A great deal of biomedical research focuses on new biotechnologies such as gene editing, stem cell biology and reproductive medicine, which have created a scientific revolution. While the potential medical benefits of this research may be far-reaching, ethical issues related to non-medical applications of these technologies are demanding. We analyze, from a Jewish legal perspective, some of the ethical conundrums that society faces in pushing the outer limits in researching these new biotechnologies.
I am pleased to announce that the winner of the 2018 Maimonides Best Published Original Research Prize is Dr. Louise Kezerle, the first author of the paper entitled, “A Population-based Study of Peripartum Cardiomyopathy in Southern Israel: Are Bedouin Women a New High-risk Group?” with co-authors Iftach M. Sagy, Leah Shalev, Offer Erez, and Leonid Barski.
Deformity of the breast and axilla observed in famous paintings is a fascinating field for the medico-artists. The attempt of a retrospective diagnosis of breast tumors is highly challenging. This paper deals with a Rubens painting portraying the heroine Judith with a visible but previously unreported left breast mass. Though speculative, the present medico-artistic diagnosis is of a tumor likely to be of benign nature. It is of interest that the present case is the sixth breast disease discovered in Rubens’s works.
Background: Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne viral disease with a high mortality rate. Although CCHF has been widely investigated over the past decade, a review of the literature indicated no data on the prognostic capacity of the mean platelet volume-to-platelet count ratio (MPVPCR) and the red cell distribution width-to-platelet count ratio (RDWPCR) for the systemic inflammatory response in patients with CCHF. This study aimed to evaluate the prognostic ability of MPVPCR and RDWPCR on mortality in patients with CCHF.
Methods: A total of 807 patients that were admitted to the Cumhuriyet University Hospital’s Emergency Department from January 2010 to December 2018 were involved. The RDWPCR and MPVPCR were separately calculated via absolute blood red cell and platelet counts at the time of admission. Before performing receiver-operating characteristic (ROC) curve analysis to define the optimum cut-off values of MPVPCR and RDWPCR stepwise logistic regression analysis was used to determine the predictive factors related to mortality in CCHF patients.
Results: Values of both MPVPCR and RDWPCR were significantly lower in survivors than in non-survivors (MPVPCR: 0.20±0.23 versus 0.55±0.55, P<0.001; RDWPCR: 0.27±0.32 versus 0.77±0.77, P<0.001, respectively). The MPVPCR (odds ratio [OR], 5.95; P=0.048) was an independent predictor for the prognosis of mortality in CCHF patients. The area under the curve in the ROC curve analysis for MPVPCR was 0.876 with a cut-off of 0.21 (sensitivity 87%, specificity 76%).
Conclusion: At the time of admission, MPVPCR might be a useful predictor of mortality in patients with CCHF.
To the Editor,
We read with great interest the retrospective article of Tekin and Engin that investigated the prognostic significance of the ratio of mean platelet volume (MPV) to platelet count ratio (MPVPCR) in patients with Crimean-Congo hemorrhagic fever (CCHF). The authors found that MPVPCR was significantly lower in survivors than in non-survivors, and there-fore they suggested that this ratio could be used as a mortality marker. We think there are other factors that might have affected the results of this study.
We have carefully read and evaluated the letter writ¬ten by Drs Mungmunpuntipantip and Wiwanitkit regarding our article published in the July issue of Rambam Maimonides Medical Journal.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were elaborated to allow authors of such papers to identify quality articles for inclusion in their scholarly work. However, we have identified several issues that point to an over-reliance on the PRISMA guidelines. Firstly, we question the rigor of implementation by authors and the rigor of verification by peer reviewers and editors, and whether they have screened papers to ensure adherence to the PRISMA guidelines. Secondly, we have identified cases where the PRISMA criteria led to as much as 99.97% of the published literature being ignored, suggesting that valid publications meeting these criteria might be at risk of being ignored. Thirdly, we have noted that exclusion is not only a quantitative problem—it is also a qualitative one, since the screening procedure groups all non-conforming literature into one basket. Fourthly, we have noted that seven copies of the PRISMA guidelines exist. This being the case, which one should be cited? To replace over-reliance on PRISMA screening, we encourage authors, peer reviewers, and editors to publish systematic reviews and meta-analyses that respect the dual criteria of scientific plausibility and diversity of included papers.
Objective: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease. The NPV is the probability that a patient does not have the disease, given a negative test result for that disease. Both values depend on disease incidence or prevalence, which may be highly uncertain for unfamiliar diseases, epidemics, etc. Probability distributions for this uncertainty are usually unavailable. We develop a non-probabilistic method for interpreting PPV and NPV with uncertain prevalence.
Methods: Uncertainty in PPV and NPV is managed with the non-probabilistic concept of robustness in info-gap theory. Robustness of PPV or NPV estimates is the greatest uncertainty (in prevalence) at which the estimate’s error is acceptable.
Results: Four properties are demonstrated. Zeroing: best estimates of PPV or NPV have no robustness to uncertain prevalence; best estimates are unreliable for interpreting diagnostic tests. Trade-off: robustness increases as error increases; this trade-off identifies robustly reliable error in PPV or NPV. Preference reversal: sometimes sub-optimal PPV or NPV estimates are more robust to uncertain incidence or prevalence than optimal estimates, motivating reversal of preference from the putative optimum to the sub-optimal estimate. Trade-off between specificity and robustness to uncertainty: the robustness increases as test-specificity decreases. These four properties underlie the interpretation of PPV and NPV.
Conclusions: The PPV and NPV assess diagnostic tests, but are sensitive to lack of knowledge that generates non-probabilistic uncertain prevalence and must be supplemented with robustness analysis. When uncertainties abound, as with unfamiliar diseases, assessing robustness is critical to avoiding erroneous decisions.