Israel Medical Association Journal

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monoclonal antibody, was recently shown to be effective in treating resistant CSU.

Objectives: To investigated the treatment of CSU with omalizumab in Israel.

Methods: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012–2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients’ condition improved but required regular or intermittent doses of antihistamines.

Results: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 ± 12 years and CSU duration was 4.3 ± 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 ± 3.2 injections; 30 patients received 150 mg/month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005).

Conclusions: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy. 

Objectives: To assess the nature of joint problems encountered in a geriatric inpatient population and evaluate the contribution of a rheumatologist.

Methods: We reviewed the rheumatology consultations that were conducted in a geriatric medical center over a 10 year period.

Results: A total of 474 consultations were held; most of these patients (86%) were hospitalized in the acute geriatric departments, 10% in the rehabilitation ward and 4% in the long-term care wards. Some patients were seen more than once. The rheumatologic joint problem was the main reason for hospitalization in 53% of these patients. Monoarthritis was the most frequent complaint (50%), followed by pauci-articular arthritis (two to five joints) in 30% of patients. Arthrocentesis, diagnostic and therapeutic, was performed in 225 patients, most of them on knee joints (81%). The most frequent diagnosis was osteoarthritis with acute exacerbation (28%), followed by gout (18%), pseudo-gout (9%) and rheumatoid arthritis (9%). In 86 cases (18%) the diagnosis was a non-specific rheumatologic problem: arthralgia, non-specific generalized pain, or fibromyalgia.

Conclusions: Prompt and appropriate evaluation, as well as arthrocentesis and treatment initiation, including local injections, were made possible by the presence of an in-house rheumatologist. 

Objectives: To evaluate the predictive value regarding patients' survival once the diagnosis of “general deterioration” replaces an ICD-9 diagnosis upon re-admission.

Methods: In a retrospective cohort case-control study, we screened the records of patients re-admitted at least three times during the past 2 years. For each patient's death during the third hospitalization, we matched (for age and gender) a patient who survived the third hospitalization. We evaluated 14 parameters potentially accountable for increased risk of mortality, e.g., length of stay at each admission, interval to re-admission, etc. We applied a multifactorial analysis using logistic regression to predict the risk of mortality during the third hospitalization as potentially affected by the aforementioned parameters.

Results: The study included 81 study patients and 81 controls. Of the 14 parameters potentially explaining an increased risk of mortality during the third hospitalization, several were found to be statistically significant. The most significant was the diagnostic switch from a specific ICD-9 diagnosis on first admission to the non-specific diagnosis of “general deterioration” at the second hospitalization. In such cases, the risk of death during the third hospitalization was increased by 5300% (odds ratio = 54, P = 0.008). The increased risk of mortality was not restricted to patients with malignancy as their background diagnosis.

Conclusions: At re-admission, a switch from disease-specific diagnosis to the obscure diagnosis “general deterioration” increases the subsequent risk of mortality.

Background: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular medications. Bevacizumab is mostly used in this group of medications.

Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab.

Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30–70 mmHg, 3–30 days after injection.

Results: Mean IOP was 42.6 mmHg (range 30–70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3–13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001.

 Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments. 

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

Background: Patients with allergy as well as their parents frequently fail to use the self-administered epinephrine injection (EpiPen®) properly in cases of allergic emergencies.

Objectives: To determine the benefit of an instruction session with follow-up instruction.

Methods: We evaluated 141 patients aged 1.9–23.4 years (median 5.8 years, 83% with food allergy) or their parents (for those aged < 12 years) who were trained in the use of the EpiPen during the first diagnostic visit to the allergy clinic during 2006–2009. At the next follow-up visit, the patients or their parents were asked to list the indications for epinephrine administration and to demonstrate the five steps involved in using the EpiPen. Each step was scored on a scale of 0–2.

