Biosimilars in rheumatology: recommendations for regulation and use in Middle Eastern countries

The increasing availability of biosimilar medicines in Middle Eastern regions may provide an opportunity to increase the number of rheumatology patients who have access to traditionally more expensive biologic medicines. However, as well as a lack of real-world data on the use of biosimilar medicines in practice, the availability of intended copies in the region may undermine physician confidence in prescribing legitimate biosimilar medicines. There is a need for regional recommendations for healthcare professionals to ensure that biosimilar drugs can be used safely. Therefore, a literature search was performed with the aim of providing important recommendations for the regulation and use of biosimilar medicines in the Middle East from key opinion leaders in rheumatology from the region. These recommendations focus on improving the availability of relevant real-world data, ensuring that physicians are aware of the difference between intended copies and true biosimilars and ensuring that physicians are responsible for making any prescribing and switching decisions.     

Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers.

OBJECTIVES: This study prospectively evaluated the relationship between cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the progression of coronary artery calcification (CAC) in type 2 diabetic subjects. BACKGROUND: Coronary artery calcification is pathognomonic of coronary atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone remodeling that has been implicated in the regulation of vascular calcification and atherogenesis. METHODS: Three hundred ninety-eight type 2 diabetic subjects without prior coronary disease or symptoms (age 52 +/- 8 years, 61% male, glycated hemoglobin [HbA(1)c] 8 +/- 1.5) were evaluated serially by CAC imaging (mean follow-up 2.5 +/- 0.4 years). Progression/regression of CAC was defined as a change > or =2.5 between the square root transformed values of baseline and follow-up volumetric CAC scores. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured at baseline and follow-up. RESULTS: Two hundred eleven patients (53%) had CAC at baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3 patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC, HbA(1)c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were univariable predictors of CAC progression. In the multivariate model, baseline CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to 15.5, p < 0.001), HbA(1)c >7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC progression. CONCLUSIONS: Baseline CAC severity and suboptimal glycemic control are strong risk factors for CAC progression in type 2 diabetic subjects.     

Effectiveness of primary percutaneous coronary intervention for acute ST-elevation myocardial infarction from a 5-year single-center experience

Primary percutaneous coronary intervention (PCI) is currently viewed as the preferred reperfusion strategy in patients with ST-elevation acute myocardial infarction (STEMI). This method was introduced in our hospital in 2000. From January 1, 2000, to December 31, 2004, a total of 2,393 consecutive patients with STEMI were admitted (27% transferred from 9 non-PCI hospitals and 31 prehospital emergency units/outpatient clinics). Of these patients, 1,666 (70%) underwent urgent coronary angiography and primary PCI. Platelet glycoprotein llb/llla inhibitors were used in 40% and stent placement, in 78%. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow was documented in 86%. Intra-aortic balloon counterpulsation was used in 6%; mechanical ventilation, in 8.6%; and inotropic drugs/vasopressors, in 15.8%. Mortality rates in patients with Killip's class I or II ranged from 1% to 4.9% without negative influence of ischemic time. In patients with Killip's class III or IV, mortality rates increased from 18% to 54% with increasing ischemic delay up to 6 hours (p = 0.06) and remained at around 40% afterward. Independent predictors of mortality were age (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p = 0.04), resuscitated cardiac arrest (OR 2.44, 95% CI 1.18 to 5.05, p = 0.02), and postprocedural TIMI flow (OR 0.31, 95% CI 0.16 to 0.59). Overall mortality rates of patients who underwent a primary PCI strategy from 2000 to 2004 were significantly lower than in the control group of 152 consecutive patients who underwent thrombolysis from 1995 to 1996 (6.2% vs 16.4%; p <0.001). In conclusion, introduction of a primary PCI strategy significantly decreased hospital mortality in our unselected group of patients with STEMI compared with the thrombolytic era. Our study further emphasized the importance of shortening myocardial ischemic time, particularly in the presence of severe heart failure on admission.     

Kir6.2 is required for adaptation to stress

Reaction to stress requires feedback adaptation of cellular functions to secure a response without distress, but the molecular order of this process is only partially understood. Here, we report a previously unrecognized regulatory element in the general adaptation syndrome. Kir6.2, the ion-conducting subunit of the metabolically responsive ATP-sensitive potassium (K(ATP)) channel, was mandatory for optimal adaptation capacity under stress. Genetic deletion of Kir6.2 disrupted K(ATP) channel-dependent adjustment of membrane excitability and calcium handling, compromising the enhancement of cardiac performance driven by sympathetic stimulation, a key mediator of the adaptation response. In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart.     

Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy

The objective of this study was to assess the efficacy and safety of amitriptyline as a treatment of FM. A comprehensive computerized search in Medline (Pubmed), EMBASE and The Cochrane Library was performed. Randomized controlled trials (RCTs) comparing amitriptyline vs placebo in adult patients suffering from FM were identified, the methodological quality was assessed and the results of the main outcomes were evaluated. Ten RCTs were identified. Large clinical variability and statistical heterogeneity precluded quantitative meta-analysis. Overall, the study quality was moderate to high. Amitriptyline 25 mg/day (six RCTs) demonstrated a therapeutic response compared with placebo in the domains of pain, sleep, fatigue and overall patient and investigator impression. This benefit was generally seen at 6-8 weeks of treatment but no effect was noted at 12 weeks. Amitriptyline 50 mg/day (four RCTs) did not demonstrate a therapeutic effect compared with placebo. Neither dose of amitriptyline had an effect on tender points count. No clear statements on adverse events with amitriptyline can be made due to inconsistencies in data among the studies. A definitive clinical recommendation regarding the efficacy of amitriptyline for FM symptoms cannot be made. There is some evidence to support the short-term efficacy of amitriptyline 25 mg/day in FM. There is no evidence to support the efficacy of amitriptyline at higher doses or for periods >8 weeks. More stringent RCTs with longer follow-up periods are required to determine the long-term efficacy and safety of the amitriptyline and define its role in the multidisciplinary management of FM.     

The Cameriere,Haavikko, Demirjian,and Willems methods for the assessment of dental age in Croatian children

International Journal of Legal Medicine - This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental...