Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in rheumatoid arthritis

Objectives:

To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors.

Methods:

Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs was almost the same among Saudis and non-Saudis with no significant difference (p>0.05) for each DMARD; MTX was the most commonly used DMARD (71-76%).

Results:

There was no association between anti-MCV positivity and different DMARDs use. Methotrexate was used 76 times as combination, scoring the highest in this respect. There was a significant correlation (p<0.05) between Plaquenil with Methotrexate and with Sulfasalazine; Leflunomide with anti-TNF and with Prednisolone; age with Methotrexate and with Plaquenil; anti-MCV positivity with Prednisolone. Saudi/non-Saudi status showed no correlation with all factors or drugs. There was no significant association between DMARDs and comorbidity.

Conclusion:

Similar to worldwide results, MTX was the most commonly used DMARD; with the addition of anti-TNF to increase the effect, and folic acid to minimize the side effects. In this cohort, the pattern of use for all DMARDs was similar among Saudis and non-Saudis; treatment depended neither on anti-MCV positivity nor on the presence of comorbid conditions. A study of the association of DMARDs with disease activity is recommended.The effective treatment of rheumatoid arthritis (RA) can be achieved by disease-modifying antirheumatic drugs (DMARDs) that decrease joint damage with improvement of symptoms and functional abilities.1 The DMARDs have been classified into synthetic (sDMARDs) and biological.2 The sDMARDs are traditional drugs; such as methotrexate (MTX), sulfasalazine, leflunomide, and hydroxychloroquine (Plaquenil).2 The sDMARDs also include synthetic glucocorticoids (such as Prednisolone).3 If an sDMARDs is not effective after a trial of 3 months,4 they are usually combined with a biological DMARD, such as tumor necrosis factor alpha (TNF-α) blockers.1 To achieve disease remission in approximately 50 of people and improved overall outcomes, the DMARDs should be started very early in the disease.5 The frequently used DMARDs include MTX (the most commonly used one), Plaquenil (hydroxychloroquine), Azulfidine (sulfasalazine), and Arava (leflunomide), either as monotherapy, or in combination.1 Methotrexate is the most commonly used DMARD wordwide,6,7 and is the first line of treatment;8-10 even according to the treatment guidelines from the American College of Rheumatology (2012),11 and the European League Against Rheumatism (2010).12 Methotrexate is usually combined with folic acid (a vitamin),13 in order to reduce its adverse effects including nausea, vomiting or abdominal pain (gastrointestinal), hematologic, pulmonary, and hepatic.10 Methotrexate is teratogenic, thus, pregnancy should be avoided.8,10 Prednisolone (a synthetic glucocorticoids) can be used in the short term, while waiting for slow-onset drugs to take effect,1 and also as an injections into individual joints.1 Although its long-term use reduces joint damage, it also results in osteoporosis and susceptibility to infections, and thus is not recommended.1 A better effect can be achieved by combining MTX with anti-TNF than with MTX monotherapy.14 The response rate is better when switching from MTX monotherapy to MTX plus anti-TNF than combined DMARDs to MTX plus anti-TNF.14 In this study, our aim was to determine the pattern of disease modifying antirheumatic drugs use, and their association with anti-mutated citrullinated vimentin antibody (anti-MCV) in rheumatoid arthritis patients.     

Calcium Antagonists in Patients with Type 2 Diabetes and Hypertension

Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require.     

Deletion of the lon gene augments expression of Salmonella Pathogenicity Island (SPI)-1 and metal ion uptake genes leading to the accumulation of bactericidal hydroxyl radicals and host pro-inflammatory cytokine-mediated rapid intracellular clearance

ABSTRACT

In the present study, we characterized the involvement of Lon protease in bacterial virulence and intracellular survival in Salmonella under abiotic stress conditions resembling the conditions of a natural infection. Wild type (JOL401) and the lon mutant (JOL909) Salmonella Typhimurium were exposed to low temperature, pH, osmotic, and oxidative stress conditions and changes in gene expression profiles related to virulence and metal ion uptake were investigated. Expression of candidate genes invF and hilC of Salmonella Pathogenicity Island (SPI)-1 and sifA and sseJ of SPI-2 revealed that Lon protease controls SPI-1 genes and not SPI-2 genes under all stress conditions tested. The lon mutant exhibited increased accumulation of hydroxyl (OH·) ions that lead to cell damage due to oxidative stress. This oxidative damage can also be linked to an unregulated influx of iron due to the upregulation of ion channel genes such as fepA in the lon mutant. The deletion of lon from the Salmonella genome causes oxidative damage and increased expression of virulence genes. It also prompts the secretion of host pro-inflammatory cytokines leading to early clearance of the bacteria from host cells. We conclude that poor bacterial recovery from mice infected with the lon mutant is a result of disrupted bacterial intracellular equilibrium and rapid activation of cytokine expression leading to bacterial lysis.     

Fructose-1,6-bisphosphatase deficiency with confirmed molecular diagnosis: An important cause of hypoglycemia in children

Objectives:To draw attention towards fructose-1,6-bisphosphatase (FBPase) deficiency as an important cause of hypoglycemia and lactic acidosis and to implement preventive strategies.Methods:This observational, cross-sectional study was conducted on 7 Saudi patients with genetically confirmed FBPase deficiency from 2008 to 2018 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Results:Participants ranged in age from 1-10 years, and all presented with recurrent hypoglycemia. All but one had associated severe metabolic acidosis, and 3 patients (42.9%) presented with hypoglycemia and severe acidosis since birth. The mean duration from presentation to diagnosis was 39.4 months, as other diagnoses, like glycogen storage diseases and mitochondrial diseases needed to be ruled out. Development was normal apart from speech delay in one patient with a novel variant of the FBP1 gene. All patients have homozygous variants in the FBP1 gene.Conclusion:Fructose-1,6-bisphosphatase is an important cause of hypoglycemia and acidosis; therefore, it is important to offer early molecular diagnostics in any child presenting with these symptoms. Molecular diagnostics should always be undertaken to confirm the diagnosis and for further preventive strategies.     

Oncology research in Saudi Arabia over a 10-year period: A synopsis

Objectives:To assess the quality and quantity of Saudi publications in oncology over a 10-year period.Methods:A systematic PubMed search was conducted between January 2008 and December 2017 to retrieve all Saudi oncology publications. Data about the articles was collected. The level of evidence (LOE) was independently assessed by 2 authors. Two 5-year periods (2008-2012 and 2013-2017) were compared using the relevant parameters. Clinicaltrials.gov was also searched for all oncology trials registered in Saudi Arabia.Results:A total of 839 publications met our inclusion criteria. The most common type of research was case series, totaling 32% of all publications. Clinical trials formed less than 2% of the total. The LOE was I, II, III, and IV in 0.3%, 2.1%, 58.4%, and 39.3% of the included publications, respectively. The LOE was the same in the 2 periods. There were more publications in international journals (p=0.004), more international collaborations (p=0.001), and higher journal impact factors (p=0.037) in 2013-2017 than in 2008-2012. Only 76 registered clinical trials were found in the Clinicaltrials.gov registry.Conclusion:Despite an increase in the number of Saudi publications in the field of oncology over time, the LOE did not change. There were, however, some improvements in the international collaboration and journal impact factor, as well as an increase in the number of studies published in international journals. These observations call for a national strategy to improve oncology research in Saudi Arabia.