Israel Medical Association Journal

Background: Since the implementation of a hepatitis A virus (HAV) immunization program for children, which began in 1999 in Israel, HAV infections in the country have occurred mostly in adults. HAV infection in adults is usually symptomatic and may present with hepatic, as well as extrahepatic, abdominal complications.

Objectives: To estimate the prevalence of extrahepatic abdominal complications in patients diagnosed with HAV.

Methods: Most extrahepatic abdominal complications corresponding to HAV infection have ultrasonographic manifestations; therefore, we retrospectively collected findings from ultrasound examinations in addition to laboratory data from adult patients with HAV infection who were admitted to our medical center between 2004 and 2016. Associations between ultrasonographic findings and laboratory parameters that reflect disease severity were identified.

Results: A total of 43 consecutive adult patients were included in this study. None presented with fulminant hepatic failure. Thirty patients (70%) had at least one ultrasonographic finding. Ascites was noted in 8 patients, a thickened gallbladder wall was observed in 14, pericholecystic fluid was found in 8, and biliary sludge was observed in 4. Significant associations included the presence of any ultrasonographic finding and peak total bilirubin levels (P = 0.021), the presence of ascites with peak aspartate and alanine aminotransferase levels (P = 0.041 and P = 0.038, respectively), and the presence of biliary sludge and nadir albumin during the HAV disease course (P = 0.037).

Conclusions: Abdominal ultrasonographic findings, such as ascites and gallbladder abnormalities, are frequently observed during acute HAV infection and are significantly associated with disease severity.

Background: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.

Objectives: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.

Methods: A retrospective analysis (2000–2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.

Results: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15–5.99) and revascularization (HR 4.30, 95%CI 2.01–9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl.

Conclusions: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Aging has been associated with perceived lowering of health, especially in post-traumatic individuals. The effects may be more complex or even different for Holocaust survivors as they age due to their inherited resilience and life perspective. A cross-sectional study was conducted of Holocaust survivors and a matched comparison group recruited from the general Israeli population. All participants underwent a personal interview and completed the Cumulative Illness Rating Scale and a survey of subjective Likert-scale questions about perceived health. The study comprised 214 older adults: 107 Holocaust survivors and 107 comparison participants; 101 women and 113 men. The mean age for the participants was 80.7 ± 4.7 years (range 68–93). Holocaust survivors did not differ from comparison subjects in general health measures (mean 51.50 ± 3.06 vs. 52.27 ± 3.24, respectively). However, the Holocaust survivors' subjective health was significantly lower, F (2,211) = 4.18, P < 0.05, and associated with decreased quality of life. The present study demonstrates the complex interplay between general and subjective health and suggests that future interventions need to focus on improving the psychological and social well-being of Holocaust survivors to achieve successful aging.

Background: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease with poor prognosis despite intensive therapy.

Objectives: To discuss the ideal therapy of EBV-associated HLH for adults.

Methods: We retrospectively studied 23 adult patients with EBV-associated HLH at our institution between January 2000 and June 2015. The clinical characteristics, treatment, and prognosis of adult EBV-associated HLH were analyzed. The median age was 38 years (range 18–72).

Results: All patients were found to have high fever, thrombocytopenia, abnormal liver function, elevated ferritin, and lactate dehydrogenase. Leukopenia, anemia, coagulopathy, hypofibrinogenemia, and splenomegaly were found in more than 80% of patients. Ten patients were treated with HLH-2004 protocol. Eventually, 95.7% of patients died of EBV-associated HLH. Non-HLH-2004 treatment and bone marrow suppression may predict early relapse independently, and the poor performance status and high lactate dehydrogenase level can be poor prognostic factors. It was also validated in comprehensive analysis of published articles.

Conclusions: Adult EBV-associated HLH occurs most often in people of Asian descent who are older than 35 years. These patients had a disappointing outcome despite intensive treatment, especially with high lactate dehydrogenase levels, poor performance status, and bone marrow suppression. HLH-2004 protocol has shown a glimmer of hope in the adult populations.

Background: During the past decades, beta thalassemia major (TM) and beta thalassemia intermedia (TI) have transformed from a universally fatal disease at a young age into a chronic disease. This advancement is attributed to improved chelation therapy as well as enhanced management strategies, with focused attention on disease and treatment-related complications.

Objectives: To describe characteristics of adults with thalassemia as well as treatment modalities, disease and treatment-related complications, and socioeconomic information of the patients.

Methods: We preformed a retrospective analysis of 14 adult patients > 35 years of age with TM and TI who were treated at our institute, a single center specializing in the care of adult thalassemia patients living in Israel, between the years 2006 and 2016.

Results: The median age of patients was 37 years and most patients were transfusion-dependent. The median number of chelation therapeutic lines was three, and 85.7% of patients were treated at one point by combination chelation therapy. Most patients suffered from at least some form of endocrine dysfunction (n=12), and four patients developed overt heart failure. Of the patients, 85% had completed at least a high school education, 78% were employed, and 64.2% were married.

