Background: Overall accuracy measures of medical tests are often used with unclear interpretations.
Objectives: To develop methods of calculating the overall accuracy of medical tests in the patient population.
Methods: Algebraic equations based on Bayes’ theorem.
Results: A new approach is proposed for calculating overall accuracy in the patient population. Examples and applications using published data are presented.
Conclusions: The overall accuracy is the proportion of the correct test results. We introduce a clear distinction between the overall accuracy measures of medical tests that are aimed at the detection of a disease in a screening of populations for public health purposes in the general population and the overall accuracy measures of tests aimed at determining a diagnosis in individuals in a clinical setting. We show that the overall detection accuracy measure is obtained in a specific study that explores test accuracy among persons with known diagnoses and may be useful for public health screening tests. It is different from the overall diagnostic accuracy that could be calculated in the clinical setting for the evaluation of medical tests aimed at determining the individual patients’ diagnoses. We show that the overall detection accuracy is constant and is not affected by the prevalence of the disease. In contrast, the overall diagnostic accuracy changes and is dependent on the prevalence. Moreover, it ranges according to the ratio between the sensitivity and specificity. Thus, when the sensitivity is greater than the specificity, the overall diagnostic accuracy increases with increasing prevalence, and vice versa, that is, when the sensitivity is lower than the specificity, the overall diagnostic accuracy decreases with increasing prevalence so that another test might be more useful for diagnostic procedures. Our paper suggests a new and more appropriate methodology for estimating the overall diagnostic accuracy of any medical test. This may be important for helping clinicians avoid errors.
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.
Cancer patients have a pro-thrombotic state attributed to the ability of cancer cells to activate the coagula¬tion system and interact with hemostatic cells, thus tilting the balance between pro- and anticoagulants. Mechanisms underlying the coagulation system activation involve tumor cells, endothelial cells, platelets, and white blood cells. Anti-cancer therapies, including anti-angiogenic drugs, significantly increase the risk of thrombosis during treatment. Along with the role of coagulation proteins in the hemostatic system, these proteins also serve as growth factors to the tumor. Heparanase is a pro-angiogenic and pro-metastatic protein. Our previous studies have demonstrated that it enhances tissue factor (TF) activity and is present at high levels in tumor cells and patients’ blood. Strategies to attenuate heparanase effects by heparin mimetics or peptides interrupting the TF–heparanase interaction are good candidates to attenuate tumor growth and thrombotic manifestations.
Objective of the work: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer.
Research aim: Pancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer.
Methods: Between 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described.
Results: Three patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings.
Conclusions: Adherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.
In recent years, it has become increasingly important to improve efficiency and economic balance in hospitals. The department chairperson (or Chair) contends with a production function consisting of inputs and outcomes, rife with managerial constraints. These constraints can be reduced with proper management by diverting resources and activity. Lack of a proper management algorithm at the department level is a significant impediment to improving operational efficiency in hospitals without significant additional costs. In this work we aimed to develop and implement a management algorithm in a teaching hospital department, in order to improve performances and quality of care. From September 2012 to December 2017 we developed a novel management algorithm for a surgical department and implemented it in the Head and Neck Surgery Department at Rambam Medical Center, Haifa, Israel. Changes were made to the organization structure and the concept of service provision. We defined core measures reflecting operative actions and outcomes and identified actions that could affect these measures. Based on our analysis of outcomes we constructed a management intervention process that defines operative actions leading to improved performance. The result was over 400% improvement in the department’s outcome measures including quality, activity, and service. Analysis of data from the Israeli Ministry of Health revealed that the department’s ranking in performance measures and volume improved from no. 14 of 23 departments in Israel in 2011, to no. 1 in 2013, which was sustained through 2014–2016. Improvement in efficiency also translated to economic balance and transformation from deficit to profitability. If this algorithm is implemented in the rest of the system, it is expected to improve the function of the hospital as a whole. Our results have the potential to foster the development of a new organizational culture of measurement and improvement in the hospital, and subsequently in the entire health system.
Achalasia is a chronic idiopathic disease characterized by the absence of esophageal body peristalsis and by defective lower esophageal sphincter (LES) relaxation. The incidence rate ranges from 1.07 to up to 2.8 new cases per year per 100,000 population. Presenting symptoms include dysphagia, regurgitation, vomiting, and weight loss. The diagnosis of achalasia has undergone a revolution in the last decade due to the advent of high-resolution manometry (HRM) and the consequent development of the Chicago Classification. Recent progress has allowed achalasia to be more precisely diagnosed and to be categorized into three subtypes, based on the prevalent manometric features of the esophageal peristalsis. Treatment options are pharmacotherapy, endoscopic management (Botox injection or pneumatic dilation), and surgery, e.g. laparoscopic Heller myotomy (LHM). More recently, a new endoscopic technique, per oral endoscopic myotomy (POEM), has developed as a less invasive approach alternative to the traditional LHM. Since the first POEM procedure was performed in 2008, increasing evidence is accumulating regarding its efficacy and safety profiles. Currently, POEM is being introduced as a reasonable therapeutic option, though randomized controlled trails are still lacking. The current review sheds light onto the diagnosis and manage¬ment of achalasia, with special focus on the recent advances of HRM and POEM.
All natural animals and plants are holobionts, consisting of the host and microbiome, which is composed of abundant and diverse microorganisms. Health and disease of holobionts depend as much on interactions between host and microbiome and within the microbiome, as on interactions between organs and body parts of the host. Recent evidence indicates that a significant fraction of the microbiome is transferred by a variety of mechanisms from parent to offspring for many generations. Genetic variation in holobionts can occur in the microbiome as well as in the host genome, and it occurs more rapidly and by more mechanisms in genomes of microbiomes than in host genomes (e.g. via acquisition of novel microbes and horizontal gene transfer of microbial genes into host chromosomes). Evidence discussed in this review supports the concept that holobionts with their hologenomes can be considered levels of selection in evolution. Though changes in the microbiome can lead to evolution of the holobiont, it can also lead to dysbiosis and diseases (e.g. obesity, diarrhea, inflammatory bowel disease, and autism). In practice, the possibility of manipulating microbiomes offers the potential to prevent and cure diseases.
This review examines the risk of developing celiac disease (CD) and other autoimmune diseases in individ¬uals receiving the rotavirus (RV) vaccine compared to the normal population. Celiac disease is a malabsorp¬tive, chronic, immune-mediated enteropathy involving the small intestine. The pathogenesis of CD is multifactorial, and mucosal immunity plays an important role in its development. Low mucosal IgA levels significantly increase the risk of developing the disease. Rotavirus is an infectious agent that causes diar¬rhea, particularly in children aged 0–24 months, and is frequently involved in diarrhea-related deaths in these children. An oral vaccine against RV has been developed. While it is effective on RV infection, it also contributes to increasing mucosal immunity. Studies have indicated that individuals immunized with the RV vaccine are at lower risk of developing CD than unvaccinated individuals. In addition, the mean age for developing CD autoimmunity may be higher in the vaccinated group than in controls receiving placebo. Additional studies that include children immunized with different RV vaccines and unvaccinated children would provide more meaningful results. Although current data suggest a possible association of RV vaccina¬tion with a reduced risk of developing CD and other autoimmune diseases, this remains an unanswered question that merits greater international investigation.
Objectives: To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa.
Methods: Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively.
Results: Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant.
Conclusion: The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
Background: Eosinophils constitute 1%–5% of peripheral blood leukocytes, less in the presence of acute infections (referred to as eosinopenia). Studies indicate that eosinopenia can be used as a prognostic predictor for chronic obstructive pulmonary disease exacerbation, sepsis, or acute myocardial infarction disease. There are only a few studies about predicting mortality in emergency departments and intensive care units (ICUs). Prognostic studies about patients in ICUs are generally carried out using different scoring systems. We aimed to analyze if the eosinophil count can estimate the prognosis among non-traumatic patients who underwent cardiopulmonary resuscitation and were hospitalized in ICU thereafter.
Methods: The data were evaluated of 865 non-traumatic adult patients (>18 years of age) who were admitted with cardiopulmonary arrest or developed cardiopulmonary arrest during clinical follow-ups. Admission venous blood sample tests, complete blood count, and biochemical laboratory results were recorded. Arterial blood gas results were also evaluated. The mean results of the recorded laboratory results were compared between the surviving and non-surviving patients groups.
Results: There was a significant difference between the two groups in regard to platelet, eosinophil count, pH, PaO2, SaO2, and HCO3- (P<0.001 for all). In the multiple linear regression analysis, eosinophil counts were found to be an independent factor (odds ratio=0.03, 95% confidence interval 0.33–0.56, P<0.001) associated with the mortality after cardiopulmonary resuscitation.
Conclusion: Because admission eosinophil counts can be measured easily, they are inexpensive biomarkers that can be used for predicting the prognosis among the patients who have return of spontaneous circulation and are treated in ICUs.
