Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood.

BACKGROUND: In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood. METHODS: We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used. RESULTS: During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular causes, after adjustment for sex, age, birth year, sociodemographic characteristics, and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses. CONCLUSIONS: A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood. (Funded by the Environment and Health Fund.).

Hypertension in late adolescence and cardiovascular mortality in midlife: a cohort study of 2.3 million 16- to 19-year-old examinees.

BACKGROUND: The effect of early hypertension on midlife cardiovascular (CV) mortality remains controversial. We assessed the association of established hypertension in late adolescence with subsequent CV mortality. METHODS: Of 2,298,130 Israeli adolescents (60% males; age 17.4 ± 0.3 years) who underwent a compulsory medical examination prior to military service between 1967 and 2010, 8720 teenagers (0.4%) were formally diagnosed with persistent hypertension. Using Cox proportional hazards modeling, we compared the hypertensive group to the large normotensive group with regard to time to event analysis of midlife mortality due to cerebrovascular accidents (CVA), coronary heart disease (CHD), sudden death (SD) and their summation as cardiovascular disease (CVD). RESULTS: During 45,729,521 person-years of follow-up, we identified 2918 CV deaths-2879 and 39 among the 2,289,410 normotensive and 8720 hypertensive adolescents, respectively. Hypertension at a young age was associated with a threefold elevation of stroke mortality compared to normotension when adjusted for sex, age at examination, birth year, country of origin, socioeconomic status, education, body mass index (BMI) and height [hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.76-5.54; p < 0.001]. There was no significant association of hypertension with CHD mortality or SD. An increased risk for overall CVD mortality among hypertensive youngsters (HR 1.51; 95 % CI 1.10-2.07) was attenuated after adjusting for BMI and other covariates (HR 1.24; 95% CI 0.90-1.72). CONCLUSIONS: Established hypertension at a young age was independently associated with elevated stroke mortality in midlife. This finding warrants confirmatory large-scale long-term follow-up studies to address the distant effects of adolescent hypertension.

A large-scale study on epidemiology and risk factors for chronic ankle instability in young adults.

Up to 40% of ankle sprains can result in chronic ankle instability (CAI). The prevalence of CAI and its association with body mass index (BMI) and height in the general young adult population has not been reported. The database records of young adults before recruitment into mandatory military service were studied. Information on the disability codes associated with CAI was retrieved. Logistic regression models were used to assess the association between the BMI and body height with various grades of CAI severity. The study cohort included 829,791 subjects (470,125 males and 359,666 females). The prevalence was 0.7% for mild CAI and 0.4% for severe instability in males and 0.3% and 0.4%, respectively, for females (p < .001). An increased BMI was associated with ankle instability in males (overweight, odds ratio [OR] 1.249, p < .001; obese, OR 1.418, p < .001) and females (overweight, OR 1.989 p < .001; obese, OR 2.754, p < .001). The body height was associated with an increased risk of CAI when the highest height quintile was compared with the lowest height quintile in both males (OR 2.443, p < .001) and females (OR 1.436, p < .001) for all levels of instability severity. The present study has shown a greater prevalence of CAI among males than females in a general healthy young adult population. CAI was associated with an increased BMI and greater body height for all grades of instability severity.

Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.

OBJECTIVE: There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. METHODS: We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16-20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. RESULTS: During 30 years of follow-up, death rates were 8.73/10(4) versus 4.32/10(4) person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. CONCLUSIONS: FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.

The association between body mass index and increased utilization of healthcare services: a retrospective cohort study of 51,521 young adult males.