Conclusions: Prolonged survival of thalassemia patients in recent years has been accompanied by a new set of challenges for both the patients and the treating staff. Further research is warranted to improve both medical management and the socioeconomic well-being of this unique group of adult thalassemia patients.

Background: Deliberate self-harm (DSH) increases the danger of future suicide death and the risk increases with age. Self-harm in older adults is often associated with greater suicidal intent and lethality. 

Objectives: To investigate clinical and psychosocial variables of older patients (age ≥ 65 years) assessed due to DSH, compared with younger adults.

Methods: Patients admitted to the Emergency Department following DSH during an 8 year period were included.

Results: Of 1149 participants, 187 (16.6%) were older adults (age ≥ 65) and 962 (83.4%) were younger adults (< 65). The older adults reported DSH closer to mid-day (P < 0.01) and suffered more frequently from adjustment disorder and depression. Personality disorders and schizophrenia were less commonly diagnosed (P < 0.001). Prescription medication (sedatives and hypnotics) were a more frequent means (88% vs. 71%) of DSH among older patients. Younger patients with DSH used over-the-counter medications (21.9% vs. 6.4%) three times more than did the older patients (P < 0.01). Past DSH was significantly more frequent in younger adults. Following DSH the older patients were frequently admitted for further general hospitalization (P < 0.001). 

Conclusions: Older adults with DSH are a unique group with different clinical characteristics. There is a need for targeted prevention strategies and education of caregivers regarding DSH in older adults.

 

Background: Guidelines recommend hepatitis B virus (HBV) vaccination of all adults positive for human immunodeficiency virus (HIV). Immune responses to single-antigen HBV vaccine among HIV-positive patients are low when compared with HIV-negative adults. Sci-B-Vac™ is a recombinant third-generation HBV that may be advantageous in this population.

Objectives: To examine the immune responses to Sci-B-Vac among HIV-positive adults.

Methods: We conducted a prospective cohort study involving HIV-positive adults who had negative HBV serology (HBSAg, HBSAb, HBcoreAb). Sci-B-Vac at 10 µg/dose was administered intramuscularly upon recruitment and after 1 and 6 months. HBSAb levels were checked 1 month after each dose; a level > 10 mlU/ml was considered protective. Data regarding age, gender, CD4 level, and viral load were collected.

Results: The study group comprised 31 patients. Average CD4 count was 503 ± 281 cells/ml, and average viral load was 44 copies/ml. Median interquartile range (IQR) HBVAb titers after the first, second and third immunizations were 0 (0, 3.5), 30 (6, 126) and 253 (81, 408) mlU/ml. Significant titer elevations were found between the second and third immunizations (P = 0.0003). The rate of patients considered protected was 16% after the first, 65% after the second (P < 0.0001), and 84% after the third dose (P = 0.045). No adverse events were reported. More patients under the age of 40 years responded to the first immunization (28% vs. 0%, P = 0.038). CD4 level had no influence on immunization rates.

Conclusions: Sci-B-Vac might achieve better immunization rates among HIV-positive adults compared to the single-antigen vaccine and thus deserves further evaluation in a randomized, double-blind study in this population.

Background: Reference ranges for adult peripheral blood lymphocyte subsets have been established in a few countries. To the best of our knowledge no broad lymphocyte subset analysis of the Israeli population has been reported. 

Objectives: To establish reference ranges for healthy adults in Israel and to describe age- and gender-specific differences, if present.

Methods: Lymphocyte subsets CD3, CD3/CD4, CD3/CD8, CD3-/CD16+/CD56+, CD3/TCRαβ, CD3/TCRγδ, and CD19 were examined by flow cytometry in 326 subjects. Samples were subdivided according to age and gender.

Results: Women of all ages had a significantly higher percentage and absolute counts of CD3/CD4 cells than their male counterparts. Higher CD3/CD4 cells were observed also in the older population (> 50 years). CD3/CD8 and CD3-/CD16+/CD56+ were higher in males. Older males had a lower total lymphocyte percentage and CD19 cells compared to younger men. No significant gender-related differences were observed in percent and number of CD19, CD3/TCRαβ or CD3/TCRγδ at all ages.

Conclusions: These reference values could be useful in further studies for assessing changes that occur in different populations in human pathology.

 

Background: Patients with type 1 diabetes (T1D) are exempt from conscript military service, but some volunteer for national service. 

Objectives: To evaluate the effect of national service (military or civil) on metabolic control and incidence of acute diabetes complications in young adults with T1D. 

Methods: Clinical and laboratory data of 145 T1D patients were retrieved from medical records. The cohort comprised 76 patients volunteering for national service and 69 non-volunteers. Outcome measures were HbA1c, body mass index-standard deviation scores (BMI-SDS), insulin dosage, and occurrence of severe hypoglycemia or diabetic ketoacidosis (DKA). 

