Israel Medical Association Journal

Background: A pandemic (H1N1) influenza A virus was identified in 2009.

Objectives: To investigate predictors for pandemic (H1N1) 2009 virus infection among hospitalized patients with a flu-like illness and to identify parameters suggesting a severe clinical course.

Methods: We analyzed a cohort of all patients hospitalized during a 2 month period with a flu-like syndrome who were tested for pandemic (H1N1) 2009 infection. Demographic, clinical and laboratory, along with outcome parameters, were recorded and compared between pandemic (H1N1) 2009 virus-positive and negative hospitalized patients.

Results: Of the 179 examined hospitalized patients suspected of having pandemic (H1N1) 2009 infection 65 (36%) were found positive. These patients tended to be younger and had significantly fewer comorbidities. In addition, they had a significantly higher frequency of fever (94%), cough (86%) and myalgia (29%). Furthermore, age < 65 years and cough were independent predictors for pandemic (H1N1) 2009 virus positivity in a multivariate regression analysis. Notably, 14 of the 65 positive patients (21.5%) had acute respiratory insufficiency requiring treatment in the intensive care unit. These patients were neither older nor previously sicker than patients with non-severe disease, but were distinguished by augmented inflammatory markers, significant lymphopenia associated with disease severity, and overall mortality of 21.4%.

Conclusions: Pandemic (H1N1) 2009 virus-positive hospitalized patients tend to be younger and have fewer comorbidities as compared to compatible negative patients. A significant number of relatively young and previously healthy positive patients might develop severe disease associated with a robust inflammatory reaction and significant lymphopenia.

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: 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: The best therapeutic alternative for patients suffering from in-stent restenosis after drug-eluting stent implantation remains to be elucidated.

Objective: To characterize the pattern, treatment and outcomes of DES[1]-related in-stent restenosis in patients treated at our institution.

Methods: We determined the incidence and major adverse clinical events in 71 consecutive patients with DES failure among 2473 patients who were treated with 2548 drug-eluting stents between 2004 and 2007. We analyzed the clinical data, procedural parameters and clinical outcomes.

Results: The type and number of stents implanted were as follows: Cypher (n=1808), Endeavor (421) and Taxus (319) of these, 53 (2.9%), 10 (2.4%), and 8 (2.5%) patients respectively presented with restenosis. The mean time to restenosis was 11.3 ± 9.9 months. Patients’ mean age was 65 ± 11 years 75% were male, and 68% had diabetes mellitus. Unstable angina was the clinical presentation in 52 (73%). At 6 months, 3 patients had developed myocardial infarction (4.2%), repeat restenosis at follow-up was diagnosed in 8 patients (11.3%), the overall major adverse clinical events rate was 18.3% (13 patients), and 2 patients died (2.8%).

Conclusions: Drug-eluting stent-related restenosis is relatively infrequent but remains a clinical challenge. It occurs more frequently in complex lesion subsets, but the overall intermediate-term prognosis is tolerable.  

[1] DES = drug-eluting stent

Background: High frequency oscillatory ventilation based on optimal lung volume strategy is one of the accepted modes of ventilatory support for respiratory distress syndrome in very low birth weight infants. In 1999 it was introduced in our unit as the primary ventilation modality for RDS[1].

Objectives: To evaluate if the shift to HFOV[2] influenced the outcome of ventilated VLBW[3] infants in the neonatal intensive care unit of Carmel Medical Center.

Methods: Data were obtained from the medical charts of VLBW infants born at Carmel Medical Center, and late mortality data were taken from the Israel Ministry of Internal Affairs records. A retrospective analysis and a comparison with a historical control group ventilated by the conventional method were performed.

Results: A total of 232 VLBW infants with RDS were mechanically ventilated, from 1995 to 2003: 120 were ventilated using HFOV during the period 1999–2003 and 102 infants using CV[4] during 1995–1999. The mean gestational age of survivors was 27.4 ± 2 weeks in the HFOV group and 28.4 ± 2 in the conventional ventilation group (P = 0.03). The sub-sample of infants with birth weights <1000 g ventilated with HFOV showed higher survival rates than the infants in the conventional ventilation group, 53 vs. 25 (64.6% vs. 44.6%) respectively (P < 0.05). A trend for lower incidence of pulmonary interstitial emphysema was observed in the HFOV group.

Conclusions: The introduction of HFOV based on optimal lung volume strategy proved to be an efficient and safe method of ventilation support for VLBW infants in our unit.

Background: Severe hearing impairment can have devastating effects on social integration and vocational opportunities.

Objectives: To investigate how well – or poorly – individuals who underwent cochlear implantation as children integrated into the general Israeli hearing community.

Method: We sent a questionnaire to the 30 subjects ≥ 18 years old who underwent cochlear implants our department from 1990 to 2004 when they were < 18 years of age and had used their device for at least 3 years before replying.

Results: Eighteen implant users responded (14 males), yielding a 60% response rate. Their mean age was 13.3 ± 7.0 years (range 6–17) at implantation and 21.1 ± 3.6 years (range 18–34) when they filled in the questionnaire. Five were attending rabbinical school (yeshiva students), four were in regular military service, five were university students (three also held jobs), two were attending high school, one was employed (and had a university degree), and one had left the yeshiva and was unemployed when he returned the questionnaire. Fourteen respondents use the oral communication mode for conversation and the other 4 use both oral and sign languages. Longer daily implant use was significantly associated with coping with the difficulties in the setting in which they were currently active, with a higher level of satisfaction with their current lifestyle and with recognition of the implant’s contribution to this satisfaction (P = 0.037, P = 0.019 and P = 0.001, respectively).

Conclusions: Advances in cochlear implant technologies enable profoundly deaf implanted children to integrate well into the Israeli hearing society, albeit with a large inter-subject variability.

Background: Parallel to increased life expectancy, the number of very elderly patients hospitalized in internal medicine departments is growing rapidly, although clinical data on hospital care are lacking.

Objectives: To investigate the sociodemographic data, hospitalization characteristics and outcomes of nonagenarian patients, as these measures are necessary for evaluating prognostic information and predictors of mortality.

Methods: We reviewed the medical records of all patients aged ≥ 90 hospitalized in our institute's Department of Internal Medicine. The data comprised 482 admissions of 333 patients hospitalized over a one year period.

Results: Half of the study patients were residents of nursing institutions. A high rate of atrial fibrillation was documented (106 patients, 32%). Acute infectious diseases constituted the leading diagnosis (276/482 admissions, 57%), followed by acute coronary syndrome (17% of admissions). In-hospital mortality occurred in 74 patients (22%). Chronic therapy with statins or acetylsalicylic acid was inversely related to mortality (P < 0.05). The main predictors for in-hospital death of nonagenarians were pressure sores, older age, atrial fibrillation, malignant disease, and admission due to an acute infection, especially Clostridium difficile-associated diseases. In addition, mental decline, permanent urinary catheter, leukocytosis, renal failure and hypoalbuminemia predicted post-discharge mortality. Admission due to an infectious disease but not acute coronary syndrome was significantly correlated to in-hospital and post-discharge mortality (P < 0.001).

Conclusions: Hospitalized nonagenarians comprise a growing group with distinct characteristics and increasing significance in the daily practice of internal medicine departments. Comprehensive assessment of the elderly at admission together with identification of the above clinical and laboratory risk factors for mortality will help determine in-hospital management, discharge planning and rehabilitation programs.

Background: Intravenous tissue plasminogen activator has been approved treatment for acute (≤ 3 hours) ischemic stroke in Israel since late 2004. The Israeli experience with IV tPA[1] is still limited. Several factors may influence the response to IV thrombolysis, including time-to-treatment parameters and tandem internal carotid artery/middle cerebral artery stenosis/occlusion.

Objectives: To compare our experience with IV tPA treatment of patients with acute ischemic stroke to the findings of the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy, international data) and of the Sheba Medical Center (national data) and to compare the early outcome among patients with ischemic stroke in the MCA[2] with and without severe ICA[3] stenosis.

