Homocysteine serum levels correlate with the number of failed IVF cycles even when within normal range.

INTRODUCTION: Repeated implantation failure is a common challenge in daily practice. Homocysteine and vitamin B12 have been associated with reproductive processes among patients undergoing in vitro fertilization; however, their involvement in repeated implantation failure has not been assessed. We explored possible associations of serum homocysteine and vitamin B12 with repeated implantation failure. MATERIAL AND METHODS: A retrospective analysis of 127 women who underwent ≥ 3 unsuccessful embryo transfers during 2005-2016, at the Fertility and In Vitro Fertilization Unit at Carmel Medical Center. After at least 3 IVF failures serum levels of homocysteine and vitamin B12 were measured. RESULTS: The mean patient age was 33.5 ± 5.2 years. The mean number of embryo transfers was 4.6 ± 1.5. The mean total cumulative number of embryos transferred was 10.4 ± 5.2. Mean serum levels of homocysteine were 8.6 ± 3.7 µM/L, and of vitamin B12 were 302.5 ± 155.3 pg/ml. Homocysteine levels were within the normal range (< 14 µM/L) in 95.8% of the patients. Yet, the levels of homocysteine correlated with both the number of failed embryo transfers (r = 0.34, p = 0.004) and the total cumulative number of transferred embryos (r = 0.36, p = 0.002). CONCLUSIONS: Our findings suggest an association between serum homocysteine levels and the occurrence of repeated implantation failure, even when homocystein levels were within the normal range. It should be studied whether nutritional supplementation to modulate serum homocysteine levels may improve treatment outcome.

Perceived reliability of medical device alarms-a major determinant of medical errors driven by frozen medical thinking.

This concept paper introduces the phenomenon of self-assigning a 'perceived reliability' value to medical device readings as a potential source of cognitive bias in medical decision-making. Medical errors can result from clinical decisions based on partial clinical data despite medical device readings providing data to the contrary. At times, this results from clinician distrust of medical device output. Consequentially, clinicians engage in a form of 'frozen thinking', a fixation on a particular thought process despite data to the contrary. Many medical devices, such as intensive care unit (ICU) monitors and alarms, lack validated statistics of device output reliability and validity. In its absence, clinicians assign a self-perceived reliability value to device output data and base clinical decisions therefrom. When the perceived reliability value is low, clinicians distrust the device and ignore device readings, especially when other clinical data are contrary. We explore the cognitive and theoretical underpinnings of this 'perceived reliability' phenomenon. The mental assignment of a perceived reliability value stems from principles of 'script theory' of medical decision-making. In this conceptual framework, clinicians make decisions by comparing current situations to mental 'scripts' of prior clinical decisions and their outcomes. As such, the clinician utilizes scripts of prior experiences to create the perceived reliability value. Self-assigned perceived reliability is subject to multiple dangers of reliability and cognitive biases. Some of these biases are presented. Among these is the danger of dismissing device readings as 'noise'. This is particularly true of ICU alarms that can emit frequent false alarms and contribute to clinician sensory overload. The cognitive dangers of this 'noise dismissal' are elaborated via its similarity to the phenomenon of 'spatial disorientation' among aviation pilots. We conclude with suggestions for reducing the potential bias of 'perceived reliability'. First presented are regulatory/legislative and industry-based interventions for increasing the study of, and end-user access to, validated device output reliability statistics. Subsequently, we propose strategies for overcoming and preventing this phenomenon. We close with suggestions for future research and development of this 'perceived reliability' phenomenon.

Correlates of Hookah Smoking among Arab Adults in Israel Identified by a Machine Learning Algorithm.

BACKGROUND: Hookah smoking is a common activity around the world and has recently become a trend among youth. Studies have indicated a relationship between hookah smoking and a high prevalence of chronic diseases, cancer, cardiovascular, and infectious diseases. In Israel, there has been a sharp increase in hookah smoking among the Arabs. Most studies have focused mainly on hookah smoking among young people. OBJECTIVES: To examine the association between hookah smoking and socioeconomic characteristics, health status and behaviors, and knowledge in the adult Arab population and to build a prediction model using machine learning methods. METHODS: This quantitative study based is on data from the Health and Environment Survey conducted by the Galilee Society in 2015-2016. The data were collected through face-to-face interviews with 2046 adults aged 18 years and older. RESULTS: Using machine learning, a prediction model was built based on eight features. Of the total study population, 13.0% smoked hookah. In the 18-34 age group, 19.5% smoked. Men, people with lower level of health knowledge, heavy consumers of energy drinks and alcohol, and unemployed people were more likely to smoke hookah. Younger and more educated people were more likely to smoke hookah. CONCLUSIONS: Hookah smoking is a widespread behavior among adult Arabs in Israel. The model generated by our study is intended to help health organizations reach people at risk for smoking hookah and to suggest different approaches to eliminate this phenomenon.

Applying health-six-sigma principles helps reducing the variability of length of stay in the emergency department.

BACKGROUND: Reducing length of stay (LOS) is one of the urgent problems in healthcare systems worldwide. Popular methods that are used to reduce LOS are the Lean and the 6 Sigma, which in practice result in limited improvements. In this paper, we introduce and test a tailored method for implementing the 6 Sigma principles in healthcare (we call H-6S). OBJECTIVE: To reduce the variability in the time between admission and discharge of patients in the emergency department. METHODS: The study took place within the emergency department (ED) of Josephtal Medical Center in Eilat, Israel. Our analysis focused on the processes of examining and treating patients from admission to ED until discharge home. The analysis was done during the second quarter of 2018. The implementation of the recommendations took place during Q3 2018. The reported results are from Q3 2018 to Q2 2019, compared to the corresponding period in 2017 (experienced team). RESULTS: In Q2 2017, LOS was 2.42 ± 2.07 h (experienced team, n = 9928). In Q2 2018, the LOS was 2.62 ± 7.04 h (before the H-6S, inexperienced team, n = 9484). In Q2 2019 following the intervention, it reached 2.3 ± 1.74 h (n = 7647). The differences between the standard deviations of the three periods are significant. CONCLUSION: Implementing H-6S dropped the variance of LOS within 3 months and remained low for the whole year. Each new team of physicians who enter the ED should be thoroughly instructed as to the routines and expectations of the system from them, which should narrow the differences of previous education between them.

Protein C global assay evaluation in naturally conceived vs. assisted reproduction-achieved twin pregnancies: a prospective longitudinal study.

PURPOSE: Protein C global assay tests the global function of the protein C pathway, the most clinically significant anticoagulant pathway in humans. The objective of this study is to assess the difference in protein C global assay levels, throughout twin gestation, in naturally conceiving and ART-treated women. METHODS: This is a prospective cohort longitudinal study of pregnant women with twin gestation. Protein C Global evaluation was performed on frozen blood samples. Ninety-eight women with twin pregnancy, thirty-eight naturally conceived and sixty following ART, were evaluated on four occasions: during the first, second, and third trimesters, and 6 weeks or later after delivery (baseline). RESULTS: Protein C global assay levels were lower throughout pregnancy as compared to basal levels in both the naturally conceived and ART-conceived groups. However, protein C global assay levels were similar between the ART-conceived and naturally conceived twin pregnancies in all three trimesters. Perinatal complications were associated with decreased protein C global assay levels during the third trimester, although no difference was encountered between naturally conceived and ART-complicated twin pregnancies. CONCLUSION: While protein C global assay levels drop during twin pregnancy, there is no difference between ART-conceived and naturally conceived gestations. Decreased levels of protein C global assay during the third trimester were similarly associated with perinatal complications in both groups. Our results imply that twin pregnancy of itself is a more dominant factor for perinatal complications as compared to other factors, such as subfertility or the exposure to ART per se.

The Impact of Prenatal Depression in Patients of High Risk Pregnancy Clinic on Obstetric Outcomes.

