Israel Medical Association Journal

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.

 

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

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.

The major route of hepatitis C virus (HCV) infection in the pediatric age group is vertical, with infection occurring in up to 5% of infants born to mothers positive for HCV-RNA. The natural course of pediatric HCV infection is characterized by a high rate of spontaneous clearance, an asymptomatic clinical course, and normal or mild histologic changes. Cirrhosis is reported in 1–2% of children and progression to severe chronic liver disease and HCC occurs 20–30 years after infection. Treatment with pegylated interferon (Peg-IFN) + ribavirin results in a sustained viral response (SVR) of up to 100% in children with HCV genotypes 2 or 3 but only 45–55% in those infected with genotypes 1 or 4. Treatment is associated with adverse effects ranging from flu-like symptoms, myalgia, anemia and thrombocytopenia, to less commonly observed thyroid-related symptoms, alopecia, neuropsychiatric manifestations and possible long-term effects on growth. Ongoing trials with direct-acting antiviral agents in adults show promising results with treatment regimens of shorter duration and high tolerance. The next few years will likely see these advances introduced to the pediatric population as well. In the meantime, in children with HCV an expectant approach is advocated and treatment should be offered only to those at high risk for more severe, progressive disease. 

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: Determining the accuracy of interferon gamma-releasing assays (IGRAs) is difficult due to the lack of a gold standard test for diagnosing latent tuberculosis (LTB). 

Objectives: To analyze the guidelines used for interpreting IGRAs in determining prophylactic treatment management for latent tuberculosis (LTB) in Israel.

Methods: We analyzed the retrospective data of 367 subjects who were referred to our laboratory during the period 2007–2011 for QuantiFERON Test-Gold In Tube (QFT-GIT) tests because of suspected LTB. Demographics and clinical data were retrieved from a questionnaire at enrollment, and 166/367 (45%) were further interviewed by phone in order to complete follow-up information on prophylactic TB treatment. 

Results: The majority of subjects (116/166, 69.9%, P < 0.0001) were spared prophylactic treatment subsequent to QFT-GIT testing. Subjects with negative QFT-GIT and positive tuberculin skin test (TST) results who were BCG-vaccinated had the lowest treatment rates (6/68, 8.8%, P < 0.0001). Most BCG-vaccinated subjects with positive TST and negative QFT-GIT test results received treatment with anti-tumor necrosis factor-alpha (TNFα) (17/19, 89.5%, P = 0.004). We found more negative QFT-GIT test results in subjects who were receiving anti-TNFα or steroid and other immunosuppressive treatment prior to testing (11/11, 100%, P = 0.029; 22/26, 84.6%, P = 0.06; 15/17, 88%, P = 0.06, respectively). 

Conclusions: Deciding on LTB prophylactic treatment in Israel is highly influenced by QFT-GIT test results. QFT-GIT findings contribute to clinical decisions, but their interpretation must also consider the patient’s medical history and clinical characteristics. 

 

Background: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. 

Objectives: To summarize the single-center experience in the treatment of anal carcinoma using various radiation techniques.

Methods: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B).

Results: A total of 42 patients – 25 (59.5%) females and 17 males (40.5%) – underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups, only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. 

Conclusions: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions, but did not differ from 3D with regard to treatment efficacy. 

 

Background: Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. 

Objectives: To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department.

Methods: The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by metered dose inhaler (100 μg/puff) attached to a spacer device. The number of puffs was determined by severity of disease according to GINA recommendations. After 2 years the outcome and cost analysis were examined.

Results: During 3 years since the initial policy change 92.5% patients were treated with spacers throughout their hospital stay (emergency department and pediatric ward). Costs were reduced by an estimated 63%. 

Conclusions: In view of its many advantages the replacement of nebulizers by MDI+S for the treatment of acute asthma is feasible, if performed in collaboration with the staff, hospital authority and patients.

 

Background: Benign prostate hyperplasia (BPH) is a common age-dependent urological condition that can disrupt quality of life if the patient's treatment choice is inappropriate. 

Objectives: To examine whether patients’ demography and personality affect their decision regarding the type of treatment: namely, conservative or surgical. 

Methods: A total of 105 BPH patients treated during the period 2005–2008 were retrospectively categorized into three groups according to treatment received: (i) medication only (n=056), (ii) combined treatment (the initial medication treatment was switched to surgical treatment) (n=32), and (iii) surgery only (n=17). A prerequisite for inclusion in the study was use of BPH medication for at least half a year before the study (groups 1 and 2). These groups completed the International Prostate Symptom Score (IPSS) questionnaire at the start of BPH medical treatment (IPSS 1) and at the start of the trial (IPSS 2), and the staff calculated the difference (IPSS 1-IPSS 2 = Delta IPSS = DIPSS).  All three groups provided demographic data (age, country of origin, education) and completed tri-dimensional personality questionnaires (TPQ) to measure three independent "temperament" personality dimensions to evaluate how different individuals feel or behave: novel seeking (NS), harm avoidance (HA), and reward dependence (RD). Data were analyzed using chi-square, t-test, one-way ANOVA and logistic regression.

Results: Demographic variables and the RD dimension differed according to choice of BPH treatment. 

Conclusions: Our study suggests that symptomatic BPH treatment is influenced less by the patient's personality and more by his life circumstances. Israeli-born patients were more conservative, Russian-born patients were ambivalent, and other foreign-born patients predominantly preferred surgical treatment. We assume that personality has a more decisive effect on patients with malignant disease and they accept the medical advice more easily.