The chewing gum dosage content was about 86.2%. The release rate of metformin chewing gum was about 70% after 5 min of mastication. Masking the bitter taste of drug was achieved by using acesulfame-isomalt as sweeteners and prepared it by freeze drying equipment. Conclusion: Metfornin chewing gum had suitable appearance and appropriate invitro characteristics that fallow the pharmacopeia suggestions. This chewable gum showed bitterness suppression with a suitable release rate

Emergency Contraception and the Knowledge of Community Pharmacists in Isfahan, Iran

Objectives: Emergency contraception (EC) is a special contraception method that prevents pregnancy after an unsafe sexual contact. Pharmacists, as the most available member of medical team have a unique role in patient education for appropriate use of contraceptive methods. In this study, we assessed the pharmacists′ knowledge about emergency contraception. Methods: A researcher made questionnaire was developed and used according to national guide line and electronic databanks. A group of experts and pharmacists validated the questionnaire. Reliability was measured by Half-Split Test. The questionnaires were filled by pharmacists. Results: Average knowledge score were 8.12 ± 0.28 for women and 7.83 ± 0.31 for men (from a maximum of 15) which showed no significant difference between men and women (P = 0.492). There was no significant difference between pharmacists who had precipitated in continuing education programs and that of those who had not (P = 0.286). Scores of pharmacists who graduated 13 years ago or more did not significantly differ from others (P = 0.287). Conclusions: Because of low scores of pharmacist′s knowledge about EC and the importance of unintended pregnancy prevention, its improvement is an urgent need. Regular and frequent continuing education programs could be one of the recommended interventions

Development and Evaluation of Orally Disintegrating Tablets of Pramipexole Using Full Factorial Design: Orally disintegrating tablets of Pramipexole

Pramipexole is the mostly prescribed drug in patients with Parkinson disease. The incidence of Parkinson disease is related to aging and mostly developed in elderly people with difficulty in swallowing or dysphagia. In the current study we aimed to develop an orally fast disintegrating tablet (ODT) of pramipexole as a preferable alternative in geriatric patients. Hence, the fast disintegration is a critical for ODTs, the effects of four different superdisintegrants including, crospovidone, croscarmellose, sodium starch glycolate, and agar were evaluated on physical characteristics of the tablets. All of the formulations were prepared through direct compression method using aspartame and mannitol as taste masking agents. The flow properties of all of the mixtures were in the acceptable limits. Croscarmellose and Avicel® were chosen as the best superdisintegrants which resulted in the lowest disintegration time and the least friability. In subsequent studies, a 32 full factorial design was adopted to assess the impact of different amounts of croscarmellose and Avicel®. The overall results suggest that the tablet containing 2.5 mg croscarmellose and 70 mg Avicel® as superdisintegrants is the best formulation. Mean hardness, disintegration time, friability, and the drug release percent during 5 min for the optimized formulation were confirmed 42.05 ± 4.6 Kg/cm2, 24.98 ± 6.8 Sec, 0.13 %, and 95.52 ± 2.23% , respectively

Pharmacokinetics of Amoxicillin/Clavulanic Acid Combination after Oral Administration of New Suspension Formulations in Human Volunteers: Pharmacokinetics of coamoxiclave suspension

The pharmacokinetic properties of amoxicillin and clavulanic acid when used alone or in combination may be different and show interaction between these two agents that might decrease the absolute bioavailability of clavulanic acid. In an open, randomized, replicated Latin square under fasting condition, pharmacokinetics of new formulations of amoxicillin/clavulanic acid were compared with a reference formulation after single dose administration in 15 healthy male volunteers. Subjects were given equal molar doses of new suspension formulations of amoxicillin/clavulanic acid (312 mg/5 ml or 156 mg/5 ml) or Augmentin® (312 mg/5 ml) as the reference product. The wash-out period was one week between the administrations of these antibacterial agents. Blood samples were collected exactly before and after drug administration of each of the formulations at different time points up to 6 h. The concentrations of the antibiotics in plasma were measured by validated HPLC methods. Three formulations exhibited a similar mean C max of about 7.5±1.6 mg/l after Tmax of about 75±25 min. for amoxicillin and Cmax of about 2.5±0.6 mg/l after Tmax of about 61±15 min. for clavulanic acid. The AUC0-inf (total area under the curve) for amoxicillin was about 1278±172 g.min/ml and it was about 354±66 g.min/ml for clavulanic acid. There were no significant differences in pharmacokinetic parameters among these formulations. Pharmacokinetic parameters of amoxicillin and clavulanic acid found in this study were similar to previouslypublished data. The two generic formulations investigated in this study proved to be bioequivalent with brand-name Augmentin® with regard to the pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf and Tmax. Moreover, the parametric confidence intervals (90%) for the ratio of the Cmax, Tmax, AUC0-t, and AUC0-Q values lie between 0.8-1.2 based on log transformed values. We may conclude that the two new formulations are bioequivalent with the reference suspension and could be considered equally effective in medicinal practice. Moreover, there were no interaction in pharmacokinetic parameters between amoxicillin and clavulanic acid. No serious adverse event was observed with the studied drugs

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

BackgroundEstimates 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.Methods22 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.FindingsGlobal 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.InterpretationGlobal 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