Prenatal depression is common and has been associated with risky maternal behavior, postpartum depression, and atypical child development. Still, its association with adverse perinatal outcomes is complex. The aim of our study was to look for this potential association in our region. The medical charts of women who were treated at our High-Risk Pregnancy Clinic and gave birth at our hospital were reviewed. The Edinburgh Postnatal Depression Scale (EPDS) was used to discover prenatal depression. Patients who reported past or current mental illness were excluded. We enrolled 202 women at a mean age of 32.81. Twin pregnancy was the most common reason for referral to the clinic (17.3%). The mean EPDS score was 4.63 (±4.66), with 15.3% scoring 10 or more. A significant correlation was found between the EPDS score and intrapartum fetal heart rate abnormalities, as well as with low birth weight. There were significant associations between the EPDS score and the maternal status of genetic disorder carrier, and the number of previous pregnancies, miscarriages, and elective termination of pregnancy. This study demonstrates a significant impact of the maternal psychological state on the obstetric outcome. In addition, we observed a significant association between maternal obstetric history, genetic data, and the risk of prenatal depression. Our study shows that completing the EPDS questionnaire is a very important part of the pregnancy follow-up, as it illuminates risk factors for prenatal depression and adverse perinatal outcomes.

Unstructured brainstorming is not enough: structured brainstorming based on four verification and validation questions yields better hazard identification in healthcare.

OBJECTIVES: (1) To introduce the Methodical Hazard Identification Checklist (MHIC) for structured brainstorming and the four V&V categories on which it is based, and (2) to compare its efficacy with that of brainstorming (BS) in identifying hazards in healthcare. DESIGN: Comparative analysis of MHIC and team BS results. SETTING: Baruch Padeh Medical Center, Poriya, Israel. STUDY PARTICIPANTS: Quality engineering students, facilitators, validation teams and hospital staff who were familiar with the specific processes. INTERVENTION(S): The number of hazards identified by team BS were compared with those deduced by applying the four V&V hazard categories to each step (the MHIC) of 10 medical and 12 administrative processes. MAIN OUTCOME MEASURE(S): The total number of hazards (1) identified by BS, (2) identified by MHIC, (3) validated by the validation team and (4) hazards identified by both methods that the validation team deemed unreasonable. RESULTS: MHIC was significantly more successful than BS in identifying all hazards for the 22 processes (P < 0.0001). The estimated probabilities of success for BS for administrative and medical processes were 0.4444, 95%CI = [0.3506, 0.5424] and 0.3080, 95%CI = [0.2199, 0.4127], respectively. The estimated probabilities of success for MHIC for administrative and medical processes were 0.9885, 95%CI = [0.9638, 0.9964] and 0.9911, 95%CI = [0.9635, 0.9979], respectively. CONCLUSIONS: Compared to traditional BS, MHIC performs much better in identifying prospective hazards in the healthcare system. We applied MHIC methodology to administrative and medical processes and believe it can also be used in other industries that require hazard identification.

Frequency of canine nt230(del4) MDR1 mutation in prone pure breeds, their crosses and mongrels in Israel - insights from a worldwide comparative perspective.

BACKGROUND: Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan. RESULTS: The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds. CONCLUSIONS: This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.

De-freezing frozen patient management.

OBJECTIVE: To compare the effectiveness of two methods in encouraging the consideration of a leap from one patient management routine to another: (i) real-time review of the facts by an external medical team (ii) implementation of the 're-thinking-protocol' ('de-Freezing') by both treating and external medical teams. DESIGN: Students accompanied doctors, nurses and patients as non-interrupting observers. When an obvious gap between the expected and actual findings occurred, it was discussed four times: by two teams (treating team, external medical team) in two discussion modes (real-time review, de-Freezing-questionnaire). The students then recorded if a leap was considered for each discussion. SETTING: The study was conducted in the emergency department of the Baruch Padeh Medical Centre, Poriya, Israel. PARTICIPANTS: All patients were included during times when both medical teams (treating, external) were present. INTERVENTION(S): During 14 periods of 5-7 h each, 459 patients were sampled. In 183 patients, 200 gaps were discovered. RESULTS: The external team considered a leap 76 times, compared with 47 by the treating team (P < 0.001). Using the de-Freezing-protocol, the treating team considered a leap 133 times. Interestingly, even the external team benefited from the de-Freezing protocol and considered a leap 140 times (NS compared to the treating team). CONCLUSIONS: While the importance of timely leaping from one patient management routine to another is emphasized in the training of physicians, medical teams too often fail to do so. The de-Freezing-protocol inexpensively encourages the consideration of a leap beyond what is evoked by the involvement of an external team. The protocol is applicable to all medical processes and should be incorporated into medical practice and education.

