Outcomes of orbital decompression for thyroid eye disease over a 10-year period at a tertiary eye care referral center

Background: Orbital decompression is frequently indicated to treat exophthalmos and compressive optic neuropathy, among other indications for thyroid eye disease (TED). This study aimed to evaluate the outcomes of orbital decompression and compare the results by urgency and type of surgery in patients with TED. Methods: In this cross-sectional study, we recruited patients with TED who had undergone emergency or elective orbital decompression surgery at a tertiary eye care referral center in Tehran, Iran, between 2010 and 2020. Ophthalmic examination findings, demographic and clinical profiles, and types and outcomes of surgical interventions were reviewed and analyzed. Results: Fifty-one orbits of 35 patients with a mean (standard deviation [SD]) age of 36.2 (12.0) years and male-to-female ratio of 23 (66%)/12 (34%) were included. The mean (SD) duration from the diagnosis to the surgery was 41.0 (39.0) months. The surgical method was fat decompression in 1 (2%) orbit; fat and inferior wall decompressions in 2 (4%) orbits; fat, inferior, and medial wall (two-wall) decompressions in 43 (84%) orbits; and fat, inferior, medial, and lateral wall (three-wall) decompressions in five (10%) orbits. Three-wall decompression surgery resulted in significantly lower exophthalmometry readings than those associated with two-wall surgery at all postoperative follow-ups (P < 0.05). Ten (20%) orbits required emergency decompression because of sight-threatening conditions and revealed comparable exophthalmometry readings with electively decompressed orbits at the 1-year visit (P > 0.05). Thirty-seven (73%) orbits required other surgeries within the 1-year follow-up. The mean (SD) exophthalmometry readings before and 1-year after surgery were 26.3 (4.0) and 18.3 (2.7) mm, respectively, with a significant decrease and significant 5.5 (3.3)-mm change from baseline in decompressed orbits (both P < 0.001). Diplopia was reported in 29% (n = 10) of patients less than 2 months postoperatively. Conclusions: Emergency or elective orbital decompression significantly reduced exophthalmos in patients with TED within 1 year postoperatively. Three-wall orbital decompression produced the more immediate impact, while two-wall orbital decompression showed the higher effect at a later timepoint. The most common complication was diplopia, while other serious complications occurred infrequently. Further prospective comparative studies involving more participants and longer postoperative follow-up periods are required to verify these preliminary findings

5-Oxo-hexahydroquinoline derivatives and their tetrahydroquinoline counterparts as multidrug resistance reversal agents

Cancer is a leading cause of death worldwide. Multidrug resistance (MDR) is a main reason of chemotherapy failure in many patients and is often related to overexpression of ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp/ABCB1). Agents that are capable of modulation of the activity of these transporters might be effective in overcoming MDR. In this study, a new set of 1,4,5,6,7,8-hexahydro 5-oxo quinoline-3-carboxamide derivatives bearing 4-methylthiazole moiety and their tetrahydroquinoline counterparts were synthesized. MDR reversal activity of these 16 newly synthesized derivatives was tested in P-gp overexpressing MES-SA-DX5 human uterine sarcoma cells by flow cytometric determination of Rhodamine123 efflux. The effect of the most potent compounds in induction of apoptosis and alterations of cell cycle was examined in these cells by a flow cytometric method. Inherent cytotoxicity of the synthesized compounds was evaluated against MCF-7, A-549 and K562 cancer cell lines, as well as MES-SA-DX5 and their parental non-resistant MES-SA and also HEK-293 non-cancerous cells by MTT assay. Compounds A1 and A2 with 5-oxo-hexahydroquinoline structure bearing 2,4-dichlorophenyl and 4-bromophenyl moieties, respectively, and their tetrahydroquinoline counterparts B1 and B2 significantly blocked P-gp efflux, induced apoptosis and showed the highest cytotoxicities against MES-SA-DX5 cells. However, only A2 and B2 compounds were relatively selective against cancer and MDR cells as compared to non-resistant and non-cancerous cells. These findings demonstrate that 5-oxo-hexahydroquinoline and 5-oxo-tetrahydroquinoline derivatives represent promising agents with therapeutic potential in drug resistant cancers

Health-related quality of life and medication adherence in elderly patients with epilepsy

Objective. Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. Methods. In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. Results. Medication adherence was significantly correlated with both seizure severity (β = –0.33, p < 0.0001) and serum AED level (β = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (β = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = –3.47, p < 0.001) with QoL were supported by the Sobel test. Conclusion. This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL

Worthing Physiological Score vs Revised Trauma Score in Outcome Prediction of Trauma patients; a Comparative Study

