Recent developments in SARS-CoV-2 vaccines: A systematic review of the current studies.

Designing and manufacturing efficient vaccines against coronavirus disease 2019 (COVID-19) is a major objective. In this systematic review, we aimed to evaluate the most important vaccines under construction worldwide, their efficiencies and clinical results in healthy individuals and in those with specific underlying diseases. We conducted a comprehensive search in PubMed, Scopus, EMBASE, and Web of Sciences by 1 December 2021 to identify published research studies. The inclusion criteria were publications that evaluated the immune responses and safety of COVID-19 vaccines in healthy individuals and in those with pre-existing diseases. We also searched the VAERS database to estimate the incidence of adverse events of special interest (AESI) post COVID-19 vaccination. Almost all investigated vaccines were well tolerated and developed good levels of both humoural and cellular responses. A protective and efficient humoural immune response develops after the second or third dose of vaccine and a longer interval (about 28 days) between the first and second injections of vaccine could induce higher antibody responses. The vaccines were less immunogenic in immunocompromised patients, particularly those with haematological malignancies. In addition, we found that venous and arterial thrombotic events, Bell's palsy, and myocarditis/pericarditis were the most common AESI. The results showed the potency of the SARS-CoV-2 vaccines to protect subjects against disease. The provision of further effective and safe vaccines is necessary in order to reach a high coverage of immunisation programs across the globe and to provide protection against infection itself.

Electroencephalographic findings post-COVID-19 vaccination: A systematic review of case reports and case series.

A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID-19). Electroencephalogram (EEG) is one of the modalities used to evaluate the neurological complications of diseases. The aim of the present study was to identify the EEG changes in participants vaccinated against COVID-19. PubMed, Scopus, Web of Science, medRxiv, and Google Scholar were searched up to 1 September 2022, with terms related to COVID-19 vaccines, EEG, neurological signs/symptoms, or neurological disorders. All case reports and case series were included if the participants had received at least one dose of a COVID-19 vaccine and a post vaccination EEG report was also reported. We used the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports and case series to appraise the methodological quality of the included studies. Thirty-one studies were included, which were comprised of 24 case reports and seven case series and a total of 36 participants. Generalised slowing and non-convulsive focal status epilepticus were the most common EEG findings post-COVID-19 vaccination. The most frequent symptoms were headache, fatigue, generalised weakness, and vomiting. In addition, the most common signs were encephalopathy, post-ictal phases, and confusion. Encephalitis, acute disseminated encephalomyelitis, and post-vaccinal encephalopathy were the most commonly diagnosed adverse events. Furthermore, most of the imaging studies appeared normal. The EEG reports mainly showed background slowing and epileptiform discharges, encephalitis, encephalopathies, and demyelinating disorders. Future studies with larger samples and more vaccine types may help to further unravel the potential neurological effects of COVID-19 vaccinations on recipients.

Association between metabolic syndrome and myocardial infarction among patients with excess body weight: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality worldwide. Controversial views exist over the effects of metabolically unhealthy obesity phenotypes on CVDs. This study aimed to perform a meta-analysis to assess the association between metabolic syndrome and myocardial infarction (MI) among individuals with excess body weight (EBW). METHODS: We searched PubMed/Medline, Scopus, and Web of Science databases as of December 9, 2023. Cohort studies involving patients with overweight or obesity that reported the relevant effect measures for the association between metabolic syndrome and MI were included. We excluded studies with incomplete or unavailable original data, reanalysis of previously published data, and those that did not report the adjusted effect sizes. We used the Newcastle Ottawa Scale for quality assessment. Random-effect model meta-analysis was performed. Publication bias was assessed by Begg's test. RESULTS: Overall, nine studies comprising a total of 61,104 participants were included. There was a significant positive association between metabolic syndrome and MI among those with obesity (hazard ratio (HR): 1.68; 95% confidence interval (CI): 1.27, 2.22). Subgroup analysis showed higher HRs for obesity (1.72; 1.03, 2.88) than overweight (1.58; 1.-13-2.21). Meta-regression revealed no significant association between nationality and risk of MI (p = 0.75). All studies had high qualities. There was no significant publication bias (p = 0.42). CONCLUSIONS: Metabolic syndrome increased the risk of MI in those with EBW. Further studies are recommended to investigate other risk factors of CVDs in EBW, in order to implement preventive programs to reduce the burden of CVD in obesity.

