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.

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.

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.

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.

The Misattributed and Silent Causes of Poor COVID-19 Outcomes Among Pregnant Women.

Abundant evidence strongly suggests that the condition of pregnancy makes women and their fetuses highly vulnerable to severe Corona-virus 2019 (COVID-19) complications. Here, two novel hypoxia-related conditions are proposed to play a pivotal role in better understanding the relationship between COVID-19, pregnancy and poor health outcomes. The first condition, "misattributed dyspnea (shortness of breath)" refers to respiratory symptoms common to both advanced pregnancy and COVID-19, which are mistakenly perceived as related to the former rather than to the latter; as a result, pregnant women with this condition receive no medical attention until the disease is in an advanced stage. The second condition, "silent hypoxia", refers to abnormally low blood oxygen saturation levels in COVID-19 patients, which occur in the absence of typical respiratory distress symptoms, such as dyspnea, thereby also leading to delayed diagnosis and treatment. The delay in diagnosis and referral to treatment, due to either "misattributed dypsnea" or "silent hypoxia", may lead to rapid deterioration and poor health outcome to both the mothers and their fetuses. This is particularly valid among women during advanced stages of pregnancy as the altered respiratory features make the consequences of the disease more challenging to cope with. Studies have demonstrated the importance of monitoring blood oxygen saturation by pulse oximetry as a reliable predictor of disease severity and outcome among COVID-19 patients. We propose the use of home pulse oximetry during pregnancy as a diagnostic measure that, together with proper medical guidance, may allow early diagnosis of hypoxia and better health outcomes.

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.

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.

Super-rapid race for saving lives by developing COVID-19 vaccines.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people and claimed thousands of lives. Starting in China, it is arguably the most precipitous global health calamity of modern times. The entire world has rocked back to fight against the disease and the COVID-19 vaccine is the prime weapon. Even though the conventional vaccine development pipeline usually takes more than a decade, the escalating daily death rates due to COVID-19 infections have resulted in the development of fast-track strategies to bring in the vaccine under a year's time. Governments, companies, and universities have networked to pool resources and have come up with a number of vaccine candidates. Also, international consortia have emerged to address the distribution of successful candidates. Herein, we summarize these unprecedented developments in vaccine science and discuss the types of COVID-19 vaccines, their developmental strategies, and their roles as well as their limitations.

Clinical presentation of COVID-19 - a model derived by a machine learning algorithm.

COVID-19 pandemic has flooded all triage stations, making it difficult to carefully select those most likely infected. Data on total patients tested, infected, and hospitalized is fragmentary making it difficult to easily select those most likely to be infected. The Israeli Ministry of Health made public its registry of immediate clinical data and the respective status of infected/not infected for all viral DNA tests performed up to Apr. 18th, 2020 including almost 120,000 tests. We used a machine-learning algorithm to find out which immediate clinical elements mattered the most in identifying the true status of the tested persons including age or gender matter, to enable future better allocation of surveillance policy for those belonging to high-risk groups. In addition to the analyses applied on the first batch of the available data (Apr. 11th), we further tested the algorithm on the independent second batch (Apr. 12th to 18th). Fever, cough and headache were the most diagnostic, differing in degree of importance in different subgroups. Higher percentage of men were found positive (9.3 vs. 7.3%), but gender did not matter for the clinical presentation. The prediction power of the model was high, with accuracy of 0.84 and area under the curve 0.92. We provide a hand-held short checklist with verbal description of importance for the leading symptoms, which should expedite the triage and enable proper selection of people for further follow-up.

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.

Maternal and neonatal outcome of asymptomatic bacteriuria at term pregnancy.

OBJECTIVES: Guidelines recommend antibiotic treatment for every episode of asymptomatic bacteriuria throughout pregnancy in order to reduce maternal and fetal complications. We evaluated intra- and post-partum, as well as puerperal maternal and neonatal outcomes of an untreated group of pregnant women with asymptomatic bacteriuria at term. METHODS: This was a single center prospective cohort study. We enrolled women who came for labor or checkups, 37-42 weeks gestation, with singleton, vertex presentation. On admission, women gave a urine sample; we compared maternal, obstetric and neonatal data from the positive culture group to the negative culture. RESULTS: Among 248 pregnant women recruited, 205 negative and 32 positive urine cultures were collected. None of the women that participated in this study developed pyelonephritis during hospitalization or during the puerperium. No significant differences were detected between the two groups in terms of age, nulliparity, gestational age at delivery, length of hospitalization, birth type, intra- or post-partum fever, antibiotic treatment during labor or post-partum. CONCLUSIONS: No increased maternal or neonatal adverse effects were observed in women with untreated ASB detected at term.

Impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve: a systematic review and meta-analysis.