Results: Fourteen participants (9.9%) had used self-injectable epinephrine in the past. Only 65 (46%) brought the device with them to the follow-up visit. The mean total score for the whole sample was 4.03 ± 3. Fifty-three participants (38%) failed to remove the cap before trying to apply the device. Only 8 (5.6%) had a maximum score. The patients and their parents were reinstructed in the use of the device: 41 participants were reexamined at a subsequent follow-up visit after 1.02 ± 0.56 years their mean score improved from 4.71 ± 3.04 to 6.73 ± 3.18 (P < 0.001).

Conclusions: Patients with severe allergic reactions, as well as their parents, are not sufficiently skilled in the use of the EpiPen after only one instruction session with a specialist. Repeated instruction may improve the results and we therefore recommend that the instructions be repeated at every follow-up visit.

Background: Control of diabetes is challenging, and frequent treatment changes are needed. 

Objective: To study the effect of the recommendation to start insulin glargine or insulin determir (long-acting insulin treatment, LAI) at discharge from hospital, on glucose control in the community setting.

Methods: Included were type II diabetes patients who were referred to and received a consultation from the hospital diabetes clinic during their hosptialization, as part of a routine consultation for diabetes management. During the visit, all patients were recommended long-acting insulin-based treatment, as inpatient treatment and at discharge. Follow-up was done by the primary physician in the community or by a community-based diabetes clinic. Glycosylated hemoglobin, glucose levels and other laboratory tests were obtained from the community health records before hospitalization and 6–12 months later. Medical treatment was ascertained by reviewing the actual usage of prescriptions.

Results: Eighty patients (58% males, mean age 64.1 ± 12.7 years) were included in the analysis. HbA1c levels were 10.1 ± 2.4% before admission, but improved significantly at follow-up (8.6 ± 2.2%, P < 0.001). Seventy-one percent of the patients were taking the LAI treatment and the rest were using non-LAI medications. Changes in diabetes control were similar between the LAI and non-LAI groups (HbA1c was reduced by 1.5 ± 3.2% and 1.9 ± 3.1% respectively). The rate of repeated admissions was also similar, averaging at 1.3 admissions for both groups, the minority of which were related to glucose control.

Conclusions: Insulin glargine or determir-based treatment does not show any superiority over other anti-diabetes treatment. It is our opinion that this treatment should be used as tailored therapy and should not be recommended routinely to all patients.
 

Background: Ritual circumcision in neonates may cause a urinary tract infection within 2 weeks of the procedure.

Objectives: To evaluate the prevalence of urinary tract infection among Jewish male circumcised neonates (¡Ü 28 days old) evaluated for fever in the emergency room.

Methods: All available medical records of neonates presenting to the pediatric emergency room for evaluation of fever over a 10 year period were reviewed. Data included gender, ethnic background, age in days on presentation to the emergency room, age in days when circumcision was performed (in males ¡Ý 8 days of age), and results of urine, blood and cerebrospinal fluid cultures. Families of males older than 8 days of age who had a UTI[1] were contacted by telephone to verify the circumcision status when the infant presented to the ER[2], to ascertain whether the circumcision was performed ritually by a mohel* or by a physician, and, when not recorded in the chart, to verify the day of life on which circumcision was performed.

Results: Among neonates older than 8 days of age, 60 (24.7%) of the 243 febrile Jewish males had a UTI, as compared to 12 (8.4%) of 143 females (P < 0.0001). In 39 of 54 male neonates (72%) for whom circumcision was performed ritually on the eighth day of life, UTI occurred within 9 days of the circumcision. For females, there was no such clustering of UTI cases in the second week of life, nor during any other time period.

Conclusions: Febrile male neonates who have undergone ritual circumcision have a high prevalence of UTI and must be evaluated and treated accordingly. 

[1] UTI = urinary tract infection

[2] ER = emergency room

* Mohel is a Jewish man trained in the practice of Brit milah (circumcision).

Background: Falls are common events among hospital inpatients and constitute a major health problem in the rehabilitation setting. Many risk factors for falls have been identified for stroke patients, such as muscle weakness, medication side effects, hypoglycemia, hypotension, etc.