The safety and efficacy of binimetinib for lung cancer: a systematic review.

BACKGROUND: Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment. METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool. RESULTS: Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine. CONCLUSIONS: Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.

The effect of obesity phenotype changes on cardiovascular outcomes in adults older than 40 years in the prospective cohort of the Tehran lipids and glucose study (TLGS): joint model of longitudinal and time-to-event data.

BACKGROUND: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data. METHODS: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1). RESULTS: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model. CONCLUSIONS: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD.

The burden of dermatitis from 1990-2019 in the Middle East and North Africa region.

BACKGROUND: There are several types of dermatitis, each capable of causing enduring changes that extend beyond physical discomfort. In severe cases, dermatitis can significantly affect mental health, social interactions, and the overall quality of life. This study reports the burden of dermatitis in the Middle East and North Africa (MENA) region from 1990 to 2019, according to sex, age category, and socio-demographic index (SDI). METHODS: Publicly available data regarding the point prevalence, incidence, and years lived with disability (YLDs) were collected from the Global Burden of Disease 2019 study for both the MENA region and its constituent countries. The point prevalence, incidence, and YLDs of dermatitis were represented as counts and age-standardised rates with 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence of dermatitis was 2744.6 (2517.8-3003.1) per 100,000 population, which was 2.3% lower than in 1990. The YLD rate was 92.3 (55.6-143.4) per 100,000 population, which was 3.1% lower than in 1990. The largest point prevalence rates were observed among those aged 70-74, for both sexes. The 2019 MENA/Global DALY ratio was not above one in any age group for either sex. During the period 1990 to 2019, there was no clear correlation between the burden of dermatitis and the SDI level. CONCLUSION: The dermatitis burden in the MENA region remained relatively stable from 1990 to 2019. Future prevention efforts should focus on improving healthcare access, health education, and workplace safety regulations.

Factors affecting sexual health in individuals with spinal cord injury: A systematic scoping review.

PURPOSE: This study aims to review the literature to explore some factors affecting sexual and partnership adjustment in individuals with spinal cord injury (SCI). METHODS: This study was based on the methodological framework of scoping reviews, including 3 methodological steps: (1) identifying relevant studies (searching for related studies); (2) selecting related studies; (3) collecting key findings, summarizing, and reporting the results. The electronic databases were searched including Medline (PubMed), Scopus, Web of Science, Embase, and Cochrane Library. Studies were included if they reported data about the related factors of sexual and partnership adjustment in individuals with SCI. No limitations were considered in terms of time or methodology of the search. RESULTS: After the full-text screening, 52 studies were included from the year of 1978 - 2019 with various methodologies. The present review demonstrated that proper sexual health among individuals with SCI is related to several factors including the anatomical factor, level of the injury, completeness of the injury, psycho-social factor, socio-economic status, and type of relationship. CONCLUSION: With consideration of factors affecting sexual and partnership adjustment in individuals with SCI, a better estimation of sexual health can be achieved in clinical to improve the relationship and quality of life.

The relationship between blood groups and risk of infection with SARS-CoV-2 or development of severe outcomes: A review.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a global catastrophe that has overwhelmed health care systems. Since initiation of the pandemic, identification of characteristics that might influence risk of infection and poor disease outcomes have been of paramount interest. Blood group phenotypes are genetically inherited characteristics whose association with certain infectious diseases have long been debated. The aim of this review is to identify whether a certain type of blood group may influence an individual's susceptibility to SARS-CoV-2 infection and developing severe outcomes. Our review shows that blood group O protects individuals against SARS-CoV-2, whereas blood group A predisposes them to being infected. Although the association between blood groups and outcomes of COVID-19 is not consistent, it is speculated that non-O blood group carriers with COVID-19 are at higher risk of developing severe outcomes in comparison to O blood group. The interaction between blood groups and SARS-CoV-2 infection is hypothesized to be as result of natural antibodies against blood group antigens that may act as a part of innate immune response to neutralize viral particles. Alternatively, blood group antigens could serve as additional receptors for the virus and individuals who are capable of expressing these antigens on epithelial cells, which are known as secretors, would then have a high propensity to be affected by SARS-CoV-2.

Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.

BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.

ABO blood groups and risk of human immunodeficiency virus infection: A systematic review and meta-analysis.

The last few decades have seen a pandemic of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), which continues to cause substantial morbidity and mortality. ABO blood groups are anthropological and genetic characteristics of a population whose associations with HIV infection are still controversial. This systematic review with meta-analysis was undertaken to investigate whether certain blood groups may have associations with HIV infection. PubMed, Scopus and Web of Science databases were systematically searched as of 6 September 2021. Grey literature was identified through screening Google Scholar, and reference lists of relevant studies. All observational studies providing data on ABO blood group distribution among HIV-infected and uninfected participants were included. Using a random effect model, risk ratios (RR) and 95% confidence intervals (CIs) were pooled to quantify this relationship. Fifty eligible studies with a total of 3,068,244 participants and 6508 HIV-infected cases were included. The overall analysis found that blood group AB increased the risk of HIV infection by 19% as compared with non-AB blood groups (RR = 1.19, 95% CI: 1.03-1.39, p = 0.02). Pooled estimates for other blood groups failed to reach statistical significance. Subgroup analyses identified a positive relationship between AB blood group and HIV infection within Asia, patient populations (as opposed to blood donors and general populations), studies with lower sample sizes, high-income countries and studies with a moderate quality score. The sequential omission and re-analysis of studies within sensitivity analyses produced no change in the overall pooled effect. In conclusion, this study identified that blood group AB carriers were more susceptible to HIV infection. Future investigations should be directed toward clarification of the exact role of ABO blood groups in HIV infection and the possible underlying mechanisms.

Cardiac complications following mRNA COVID-19 vaccines: A systematic review of case reports and case series.

There have been several local and systemic adverse events associated with mRNA COVID-19 vaccines. Pericarditis, myocarditis and myocardial infarction are examples of cardiac complications related to these vaccines. In this article, we conducted a systematic review of case reports and case series to identify the clinical profile, investigations, and management of reported cardiac complications post-mRNA COVID-19 vaccines. We systematically searched PubMed, Scopus, Web of Science, and Google Scholar, as well as the medRxiv preprint server, with terms including: 'SARS-CoV-2', 'COVID-19', 'messenger RNA vaccine*', 'mRNA-1273 vaccine', 'BNT162 vaccine', 'myocarditis', 'pericarditis', 'stroke' and 'Myocardial Ischemia' up to 25 September 2021. Studies were excluded if they were not case reports or case series, or reported cases from non-mRNA vaccines. Case reports and case series were included that investigated the potential cardiac complications associated with mRNA COVID-19 vaccines. The JBI checklist was used to assess quality and data synthesis was conducted using a qualitative methodology called narrative synthesis. Sixty-nine studies, including 43 case reports and 26 case series, were included. Myocarditis/myopericarditis and pericarditis were the most common adverse events among the 243 reported cardiac complications, post mRNA COVID-19 vaccination. Males with a median age of 21 years had the highest frequency of myocarditis. Almost three quarters (74.4%) of cases with myocarditis had received the BNT162b2 vaccine and 87.7% had received the second dose of the vaccine. Chest pain (96.1%) and fever (38.2%) were the most common presentations. CK-MB, troponin, and NT-proBNP were elevated in 100%, 99.5% and 78.3% of subjects, respectively. ST-segment abnormality was the most common electrocardiogram feature. Cardiac magnetic resonance imaging, which is the gold-standard approach for diagnosing myocarditis, was abnormal in all patients diagnosed with myocarditis. Non-steroidal anti-inflammatory drugs were the most prescribed medication for the management of myocarditis. Apart from inflammatory conditions, some rare cases of Takotsubo cardiomyopathy, myocardial infarction, myocardial infarction with non-obstructive coronary arteries, and isolated tachycardia were also reported following immunisation with mRNA COVID-19 vaccines. We acknowledge that only reviewing case reports and case series studies is one potential limitation of our study. We found that myocarditis was the most commonly reported adverse cardiac event associated with mRNA COVID-19 vaccines, which presented as chest pain with a rise in cardiac biomarkers. Further large-scale observational studies are recommended.

Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review.

Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 109 /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.

MicroRNAs expression in peripheral blood mononuclear cells of patients with multiple sclerosis propose.

BACKGROUND: MicroRNAs (miRs) are involved in the autoimmune and neurological diseases, including multiple sclerosis (MS), through modulating post-transcriptional gene regulation. Accumulating evidence indicates that miR-10, miR-24a, miR-124, and miR-21 play an imperative role in MS pathogenesis. Therefore, the current research aimed to analyze the expression of the selected miRNAs for MS in Iranian population. METHODS AND RESULTS: Blood sample of 75 relapsing-remitting MS (RRMS) patients and 75 healthy individuals suffering no neurodegenerative illness was collected. Subsequently, the isolation of peripheral blood mononuclear cells (PBMCs) was performed by employing Ficoll-Hypaque density gradient method. Afterward, total RNA was extracted and subjected to qRT-PCR analysis. The obtained results evidenced that the relative expression of miR-10 (P = 0.0002), miR-21 (P = 0.0014), and miR-124 (P = 0.0091) significantly decreased in RRMS patients compared to healthy participants. On the contrary, no notable change was observed between the studies groups regarding miR-24a expression levels (P = 0.107). ROC curve analysis estimated an area under the curve (AUC) value equal to 0.75 with P = 0.0006 for miR-10, while it was decreased for miR-21 (AUC = 0.67 and P = 0.0054) and miR-124 (AUC = 0.66 and P = 0.012). CONCLUSION: The change in miR-10, miR-124, and miR-21 expression patterns was implied to participate in MS development. Further large scale observational studies are recommended.

The burden of pancreatic cancer and its attributable risk factors in the Middle East and North Africa region, 1990-2019.

BACKGROUND AND AIM: Globally, pancreatic cancer is recognized as one of the most lethal types of cancers. We report the burden of pancreatic cancer and its attributable risk factors in the Middle East and North Africa (MENA) region, from 1990 to 2019, by age, sex, and socio-demographic index. METHODS: Publicly available data from the Global Burden of Disease 2019 study were used to report the incidence, deaths, and disability-adjusted life years (DALYs) attributable to pancreatic cancer, as counts and age-standardized rates with 95% uncertainty intervals. RESULTS: In 2019, pancreatic cancer had an age-standardized incidence rate of 5.3 and a death rate of 5.5 (per 100 000) in MENA, which have increased by 97.5% and 93.4%, respectively, since 1990. There were 563.6 thousand DALYs attributable to pancreatic cancer in 2019, with an age-standardized DALY rate of 123.0, which has increased by 84.9% since 1990. The highest number of incident cases was found in the 60-64 and 65-69 age groups, among male and female, respectively. In addition, the MENA/global DALY ratios were higher in all age groups for both sexes in 2019, than they were in 1990. There was a positive association between socio-demographic index and the burden of pancreatic cancer. Smoking, high fasting plasma glucose, and high body mass index were responsible for 19.2%, 9.3%, and 9.3% of the attributable DALYs in 2019, respectively. CONCLUSIONS: There was a clear and substantial increase in the burden of pancreatic cancer in the MENA region. Prevention programs should be implemented in the region that target these three risk factors.

The burden of Alzheimer's disease and other types of dementia in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and this progressive neurological disorder is associated with substantial mortality and morbidity. We aimed to report the burden of AD and other types of dementia in the Middle East and North Africa (MENA) region, by age, sex and sociodemographic index (SDI), for the period 1990-2019. METHODS: publicly accessible data on the prevalence, death and disability-adjusted life years (DALYs) because of AD, and other types of dementia, were retrieved from the global burden of disease 2019 project for all MENA countries from 1990 to 2019. RESULTS: in 2019, the age-standardised point prevalence of dementia was 777.6 per 100,000 populations in MENA, which was 3.0% higher than in 1990. The age-standardised death and DALY rates of dementia were 25.5 and 387.0 per 100,000, respectively. In 2019, the highest DALY rate was observed in Afghanistan and the lowest rate was in Egypt. That same year, the age-standardised point prevalence, death and DALY rates increased with advancing age and were higher for females of all age groups. From 1990 to 2019, the DALY rate of dementia decreased with increasing SDI up to 0.4, then slightly increased up to an SDI of 0.75, followed by a decrease for the remaining SDI levels. CONCLUSIONS: the point prevalence of AD and other types of dementia has increased over the past three decades, and in 2019, the corresponding regional burden was higher than the global average.

The estimated burden of bulimia nervosa in the Middle East and North Africa region, 1990-2019.

OBJECTIVE: We aimed to report the burden of bulimia nervosa (BN) in the Middle East and North Africa (MENA) region by age, sex, and sociodemographic index (SDI), for the period 1990-2019. METHODS: Estimates of the prevalence, incidence, and disability-adjusted life-years (DALYs) attributable to BN were retrieved from the Global Burden of Disease study 2019, between 1990 and 2019, for the 21 countries in the MENA region. The counts and age-standardized rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, the estimated regional age-standardized point prevalence and incidence rates of BN were 168.3 (115.0-229.6) and 178.6 (117.0-255.6) per 100,000, which represented 22.0% (17.5-27.2) and 10.4% (7.1-14.7) increases, respectively, since 1990. Moreover, in 2019 the regional age-standardized DALY rate was 35.5 (20.6-55.5) per 100,000, which was 22.2% (16.7-28.2) higher than in 1990. In 2019, Qatar (58.6 [34.3-92.5]) and Afghanistan (18.4 [10.6-29.2]) had the highest and lowest age-standardized DALY rates, respectively. Regionally, the age-standardized point prevalence of BN peaked in the 30-34 age group and was more prevalent among women. In addition, there was a generally positive association between SDI and the burden of BN across the measurement period. DISCUSSION: In the MENA region, the burden of BN has increased over the last three decades. Cost-effective preventive measures are needed in the region, especially in the high SDI countries. PUBLIC SIGNIFICANCE: This study reports the estimated burden of BN in the MENA region and shows that its burden has increased over the last three decades.

Systematic Review and Meta-Analysis of the Placebo Effect and its Correlates in Obsessive Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD. OBJECTIVES: We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD. METHODS: We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses. RESULTS: Forty-nine clinical trials (placebo group n = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias (P = 0.029). CONCLUSION: Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019125979.

The burden of Parkinson's disease in the Middle East and North Africa region, 1990-2019: results from the global burden of disease study 2019.

BACKGROUND: Parkinson's disease (PD) remains a common disabling progressive neurodegenerative disorder. We aimed to report the prevalence, death and disability-adjusted life-years (DALYs) attributable to PD in the Middle East and North Africa (MENA) region and its 21 countries by age, sex and socio-demographic index (SDI), between 1990 and 2019. METHODS: Publicly available data on the burden of PD in the MENA countries were retrieved from the Global Burden of Disease (GBD) 2019 project. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, PD had an age-standardised point prevalence of 82.6 per 100,000 population in MENA and an age-standardised death rate of 5.3, which have increased from 1990 to 2019 by 15.4% and 2.3%, respectively. In 2019, the age-standardised DALY rate of PD was 84.4, which was 0.9% higher than in 1990. The highest and lowest age-standardised DALY rates of PD in 2019 were found in Qatar and Kuwait, respectively. Also in 2019, the highest number of prevalent cases and number of DALYs were found in the 75-79 age group for both sexes. In 2019, females in MENA had an overall higher DALY rate. Furthermore, from 1990 to 2019 the burden of PD generally decreased with increasing socio-economic development, up to an SDI of around 0.4, and then increased with higher levels of SDI. CONCLUSION: An upward trend was observed in the point prevalence of PD over the last three decades. This highlights the need to allocate more resources for research. Furthermore, properly equipped healthcare services are needed for the increasing number of patients with PD.

