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Background: Most studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases., Methods and Findings: In this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16-23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events., Conclusion: The low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA., Competing Interests: The authors have declared that no competing interests exist.

Background: Hip fractures increase the risks of mortality and major morbidity in the elderly. Hip fractures are associated with chronic pain, reduced mobility, disability and increasing dependence. We evaluated the direct costs incurred to the Israeli healthcare system in 2013 as a result of hip fracture injuries in elderly patients., Methods: Hip fractures costs evaluation consisted of first-year and long-term direct costs. Data on the incidence of hip fractures resulting in hospitalizations were retrieved from the Israeli Ministry of Health's (MOH) Central Database of Hospital Admissions. Hospitalization, rehabilitation and nursing utilization rates and costs were estimated based on the professional literature and according to the MOH's price list., Results: During 2013, 6285 elderly patients were hospitalized in Israel due to hip fractures. Direct costs of hip fracture, comprising hospitalization, rehabilitation and nursing costs incurred during the first year after the injury, were estimated at 454 million New Israeli Shekels (NIS; 83,841 NIS per person). Long-term nursing care costs in 2013 were 265 million NIS, with an average cost of approximately 49,000 NIS for 1600 elderly persons receiving long-term nursing care as a result of a hip fracture. Overall, the total direct costs of hip fracture in the elderly population in Israel in 2013 were 719 million NIS., Conclusions: The direct costs of hip fractures in Israel among the elderly are approximately 719 million NIS per year. The majority of costs are associated with the first year following the injury. To reduce healthcare costs in Israel, changes in the country's healthcare policy on hip fractures are required. For example, there is a need for a program for detecting high- risk populations, and for early intervention following the injury.

To compare positron emission tomography (PET) standardized uptake value (SUV) with magnetic resonance (MR) apparent diffusion coefficient (ADC) of nodal target lesions in patients with F-fluoro-2-deoxyglucose (FDG)-avid lymphomas by simultaneous PET/MR.Patients with histologically proven Hodgkin and non-Hodgkin lymphoma underwent PET/MR limited field of view of FDG-avid target nodal lesions. For PET images, a region of interest (ROI) was drawn around the target nodal lesion and the SUVmax and SUVmean was measured. For MR ADC measurements a ROI was placed over the target nodal lesion on diffusion-weighted imaging (DWI) and ADCmin and ADCmean (mean ADC) values within the ROI were recorded.Thirty-nine patients (19 women, 20 men; 13 patients with Hodgkin lymphoma and 26 with non-Hodgkin lymphoma) were included in the analysis. Sixty-six nodal lesions detected by PET/CT (19 PET-negative and 47 PET-positive) were analyzed by PET/MR. PET/MR quantitative assessments showed that ADCmin and ADCmean were accurate for discriminating positive from negative nodal lymphoma, with an AUC of 0.927 and 0.947, respectively. The ROC curve analysis of ADCmean versus SUVmax and SUVmean was not statistically significant (difference=0.044, P = .08 and difference = 0.045, P = .07; respectively). A substantial inverse association was observed between ADCmean with SUVmean and SUVmax (rho = -0.611; -0.607; P < .0001, respectively). A moderate inverse association was found between ADCmin with SUVmean and SUVmax (rho = -0.529, -0.520; P < .0001, respectively). Interobserver variability of quantitative assessment showed very good agreement for all variables (ICC>0.87).A significant correlation between ADCs and SUVs is found in FDG avid lymphomas. ADCmean is not inferior to PET SUV in discriminating positive and negative nodal lymphomas. Further larger studies are warranted to validate quantitative PET/MR for lymphoma patient management.

Background: To investigate same day 18F-FDG (Fluorodeoxyglucose) PET (Positron Emission Tomography)/MR (Magnetic Resonance) test-retest repeatability of Standardized Uptake Value measurements normalized for body weight (SUV) and lean body mass (SUL) in different locations in the liver., Methods: This prospective study was IRB approved with written informed consent obtained. 35 patients (20 women and 15 men, 61 ± 11.2 years) that performed a whole-body 18F-FDG PET/MR followed by liver-dedicated contrast-enhanced 18F-FDG PET/MR were included. SUV/L max, mean, and peak were measured inferior to, superior to, and at the right portal vein and in the left lobe of the liver. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated and Bland-Altman plots were obtained., Results: The variability for SUV/L's measurements was lowest inferior to the portal vein (<9.2%) followed by measurements performed at the level of the portal vein (<14.6%)., Conclusion: The area inferior to the portal vein is the most reliable location for hepatic 18F-FDG uptake measurements on PET/MR.

Background: To determine PET/CT and PET/MR reproducibility and PET/MR repeatability of fluorine 18 fluorodeoxyglucose (FDG) uptake measurements in tumors in cancer patients., Methods: This IRB approved prospective study was performed between October 2015 and February 2016 in consecutive patients who performed same day PET/CT and two sequential PET/MR. Thirty three patients with visible tumors (N = 63) were included. SUV for body weight (SUV) and lean body mass (SUL) were obtained. Volume of interest (VOI) with a threshold of 40% was used and SUV/L's, metabolic tumor volume (MTV) and tumor to liver ratio (T/L) were calculated. Measurements were plotted in a scattered diagram to visually identify correlation, a regression line was drawn and the equation of the line was calculated. Bland-Altman plots expressed as percentages were constructed to assess the agreement between measurements. The maximal clinically acceptable limits range was defined as ±30%., Results: Lesional SUV's, SUL's and MTV corrected to body weight (BW) and lean body mass (LBM) demonstrated strong positive linear correlation between PET/CT and PET/MR and between two sequential PET/MR. The 95% limits of agreement ranged from -27.7 to 17.5 with a mean of -5.1 and -27.6 to 17.9 with a mean of -4.9 for SUVpeak and SULpeak, respectively for sequential PET/MR. Other PET metrics demonstrated limits range that is above ±30% between PET/CT and PET/MR and between two sequential PET/MR., Conclusion: PET/MR SUV/L peak has a clinically acceptable repeatability performance and can be used to evaluate the response to treatment.

Purpose: This study assesses the inter-observer variability of mammographic breast density scoring (BDS) between technologists and radiologists and evaluates the effect of technologist patient referral on the load of adjuvant ultrasounds., Materials and Methods: In this IRB approved study, a retrospective analysis of 503 prospectively acquired, random mammograms was performed between January and March 2014. Each mammogram was evaluated for BDS independently and blindly by both the performing technologist and the interpreting radiologist. Statistical calculation of the Spearman correlation coefficient and weighted kappa were obtained to evaluate the inter-observer variability between technologists and radiologists and to examine whether it relates to the technologist's seniority or women's age. The effect on the load of adjuvant ultrasounds was evaluated., Results: 10 mammography technologists and 7 breast radiologists participated in this study. BDS agreement levels between technologists and radiologists were in the fair to moderate range (kappa values: 0.3-0.45, Spearman coefficient values: 0.59-0.65). The technologists markedly over-graded the density compared to the radiologists in all the subsets evaluated. Comparison between low and high-density groups demonstrated a similar trend of over-grading by technologists, who graded 51% of the women as having dense breasts (scores 3-4) compared to 27% of the women graded as such by the radiologists. This trend of over grading breast density by technologists was unrelated to the women's age or to the technologists' seniority., Conclusion: Mammography technologists over-grade breast density. Technologists' referral to an adjuvant ultrasound leads to redundant ultrasound studies, unnecessary breast biopsies, costs and increased patient anxiety., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The objective of this study is to describe the design and validation of a newly developed brief, treatment-focused scale for use with type 1 and type 2-diabetes, exploring patient-perceived difficulties that are associated with treatment., Methods: The content of the construct was derived from consultation with experts, from existing instruments and the literature, as well as from diabetic patients. The original draft was comprised of 11 attributes. Based on an interim analysis, an additional 12th attribute was added. The final scale was tested on 988 diabetic patients from 25 practices in Israel. Respondents also completed a diabetes-specific quality of life (QoL) questionnaire and indicated their current perceived overall health status., Results: The patient-perceived difficulty of diabetes treatment (PDDT) scale contains 12 items reflecting diabetes-treatment characteristics: adherence to self-monitoring of glucose schedule, frequency of self-monitoring of glucose, adherence to medication administration schedule, frequency of medication administration, multiple number of medications, synchronization between meals and medications, dependence on the medications, pain associated with treatment, diet restrictions, self-care, multiple healthcare providers, and costs of treatment. Response rate to all attributes was very high. Construct validity was shown by significant correlations between PDDT attributes and diabetes-specific quality of life (r = 0.31-0.46) and self-report adherence to recommended treatment (r = 0.14-0.28), as well as between overall perceived difficulty and diabetes-specific quality of life (r = 0.60). Furthermore, the PDDT items showed discriminant capabilities with respect to known groups of patients., Conclusions: The PDDT scale is a simple and valid instrument that may assist in identifying potential barriers in adherence to recommended treatments and to new treatment options., (Copyright © 2011 John Wiley & Sons, Ltd.)

The reformation in the marketing of non-prescription medicinal products has been launched. As of May 10th 2005, the pharmacist regulations 2004 (marketing of over-the-counter (OTC) drugs outside of pharmacies, as well as not by a pharmacist) will be in effect. This change aLlows the marketing of medicines outside of pharmacies, as has been the custom in the U.S.A., England and some of the European Union countries for many years. This reformation is incorporated in a policy that encourages self-medication by the use of non-prescription drugs. The self-medication policy originates from the point of view of the consumers who wish to be responsible for their own health and save precious time wasted on doctor visits; and the government's assumption that self-medication of OTC medicines by citizens wiLL decrease expenses for the HMOs in both doctor's billings as well as medication costs. In order to regulate the marketing terms of these medicinal products, regulations and complimentary guidelines were written and published. These documents encompass the following issues: the list of OTC medicines, marketing reguLations, packaging regulations, Licensed marketing Locations, storage regulations as well as display regulations, advertising regulations, monitoring and control. The medicinal products in this category only included medicines containing "safe" active ingredients with restrictions regarding the strength/concentration and packaging size; this category does not include medicines requiring special storage conditions (such as refrigeration or freezing), medicines containing an active ingredient that is addictive, medicines containing an active ingredient with danger of poisoning if misused, and medicines containing an active ingredient that has the potential to harm. The implementation of the regulations and guidelines will improve the consumer's ability to diagnose and treat oneself when sick with minor ailments, without consulting a doctor.

Introduction: In the last two decades there has been a world wide increase in the number of drugs that are being switched from the prescription-only category to non-prescription categories. In Israel, until recently, non-prescription medicines were only permitted to be sold by a pharmacist in pharmacies. In May 2005, following amendments to the law, several non-prescription medicines which were previously sold under a pharmacist's supervision, were reclassified as general-sales-list (GSL) medicines and permitted to be displayed and sold directly off the shelves in pharmacies and in other places such as grocery stores and petrol stations., Objective: To study the change in the patterns of consumption of non-prescription drugs in Israel two years after the reform began., Methods: A representative sample of the population of Israel was chosen and interviews were conducted at two time points: before the reform commenced and two years after the beginning of the reform. Statistical processing was performed in order to examine the changes in patterns of consumption of non-prescription drugs in Israel between these two time points., Results: In both surveys it was found that: approximately 70% of the Israeli public buys non-prescription medicines; 70% of the people interviewed said that they had been aware of the reform, but of these, about 75% continued buying nonprescription drugs from the pharmacist while 21% bought medicines off the shelves at the pharmacy and 4% purchased medications at grocery stores. The most common reasons for buying medicines off the shelves without a pharmacist were earlier knowLedge about the medication, convenience and availabiLity when the pharmacies were closed. An insignificant difference was observed for the purchase of non-prescription drugs from the different types of pharmacies: the health maintenance organizations (HMO) pharmacies continue to be the leading pharmacies from which the public purchased their non-prescription medicines, white there was a slight increase in the purchases from pharmacy chains. In the two surveys, the purchaser's personal experience was the biggest factor influencing the decision to buy a certain drug, followed by the doctor's and the pharmacist's recommendation. Only 15% thought that non-prescription medicines are not safe., In Conclusion: Two years after the reform began no breakthrough was observed in the pattern of purchase of non-prescription medicines. Despite exposure to the reform, most Israelis continue to buy these medicines from the pharmacists. Therefore, it appears that more time will be needed for this reform to actually start making an impact and changing the habits of Israeli consumers when purchasing non-prescription drugs.

Background: The European Quality of Life 5-Dimensions questionnaire is one of the most commonly used measures of health-related quality of life., Objectives: To present the feasibility, reliability and validity of the Hebrew version of the EQ-5D., Methods: We conducted face-to-face interviews with a representative sample (n = 1666) of the Israeli Jewish population. The data collected included demographic and medical information, and self-valuation of health using the EQ-5D descriptive system, Visual Analogue Scale and Time Trade-Off. Construct validity was assessed by assuming that older individuals, those with a greater burden of diseases, and those reporting experience with their own severe illness would have lower EQ-5D indexes, VAS and TTO values. Test-retest reliability was assessed in a small sample (n = 50) that was reevaluated after a 3 week interval., Results: Test-retest reliability of the EQ-5D and VAS was very high (r > or = 0.85). Reliability of the TTO was moderate (r = 0.48). There were significant differences in the EQ-5D index, profiles, VAS and TTO between healthy and sick respondents and younger and older respondents, indicating good validity of the instrument., Conclusions: The Hebrew translation of the EQ-5D is a practical, reliable and valid instrument for assessing the health-related quality of life of the general Israeli Jewish population.

Preference Based questionnaires are instrumental in the use of Health Related Quality of Life in economic analyses in medicine. These questionnaires combine the features of Health State Measures with those of direct methods of valuations, and therefore link between a profile, which describes a certain health state, to the utility of living in that state. Using statistical models, which are based on values to a sample of profiles, a complete table of utilities for all profiles may be constructed. These utilities serve to evaluate the effectiveness, and cost-effectiveness, of medical interventions. This article describes the method of creating and valuing preference based questionnaires and discusses the problems inherent in using the utilities they produce. The article also covers four of the most common questionnaires- Health Utility Index (HUI), Quality of Well Being (QWB), EuroQoL 5 Dimensions (EQ-5D) and Short Form 6 Dimensions (SF-6D). Finally, it briefly mentions the subject of specific preference based questionnaires.

Health State Measures (HSMs) are one of the existing methods for assessing Health Related Quality of Life. These measures provide a quantitative description of the quality of life across different aspects of living--physical, emotional and social. They allow us to determine the effects of diseases and medical interventions on each of those aspects. Health state measures may be generic--applicable to all conditions and populations, or focus on the unique features of a specific disease, state or group. This article discusses the differences in scope and responsiveness between generic and specific HSMs, with an emphasis on Minimal Clinically Important Difference, and their significance in regard to the selection and use of these questionnaires. The article also provides a short overview of the most commonly used HSMs--Sickness Impact Profile (SIP), Nottingham Health Profile (NHP) and Medical Outcome Study 36-Item Short Form (SF-36).

Assessment of the impact of medical interventions on patient's quality of life is becoming a major aspect in evaluating the effectiveness of these interventions. Based on the concept of combining life expectancy and quality of life in a single value, many tools for measuring this effect have been developed in the last few decades. Quality-adjusted life years (QALYs) are calculated by multiplying life expectancy by a factor representing the quality of life during that period. Health related quality of life may be measured directly by several methods. The most commonly used are Visual Analogue Scale (VAS), Standard gamble (SG) and Time Trade-Off (TTO). This article reviews these three methods, their applications and their advantages and disadvantages. It also addresses some of the problems characteristic of each measure, their theoretical and practical differences and the implications of those differences on the values obtained from each one. Finally, the article discusses the attempts to map the relationships between the three measures, in order to be able to convert values from one to another.

Objective: Parental employment in occupations that have potential exposures to organic solvents or pesticides could be associated with the risk of childhood acute lymphoblastic leukemia (ALL) in their offspring., Methods: We explored this hypothesis by studying the association with respect to exposure time windows. Our case-control study included 224 children, 112 diagnosed with ALL and 112 matched controls., Results: A significantly higher odds ratio (OR) was found between childhood ALL and reported parental occupational exposures. Analysis of exposures of both parents by exposure time windows revealed significant OR during the preconception and postnatal periods separately., Conclusions: The results provide support to the association between parental occupational exposures and ALL in their children. These results should be interpreted cautiously because of the small numbers, biases characterizing case-control studies, and the use of hospital-based controls.

New medical technologies that offer to improve upon or completely replace existing ones are continuously appearing. These technologies are forcing healthcare policymakers to consistently evaluate new treatment options. However, emerging medical technology has been viewed as a significant factor in increasing the cost of healthcare. The abundance of new medical alternatives, combined with scarcity of resources, has led to priority setting, rationing, and the need for further technology management and assessment. Economic evaluation of medical technologies is a system of analysis within the framework of health technology assessment to formally compare the costs and consequences of alternative healthcare interventions. EEMT can be used by many healthcare entities, including national policymakers, manufacturers, payers and providers, as a tool to aid in resource allocation decisions. In this paper we discuss the historical evolution and potential of EEMT, the practical limitations hindering more extensive implementation of these types of studies, current efforts at improvement, and the ethical issues influencing ongoing development. The Medical Technologies Administration in Israel's Ministry of Health is given as an example of an entity that has succeeded in practically implementing EEMT to optimize healthcare resource allocation.