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  • The Significance of Normal Pretreatment Levels of CA125 (<35 U/mL) in Epithelial Ovarian Carcinoma

    Objective: To assess the association between normal CA125 levels at diagnosis of epithelial ovarian carcinoma (EOC) with prognostic factors and with outcome. Methods: The study group consisted of histologically confirmed EOC patients with normal pretreatment CA125 levels, and the controls consisted of EOC patients with elevated (≥35 U/mL) pretreatment CA125 levels, diagnosed and treated between 1995 and 2012. Study and control group patients fulfilled the following criteria: 1) their pretreatment CA125 levels were assessed; 2) they had full standard primary treatment, i.e. cytoreductive surgery and cisplatin-based chemotherapy; and 3) they were followed every 2–4 months during the first two years and every 4–6 months thereafter. Results: Of 114 EOC patients who fulfilled the inclusion criteria, 22 (19.3%) had normal pretreatment CA125 levels. The control group consisted of the remaining 92 patients with ≥35 U/mL serum CA125 levels pretreatment. The proportion of patients with early-stage and low-grade disease, with optimal cytoreduction, and with platin-sensitive tumors was significantly higher in the study group than in the control group. The progression-free survival (PFS) and overall survival (OS) were significantly higher in the study group than in the control group on univariate analysis but not on multivariate analysis. Conclusion: It seems that a normal CA125 level at diagnosis in EOC may also be of prognostic significance for the individual patient.
  • Dr. Otto Heinrich Warburg—Survivor of Ethical Storms

    Otto Heinrich Warburg (1883–1970; not to be confused with the Zionist of the same name) was a member of an illustrious Jewish family, known for some five centuries. From humble beginnings, the family became prominent in the world for their contributions to all aspects of society. The son of a German mother and a Jewish (converted) father, Otto H. Warburg became a major contributor to medical science in the field of cancer research. Considered for Nobel Prize more than once, he finally received it in 1931 for his discovery of the nature and mode of action of the cellular respiratory enzyme. Warburg’s personality was controversial: he was intolerant of opposing scientific views yet tolerant toward Nazi abuses. Accused of collaboration under the Nazi regime, Otto H. Warburg was nevertheless readmitted to the global scientific community after World War II. His contribution to cancer research remains influential to this day and has been superseded by discoveries that have built upon his work.
  • Academic Debate: Publications Which Promote Political Agendas Have no Place in Scientific and Medical Journals, and Academics Should Refrain from Publishing in Such Journals

    This paper presents the full debate held on October 1, 2014, which focused on the following resolution: “Publications which promote political agendas have no place in scientific and medical journals, and academics should refrain from publishing in such journals.” The debate moderator was Professor Shimon Glick. Taking the pro stance was Professor A. Mark Clarfield; the con stance was held by Professor Rael D. Strous. Following the first part of the debate, Dr Richard Horton, Editor-in-Chief of The Lancet, gave his thoughts on the topic. This was followed by the opportunity for rebuttal by Professors Clarfield and Strous. The debate was summarized and closed by Professor Glick. This paper provides a slightly edited text of the debate, for ease of reading.
  • A Chaplain-led Spiritual Life Review Pilot Study for Patients with Brain Cancers and Other Degenerative Neurologic Diseases

    Objective: This pilot study was designed to describe changes in spiritual well-being (SWB), spiritual coping, and quality of life (QOL) in patients with brain cancer or other neurodegenerative diseases participating in a chaplain-led spiritual life review interview and development of a spiritual legacy document (SLD). Methods: Eligible participants were enrolled and completed baseline questionnaires. They were interviewed by a board-certified chaplain about spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD was prepared for each participant, and one month follow-up questionnaires were completed. Two cases are summarized, and spiritual development themes are illustrated within a spiritual development framework. Results: A total of 27 patients completed baseline questionnaires and the interview; 24 completed the SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious coping, and QOL were detected. The majority maintained the highest (best) scores of negative religious coping, demonstrating minimal spiritual struggle. Conclusions: Despite the challenges of brain cancers and other neurodegenerative diseases, participants demonstrated improvements in SWB, positive religious coping, and QOL. Patient comments indicate that benefit is related to the opportunity to reflect on and integrate spiritual experiences and to preserve them for others. Research with a larger, more diverse sample is needed, as well as clinical applications for those too vulnerable to participate in longitudinal follow-up.
  • Teaching and Assessing Professionalism in Medical Learners and Practicing Physicians