Results: Metabolic control was similar in volunteers and non-volunteers: mean HbA1c at various time points was: 7.83 ± 1.52% vs. 8.07% ± 1.63 one year before enlistment age, 7.89 ± 1.36% vs. 7.93 ± 1.42% at enlistment age, 7.81 ± 1.28% vs. 8.00 ± 1.22% one year thereafter, 7.68 ± 0.88% vs. 7.82 ± 1.33% two years thereafter, and 7.62 ± 0.80% vs. 7.79 ± 1.19% three years thereafter. There were no significant changes in HbA1c from baseline throughout follow-up. BMI and insulin requirements were similar and remained unchanged in volunteers and controls: mean BMI-SDS one year before enlistment age was 0.23 ± 0.83 vs. 0.29 ± 0.95, at enlistment age 0.19 ± 0.87 vs. 0.25 ± 0.98, one year thereafter 0.25 ± 0.82 vs. 0.20 ± 0.96, two years thereafter 0.10 ± 0.86 vs. 0.15 ± 0.94, and three years thereafter 0.20 ± 0.87 vs. 0.16 ± 0.96. Mean insulin dose in U/kg/day one year before enlistment age was 0.90 ± 0.23 vs. 0.90 ± 0.37, at enlistment age 0.90 ± 0.28 vs. 0.93 ± 0.33, one year thereafter 0.86 ± 0.24 vs. 0.95 ± 0.33, two years thereafter 0.86 ± 0.21 vs. 0.86 ± 0.29, and three years thereafter 0.87 ± 0.23 vs. 0.86 ± 0.28. There were no episodes of severe hypoglycemia or DKA in either group. 

Conclusions: Our data indicate that during voluntary national service young adults with T1D maintain metabolic control similar to that of non-volunteers. 

 

Background: Childhood attention deficit hyperactivity disorder (ADHD) is a chronic health problem with significant risk for long-term morbidity in adulthood.

Objectives: We examined long-term outcomes of ADHD in a population-based sample of childhood ADHD cases prospectively assessed as adults.

Methods: Long-term outcomes for 70 adults who were diagnosed with ADHD during childhood were examined and compared with data on the general population.

Results: Most subjects admitted to persistence of ADHD-related symptoms in adulthood, despite discontinuation of regular medical treatment and follow-up. Areas most severely affected by past and ongoing symptoms included driving performance and incidence of motor vehicle accidents, and rates of marriage stability over time. Relatively unaffected were occupational and academic achievements and military service. 

Conclusions: There is a need for outreach and better services for adults who were previously diagnosed with ADHD. 

 

Objectives: To determine whether exposure to the Holocaust from preconception to early infancy is a cause of chronic morbidity in adulthood.

Methods: This pilot study involved 70 European Jews born in countries under Nazi rule (exposed group) during the period 1940–1945 who were interviewed to determine the presence of chronic diseases. A control group of 230 Israeli-born individuals of the same descent, age, and gender distribution were extracted from the Israel National Health Interview Survey-2 (unexposed group). The prevalence of selected risk factors and chronic diseases was compared between the groups.

Results: The prevalence of cardiovascular risk factors and morbidity was significantly higher in the exposed group: body mass index (BMI) (29.06 ± 3.2 vs. 26.97 ± 4.42, P = 0.015), hypertension (62.9% vs. 43%, P = 0.003), dyslipidemia (72.9% vs. 46.1%, P < 0.001), diabetes (32.9% vs. 17.4%, P = 0.006), angina pectoris (18.6% vs. 4.8%, P = 0.001) and congestive heart failure (8.6% vs. 1.7%, P = 0.013). The prevalence of cancer (30.0% vs. 8.7% P < 0.001), peptic ulcer disease (21.4% vs. 7%, P = 0.001), headaches/migraines (24.3% vs. 12.6%, P < 0.001) and anxiety/depression (50.0% vs. 8.3%, P < 0.001) was also higher in the exposed group.

Conclusions: These results suggest that exposure to Holocaust conditions in early life may be associated with a higher prevalence of obesity, dyslipidemia, diabetes, hypertension, cardiovascular morbidity, malignancy and peptic diseases in adulthood. These findings set the stage for further research, which might define those exposed as a high risk group for chronic morbidity.

Methods: In this retrospective multicenter open-label study we examined the efficacy and tolerability of VNS in patients in five adult and pediatric epilepsy centers in Israel. All patients had drug-resistant epilepsy and after VNS implantation in 2006–2007 were followed for a minimum of 18 months. Patients were divided into two age groups: < 21 and > 21 years old.

Results: Fifty-six adults and children had a stimulator implanted in 2006–2007. At 18 months post-VNS implantation, none of the patients was seizure-free, 24.3% reported a reduction in seizures of ≥ 75%, 19% reported a 50–75% reduction, and 10.8% a 25–50% reduction. The best response rate occurred in patients with complex partial seizures. Among these patients, 7 reported a ≥ 75% reduction, 5 patients a 50–75% reduction, 3 patients a 25–50% reduction, and 8 patients a < 25% reduction. A comparison of the two age groups showed a higher reduction in seizure rate in the older group (< 21 years old) than the younger group.

Conclusions: VNS is a relatively effective and safe palliative method for treating refractory epilepsy in both adults and children. It is an alternative treatment for patients with drug-resistant epilepsy, even after a relatively longed disease duration, who are not candidates for localized epilepsy surgery.