Israel Medical Association Journal

Background: Ultrasound examination of the fetus enables diagnosis of many major malformations during pregnancy, providing the possibility to consider interruption of the pregnancy. As a result, in many cases the incidence of malformations at birth does not represent their true incidence.

Objectives: To determine the impact of prenatal diagnosis and termination of pregnancy on the relative incidence of malformations at birth among Jews and Muslim Arabs in Israel.

Methods: Data on selected major malformations in 2000–2003 were collected from the two large central databases of the Ministry of Health and the Central Bureau of Statistics which contain information regarding births, stillbirths and terminations of pregnancies.

Results: For many malformations the total incidence was much higher than the incidence at birth. For almost all of the malformations studied, the total incidence was higher in Muslims than in Jews and the differences were further accentuated among the liveborn because of the differences in the rate of pregnancy terminations.

Conclusions: In order to detect possible influences of environmental or genetic factors on major malformations in Israel, it is critical to look at data including pregnancy terminations, stillbirths and live births.

Background: Enteral nutrition in the critically ill patient is often complicated by gastrointestinal intolerance, manifested by a large gastric residual volume. The frequency of GRV[1] assessment and the intolerant level above which feeding is stopped is controversial.

Objectives: To evaluate a novel approach to EN[2] by allowing high GRV and once-daily assessment that was correlated with the paracetamol absorption test.

Methods: We conducted a pilot prospective study in an 18 bed general intensive care unit. The study group comprised 52 consecutive critically ill mechanically ventilated patients. Enteral nutrition was started at full delivery rate. Once-daily assessment of GRV with three consecutively repeated threshold volumes of 500 ml was performed before stopping EN. The paracetamol absorption test was performed and correlated to GRV. Patients were divided into two groups: low GRV (< 500 ml), and high GRV (at least one measurement of GRV > 500 ml). Clinical outcome included maximal calories delivered, incidence of pneumonia, ICU[3] length of stay, and ICU and hospital mortality.

Results: There were 4 patients (9.5%) with ventilator-associated pneumonia in the low GRV group and 3 (30%) in the high GRV group (P = 0.12). GRV was inversely correlated to paracetamol absorption; however, neither GRV nor paracetamol absorption was associated with the development of pneumonia. Both groups had similar ICU length of stay (11.0 ± 8.2 vs. 13.8 ± 14.4 days, P = 0.41), and similar ICU (21% vs. 40%, P = 0.24) and hospital mortality (35% vs. 40%, P = 1.0).

Conclusions: In critically ill mechanically ventilated patients, allowing larger gastric residual volumes, measured once daily, enables enteral feeding with fewer interruptions which results in high calorie intake without significant complications or side effects.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative for APC gene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

Objectives: To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.

Methods: Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to ≥ 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC[1] patients fulfilling “Bethesda” (laboratory investigation) criteria for Lynch syndrome.

Results: Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI²-High with immunohistology consistent with MLH1 mutation.

Conclusions: Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.

Background: Poisonings are a significant cause of pediatric morbidity and mortality. The Israel Poison Information Center provides clinical consultations on poisonings and drug information 24 hours a day.

Objective: To evaluate epidemiologic characteristics of pediatric poison exposures in Israel.

Methods: We reviewed computerized queries and performed a descriptive analysis of the Poison Center database pertaining to patients less than 18 years old during 2007.

Results: A total of 15,005 pediatric poison exposures were recorded, 80.3% of them occurring in children under 6 years old. Of the calls to the Poison Center, 78.6% were made by the public, 20.7% by physicians, and in 74.4% the call was within 2 hours of exposure. Most exposures occurred at home (89.3%) and were unintentional (89.5%). Among adolescents, most exposures were intentional (49.3%, 38.2% suicides), the time lapse until consultation was longer (37% > 2 hours), and more physicians (54.8%) consulted the Poison Center. Most cases were asymptomatic or mildly affected (92.3%), 54.4% in adolescents. The commonest substances involved in single poison exposure were detergents, antimicrobials, topical preparations, acetaminophen and scale removers; in adolescents the most common substances were acetaminophen, methylphenidate, non-steroidal anti-inflammatory drugs, atropine and ethanol. Moderate to severe toxicity was commonly associated with organophosphates, alkali, ethanol, Vipera palaestinae and neuroleptics. Most patients could be observed at home (66.6%), while more adolescents were referred to emergency departments (42.2% vs. 9.9%) or hospitalized (14.5% vs. 1.9%).

Conclusions: Pediatric poisonings are a significant health problem. The magnitude of the problem is greater in the young age group but more severe in adolescence, probably due to deliberate self-poisoning. Greater national efforts should be directed towards improved poison prevention, rational management of pediatric poisoning, and creating a national poisoning registry.
 

Background: One of the ominous complications following proximal gastrectomy or total gastrectomy is a leak from the esophagogastric or esophagojejunal anastomosis. An upper gastrointestinal swallow study is traditionally performed to confirm the anastomotic patency and lack of any leak before oral feeding can be initiated.

Objectives: To challenge the routine use of UGISs[1] following proximal or total gastrectomy in order to check the integrity of the gastroesophageal or jejunoesophageal anastomosis.

Methods: The charts of 99 patients who underwent PG[2] or TG[3]  for malignant pathology were retrospectively reviewed. UGISs were performed on day 6 following surgery using a water-soluble material.

Results: The UGISs were normal in 95 patients, with none displaying any complication related to the gastroesophageal or jejunoesophageal anastomosis. All four patients who experienced a leak from the anastomosis had an early stormy postoperative course.

Conclusions: Routine use of an UGIS to detect a leak following PG or TG is not justified. UGIS should be performed whenever signs of abdominal sepsis develop following this type or surgery.

Background: Trans-aortic pressure gradient in patients with aortic stenosis and left ventricular systolic dysfunction is typically low but occasionally high.

Objectives: To examine the distribution of trans-aortic PG[1] in patients with severe AS[2] and severe LV[3] dysfunction and compare the clinical and echocardiographic characteristics and outcome of patients with high versus low PG.

Methods: Using the echocardiographic laboratory database at our institution, 72 patients with severe AS (aortic valve area ≤ 1.0 cm²) and severe LV dysfunction (LV ejection fraction ≤ 30%) were identified. The characteristics and outcome of these patients were compared.

Results: PG was high (mean PG ≥ 35 mmHg) in 32 patients (44.4%) and low (< 35 mmHg) in 40 (55.6%). Aortic valve area was slightly smaller in patients with high PG (0.63 ± 0.15 vs. 0.75 ± 0.16 cm² in patients with low PG, P = 0.003), and LV ejection fraction was slightly higher in patients with high PG (26 ± 5 vs. 22 ± 5% in patients with low PG, P = 0.005). During a median follow-up period of 9 months 14 patients (19%) underwent aortic valve replacement and 46 patients (64%) died. Aortic valve replacement was associated with lower mortality (age and gender-adjusted hazard ratio 0.19, 95% confidence interval 0.05–0.82), whereas trans-aortic PG was not (P = 0.41).

Conclusions: A large proportion of patients with severe AS have relatively high trans-aortic PG despite severe LV dysfunction, a finding partially related to more severe AS and better LV function. Trans-aortic PG is not related to outcome in these patients.

Background: The existence of "ophthalmoltonic consensual reaction," a contralateral change in intraocular pressure in the fellow eye induced by treatment of the first eye only, was suggested in 1924. Since then, the validity of this mechanism has been controversial.

Objectives: To assess intraocular pressure changes in the contralateral fellow eyes of patients treated with IOP[1]-lowering medication in one eye, and investigate the existence of an ophthalmotonic consensual reaction.

Methods: The study population included 38 patients with newly diagnosed bilateral ocular hypertension or early open angle glaucoma. One eye of each patient was randomly treated with one of five compounds: prostaglandin analogues, beta-blockers, alpha-2 agonists, carbonic anhidrase inhibitors and a combination therapy: dorzolamide hydrochloride–timolol maleate (Cosopt®, Sharpe & Dohme). The eye with the higher baseline IOP was selected to be the treated eye. After 3 weeks a masked examiner measured the IOP in both the treated and untreated eye.

Results: Mean IOP of the treated eyes at baseline was 26.1 ± 4.2 mmHg and at follow-up 20.2 ±2.9 mmHg, a reduction of IOP from baseline of -6 ± 3.8 mmHg, a mean percent reduction of -22 ± 10.1%. In the contralateral eyes, the mean IOP at baseline was 24.2 ± 3 mmHg and 23.1 ± 3.1 mmHg at follow-up; IOP reduction from baseline was -1.2 ± 1.8 mmHg, or mean percent reduction -4.7 ± 7.1%. A major contralateral IOP decrease was seen only in the beta-blockers and the combination (Cosopt®) treatment groups (-6.1 ± 8.3% and -12.3 ± 8.3% mean percent reduction, respectively, P < 0.05). The contralateral eyes in the prostaglandin analogues, CAI[2] or α2-agonist groups showed only a small change in IOP (-2.6 ± 4.6%, -3.2 ± 2.6%, +0.7 ± 3.3%, mean percent reduction, respectively, P < 0.05).

Conclusions: The existence of an ophthalmoltonic consensual reaction was not supported.

The laparoscopic approach to the treatment of colon and rectal cancer was controversial long after it was accepted for benign conditions. Laparoscopic cancer resection should meet appropriate oncologic standards and achieve a long-term oncologic outcome at least equivalent to that of open resection. Several international randomized controlled trials have provided adequate data to ascertain the oncologic quality of laparoscopic colon resection, showing a benefit in short-term outcome over open resection. The use of laparoscopic resection for rectal cancer is awaiting further investigation.

Background: Simulation-based medical education has become a powerful tool in improving the quality of care provided by health professionals.

Objectives: To evaluate the effect of a simulated patient-based educational program for military recruitment center physicians on the quality of medical encounters with adolescent candidates for military service.

Methods: Twelve physicians participated in an educational intervention that included a one day SP[1]-based workshop, where simulations of eight typical candidates for military service were conducted. Assessment of the physicians' performance before and after the intervention was based on questionnaires filled by 697 and 508 military candidates respectively, upon completion of their medical examination by these physicians. The questionnaire explored health topics raised by the examining physician as well as the atmosphere during the encounter. The candidates were also asked whether they had omitted important medical information during the medical encounter.

Results: Pre- and post-intervention comparison revealed significant changes in the percentages of candidates who reported that they were asked questions related to psychosocial topics: school problems – 59.7% and 68.9% (P = 0.01), protected sex – 29.6% and 36.4% (P = 0.01), mood changes – 46.9% and 52.2% (P = 0.05) respectively. Physicians were perceived as being interested in the candidates by 68.2% of the candidates before the intervention and 77.5% after (P < 0.01). The percentage of candidates who reported omitting medical information decreased from 6.6% before the intervention to 2.4% after (P < 0.01).

Conclusions: A simulated patient-based educational program for military physicians improved the quality of physician-candidate encounters. Such programs may serve as an effective instrument for training physicians to communicate with adolescents.

Background: It is currently recommended that capillary glucose levels of non-critically ill hospitalized diabetic patients be maintained at between 140 and 180 mg/dl. Implementation of these recommendations and evaluation of their effectiveness require that data regarding the glucose control of these hospitalized patients be accessible.

Objective: To analyze glucose control and monitoring of all the diabetic patients hospitalized in the general medicine wards of our medical center.

Methods: Capillary glucose measurements of all diabetic patients hospitalized in our departments of medicine between June and December 2008 were recorded by a central computerized institutional glucometer. Median glucose values and frequency of daily glucose checks per patient were analyzed in the internal medicine wards.

Results: We evaluated 14,366 capillary measurements from 2475 patients; 43% were taken before breakfast and 25% before dinner. A median of one daily determination per patient was obtained. This number increased 1.4-fold in patients with hyperglycemia > 200 mg/dl and 2.5-fold in patients with hypoglycemia. Seventy-five percent of the recorded glucose values were within the recommended target range, with a median daily level of 161 mg/dl and median fasting glucose of 142 mg/dl. A significant variance was found between wards.

Conclusions: The frequency of capillary glucose measurements in diabetic patients hospitalized in general medicine wards was low; most capillary glucose values, however, were within the recommended target range. The optimal monitoring of glucose in these patients remains to be determined.

Background: The prevalence of aortic stenosis increases with advancing age. Once symptoms occur the prognosis in patients with severe aortic stenosis is poor. The current and recommended treatment of choice for these patients is surgical aortic valve replacement. However, many patients, mainly the very elderly and those with major comorbidities, are considered to be at high surgical risk and are therefore denied treatment. Recently, a transcatheter alternative to surgical AVR[1] has emerged.

Objectives: To describe the first year experience and 30 day outcome of transcatheter aortic self-expandable CoreValve implantation in Israel.

Methods: Transcatheter aortic valve implantation using the CoreValve system has been performed in Israel since September 2008. In the following year 55 patients underwent CoreValve TAVI[2] in four Israeli centers.

Results: Patients' mean age was 81.7 ± 7.1 years; there were 35 females and 20 males. The mean valve area by echocardiogram was 0.63 ± 0.16 cm². The calculated mean logistic Euroscore was 19.3 ± 8%. Following TAVI, mean transvalvular gradient decreased from baseline levels of 51 ± 13 to 9 ± 3 mmHg. The rate of procedural success was 98%. One patient died on the first day post-procedure (1.8%) and all-cause 30 day mortality was 5.5% (3 of 55 patients). One patient had a significant post-procedural aortic regurgitation of > grade 2. Symptomatic improvement was evident in most patients, with reduction in functional capacity grade from 3.2 ± 0.6 at baseline to 1.4 ± 0.7. The most common post-procedural complication was complete heart block, which necessitated permanent pacemaker implantation in 37% of patients.

Conclusions: The Israeli first year experience of transcatheter aortic valve implantation using the CoreValve self-expandable system demonstrates an effective and safe procedure for the treatment of severe aortic stenosis in patients at high surgical risk.

Background: Community-acquired pneumonia is a common infection and is associated with high rates of morbidity and mortality. Most patients with CAP[1] are treated empirically.

Objectives: To identify common pathogens causing CAP in hospitalized patients in northern Israel and to evaluate the correlation between etiology and disease severity.

Methods: We conducted a prospective study of patients with CAP hospitalized at HaEmek Medical Center, Afula. We collected demographic, clinical and laboratory data (blood and sputum cultures, serology, pneumococcal urinary antigen test, and respiratory multiplex-polymerase chain reaction from nasopharyngeal swab), and radiologic evaluation was performed.

Results: A total of 126 patients and 24 controls were enrolled. At least one pathogen was identified in 84 cases (66.7%), more than one in 43 patients (34.1%), and no pathogens in 42 (33.3%). Typical bacteria were found in 23 (18.3%), atypical bacteria in 66 (52.4%), and viruses in 42 (33.3%). The number (%) of patients with pathogens isolated was: Chlamydophila pneumoniae 26 (20.6%), Streptococcus pneumoniae 23 (18.3%), Mycoplasma pneumoniae 23 (18.3%), influenza virus A-B 20 (15.9%), Coxiella burnetti 8 (6.3%), and parainfluenza and adenovirus 13 (10.3%) each. A correlation was found only between a high PORT score on admission and S. pneumoniae, although atypical pathogens did not show class predominance.

Conclusions: S. pneumoniae, M. pneumoniae and C. pneumoniae were the most common pathogens isolated, while co-infection was very frequent. PORT score did not predict any of the pathogens involved. The choice of empiric antimicrobial treatment for CAP should be made according to local epidemiologic data.

Background: Guidelines are frequently under-implemented in older patients with heart failure. Octogenerians are often excluded from clinical trials.

Objectives: To characterize the clinical profile of the oldest-old (age ≥ 80 years) heart failure patients hospitalized in a subacute geriatric hospital and to evaluate their management and 1 year outcome.

Methods: Patient characteristics and in-hospital course were retrospectively collected. Diagnosis of heart failure was based mainly on clinical evaluation in addition to chest X-ray results and echocardiographic findings when available.

Results: The study population comprised 96 consecutive unselected heart failure patients hospitalized from January to June 2003. The patients were predominantly women (67%), aged 85 ± 5 years, fully dependent or frail with a high rate of comorbidities. Adherence to guidelines and recommended heart failure medications was poor. Their 1 year mortality was 57%. According to logistic regression analysis, predictors of 1 year mortality were lower body mass index (odds ratio 0.86, 95% confidence interval 0.78–0.96) and high urea levels (OR[1] 1.04, 95% CI[2] 1.02–1.06).

Conclusions: Our study confirms that the management of oldest-old heart failure patients hospitalized in a subacute geriatric hospital was suboptimal and their mortality was exceptionally high.

Background: Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease.

Objectives: To assess – in relation to New York Heart Association class – the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions.

Methods: GFR[1] was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula.

Results: According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA[2] class. Significant correlations were observed between eGFR[3] and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI[4], including bleeding, and major adverse cardiac events.

Conclusions: The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.