Israel Medical Association Journal

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, impulsivity and hyperactivity. Recently, increases in ADHD prevalence and methylphenidate use have been reported. There is evidence that children and adolescents use ADHD medication only during the school year. 

Objectives: To investigate trends in methylphenidate dispensing over a period of 3 years (2010–2012) at the monthly level and to investigate whether there is any monthly variation, especially during the summer season.

Methods: The database of Clalit Health Services (the largest of the four health funds in Israel) was used to identify (i) patients aged 6–17 years with a diagnosis of ADHD, and (ii) methylpenidate dispensation during the period 2010–2012. 

Results: Among children aged 6–17 years diagnosed with ADHD, 43% were treated with methylphenidate. For the period 2010 to 2012 there was an annual drop in methylphenidate dispensing, beginning in June and continuing through the 2 months of summer vacation, with a 2.5-fold reduction from July as compared to May. This decline was consistently followed by a rise in medications dispensed starting August. A similar small drop was observed during the Passover school vacation. The summer drop decreased over the years.

Conclusions: Our findings showed a decrease in the number of methylphenidate prescriptions dispensed during the summer months and Passover as compared to the rest of the year. However, this phenomenon appears to be decreasing. Given that ADHD is a chronic disease state that can effectively be managed with pharmacotherapy, discontinuation of treatment may be harmful for patients and should be considered only on a patient-by-patient basis.

 

Background: Automated breast volumetric sonography (ABVS) is a new technology with various possible applications.

Objectives: To compare ABVS and breast magnetic resonance imaging (MRI) in the surveillance of women with BRCA1/2 gene mutation carriers.

Methods: We conducted a prospective study in Jewish female BRCA1/2 mutation carriers who underwent breast MRI and ABVS. The results of both exams performed 6 months apart or less, and relevant clinical data, were reviewed. The BIRADS results were divided into three subgroups according to subsequent expected management: BIRADS 1-2 (normal study), BIRADS 3 (probably benign finding), and BIRADS 4 and 5 (suspicious findings). BIRADS 0 and 6 scores were excluded from the study. Distribution of ABVS and MRI BIRADS scores were compared using McNemar's test, and concordance was calculated using the Cohen kappa test.

Results: Overall, 68 women, 40 BRCA1 and 28 BRCA2 mutation carriers, age range 26–69 (mean 44.55 ± 12.1 years), underwent 79 paired ABVS and MRI examinations. McNemar's test calculations showed no significant difference between MRI and ABVS BIRADS score distribution. Cohen’s kappa test resulted in k = 0.158, an agreement that can be described as only "slight agreement" between both modalities. Of 14 discordant cases there was one cancer, revealed by MRI and not by ABVS performed 6 months prior to MRI.

Conclusions: ABVS showed slight agreement with MRI in BRCA1/2 mutation carriers. These preliminary results on a small group of healthy high risk patients suggest that the diagnostic abilities of ABVS are inferior to MRI. Further studies encompassing larger groups are needed.

 

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Immune function is the most basic physiological process in humans and indeed throughout the animal kingdom. Interestingly, the vast majority of textbooks of physiology do not include a chapter on immunity. Our species survival is dependent on the diversity of the immune response and the ability for antigen presentation and effector mechanisms to be enormously promiscuous. As physicians, we are likely all too aware of how brief our life span is and the myriad of diseases and events that shorten it. It is not surprising that we question where our life comes from and our relationship within the universe. Many hypotheses have been offered regarding the likelihood that intelligent life exists elsewhere. We propose that such issues be discussed in the context of basic biologic observations on earth, such as the sight of a dense flock of tens of thousands of starlings maneuvering in rapid twists and turns at dusk before settling in trees for the night. The mathematical likelihood for life elsewhere was proposed by Frank Drake in a classic equation whose 'thesis' has stimulated the search for alien civilizations and the nature of life. A fundamental gap in this equation is the presence of a diverse immune response, a feature essential for survival of Life, presumably also extra-terrestrially.

