Israel Medical Association Journal

In this article, we offer a brief summary of the report from the Task Force for the Promotion of the Status of Women in Medicine in Israel. The task force, formed by the Israel Medical Association in 2013, published a comprehensive report in May 2015 dedicated to the promotion of equal opportunities for female doctors in the Israeli healthcare system and in the academic world. The aim of this paper is to present the work of the task force and to highlight its main principles and recommendations against the backdrop of the gender revolution in the Israeli healthcare system and worldwide.

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in Caucasian adults. Most patients have good renal prognosis, but 30–40% may progress to end stage renal disease (ESRD). 

Objectives: To evaluate the efficacy and safety of immunosuppressive treatment (IST) in high-risk patients.

Methods: All IMN patients diagnosed by kidney biopsy from 2004–2010 were included. Clinical and laboratory data were collected at each follow-up visit. Risk assessment for renal progression classified patients as high risk if: 24 hour protein excretion > 6 g/day, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and severe disabling or life-threatening clinical symptoms of NS were present.

Results: Among 290 biopsies, 37 patients (12.7%) were IMN. They were allocated to the high-risk IST group (n=16) or low-risk supportive treatment (ST) group (n=21) according to the likelihood of developing renal failure. Mean follow-up was 47 ± 17.3 months. Complete and partial remission rate was 68.7% for high-risk IST vs. 90.4% for low-risk ST. In the high-risk IST group, eGFR was significantly lower at 30 months (65.5 ± 28.6 vs. 85.3 ± 21.6 at baseline, P < 0.05). Four high-risk patients reached ESRD. In the low-risk ST group, eGFR remained stable at 30 and 60 months. 

Conclusions: This study showed a high remission rate for IMN. IST with prednisolone and cyclophosphamide provided favorable renal outcomes in most high-risk patients. The very high remission rate obtained in the low-risk patients confirms the adequacy of supportive treatment in this group.

Background: Children and adolescents are commonly referred to an orthopedic surgeon to assess knee malalignment.

Objectives: To assess the prevalence of genu varum and valgum among adolescents, and to identify correlates of these conditions.

Methods: A medical database of 47,588 candidates for military service presenting to the northern recruitment center during an 11 year period was analyzed to identify clinical knee alignment. Based on the standing skin surface intercondylar distance (ICD) or intermalleolar distance (IMD), the prevalence rates of genu varum (ICD ≥ 3 cm) and genu valgum (IMD ≥ 4 cm) were calculated. The association of gender, body mass index (BMI), and place of residence to knee alignment was studied.

Results: The rates of genu varum and valgum were 11.4% (5427) and 5.6% (2639), respectively. Genu varum was significantly more prevalent among males than females (16.2% vs. 4.4%, P < 0.001). It was also more prevalent among underweight subjects and less prevalent among overweight and obese subjects (P < 0.001). Genu valgum was significantly more prevalent among females than males (9.4% vs. 2.9%) and in overweight and obese subjects compared to those with normal BMI, while less prevalent in underweight subjects (P < 0.001). Multivariate analysis revealed that genu varum was independently positively associated with male gender, underweight, and living in a rural area. Genu valgum was independently positively associated with female gender, overweight, and obesity.

Conclusions: This study establishes a modern benchmark for the cutoff and prevalence of genu varum and valgum as well as associations with gender and BMI.

Background: Biological agents for anti-tumor necrosis factor-α therapy have revolutionized treatments for autoimmune diseases; however, approximately 20% of rheumatology and 40% of gastroenterology patients do not respond to the therapy, or they show reduced drug efficacy because of anti-drug antibody (ADA) formation.

Objectives: To evaluate laboratory tools for individual monitoring of infliximab therapy and the relationship between ADA and infliximab serum levels, ADA and clinical response, and ADA and autoantibodies.

Methods: Our study comprised patients treated with infliximab and affected by selected rheumatology and gastroenterology diseases. Sera were analyzed for infliximab, total-anti-drug antibodies (Total-ADA), and free-anti-drug antibodies (Free-ADA) serum levels and for the detection of specific autoantibodies.

Results: We analyzed 73 patients. Total-ADA were detected in 26 rheumatology and 21 gastroenterology patients. Serum infliximab levels were significantly lower in Total-ADA positive patients (P = 0.01 for rheumatology group, P = 0.02 for gastroenterology group). A lack of response was observed in 7 rheumatology and 15 gastroenterology samples. Total-ADA serum levels were statistically significantly higher in patients with treatment failure in both groups (P = 0.01 and P = 0.001, respectively). There was no significant association between the presence of Total-ADA and other autoantibodies. Free-ADA were detected in only 27 rheumatology patients. Results showed a significant correlation with clinical outcome (P = 0.006).

Conclusions: The correlation with clinical response suggests that the presence of ADA could interfere with efficacy of therapy. The tests for monitoring therapy may be an important tool to assist clinicians in early detection and prevention of therapy failure.

Background: Physical inactivity is a pivotal factor in the development and progression of various chronic diseases. However, most fitness facilities exclude unhealthy individuals. Therefore, an exercise program that admits such patients is imperative.

Objectives: To evaluate the effectiveness of a fitness facility that admits adult subjects with multiple chronic diseases.

Methods: We conducted a retrospective screening of patient records from the Medical Fitness Facility at Meir Medical Center, Israel. Intake of subjects was done by a multidisciplinary team. For each individual, personalized diet and exercise plans were developed and patients attended the facility twice a week. Each participant was evaluated at enrolment and after 4 months for well-being, metabolic parameters, exercise capacity, and laboratory blood tests.

Results: A total of 838 individuals were enrolled, mean age 57 years. Their medical conditions included dyslipidemia (48.8%), hypertension (37.6%), and diabetes mellitus (24.9%), followed by musculoskeletal problems (arthropathy 19%, lower back pain 16.1%) and ischemic heart disease (13.4%). Less common diagnoses were vascular diseases, pulmonary diseases, and malignancy. Only 40.5% of participants adhered to the regimen with advanced age being the best predictor for adherence. At the follow-up visit, body mass index was lower (31.2 vs. 30.2 kg/m², P <0.0001), exercise capacity increased (measured as maximal MET; 7.1 vs. 8.1, P < 0.0001), and well-being improved (measured by Short Form Survey [SF-36]; 69.3 vs. 76.0, P <0.0001).

Conclusions: We show that a fitness program for patients with multiple chronic diseases is feasible and effective in improving prognostic parameters, albeit significantly challenged by adherence limitations.

Background: There is little evidence about awareness and functional outcome of hip fracture-related falls among patients with a history of recurrent falling.

Objectives: To measure the awareness of recurrent falling in patients and to compare their functional outcomes with those who suffered hip fracture after a sporadic isolated fall.

Methods: A prospective comparative study of patients after a hip fracture-related fall was conducted. Awareness of falls was measured and functional outcome was assessed by total and motor Functional Independence Measure (FIM) score changes and efficiency and scores at admission and on discharge.

Results: Of 97 eligible participants, 49 (50.5%) were recurrent fallers. Of these recurrent falls, 19 (38.8%) were not reported, 16 (32.7%) were reported but no action was taken, and 7 (14.3%) were reported and a partial assessment performed. A full assessment was performed in only 7 cases (14.3%). FIM scores on admission and discharge were significantly higher in once-fallers. A multiple linear regression analysis showed that being a once-faller was independently associated with higher total FIM at admission (β coefficient = 0.290, P = 0.004), higher motor FIM at admission (β coefficient = 0.295, P = 0.003), higher total FIM at discharge (β Coefficient = 0.264, P = 0.009), and higher motor FIM at discharge (β coefficient = 0.230, P = 0.023).

Conclusions: Awareness of the syndrome of recurrent falling is extremely low. Recurrent falls before a hip fracture-related fall is associated with substantial loss of functional independence. Being a recurrent faller adversely affects rehabilitation outcome of hip fracture patients.

Background: Nebulized hypertonic saline (HS) treatment is unavailable to large populations worldwide.

Objectives: To determine the bacterial contamination and electrolyte concentrations in homemade (HM-HS) vs. pharmacy made (PM-HS).

Methods: We conducted three double-blind consecutive trials: 50 boiled-water homemade 3%-HS (B-HM-HS) bottles and 50 PM-HS. The bottles were cultured after 48 hours. Electrolyte concentrations were measured in 10 bottles (5 per group). Forty bottles (20 per group) were distributed to volunteers for simulation of realistic treatment by drawing 4 ml HS three times daily. From each bottle, 4 ml samples were cultured after 1, 5, and 7 days. Volunteers prepared 108 bottles containing 3%-HS, sterilizing them using a microwave oven (1100–1850W). These bottles were cultured 24 hours, 48 hours, and 1 month after preparation.

Results: Contamination rates of B-HM-HS and PM-HS after 48 hours were 56% and 14%, respectively (P = 0.008). Electrolyte concentrations were similar: 3.7% ± 0.4 and 3.5% ± 0.3, respectively (P = NS). Following a single day of simulation B-HM-HS bottles were significantly more contaminated than PM-HS bottles: 75% vs. 20%, respectively (P < 0.01). By day 7, 85% of PM-HS bottles and 100% of B-HM-HS bottles were contaminated (P = 0.23). All 108 microwave-oven prepared bottles (MICRO-HS) were sterile, which was significantly better than the contamination rate of B-HM-HS and PM-HS (P < 0.001). Calculated risk for a consecutive MICRO-HS to be infected was negligible.

Conclusion: Microwave preparation provides sterile HS with adequate electrolyte concentrations, and is a cheap, fast, and widely available method to prepare HS.

Background: Enthesopathy may lead to calcification of the stylohyoid ligament and can cause elongation of the styloid process (SP).

Objectives: To evaluate whether SP elongation is associated with two common enthesitis-related diseases: ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).

Methods: Cervical spine computed tomography (CT) examinations of patients with DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH group was further divided into patients with and without cervical DISH. The length of right and left SP was measured independently by two readers on coronal and sagittal curved reformats. The average right and left styloid length and average length per person were compared among the groups.

Results: Demographic characteristics were similar between the DISH and control groups (average age 68.2 ± 15.7, 69.2 ± 12.7 years, male:female ratio 48:16 and 35:19, respectively, P > 0.05), whereas age was significantly lower (average age: 53 ± 15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The AS and DISH groups had significantly longer SP compared to controls (AS 37.9 ± 9.6 mm, DISH 34.4 ± 9 mm, control 30.3 ± 10.1 mm, P < 0.05). There was no correlation between age and SP length. Inter-reader reliability of SP measurements was excellent in all groups (ICC = 0.998, P < 0.0001).

Conclusions: SP elongation is associated with both AS and DISH substantiating the enthesopathy-related pathophysiology of this finding.

Background: Blogs have become a major venue of information sharing and emotional release for people worldwide. Illness blogs are a specific type of blog in which patients describe their experience with illness and coping with disease. Illness blog research has been conducted on several disorders; however, blogs by Parkinson's disease (PD) patients have been neglected.

Objectives: To categorize the characteristics of PD patients from blogs and explore whether we can learn about the medical issues with which they are most concerned, as conveyed through their blog posts.

Methods: Using located PD patients' blogs, we analyzed the contents of 78 blogs, and employed thematic analysis of eight arbitrarily selected blogs.

Results: The majority of blog authors in our sample (N=78) were from the United States (42%). The number of blogs written by male and female authors was fairly similar: 49% and 44%, respectively, while gender was unknown for 7%. Blogs were written by both early- and late-onset PD patients. The thematic analysis revealed five major themes: diagnosis, symptoms, treatment, coping mechanisms, and information.

Conclusions: Thematic analysis of blogs by PD patients provided considerable information and insight regarding the experience of these patients, which is significant to other patients and their families, as well as to medical professionals. Further qualitative studies of larger blog samples utilizing data mining techniques are needed to further explore the subjective experiences of patients.

Enthesitis is a term that refers to inflammation at tendon, ligament, or joint capsule insertions. The entheses are increasinlgly considered to be the primary site of joint inflammation in the spondyloarthropathies including psoriatic arthritis (PsA). Great advances have occurred in the understanding of enthesopathy, which has resulted in a better understanding of the etiopathogenesis of PsA. Enthesitis is difficult to assess on both clinical examination and on imaging because of the overlap in features between mechanical, degenerative, and inflammatory pathologies. Ultrasonography frequently detects entheseal abnormalities in patients with psoriasis, despite the absence of clinical symptoms of arthropathy and the longitudinal value of such lesions for PsA prediction remains unknown. The role of magnetic resonance imaging (MRI) in the assessment and monitoring of enthesitis is not fully agreed on but it is clearly superior for the assessment of spinal polyenthesitis and for diffuse peri-enthseal osteitis that can occur anywhere in the skeleton. Nuclear medicine, including conventional positron-emission tomography (PET) and high-resolution PET scan (hrPET), is more of a research tool for enthesitis and can, for example, help distinguish between PsA and osteoarthritis. Entheseal abnormalities are common in osteoarthritis, which creates diagnostic difficulty from PsA. Entheseal changes, especially on imaging, may also occur in rheumatoid arthritis (RA) and likely reflect the extension of the inflammatory process from the adjacent synovium. The nail is anatomically anchored to the skeleton via a mini-enthesis network. An association between ultrasonography determined distal interphalageal joint (DIP) extensor tendon enthesopathy and clinical nail disease was found, which highlights the pivotal role of the enthesis in this PsA risk factor. This review summarizes the relevant insights and implication of imaging for enthesitis, primarily in PsA but also in other arthropathies.

Over the last 15 years ultrasound has gained importance for the clinical management of patients with inflammatory rheumatic diseases, especially rheumatoid arthritis. This review summarizes the recent developments and achievements in the use of ultrasound in RA, as well as the unmet needs.