[MEDICINE IN THE GALILEE: FACTS, INSIGHTS AND OPERATIVE THOUGHTS - PUBLIC APPEAL TO A PARADIGM CHANGE].

In Israel, considerable gaps are found on all quality and other measures of health between the north and south districts and Israel's center. Although the Ministry of Health leads a policy of reducing the existing gaps in medical services in the periphery, not enough has yet been done. The conclusions of various committees strove to narrow these gaps but none have been implemented. In this article we propose a new paradigm, pooling resources and other proposals to improve health care services in the north and south districts of Israel.

[RARE CASE OF HUGE OMENTAL DERMOID].

INTRODUCTION: Ovarian dermoid cyst is a benign germ cell tumor usually occurring during fertile age. In contrast, giant omental dermoid is extremely rare and is thought to originate from ovarian torsion, detachment and omental implantation. We present a case of a 73 year old patient with 26 cm giant omental dermoid weighing more than 6 kg. During surgery, aspiration of the cystic part facilitated the delivery of the big mass through a relative small abdominal incision.

Dispersal of an ancient retroposon in the TP53 promoter of Bovidae: phylogeny, novel mechanisms, and potential implications for cow milk persistency.

BACKGROUND: In recent years, the perception of transposable genetic elements has changed from "junk DNA" to a focus of interest when appearing near or inside genes. Bov-A2 is a short interspersed nuclear element (SINE) that was first found in Bovidae and later in other ruminants. This retroposon is mostly used as a marker for phylogenetic analysis. RESULTS: We describe insertions of Bov-A2 in the promoter region of TP53, a key tumor suppressor gene that is indispensable for diverse developmental processes, in Antilopinae and Tragelaphini (belonging to the Bovinae subfamily). In Tragelaphini two Bov-A2 elements were inserted sequentially, whereas in 5 tribes of Antilopinae only one Bov-A2 element was inserted, in a different site and reverse orientation. The entrance site in both cases employed short palindromes that can form hairpin secondary structures. Interestingly, mutations that create or disrupt base pairing in the palindrome sequence dictated the presence or absence of Bov-A2, such as in the domestic cow and buffalo, which lack Bov-A2. Transcription factor binding site analysis revealed unique binding sites for STAT3 and NFκB within the Bov-A2 sequence, which together with TP53 itself are known to play a crucial role in mammary involution. CONCLUSIONS: This report demonstrates how short palindromes serve as hot spots for Bov-A2 retroposon insertion into the mammalian genome. The strict correlation between point mutation in the palindromes and the presence/absence of Bov-A2 retroposon insertions, questions the use of singular insertion events as valid phylogenetic markers inside families. Bov-A2 insertion into the TP53 promoter in Antilopinae and Tragelaphini may not only provide a genetic network that regulates mammary involution, but can also answer the need for rapid mammary involution in Savanna antelopes after weaning, partially in response to predation stress. The absence of Bov-A2 in domestic bovids may constitute the molecular background for greater lactation persistency.

Pregnancy Prevention and Termination of Pregnancy in Adolescence: Facts, Ethics, Law and Politics.

We present an overview of the current sexual behavior of adolescents in Israel, including the related social and moral issues, and compare it to that in Western countries. An important factor is the existence of liberal versus conservative views regarding the use of contraception and termination of pregnancy in these young subjects. We describe the current situation where in most cases the medical providers do not provide adequate contraceptive advice to adolescent girls, resulting ultimately in a high rate of unintended pregnancy. In our opinion, it is essential to make effective contraception more accessible to this vulnerable group.