Introduction: Awareness about the outcome of trauma patients in the emergency department (ED) has become a topic of interest. Accordingly, the present study aimed to compare the rapid trauma score (RTS) and worthing physiological scoring system (WPSS) in predicting in-hospital mortality and poor outcome of trauma patients.Methods: In this comparative study trauma patients brought to five EDs in different cities of Iran during the year 2016 were included. After data collection, discriminatory power and calibration of the models were assessed and compared using STATA 11.Results: 2148 patients with the mean age of 39.50±17.27 years were included (75.56% males). The AUC of RTS and WPSS models for prediction of mortality were 0.86 (95% CI: 0.82-0.90) and 0.91 (95% CI: 0.87-0.94), respectively (p=0.006). RTS had a sensitivity of 71.54 (95% CI: 62.59-79.13) and a specificity of 97.38 (95% CI: 96.56-98.01) in prediction of mortality. These measures for the WPSS were 87.80 (95% CI: 80.38-92.78) and 83.45 (95% CI: 81.75-85.04), respectively. The AUC of RTS and WPSS in predicting poor outcome were 0.81 (95% CI: 0.77-0.85) and 0.89 (95% CI: 0.85-0.92), respectively (p<0.0001).Conclusion: The findings showed a higher prognostic value for the WPSS model in predicting mortality and severe disabilities in trauma patients compared to the RTS model.  Both models had good overall performance in prediction of mortality and poor outcome

Detection of Nocardia, Streptomyces and Rhodococcus from bronchoalveolar lavage specimens of patients with HIV by Multiplex PCR Assay

Background: Nocardia, Streptomyces and Rhodococcus are life threatening opportunistic pathogens under immunodeficiency conditions, particularly among patients infected with HIV. Rapid and accurate detection of these infections can improve immune health quality, patient management and appropriate treatment. The aim of this study was to design a novel multiplex-PCR assay for rapid diagnosis of these three organisms directly from bronchoalveolar lavage (BAL) specimens of patients infected with HIV.Methods: The genus specific primers were designed for directdetection of Nocardia, Streptomyces and Rhodococcus in a single tube multiplex PCR. This PCR specifically amplified the target genes from pure cultures. It subsequently was applied on BAL specimens of 29 HIV positive patients that had previously been culture negative for actinomycete bacteria, of which Nocardia, Streptomyces and Rhodococcus are members.Results: Of 29 respiratory clinical specimens, there were positive for Nocardia spp. and one was positive for Streptomyces spp using the multiplex PCR assay. The sequencing of the PCR products identified the species as Nocardia cyriacigeorgica (n=2), Nocardia farcinica and Streptomyces albus.Conclusion: This novel multiplex PCR assay yielded reliable results for accurate identification of Nocardia, Streptomyces and Rhodococcus from BAL while the results of bacterial culture were negative.

Time-related survival prediction in molecular subtypes of breast cancer using time-to-event deep-learning-based models

BackgroundBreast cancer (BC) survival prediction can be a helpful tool for identifying important factors selecting the effective treatment reducing mortality rates. This study aims to predict the time-related survival probability of BC patients in different molecular subtypes over 30 years of follow-up.Materials and methodsThis study retrospectively analyzed 3580 patients diagnosed with invasive breast cancer (BC) from 1991 to 2021 in the Cancer Research Center of Shahid Beheshti University of Medical Science. The dataset contained 18 predictor variables and two dependent variables, which referred to the survival status of patients and the time patients survived from diagnosis. Feature importance was performed using the random forest algorithm to identify significant prognostic factors. Time-to-event deep-learning-based models, including Nnet-survival, DeepHit, DeepSurve, NMLTR and Cox-time, were developed using a grid search approach with all variables initially and then with only the most important variables selected from feature importance. The performance metrics used to determine the best-performing model were C-index and IBS. Additionally, the dataset was clustered based on molecular receptor status (i.e., luminal A, luminal B, HER2-enriched, and triple-negative), and the best-performing prediction model was used to estimate survival probability for each molecular subtype.ResultsThe random forest method identified tumor state, age at diagnosis, and lymph node status as the best subset of variables for predicting breast cancer (BC) survival probabilities. All models yielded very close performance, with Nnet-survival (C-index=0.77, IBS=0.13) slightly higher using all 18 variables or the three most important variables. The results showed that the Luminal A had the highest predicted BC survival probabilities, while triple-negative and HER2-enriched had the lowest predicted survival probabilities over time. Additionally, the luminal B subtype followed a similar trend as luminal A for the first five years, after which the predicted survival probability decreased steadily in 10- and 15-year intervals.ConclusionThis study provides valuable insight into the survival probability of patients based on their molecular receptor status, particularly for HER2-positive patients. This information can be used by healthcare providers to make informed decisions regarding the appropriateness of medical interventions for high-risk patients. Future clinical trials should further explore the response of different molecular subtypes to treatment in order to optimize the efficacy of breast cancer treatments

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

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