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  • Alfred Nobel and His Prizes: From Dynamite to DNA

    Alfred Nobel was one of the most successful chemists, inventors, entrepreneurs, and businessmen of the late nineteenth century. In a decision later in life, he rewrote his will to leave virtually all his fortune to establish prizes for persons of any nationality who made the most compelling achievement for the benefit of mankind in the fields of chemistry, physics, physiology or medicine, literature, and peace among nations. The prizes were first awarded in 1901, five years after his death. In considering his choice of prizes, it may be pertinent that he used the principles of chemistry and physics in his inventions and he had a lifelong devotion to science, he suffered and died from severe coronary and cerebral atherosclerosis, and he was a bibliophile, an author, and mingled with the literati of Paris. His interest in harmony among nations may have derived from the effects of the applications of his inventions in warfare (“merchant of death”) and his friendship with a leader in the movement to bring peace to nations of Europe. After some controversy, including Nobel’s citizenship, the mechanisms to choose the laureates and make four of the awards were developed by a foundation established in Stockholm; the choice of the laureate for promoting harmony among nations was assigned to the Norwegian Storting, another controversy. The Nobel Prizes after 115 years remain the most prestigious of awards. This review describes the man, his foundation, and the prizes with a special commentary on the Nobel Prize in Physiology or Medicine.
  • Comparison of the Supraclavicular, Infraclavicular and Axillary Approaches for Ultrasound-Guided Brachial Plexus Block for Surgical Anesthesia

    Objective: We hypothesized that ultrasound (US)-guided technique of the supra- and infraclavicular and axillary approaches of brachial plexus block (BPB) will produce a high quality of surgical anesthesia for operations below the shoulder independently of the approach and body mass index (BMI). Intercosto-brachial and medial brachial cutaneous nerves will be blocked separately because they are not a part of the brachial plexus. Methods: This is a prospective randomized observer-blinded study. The three approaches of the US-guided BPB without neurostimulation were compared for quality, performance time, and correlation between performance time and BMI. Intercostobrachial and medial brachial cutaneous nerve blocks were used in all patients. Results: A total of 101 patients were randomized into three groups: SCL (supraclavicular), ICL (infra-clavicular), and AX (axillary). Seven patients were excluded due to various factors. All three groups were similar in demographic data, M:F proportion, preoperative diagnosis and type of surgery, anesthesiologists who performed the block, and surgical staff that performed the surgical intervention. The time between the end of the block performance and the start of the operation was also similar. The quality of the surgical anesthesia and discomfort during the operation were identical following comparison between groups. No direct positive correlation was observed between BMI and the block performance time. The time for the axillary block was slightly longer than the time for the supra- and infraclavicular approaches, but it had no practical clinical significance. Transient Horner syndrome was observed in three patients in the SCL group. No other adverse effects or complications were observed. Conclusions: All three approaches can be used for US-guided BPB with similar quality of surgical anesthesia for operations of below the shoulder. A block of the intercostobrachial and medial brachial cutaneous nerves is recommended. Obesity is not a significant factor in relation to the time of US-guided BPB performance, or the quality of surgical anesthesia. (ClinicalTrials.gov number, NCT01442558.)
  • Palliative Care: Too Good to Be True?

    Introduction: Many patients and their families are hesitant to consult a palliative care (PC) team. In 2014, approximately 6,000,000 people in the United States could benefit from PC, and this number is expected to increase over the next 25 years. Objectives: The purpose of this review is to shed light on the significance of PC and provide a holistic view outlining both the benefits and existing barriers. Methods: A literature search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, and Web of Science to identify articles published in journals from 1948 to 2019. A narrative approach was used to search the grey literature. Discussion: Traditionally, the philosophy behind PC was based on alleviating suffering associated with terminal illnesses; PC was recommended only after other treatment options had been exhausted. However, the tenets of PC are applicable to anyone with a life-threatening illness as it is beneficial in conjunction with traditional treatments. It is now recognized that PC services are valuable when initiated alongside disease-modifying therapy early in the disease course. Studies have shown that PC decreased total symptom burden, reduced hospitalizations, and enabled patients to remain safely at home. Conclusion: As the population ages and chronic illnesses become more widespread, there continues to be a growing need for PC programs. The importance of PC should not be overlooked despite existing barriers such as the lack of professional training and the cost of implementation. Education and open discussion play essential roles in the successful early integration of PC.
  • Less is More: Modern Neonatology

