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עמוד בית
Thu, 18.07.24

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September 2014
Ignasi Rodríguez-Pintó MD, Alessandra. Soriano MD, Gerard Espinosa MD PhD, Yehuda Shoenfeld MD FRCP and Ricard Cervera MD PhD FRCP
Smadar Gertel MD and Howard Amital MD MHA

The major autoantigens in the inflamed synovium in rheumatoid arthritis (RA) are citrullinated peptides. Citrullinated peptides are employed in diagnostic kits for detection of anti-citrullinated protein antibodies (ACPA), a serological marker with high specificity and sensitivity in the diagnosis of RA, and have been included in the new ACR/EULAR classification criteria for RA. ACPA-positive RA patients suffer from an erosive and more aggressive disease compared to ACPA-negative patients. In view of the mounting indications that ACPA plays a seminal role in the pathogenesis of RA, it might be valuable to pursue a specific treatment aiming ACPA as a target. We found that citrullinated peptides, which contain a unique amino acid, citrulline, alter the protein structure within the connective tissue, leading to tolerance breakdown and triggering the autoimmune response in RA. However, with different doses and routes of administration, citrullinated peptides can promote immune tolerance rather than induction of disease. 

May 2014
Miriam E. Pepys Vered MB BS and Mark B. Pepys MD PhD FRCP FRCPath FRS FMedSci
Yael Zenziper BPharm, Daniel Kurnik MD, Noa Markovits MD, Amitai Ziv MD MHA, Ari Shamiss MD MPA, Hillel Halkin MD and Ronen Loebstein MD

Background: Prescription errors are common in hospitalized patients and result in significant morbidity, mortality and costs. Electronic prescriptions with computerized physician order entry systems (CPOE) and integrated computerized decision support systems (CDSS providing online alerts) reduce prescription errors by approximately 50%. However, the introduction of CDSS is often met by opposition due to the flood of alerts, and most prescribers eventually ignore even crucial alerts (“alert fatigue”). 

Objectives: To describe the implementation and customization of a commercial CDSS (SafeRx®) for electronic prescribing in Internal Medicine departments at a tertiary care center, with the purpose of improving comprehensibility and substantially reducing the number of alerts to minimize alert fatigue. 

Methods: A multidisciplinary expert committee was authorized by the hospital administration to customize the CDSS according to the needs of six internal medicine departments at Sheba Medical Center. We assessed volume of prescriptions and alert types during the period February–August 2012 using the statistical functions provided by the CDSS. 

Results: A mean of 339 ± 13 patients per month per department received 11.2 ± 0.5 prescriptions per patient, 30.1% of which triggered one or more CDSS alerts, most commonly drug-drug interactions (43.2%) and dosing alerts (38.3%). The review committee silenced or modified 3981 alerts, enhancing comprehensibility, and providing dosing instructions adjusted to the patient’s renal function and recommendations for follow-up. 

Conclusions: The large volume of drug prescriptions in internal medicine departments is associated with a significant rate of potential prescription errors. To ensure its effectiveness and minimize alert fatigue, continuous customization of the CDSS to the specific needs of particular departments is required.

 

Cassandra Ocampo MD, Molebedi L. Segwagwe MB ChB MRCP, Julian Deonarain MB ChB FCPath, Francesca Cainelli MD and Sandro Vento MD
April 2014
Maitseo Kuno Nwako-Mohamadi MBChB BAO MSc, Vidushi Madan MD, Matthew N. Tanko MBBS FMCPath (Nig) and Sandro Vento MD
October 2013
L. Avisar, A. Shiyovich, L. Aharonson-Daniel and L. Nesher
 Background: Sudden cardiac death is the most common lethal manifestation of heart disease and often is the first and only indicator. Prompt initiation of cardiopulmonary resuscitation (CPR) undoubtedly saves lives. Nevertheless, studies report a low competency of medical students in CPR, mainly due to deterioration of skills following training.

Objectives: To evaluate the retention of CPR skills and confidence in delivering CPR by preclinical medical students.

Methods: A questionnaire and the Objective Structured Clinical Examination (OSCE) were used to assess confidence and CPR skills among preclinical, second and third-year medical students who had passed a first-aid course during their first year but were not retrained since.

Results: The study group comprised 64 students: 35 were 1 year after training and 29 were 2 years after training. The groups were demographically similar. Preparedness, recollection and confidence in delivering CPR were significantly lower in the 2 years after training group compared to those 1 year after training (P < 0.05). The mean OSCE score was 19.8 ± 5.2 (of 27) lower in those 2 years post- training than those 1 year post-training (17.8 ± 6.35 vs. 21.4 ± 3.4 respectively, P = 0.009). Only 70% passed the OSCE, considerably less in students 2 years post-training than in those 1 year post-training (52% vs. 86%, P < 0.01). Lowest retention was found in checking safety, pulse check, airway opening, rescue breathing and ventilation technique skills. A 1 year interval was chosen by 81% of the participants as the optimal interval for retraining (91% vs. 71% in the 2 years post-training group vs. the 1 year post- training group respectively, P = 0.08).

Conclusions: Confidence and CPR skills of preclinical medical students deteriorate significantly within 1 year post-training, reaching an unacceptable level 2 years post-training. We recommend refresher training at least every year.

 

September 2013
K. Goldman, S.Gertel and H. Amital
 Anti-citrullinated peptide antibodies (ACPA) are detected in the sera of rheumatoid arthritis (RA) patients and have a profound role in diagnosis of the disease. In this review we discuss the different cohorts of RA patients in whom the presence, sensitivity and specificity of ACPA were evaluated. The significance of ACPA in the pathogenesis and prognosis RA is also interpreted. Recent advances in the understanding of molecular pathways involved in the pathogenesis of RA have led to the identification of novel biologic agents that are now widely used in patients with RA

 

December 2012
M. Shamir, R. Dickstein and E. Tirosh

Background: The effectiveness of intensive versus standard physical therapy for motor progress in children with cerebral palsy is controversial. Sitting acquisition is considered an important developmental milestone.  

Objectives: To assess the acquisition of sitting and gross motor progress in infants with cerebral palsy treated with intermittent intensive physical therapy as compared to a matched group treated with a standard physical therapy regimen.

Methods: We conducted a randomized controlled crossover study in 10 infants aged 12–22 months with cerebral palsy; 5 were assigned to the intensive intermittent therapy group and 5 to the control group. After 4 weeks of baseline intervention, the intervention program was administered to the experimental group for 8 weeks and the regularly scheduled weekly program to the comparison group, targeting sitting as the treatment goal. Thereafter the comparison group crossed over. The Gross Motor Function Measure 66 and 88 (GMFM 66 and 88) were used at 4 week intervals.

Results: The intermittent intensive regimen yielded a mean improvement of 7.8% and 1.2% in the two groups respectively. However, these results were attributed to infants with a low functional level only (P < 0.01).

Conclusions: Goal-directed intensive intermittent regimen could possibly be beneficial in infants with a low functional level.
 

July 2011
O. Tzischinsky, S. Shahrabani and R. Peled

Background: Obstructive sleep apnea syndrome (OSAS) is a sleep-related breathing disorder characterized by excessive daytime sleepiness, accidents and high medical expenses. The first line of treatment for OSAS is continuous positive airway pressure (CPAP).

Objectives: To examine attitudes and beliefs as well as physiological and sociodemographic factors affecting OSA patients' decision whether or not to purchase a CPAP device.

Methods: The study was divided into two stages; in the first, 83 subjects completed self-administered questionnaires prior to sleep examination (polysomnographic study). The questionnaires related to sleep habits, sleep disorders, questions organized around health belief model (HBM) concepts, sociodemographic information, health status and PSG[1] examination. In the second stage, 3 months later, 50 OSAS patients were interviewed by telephone, which included questions about their reasons for purchasing/not purchasing the CPAP device.

Results: Only 48% of the OSAS patients purchased the CPAP device. The significant factors positively affecting the decision included higher levels of physiological factors such as body mass index (coefficient 0.36, P < 0.05) and respiratory disturbance index (coefficient 0.16, P < 0.05), higher income levels (coefficient 3.26, p < 0.05), and higher levels of knowledge about OSAS (coefficient -2.98, P < 0.1).

Conclusions: Individuals who are more aware of their own health condition, are better informed about OSAS and have higher incomes are more likely to purchase the device. We suggest reducing the level of co-payment and providing patients with more information about the severe effects of OSAS.






[1] PSG = polysomnography


May 2011
January 2008
A. Kapitany, Z. Szabo, G. Lakos, N. Aleksza, A. Vegvari. L. Soos, Z. Karanyi, S. Sipka, G. Szgedi and Z. Szekanecz


Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations






[1] RA = rheumatoid arthritis

[2] anti-CCP = anti-cyclic citrullinated peptide

[3] RF = rheumatoid factor

[4] CRP = C-reactive protein

[5] SE = shared epitope


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