Background: Temporomandibular joint (TMJ) disorders affect roughly 5% of the population. Chronic closed lock is one of the more common temporomandibular disorders and is characterized by limited mouth opening and various degrees of joint pain and dysfunction. 

Objectives: To evaluate the efficacy and safety of arthroscopic lysis and lavage of the TMJ to treat limited mouth opening in patients suffering from chronic closed lock. 

Methods: This is a retrospective analysis of the medical records of 47 patients with chronic closed lock treated with arthroscopic lysis and lavage. Patients were diagnosed preoperatively with closed lock of the TMJ and were unresponsive to previous conservative therapy. Three outcome variables were used to assess the efficacy of treatment: maximal mouth opening, subjective evaluation of overall improvement by the patient (on a 3 grade scale: “excellent,” “fair,” and “poor”), and length of hospital stay. In addition, complications were reported. 

Results: The maximal mouth opening values increased from a mean of 27 ± 4.7 mm preoperatively to a mean of 38 mm ± 5.4 mm postoperatively. The subjective evaluation of overall improvement was “excellent” in 15 patients (32%), “fair” in 21 (45%), and “poor” in 11 (23%). Success was defined as a maximal mouth opening of 35 mm or more after arthroscopy, and not reporting a “poor” result in the subjective evaluation. This was achieved in 36 patients, yielding a success rate of 77%. The mean length of hospital stay was less than one day (0.78 days). The complication rate was low (8%) and all complications resolved within 2 weeks. 

Conclusion: Arthroscopic lysis and lavage is a simple, safe, and efficient minimally invasive intervention for the treatment of chronic closed lock of the TMJ. 

 

Background: Helicobacter pylori (HP) infection of the gastric mucosa may be involved in the development of insulin resistance (IR). 

Objectives: To investigate the association between HP status in stomach biopsies and weight reduction in patients who underwent laparoscopic sleeve gastrectomy (LSG). 

Methods: In this retrospective analysis of medical charts, all patients who underwent LSG for weight reduction and had at least 1 year of follow-up were included. HP status was ascertained by two to four biopsies of the removed stomach. 

Results: The study group comprised 70 patients; their mean age was 45.9 ± 11.9 years and 31.9% were males. Fourteen patients (20%) tested positive for HP colonization in gastric mucosa. HP status was not associated with age or smoking status. No difference was noted in the rate of diabetes mellitus (DM) or hypertension, but patients with HP had lower rates of hyperlipidemia (0 vs. 29 patients, 52%, P < 0.001). Patients lost an average of 10.5 kg/m2 after 12 months of follow-up, and no difference was noted between HP-positive and HP-negative patients. The rate of DM control was also similar between HP-positive and HP-negative patients at baseline (33.3 vs. 29.4, P = NS) and at 12 months of follow-up (70% vs. 50%, P = NS). 

Conclusions: HP status was not associated with changes in metabolic profiles and co-morbidity status, or in the efficacy of LSG. 

 

Background: Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population.

Objectives: To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM).

Methods: The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. 

Results: The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162–300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P < 0.001, r = 0.58). Proteinuria cutoff, based on albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. 

Conclusions: A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure. 

 

Background: Syncope is a common clinical condition spanning from benign to life-threatening diseases. There is sparse information on the outcomes of syncopal patients who received an implantable cardiac defibrillator (ICD) for primary prevention of sudden cardiac death (SCD). 

Objectives: To assess the outcomes and prognosis of patients who underwent implantable cardiac defibrillator (ICD) implantation for primary prevention of SCD and compare them to patients who presented with or without prior syncope.

Methods: We compared the medical records of 75 patients who underwent ICD implantation for primary prevention of SCD and history of syncope to those of a similar group of 80 patients without prior syncope. We assessed the episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), shock, anti-tachycardia pacing (ATP) and mortality in each group during follow-up.

