Israel Medical Association Journal

Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now® (TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. 

Objectives: To explore retrospectively the predictive value of TN for patients with colorectal and gastric carcinomas. 

Methods: The study group comprised colorectal and gastric carcinoma patients with TN test reports. We identified chemotherapy regimens given for stage IV disease for which TN reports indicated prediction. Protocols were classified as having clinical benefit (CB; i.e., stable disease or any objective response) or progressive disease, and this was compared with the TN prediction. 

Results: Nineteen patients – 12 colorectal and 7 gastric carcinomas – met the inclusion criteria. There were 26 evaluable treatment protocols; of 18 with a CB 15 were predicted to have a CB while 3 were predicted to have a lack of CB. Of eight protocols that had no CB, seven were predicted to have a CB and one was predicted to have a lack of CB. A chi-square test was non-significant (P = 0.78). An exploratory analysis yielded a positive predictive value of 68% and a sensitivity of 83% for the TN test. 

Conclusions: This study emphasizes the need for larger multicenter studies to validate the TN test before it is adopted into clinical practice. 

 

Background: Approximately 80% of patients with myelodysplastic syndromes (MDS) receive multiple red blood cells (RBC), often multiple transfusions, and are therefore prone to develop alloantibodies against RBC. Because of increasing evidence for the role of immune dysregulation in the pathobiology of MDS, we hypothesized that in patients with MDS there is an increase in alloantibody formation beyond that expected by multiple transfusions.

Objectives: To determine the prevalence rates of alloantibodies in patients with MDS who are transfusion dependent and compare them to those of non-MDS patients matched for number of RBC units they received. 

Methods: The blood bank database was screened to identify non-MDS patients matched for age and number of units transfused. Logistic regression analysis was applied to determine factors affecting alloantibody formation. 

Results: Of 60 patients with MDS, 18 (30%) developed alloantibodies against RBC. Transfusion-dependent MDS and non-MDS patients (N=56 each), matched for number of RBC units and age, were compared. Fifteen MDS patients (27%) but only 12 non-MDS patients (12%) developed alloantibodies (P = 0.057). The relative risk for developing antibodies in MDS patients was 2.14, and MDS was the strongest predictor for formation of alloantibodies during transfusion therapy (odds ratio 3.66, confidence interval 1.4–9.3). 

Conclusions: Patients with MDS are at increased risk to develop RBC alloantibodies, partly because these patients receive multiple RBC transfusions. Whether matching for RH and KEL would lead to lower rates of RBC alloantibodies remains to be determined.

 

Background: Exposure to air pollution in the form of particulate matter smaller than 10 µm in diameter (PM10) has been associated with increased morbidity and mortality. However, since air pollution is correlated with confounding factors that might otherwise affect health, identifying the causal link has proven challenging. 

Objectives: To identify the effect of PM10 on hospital admissions due to respiratory illnesses. 

Methods: We used the Instrumental Variable (IV) methodology to control for confounding factors affecting hospital admissions. Exploiting the timing of sandstorms as an instrumental variable allows for a better estimate of the relationship between PM10 and hospital admissions. Data on PM concentrations and hospital admissions rates were compiled for Israel’s two largest cities, Jerusalem and Tel Aviv, for 2007–2009. We compared our IV estimates to those derived from a Poisson regression, which is commonly used in the existing literature. 

Results: Sandstorms led to an increase of 307 µg/m3 of PM10 concentrations. A 10 µg/m3 increase in PM10 is associated with a 0.8% increase in hospital admissions due to respiratory conditions, using Poisson regression. The same finding was noted using the IV methodology. 

Conclusions: The association between PM10 and hospital admission reflects a primarily causal relationship. Instrumental variable methodology could be applied to analysis of the effect of air pollution on hospital admissions. 

 

Background: Physical restraints are a common, albeit controversial, tool used in the acute care setting. 

Objectives: To determine the prevalence of physical restraint use in an acute care hospital. Secondary objectives were to determine whether physical restraints are used more commonly in night shifts, identify patient risk factors for physical restraint use, and establish if staff-to-patient ratio correlated with physical restraint use.

Methods: An observational cross-sectional study was conducted over 3 months in 2013 in the medical, surgical and intensive care units in a mid-sized general hospital. All the physically restrained patients in each observation were added to the registry. At each observation one department was selected for comparison and all non-restrained patients were added to the registry.

Results: The study population comprised 2163 patients. Seventy-six were restrained and 205 were included as case-controls. The prevalence of physical restraint use was 3.51% (95%CI = 2.79–4.37%). Physical restraint use was more common in night shifts than day shifts: 4.40% vs. 2.56% (P = 0.03). Male gender, dependency, invasive ventilation, invasive tubes (nasogastric tube or urine catheter), and bedsores were all significantly correlated with restraint use. Staff-to-patient ratios were not significantly correlated with use of physical restraints.

Conclusions: Physical restraints are relatively common in acute care wards. The use of physical restraints seems to correlate with certain patient characteristics but not with staff-to-patient ratios, and seems more common at night. 

 

Background: Extracorporeal membrane oxygenation (ECMO) may serve as a bridge to regain cardiac function in refractory resuscitation. However, its use has so far been limited owing to low availability, especially in emergency departments. 

Objectives: To describe two children with acute myocarditis successfully treated with ECMO in the emergency department of a tertiary pediatric medical center. 

Description: The children presented with vomiting, followed by rapid deterioration to cardiogenic shock that failed to respond to conservative treatment. Given the urgency of their condition and its presumably reversible (viral) etiology, treatment with ECMO was initiated in the department’s resuscitation room. 