    Iatrogenesis is more common in neonatal intensive care units (NICUs) because the infants are vulnerable and exposed to prolonged intensive care. Sixty percent of extremely low-birth-weight infants are exposed to iatrogenesis. The risk factors for iatrogenesis in NICUs include prematurity, mechanical or non-invasive ventilation, central lines, and prolonged length of stay. This led to the notion that “less is more.” In the delivery room delayed cord clamping is recommended for term and preterm infants, and suction for the airways in newborns with meconium-stained fluid is not performed anymore. As a symbol for a less aggressive attitude we use the term neonatal stabilization rather than resuscitation. Lower levels of oxygen saturations are accepted as normal during the first 10 minutes of life, and if respiratory assistance is needed, we no longer use 100% oxygen but 0.21–0.3 FiO2, depending on gestational age and the level of oxygen saturation. We try to avoid endotracheal ventilation by using non-invasive respiratory support and administering continuous positive airway pressure early on, starting in the delivery room. If surfactant is needed, non-invasive methods of surfactant administration are utilized. Use of central lines is shortened, and early feeding of human milk is the routine. Permissive hypercapnia is allowed, and continuous non-invasive monitoring not only of the O2 but also of CO2 is warranted. “Kangaroo care” and Newborn Individualized Developmental Care and Assessment Program (NIDCAP) together with a calm atmosphere with parental involvement are encouraged. Whether “less is more,” or not enough, is to be seen in future studies.
  • Effect of Socioeconomic Status and Ethnicity on Glycemic Control in Arab and Jewish Youth with Type 1 Diabetes Mellitus

    Objectives: Research and theory suggests that socioeconomic status may affect diabetes control. We investigated the effect of socioeconomic status and ethnicity on glycated hemoglobin (HbA1c) in Arab and Jewish children with type 1 diabetes mellitus in northern Israel. Methods: Data were collected from medical records of 80 Arab and 119 Jewish children attending a pediatric diabetes clinic in a tertiary health care center. Multivariate regression analysis was used to assess factors independently affecting HbA1c level. Results: Mean age was 12.9±4.7 years. Arab families had more children compared to Jewish families (3.7±1.5 versus 2.9±1.2, respectively, P=0.0007). Academic education was significantly less common in Arab families (25% versus 66.2%, respectively, P=0.0001). Income of Jewish parents was significantly higher compared to that of Arab parents (7,868±2,018 versus 5,129±906 NIS/month, respectively, P=0.0001). Mean age at diagnosis of diabetes was 9.6±4.6 years and disease duration was 3.4±2.3 years in both groups. Half of Arab and Jewish children were treated with multiple insulin injections and half with insulin pumps. Mean number of self-glucose testing/day was higher in Jewish children than in Arab children (4.7±2.5 versus 4.0±1.5, respectively, P=0.033). Mean HbA1c was above recommendations, 9.5% (12.6 mmol/L) in Arab children and 8.7% (11.3 mmol/L) in Jewish children (P=0.004). In multivariate analysis, disease duration (P=0.010) and ethnicity (P=0.034 for Arabs versus Jews) were independently associated with HbA1c. Conclusions: Both Arab and Jewish children failed to meet HbA1c goals, but this effect was significantly greater for Arabs. Ethnicity remained a predictor of failure even following adjustment for potential confounders.
  • COVID-19 and Preeclampsia: Overlapping Features in Pregnancy

