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  • Something Must Be Wrong with the Implementation of Cancer-pain Treatment Guidelines. A Lesson from Referrals to a Pain Clinic

    Objective: The World Health Organization’s (WHO) guidelines for cancer pain management were intentionally made simple in order to be widely implemented by all physicians treating cancer patients. Referrals to pain specialists are advised if pain does not improve within a short time. The present study examined whether or not a reasonable use of the WHO guideline was made by non-pain specialists prior to referral of patients with cancer-related pain to a pain clinic. Methods: Cancer patients referred to a pain specialist completed several questionnaires including demographics, medical history, and cancer-related pain; the short-form McGill Pain Questionnaire (SF-MPQ); and the Short Form Health Survey SF-12. Data from referral letters and medical records were obtained. Treatments recommended by pain specialists were recorded and categorized as “unjustified” if they were within the WHO ladder framework, or “justified” if they included additional treatments. Results: Seventy-three patients (44 women, 29 men) aged 55 years (range, 25–85) participated in the study. Their pain lasted for a mean of 6 (1–192) months. Mean pain intensity scores on a 0–10 numerical rating scale were 7 (2–10) at rest and 8 (3–10) upon movement. Most patients complied with their referring physician’s recommendations and consumed opioids. Adverse events were frequent. No significant correlation was found between the WHO analgesic medication step used and mean pain levels reported. There were 63 patient referrals (85%) categorized as “unjustified,” whereas only 11 patients (15%) required “justified” interventions. Conclusions: These findings imply that analgesic treatment within the WHO framework was not reasonably utilized by non-pain specialists before referring patients to pain clinics.
  • A Comparison of Manual versus Electric Bicycle Injuries Presenting to a Pediatric Emergency Department

    Background: The use of electric bicycles (E-bikes) has dramatically increased over the last decade. E-bikes offer an inexpensive, alternative form of transport, but also pose a new public health challenge in terms of safety and injury prevention. Objective: The aim of this study was to describe the epidemiology and severity of E-bike related injuries among children treated in the emergency department (ED) and to compare these to manual bicycle related injuries. Methods: A retrospective observational study of all pediatric patients presenting to the ED between December 2014 and November 2015 with an injury related to E-bike or manual bicycle use. Data including demographics, diagnosis, injury severity score (ISS), and outcome were compared. Results: A total of 196 cyclist injuries presented to the ED; 85 related to E-bike use and 111 to manual bicycle riders. The mean age of E-bikers was 13.7 years (7.5–16 years) and of manual bicycle riders was 9.9 years (3–16 years). Injuries to the head and the extremities were common in both groups. E-bikers had significantly more intra-abdominal organ injury (P=0.047). Injury severity scores were low overall, but injuries of higher severity (ISS>9) only occurred among the E-bikers. Conclusions: Pediatric E-bike injuries tend to be more severe than those sustained during manual bicycle riding. Further research into bicycle and other road and pavement users could lead to enhanced regulation regarding E-bike usage.
  • Expression Pattern of the Cancer Stem Cell Marker “Nestin” in Leukoplakia and Oral Squamous Cell Carcinoma

    Objective: The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis. Methods: Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expres¬sion was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters. Results: Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leuko-plakia, to oral squamous cell carcinoma. Conclusion: This study has two major findings: 1) identification of nestin as an effective indicator of neo-angiogenesis, and 2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis.
  • Letter to the Editor Regarding Vaping Article

    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.
  • Too Many Avoidable Suicides Occur Worldwide in Young Patients

    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.
  • Response to “Letter to the Editor Regarding Vaping.” Seven Reasons E-cigarettes Must Be “Downright Prohibited” Now!

    To the Editor, I thank Rabbi Spitz for his thoughtful analysis. However, I humbly disagree with his conclusion that it is premature to classify e-cigarettes as “downright prohibited.”
  • Biomarkers for Autism Spectrum Disorders (ASD): A Meta-analysis

    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.
  • Third-trimester Reference Ranges for Cerebroplacental Ratio, Middle Cerebral Artery, and Umbilical Artery Pulsatility Index in Normal-growth Singleton Fetuses in the Israeli Population

    Background: The ratio between the fetal umbilical artery pulsatility index (UA-PI) and the middle cerebral artery pulsatility index (MCA-PI) is termed the cerebroplacental ratio (CPR). The CPR represents fetal blood flow redistribution at the early stages of placental insufficiency; moreover, it has predictive value for adverse intrapartum and neonatal outcomes. However, internationally accepted reference ranges for CPR are lacking. Objective: This study sought to establish UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester of pregnancy. Methods: A retrospective cohort cross-sectional study was performed in the obstetrics ultrasound unit of a university hospital in Israel. We reviewed all fetal and maternal electronic records of pregnant women referred for ultrasound assessment during the third trimester between January 2014 and January 2019. We included only singleton pregnancies with normal anatomy scans and a normal third-trimester estimated fetal weight. The UA-PI, MCA-PI, and CPR reference ranges were reconstructed for each of the vessels for each gestational age between 29 and 41 weeks. Results: A total of 560 pregnancies met the inclusion criteria. Satisfactory waveforms and measurements were obtained in all cases. At least 18 women enrolled at each gestational week. The MCA-PI and CPR val-ues showed a similar parabolic curve during the third trimester of pregnancy, with a peak value at 32 and 33 gestational weeks, respectively. The UA-PI showed a linear and gradual decrease over the gestational age. Conclusions: In this study we established UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester based on the Israeli population.
  • Are Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Associated with Mortality in Pediatric Trauma Patients? A Retrospective Study

    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.
  • Pain is a Limiting Factor in Patients Suitable for Transilluminated Powered Phlebectomy

    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.