Exploring the reported adverse effects of COVID-19 vaccines among vaccinated Arab populations: a multi-national survey study.

The coronavirus disease 2019 (COVID-19) pandemic has been a major challenge worldwide for the past years with high morbidity and mortality rates. While vaccination was the cornerstone to control the pandemic and disease spread, concerns regarding safety and adverse events (AEs) have been raised lately. A cross-sectional study was conducted between January 1st and January 22nd, 2022, in six Arabic countries namely Saudi Arabia, Egypt, Syria, Libya, Iraq, and Algeria. We utilized a self-administered questionnaire validated in Arabic which encompassed two main parts. The first was regarding sociodemographic data while the second was about COVID-19 vaccination history, types, doses, and experienced AEs. A multistage sampling was employed in each country, involving the random selection of three governorates from each country, followed by the selection of one urban area and one rural area from each governorate. We included the responses of 1564 participants. The most common AEs after the first and second doses were local AEs (67.9% and 46.6%, respectively) followed by bone pain and myalgia (37.6% and 31.8%, respectively). After the third dose, the most common AEs were local AEs (45.7%) and fever (32.4%). Johnson and Johnson, Sputnik Light, and Moderna vaccines showed the highest frequency of AEs. Factors associated with AEs after the first dose included an increase in age (aOR of 61-75 years compared to the 12-18 years group: 2.60, 95% CI: 1.59-4.25, p = 0.001) and male gender (OR: 0.72, 95% CI: 0.63-0.82, p < 0.001). The cumulative post-vaccination COVID-19 disease was reported with Sinovac (16.1%), Sinopharm (15.8%), and Johnson and Johnson (14.9) vaccines. History of pre-vaccination SARS-CoV-2 infection significantly increases the risk of post-vaccination COVID-19 after the first, second, and booster doses (OR: 3.09, CI: 1.9-5.07, p < 0.0001; OR: 2.56, CI: 1.89-3.47, p < 0.0001; and OR: 2.94, CI: 1.6-5.39, p = 0.0005 respectively). In conclusion, AEs were common among our participants, especially local AEs. Further extensive studies are needed to generate more generalizable data regarding the safety of different vaccines.

A Case Report of 17α-Hydroxylase Deficiency in Two Saudi Siblings With Different Karyotyping.

Congenital adrenal hyperplasia (CAH) consists of variable disorders of sex determination and differentiation. 17α-hydroxylase deficiency (17OHD) is an uncommon form of those disorders, which is typically characterized by hypertension, hypokalemia, failure of puberty, and ambiguous genitalia. The 17α-hydroxylase enzyme is encoded by the CYP17A1 gene and it is required for the synthesis of cortisol and sex steroids. The affected females with 17OHD usually present with primary amenorrhea and delayed puberty, which are associated with hypertension and hypokalemia while male patients might show female external genitalia, pseudohermaphroditism, or variable degrees of ambiguous genitalia with intra-abdominal testes in addition to hypertension and hypokalemia as well. We present two Saudi siblings (19 and 16 years old) who were diagnosed with the rare CAH subtype of 17OHD after presenting with long-standing hypertension, refractory hypokalemia, and failure of puberty. It is interesting that both siblings had biochemical primary adrenal insufficiency; however, both patients did not clinically present with an acute adrenal crisis, which is likely due to the effect of increased levels of deoxycorticosterone. Additionally, although both patients have similar phenotypes and clinical presentations, they have different karyotypes. This again highlights the variability of the manifestations that can result from 17OHD even with an identical mutation in the same family. Both patients were treated successfully with dexamethasone, which has led to the normalization of hypertension, resolution of hypokalemia, and discontinuation of anti-hypertensive medications and potassium supplements after several years of treatment. However, the entire management is quite challenging and requires a multidisciplinary approach regarding difficult issues such as gender identity and assignment and fertility issues in addition to a life-long follow-up.

Cancer Research in Vulnerable Populations: A Call for Collaboration and Sustainability From MENAT Countries.

PURPOSE: Cancer is a major burden across Middle East, North Africa, Türkiye (MENAT). Many MENAT countries experience multiple conflicts that compound vulnerabilities, but little research investigates the linkages between vulnerability and cancer research. This study examines the current level and the potential for cancer research among vulnerable populations in the MENAT region, aiming to provide direction toward developing a research agenda on the region's vulnerable populations. METHODS: Expert-driven meetings were arranged among the 10 authors. After obtaining institutional review board approval, a self-administered online survey questionnaire was circulated to more than 500 cancer practitioners working in 22 MENAT countries. RESULTS: Two hundred sixteen cancer practitioners across the MENAT region responded. Fifty percent of the respondents identified clinical research in vulnerable patients with cancer as a significant issue; 21.8% reported previous research experience that included vulnerable populations, and 60% reported encountering vulnerable populations in their daily clinical practice. The main barriers to conducting research were lack of funding (60%), protected time (42%), and research training (35%). More than half of the respondents believed that wars/conflicts constituted an important source of vulnerability. The most vulnerable cancer populations were the elderly, palliative/terminally ill, those with concomitant mental health-related issues, those with other chronic illnesses, and socioeconomically deprived patients. CONCLUSION: Results support that a major effort is needed to improve cancer research among vulnerable cancer populations in the MENAT region. We call for interdisciplinary research that accounts for the region's unique, compounding, and cumulative forms of vulnerability. This cancer research agenda on different vulnerable populations must balance sociobehavioral studies that explore sociopolitical barriers to quality care and clinical studies that gauge and refine treatment protocols. Building a research agenda through collaboration and solidarity with international partners is prime time.

Use of camel urine is of no benefit to cancer patients: observational study and literature review.

Background: Complementary and alternative medicine is widely used in Saudi Arabia. One of the common practices is the use of camel urine alone or mixed with camel milk for the treatment of cancer, which is often supported by religious beliefs. Aims: To observe and follow-up cancer patients who insisted on using camel urine, and to offer some clinically relevant recommendations. Methods: We observed 20 cancer patients (15 male, 5 female) from September 2020 to January 2022 who insisted on using camel urine for treatment. We documented the demographics of each patient, the method of administering the urine, reasons for refusing conventional treatment, period of follow-up, and the outcome and side effects. Results: All the patients had radiological investigations before and after their treatment with camel urine. All of them used a combination of camel urine and camel milk, and treatment ranged from a few days to 6 months. They consumed an average of 60 ml urine/milk per day. No clinical benefit was observed after the treatment; 2 patients developed brucellosis. Eleven patients changed their mind and accepted conventional antineoplastic treatment and 7 were too weak to receive further treatment; they died from the disease. Conclusion: Camel urine had no clinical benefits for any of the cancer patients, it may even have caused zoonotic infection. The promotion of camel urine as a traditional medicine should be stopped because there is no scientific evidence to support it.

Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

How does Linkage to the National Death Index Affect Population-Based Net Survival Estimates for Women with Cervical Cancer in Saudi Arabia?

BACKGROUND: Population-based cancer survival is a key metric for the assessment of cancer control strategies. Accurate estimation of cancer survival requires complete follow-up data for all patients. AIM: To explore the impact of linking national cancer registry data to the national death index on net survival estimates for women diagnosed with cervical cancer in Saudi Arabia during 2005-2016. METHODS: We acquired data on 1,250 Saudi women diagnosed with invasive cervical cancer during the 12- year period 2005-2016 from the Saudi Cancer Registry. These included the woman's last known vital status and the date of last known vital status, but this was restricted to information from clinical records and death certificates that mention cancer as a cause of death ("registry follow-up"). We submitted available national ID numbers to the National Information Center (NIC) of the Ministry of Interior, to ascertain the date of death, from any cause of death, for women who had died up until 31 December 2018 ("NIC follow-up"). We estimated age-standardised 5-year net survival using the Pohar-Perme estimator under five different scenarios using the two sources of follow-up, and censoring at the date of last contact with the registry versus extending survival until the closing date if no information on death was obtained. RESULTS: 1,219 women were eligible for survival analysis. Five-year net survival was lowest when using NIC followup only (56.8%; 95%CI 53.5 - 60.1%), and highest when registry follow-up only was used and survival time was extended until closure date for those with no information on death (81.8%; 95%CI 79.6 - 84%). CONCLUSION: Reliance solely on information from deaths certified as due to cancer and clinical records leads to a high proportion of missing deaths in the national cancer registry. This is probably due to low quality of certification of the cause of death in Saudi Arabia. Linkage of the national cancer registry to the national death index at the NIC identifies virtually all deaths, providing more reliable survival estimates, and it eliminates the ambiguity in determining the underlying cause of death. Therefore, this should become the standard approach to estimating cancer survival in Saudi Arabia.

Progress and remaining challenges for cancer control in the Gulf Cooperation Council.

Cancer is a growing global health-care problem, especially in under-resourced countries. Cancer prevalence in Gulf Cooperation Council (GCC) countries is projected to increase, potentially leading to a major burden on the economy. Policy makers in GCC countries have invested in the development of National Cancer Control Strategies to address the current and future burden of cancer through different initiatives and policies for prevention, early detection, and management of cancer. These strategies include capacity building, health education, and global partnerships to strengthen health-care systems. The aim of this Review is to highlight the status of cancer control programmes in GCC countries, describe what has been achieved to date, and identify the gaps, with recommendations on how to lower the burden of cancer in the Gulf region in the future. TRANSLATION: For the Arabic translation of the abstract see Supplementary Materials section.

Case report: A fatal outcome from co-infection of COVID-19 and dengue in the western region of Jeddah, Saudi Arabia.

Introduction: Co-infection of coronavirus disease 2019 (COVID-19) and dengue may coexist, as both viruses share similar laboratory and clinical features, making diagnosis and treatment challenging for health care professionals to prescribe, negatively impacting patient prognosis, and outcomes. Results and discussions: Both cases were positive for PCR and X-ray laboratory investigation at clinical examination, confirming COVID-19 and dengue co-infection, admission, and better management in referral hospitals are presented and discussed. The timeline provides detailed cases of situational analysis and the medical actions taken, as well as the outcomes. Conclusion: Both co-infection cases' (patients) health conditions had a poor prognosis and diagnosis and ended with undesired outcomes. Scaling up dual mosquito-vector linked viral diseases surveillance in understanding the transmission dynamics, early diagnosis, and the timely and safe monitoring of case management in clinical and hospital settings nationwide is paramount in curbing preventable co-infections and mortality.

Secure Health Monitoring Communication Systems Based on IoT and Cloud Computing for Medical Emergency Applications.

Smart health surveillance technology has attracted wide attention between patients and professionals or specialists to provide early detection of critical abnormal situations without the need to be in direct contact with the patient. This paper presents a secure smart monitoring portable multivital signal system based on Internet-of-Things (IoT) technology. The implemented system is designed to measure the key health parameters: heart rate (HR), blood oxygen saturation (SpO2), and body temperature, simultaneously. The captured physiological signals are processed and encrypted using the Advanced Encryption Standard (AES) algorithm before sending them to the cloud. An ESP8266 integrated unit is used for processing, encryption, and providing connectivity to the cloud over Wi-Fi. On the other side, trusted medical organization servers receive and decrypt the measurements and display the values on the monitoring dashboard for the authorized specialists. The proposed system measurements are compared with a number of commercial medical devices. Results demonstrate that the measurements of the proposed system are within the 95% confidence interval. Moreover, Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), and Mean Relative Error (MRE) for the proposed system are calculated as 1.44, 1.12, and 0.012, respectively, for HR, 1.13, 0.92, and 0.009, respectively, for SpO2, and 0.13, 0.11, and 0.003, respectively, for body temperature. These results demonstrate the high accuracy and reliability of the proposed system.

Identification of Gene Signature as Diagnostic and Prognostic Blood Biomarker for Early Hepatocellular Carcinoma Using Integrated Cross-Species Transcriptomic and Network Analyses.

Background: Hepatocellular carcinoma (HCC) is considered the most common type of liver cancer and the fourth leading cause of cancer-related deaths in the world. Since the disease is usually diagnosed at advanced stages, it has poor prognosis. Therefore, reliable biomarkers are urgently needed for early diagnosis and prognostic assessment. Methods: We used genome-wide gene expression profiling datasets from human and rat early HCC (eHCC) samples to perform integrated genomic and network-based analyses, and discovered gene markers that are expressed in blood and conserved in both species. We then used independent gene expression profiling datasets for peripheral blood mononuclear cells (PBMCs) for eHCC patients and from The Cancer Genome Atlas (TCGA) database to estimate the diagnostic and prognostic performance of the identified gene signature. Furthermore, we performed functional enrichment, interaction networks and pathway analyses. Results: We identified 41 significant genes that are expressed in blood and conserved across species in eHCC. We used comprehensive clinical data from over 600 patients with HCC to verify the diagnostic and prognostic value of 41-gene-signature. We developed a prognostic model and a risk score using the 41-geneset that showed that a high prognostic index is linked to a worse disease outcome. Furthermore, our 41-gene signature predicted disease outcome independently of other clinical factors in multivariate regression analysis. Our data reveals a number of cancer-related pathways and hub genes, including EIF4E, H2AFX, CREB1, GSK3B, TGFBR1, and CCNA2, that may be essential for eHCC progression and confirm our gene signature's ability to detect the disease in its early stages in patients' biological fluids instead of invasive procedures and its prognostic potential. Conclusion: Our findings indicate that integrated cross-species genomic and network analysis may provide reliable markers that are associated with eHCC that may lead to better diagnosis, prognosis, and treatment options.

Fibrolamellar hepatocellular carcinoma treated with atezolizumab and bevacizumab: two case reports.

BACKGROUND: Fibrolamellar hepatocellular carcinoma is a unique tumor of the liver that differs from the classical hepatocellular carcinoma in diagnosis, behavior, and possibly treatment. There is usually absent underlying liver disease, and it usually occurs in young patients. The survival outcomes in localized fibrolamellar hepatocellular carcinoma are perhaps better than in classical hepatocellular carcinoma if treated early and radically. On the other hand, the prognosis remains poor for locally advanced and metastatic fibrolamellar hepatocellular carcinoma. Many reports suggested a limited benefit from systemic chemotherapy. Sorafenib also did not show major effects on fibrolamellar hepatocellular carcinoma. Given the rarity of fibrolamellar hepatocellular carcinoma, lack of large studies, and absence of standard treatment, the treatment decisions rely on case reports, previously reported cases series, and expert opinions. Recent studies have shown promising effects of immunotherapy with checkpoint inhibitors in the first- and second-line therapy of hepatocellular carcinoma. Atezolizumab with bevacizumab regimen has been approved recently as a first-line treatment for classical hepatocellular carcinoma. Currently, there are no reports yet on the use of atezolizumab with bevacizumab for fibrolamellar hepatocellular carcinoma. CASE REPORT: In this article, we present two Arabic patients with advanced fibrolamellar hepatocellular carcinoma who received atezolizumab and bevacizumab combinations but did not show any clinical benefits. CONCLUSION: While atezolizumab and bevacizumab combinations had shown benefits in classical hepatocellular carcinoma, the current data showed a lack of benefit and tumor response in fibrolamellar hepatocellular carcinoma.

Incidence and Trends of Liver Cancer in the Gulf Cooperation Council States, 1998-2012.

BACKGROUND: Liver cancer has been identified as the fifth most common cancer in males and ninth in females in the Gulf Cooperation Council (GCC) States. Taking into consideration that GCC states have comparable cultural and demographic backgrounds, this study aimed to examine the trends and patterns of liver cancer cases in the GCC states and to compare these with other regions. MATERIALS AND METHODS: The data were obtained from the Gulf Centre for Cancer Control and Prevention, which has maintained its database for GCC states since 1998. In total, 8,012 primary liver cancer cases were recorded for 15 years, from 1998 to 2012. Demographic information and cancer data for all cases were reviewed and analyzed, including sex, age, nationality, histological type and staging. Trends in the frequency of cases, agespecific incidence and stage at diagnosis were presented and compared for three periods (1998-2002, 2003-2007 and 2008-2012) for the six GCC countries. RESULTS: The trends show a balanced decrease in the number of liver cancer cases between 1998 and 2012. Over one-third of patients who presented were diagnosed with advanced liver cancer; however, 45.4% of the cases were left unknown. CONCLUSION: While the Gulf countries have achieved some success in reducing the number of liver cancer cases, there is a clear defect in the documentation of the cancer staging in some countries, and more effort is needed to improve early diagnosis.

