Israel Medical Association Journal

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered  in the general population with a reported prevalence of 1% to 5%  However, APS is far more infrequent with a prevalence of 40–50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Background: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. 

Objectives: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process.

Methods: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009–2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression.

Results: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P < 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95%CI 1.3–12.4%, P = 0.014). 

Conclusions: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups. 

 

Background: Transvenous lead extraction can lead to tricuspid valve damage. 

Objectives: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction.

Methods: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR.

Results: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8–93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%).

Conclusions: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined. 

 

Background: High density breast mammography has been associated with a greater risk for breast cancer and an increased likelihood of false negative results. 

Objectives: To assess whether the degree of mammographic breast density correlates with an increased risk for the presence of radiographic findings requiring further histological investigation. 

Methods: Included in the study were 2760 consecutive screening mammograms performed in a large volume, early detection mammography unit. All mammograms were complemented by high resolution ultrasound and interpreted by a single expert radiologist. Breast density (BD) was evaluated using a semi-quantitative 5 grade scale and grouped into low breast density (LBD) and high breast density (HBD) mammograms. Demographic and all relevant obstetric, personal and family history of breast cancer data were recorded. 

Results: Of the 2760 mammograms 2096 (76%) were LBD and 664 (24%) were HBD. Mean age of the LBD and HBD groups was 59 ± 10.5 and 50.9 ± 9.3 years respectively (P = 0.001). Breast density significantly correlated with presence of mammographic findings requiring further histological assessment (8.7% and 12.3% for LBD and HBD respectively, P < 0.01). In women younger than 60 years in whom histological assessment was required due to these findings, malignant pathology was significantly more prevalent in the HBD group (2.3% and 4.1% respectively, P = 0.03). Age, parity, patient history and HBD were identified as independent risk factors for any pathological mammographic finding. 

Conclusions: Highly dense mammography, aside from being an indicator of higher risk for breast cancer, appears to be associated with a significantly higher incidence of findings that will prompt further investigation to achieve a definite diagnosis. 

 

Background: Stroke is a leading cause of death and disability worldwide. The risk factors for stroke overlap those for cardiovascular disease. Atrial fibrillation (AF) is a particularly strong risk factor and is common, particularly in the elderly. Maccabi Healthcare Services (MHS) has maintained a vascular registry of clinical information for over 100,000 members, among them patients with heart disease and stroke. 

Objectives: To determine the prevalence of stroke in MHS, and whether the association of AF and stroke, along with other risk factors, in the Maccabi population is similar to that in published studies.

Methods: Data on stroke and AF patients aged 45 and older were collected from the database for the year 2010, including age, previous transient ischemic attack (TIA), body mass index (BMI), prior myocardial infarction (MI), diabetes, hypertension, anticoagulation and dyslipidemia. A cross-sectional analysis was used to estimate stroke prevalence by AF status. A case-control analysis was also performed comparing a sample of stroke and non-stroke patients. This permitted estimation of the strength of associations for atrial fibrillation and various other combinations of risk factors with stroke. 

Results: Stroke prevalence ranged from 3.5 (females, age 45–54 years) to 74.1 (males, age 85+) per thousand in non-AF members, and from 29 (males, age 45–54) to 165 (males, age 85+) per thousand for patients with AF. AF patients had significantly more strokes than non-AF patients in all age groups. Stroke prevalence increased with age and was significantly higher in males. Multivariable analysis revealed that male gender, increasing age, AF, hypertension, diabetes, and history of TIA were highly significant risk factors for stroke. In addition, for males, dyslipidemia and prior MI were moderately strong risk factors. 

Conclusions: Analysis of the MHS vascular database yielded useful information on stroke prevalence and association of known risk factors with stroke, which is consistent with the epidemiological literature elsewhere. Further analysis of health fund data could potentially provide useful information in the future. 

 

Background: Obstructive sleep apnea (OSA) is a common health problem with an estimated prevalence of 4% among men, many of whom are undiagnosed and untreated. 