Objectives: To assess the risk factors for falls among patients hospitalized for rehabilitation following acute stroke.

Methods:  In a retrospective study of 56 falls over a period of 5 years in 41 stroke patients hospitalized for rehabilitation we surveyed the nurses’ safety risk assessment of the fall. Thirty patients fell once, 9 patients twice and 2 patients four times. The data were obtained from the medical and nursing records. Safety precautions were taken by the nurses for the entire group of patients.

Results: Most of the falls occurred among male patients who had reduced muscular tone (70%), paralysis (54%) and/or hypoesthesia in the involved side of the body. Patients who suffered from hemiplegia fell more often than those with hemiparesis (Wilcoxon rank sum test, P = 0.04, one-sided). Forty-eight percent of the falls occurred during the first month after the last stroke onset, 70% during the morning or the afternoon, and 62% occurred close to the patient’s bed. In 89% of falls the patients used hypoglycemic, antihypertensive, tranquilizing or neuroleptic drugs. Communication disorders (29%), hemianopia or blindness (21%) and visuospatial agnosia (18%) were incremental risk factors for falls. Fifty percent of the falls were caused by either an intrinsic or extrinsic mechanism.

Conclusions: These data suggest that the group of stroke patients at risk for falls in a rehabilitation department can be identified by a variety of impairment and functional assessments. The information may be potentially useful for designing interventions directed at reducing fall frequency among stroke survivors. 

Background: The QT interval reflects the total duration of ventricular myocardial repolarization. Its prolongation is associated with increased risk of polymorphic ventricular tachycardia, or torsade de pointes, which can be fatal.

Objectives: To assess the prevalence of both prolonged and short QT interval in patients admitted to an acute geriatric ward.

Methods: This retrospective study included the records over 6 months of all patients hospitalized in an acute geriatric ward. Excluded were patients with pacemaker, bundle branch block and slow or rapid atrial fibrillation. The standard 12 lead electrocardiogram of each patient was used for the QT interval evaluation.

Results: We screened the files of 422 patients. QTc prolongation based on the mean of 12 ECG leads was detected in 115 patients (27%). Based on lead L2 only, QTc was prolonged in 136 (32%). Associated factors with QT prolongation were congestive heart failure and use of hypnotics. Short QT was found in 30 patients (7.1%) in lead L2 and in 19 (4.5%) by the mean 12 leads. Short QT was related to a higher heart rate, chronic atrial fibrillation and schizophrenia.

Conclusions: Our study detected QT segment disturbances in a considerable number of elderly patients admitted acutely to hospital. Further studies should confirm these results and clinicians should consider a close QT interval follow-up in predisposed patients.
 

Background: Pulmonary tuberculosis continues to be a major cause of mortality, particularly in developing countries. Despite modern anti-TB[1] treatment, the elderly and immigrants from TB-endemic countries are at risk. Multidrug resistance has yet to be resolved..

Objectives: To determine the mortality rate and predictors of mortality among patients hospitalized with TB in Israel.

Methods: We evaluated the medical records of 461 patients with active pulmonary TB who were hospitalized in the department of respiratory care during the 5 year period 2000–2004. Data included demographic, clinical, laboratory and radiological findings, drug resistance as well as adverse reactions to anti-TB treatment.

Results:| Three main ethno-geographic groups were observed: 253 patients from the former USSR, 130 from Ethiopia, and 54 of Israeli origin (as well as 24 residents of other countries). Of the 461 patients 65 patients (13%) died in hospital. The factors that were best predictors of mortality were older age, ischemic heart disease, cachexia, prior corticosteroid treatment, hypoalbuminemia and pleural effusion (P < 0.005 for all). The ethno-geographic factor and the presence of multidrug-resistant bacteria had no significant effect on mortality in our study group.

Conclusions: The mortality rate in our study was relatively low, and there was no significant difference between the three ethno-geographic groups.