Results: Outcome was excellent, and cardiac function remained normal throughout 6 and 10 months follow-up. 

Conclusions: Extracorporeal life support has enormous potential in the emergency department and warrants further assessment.  

Background: In criminal law, psychiatrists are consulted regarding the "insanity defense" and the defendant's competency to stand trial. Court-ordered hospital admissions for such evaluations are on the increase, creating a major burden on the health system.

Objectives: To assess, in a hospital setting, whether hospitalization of the defendant is necessary for conducting a psychiatric evaluation.

Methods: A 6 month prospective observational study exploring the phenomenon was conducted at the Beer Yaakov Mental Health Center. The psychiatrist was asked both at the initiation and again at the end of the assessment process whether the subject was competent to stand trial and responsible for his/her actions and if hospitalization was necessary in order to conduct the evaluation. 

Results: During the study period there were 112 admissions with a court request for a psychiatric evaluation. In 73 of the cases (65.2%) the evaluating psychiatrist believed there was no need for hospitalization. This assessment did not change by the end of the hospitalization in all cases. Employment and alcohol use were the only factors associated with a lower need for hospitalization (OR 0.24, 95%CI 0.07–0.77, and 0.34, 95%CI 0.13–0.90, respectively).

Conclusions: In the majority of cases, based on the evaluating psychiatrist's responses, the evaluation could have been conducted without need for hospitalization. The findings indicate that an outpatient unit designated to write court-requested psychiatric evaluations could significantly reduce the rates of hospital admissions for this purpose.

 

Background: The practice of administering intravenous contrast to children varies by institution depending on their routine. 

Objectives: To assess the necessity of routine contrast administration in brain magnetic resonance imaging (MRI) of pediatric outpatients referred for chronic headache workups. 

Methods: We conducted a retrospective review of consecutive pediatric brain MRI examinations performed during January and February 2014 in 30 pediatric outpatients referred for evaluation of chronic headache. Independent review was performed by two board-certified neuroradiologists. The raters reviewed each MRI first as a non-contrast examination (without seeing the post-contrast images) and then with post-contrast images. 

Results: No abnormalities were found in six patients. One patient had an indeterminate finding of a tubular cerebellar lesion requiring follow-up. In the remaining patients (n=23), the findings were subclinical and included: mucosal thickening in the paranasal sinuses in 9 patients, cystic changes of the pineal gland in 8 (size 2–9 mm), small developmental venous anomalies in 6, non-specific FLAIR hyperintensities in 4, opacification of the mastoids in 2, and telangiectasia in 1 patient. The subclinical cases that were missed on pre-contrast images were: one small developmental venous anomaly, one telangiectasia and one small pineal cyst, none of which hold clinical significance. All kappa inter-rater and intra-rater agreement scores resulted in values above 0.75, excellent agreement according to Fleiss guidelines.

Conclusions: There seems to be little reason to medically justify large-scale use of routine IV contrast administration to evaluate a brain MRI of pediatric patients referred for chronic headache. 

 

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

Background: Isolation of methicillin-resistant Staphylococcus aureus (MRSA) in healthy individuals is not common in Israel. In our hospital, about 30% of MRSA isolates were SCCmec types IV and V.

Objectives: To identify the demographic and clinical characteristics of patients carrying MRSA SCCmec type IV or V, and to compare them with each other and with those of patients with SCCmec types I-III.

Methods: We conducted a case-control study that included 501 patients from whom MRSA was isolated: 254 with SCCmec type I, II, or III, and 243 isolates from SCCmec types IV or V. 

Results: MRSA was isolated from surveillance cultures in 75% of patients and from a clinical site in 25%. The majority of our study population was elderly, from nursing homes, and with extensive exposure to health care. First, we compared characteristics of patients identified through screening. Statistically significant predictors of SCCmec V vs. IV were Arab ethnicity (OR 7.44, 95%CI 1.5–37.9) and hospitalization in the year prior to study inclusion (OR 5.7, 95%CI 1.9–16.9). No differences were found between patients with SCCmec types I-III and patients with SCCmec type IV or V. Analysis of the subset of patients who had clinical cultures yielded similar results. 

Conclusions: SCCmec types IV and V were common in the hospital setting although rare in the community. It seems that in Israel, SCCmec IV and V are predominantly health care-associated MRSA. 

 

Background: Childhood attention deficit hyperactivity disorder (ADHD) is a chronic health problem with significant risk for long-term morbidity in adulthood.

Objectives: We examined long-term outcomes of ADHD in a population-based sample of childhood ADHD cases prospectively assessed as adults.

Methods: Long-term outcomes for 70 adults who were diagnosed with ADHD during childhood were examined and compared with data on the general population.

Results: Most subjects admitted to persistence of ADHD-related symptoms in adulthood, despite discontinuation of regular medical treatment and follow-up. Areas most severely affected by past and ongoing symptoms included driving performance and incidence of motor vehicle accidents, and rates of marriage stability over time. Relatively unaffected were occupational and academic achievements and military service. 

Conclusions: There is a need for outreach and better services for adults who were previously diagnosed with ADHD. 

 

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

Background: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. 

Objective: To investigate whether in-hospital hyperglycemia alone and after adjustment for age, gender and lipidemia correlates with in- and out-of-hospital mortality.

Methods: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. 

Results: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 ± 64 vs. 180 ± 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality.

Conclusions: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia.