Israel Medical Association Journal

Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix®, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1)pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed “black box” attitude towards all vaccines. The focus of this review article is to revisit this “black box” using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

The increasing use of computerized medical records has made the clinical data of the entire population available for epidemiological research. The resultant accessibility to this information mandates careful adaptions of ethical guidelines regarding the handling of clinical data. At the same time it grants a unique opportunity to explore the clinical nature of health and disease in large populations across all of society’s strata, socioeconomic levels, ethnicities, and geographic locations regardless of their vicinity or distance to tertiary care centers. Analysis of large databases allows us to learn the public‘s behavior towards medical services and to investigate how medical interventions affect outcomes over time. Moreover, interaction between different co-morbidities can also be better understood by large population studies. The huge numbers of patients involved in these studies provide a good model of multivariate analysis, a statistical tool that by following proper population adjustments underlines the true independent associations between different conditions. Nevertheless, the limitations of these studies should be borne in mind, such as in-built imprecision of diagnoses, incompleteness of the medical data, and the fact that these databases were initially planned for clinical and not investigational use. 

Background: The role of autoimmune factors in the etiology of coronary artery disease (CAD) was suggested in numerous studies but has not been definitively determined.

Objectives: To assess the possible influence of antiphospholipid and antinuclear antibodies on atherosclerosis development in young patients after myocardial revascularization procedures.

Methods: The study group included 39 patients younger than 45 years with coronary artery disease (CAD) who underwent myocardial revascularization. Serum levels of antiphospholipid (aPL), antinuclear (ANA) and antineutrophil cytoplasmatic (ANCA) antibodies were tested within 1 month after the procedure.

Results: All three types of aPL were significantly higher in CAD patients when compared to healthy controls: anti-β2-glycoprotein I (aβ2GPI), both immunoglobulin (Ig)G and IgM classes (median 4.10 SGU, range 3.45–21.63 vs. 0.76, 0.12–6.01, P < 0.001, and 2.82 SGU, 1.44–11.70 vs. 1.08, 0.44–3.64, P < 0.001, respectively); anticardiolipin antibodies (aCL) both IgG and IgM classes (3.13 GPL, 1.32–14.03 vs. 2.42, 0.96–18.45, P = 0.0037, and 6.94 MPL, 1.90–26.40 vs. 4.32, 1.9–28.73, P < 0.008, respectively); and lupus anticoagulant (LA) (27.7% vs. 0%, P = 0.005). ANA were elevated in one patient and ANCA in 23 (60%). The levels of aPL did not correlate with the presence of a clot in a coronary vessel detected during angiography or with exacerbation of coronary artery atherosclerosis.

Conclusions: In young patients with CAD who underwent myocardial revascularization the levels of aPL were significantly higher than in young healthy subjects. Thus, besides the classic risk factors for CAD, autoimmunity may play an important role in atherosclerotic plaque formation and progression.

Background: Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response.

Objectives: To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. 

Methods: The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA.

Results: At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in both groups, while a significant increase (P < 0.001) in CTX-II serum levels was observed in the mud-bath group after the treatment.

Conclusions: A cycle of mud-bath therapy added to usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed only a significant increase of CTX-II, perhaps due to an increase of cartilage turnover induced by thermal stress.

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected, and includes corticosteroids, azathioprine, interferon, cyclophosphamide, methotrexate or tumor necrosis factor-alpha and interleukin-1 blockers. We present a case series of four refractory BD patients successfully treated with intravenous immunoglobulins (IVIG). All patients fulfilled International Study Group criteria. The patients’ mean age was 38.75 ± 12.09 years and mean disease duration 10.25 ± 8.5 years. Human leukocyte antigen B51 was positive in two of four patients. In addition to oral aphthosis, all patients suffered from genital ulcers and cutaneous BD-related manifestations; central nervous system involvement and arthralgia were found in two patients. Peripheral nervous system, gastrointestinal and eye involvement occurred in 25% of cases. In all patients, previously treated according to EULAR recommendations without reaching satisfactory results, IVIG induced immediate and sustained response over time without incurring any side effects. We propose IVIG administration as an additional effective and safe treatment option in patients with severe and resistant BD.

We present a literature review of collaborative enterprises between psychiatrists and primary care physicians in Israel and other countries. Also described are local psychiatric liaison initiatives in Israel, as well as landmark studies of collaborative psychiatric care. These studies demonstrate the superiority of community psychiatric liaison models in the treatment of patients suffering from depressive anxiety disorders and somatization disorder. In light of the mental health reform process currently underway in Israel, it is important to develop, implement and assess such liaison models. 

Background: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable.

Objectives: To evaluate the association of biomarkers with coronary and carotid disease.

Methods: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P < 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated.

Conclusions: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

 

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Background: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.