    Coronavirus disease 2019 (COVID-19) is a global respiratory disease with unique features that have placed all medical professionals in an alarming situation. Preeclampsia is a hypertensive disorder of pregnancy affecting 8%–10% of India’s pregnant population. Assuming that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, the resulting symptoms are due to vasoconstriction, caused by disturbances in the renin–angiotensin system (RAS). Other features of preeclampsia include endothelial dysfunction due to placental ischemia, leading to imbalances in angiogenic and antiangiogenic factors which result in increased blood pressure, proteinuria, altered hepatic enzymes, renal failure, and thrombocytopenia, amongst others. The increased prevalence of preeclampsia that was seen among mothers with SARS-CoV-2 infection might be due to misdiagnosis, as COVID-19 and preeclampsia have coincidental medical features. The major similarities of SARS-CoV-2-infected and preeclamptic women are a rise in pro-inflammatory cytokines, and increased serum ferritin and thrombocytopenia. Therefore, differential diagnosis might be difficult in pregnant women with COVID-19 who present with hypertension and proteinuria, thrombocytopenia, or elevated liver enzymes. The most promising markers for earlier diagnosis of preeclampsia is soluble endoglin (sEng), pregnancy-associated plasma protein-A (PAPP-A), soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF). Due to placental hypoxia, sFlt-1 will be overproduced, thus inhibiting PlGF, and this alteration will be observed in the circulation five weeks or more before the onset of symptoms. The sFlt-1/PlGF ratio may also be modified via infectious states, but unregulated levels of those mediators are related to placental insufficiency. Hence, pregnant women with COVID-19 may develop a preeclampsia-like syndrome that might be differentiated properly by angiogenic markers to avoid unnecessary interventions and induced preterm labor.
  • Comparison of Fasting Insulin Level, Homeostatic Model of Insulin Resistance, and Lipid Levels between Patients with Primary Hypertension and Normotensive Subjects

    Background: Hyperinsulinemia and insulin resistance occurs in obese patients with primary hypertension independent of diabetes and obesity. This study was aimed at assessing serum fasting insulin levels, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum lipid levels in non-obese patients with primary hypertension when compared to normotensive subjects. Methods: This observational study comprised 100 patients over 18 years of age, divided into two groups. The hypertensive group comprised non-obese patients with primary hypertension (n=50); the normotensive group comprised normotensive age- and sex-matched individuals (n=50). Patients with diabetes, impaired fasting glucose, obesity, and other causative factors of insulin resistance were excluded from the study. Serum fasting insulin levels and fasting lipid profiles were measured, and insulin resistance was calculated using HOMA-IR. These data were compared between the two groups. Pearson’s correlation coefficient was used to assess the extent of a linear relationship between HOMA-IR and to evaluate the association between HOMA-IR and systolic and diastolic blood pressures. Results: Mean serum fasting insulin levels (mIU/L), mean HOMA-IR values, and fasting triglyceride levels (mg/dL) were significantly higher in the hypertensive versus normotensive patients (10.32 versus 6.46, P<0.001; 1.35 versus 0.84, P<0.001; 113.70 versus 97.04, P=0.005, respectively). The HOMA-IR levels were associated with systolic blood pressure (r value 0.764, P=0.0005). Conclusion: We observed significantly higher fasting insulin levels, serum triglyceride levels, and HOMA-IR reflecting hyperinsulinemia and possibly an insulin-resistant state among primary hypertension patients with no other causally linked factors for insulin resistance. We observed a significant correlation between systolic blood pressure and HOMA-IR.
  • COVID-19: Healthcare Workers May Be at Greater Risk Outside Their Work Environment—A Retrospective Observational Study