Objectives: To compare demographic characteristics, health profiles, risk factors, and disease severity in Arab and Jewish men with OSA syndrome.

Methods: In this cross-sectional study we retrospectively analyzed clinical data from the medical files of men ≥ 22 years old who were referred to the Rambam Medical Center sleep clinic during the period 2001–2009 with a suspected diagnosis of OSA. OSA severity was measured using the apnea-hypopnea index (AHI). Categorical variables were compared using the chi-square test. Relations between OSA severity and a set of independent risk factors were assessed by linear regression analysis.

Results: A total of 207 men were included (39 Arabs, 19%; 168 Jews, 81%). Arab participants were younger than their Jewish counterparts (45.5 ± 8.9 years vs. 49.8 ± 11.8, P = 0.04) and their body mass index (BMI) was higher (33.1 ± 5.1 vs. 30.0 ± 4.4, P = 0.001). OSA severity (AHI score) was higher among Arab men, with low, medium and high severity scores seen in 10%, 33% and 56% of Arab men vs 35%, 29% and 37% of Jewish men, respectively [T(198)=2.39, P = 0.02]. Mean blood oxygen saturation was comparable.

Conclusions: Arab men presenting for evaluation of sleep apnea harbored more severe OSA symptoms, were younger, and had higher BMI compared to Jewish men. Since OSA syndrome evolves for several years until it becomes severe, these findings suggest that Arab men seek medical assistance later than Jewish men with OSA.

 

Abstract

Background: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life.

Objectives: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients.

Methods: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009.

Results: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs.45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04–1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01–1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26–2.24, P < 0.001) significantly increased one year mortality risk.

Conclusions: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.

Background: Late nephrology referral, before initiation of dialysis treatment, is associated with adverse outcome.

Objectives: To investigate the implications of late nephrology referral on mortality among dialysis patients in Israel.

Methods: We retrospectively analyzed 200 incident dialysis patients. Patients were defined as late referrals if they started dialysis less than 3 months after their first nephrology consultation. Survival rates and risk factors for mortality were analyzed

Results: The early referral (ER) group comprised 118 patients (59%) and the late referral (LR) group 82 patients (41%). The mortality rate was 44.5% (53 patients) in the ER and 68% (n=56) in the LR group. The 4 year survival rate was 41.1% in the ER and 18.7% in the LR group (P < 0.0001). The mortality rate increased with late nephrology referral (HR 1.873, 95%CI 1.133–3.094), with age (HR 1.043 for each year, 95%CI 1.018–1.068), with diabetes (HR 2.399, CI 1.369-4.202), and with serum albumin level (HR 0.359 for an increase of each 1 g/dl, 95%CI 0.242–0.533). The median survival time was higher for the ER group in women, in patients younger than 70, and in diabetic patients. A trend for longer survival time was found in non-diabetic patients. Survival time was not increased in early referred patients older than 70 and in male patients.

Conclusions: Late nephrology referral is associated with an overall higher mortality rate in dialysis patients. The survival advantage of early referral may have a different significance in specific subgroups. The timing of nephrology referral should be considered as a modifiable risk factor for mortality in patients with end-stage renal disease. 

Objectives: To assess the relationship between sleep deprivation, key metabolic markers, and professional performance in medical residents.

Methods: We compared 35 residents working the in-house night shift with 35 senior year medical students in a cross-sectional cohort study. The Epworth Sleepiness Scale (ESS) questionnaire was administered and blood tests for complete blood count (CBC), blood chemistry panel, lipid profile and C-reactive protein (CRP) were obtained from all participants.