Methods: We obtained demographic data, timing details, stroke severity, hemorrhagic complications, mortality, and early outcome from the records of IV tPA-treated acute ischemic stroke patients.

Results: Fifty-eight patients (median age 69 years, 26 females) with acute ischemic stroke were treated by IV tPA at the Tel Aviv Sourasky Medical Center in 2006–2007. Median time between stroke onset and IV tPA administration was 148 minutes for the Sourasky center, 150 minutes for the Sheba center, and 140 minutes for SITS-MOST. The Sourasky mortality rate was 10.5%. Of the 31 patients who suffered MCA stroke, 8 had severe ipsilateral ICA stenosis. These 8 had significantly lower neurological improvement than the 23 without ipsilateral ICA stenosis (1/8 versus 15/23, P <0.001).

Conclusions: Our data demonstrate fairly similar parameters of IV tPA treatment compared to other centers and suggest that patients with severe ICA stenosis might be less likely to benefit from IV tPA.

Background: Research on synergistic effects of patient-targeted interventions combined with physician-targeted interventions has been limited.

Objectives: To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.

Methods: In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure; the proportion of patients with HbA1c[1] < 9%, LDL[2] < 130 mg/dl and SBP[3] < 140 mmHg both as separate outcomes and combined.

Results: After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c < 9%, LDL < 130 mg/dl and SBP < 140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).

Conclusions: Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease. 

Background: Patients with thick melanomas > 4 mm deep are at great risk for regional and distant metastatic disease. Historically, the appropriate management of thick melanomas has remained unclear and there is no consensus in the literature. Many have taken the nihilistic view that surgical intervention to excise regional nodal basins is not justified in light of the poor overall prognosis and risk of occult distant disease.

Objectives: To review the outcome of patients with thick node negative melanoma treated at a multidisciplinary academic center

Methods: We retrospectively reviewed a database of melanoma patients to identify patients with thick melanomas, > 4 mm, who were either clinically or sentinel node biopsy negative, staged T4N0, stage IIb or IIc. The charts of these patients were reviewed and updated, with a median follow-up of 4 years.

Results: We identified 23 patients who fit these criteria. Of these, 18 (78%) remain alive with a median follow-up of 4 years. Five patients died of metastatic disease. Of the 18 surviving patients, 14 remained with no evidence of disease after initial resection of their primary lesions. The majority of the recurrences were non-nodal.
Conclusions: The overall survival of patients in our study remains above 75%, at median follow-up of 4 years, even with thick initial index tumor depths. Most of the failures were due to hematogenous spread with lymphatic sparing. Tumor biology that may inhibit lymphatic spread could be a target of future investigation

Background: Despite progress in medical and surgical care the mortality rate of congenital diaphragmatic hernia remains high. Assessment of short-term outcome is important for comparison between different medical centers.

Objectives: To evaluate the short-term outcome of infants born with symptomatic CDH[1] and to correlate demographic and clinical parameters with short-term outcome.

Methods: We performed a retrospective cohort study in which demographic, obstetric and perinatal characteristics were extracted from infants' files. For comparison of categorical variables chi-square test and Fisher's exact test were used and for continuous variables with categorical variables the Mann-Whitney test was used. Sensitivity and specificity were estimated by receiver operator curve.

Results: The study group comprised 54 infants with CDH, of whom 20 (37%) survived the neonatal period. Demographic characteristics were not associated with survival. Regarding antenatal characteristics, absence of polyhydramnion and postnatal diagnosis were correlated with better survival. Apgar scores (above 5 at 1 minute and 7 at 5 minutes), first arterial pH after delivery (above 7.135) and presence of pulmonary hypertension were significantly correlated with survival. Also, infants surviving up to 6 days were 10.71 times more likely to survive the neonatal period.

Conclusions: The survival rate of symptomatic newborns with CDH at our center was 37% for the period 1988–2006. Prenatal diagnosis, Apgar score at 5 minutes and first pH after delivery were found to be the most significant predictors of survival. Prospective work is needed to evaluate the long-term outcome of infants with CDH.