    Background: With the availability of coronavirus disease 2019 (COVID-19) vaccine, concerns have been raised regarding pre-vaccination seroprevalence in healthcare workers (HCW). This study examines the seroprevalence of HCW at an Israeli tertiary medical center before first BNT162b2 vaccination. Methods: This was a retrospective observational study. Before vaccination, HCW at our center were offered serological testing. Data on their epidemiological, workplace, and quarantine history were collect¬ed. The SARS-CoV-2 IgG assay was performed pre-vaccination. Results: A total of 4,519 (82.5%) of the HCW were tested. Of these, 210 were seropositive; 101 had no known history of COVID-19. Of the 101 asymptomatic HCW, only 3 (3%) had worked at COVID-19 depart¬ments, and 70 (69.3%) had not been previously quarantined. Positive serology was similarly distributed across age groups, and about 40% had no children. Nearly half of the HCW tested were administrative and service staff. Overall, seropositive tests were associated with having no children (OR 1.42, 95% CI 1.06–1.89; P=0.0218), history of having been quarantined without proof of disease (OR 6.04, 95% CI 4.55–8.01; P<0.001), and Arab ethnicity (OR 3.36, 95% CI 2.54–4.43; P<0.001). Seropositivity was also more prevalent in members of the administration compared to other sectors, medical and paramedical, who are exposed to patients in their daily work (OR 1.365, 95% CI 1.02–1.82; P=0.04). Conclusions: The low percentage of asymptomatic COVID-19 among our HCW may reflect the high compliance to personal protective equipment use despite treating hundreds of COVID-19 patients. The relatively high number of childless seropositive HCW could reflect misconceptions regarding children as a main source of infection, leading to carelessness regarding the need for appropriate out-of-hospital protection.
  • Quality Assurance of Undergraduate Medical Education in Israel by Continuous Monitoring and Prioritization of the Accreditation Standards

    External accreditation reviews of undergraduate medical curricula play an important role in their quality assurance. However, these reviews occur only at 4–10-year intervals and are not optimal for the immediate identification of problems related to teaching. Therefore, the Standards of Medical Education in Israel require medical schools to engage in continuous, ongoing monitoring of their teaching programs for compliance with accreditation standards. In this paper, we propose the following: (1) this monitoring be assigned to independent medical education units (MEUs), rather than to an infrastructure of the dean’s office, and such MEUs to be part of the school governance and draw their authority from university institu¬tions; and (2) the differences in the importance of the accreditation standards be addressed by discerning between the “most important” standards that have been shown to improve student well-being and/or patient health outcomes; “important” standards associated with student learning and/or performance; “possibly important” standards with face validity or conflicting evidence for validity; and “least important” standards that may lead to undesirable consequences. According to this proposal, MEUs will evolve into entities dedicated to ongoing monitoring of the education program for compliance with accreditation standards, with an authority to implement interventions. Hopefully, this will provide MEUs and faculty with the common purpose of meeting accreditation requirements, and an agreed-upon prioritization of accreditation standards will improve their communication and recommendations to faculty.
  • Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study

    Background and Objective: Medical cannabis is becoming an acceptable treatment modality in medicine, especially for pain relief. Concurrently, cannabis use is becoming more prevalent worldwide, a public demand-driven trend despite the lack of established scientific basis. This observational open-label study sought to investigate the effectiveness of cannabis therapy for alleviating low back pain symptoms. Methods: Two types of cannabis treatment modalities were sequentially administered to chronic low back pain patients. After an initial 1-month washout period (WO1), the first modality was cannabidiol (CBD)-rich sublingual extract treatment administered for 10 months. Following another washout period, the second modality, Δ⁹-tetrahydrocannabinol (THC)-rich smoked inflorescence (whole dried cannabis flowers) was administered for 12 months. Results: Enrolled in the study were 24 patients whose advanced imaging studies (i.e. computerized tomography or magnetic resonance imaging of the lumbar spine) revealed disc herniation or spinal stenosis. Three patients dropped out of extract therapy treatment but resumed study participation to receive THC-rich smoking therapy. After a minimum of 2 years, cannabis therapy had reduced lower back pain symptoms, as assessed by Oswestry Disability Index, the SF-12 patient-reported outcome questionnaire, and the visual analogue scale. Pain reduction was not significant during the extract treatment part of the study; however, pain reduction was significant during the inhaled therapy part of the study. Conclusions: Our findings indicate that inhaled THC-rich therapy is more effective than CBD-rich sublingual extract therapy for treating low back pain and that cannabis therapy is safe and effective for chronic low back pain.