Israel Medical Association Journal

There has been a paradigm shift in the treatment of rheumatoid arthritis in recent years. Early and aggressive treatment with good control of disease activity has improved the prognosis of the disease, however, there is significant variability in the response of patients to different therapeutic agents. Hence it is essential to find the predictors of response to a drug at baseline so that we can avoid the delay in achieving remission and improve the outcome. Here we review the literature on available predictors for treatment response in general and specifically for methotrexate and biological agents. We also look at specific scores or indices that can help predict the response in individual patients.

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations

Background: In the course of occurrence of cerebral infarction, cerebral hemorrhage and subarachnoidal hemorrhage episodes, periodicities resembling those found in the solar and geomagnetic activity were found by Kováč and Mikulecký (2005).

Objectives: To investigate putative relationships between two indices of solar activity and one index of geomagnetic activity on one side and the occurrence of cerebral infarction on the other.

Methods: In addition to the 192 monthly cases out of 6100 new cases of cerebral infarction that occurred between January 1989 and December 2004, monthly averages for Wolf numbers, solar flares index and Ap index were included in the analysis. The cross-correlation between each cosmo-geophysical variable on the one hand and the number of new cases of the disease on the other was computed. The quadratic regression with the chosen time delay was also studied using, separately, the Wolf numbers, solar flares and Ap index as the explanatory variable and the number of cases of cerebral infarction as the responding variable.

Results: Significantly negative correlation coefficients between the monthly means of the Wolf numbers, of solar flares and of Ap index on the one hand and monthly numbers of new cases of the disease on the other were found for the delays between -6 and +17 months. The cross-regression results for the delay of +5 months (infarction delayed after each cosmo-geophysical variable by 5 months) displayed a linear decrease except for the Wolf numbers where the parabolic decrease of cases was significant.

Conclusions: An increased intensity of the studied cosmo-geophysical parameters appears to be significantly connected with decreased occurrence of cerebral infarctions, and vice versa. This effect seems to last up to 17 months. The results are supported by a few similar findings in the literature. Putative cosmo-biomedical connections warrant further study to verify them in larger samples and longer time scales. If confirmed, their mechanisms should be elucidated.
 

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment. 

Background: Open access gastroscopy allows physicians to refer patients for endoscopic procedures without a prior consultation.

Objectives: To compare the safety and efficacy of OAG[1] with gastroscopy performed after a gastroenterological consultation.

Methods: Patients referred for gastroscopy directly (open access) or after consultation with a gastroenterologist, by physicians in the departments of internal medicine and surgery at a major tertiary center, were compared for indications, background disease, outcome and diagnostic yield. The data were collected prospectively over a 5 month period following the introduction of OAG at the center. Physicians in both departments participated in an education program on the indications and procedure of gastroscopy. For each patient referred for OAG the attending physician completed a specially designed questionnaire that had to be signed by a senior physician. Data were managed and analyzed with Excel and SPSS software.

Results: The study sample comprised 494 patients: of whom 236 were referred for OAG and 258 after prior consultation. On multivariate analysis, hospitalization in the department of internal medicine was the only independent factor for OAG. Severe background disease and aspirin treatment had no effect on physician use of OAG, although they served as a “red light” for the gastroenterology consultants. There was no difference in the diagnostic yield of the procedures (26.4% normal findings for OAG and 28.3% for consultations) or in mortality rates. The main indications for referral to gastroscopy in the surgery department were melena, hematemesis, and "coffee grounds," and anemia and vomiting in the internal medicine department.
Conclusions: OAG is feasible and beneficial in an academic medical center setting, with no bias in appropriateness of indications or decrease in the diagnostic yield compared to the traditional approach. More attention should be directed to safety issues by the referring physicians

Background: Trauma management includes the care provided both in hospital and by emergency medical systems in the community. In many cases it is the parents who decide where to take an injured child for care, depending on the circumstances and severity of the injury, the personal characteristics of the injured or the carer and the availability and accessibility of services.

Objectives: To examine the use of pre-hospitalization services and reasons for their use by children and adolescents according to the injury and personal characteristics.

