Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review.

In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs' efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.

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.

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.

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.

Epidemiology, prognosis and management of potassium disorders in Covid-19.

Coronavirus disease (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre-existing comorbidities and laboratory parameters such as white blood cell count, D-dimer, C-reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid-19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid-19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid-19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.

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.

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.

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.

The burden of low back pain and its association with socio-demographic variables in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019. METHODS: Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35-39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period. CONCLUSION: The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region.

The burden of major depressive disorder in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability. We aimed to report the MDD-attributable prevalence, incidence and years lived with disability (YLDs) in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex and socio-demographic index (SDI). METHODS: Publicly available data on the burden of MDD were retrieved from the Global Burden of Disease (GBD) study 2019 for the 21 countries in MENA. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, MDD had an age-standardised point prevalence of 3322.1 and an incidence rate of 4921.7 per 100,000 population in MENA. Furthermore, there were 4.1 million YLDs in 2019. However, there were no substantial changes in the MDD burden over the period 1990-2019. In 2019, Palestine had the highest burden of MDD. The highest prevalence, incidence and YLDs attributable to MDD were found in the 35-39 age group. In 2019, the YLD rate in MENA was higher than the global rate for almost all age groups. Furthermore, there was a broadly negative association between the YLD rate and SDI. CONCLUSION: The study highlights the need to prevent the disorder using a multidisciplinary approach and for the provision of cost-effective treatments for those affected, in order to increase their quality of life.

Global disease burden attributed to low physical activity in 204 countries and territories from 1990 to 2019: Insights from the Global Burden of Disease 2019 Study.

The purpose of this investigation is to estimate the global disease burden attributable to low physical activity (PA) in 204 countries and territories from 1990 to 2019 by age, sex, and Socio-Demographic Index (SDI). Detailed information on global deaths and disability-adjusted life years (DALYs) attributable to low PA were collected from the Global Burden of Disease Study 2019. The ideal exposure scenario of PA was defined as 3000-4500 metabolic equivalent minutes per week and low PA was considered to be less than this threshold. Age-standardization was used to improve the comparison of rates across locations or between time periods. In 2019, low PA seems to contribute to 0.83 million [95% uncertainty interval (UI) 0.43 to 1.47] deaths and 15.75 million (95% UI 8.52 to 28.62) DALYs globally, an increase of 83.9% (95% UI 69.3 to 105.7) and 82.9% (95% UI 65.5 to 112.1) since 1990, respectively. The age-standardized rates of low-PA-related deaths and DALYs per 100,000 people in 2019 were 11.1 (95% UI 5.7 to 19.5) and 198.4 (95% UI 108.2 to 360.3), respectively. Of all age-standardized DALYs globally in 2019, 0.6% (95% UI 0.3 to 1.1) may be attributable to low PA. The association between SDI and the proportion of age-standardized DALYs attributable to low PA suggests that regions with the highest SDI largely decreased their proportions of age-standardized DALYs attributable to low PA during 1990-2019, while other regions tended to have increased proportions in the same timeframe. In 2019, the rates of low-PA-related deaths and DALYs tended to rise with increasing age in both sexes, with no differences between males and females in the age-standardized rates. An insufficient accumulation of PA across the globe occurs together with a considerable public health burden. Health initiatives to promote PA within different age groups and countries are urgently needed.

Global, regional, and national cancer deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption in 204 countries and territories, 1990-2019.

BACKGROUND: Alcohol consumption is a risk factor for a number of communicable and non-communicable diseases, including several types of cancer. This article reports the burden of cancers attributable to alcohol consumption by age, sex, location, sociodemographic index (SDI), and cancer type from 1990 to 2019. METHODS: The Comparative Risk Assessment approach was used in the 2019 Global Burden of Disease study to report the burden of cancers attributable to alcohol consumption between 1990 and 2019. RESULTS: In 2019, there were globally an estimated 494.7 thousand cancer deaths (95% uncertainty interval [UI], 439.7 to 554.1) and 13.0 million cancer disability-adjusted life-years (DALYs; 95% UI, 11.6 to 14.5) that were attributable to alcohol consumption. The alcohol-attributable DALYs were much higher in men (10.5 million; 95% UI, 9.2 to 11.8) than women (2.5 million; 95% UI, 2.2 to 2.9). The global age-standardized death and DALY rates of cancers attributable to alcohol decreased by 14.7% (95% UI, 6.4% to 23%) and 18.1% (95% UI, 9.2% to 26.5%), respectively, over the study period. Central Europe had the highest age-standardized death rates that were attributable to alcohol consumption(10.3; 95% UI, 8.7 to12.0). Moreover, there was an overall positive association between SDI and the regional age-standardized DALY rate for alcohol-attributable cancers. CONCLUSIONS: Despite decreases in age-standardized deaths and DALYs, substantial numbers of cancer deaths and DALYs are still attributable to alcohol consumption. Because there is a higher burden in males, the elderly, and developed regions (based on SDI), these groups and regions should be prioritized in any prevention programs.

Prevalence, incidence and years lived with disability due to polycystic ovary syndrome in 204 countries and territories, 1990-2019.

STUDY QUESTION: What is the global, regional and national burden of polycystic ovary syndrome (PCOS), by age and socio-demographic index (SDI), over the period 1990-2019? SUMMARY ANSWER: In 2019, the global age-standardized point prevalence, incidence and years lived with disability (YLD) of PCOS were 30.4, 29.5 and 29.9 per 100 000 population, respectively. WHAT IS KNOWN ALREADY: Data from the Global Burden of Disease (GBD) study 2017 showed that the global age-standardized PCOS incidence rate increased 1.45% over the period 1990-2017. STUDY DESIGN, SIZE, DURATION: A systematic analysis of the PCOS prevalence, incidence and YLDs across 204 countries and territories was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on the point prevalence, annual incidence and YLDs due to PCOS were retrieved from the GBD study 2019 for 204 countries and territories from 1990 to 2019. The counts and age-standardized rates (per 100 000) are presented, along with their corresponding 95% uncertainty intervals (UIs). MAIN RESULTS AND THE ROLE OF CHANCE: In 2019, the global age-standardized point prevalence and annual incidence rates for PCOS were 1677.8 (95% UI: 1166.0 to 2192.4) and 59.8 (95% UI: 41.7 to 78.9) per 100 000, which represents a 30.4% and 29.5% increase since 1990, respectively. Moreover, the global age-standardized YLD rate in 2019 was 14.7 (6.3-29.5), an increase of 29.9% since 1990. In 2019, Italy (7897.0), Japan (6298.7) and New Zealand (5419.1) had the highest estimated age-standardized point prevalences of PCOS. Globally, the number of prevalent cases and the point prevalence of PCOS peaked in the 25-29 years and 40-44 years age groups, respectively. Positive associations were found between the burden of PCOS and the SDI at the regional and national levels. LIMITATIONS, REASONS FOR CAUTION: Variations in how PCOS was defined is a major limitation that prevents valid comparisons between different regions. WIDER IMPLICATIONS OF THE FINDINGS: Globally, the burden of PCOS has increased at an alarming rate, making it a major public health concern. Increasing public awareness about this common condition, improving management options and increasing support to reduce factors which lead to further complications, need to be public health priorities. STUDY FUNDING/COMPETING INTEREST(S): The Bill and Melinda Gates Foundation, who were not involved in any way in the preparation of this manuscript, funded the GBD study. The Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grant No. 28709) also supported the present report. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.