    Professionalism is a core competency of physicians. Clinical knowledge and skills (and their maintenance and improvement), good communication skills, and sound understanding of ethics constitutes the foundation of professionalism. Rising from this foundation are behaviors and attributes of professionalism: accountability, altruism, excellence, and humanism, the capstone of which is professionalism. Patients, medical societies, and accrediting organizations expect physicians to be professional. Furthermore, professionalism is associated with better clinical outcomes. Hence, medical learners and practicing physicians should be taught and assessed for professionalism. A number of methods can be used to teach professionalism (e.g. didactic lectures, web-based modules, role modeling, reflection, interactive methods, etc.). Because of the nature of professionalism, no single tool for assessing it among medical learners and practicing physicians exists. Instead, multiple assessment tools must be used (e.g. multi-source feedback using 360-degree reviews, patient feedback, critical incident reports, etc.). Data should be gathered continuously throughout an individual’s career. For the individual learner or practicing physician, data generated by these tools can be used to create a “professionalism portfolio,” the totality of which represents a picture of the individual’s professionalism. This portfolio in turn can be used for formative and summative feedback. Data from professionalism assessments can also be used for developing professionalism curricula and generating research hypotheses. Health care leaders should support teaching and assessing professionalism at all levels of learning and practice and promote learning environments and institutional cultures that are consistent with professionalism precepts.
  • International Collaboration: Promises and Challenges

    We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative means to bring talented teams together to tackle these challenges across the globe.
  • A Preliminary Study of Three-dimensional Sonographic Measurements of the Fetus

    Objectives: This study was aimed at establishing an ideal method for performing three-dimensional measurements of the fetus in order to improve the estimation of fetal weight. Methods: The study consisted of two phases. Phase I was a prospective cross-sectional study performed between 28 and 40 weeks’ gestation. The study population (n=110) comprised low-risk singleton pregnancies who underwent a routine third-trimester sonographic estimation of fetal weight. The purpose of this phase was to establish normal values for the fetal abdominal and head volumes throughout the third trimester. Phase II was a prospective study that included patients admitted for an elective cesarean section or for induction of labor between 38 and 41 weeks’ gestation (n=91). This phase of the study compared the actual birth weight to two- (2D) and three-dimensional (3D) measurements of the fetus. Conventional 2D ultrasound fetal biometry was performed measuring the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FL). Volume estimates were computed utilizing Virtual Organ Computer-aided AnaLysis (VOCAL), and the correlation between measured volumes and actual neonatal weight was calculated. Results: Overall, this longitudinal study consisted of 110 patients between 28 and 41 weeks’ gestation. Normal values were computed for the fetal abdomen and head volume throughout the third trimester. Ultrasound examination was performed within three days prior to delivery on 91 patients. A good correlation was found between birth weight and abdominal volume (r=0.77) and between birth weight and head volume (r=0.5). Correlation between bidimensional measurements and actual fetal weights was found to be comparable with previously published correlations. Conclusion: Volume measurements of the fetus may improve the accuracy of estimating fetal size. Additional studies using different volume measurement of the fetus are necessary.
  • The Number Needed to Treat: 25 Years of Trials and Tribulations in Clinical Research

    The number needed to treat (NNT) is a simple measure of a treatment’s impact, increasingly reported in randomized trials and observational studies. It has been found to be incorrectly calculated in several studies involving varying follow-up times. We discuss the NNT in these contexts and illustrate the concept using several published studies. The computation of the NNT is founded on the cumulative incidence of the outcome. Instead, several published studies use simple proportions that do not account for varying follow-up times, or use incidence rates per person-time. We show how these approaches can lead to erroneous values of the NNT and misleading interpretations. For example, a trial of 3,845 very elderly hypertensives randomized to a diuretic or placebo reported a NNT of 94 treated for 2 years to prevent one stroke, though the correct approach results in a NNT of 63. We also note that meta-analyses involve trials of differing lengths, but often report a single NNT. For example a meta-analysis of 22 trials of the anticholinergic tiotropium in chronic obstructive pulmonary disease reported a NNT of 16 patients “over one year,” even if the trials varied in duration from 3 to 48 months, with the more specifically computed NNTs varying widely from 72, 15, and 250 for the 3-month, 12-month, and 48-month trials, respectively. Finally, we describe the value of the NNT in assessing benefit–risk, such as low-dose aspirin use in secondary prevention, where prevention of mortality was assessed against the risk of gastrointestinal bleeding. As the “number needed to treat” becomes increasingly used in the comparative effectiveness and safety of therapies, its accurate estimation and interpretation become crucial to avoid distorting clinical, economic, and public health decisions.
  • Fifth Anniversary of Rambam Maimonides Medical Journal: From Concept to Action and Success

    An anniversary is not only a point of memory—it provides the opportunity for self-examination and paves the way to the future. Every anniversary marks a starting-point that was preceded by a vision. The beginning of any vision is a personal dream—someone wants to improve or repair the world as far as he is able. The vision motivates action; in its aftermath comes the reality. This is the 21st issue of Rambam Maimonides Medical Journal. This issue is particularly important as it marks the completion of five years of creative work pursuing our vision for a high-caliber scientific medical journal. Our vision has become reality.
  • The Angelina Jolie Effect in Jewish Law: Prophylactic Mastectomy and Oophorectomy in BRCA Carriers

    Background: Following the announcement of actress Angelina Jolie’s prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery. Objective: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law. Results: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy. Conclusion: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery.