This review examines ways to decrease preventable effects of hospitalization on older adults in acute care medical (non-geriatric) units, with a focus on the Israeli experience at the Rambam Health Care Campus, a large tertiary care hospital in northern Israel. Hospitalization of older adults is often followed by an irreversible decline in functional status affecting their quality of life and well-being after discharge. Functional decline is often related to avoidable effects of in-hospital procedures not caused by the patient’s acute disease. In this article we review the literature relating to the recognized effects of hospitalization on older adults, pre-hospitalization risk factors, and intervention models for hospitalized older adults. In addition, this article describes an Israeli comprehensive research study, the Hospitalization Process Effects on Functional Outcomes and Recovery (HoPE-FOR), and outlines the design of a combined intervention model being implemented at the Rambam Health Care Campus. The majority of the reviewed studies identified preadmission personal risk factors and psychosocial risk factors. In-hospital restricted mobility, under-nutrition care, the over-use of continence devices, polypharmacy, and environmental factors were also identified as avoidable processes. Israeli research supported the findings that preadmission risk factors together with in-hospital processes account for functional decline. Different models of care have been developed to maintain functional status. Much can be achieved by interdisciplinary teams oriented to the needs of hospitalized elderly in making an impact on hospital processes and continuity of care. It is the responsibility of health care policy-makers, managers, clinicians, and researchers to pursue effective interventions to reduce preventable hospitalization-associated disability.
Objectives: This study was aimed at establishing an ideal method for performing three-dimensional measurements of the fetus in order to improve the estimation of fetal weight.
Methods: The study consisted of two phases. Phase I was a prospective cross-sectional study performed between 28 and 40 weeks’ gestation. The study population (n=110) comprised low-risk singleton pregnancies who underwent a routine third-trimester sonographic estimation of fetal weight. The purpose of this phase was to establish normal values for the fetal abdominal and head volumes throughout the third trimester. Phase II was a prospective study that included patients admitted for an elective cesarean section or for induction of labor between 38 and 41 weeks’ gestation (n=91). This phase of the study compared the actual birth weight to two- (2D) and three-dimensional (3D) measurements of the fetus. Conventional 2D ultrasound fetal biometry was performed measuring the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FL). Volume estimates were computed utilizing Virtual Organ Computer-aided AnaLysis (VOCAL), and the correlation between measured volumes and actual neonatal weight was calculated.
Results: Overall, this longitudinal study consisted of 110 patients between 28 and 41 weeks’ gestation. Normal values were computed for the fetal abdomen and head volume throughout the third trimester. Ultrasound examination was performed within three days prior to delivery on 91 patients. A good correlation was found between birth weight and abdominal volume (r=0.77) and between birth weight and head volume (r=0.5). Correlation between bidimensional measurements and actual fetal weights was found to be comparable with previously published correlations.
Conclusion: Volume measurements of the fetus may improve the accuracy of estimating fetal size. Additional studies using different volume measurement of the fetus are necessary.
On May 28, 2014, colleagues from the Mayo Clinic visited Rambam Health Care Campus to gather and exchange ideas and knowledge. American and Israeli caregivers and scientists shared with each other the daily challenges of their practice in many and varied settings. This issue is dedicated to the presentations given and the collaborative efforts we are building as a result of that visit. We hope this issue will serve as an example of the fruitfulness of international collaboration to enhance and propagate medical knowledge worldwide.
Essential monoclonal gammopathy is usually an asymptomatic condition, the characteristics of which have been defined over approximately 70 years of study. It has a known population-attributable risk of undergoing clonal evolution to a progressive, symptomatic B-cell neoplasm. In a very small fraction of patients, the monoclonal immunoglobulin has biophysical characteristics that can lead to tissue deposition syndrome (e.g. Fanconi renal syndrome) or, by chance, have characteristics of an autoantibody that may inactivate critical proteins (e.g. acquired von Willebrand disease). In this report, we describe the very uncommon forms of ocular injury that may accompany essential monoclonal gammopathy, which include crystalline keratopathy, crystal-storing histiocytosis, hypercupremic keratopathy, and maculopathy. The first three syndromes result from uncommon physicochemical alterations of the monoclonal immunoglobulin that favor crystallization or exaggerated copper binding. The last-mentioned syndrome is of uncertain pathogenesis. These syndromes may result in decreased visual acuity. These ocular findings may lead, also, to the diagnosis of monoclonal gammopathy.