The burden of lower respiratory infections and their underlying etiologies in the Middle East and North Africa region, 1990-2019: results from the Global Burden of Disease Study 2019.

BACKGROUND: Lower respiratory infections (LRIs) cause substantial mortality and morbidity. The present study reported and analysed the burden of LRIs in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, etiology, and socio-demographic index (SDI). METHODS: The data used in this study were sourced from the Global Burden of Disease (GBD) study 2019. The annual incidence, deaths, and disability-adjusted life-years (DALYs) due to LRIs were presented as counts and age-standardised rates per 100,000 population, along with their 95% uncertainty intervals (UIs). The average annual percent changes (AAPC) in the age-standardised incidence, death and DALYs rates were calculated using Joinpoint software and correlations (Pearson's correlation coefficient) between the AAPCs and SDIs were calculated using Stata software. RESULTS: In 2019, there were 34.1 million (95% UI 31.7-36.8) incident cases of LRIs in MENA, with an age-standardised rate of 6510.2 (95% UI 6063.6-6997.8) per 100,000 population. The number of regional DALYs was 4.7 million (95% UI 3.9-5.4), with an age-standardised rate of 888.5 (95% UI 761.1-1019.9) per 100,000 population, which has decreased since 1990. Furthermore, Egypt [8150.8 (95% UI 7535.8-8783.5)] and Afghanistan [61.9 (95% UI 52.1-72.6)] had the highest age-standardised incidence and death rates, respectively. In 2019, the regional incidence and DALY rates were highest in the 1-4 age group, in both females and males. In terms of deaths, pneumococcus and H. influenza type B were the most and least common types of LRIs, respectively. From 1990 to 2019, the burden of LRIs generally decreased with increasing SDI. There were significant positive correlations between SDI and the AAPCs for the age-standardised incidence, death and DALY rates (p < 0.05). Over the 1990-2019 period, the regional incidence, deaths and DALYs attributable to LRIs decreased with AAPCs of - 1.19% (- 1.25 to - 1.13), - 2.47% (- 2.65 to - 2.28) and - 4.21% (- 4.43 to - 3.99), respectively. CONCLUSIONS: The LRI-associated burden in the MENA region decreased between 1990 and 2019. SDI had a significant positive correlation with the AAPC and pneumococcus was the most common underlying cause of LRIs. Afghanistan, Yemen and Egypt had the largest burdens in 2019. Further studies are needed to investigate the effectiveness of healthcare interventions and programs to control LRIs and their risk factors.

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials.

BACKGROUND: Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate tislelizumab's safety and efficacy for treating non-small cell lung cancer (NSCLC). METHODS: Embase, Scopus, PubMed, Web of Science, and Google Scholar were searched up to December 20, 2022. The review only included randomized controlled trials (RCTs) that evaluated the safety or efficacy of tislelizumab for treating patients with lung cancer. The revised Cochrane risk-of-bias tool (RoB2) was utilized to evaluate study quality. RESULTS: There were four RCTs identified, which included 1565 patients with confirmed locally advanced or metastatic squamous and/or non-squamous types of NSCLC. Treatment with tislelizumab was associated with better progression-free survival (PFS) and objective response rate (ORR), particularly when used in combination with chemotherapy. Almost all patients in both arms reported at least one treatment-emergent adverse event (TEAE). Decreased hematologic indexes accounted for more than 20% of the grade ≥ 3 TEAEs in the tislelizumab plus chemotherapy group. The proportion of TEAE that led to death in the tislelizumab plus chemotherapy arms ranged from 3.2 to 4.2%. Hypothyroidism, pneumonitis, and hyperglycemia were the most frequently noted immune-mediated adverse events in the tislelizumab group. CONCLUSIONS: Tislelizumab, whether used alone or in combination with chemotherapy, seems to demonstrate both a safety and efficacy as a treatment for NSCLC.