Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are inte¬grated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunc¬tional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.
Objectives: To study mortality changes in Greece prior to and during the financial crisis.
Study design: Analysis of data by the Hellenic Statistical Authority (1955–2013).
Results: During the crisis, mortality increased from 9.76/1000 in 2009 to 10.52/1000 in 2012 and to 11.16/1000 in 2015, driven by an increase in the number of deaths and a decrease in the estimated population. The annual increase of the expected mortality accelerated during the crisis; in contrast, age-adjusted mortality continued to decrease up to 2014 and increased in 2015. The subpopulations that seemed to be affected more during the crisis were the elderly (especially those over 70 years), women, and citizens in southern Greece. The common denominator of all these subgroups was older age. Mortality due to heart diseases continued to decline at an accelerated pace, due to neoplasia continuing to increase at an accelerated pace and due to a reversal in the rate of stroke (from decline to increment).
Conclusions: The increment of crude mortality during the financial crisis in Greece should be attributed to the increase in deaths, only in part due to the aging population, the reduction in births, and the increase in emigration that contracted the population.
Idiopathic hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder characterized by a strikingly high eosinophil count (>1,500 cells/µL), over a long period of time (>6 months), with end organ damage. We present a 60-year-old patient with idiopathic HES with isolated liver involvement, a rare systemic dis¬ease and a rare solid organ involvement. The patient had a thorough investigational work up until HES was established, including liver biopsy. He needed intensive immunosuppressive treatment at first with steroids, then with azathioprine in conjunction with a low dose of steroids. After 16 years of follow-up, the patient showed no evidence of liver dysfunction. To the best of our knowledge, this is the longest follow-up for a patient with HES-associated chronic hepatitis. Our observation suggests that, with appropriate treatment, liver involvement in HES may be well controlled without deterioration to advanced liver failure.
Objective: To review current medical literature on the risks and potential benefits of e-cigarette use and its permissibility under Jewish law.
Methods: A survey of current medical literature about the risks and potential benefits of e-cigarette use, and a review of existing rabbinic literature regarding both combustible and e-cigarette products.
Results: E-cigarettes contain fewer harmful materials than do combustible cigarettes. However, they are not risk-free. Their skyrocketing use among youth is of concern, as e-cigarettes lead to nicotine addiction and are a gateway to combustible cigarettes. Preliminary data indicate that e-cigarettes increase the risk of myocardial infarction, chronic obstructive pulmonary disease (COPD), and emphysema and are no more effective as aids to smoking cessation than US Food and Drug Administration (FDA)-approved interventions with acceptable safety profiles. Few halakhic decisors have opined on the permissibility of e-cigarettes, but extrapolating from halakhic discussions regarding combustible cigarettes strongly suggests that they would prohibit e-cigarettes based on government warnings and preliminary data demonstrating increased risk of cardiovascular and respiratory diseases, at the least because of possible danger (safek sakana). Among youth and pregnant women, for whom e-cigarettes are particularly dangerous and for whom the government has administered explicit warnings, a Jewish legal prohibition should be absolute. There is a unique obligation to prevent youth from obtaining these products. Jewish law might also prohibit deriving benefit from the sale or advertisement of these products.
Conclusions: Extrapolating from rabbinic literature regarding combustible cigarettes, the preliminary data establishing the dangers of e-cigarettes and the government warnings against usage would render these products prohibited under Jewish law, especially for youth and pregnant women.
To the Editor,
I am writing in response to Dr Sharon Galper Grossman’s recent fascinating article, “Vape Gods and Judaism—E-cigarettes and Jewish Law.”1 The author extrapolates from rabbinic literature regard-ing combustible cigarettes and suggests that the preliminary data establishing the dangers of e-cigarettes, and the government warnings against usage, would render these products prohibited under Jewish law, especially for youth and pregnant women.
United States (US) and European Union (EU) laws attempt to counterbalance the presumed discrimination of children in drug treatment and drug development. The US Food and Drug Administration (FDA)-rewarded pediatric studies with antidepressants triggered in 2004 an FDA black-box warning of suicidality in young patients. Fewer antidepressants were prescribed, and the number of completed suicides of young persons increased. The dilemma between this warning and the need to adequately treat young depressed patients remains unsolved. We analyzed the history of drug development, the evolving view of diseases in young patients, US/EU pediatric laws, and pediatric studies triggered by FDA/European Medicines Agency (EMA) in depression and other diseases on the background of developmental pharmacology; financial, institutional, and other interests; and the literature. The FDA/EMA define children administratively, not physio¬logically, as <17 (FDA)/<18 years old (EMA). But young persons mature physiologically well before their 17th/18th birthday. Depression occurs in young persons, has special characteristics, but is not fundamentally different from adult depression. Young persons are not another species. Regulatory requirements for “pediatric” studies focus on “pediatric” labels. Many “pediatric” studies, including those in depression, lacked and lack medical sense and harm patients by placebo treatment although effective drugs exist. The FDA has partially abandoned separate “pediatric” efficacy studies, but not in psychiatry. Clinicians, parents, institutional review boards, and ethics committees should become aware of questionable “pediatric” studies, should re-evaluate ongoing ones, consider to suspend them, and to reject new ones. The concept of separate “pediatric” drug approval needs to be abandoned.
Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis.
Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test.
Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%.
Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.
Background: There are very limited data on the prognostic capacity of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the systemic inflammatory response in pediatric trauma (PT) patients. The purpose of this study was to evaluate the prognostic ability of NLR and PLR on mortality in pediatric trauma patients.
Methods: This study looked at 358 PT patients who were admitted to the Cumhuriyet University Hos-pital’s Emergency Department between January 2010 and June 2018. The NLR and PLR were calculated by dividing the blood neutrophil count and blood platelet count, respectively, by the lymphocyte count, at the time of admission. After performing a stepwise logistic regression analysis to determine the predictive factors on the mortality risk of post-traumatic systemic inflammatory response syndrome (SIRS), receiver operating characteristic (ROC) curve analysis was used to define the optimum cut-off values of the NLR and the PLR parameters for survival.
Results: The NLR, and PLR values were significantly higher in survivors than in non-survivors (NLR, 6.2±5.7 versus 2.6±2.5, P<0.001; PLR, 145.3±85.0 versus 46.2±25.2, P<0.001 ). The NLR (odds ratio [OR], 3.21; P=0.048), PLR (OR, 0.90; P=0.032), blood glucose (OR, 1.02; P=0.024), and Injury Severity Score (ISS) (OR, 1.28; P=0.011) were independent predictors of the mortality risk in PT patients. The area under the curve in the ROC curve analysis was 0.764 with a cut-off of 2.77 (sensitivity 70%, specificity 77%) for the NLR; and 0.928 with a cut-off of 61.83 (sensitivity 90%, specificity 85%) for the PLR.
Conclusion: Acquiring the NLR and PLR at the time of admission could be a useful predictor for mortality in PT patients.
Objectives: To analyze, perioperatively and in follow-up, transilluminated powered phlebectomy (TIPP), a surgical technique for the treatment of varicose veins.
Method: Retrospective study in one medical institution of patients undergoing TIPP between July 2015 and December 2017. Data analyzed included demographic data, surgery, and results. Postoperatively, pain was evaluated by a 10-point visual analogue scale. The Venous Clinical Severity Score (VCSS) was assessed 5–8 weeks following surgery.
Results: Sixty-six patients with extensive varicosities who underwent TIPP were included. Postoperative pain scores were higher in patients undergoing bilateral compared to unilateral TIPP (visual analogue score 7 versus 5; P=0.031). Following surgery, the VCSS improved in 81.8% (54/66) of the patients. However, 39.7% (25/63; data missing in 3 patients) reported that they would not be willing to undergo a similar procedure in the future. Pain was the most common reason for dissatisfaction.
Conclusions: Transilluminated powered phlebectomy was associated with considerable pain and discom¬fort in many patients included in this study. For this reason, it should be reserved for a select group of patients in whom other treatment options are limited; TIPP could be considered in the following cases: patients with a large number of varicosities, reoperations, after extensive thrombophlebitis, obesity, or following bariatric surgery.
Public health is connected to cannabis with regard to food, animal feed (feed), and pharmaceuticals. There¬fore, the use of phytocannabinoids should be examined from a One Health perspective. Current knowledge on medical cannabis treatment (MCT) does not address sufficiently diseases which are of epidemiological and of zoonotic concern. The use of cannabinoids in veterinary medicine is illegal in most countries, mostly due to lack of evidence-based medicine. To answer the growing need of scientific evidence-based applicable medicine in both human and veterinary medicine, a new approach for the investigation of the therapeutic potential of cannabinoids must be adopted. A model that offers direct study of a specific disease in human and veterinary patients may facilitate development of novel therapies. Therefore, we urge the regulatory authorities—the ministries of health and agriculture (in Israel and worldwide)—to publish guidelines for veterinary use due to its importance to public health, as well as to promote One Health-related preclinical translational medicine studies for the general public health.
