Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial

IntroductionAzathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves’ disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.MethodsWe conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40–120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.ResultsA total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.ConclusionAZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.Trial registryThe trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180)

Assessing disparities in medical students’ knowledge and attitude about monkeypox: a cross-sectional study of 27 countries across three continents

Background and aimsThe recent monkeypox (Mpox) outbreak confirmed by the World Health Organization (WHO) underscores the importance of evaluating the knowledge and attitude of medical students toward emerging diseases, given their potential roles as healthcare professionals and sources of public information during outbreaks. This study aimed to assess medical students’ knowledge and attitude about Mpox and to identify factors affecting their level of knowledge and attitude in low-income and high-income countries.MethodsA cross-sectional study was conducted on 11,919 medical students from 27 countries. A newly-developed validated questionnaire was used to collect data on knowledge (14 items), attitude (12 items), and baseline criteria. The relationship between a range of factors with knowledge and attitude was studied using univariate and multivariate analyses.Results46% of the study participants were males; 10.7% were in their sixth year; 54.6% knew about smallpox; 84% received the coronavirus disease 2019 (COVID-19) vaccine; and 12.5% had training on Mpox. 55.3% had good knowledge of Mpox and 51.7% had a positive attitude towards it. Medical students in their third, fifth, or sixth year high- income countries who obtained information on Mpox from friends, research articles, social media and scientific websites were positive predictors for good knowledge. Conversely, being male or coming from high-income countries showed a negative relation with good knowledge about Mpox. Additionally, a positive attitude was directly influenced by residing in urban areas, being in the fifth year of medical education, having knowledge about smallpox and a history of receiving the coronavirus disease 2019 (COVID-19) vaccine. Receiving information about Mpox from social media or scientific websites and possessing good knowledge about Mpox were also predictors of a positive attitude. On the other hand, being male, employed, or receiving a training program about Mpox were inversely predicting positive attitude about Mpox.ConclusionThere were differences in knowledge and attitude towards Mpox between medical students in low and high-income countries, emphasizing the need for incorporating epidemiology of re-emerging diseases like Mpox into the medical curriculum to improve disease prevention and control

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

BackgroundDisorders 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.MethodsWe 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.FindingsGlobally, 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.InterpretationAs 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 burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Pediatric Hodgkin's lymphoma presenting with pseudo-achalasia and para-neoplastic neurological syndrome (Guillain-Barre): A case report

Introduction: Pseudo-achalasia (secondary achalasia): is a disorder produced by tumor at or near the gastro-esophageal junction, resulting in manifestation similar to those produced by achalasia. Dysphasia, regurgitation, and weight loss are the main presenting symptoms. Hodgkin's lymphoma is associated with multiple para-neoplastic neurological syndromes, of which demyelinating polyneuropathies are very unusual. Para-neoplastic neuropathies are difficult to diagnose, especially when they are the presenting features. Case presentation: We report a rare case of 11years old child who presented with pseudo-achalasia and Guillain-Barre syndrome, eventually diagnosed as Hodgkin's lymphoma. Conclusion: Hodgkin's lymphoma can present with pseudo-achalasia and may be associated with para-neoplastic neurological syndrome's

Biliary atresia recent insight

Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that exclusively affects newborn infants. The etiology of the disease is not known. BA is considered to be a phenotype resulting from several pathogenic processes leading to obstruction of the biliary tree. It usually presents shortly after birth, characterized by persistent jaundice, hepatosplenomegaly, clay-colored stool, and dark urine. It affects both the extra-hepatic biliary ducts (EHBDs) and the intra-hepatic biliary system (IHBDs), but the former is more severely affected. Diagnosis of BA is a great challenge and must be achieved as early as possible to delay progression to cirrhosis. Laboratory tests reveal direct hyperbilirubinemia and, variable levels of transaminases, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), which overlap significantly with other causes of neonatal cholestasis. The intraoperative cholangiogram is considered the gold standard for the diagnosis of BA and is performed routinely in many institutions. BA can be divided into correctable and non-correctable types; the former accounts for (10–15%) of cases, in which the proximal common hepatic duct is patent, allowing primary anastomosis of the EHBDs to the bowel. All patients are subjected to identical surgical and medical treatments; consisting of Kasai portoenterostomy (KPE), which entails removal of the atretic extra-hepatic tissue and a Roux-en-Y jejunal loop anastomosed to the hepatic hilum. Kasai portoenterstomy is considered a transition to liver transplantation, as the pathology may be still ongoing. BA is the most frequent indication for liver transplantation in infants, which is the only treatment that can definitively arrest the natural disease course. In conclusion: BA is a serious liver disease that needs to be further studied, and awareness of BA should be increased among the public and health care workers to prevent the complications of this disease

Parental intention to vaccinate children against seasonal influenza in the Eastern Mediterranean region: A cross-sectional study using the health belief model

Seasonal influenza vaccine is the most effective strategy for reducing influenza incidence and severity. Parental decision-making regarding childhood vaccination is influenced by one’s vaccine-related beliefs. A cross-sectional study was conducted to determine the role of the Health Belief Model (HBM) in predicting parental intention to vaccinate their children against influenza in the Eastern Mediterranean Region (EMR). An anonymous online survey was distributed to parents of children aged 6 months to 18 years in 14 EMR countries. Out of the 5964 participants, 28.2% intended to vaccinate their children against influenza. Urban residents (OR = 0.55, 95%CI: 0.35–0.85), decision-making regarding child’s health by the father alone (OR = 0.43, 95%CI: 0.34–0.55) or the mother alone (OR = 0.78, 95%CI: 0.65–0.93), having a child with a chronic illness (OR = 0.45, 95%CI: 0.38–0.53), reporting high perceived severity, susceptibility, and benefits (OR = 0.35, 95%CI: 0.30–0.40), and cues to action (OR = 0.45, 95%CI: 0.39–0.51) were inversely associated with parental unwillingness to vaccinate their children against influenza. While parents with a higher number of children in the household (OR = 1.08, 95%CI:1.03–1.12) and higher perceived barriers (OR = 2.92, 95%CI: 2.56–3.34) showed an increased likelihood of unwillingness to vaccinate their children. Interventions targeting parental beliefs and perceptions are necessary to improve influenza vaccination acceptance and coverage among children

Development, Validity, and Reliability of the Perceived Telemedicine Importance, Disadvantages, and Barriers (PTIDB) Questionnaire for Egyptian Healthcare Professionals.

BackgroundThis study aimed to develop and investigate the psychometric properties of the Perceived Telemedicine Importance, Disadvantages, and Barriers (PTIDB) questionnaire for healthcare professionals (HCPs) in Egypt. This study was conducted in three phases: (1) development of the questionnaire, (2) preliminary testing of the questionnaire, and (3) investigation of its validity and reliability using a large survey.MethodsA cross-sectional survey was conducted over two months. A convenience sample of 691 HCPs and clerks from 22 governorates accessed the online survey. The construct validity was assessed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and internal reliability.ResultsThe initial Eigenvalues showed that all 19 items of the questionnaire explained 56.0% of the variance in three factors. For Factor 1 (importance), eight items were loaded on one factor, with factor loading ranging from 0.61 to 0.78. For Factor 2 (disadvantages), seven items were loaded on one factor with factor loading ranging from 0.60 to 0.79. For Factor 3 (barriers), four items were loaded on one factor, with factor loading ranging from 0.60 to 0.86. The CFA showed that All loadings ranged from 0.4 to 1.0, with CFI = 0.93 and RMSEA = 0.061. All the factors had satisfactory reliability; 0.87 for ''Importance'', 0.82 for ''Disadvantages'', and 0.79 for ''Barriers''.ConclusionThe PTIDB questionnaire has an acceptable level of validity and internal consistency, at a readability level of 12th grade. The retest reliability, however, still needs to be tested

The Effect of Combining the COVID-19 Vaccine with the Seasonal Influenza Vaccine on Reducing COVID-19 Vaccine Rejection Among Libyans

Background: Coronavirus disease 2019 (COVID-19) vaccine coverage remains low in Libya compared to other countries in the Eastern Mediterranean Region. This study aimed to evaluate the willingness of the general public in Libya to receive COVID-19 and seasonal influenza vaccines. Additionally, the study aimed to investigate the potential effect of combining the two vaccines to reduce COVID-19 vaccine rejection. Methods: An anonymous nationwide online cross-sectional survey was carried out from 1st September to 16th October 2022. Libyans aged 18 years or older were recruited using convenience and snowball sampling approaches. The participants were surveyed for sociodemographic information, health status, and vaccination attitude towards COVID-19 and seasonal influenza vaccines. Results: A total of 2484 participants formed the final study sample: 68.7% were females, 39.4% were aged 18–25 years, 50.4% were single, 32.5% had previous COVID-19 infection, and 47.2% experienced COVID-19 death among relatives. Three-fourths of the respondents showed COVID-19 vaccine rejection: 57.3% did not receive COVID-19 vaccination, 10.1% would not complete the primary vaccination series, and 7.8% refused booster doses. About 55.0% rejected seasonal influenza vaccination, while 1.9% reported influenza vaccine uptake and 21.2% were willing to get the influenza vaccine for the first time. Additionally, 18.8% had already received influenza vaccination in the last year and intended to get the vaccine this season, while 3.3% were unwilling to get influenza vaccination this year despite receiving it in the last influenza season. Age, sex, and occupation were significantly associated with COVID-19 and influenza vaccine rejection. Rejection of COVID-19 vaccination decreased if its combination with influenza vaccine as a single dose was suggested, with 28.2% of the COVID-19 vaccine rejector group accepting the combined vaccine as it would be safer (50.9%), needing fewer injections (24.0%), would be more effective (19.1%), and would be less expensive (3%). Approximately 73.0% of the COVID-19 vaccine rejector group refused this combination due to fear of side effects (48.7%), absence of published studies on this combination (29.8%), and considering this combination as useless (11.2%). Conclusion: In Libya, the prevalence of COVID-19 vaccine rejection was high, while the rejection of seasonal influenza vaccination was relatively lower. If influenza and COVID-19 vaccines are administered simultaneously as a single injection, this may reduce the rejection of the COVID-19 vaccine due to better-perceived vaccine safety and efficacy besides being more convenient in terms of the number of injections and cost