Suicidal phenomena in the general hospital can take a variety of forms that can be parsed by taking into account whether or not the patient 1) intended to hasten death, and 2) included collaborators, including family and health care providers, in the decision to act. These two criteria can be used to distinguish entities as diverse as true suicide, non-compliance, euthanasia/physician-assisted suicide, and hospice/palliative care. Characterizing the nature of “suicide” events facilitates appropriate decision-making around management and disposition.
Combat trauma may affect servicemen from indigenous, traditional communities in ways that warrant special attention. The Bedouins, who enlist in the Israel Defense Forces (IDF) voluntarily, represent a unique, closed, collectivist cultural minority, potentially in a predicament in light of ongoing sociopolitical events. This paper summarizes findings and lessons learned from a community study of Bedouin IDF servicemen and their families residing in Israel’s Western Galilee. This is the only research endeavor to have addressed trauma exposure and posttraumatic reactions in this community. The sampling strategies and interview schedule were designed in consideration of participation barriers typical of hard-to-reach populations. Data collection followed an extended phase of liaising with key informants and building trust. Study limitations are discussed in terms of the challenges presented by this type of research. Interviews conducted with 317 men, 129 wives, and 67 mothers revealed high levels of trauma exposure and posttraumatic stress disorder (PTSD) in the men, and related distress in wives and mothers, but not in the children. The role of aggression in mediating the impact of PTSD and concepts such as shame, the loss of personal resources, and beliefs about retribution are highlighted as key issues for a culturally relevant understanding of traumatized indigenous communities.
The human body hosts rich and diverse microbial communities. Our microbiota affects the normal human physiology, and compositional changes might alter host homeostasis and, therefore, disease risk. The microbial community structure may sometimes occupy discrete configurations and under certain circumstances vary continuously. The ability to characterize accurately the ecology of human-associated microbial communities became possible by advances in deep sequencing and bioinformatics analyses.
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.
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.
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.
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.
The number needed to treat (NNT) is a simple measure of a treatment’s impact, increasingly reported in randomized trials and observational studies. It has been found to be incorrectly calculated in several studies involving varying follow-up times. We discuss the NNT in these contexts and illustrate the concept using several published studies. The computation of the NNT is founded on the cumulative incidence of the outcome. Instead, several published studies use simple proportions that do not account for varying follow-up times, or use incidence rates per person-time. We show how these approaches can lead to erroneous values of the NNT and misleading interpretations. For example, a trial of 3,845 very elderly hypertensives randomized to a diuretic or placebo reported a NNT of 94 treated for 2 years to prevent one stroke, though the correct approach results in a NNT of 63. We also note that meta-analyses involve trials of differing lengths, but often report a single NNT. For example a meta-analysis of 22 trials of the anticholinergic tiotropium in chronic obstructive pulmonary disease reported a NNT of 16 patients “over one year,” even if the trials varied in duration from 3 to 48 months, with the more specifically computed NNTs varying widely from 72, 15, and 250 for the 3-month, 12-month, and 48-month trials, respectively. Finally, we describe the value of the NNT in assessing benefit–risk, such as low-dose aspirin use in secondary prevention, where prevention of mortality was assessed against the risk of gastrointestinal bleeding. As the “number needed to treat” becomes increasingly used in the comparative effectiveness and safety of therapies, its accurate estimation and interpretation become crucial to avoid distorting clinical, economic, and public health decisions.
Feelings of guilt have tormented Holocaust survivors, ranging from immediately after the liberation to later in life, for shorter or longer periods, and persisting for some throughout their entire post-war lives. Descriptions of the guilt experienced by survivors of the Nazi camps occupy an impressive amount of literature: “Why me?” was the question, when a younger and more able family member perished; “Why me?” when more productive members of the community perished; “Why me?” when a million and a half children were deprived of their lives. Many found the answer by retelling their stories, witnesses of what happened. This type of guilt is much different from the recently described phenomenon of survivor syndrome, namely the secondary guilt felt by Nazi-persecuted Jewish writers. Despite successes in all aspects of their life, these writers developed a self-incriminating guilt due to their perceived inadequacy of communicating, particularly in light of the resurging anti-Semitism worldwide. This paper deals with the survival and suicides of Nazi-persecuted Jewish writers and offers a possible explanation for their late self-destructive acts.
During the past 50 years, a dramatic reduction in the mortality rate associated with cardiovascular disease has occurred in the US and other countries. Statistical modeling has revealed that approximately half of this reduction is the result of risk factor mitigation. The successful identification of such risk factors was pioneered and has continued with the Framingham Heart Study, which began in 1949 as a project of the US National Heart Institute (now part of the National Heart, Lung, and Blood Institute). Decreases in total cholesterol, blood pressure, smoking, and physical inactivity account for 24%, 20%, 12%, and 5% reductions in the mortality rate, respectively. Nephrology was designated as a recognized medical professional specialty a few years later. Hemodialysis was first performed in 1943. The US Medicare End-Stage Renal Disease (ESRD) Program was established in 1972. The number of patients in the program increased from 5,000 in the first year to more than 500,000 in recent years. Only recently have efforts for risk factor identification, early diagnosis, and prevention of chronic kidney disease (CKD) been undertaken. By applying the approach of the Framingham Heart Study to address CKD risk factors, we hope to mirror the success of cardiology; we aim to prevent progression to ESRD and to avoid the cardiovascular complications associated with CKD. In this paper, we present conceptual examples of risk factor modification for CKD, in the setting of this historical framework.