In rare cases, the monoclonal immunoglobulin that characterizes essential monoclonal gammopathy interacts with a self-antigen with functional consequences and a resulting clinical syndrome. This event is presumably random and results from the clone of B lymphocytes making a monoclonal immunoglobulin that simulates an autoimmune antibody. Thus, by chance, the monoclonal immunoglobulin has sufficient affinity for an epitope on a normal protein that functional consequences ensue. One such rare event is the synthesis and secretion of a monoclonal immunoglobulin that binds to human insulin. Inactivation of insulin by antibody results in (1) an early postprandial hyperglycemia, (2) followed by either or both (i) a reactive overshot in insulin secretion, as a result of hypertrophied or hyperplastic islet beta cells, later falling glucose levels, and (ii) an unpredictable dissociation of insulin from the complex, and, several hours later, (3) a resultant increase in free insulin levels and severe hypoglycemia with clinical consequences, ranging from sweating, dizziness, headache, and tremors to confusion, seizures, and unconsciousness. These attacks are invariably responsive to glucose administration. This very uncommon manifestation of a monoclonal gammopathy can occur in patients with essential monoclonal gammopathy or myeloma. The monoclonal anti-insulin immunoglobulin in monoclonal gammopathy has a low affinity for insulin, but has a high capacity for insulin-binding, resulting in the syndrome of episodic hypoglycemic attacks. This phenomenon of an insulin-binding monoclonal immunoglobulin simulates the acquired insulin autoimmune syndrome, although the latter is mediated by a polyclonal antibody response in the majority of cases studied, and has linkage to HLA class II alleles.
Mueller is to be congratulated for a comprehensive and detailed exposition on medical professionalism. There is no question but that professionalism is important—however, Mueller is correct to point out the complexities of the subject and the fact that there is no single or simple way to teach or assess professionalism. ...
Background: Postural tachycardia syndrome (POTS) is a common form of chronic orthostatic intolerance. The remarkable increase in heart rate (HR) upon standing is the hallmark of this syndrome. Treatment of POTS patients is challenging and includes drugs that slow the HR. Ivabradine is a selective If channel blocker designed to slow the HR, as an anti-anginal agent. In view of its ability to slow the HR, we posited that ivabradine may be an ideal medication for treating POTS patients. This report provides the results of an investigation in which we studied ivabradine’s effect on the hemodynamics and sympathovagal balance in POTS patients.
Methods: An open-label trial, without a placebo control, was performed in eight patients with POTS of two years’ standing. Characterization of symptoms, hemodynamics, autonomic function tests, and HR and blood pressure (BP) variability were determined while patients were in a supine position and during a 20-minute head-up tilt before and after a single oral dose of 7.5 mg ivabradine.
Results: Ivabradine slowed the HR of POTS patients at rest by 4±1 bpm (P<0.05). During a 5-minute head-up tilt, the HR decreased from 118±4 bpm to 101±5 bpm (P<0.01). Ivabradine did not affect the BP when patients were at rest in a supine position or in head-up tilt position. Cardiovascular vagal and sympathetic tone, extrapolated from the time and frequency domains of the HR and BP variability, were also not affected by ivabradine.
Conclusions: Ivabradine is an effective drug for slowing the HR of POTS patients at rest and during tilting, without producing significant adverse effects. Moreover, ivabradine exerts its effects without influencing the sympathovagal balance.
The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.
This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind.
Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy.
Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.
CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells. More recently, it has been suggested that FGL2 accounts for the immunosuppressive activity of a highly suppressive subset of Treg that express T cell immunoreceptor with Ig and ITIM domains (TIGIT). Here we discuss the important role of Treg and FGL2 in preventing alloimmune and autoimmune disease. The FGL2–FcγRIIB pathway is also known to be utilized by viruses and tumor cells to evade immune surveillance. Moving forward, therapies based on modulation of the FGL2–FcγRIIB pathway hold promise for the treatment of a wide variety of conditions ranging from autoimmunity to cancer.