Results: Mean follow-up was 893 days (810–976, 95%CI) (no difference between groups). There was no significant difference in gender or age. Patients with prior syncope had a higher ejection fraction rate (35.5 ± 12.6 vs. 31.4 ± 8.76, P = 0.02), experienced more episodes of VT (21.3% vs. 3.8%, P = 0.001) and VF (8% vs. 0%, P = 0.01), and received more electric shocks (18.7% vs. 3.8%, P = 0.004) and ATP (17.3% vs. 6.2%, P = 0.031). There were no differences in inappropriate shocks (6.7% vs. 5%, P = 0.74), cardiovascular mortality (cumulative 5 year estimate 29.9% vs. 32.2%, P = 0.97) and any death (cumulative 5 year estimate 38.1% vs. 48.9%, P = 0.18).

Conclusions: Patients presenting with syncope before ICD implantation seemed to have more episodes of VT/VF and shock or ATP. No differences in mortality were observed

 

Background: Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. 

Objectives: To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors.

Methods: We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit.

Results: All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95%CI 1.27–1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95%CI 0.393–2.5).

Conclusions: In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

 

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: Diabetes mellitus (DM) is a metabolic sequel in people infected with HIV, especially following the advent of HAART. This may be a particular concern in immigrants due to lifestyle changes. 

Objectives: To characterize the prevalence of DM in HIV-infected Ethiopians in Israel, and to define the risk factors.

Methods: We retrospectively screened the records of 173 HIV-infected Ethiopians and 69 HIV-infected non-Ethiopian HIV patients currently registered at the HIV Clinic of Meir Medical Center. Data were also retrieved from 1323 non-HIV Ethiopians treated in the hospital between 2007 and 2012. The presence of DM was determined by family physician diagnosis as recorded in the hospital database or by the presence of one or more of the following: fasting glucose > 127 mg/dl, hA1C > 6.5% (> 48 mmol/mol), or blood glucose > 200 mg/dl. Population data and risk factors for DM were analyzed by univariate and multivariate analyses. 

Results: Among HIV-infected Ethiopian subjects, the prevalence of DM was 31% (54/173) compared to 4% (3/69) in HIV-infected non-Ethiopians and 8% (102/1323) in non-HIV-infected Ethiopians (P < 0.0001). The relatively increased prevalence of DM was age independent, but most noticeable in those under the median age (< 42 years). Body mass index (BMI) was a predictor for DM (OR 1.263, CI 1.104–1.444, P = 0.001), although its values did not vary between the two ethnic groups. 

Conclusions: HIV-infected Ethiopians are more likely to develop DM at low BMI values compared to non-Ethiopians. This observation questions the relevance of accepted BMI values in this population and suggests that preventive measures against DM be routinely taken in these subjects. 

 

Background: Exposure to air pollution in the form of particulate matter smaller than 10 µm in diameter (PM10) has been associated with increased morbidity and mortality. However, since air pollution is correlated with confounding factors that might otherwise affect health, identifying the causal link has proven challenging. 

Objectives: To identify the effect of PM10 on hospital admissions due to respiratory illnesses. 

Methods: We used the Instrumental Variable (IV) methodology to control for confounding factors affecting hospital admissions. Exploiting the timing of sandstorms as an instrumental variable allows for a better estimate of the relationship between PM10 and hospital admissions. Data on PM concentrations and hospital admissions rates were compiled for Israel’s two largest cities, Jerusalem and Tel Aviv, for 2007–2009. We compared our IV estimates to those derived from a Poisson regression, which is commonly used in the existing literature. 

Results: Sandstorms led to an increase of 307 µg/m3 of PM10 concentrations. A 10 µg/m3 increase in PM10 is associated with a 0.8% increase in hospital admissions due to respiratory conditions, using Poisson regression. The same finding was noted using the IV methodology. 

Conclusions: The association between PM10 and hospital admission reflects a primarily causal relationship. Instrumental variable methodology could be applied to analysis of the effect of air pollution on hospital admissions.