BRAF and KRAS mutations in papillary thyroid carcinoma in the United Arab Emirates.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm comprising 80-90% of all thyroid malignancies. Molecular changes in thyroid follicular cells are likely associated with the development of PTC. Mutations in serine/threonine-protein kinase (BRAF) and Rat sarcoma viral oncogene homolog (RAS) are commonly seen in PTC. METHODS: In total, 90 cases of PTC are randomly selected from archive paraffin blocks and 10µm sections were cut and processed for DNA extraction. BRAF V600E mutation and 8 types of KRAS mutations were investigated using Real Time PCR. RESULTS: BRAF V600E mutation was identified in 46% of PTC while KRAS mutations were seen in 11% of PTC. There was significant correlation between BRAF V600E mutation and PTC larger than 5cm in diameter, positive surgical margin and lymph node metastasis. BRAF V600E mutation was significantly higher in patients with less than 55-year of age than those more than 55-year of age. BRAF V600E mutation was significantly higher in patients with family history of thyroid cancer than those without. There was no significant difference in BRAFV600E mutation between males and females, PTC classic and follicular variants, unifocal and multifocal PTC. There was a significant higher percentage of BRAF V600E mutation in classic PTC than papillary microcarcinoma variant. There was no significant age, gender, histologic type, tumor size, lymph node metastasis, tumor focality, and surgical margin status differences between KRAS mutated and non-mutated PTC. CONCLUSION: BRAF V600E and KRAS mutation are seen in a significant number of PTC in the UAE. BRAF mutation is significantly correlated with large tumor size, positive surgical margins and lymph node metastasis suggesting an association between BRAF V600E mutation and tumor growth and spread.

Spatial association between primary Middle East respiratory syndrome coronavirus infection and exposure to dromedary camels in Saudi Arabia.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic disease. Exposure to dromedary camels (Camelus dromedaries) has been consistently considered the main source of primary human infection. Although Saudi Arabia reports the highest rate of human MERS-CoV infection and has one of the largest populations of dromedary camels worldwide, their spatial association has not yet been investigated. Thus, this study aimed to examine the correlation between the spatial distribution of primary MERS-CoV cases with or without a history of camel exposure reported between 2012 and 2019 and dromedary camels at the provincial level in Saudi Arabia. In most provinces, a high proportion of older men develop infections after exposure to camels. Primary human infections during spring and winter were highest in provinces characterized by seasonal breeding and calving, increased camel mobilization and camel-human interactions. A strong and significant association was found between the total number of dromedary camels and the numbers of primary camel-exposed and non-exposed MERS-CoV cases. Furthermore, spatial correlations between MERS-CoV cases and camel sex, age and dairy status were significant. Via a cluster analysis, we identified Riyadh, Makkah and Eastern provinces as having the most primary MERS-CoV cases and the highest number of camels. Transmission of MERS-CoV from camels to humans occurs in most primary cases, but there is still a high proportion of primary infections with an ambiguous link to camels. The results from this study include significant correlations between primary MERS-CoV cases and camel populations in all provinces, regardless of camel exposure history. This supports the hypothesis of the role of an asymptomatic human carrier or, less likely, an unknown animal host that has direct contact with both infected camels and humans. In this study, we performed a preliminary risk assessment of prioritization measures to control the transmission of infection from camels to humans.

Trends in Thyroid Cancer Incidence in the Gulf Cooperation Council States: a 15-Year Analysis.

INTRODUCTION: Thyroid cancer is a predominant malignancy in the Gulf Cooperation Council (GCC) states. Explicit regional assessments of incidence are crucial among countries that share similar demographic, cultural, and economic characteristics. This study provides an assessment of trends in thyroid cancer in the GCC over fifteen years. METHODS: Data included cases in the GCC, reported to the Gulf Center for Cancer Registration during 1998-2012 (N=10,417). Age-specific rates, age-standardized rates (ASR), and stage at diagnosis are compared between the GCC states during 1998-2002, 2003-2007, and 2008-2012. Standardization of rates was performed using the World Standard Population. RESULTS: Between 1998-2002 and 2008-2012, the frequency of thyroid cancer in the GCC was approximately fourfold higher in females than males. The average ASR increased from 1.8 to 2.4/100,000 for males and 5.7 to 8.4/100,000 for females. Age-specific incidence showed a shift towards a younger age for women and an older age for males. During 1998-2012, the proportion of localized stage at diagnosis ranged from 18% in Oman to 57% in the UAE. The proportion of unknown stage varied considerably among states, ranging from 13% to 64%. Over the study period, the proportion of unknown stage increased in all but two states (Bahrain and Saudi Arabia). CONCLUSION: The incidence of thyroid cancer in the GCC has generally increased. This could reflect improved testing, leading to enhanced detection and diagnosis of thyroid cancers, as well as a possible increase in exposure to risk factors. Improved ascertainment of stage data is essential to reflect changes in early diagnosis activities.

Proportion of cancers attributable to major lifestyle and environmental risk factors in the Eastern Mediterranean region.

