Screening for Medication Errors and Adverse Events Using Outlier Detection Screening Algorithms in an Inpatient Setting.

OBJECTIVES: To evaluate the potential of a novel system using outlier detection screening algorithms and to identify medication related risks in an inpatient setting. METHODS: In the first phase of the study, we evaluated the transferability of models refined at another medical center using a different electronic medical record system (EMR) on 3 years of historical data (2017-2019), extracted from the local EMR system. Following the retrospective analysis, the system's models were fine-tuned to the specific local practice patterns. In the second, prospective phase of the study, the system was fully integrated in the local EMR and after a short run-in period was activated live. All alerts generated by the system, in both phases, were analyzed by a clinical team of physicians and pharmacists for accuracy and clinical relevance. RESULTS: In the retrospective phase of the study, 226,804 medical orders were analyzed, generating a total of 2731 alerts (1.2% of medical orders). Of the alerts analyzed, 69% were clinically relevant alerts and 31% were false alerts. In the prospective phase of the study, 399 alerts were generated by the system (1.6% of medical orders). The vast majority of the alerts (72%) were considered clinically relevant, and 41% of the alerts caused a change in prescriber behavior (i.e. cancel/modify the medical order). CONCLUSION: In an inpatient setting of a 600 bed computerized decision support system (CDSS) -naïve medical center, the system generated accurate and clinically valid alerts with low alert burden enabling physicians to improve daily medical practice.

[ABDOMINAL PAIN AND SEIZURES - A COLORFUL TURN OF EVENTS].

INTRODUCTION: The porphyria diseases are inherited and may be exacerbated by environmental triggers. The most common symptoms are abdominal pain, constitutional symptoms, and mental symptoms. The diagnosis of acute intermittent porphyria is usually made during an attack. The initial diagnosis of porphyria is made with the help of biochemical tests in the blood, urine and feces. The best diagnostic approach for carriers of the genes for porphyria, regardless of the manifestation of symptoms, is a molecular test of the genetic mutations, according to which the porphyria can be divided into different types.

Histiocytic Sarcoma

BACKGROUND: Histiocytic sarcoma (HS) is a rare hematopoietic malignancy originating from the monocyte/macrophage bone marrow lineage. HS can occur in isolation or in association with other hematological neoplasms such as non-Hodgkin lymphoma (NHL), myelodysplasia, or acute leukemia. Clinically, HS can affect lymph nodes, gastrointestinal tract, skin, bone marrow, and spleen as well as the central nervous system. Most cases of HS follow an aggressive clinical course, with most patients dying of progressive disease within one year of diagnosis.

[AN UNUSUAL DIAGNOSIS OF CHRONIC URTICARIA].

INTRODUCTION: Cutaneous lupus is an autoimmune disease that can be represented individually or as part of the systemic disease, systemic lupus erythematosus (SLE). Initial presentation of skin manifestations, such as chronic urticatia, should raise the possibility that it might be the first manifestation of an active disease, for example SLE. Despite the broad differential diagnosis of chronic urticaria, other plausible diagnosis should be ruled out with complete anamnesis that includes family background, substance exposure, new and chronic drug therapy, serological and immunological blood tests, diagnostic biopsy of the skin and imaging as needed to rule out malignancy. We present a case of a patient with a family history of various autoimmune diseases, who presented with chronic urticatia and joint pain with partial response to steroid therapy over a period of several months.

Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome.

In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.

Neuropsychiatric lupus: a mosaic of clinical presentations.

Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus erythematosus; however, the effect on disease severity, quality of life, and prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus erythematosus may range from mild diffuse ones, to acute life threatening events. Although the underlying mechanisms are still largely unraveled, several pathogenic pathways are identified, such as antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid antibodies and other mechanisms, and cytokine-induced neurotoxicity. In the current review, we describe the old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus. The possible link between neuropsychiatric symptoms and specific mechanisms may help to facilitate our understanding of the disease in the future, thus allowing for better treatment strategies.

Tolerogenic dendritic cells specific for ß2-glycoprotein-I Domain-I, attenuate experimental antiphospholipid syndrome.

Tolerogenic dendritic cells (tDCs) have the potential to control the outcome of autoimmunity by modulating the immune response. The aim of this study was to uncover the tolerance efficacy attributed to beta-2-glycoprotein-I (ß2GPI) tDCs or ß2GPI domain-I (D-I) and domain-V (D-V)-tDCs in mice with antiphospholipid syndrome (APS). tDCs were pulsed with ß2GPI or D-I or D-V derivatives. Our results revealed that ß2GPI related tDCs phenotype includes CD80(high), CD86(high) CD40(high) MHC class II(high). The miRNA profiling encompass miRNA 23b(high), miRNA 142-3p(low) and miRNA 221(low). In addition the ß2GPI related tDCs showed reduced secretion of IL-1ß, IL-12 and IL-23. D-I tDCs treatment was more efficient than ß2GPI tDCs in inducing of tolerance in APS mice, manifested by lowered titers of anti- ß2GPI antibodies (Abs) and reduced percentage of fetal loss. Tolerance induction was accompanied by poor T cell response to ß2GPI, high numbers of CD4 + CD25 + FOXP3 + T-regulatory cells (Treg), reduced levels of IFNγ, IL-17 and increased expression of IL-10 and TGFß. Tolerance was successfully transferred by Treg cells from the tolerized mice to ß2GPI immunized mice. We conclude that predominantly D-I-tDCs and ß2GPI tDCs have the potential to attenuate experimental APS by induction of Treg cells, reduction of anti- ß2GPI Abs titers and increased expression of anti-inflammatory cytokines. We suggest that ß2-GPI-D-I-tDCs may offer a novel approach for developing therapy for APS patients.

Contribution of active surveillance cultures to the control of hospital-acquired carbapenem-resistant Acinetobacter baumannii in an endemic hospital setting.

BACKGROUND: Despite the increasing rates of carbapenem-resistant Acinetobacter baumannii (CRAB) carriage among hospitalized patients in endemic settings, the role of active surveillance cultures and cohorting is still debated. We sought to determine the long-term effect of a multifaceted infection-control intervention on the incidence of CRAB in an endemic setting. METHODS: A prospective, quasi-experimental study was performed at a 670-bed, acute-care hospital. The study consisted of 4 phases. In phase I, basic infection control measures were used. In phase II, CRAB carriers were cohorted in a single ward with dedicated nursing and enhanced environmental cleaning. In phase III large-scale screening in high-risk units was implemented. Phase IV comprised a 15-month follow-up period. RESULTS: During the baseline period, the mean incidence rate (IDR) of CRAB was 44 per 100,000 patient days (95% CI, 37.7-54.1). No significant decrease was observed during phase II (IDR, 40.8 per 100,000 patient days; 95% CI, 30.0-56.7; P = .97). During phase III, despite high compliance with control measures, ongoing transmission in several wards was observed and the mean IDR was 53.9 per 100,000 patient days (95% CI, 40.5-72.2; P = .55). In phase IV, following the implementation of large-scale screening, a significant decrease in the mean IDR was observed (25.8 per 100,000 patient days; 95% CI, 19.9-33.5; P = .03). An overall reduction of CRAB rate was observed between phase I and phase IV (rate ratio, 0.6; 95% CI, 0.4-0.9; P < .001). CONCLUSIONS: The comprehensive intervention that included intensified control measures with routine active screening cultures was effective in reducing the incidence of CRAB in an endemic hospital setting.

Biologic therapy for autoimmune diseases: an update.

Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis.

The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease, septic shock and catastrophic antiphospholipid syndrome.

BACKGROUND: Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. DISCUSSION: There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still's disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. SUMMARY: Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed "Hyperferritinemic Syndrome".

Rates of adherence and persistence with allopurinol therapy among gout patients in Israel.

OBJECTIVE: To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation. METHODS: The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant. RESULTS: A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45-64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease. CONCLUSION: Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations.

Outcomes of ICU patients treated with intravenous immunoglobulin for sepsis or autoimmune diseases.

OBJECTIVES: To evaluate the outcomes of hospitalized patients in two intensive care units (ICU) treated with intravenous immunoglobulin (IVIg) added to standard-of-care therapy. The indications for IVIg therapy were sepsis or autoimmune disease. METHODS: We conducted a retrospective study involving adult patients with sepsis and autoimmune diseases, who received IVIg in the ICU at Wolfson and Sheba Medical Centers. A predefined chart was compiled on Excel to include a complete demographic collection, patient comorbidities, chronic medication use, disease severity scores (Charlson Comorbidity Index; SOFA and APACHE II index scores), indication and dosage of IVIg administration, duration of hospitalization and mortality rates. RESULTS: Patients (n - 111) were divided into 2 groups: patients with sepsis only (n-67) and patients with autoimmune disease only (n-44). Septic patients had a shorter ICU stay, received IVIg early, and had reduced mortality if treated with high dose IVIg. Patients with autoimmune diseases did not have a favorable outcome despite IVIg treatment. In this group, IVIg was administered later than in the sepsis group. CONCLUSIONS: IVIg therapy improved the outcomes for ICU patients with sepsis.

Ferritin and prolactin levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a common demyelnating disorder of the central nervous system (CNS) and ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity. OBJECTIVES: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease. METHODS: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls. RESULTS: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P < 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary-progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing-progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05) CONCLUSIONS: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.

[Mycophenolate mofetil as a novel treatment for lupus nephritis].

Systemic Lupus erythematosus often involves the kidney. Classification created by the World Health Organization (I-V) grades patients with lupus nephritis, as diagnosed by renal biopsy and those with high grade nephritis (III and above) for treatment in order to preserve renal survival. Today the accepted treatment includes combination of steroids and cycLophosphamide. Mycophenolate mofetil (MMF, Cellcept), is an immunosuppressive agent that inhibits the purine de novo synthesis pathway. Mycophenotate mofetil mainly inhibits the proliferation of Lymphocytes and is commonly used for rejection prevention after solid organ transplantations. Three meta-analyses were performed with several hundred patients in each. ALL meta-analyses showed, with statistical significance (p < 0.05), an advantage in remission rates for MMF with a relative risk (RR) of 1.5 to 3.0. All meta-anaLyses reported statisticaLLy significant Lower rates of infectious complications (RR between 0.65 to 0.5) and amenorrhea was seen with a lower rate in all meta-analyses, although it was statically significant only in one. Treatment with MMF is associated with increased rates of gastrointestinal side effects, although only one meta-analysis showed this in a statisticaLly significant manner.