The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis

Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, I2 = 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, I2 = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, I2 = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, I2 = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, I2 = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.Open access funded by Qatar National Library

Health in times of uncertainty in the eastern Mediterranean region, 1990�2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100�000 people), which increased by 17·2 since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100�000 people) in 2013, which decreased by 26·9 since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3 since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60�80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7 to 7·5 between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Biomarcadores inflamatórios e de estresse oxidativo em cadelas submetidas à ovário-histerectomia videoassistida ou convencional

RESUMO A videocirurgia é atualmente uma das principais ferramentas operatórias, com vantagens que incluem menor estresse, incisões e dor pós-operatória quando comparada aos procedimentos abertos. Objetivou-se comparar o processo inflamatório e o estresse oxidativo resultantes das técnicas de ovário-histerectomia (OVH) convencional e videoassistida, com dois portais em cadelas, por meio de hemograma, avaliação de acetilcolinesterase, butirilcolinesterase, catalase e malondialdeído séricos, imediatamente antes da operação e duas, seis, 12, 24, 48 e 72 horas após a cirurgia. Observou-se menor estresse cirúrgico nas pacientes operadas pela técnica videoassistida, e sugere-se que a técnica convencional possa implicar peroxidação lipídica, mesmo com o uso de anti-inflamatório

Myxedema psychosis: A protocol for a systematic review and a pooled analysis

Background: Myxedema psychosis (MP) is a rare presentation of hypothyroidism. Although known for >70 years, a significant lack of systematic literature describing this condition exists. This limits the clinician's ability to identify and manage this entity properly. Hence, we aimed to systematically review the literature and summarize the presentation, diagnosis, management, and outcomes of this rare entity. Methods: Systematic review following PRISMA guidance. We will perform a comprehensive search of PubMed, Medline, Embase, Google Scholar (first 300 hits), and Cochrane databases for published observational studies, case series, and case reports. We will use descriptive statistics to provide summary estimates of demographics, common presenting features, laboratory test results, imaging findings, treatment administered, and outcomes. Moreover, continuous variables will be compared by the Wilcoxon Mann Whitney test, whereas categorical variables will be assessed by the χ2 test. Bivariate and multivariate regression will be performed to assess risk factors associated with poor outcome. A scoping review revealed that a meta-analysis might not be feasible owing to the paucity of systematic studies describing the condition. Results: This is the first systematic review examining this rare entity. Thus, the result of which will be significant. We hope that this review will help in identifying relevant predictive clinical or laboratory characteristics. Additionally, it identifies the best treatment strategies. The findings of this review will help increase our knowledge of this condition so as to recognize this condition promptly. Also, it will assist in differentiating MP from masqueraders, such as Hashimoto encephalopathy (HE). The results of this review will be published in a peer-reviewed journal. Conclusion: This is the first systematic review exploring MP demographics, diagnosis treatment, and outcomes. The information gathered by this review will be necessary for patients, clinicians, researchers, and guideline makers. PROSPERO registration number: CRD42020160310.Open-access publication fees were supported by the Qatar National Library

Myxedema psychosis: Systematic review and pooled analysis

Background and Objective: The term myxedema psychosis (MP) was introduced to describe the occurrence of psychotic symptoms in patients with untreated hypothyroidism, but the optimal assessment and treatment of this condition are unclear. We aimed to synthesize data from the literature to characterize the clinical presentation and management of MP. Methods: We performed a systematic review according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines in PubMed (Medline), Embase, Google Scholar, and Cochrane databases, including observational studies, case series, and case reports published from 1/1/1980 to 31/12/2019 in the English language. Descriptive statistics along with univariate and multivariate analysis were used for data synthesis. Results: Out of 1583 articles screened, 71 case reports met our inclusion criteria providing data on 75 MP cases. The median age at diagnosis was 42 years [32–56]. About 53% had no prior hypothyroidism diagnosis. Delusions occurred in 91%, with a predominance of per-secutory ideas (84%), while hallucinations occurred in 78%. Physical symptoms and signs of hypothyroidism were absent in 37% and 26%, respectively. If symptoms occurred, nonspe-cific fatigue was seen most frequently (63%). The median thyroid-stimulating hormone value was 93 mIU/L [60–139]. Thyroid peroxidase antibodies were found positive in 75% (23/33) of reported cases. Creatinine kinase was reported abnormal in seven cases. Cranial imaging (CT or MRI) and electroencephalogram were normal in 89%, 75%, and 73% of the cases reported. The majority of patients were treated orally with thyroxine in combination with short-term antipsychotics. More than 90% of them showed complete recovery. Univariate analysis revealed a trend towards a shorter duration of psychosis with IV thyroid hormone therapy (p= 0.0502), but the effect was not consistent in a multivariate analysis. Conclusion: While we identified a substantial lack of published research on MP, our pooled analysis of case observations suggests that the condition presents a broad spectrum of psychiatric and physical symptoms lending support to the value of screening for thyroid dysfunction in patients with first-ever psychosis. Prospero Registration Number: CRD42020160310

Histomorphometric and functional studies of the rat thyroid throughout the estrous cycle Histomorfometria e função tireoidiana no ciclo estral da rata

The influence of the estrous cycle on the thyroid gland was studied. Twenty one five-to-seven-month-old Wistar female rats were divided according to the stage of the estrous cycle in two groups: metaestrus-diestrus and proestrus-estrus. After gross inspection, the thyroids were weighed, sampled, and processed for staining with hematoxilyn-eosin. Seric concentrations of total T4, free T4, total T3, TSH, progesterone, and estradiol were measured. The values of estradiol were significantly higher in the proestrus-estrus stage. However, no significant differences in the plasmatic concentrations of progesterone, free T4, total T4 and TSH throughout the cycle were found. The results of the morphometric study of the thyroid did not indicate any significant differences between the groups. These findings suggest that there is no thyreotrophic effect of estrogen during the estrous cycle in rats

Prevalence of Venous Thromboembolism in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis. Methods: We performed a systematic review and proportion meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 25/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, in an exploratory analysis, we compared the odds of VTE in patients on prophylactic compared with therapeutic anticoagulation. Results: The review comprised 24 studies and over 2,500 patients. The pooled proportion of VTE prevalence was 0.31 [95% confidence interval (CI) 0.24, 0.39; I2 94%], of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63; I2 91%), of deep venous thrombosis was 0.23 (95% CI 0.14, 0.32; I2 96%), and of pulmonary embolism was 0.14 (95% CI 0.09, 0.20; I2 90%). Exploratory analysis of few studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared with therapeutic anticoagulation [odds ratio (OR) 5.45; 95% CI 1.90, 15.57; I2 0%]. Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages may reduce VTE burden in this patient's cohort compared with standard prophylactic anticoagulation; however, this is to be ascertained by ongoing randomized controlled trials