A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients

Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip® Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A—9.70%. Consequently, we determined that R761H (n?=?23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.     

Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program.

OBJECTIVES: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs). BACKGROUND: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown. METHODS: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (< or =40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months. RESULTS: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm. CONCLUSIONS: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.     

Diagnostic value of screening tests in subgroups of women with recurrent pregnancy loss

Objective: To evaluate the diagnostic value of screening laboratory tests in women who had recurrent pregnancy loss (RPL).

Methods: A total of 252 women with RPL managed in our tertiary referral research and education hospital were included in the study. Risk factors recorded involved age, gravidity, parity, number of prior live births, number of pregnancy losses, and thrombophlia tests. The cases were divided into three different groups and each group was analyzed separately.

Results: There was no statistically significant difference between the first and second groups in terms of clinical and laboratory parameters (p?>?0.05). In the third group, there was a statistically significant difference among cases in terms of parity, gravidity, number of pregnancy losses, serum AT III levels, APCR, and age of the women. According to the logistic regression model, odds ratios (95% CI) were 6.116 (3.797–9.852), 5.665 (2.657–12.079), 4.763 (3.099–7.321), 4.729 (3.080–7.260), 2.820 (1.836–4.333), and 1.911 (1.232–2.965), respectively.

Conclusions: We do not recommend the screening of all women with RPL, but in women with high parity and those who had prior live birth pregnancies, increased AT III, and APCR may be diagnostic markers for subsequent pregnancy loss.     

Psychological Comfort of Paramedics with Field Death Pronouncement: A National Asian Study to Prepare Paramedics for Field Termination of Resuscitation

Objectives: Paramedics' decision to terminate field resuscitation without a physician present may depend on personal and external factors. This study investigates factors associated with paramedic psychological comfort with termination of resuscitation (TOR) to inform future training. Methods: We administered an anonymous survey to all practicing paramedics in a large urban Asian Emergency Medical Services system where formal TOR training had not yet been conducted and field TOR was not routinely applied. The survey assessed psychological comfort using the validated Psychological Comfort Total (PCT) scale (summed score of 28 items, with higher scores representing greater comfort). We examined scores associated with four personal (prior resolution of personal loss, knowledge of survival probability, religious affiliation and experience with death pronouncements) and two external (location of patient and perceived trust of family) factors. Data were entered into Excel and analyzed by t-tests and ANOVA. Results: Response rate was 73.6% (254/345). Respondents were 30.3 years (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60% had been involved in 6 or more field death pronouncements in the prior 12 months. Higher PCT scores were associated with prior resolution of personal loss and knowledge of survival probability. Lower PCT scores were associated with patient location in a public place and perceived family lack of trust. PCT scores were not associated with paramedic religious affiliation or number of prior death pronouncements. Conclusions: Paramedic psychological comfort with field death pronouncement is associated with personal and external factors. Since paramedic comfort is important for protocol adoption, TOR education should target not only knowledge, but also public arena management, communication skills for engaging with families, and help paramedics resolve prior personal loss.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

A joint model for interval‐censored functional decline trajectories under informative observation

Multi‐state models are useful for modelling disease progression where the state space of the process is used to represent the discrete disease status of subjects. Often, the disease process is only observed at clinical visits, and the schedule of these visits can depend on the disease status of patients. In such situations, the frequency and timing of observations may depend on transition times that are themselves unobserved in an interval‐censored setting. There is a potential for bias if we model a disease process with informative observation times as a non‐informative observation scheme with pre‐specified examination times. In this paper, we develop a joint model for the disease and observation processes to ensure valid inference because the follow‐up process may itself contain information about the disease process. The transitions for each subject are modelled using a Markov process, where bivariate subject‐specific random effects are used to link the disease and observation models. Inference is based on a Bayesian framework, and we apply our joint model to the analysis of a large study examining functional decline trajectories of palliative care patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Emotional intelligence and leadership traits among family physicians

Objectives: High emotional intelligence and leadership traits are essential for physicians in managing their responsibilities and thus building successful interactions with patients. This study explored the relationship between emotional intelligence and leadership traits among family physicians.

Methods: Participants (2975 men, 972 women, mean = 42.0 ages, SD = 7.47) were family physicians working at family health-care centers across the seven geographical regions of Turkey who were contacted by e-mail. The Trait Emotional Intelligence Questionnaire (TEIQue) and Leadership Traits Tool were used to collect data. Data were analyzed concerning physicians’ sex, age, health-care experience, and geographical region. The correlation between Trait Emotional Intelligence (TEI) and leadership was also being examined.

Results: Our findings suggest that family physicians’ TEI differs based on sex, age, health-care experience, and the geographical region where they work. Women had higher mean values than did men for well-being, emotionality, and global TEI. Physicians aged younger than 29 years had the lowest mean values for emotional intelligence. As physicians’ health-care experience increased, they received higher scores for emotional intelligence. Physicians working in the Mediterranean had the highest mean TEI scores. There was a positive correlation between family physicians’ emotional intelligence and leadership traits. Higher emotional intelligence was correlated with increased leadership traits.

Conclusion: Emotional intelligence and leadership traits play crucial roles in increasing physicians’ personal and professional development. This may also increase physicians’ caregiving competencies and thus the quality of health services, as well as potentially decreasing physicians’ burnout and health-related costs.     

Lipid-Lowering Biotechnological Drugs: from Monoclonal Antibodies to Antisense Therapies—a Clinical Perspective

Purpose

While low density lipoprotein cholesterol (LDL-C) remains a key contributor of atherosclerotic cardiovascular disease (ASCVD), additional risk factors identified through epidemiological and genetic studies have ushered in a fertile era of drug discovery in lipid-lowering therapy. Unlike contemporary small molecule medications, many of the novel agents are biologics utilizing monoclonal antibody (mAb) or RNA interference (RNAi) technologies. This report aims to review the evidence to date, focusing on completed and ongoing clinical trials and how these new agents will impact clinical practice.

Methods

We review data from pertinent studies on lipid-lowering biologics in clinical use or have translated to human studies and are undergoing clinical trials.

Results

Several targets affecting lipid metabolism have been identified to be causally associated with ASCVD including proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C3 (APOC3), and lipoprotein (a) (Lp[a]). Biotechnological modalities that have been developed for these targets include mAb, small interfering RNA (siRNA), and anti-sense oligonucleotide (ASO) agents. Agents such as alirocumab and evolocumab have shown efficacy in risk reduction of ASCVD in cardiovascular outcome trials and have been incorporated into evidence-based practice guidelines. Other agents included in this review are in various stages of clinical trials and have shown significant efficacy in the reduction of lipid parameters.

Conclusion

The development of new biologics targeting lipid risk factors will provide clinicians additional tools to reduce the risk for ASCVD. Important factors to consider will be cost-effectiveness and improving methods to personalize treatments to risk factors.