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  • Palliative Care: Too Good to Be True?

    Introduction: Many patients and their families are hesitant to consult a palliative care (PC) team. In 2014, approximately 6,000,000 people in the United States could benefit from PC, and this number is expected to increase over the next 25 years. Objectives: The purpose of this review is to shed light on the significance of PC and provide a holistic view outlining both the benefits and existing barriers. Methods: A literature search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, and Web of Science to identify articles published in journals from 1948 to 2019. A narrative approach was used to search the grey literature. Discussion: Traditionally, the philosophy behind PC was based on alleviating suffering associated with terminal illnesses; PC was recommended only after other treatment options had been exhausted. However, the tenets of PC are applicable to anyone with a life-threatening illness as it is beneficial in conjunction with traditional treatments. It is now recognized that PC services are valuable when initiated alongside disease-modifying therapy early in the disease course. Studies have shown that PC decreased total symptom burden, reduced hospitalizations, and enabled patients to remain safely at home. Conclusion: As the population ages and chronic illnesses become more widespread, there continues to be a growing need for PC programs. The importance of PC should not be overlooked despite existing barriers such as the lack of professional training and the cost of implementation. Education and open discussion play essential roles in the successful early integration of PC.
  • Effect of Inhalational Therapy on Buccal Mucosal Cells in Asthmatic Patients: A Cytological Study

    Objective: Inhalational drugs used in treating asthma have several side effects including those on oral tissues. We therefore designed a study to analyze the effects of inhalational drugs on the buccal mucosal cells of the oral cavity. Methods: Smears were obtained from clinically normal buccal mucosa of 20 randomly selected asthmatic patients who had been under inhalational therapy for at least 6 months. The Papanicolaou-stained smears were then analyzed for average nuclear area, average cytoplasmic area, and average nuclear area:cyto¬plasmic area ratio for each patient, and the values were compared with those of 10 healthy controls. Results: A statistically significant decrease in cytoplasmic area (P<0.001) was found in asthmatic patients compared to controls. A significant increase in mean nuclear area:cytoplasmic area ratio (P<0.001) was noted in asthmatic patients when compared to controls. Conclusion: Prolonged use of inhalational drugs in patients diagnosed with asthma is associated with changes in oral epithelial cells. There is a need to assess whether these are the direct adverse effects of such drugs and whether they have any long-term impact on oral tissues.
  • Bioresorbable Scaffolds: Current Technology and Future Perspectives

    Metallic drug-eluting stents have led to significant improvements in clinical outcomes but are inherently limited by their caging of the vessel wall. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations, allowing a “leave nothing behind” approach. Although theoretically appealing, the initial experience with BRS technology was limited by increased rates of scaffold thrombosis compared with contemporary stents. This review gives a broad outline of the current BRS technologies and outlines the refinements in BRS design, procedural approach, lesion selection, and post-procedural care that resulted from early BRS trials.
  • Causative Pathogens in Endophthalmitis after Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents

    Intravitreal injection of anti-vascular endothelial growth factor is currently the preferred treatment for several posterior segment diseases, including age-related macular degeneration and diabetic retinopathy, as well as macular edema and retinal vein occlusion. As an invasive procedure it involves risks. The most sig¬nificant risk is infectious endophthalmitis, a sight-threatening and even a globe-threatening acute fulminant condition. Most common pathogens include Streptococcus and Staphylococcus species, surprisingly origi¬nating from the patient’s, surgeon’s, or nurse’s mouth. Infectious endophthalmitis may have devastating and irreversible effect, with Streptococcus-induced cases having the worst visual outcome. It is therefore crucial for clinicians to promptly recognize and treat such conditions, and, far more important, to put in place protective and preventive measures against this rare, but sight-threatening complication. To that end, this paper describes the most common pathogens causing endophthalmitis after IVI of anti-VEGF, and defines their source, to aid the physician in developing strategies to prevent this catastrophic infection.
  • Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt

    Objective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at Rambam Health Care Campus in rare disease diagnostics using whole-exome sequencing (WES). Methods: Phenotypic characterization of patients was done in close collaboration with referring physi-cians. We utilized WES analysis for diagnosing families suspected for rare genetic disorders. Bioinformatic analysis was performed in-house using the Genoox analysis platform. Results: Between the years 2014 and 2017, we studied 34 families. Neurological manifestations were the most common reason for referral (38%), and 55% of families were consanguineous. A definite diagnosis was reached in 21 cases (62%). Four cases (19%) were diagnosed with variants in novel genes. In addition, six families (18%) had strong candidate novel gene discoveries still under investigation. Therefore, the true diagnosis rate is probably even higher. Some of the diagnoses had a significant impact such as alerting the patient management and providing a tailored treatment. Conclusions: An accurate molecular diagnosis can set the stage for improved patient care and provides an opportunity to study disease mechanisms, which may lead to development of tailored treatments. Data from our genetic research program demonstrate high diagnostic and novel disease-associated or causative gene discovery rates. This is likely related to the unique genetic architecture of the population in Northern Israel as well as to our strategy for case selection and the close collaboration between analysts, geneticists, and clinicians, all working in the same hospital.
  • Effect of Socioeconomic Status and Ethnicity on Glycemic Control in Arab and Jewish Youth with Type 1 Diabetes Mellitus

    Objectives: Research and theory suggests that socioeconomic status may affect diabetes control. We investigated the effect of socioeconomic status and ethnicity on glycated hemoglobin (HbA1c) in Arab and Jewish children with type 1 diabetes mellitus in northern Israel. Methods: Data were collected from medical records of 80 Arab and 119 Jewish children attending a pediatric diabetes clinic in a tertiary health care center. Multivariate regression analysis was used to assess factors independently affecting HbA1c level. Results: Mean age was 12.9±4.7 years. Arab families had more children compared to Jewish families (3.7±1.5 versus 2.9±1.2, respectively, P=0.0007). Academic education was significantly less common in Arab families (25% versus 66.2%, respectively, P=0.0001). Income of Jewish parents was significantly higher compared to that of Arab parents (7,868±2,018 versus 5,129±906 NIS/month, respectively, P=0.0001). Mean age at diagnosis of diabetes was 9.6±4.6 years and disease duration was 3.4±2.3 years in both groups. Half of Arab and Jewish children were treated with multiple insulin injections and half with insulin pumps. Mean number of self-glucose testing/day was higher in Jewish children than in Arab children (4.7±2.5 versus 4.0±1.5, respectively, P=0.033). Mean HbA1c was above recommendations, 9.5% (12.6 mmol/L) in Arab children and 8.7% (11.3 mmol/L) in Jewish children (P=0.004). In multivariate analysis, disease duration (P=0.010) and ethnicity (P=0.034 for Arabs versus Jews) were independently associated with HbA1c. Conclusions: Both Arab and Jewish children failed to meet HbA1c goals, but this effect was significantly greater for Arabs. Ethnicity remained a predictor of failure even following adjustment for potential confounders.
  • Screening to Detect Precursor Lesions of Pancreatic Adenocarcinoma in High-risk Individuals: A Single-center Experience

    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.
  • Management of Breathlessness in Palliative Care: Inhalers and Dyspnea—A Literature Review

    Introduction: Dyspnea is prominently observed in palliative care (PC). Dyspnea can be multifactorial, primarily caused by obstructive or restrictive lung diseases or secondarily induced by various comorbidities. Numerous interventions exist, with route of administration and efficacy requiring further discussion. Despite opioids being the first line of treatment, their adverse effects lead to reluctance on the side of patients to take them, creating limitations in patient management planning. Objectives: This paper reviews and highlights the role of inhalers for dyspnea management in PC. Methods: The CINAHL, CENTRAL, and OVID databases were searched for scholarly articles on the role of inhalers in dyspnea management from 1998 to the present. A grey literature Internet search was also performed via Google, the World Health Organization, and CareSearch. Twenty-five articles relevant to the subject at hand were located and summarized. The Cochrane Systematic Reviews of Health Promotion and Public Health Interventions Handbook was consulted for structuring. Result: Isolated bronchodilators can be effective in dyspnea management. However, combination with opioids leads to a 52% reduction of dyspnea, demonstrating efficacy of their combined use. There is a role for conventional inhalers not only in patients afflicted with chronic obstructive pulmonary disease, but also in those where obstruction is reversible, and in cases of dyspnea not yet diagnosed. Conclusion: Inhalers can be utilized as adjuvant therapy to opioids, to limit opioid use, augment responses to dyspnea, and/or minimize opioid side effects, especially in opioid-naïve patients. Correct administration can increase the efficacy of short-acting beta-agonists, long-acting beta-agonists, short- and long-acting anticholinergic agents, and inhaled corticosteroids, achieving reduction and alleviation of dyspnea.
  • Crises and Turnaround Management: Lessons Learned from Recovery of New Orleans and Tulane University Following Hurricane Katrina

    By their very nature both man-made and natural disasters are unpredictable, and so we recommend that all health-care institutions be prepared. In this paper, the authors describe and make a number of recommendations, regarding the importance of crisis and turnaround management using as a model the New Orleans public health system and Tulane University Medical School post-Hurricane Katrina. Leadership skills, articulation of vision, nimble decision making, and teamwork are all crucial elements of a successful recovery from disaster. The leadership team demonstrated courage, integrity, entrepreneurship, and vision. As a result, it led to a different approach to public health and the introduction of new and innovative medi¬cal education and research programs.
  • The Hologenome Concept of Evolution: Medical Implications

    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.