Methods: The study group comprised 924 Israeli citizens aged 0–17 years hospitalized for injuries in six hospitals across Israel. Carers were interviewed in the hospital regarding the circumstances of the injury event, the use of pre-hospitalization services, and sociodemographic characteristics. Data on the cause and nature of the injury were obtained from the hospital records.

Results: The proportion of severe injuries (Injury Severity Score 16+) was higher in Arab children than Jewish children (15% and 9% respectively). Sixty-three percent of the Arab children and 39% of the Jewish children used community services prior to hospitalization. The odds ratio of proceeding directly to the hospital was 0.44, 95% confidence interval 0.29–0.69, for the Arab compared to the Jewish children, controlling for severity, cause and nature of the injury, sociodemographic characteristics, and the reported availability of ambulance services.

Conclusions: More Arab than Jewish carers tended to seek care in the community for an injured child, but the effect of personal characteristics on seeking care was similar in both population groups. Issues of availability and accessibility of services may explain the differences.

Background: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. Vestibular evoked myogenic potentials test is an objective evaluation of saccular function.

Objective: To examine whether saccular function is related to the pathogenesis of seasickness.

Methods: VEMP1 was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects.

Results: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%.   

Conclusions: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.
 

Background: Smoking continues to be the most significant preventable  cause of morbidity and early mortality in the developed world. Primary care physicians are not fufilling their potentially vital and effective role regarding tobacco use and dependence.

Objectives: To evaluate current primary care physician practise in promoting smoking cessation.

Methods: This observational study evaluated physician recording of smoking status by analysis of patients’ electronic medical records. The 126 primary care physicians were based in 23 Tel Aviv clinics treating 144, 811 patients. We also assessed additional physician anti-smoking activities by telephone questionnaire of 178 randomly selected patients.

Results: Analysis of the EMRs[1] revealed that an average of 4.4% of patients per physician were recorded as smokers (as compared to a known smoking rate in this patient population of 24%). Male physicians recorded a significantly higher proportion of their patients as smokers in the EMR compared to female physicians (P < 0.05). A non-significantly higher rate of recording smokers was found in doctors who had completed postgraduate specialization in family medicine as compared to non-specialists. The questionnaire results show that 41% of patients interviewed recalled being asked if they smoked and 31% of smoking patients had been advised to quit. A non-significantly higher proportion of male as compared to female patients reported being questioned if they smoked, and if they were smokers, being advised to quit.

Conclusions: This study shows low rates of physician intervention to promote smoking cessation. It appears that a large proportion of the primary care physicians surveyed do not follow recommendations to promote smoking cessation among their patients. Intervention among adolesent smokers was particularly inadequate. Further action is needed to improve the performance of physicians in aiding smoking cessation.

Background: Age-related macular degeneration is the most common cause of legal blindness in the developed world including Israel. Ethnic background is a risk factor for advanced AMD[1] in several populations, however the relative prevalence of this disease in different ethnic groups in the Middle East is unknown.

Objectives: To compare the prevalence of advanced AMD in Arabs and Jews in Israel.

Methods: We performed a retrospective analysis of two independent groups of patients: the first group comprised a sequential series of Jerusalem residents who underwent photodynamic therapy for neovascular AMD (PDT[2] group), and the second group consisted of all individuals in Jerusalem who received a blind certificate due to AMD (legal blindness group). Control groups were assessed to exclude inherited ethnic associated bias in the two study groups.

Results: The PDT group included 146 patients: 142 were Jews (97.3%) and 4 were Arabs (2.7%). The legal blindness group included 340 Jerusalem residents: 326 Jews (96%) and 14 Arabs (4%). The number of Arab AMD patients in the two groups was lower than expected based on the ethnic composition of the age-matched Jerusalem population (P = 0.0002 for the PDT group, and P < 0.0001 for the legal blindness group). By contrast, the number of non-AMD Arab patients who were treated in the same clinic and the number of Arabs who received a blind certificate for diabetic retinopathy was not different from expected based on their relative number in the Jerusalem population.

Conclusions: Advanced AMD is less common in the Arab than the Jewish population of Jerusalem. Genetic and environmental factors may account for this difference. A population-based study is required to assess the overall prevalence of AMD in Jews and Arabs.