BACKGROUND: Ovarian endometrioma is a frequent manifestation of endometriosis in women of reproductive age. Several issues related to its space occupying effects, local reactions and surgical removal continue to be actively debated today. The impact of ovarian endometrioma per se on ovarian reserve is still controversial and the effect of ovarian surgery is still actively discussed. Furthermore, the optimal biomarker of ovarian reserve estimation in women with ovarian endometrioma is still under examination. Additionally, there is no consistent agreement on the effect of endometrioma bilaterality on ovarian reserve. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to study the impact of unilateral versus bilateral ovarian endometrioma on ovarian reserve biomarkers before and after endometrioma cystectomy. SEARCH METHODS: We performed an extensive electronic database search employing PubMed, EBSCO, Web of Science, ClinicalTrials.gov and the Cochrane Library, to identify published research articles published between January 2000 and October 2018. Search terms included endometriotic cyst OR endometrioma OR endometriomata, cystectomy OR resection OR stripping OR removal OR excision and infertility OR subfertility. Only prospective controlled studies that compared the impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve tests in the same setting were included. Studies which included cases with PCOS, ovarian failure, early menopause, oral contraception treatment, or prior chemotherapy and/or radiotherapy or ovarian surgery, were excluded from evaluation. We used the Newcastle-Ottawa Scale for assessing the quality of studies found eligible for meta-analysis. We registered the systematic review on PROSPERO and its number is CRD42018117170. OUTCOMES: Twelve studies were eligible for meta-analysis including collectively 783 women: 489 and 294 in the unilateral and bilateral groups, respectively. The included studies had a low risk of bias. The pre-operative weighted mean difference (WMD) showed that serum AMH levels did not differ significantly between the groups. Conversely, AMH levels were significantly (P < 0.05) lower in bilateral groups than in unilateral groups at the early, intermediate and late post-operative periods, corresponding WMDs of 0.78 ng/ml (95% CI: 0.41-1.15), 0.59 ng/ml (95% CI: 0.14-1.04) and 1.08 ng/ml (95% CI: 0.63 to 1.52), respectively. Heterogeneity among eligible studies reporting on before the operation and at the early and intermediate post-operative periods was high. Pre-operative and post-operative AFC values were not significantly different between the groups. The heterogeneity among the studies reporting on AFC was high. Analysis of each of the unilateral and bilateral groups separately showed a significant and sustained serum AMH drop by 39.5% and 57.0%, respectively from baseline to after the operation. WIDER IMPLICATIONS: Our results challenge the concept that endometrioma per se adversely affects ovarian reserve, whereas endometrioma cystectomy, especially as bilateral operation, has a deleterious and sustained effect on ovarian reserve. AMH seems to be a more appropriate biomarker of ovarian reserve than AFC in cases with endometrioma. Since low AMH implies a shorter reproductive lifespan, excision of endometrioma should be cautiously considered, especially in bilateral cases.

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.

Uterine rupture after previous low segment transverse cesarean is rarely catastrophic.

OBJECTIVE: The cornerstone of concerns over trial of labor after cesarean (TOLAC) is the risk of uterine rupture. The purpose of this study was to document the rate of uterine rupture during TOLAC and to delineate its severity and consequences. MATERIALS AND METHODS: We retrospectively collected the data on vaginal and cesarean deliveries after a previous cesarean section with specific emphasis on uterine rupture and dehiscence in our center from 2006 through 2013. RESULTS: 22,670 deliveries were registered, with 18.2% rate of cesarean section. 2890 women had a single cesarean scar; of them 1206 delivered vaginally and 194 were re-operated during unsuccessful TOLAC. Seven cases of uterine rupture and 16 cases of dehiscence were recorded. There were no maternal, intrapartum or neonatal deaths, and no cesarean hysterectomy. There was one re-laparotomy, one ICU admission, and one blood transfusion; one neonate was admitted to NICU. TOLAC was successful in 86.1% of cases. CONCLUSIONS: Cautious selection and close monitoring of candidates are the cornerstones of successful management of TOLAC. Readily available facilities for emergency cesarean delivery and concerted obstetrical team can save the mother and child from catastrophic complications.

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.

Better patient safety: implementing exploration and exploitation learning in daily medical practice.

BACKGROUND: Current medical daily practice relies on guidelines, protocols and procedures (GPPs), which require exploitation. However, diagnosis, treatment, risk management and process improvements require exploration. Physician are often unable to switch between exploitation and exploration. This study tested a new approach to facilitate switching that included (1) a new 'thinking protocol' that encouraged leaping from exploitation to exploration and (2) a GPP that encouraged leaping from exploration to exploitation. METHOD: Two hundred students were divided into four groups. The groups received a set of tasks that required switching between exploitation and exploration. Three groups received the thinking protocol, the GPP, or both, and the fourth group served as control. RESULTS: With each additional task, all groups increased exploitative tendency(p<0.0001). The two groups with the thinking protocol leaped from exploitation to exploration (p<0.0001); the other two groups remained in exploitation (p=0.1173, p=0.0758). For the groups that employed exploration learning, the group that received the GPP switched back to exploitation (p<0.0001), but the other group remained in exploration (p=0.2363). CONCLUSION: Despite the importance of timely leaping between exploration and exploitation, in some events, medical teams fail to make the appropriate leap. We suggest to use our novel approach and to encourage the leaping between exploration and exploitation in daily medical practice, to enable the prevention of medical errors and to enhance the effectiveness of risk managements and process improvements.