Basic research in PCOS: are we reaching new frontiers?

Polycystic ovarian syndrome (PCOS) is the leading cause for anovulatory infertility. It is diagnosed by two of the following three clinical criteria: oligomenorrhoea, hyperandrogenism and polycystic appearance of the ovaries. Weight loss and physical activity can lead to ovulation and conception. Lowering of serum insulin normalizes androgen concentrations whereas ovulation induction often causes ovarian hyperstimulation. Theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. Herein we review the research efforts at the genomic and cell function levels, as well as animal models, which have been made to elucidate the underlying mechanism that leads to PCOS. It appears that, despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood. Polycystic ovarian syndrome (PCOS) is the leading cause for infertility, which is caused by anovulation. It is diagnosed by two of the following three clinical criteria: irregular and prolonged menstrual cycles, overt symptoms of excess androgens, which is revealed by acne and excess hair, and ultrasonographic appearance of the ovaries with multiple small follicles spread mainly near the ovarian surface, which gave it its name. Intentional weight loss and physical activity can lead to resumption of ovulation and not infrequently to conception as well. It was shown that lowering of serum insulin accounts for normalization of serum androgen levels, whereas ovulation induction with FSH often causes ovarian hyperstimulation. It is suggested that theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. In this article we review the efforts to define the genes responsible for the syndrome and the studies at the cell function level, as well as animal models, which have been done to elucidate the underlying mechanism that leads to PCOS. Overall, it appears that despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood.

[Physical activity during pregnancy--facts and practical guidelines].

Physical activity during pregnancy is known to have a positive effect on both the mother and the fetus/newborn, as long as there are no specific contraindications relating to maternal pathology. Physical activity during pregnancy is known to be associated with reduced incidence of several gestational pathologies, as well as boosting physical and mental capabilities. Furthermore, a positive effect was found in newborns whose mothers continued their physical activity habits throughout pregnancy. Nevertheless, the intensity and duration, and specifically their efforts against resistance, have not been adequately emphasized. Herein, we review the main recent findings and insights on physical activity during pregnancy, and provide a practical set of recommendations.

A non-invasive direct nose to brain drug delivery platform vs. invasive brain delivery approach: patient-centered care impact analysis.

Current literature lacks structured methodologies for analyzing medical technologies' impact from the patient-centered care perspective. This study introduces, applies and validates 'Patient-Centered Care Impact Analysis' (PCIA) as a method for identifying patient-centered care associated demands and expectations for a particular technology and assessing its compliance with these demands. PCIA involves five stages: (1) demand identification, (2) ranking demands' impact magnitude, (3) scoring demand compliance (DC), (4) demand priority (DP) assignment based on impact magnitude and compliance, (5) generating a summative impact priority number (IPN). PCIA was performed as a comparative assessment of two central nervous system (CNS) drug-delivery platforms; SipNose, a novel noninvasive Direct-Nose-to-Brain (DNTB), vs. the standard-of-care invasive intrathecal/intracerebroventricular injection (Invasive I/I). Study participants included a ranking team (RT) without experience with the SipNose technology that based their scoring on experimental data; and a validation team (VT) experienced with the SipNose platform. All had experience with, or knowledge of, InvasiveI/I. Demand identification and impact magnitude were performed by one content and one assessment expert. Each participant assessed each technology's DC. DP scores, IPN's and IPN DNTB:InvasiveI/I ratios were generated for each technology, for each team, based on DC and summative DP scores, respectively. Both teams assigned DNTB higher DC scores, resulting in higher DNTB DP, IPN scores and DNTB:InvasiveI/I IPN ratios. Lack of difference between team assessments of DP and IPN ratio validate PCIA as an assessment tool capable of predicting patient-centered clinical care quality for a new technology. The significant differences between the platforms highlight SipNose's patient-care centered advantages as an effective CNS drug-delivery platform.