Israel Medical Association Journal

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Pain following brain surgery is a significant problem. Infiltration of the scalp with local intradermal anesthetics was suggested for postoperative pain control but was assessed only in the first hour postoperatively.

Objectives: To evaluate wound infiltration with a single dose of metamizol (dipyrone) for postoperative pain control in patients undergoing awake craniotomy.

Methods: This open, prospective, non-randomized observational study, conducted in anesthesiology and neurosurgical departments of a teaching hospital, included 40 patients undergoing awake craniotomy for the removal of brain tumor. Intraoperative anesthesia included wound infiltration with lidocaine and bupivacaine, conscious sedation using remifentanil and propofol, and a single dose of metamizol (dipyrone) for postoperative pain control. Outcome was assessed by the Numerical Pain Scale on arrival at the postoperative care unit, and 2, 4 and 12 hours after the end of surgery.

Results: On arrival at the postoperative care unit, patients reported NPS[1] scores of 1.2 ± 1.1 in a scale of 0–10 (mean ± SD) (median = 1, range 0–4). The scores were 0.8 ± 0.9, 0.9 ± 0.9, and 1 ± 0.9 at 2 hours, 4 hours, and 12 hours after the end of surgery, respectively. Based on patients' complaints and NPS lower then 3, 27 patients did not require any supplementary analgesia during the first 12 postoperative hours, 11 patients required a single dose of oral metamizol or intramuscular diclofenac, one patient was given 2 mg of intravenous morphine, and one patient required two separate doses of metamizol.

Conclusions: Although the clinical setup prevents the use of placebo local analgesia as a control group, the results suggest the possible role of local intradermal infiltration of the scalp combined with a single dose of metamizol to control postoperative pain in patients undergoing craniotomy.

Background: The patient package insert, an information leaflet included by law in the packaging of prescription drugs, contains information for the user on the specific medication.

Objectives: To explore how patient information leaflets influence patient anxiety and adherence.

Methods: A prospective cohort study was conducted in the practices of 15 family physicians. All patients receiving a new prescription for antibiotics, analgesics or antihypertensives were included. Physicians completed a questionnaire containing demographic data, assessment of the patient’s anxiety, a prediction about adherence to the treatment, and response to the information leaflet. Patients were contacted by telephone for a follow-up structured interview. Patients' reactions to the information leaflet, adherence to treatment, and use of other sources of information on medication were assessed.

Results: The study group comprised 200 patients. The patient information leaflet was read by 103 of them (51.5%). A higher educational level and a chronic medication were associated with reading the leaflet (P = 0.02 and 0.01 respectively). In 36 (34.9%), an increase in anxiety was reported after reading the leaflet. Among those who read the leaflet, 9.7% had decreased adherence. Patients who stated that reading the leaflet caused anxiety were more likely to reduce their use of the medication – 7/36 (19.5%) vs. 3/67 (4.5%), P = 0.01.

Conclusions: The proportion of patients reading the drug information leaflet is about 50%, lower than that found in previous studies. Reading the leaflet did not greatly affect adherence but aroused anxiety and decreased adherence in some patients.
 

Ludwik Zamenhof (1859-1917) lived in Poland under Russian and later German rule. He invented and propagated Esperanto – an artificial, easy-to-learn language. Literally meaning “language of hope,” Esperanto was constructed to avoid misunderstandings, establish communication and facilitate harmony among different nationalities. Simply, he wanted people to accept one another despite observed differences. He was a skilled ophthalmologist, but figuratively, he wished to heal the eyes of humankind to look without hate, just as the biblical Tobias removed the cataract from the corners of his father’s eyes to restore his sight.