OBJECTIVE: To examine the association between the entire body mass index (BMI) range and healthcare utilization. METHODS: Weight and height were measured during medical examinations of recruits prior to their entry into the military in Israel. All recruits were followed-up during service and all of their medical information was recorded in a central electronic medical record. We extracted medical and sociodemographic data for all Jewish male combat recruits during their first year of service. The study included 51,521 subjects who were divided into quintiles according to BMI. Using logistic regression models, we determined the association between BMI and high numbers of physician encounters, emergency room visits, referrals to specialists, imaging, laboratory tests, and medication prescriptions. RESULTS: In comparison with the lowest BMI quintile, there was a significant increase in the highest quintile with regard to an increased number of physician encounters (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.19-1.36), emergency room visits (OR, 1.2; 95% CI, 1.12-1.29), referrals to specialists (OR, 1.22; 95% CI, 1.14-1.31), and medication prescriptions (OR, 1.23; 95% CI, 1.15-1.32). An increase in the number of laboratory tests was not statistically significant and there was no difference in imaging referrals. Adjustment for various sociodemographic variables and medical conditions did not significantly change the results. CONCLUSION: Higher BMI is related to increased utilization of healthcare services, even for BMI values in the normal range.

Implementation of a clinical decision support system for computerized drug prescription entries in a large tertiary care hospital.

BACKGROUND: Prescription errors are common in hospitalized patients and result in significant morbidity, mortality and costs. Electronic prescriptions with computerized physician order entry systems (CPOE) and integrated computerized decision support systems (CDSS providing online alerts) reduce prescription errors by approximately 50%. However, the introduction of CDSS is often met by opposition due to the flood of alerts, and most prescribers eventually ignore even crucial alerts ("alert fatigue"). OBJECTIVES: To describe the implementation and customization of a commercial CDSS (SafeRx) for electronic prescribing in Internal Medicine departments at a tertiary care center, with the purpose of improving comprehensibility and substantially reducing the number of alerts to minimize alert fatigue. METHODS: A multidisciplinary expert committee was authorized by the hospital administration to customize the CDSS according to the needs of six internal medicine departments at Sheba Medical Center. We assessed volume of prescriptions and alert types during the period February-August 2012 using the statistical functions provided by the CDSS. RESULTS: A mean of 339 +/- 13 patients per month per department received 11.2 +/- 0.5 prescriptions per patient, 30.1% of which triggered one or more CDSS alerts, most commonly drug-drug interactions (43.2%) and dosing alerts (38.3%). The review committee silenced or modified 3981 alerts, enhancing comprehensibility, and providing dosing instructions adjusted to the patient's renal function and recommendations for follow-up. CONCLUSIONS: The large volume of drug prescriptions in internal medicine departments is associated with a significant rate of potential prescription errors. To ensure its effectiveness and minimize alert fatigue, continuous customization of the CDSS to the specific needs of particular departments is required.

Risk of germ cell testicular cancer according to origin: a migrant cohort study in 1,100,000 Israeli men.

Testicular cancer incidence is highest among men of northern European ancestry and lowest among men of Asian/African descent. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of testicular germ cell tumors (TGCTs), controlling for possible confounders. Data on 1,092,373 Jewish Israeli males, who underwent a general health examination prior to compulsory military service at ages 16-19 between the years 1967-2005, were linked to Israel National Cancer Registry to obtain incident TGCTs up to 2006. Cox proportional hazards was used to model time to event. Overall, 1,001 incident cases (534 seminoma and 467 nonseminoma) were detected during 19.2 million person-years of follow-up. Origin was a strong independent predictor of TGCTs with remarkably low incidence for North African-born (HR = 0.10, 95% CI: 0.04-0.21) and Asian-born (HR = 0.35, 0.20-0.62), while intermediate for Israeli-born of North African origin (HR = 0.48, 0.40-0.58) and Asian origin (HR = 0.56, 0.47-0.66), compared to European origin. A comparison of Israeli born of North African and Asian origin with North African and Asian-born yielded a HR of 2.31 (1.36-3.93). Significant risk factors controlled for were year of birth, years of education and height. Findings persisted when analyses were stratified by histologic subtypes of TGCTs. The findings of lower rates of TGCTs among men born in North Africa and Asia compared to European ancestry, but a steep increase in next generation migrants, particularly among the Israeli-born migrants from North Africa, provide clues to direct further research on the role of modern lifestyle and environment in the etiology of TGCTs.

Country of origin, age at migration and risk of cutaneous melanoma: a migrant cohort study of 1,100,000 Israeli men.

Cutaneous melanoma (CM) is a common cancer with increasing incidence in many parts of the world where light-skinned populations live. We conducted a large-scale nationally representative migrant cohort study to assess country of origin and age at migration as predictors of CM, controlling for possible confounders. Data on 1,086,569 Israeli Jewish males, who underwent a general health examination before compulsory military service at ages 16-19 between the years 1967-2005, were linked to Israel National Cancer Registry to obtain incident CM up to 2006. Cox proportional hazards was used to model time to event. Overall, 1562 incident cases were detected during 19.3 million person-years of follow-up. Origin was a strong independent predictor of CM. Incidence was higher for European (hazard ratio [HR] = 4.08, 95% confidence interval [CI]: 3.55-4.67) and Israeli origin (HR = 2.92, 95% CI: 2.25-3.79) compared to N. African/Asian origin, adjusted for year of birth, years of education, residential socio-economic position, rural residence and body surface area (or height). Among those of European origin, the adjusted risk was significantly lower for those who immigrated after the age of 10 years (HR = 0.58, 95% CI: 0.45-0.73) but not for younger ages (HR = 1.02, 95% CI 0.84-1.23) compared to Israeli born. The high rates of CM among men of European origin and the almost twofold lower risk among those immigrating after age 10 provide solid support for the deleterious role of childhood sun exposure as a risk factor for melanoma. These findings will serve in directing public health and research efforts.

Body mass index and socioeconomic status measured in adolescence, country of origin, and the incidence of gastroesophageal adenocarcinoma in a cohort of 1 million men.

BACKGROUND: To the authors' knowledge, little work has been done concerning adolescent precursors for gastroesophageal cancer. In the current study, the association of adolescent overweight as well as socioeconomic status (SES) with the incidence of esophageal adenocarcinoma (EAC), gastroesophageal junction adenocarcinoma (GEJAC), and noncardia gastric cancer (NCGC) was evaluated. METHODS: Body mass index (BMI) was measured in 1 million Israeli adolescent males who underwent a general health examination at a mean age of 17.3 ± 0.5 years from 1967 to 2005. Overweight was defined as a BMI ≥ 85th percentile of the standard US distribution in adolescence. Incident cancer was identified by linkage with the Israeli National Cancer Registry. RESULTS: A total of 182 incident cancer cases were documented (52 combined EAC and GEJAC cases and 130 NCGC cases). Adolescent overweight at baseline (BMI ≥ 85th percentile) was associated with an increased risk in the combined group of cases of EAC and GEJAC (multivariable hazards ratio [HR], 2.1; 95% confidence interval [95% CI], 1.1-4.3 [P = .032]). Low SES (the lowest category vs the highest) as well as low number of years of education (≤ 9 years) were associated with an increased risk of intestinal-type NCGC (multivariable HR, 2.2; 95% CI, 1.0-4.8 [P = .041] and multivariable HR, 1.9; 95% CI, 1.1-3.19 [P = .020], respectively). The adjusted risk of NCGC was higher in immigrants born in Asian countries and the former Soviet Union. CONCLUSIONS: Overweight during adolescence was found to be substantially associated with the subsequent development of EAC and GEJAC. In addition, although potential confounding by Helicobacter pylori infection status or lifestyle factors was not fully accounted for in the analyses, lower SES as well as immigration from higher-risk countries are important determinants of NCGC.

Adolescent obesity and paternal country of origin predict renal cell carcinoma: a cohort study of 1.1 million 16 to 19-year-old males.

PURPOSE: The incidence of renal cell carcinoma has increased in recent decades, particularly among middle-aged adults. Early precursors of renal cancer remain unclear. We evaluated the association of body mass index and height determined in late adolescence, and paternal or grandpaternal country of origin with the risk of renal cell carcinoma. MATERIALS AND METHODS: Health related data on 1,110,835 males at ages 16 to 19 years who were examined for fitness for military service between 1967 and 2005 were linked to the Israel National Cancer Registry in this nationwide, population based cohort study. We used Cox proportional hazards modeling to estimate the HR of renal cell carcinoma associated with birth year, body mass index, height, father country of origin and socioeconomic indicators. RESULTS: During 19,576,635 person-years of followup renal cancer developed in 274 examinees. Substantial excess risk was conferred by a body mass index of greater than 27.5 kg/m(2) compared to less than 22.5 kg/m(2) (HR 2.43, 95% CI 1.54-3.83, p <0.0001). Asian or African origin was protective compared to European origin (African origin HR 0.67, 95% CI 0.49-0.92). CONCLUSIONS: Overweight in late adolescence is a substantial risk factor for renal cell carcinoma. European origin is independently associated with excess risk and it persists among Israeli born males. Preventing childhood obesity may be a promising target for decreasing the burden of renal cancer.

Circulating progenitor and apoptotic progenitor cells in patients with aortic regurgitation.

BACKGROUND: Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. Reduced numbers of EPCs are related to endothelial dysfunction and adverse clinical events, suggesting that endothelial injury in the absence of sufficient repair by circulating EPCs promotes the progression of vascular disease or valvular disorder. The aim of the present study was to assess the number and role of EPCs in patients with aortic valve regurgitation (AR). METHODS AND RESULTS: We assessed the number of EPCs and apoptotic EPCs in 31 patients with significant AR and compared them with 30 patients who had similar risk factors and no valvular disease. The numbers of EPCs and apoptotic EPCs were assessed by flow cytometry. The 2 groups had similar clinical characteristics. Patients with AR had fewer circulating EPCs and late apoptotic EPCs as compared with the control group (0.054 ± 0.03% vs. 0.079 ± 0.06%, P=0.039 and 0% (0-3.4%) vs. 5% (0-14%), P=0.03, respectively). In patients with AR, circulating EPCs correlated negatively with septal thickness (r=-0.47, P=0.01), whereas late apoptotic EPCs had a negative correlation with left ventricular end-systolic diameter (r=-0.57, P=0.01). CONCLUSIONS: Patients with AR have fewer EPCs and late apoptotic EPCs. These data suggest an impaired valvular endothelial cell regenerative process in patients with AR.

Flexible pes planus in adolescents: body mass index, body height, and gender--an epidemiological study.

BACKGROUND: Most studies on the prevalence of flexible pes planus (FPP) have been conducted in pediatric populations and older adults. There is limited comparable information on these parameters for the adolescent age group. The purpose of this study was to report the prevalence of FPP and its association with body mass index (BMI), body height, and gender among healthy and fit adolescents. METHODS: The data for this study were derived from a medical database containing records of 17-year-old males and females before their recruitment into mandatory military service. Information on the disability codes associated with FPP according to the Regulations of Medical Fitness Determination was retrieved. Logistic regression models were used to assess the association between BMI, body height, and gender to various grades of FPP severity. RESULTS: The study cohort included 825 964 adolescents (467 412 males and 358 552 females). The prevalence was 12.4% for mild FPP and 3.8% for severe FPP among the males and 9.3% and 2.4%, respectively, for the females. An increased BMI was associated with FPP in both males (overweight: odds ratio [OR] 1.385, confidence interval [CI] 1.352-1.419, P < .001; obese: OR 1.765, CI 1.718-1.813, P < .001) and females (overweight: OR 1.408, CI 1.365-1.620, P < .001; obese: OR 1.549, CI 1.481-1.620, P < .001). Body height was associated with a decreased risk of FPP when the highest height quintile was compared with the lowest height quintile in both males (OR 0.782, CI 0.762-0.802, P < .001) and females (OR 0.730, CI 0.707-0.754, P < .001) for all FPP severity grades. CONCLUSIONS: There was a greater prevalence of FPP among males compared with females in a general healthy adolescent age group. FPP was associated with increased BMI and shorter body height for all grades of FPP severity. LEVEL OF EVIDENCE: Level II, diagnostic study.

The association between occupation and the incidence of knee disorders in young military recruits.

OBJECTIVE: To investigate the association between occupational risk factors and the incidence of knee disorders in a young adult population. METHODS: Israeli recruits to the Israel Defense Forces go through a rigorous medical investigation. Study participants were classified by prior knee condition status and divided into 5 categories of prospective occupational exposure to physical activity according to their assigned military duties, and were then followed for 30 months for the development of severe knee disorders (SKD). Logistic regression analysis was used to estimate the occupational risks for incident SKD, adjusted for any previous mild or moderate disorder, body mass index, and body height at induction. RESULTS: The study population consisted of 76,491 males. SKD developed in 615 (0.8%). Compared to administrative workers as referents, a higher risk of developing SKD was manifest among high intensity combat occupations, (odds ratios [OR] 2.15), those in moderate intensity combat occupations (OR 2.57) and maintenance (OR 1.59). Drivers did not demonstrate increased risk of knee disorders compared to referents. CONCLUSIONS: Occupational factors during military service are associated with incident SKD, even when taking into account previous knee disorders, body mass index, and height, which also had independent effects in our study population.

Measured body mass index in adolescence and the incidence of pancreatic cancer in a cohort of 720,000 Jewish men.

PURPOSE: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with pancreatic cancer incidence in a cohort of 720,927 Jewish Israeli men. METHODS: Body mass index (BMI) was measured during a general health examination at ages 16-19 between the years 1967 and 1995. Overweight was defined as BMI ≥ 85th percentile of the reference US-CDC distribution in adolescence. Pancreatic cancer was identified by linkage with the Israel National Cancer Registry up to 2006. RESULTS: The mean follow-up period was 23.3 ± 8.0 years. During 16.8 million person-years, 98 cases of pancreatic cancer were detected. Using Cox proportional hazards modeling, overweight in adolescence predicted an increased risk of pancreatic cancer [hazard ratio (HR) = 2.09; 95% confidence interval (CI): 1.26-3.50, p = 0.005]. Compared with adolescents with 'normal' range BMI Z-scores (-1 to +1), adolescents with Z-scores > 1 showed significantly increased risk [HR, 2.28 (95% CI: 1.43-3.64), p = 0.001]. Lower education level (10 or less years of schooling vs. 11-12 years) was also associated with increased risk of pancreatic cancer [HR 1.90 (95% CI: 1.27-2.86, p = 0.002)], whereas height, country of origin and immigration status were not. CONCLUSIONS: Adolescent overweight is substantially associated with pancreatic cancer incidence in young to middle-aged adults. Applying our point estimates to the 16.8% prevalence of excess weight in Israeli adolescents in the past decade suggests a population fraction of 15.5% (95% CI: 4.2-29.6%) for pancreatic cancer attributable to adolescent overweight in Israel.

A model for assessing the gap between physician residency demand and present status.

BACKGROUND: The medical workforce shortage worldwide varies for different residencies. OBJECTIVES: To determine future gaps in medical specialties in Israel by means of a model and to identify trends and considerations among medical students when they choose their residencies. METHODS: The gap (Gi) assessment model was based upon current demand (Di) and existing (Ei) status for each residency, using the formula [Gi = (Di-Ei)/Ei]. Ei represented the proportion of specific residencies in 2006-2010 out of all Israeli residency graduates and Di was based on questionnaires filled out by medical students at Sackler and Hadassah medical schools in Tel Aviv and Jerusalem, respectively (N = 909). RESULTS: The largest relative shortages (Gi ranges from -1 to 1) were in Pathology (G = -1), Rehabilitation Medicine (-0.9), Radiology (-0.8), Family Medicine (-0.8) and Anesthesiology (-0.8). The highest relative demands were in Surgical subspecialties (2.9) and Obstetrics/Gynecology (OB/GYN) (1.6). More females than males chose residencies in OB/GYN (19.5% vs. 7.1%, P < 0.001) and Pediatrics (28.1% vs. 15.4%, P < 0.001). Surgery subspecialties (9% vs. 23.7%, P < 0.001) were male-predominant. The workload consideration was rated higher among females, while income was rated higher among males. Among students in clinical years, compared to pre-clinical, there was a decline in the selection of some professions, including Surgical subspecialties (9.7% vs. 19.5%, P < 0.001). CONCLUSIONS: The suggested model, based on a survey of demand and current or projected future needs, can be used to assess gaps and plan early interventions. Programs at the level of medical school may affect residency preferences. The decline in selection of surgical professions and the increasing workload as a consideration for residency choice should be given attention.

Rapid detection of blaKPC carbapenemase genes by internally controlled real-time PCR assay using bactec blood culture bottles.

Rapid detection of drug-resistant bacteria in clinical samples plays an instrumental role in patients' infection management and in implementing effective infection control policies. In the study described in this report, we validated a multiplex TaqMan real-time quantitative PCR (qPCR) assay for the detection of bla(KPC) genes and the human RNase P gene in Bactec blood culture bottles. The MagNA Pure LC (version 2.0) instrument was utilized to extract nucleic acids from the inoculated broth, while bovine serum albumin (BSA) was utilized as the PCR inhibitor reliever. The multiplex assay, which was specific for the detection of bla(KPC) genes, had a limit of detection of 19 CFU per reaction mixture with human blood-spiked Bactec bottles. Of the 323 Bactec blood culture sets evaluated, the same 55 (17%) blood cultures positive for carbapenem-resistant bacteria by culture were also positive by the validated qPCR assay. Thus, the sensitivity, specificity, positive predictive value, and negative predictive value of the qPCR assay compared to the results of culture were all 100%. bla(KPC) genes were also detected from the same Bactec bottle broth after manual extraction with a QIAamp DNA minikit; however, there was an average 3-threshold-cycle delay in the qPCR readings. With the limited therapeutic options available, the accurate and rapid detection of bla(KPC)-possessing bacteria by the described bla(KPC)/RNase P assay will be a crucial first step in ensuring optimal clinical outcomes and infection control.

[The approach to the physician shortage in Israel].

The practice of medicine has changed in the last decade. Physicians no longer work largely solo but are part of interdisciplinary medical teams, and patient cases are more complex, as they suffer from multiple diseases. Today, the physician must also deal with economic, legal and public opinion issues. All of these factors pose new challenges to physicians. Apart from the changing world, there is also a shortage of physicians in Israel, as the number of new immigrant physicians has decreased over the last decade. Other medical professions and infrastructures are also lacking, including nurses, acute care hospital beds, intensive care beds and more. This increases the burden on physicians who must face a rapid turnover of patients per bed, more than in any other OECD country. In our work, we have suggested some new approaches to the physician shortage, apart from increasing the number of positions in medical schools, including changing the residency program and canceling the internship. The residency program will be divided into two stages: Two years in general medicine surgery or pediatrics and the second part in subspecialties such as pediatric surgery, neurology, gastroenterology, cardiology and others. An option to continue residency in general medicine, pediatrics, or surgery will also be possible and must be encouraged. We believe that the Scientific Council of the Israeli Medical Association is the professional organization that must evaluate this proposition.

Fast track evaluation of patients with acute chest pain: experience in a large-scale chest pain unit in Israel.

BACKGROUND: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness. OBJECTIVES: To assess the routine evaluation of patients presenting to the ED with acute chest pain by means of a cardiologist-based chest pain unit using different noninvasive imaging modalities. METHODS: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography. RESULTS: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 444 patients underwent MDCT, 445 MPS, and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 +/- 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event. CONCLUSIONS: Utilization of the CPU enabled a rapid and thorough evaluation of the patients' primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.

Association of Adolescent Hypertension With Future End-stage Renal Disease.

Importance: Hypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned. Objective: To investigate the association between hypertension and future ESRD in otherwise healthy adolescents. Design, Setting, and Participants: This retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018. Main Outcomes and Measures: End-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014. Results: The cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24). Conclusions and Relevance: Hypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.

Rapid detection of blaKPC carbapenemase genes by real-time PCR.

Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (bla(KPC)) enzymes are among the most common beta-lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of bla(KPC) genes using TaqMan chemistry. The q-PCR amplification of bla(KPC) DNA was linear over 7 log dilutions (r(2) = 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n = 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-plus-carbapenem disks and for bla(KPC) genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while bla(KPC) genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for bla(KPC) genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenem-resistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the bla(KPC) q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to bla(KPC) detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts.