Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M680I 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M680I 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for

Background Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts. Objective In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting. Materials and Methods We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department’s staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician’s real-time responses to alerts generated. Results The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients’ status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders. Conclusion A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.

Innate immunity is one of two immune defence system arms. It is present at birth and does not require ‘learning’ through exposure to foreign organisms. It activates various mechanisms collectively to eliminate pathogens and hold an infection until the adaptive response are mounted. The innate immune system consists of four elements: the epithelial barrier, cells (e.g. macrophages, NK cells), plasma proteins (e.g. complement) and cytokines. These components act in concert to induce complex processes, as well as recruitment, activation and differentiation of adaptive responses. The innate response is more than just the ‘first line of defence’, as it essentially withholds the vast majority of any intruder, has a complex interplay with the adaptive arm and is crucial for survival of the host. Finally, yet importantly, a myriad of diseases has been linked with innate immune dysregulation. In this mini-review we will shed some light on these conditions, particularly regarding autoinflammatory ones.