Results: Medical students and medical residents were comparable demographically except for age, weekly working hours, reported weight gain, and physical activity. The ESS questionnaires indicated a significantly higher and abnormal mean score and higher risk of falling asleep during five of eight daily activities among medical residents as compared with medical students. Medical residents had lower high density lipoprotein levels, a trend towards higher triglyceride levels and higher monocyte count than did medical students. CRP levels and other laboratory tests were normal and similar in both groups. Among the medical residents, 5 (15%) were involved in a car accident during residency, and 63% and 49% reported low professional performance and judgment levels after the night shift, respectively.

Conclusions: Medical residency service was associated with increased sleepiness, deleterious lifestyle changes, poorer lipid profile, mild CBC changes, and reduced professional performance and judgment after working the night shift. However, no significant changes were observed in CRP or in blood chemistry panel. Larger prospective cohort studies are warranted to evaluate the dynamics in sleepiness and metabolic factors over time.

 Background: Burn injuries are extremely common and may impose a serious load on public health around the world.

 Objectives: To compare mortality rates and length of hospitalization according to the identified risk factors, extent of burn, gender and age.

Methods: In this retrospective study, data from 558 archive files of hospitalization due to burns as the diagnosis in patients of all ages, between the years 2001 and 2002, were analyzed to identify the risk factors for mortality and length of hospitalization.

Results: Males comprised 62.4% of the hospitalized burn patients. The mortality rate was 3.2% (n=18) and among them 55.6% were women. Fifty percent of the fatality cases were over 48 years old, with statistically significant correlation of mortality rate and age. Most of the fatality cases (66.7%) had burns with total burn surface area (TBSA) larger than 40%. The multiple logistic regression model showed that leukocyte count on admission, TBSA, and age are the most important predictors of mortality. Smoke inhalation was not found to be an independent risk factor.

Conclusions: Using a statistical model for estimating the mortality rate, this study found that white blood cell count at admission, TBSA, and age were the most significant predictors of mortality. 

Objectives: To study the effects of purified allicin on the cardiovascular system.

Methods: Spontaneously hypertensive rats treated for 6 weeks with a daily dose of 80 mg/kg/day of purified allicin added to their chow were compared to control rats that were fed regular chow. Weight, systolic blood pressure (SBP), triglycerides, cholesterol, insulin and adiponectin were measured at baseline and at the end of the study.

Results: Allicin had no effect on body weight whereas it reduced SBP significantly from 190 ± 7.5 mmHg to 168 ± 5.7 (P < 0.0001) and triglyceride levels from 96 ± 25 mg/dl to 71 ± 19 (P =0.009). Allicin had no effect on plasma cholesterol, insulin and adiponectin levels.

Conclusions: Allicin lowers blood pressure and triglyceride levels in spontaneously hypertensive rats. This effect is not mediated through weight loss.

Background: Alcohol consumption in Israel has increased over the last 20 years. Patients with alcohol use disorder (AUD) who present at a hospital enable early intervention. Objectives: To examine, for the first time, the characteristics of AUD patients in an Israeli general hospital, including whether their alcohol use is documented in their file.

Methods: A group of 178 consecutive patients referred for psychiatric consultation was compared to a second group of 105 hospitalized patients who were not referred. These two groups were studied to compare risk factors for AUD. Patients in both groups were prospectively interviewed using a CAGE questionnaire, demonstrated as an effective screening instrument for AUD. Patients' files in both groups were examined for documentation of alcohol use.

Results: There was no significant difference between the prevalence of AUD in the two groups. The groups were then merged since no significant difference in the risk factor effects between the two groups was found. The risk factors for AUD in the final statistical analysis were lower educational status, living alone, being born in the Former Soviet Union and weaker religious observance. Post-traumatic stress disorder (PTSD), cigarette smoking and substance use were found to be independent risk factors. Soldier status was associated with significant alcohol misuse and AUD (CAGE1–4). Alcohol consumption was documented in the files of AUD patients in 48% of the first group and 21% of the second.

Conclusions: Physicians often neglect to take a history of alcohol consumption. Routine use of the CAGEquestionnaire is recommended in Israeli general hospitals. Special attention should be given to PTSD patients and to soldiers.