Cancer is a major contributing cause of morbidity and mortality in the Eastern Mediterranean region. The aim of the current study was to estimate the cancer burden attributable to major lifestyle and environmental risk factors. We used age-, sex- and site-specific incidence estimates for 2012 from IARC's GLOBOCAN, and assessed the following risk factors: smoking, alcohol, high body mass index, insufficient physical activity, diet, suboptimal breastfeeding, infections and air pollution. The prevalence of exposure to these risk factors came from different sources including peer-reviewed international literature, the World Health Organization, noncommunicable disease Risk Factor Collaboration, and the Food and Agriculture Organization. Sex-specific population-attributable fraction was estimated in the 22 countries of the Eastern Mediterranean region based on the prevalence of the selected risk factors and the relative risks obtained from meta-analyses. We estimated that approximately 33% (or 165,000 cases) of all new cancer cases in adults aged 30 years and older in 2012 were attributable to all selected risk factors combined. Infections and smoking accounted for more than half of the total attributable cases among men, while insufficient physical activity and exposure to infections accounted for more than two-thirds of the total attributable cases among women. A reduction in exposure to major lifestyle and environmental risk factors could prevent a substantial number of cancer cases in the Eastern Mediterranean. Population-based programs preventing infections and smoking (particularly among men) and promoting physical activity (particularly among women) in the population are needed to effectively decrease the regional cancer burden.

Cervical Cancer Incidence and Trends among Nationals of the Gulf Cooperation Council States, 1998-2012.

BACKGROUND: Cervical cancer is the ninth most common female malignancy in the Gulf Cooperation Council (GCC) States. We describe trends in cervical cancer incidence among GCC nationals. GCC states include Bahrain, Kuwait, Oman, Saudi Arabia, Qatar and the United Arab Emirates; which share similar demographic, socioeconomic and cultural backgrounds. METHODS: The Gulf Centre for Cancer Control and Prevention (GCCCP) has maintained a database of cancer in the GCC states since 1998. Women diagnosed with invasive cervical cancer during the 15 years 1998-2012 were included (N=2,332). Age-specific incidence over three periods (1998-2002, 2003-2007 and 2008-2012) are presented for all states combined. Trends in the frequency of registered cases, age-standardized incidence rates (ASRs) and in the distribution of stage at diagnosis for the six member states are compared between the three periods. RESULTS: Over the 15-year period, the peak age of cervical cancer diagnosis has slightly shifted towards older age. While the number of cases in the GCC has increased, the ASR has decreased. 39% of women were diagnosed in localized stage. The proportion of unknown stage ranged between 10% in the UAE and 58% in Oman, and has increased over time in Kuwait, Oman and the UAE. CONCLUSION: The present study indicates some success in cervical cancer preventive measures but the GCC may still see an increase in the number of cases in the coming years. More efforts should be directed towards documentation of stage and towards early diagnosis.

Spatiotemporal Clustering of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Incidence in Saudi Arabia, 2012-2019.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a great public health concern globally. Although 83% of the globally confirmed cases have emerged in Saudi Arabia, the spatiotemporal clustering of MERS-CoV incidence has not been investigated. This study analysed the spatiotemporal patterns and clusters of laboratory-confirmed MERS-CoV cases reported in Saudi Arabia between June 2012 and March 2019. Temporal, seasonal, spatial and spatiotemporal cluster analyses were performed using Kulldorff's spatial scan statistics to determine the time period and geographical areas with the highest MERS-CoV infection risk. A strongly significant temporal cluster for MERS-CoV infection risk was identified between April 5 and May 24, 2014. Most MERS-CoV infections occurred during the spring season (41.88%), with April and May showing significant seasonal clusters. Wadi Addawasir showed a high-risk spatial cluster for MERS-CoV infection. The most likely high-risk MERS-CoV annual spatiotemporal clusters were identified for a group of cities (n = 10) in Riyadh province between 2014 and 2016. A monthly spatiotemporal cluster included Jeddah, Makkah and Taif cities, with the most likely high-risk MERS-CoV infection cluster occurring between April and May 2014. Significant spatiotemporal clusters of MERS-CoV incidence were identified in Saudi Arabia. The findings are relevant to control the spread of the disease. This study provides preliminary risk assessments for the further investigation of the environmental risk factors associated with MERS-CoV clusters.

Mechanisms of action of metformin with special reference to cardiovascular protection.

Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.