 

Background: Left ventricular outflow tract (LVOT) arrhythmias are increasingly recognized. Data regarding the distribution of the sites of origin (SOO) of the arrhythmias are sparse.

Objectives: To describe the clinical characteristics of patients with LVOT arrhythmias and the distribution of their SOO. 

Methods: All 42 consecutive patients with LVOT arrhythmias who underwent radiofrequency (RF) ablation during the period 2000–2014 were included. SOO identification was based on mapping activation, pace mapping and a 3D mapping system in eight patients. 

Results: The study group comprised 28 males (66.7%) and 14 females, the mean age was 55 ±15.4 years. Most patients (76%) were symptomatic. All suffered from high grade ventricular arrhythmias. Left ventricular (LV) dysfunction (ejection fraction ≤ 50%) was observed in 15 patients (35.7%), of whom 14 (93.3%) were males. The left coronary cusp (LCC) was the most common arrhythmia SOO (64.3%). Other locations were the right coronary cusp (RCC), the junction of the RCC-LCC commissure, aortic-mitral continuity, endocardial-LVOT, and a coronary sinus branch. Acute successful ablation was achieved in 29 patients (69%) and transient arrhythmia abolition in 40 (95.2%). There was a trend for a higher success rate using cooled tip ablation catheters as compared to standard catheters. The ablation procedure significantly improved LV function in all patients with tachycardiomyopathy. 

Conclusions: LVOT arrhythmias mostly originate from the LCC and are associated with LV dysfunction in 36% of patients. Knowledge regarding the prevalence of the anatomic origin of the LVOT arrhythmias may help achieve successful ablation. The use of cooled tip ablation catheters might have beneficial effects on the success rate of the procedure.

 

Background: Prolonged life expectancy has increased the number of elderly high risk patients referred for surgical aortic valve replacement (AVR). These referred high risk patients may benefit from sutureless bioprosthesis procedures which reduce mortality and morbidity.

Objectives: To present our initial experience with sutureless aortic bioprotheses, including clinical and echocardiographic results, in elderly high risk patients referred for AVR. 

Methods: Forty patients (15 males, mean age 78 ± 7 years) with symptomatic severe aortic stenosis underwent AVR with the 3F Enable™ or Perceval™ sutureless bioprosthesis during the period December 2012 to May 2014. Mean logistic EuroScore was 10 ± 3%. Echocardiography was performed preoperatively, intraoperatively, at discharge and at follow-up.

Results: There was no in-hospital mortality. Nine patients (22%) underwent minimally invasive AVR via a right anterior mini-thoracotomy and one patient via a J-incision. Four patients underwent concomitant coronary aortic bypass graft, two needed intraoperative repositioning of the valve, one underwent valve exchange due to inappropriate sizing, three (7.5%) had a perioperative stroke with complete resolution of neurologic symptoms, and one patient (2.5%) required permanent pacemaker implantation due to complete atrioventricular block. Mean preoperative and postoperative gradients were 44 ± 14 and 13 ± 5 mmHg, respectively. At follow-up, 82% of patients were in New York Heart Association functional class I and II.

Conclusions: Sutureless AVR can be used safely in elderly high risk patients with relatively low morbidity and mortality. The device can be safely implanted via a minimally invasive incision. Mid-term hemodynamic results are satisfactory, demonstrating significant clinical improvement.

 

Background: Recent studies show that vaccination of health care workers (HCW) might reduce influenza transmission and mortality among hospitalized patients. No studies have compared the incidence of laboratory-proven influenza in vaccinated versus unvaccinated hospital HCW. 

Objectives: To evaluate the effectiveness of influenza vaccination among hospital HCW and to examine the attitudes of this population towards influenza vaccination.

Methods: We performed a prospective cohort study between 1 January and 30 April 2014 of 1641 HCW at our medical center; 733 were vaccinated and 908 not vaccinated. A random sample of 199 subjects was obtained: 97 vaccinated and 102 non-vaccinated. Participating individuals were contacted on a weekly basis during the flu season and were asked to report any respiratory or flu symptoms and, if positive, to undergo a polymerase chain reaction (PCR) test for influenza. 

Results: In the general HCW population, vaccination was more frequent among physicians 298/498 (58%) than among nurses (324/862 (38%) and among males than females. Flu symptoms were reported by 20 of 199 participants, 13 in the non-vaccinated group (12.7%) and 7 in the vaccinated group (7.2%). A positive PCR test for influenza A virus was present in 4 of 20 people tested (20%). All positive cases were from the non-vaccinated group (P = 0.0953). 

Conclusions: Non-vaccinated HCW showed a higher, although not statistically significant, tendency for contracting laboratory-proven influenza than the vaccinated population. The main reasons for vaccination and non-vaccination were personal beliefs and habits. Education efforts are needed to improve compliance. Larger studies could further clarify this issue.