Brain dehydration and neurologic deterioration after rapid correction of hyponatremia

Brain dehydration and neurologic deterioration after rapid correction of hyponatremia. We made rats severely hyponatremia varying the rate of onset and duration of the disturbance, and then compared rapid correction to slow correction. An acute fall in the plasma Na to 106 mEq/liter within seven hours caused seizures and coma, but these findings resolved and survival was 100%after either rapid or slow correction. A more gradual fall in plasma Na to 95 mEq/liter in three days caused neither seizures nor coma. Measurements of brain water and electrolytes showed that adaptive losses of brain Na and K (maximally depleted within seven hours) and slower losses of non-electrolyte solutes progressively reduced brain edema. After three days of hyponatremia, rapid correction to 119 mEq/liter with 1m NaCl or to 129 mEq/liter by withdrawing DDAVP caused brain dehydration because lost brain K and non-electrolyte solutes were recovered slowly. This treatment was followed by a delayed onset of severe neurologic findings, demyelinating brain lesions and a mortality rate of over 40%. Slow correction (0.3 mEq/liter/hr) avoided these complications and permitted 100%survival. We conclude that the rat adapts quickly to hyponatremia and can survive with extremely low plasma sodium concentrations for prolonged periods. Although rapid correction is well tolerated when hyponatremia is of brief duration, it may cause brain damage in animals that have had time to more fully adapt to the disturbance

Simulation of Ultra-High Energy Photon Propagation in the Geomagnetic Field

The identification of primary photons or specifying stringent limits on the photon flux is of major importance for understanding the origin of ultra-high energy (UHE) cosmic rays. We present a new Monte Carlo program allowing detailed studies of conversion and cascading of UHE photons in the geomagnetic field. The program named PRESHOWER can be used both as an independent tool or together with a shower simulation code. With the stand-alone version of the code it is possible to investigate various properties of the particle cascade induced by UHE photons interacting in the Earth's magnetic field before entering the Earth's atmosphere. Combining this program with an extensive air shower simulation code such as CORSIKA offers the possibility of investigating signatures of photon-initiated showers. In particular, features can be studied that help to discern such showers from the ones induced by hadrons. As an illustration, calculations for the conditions of the southern part of the Pierre Auger Observatory are presented.Comment: 41 pages, 9 figures, added references in introduction, corrected energy in row 1 of Table 3, extended caption of Table

Treatment Guidelines for Hyponatremia Stay the Course

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting the guidelines, and the validity of data challenging them, we conclude that current safeguards should not be abandoned. To do so would be akin to discarding your umbrella because you remained dry in a rainstorm. The authors of this review, who represent 20 medical centers in nine countries, have all contributed significantly to the literature on the subject. We urge clinicians to continue to treat severe hyponatremia cautiously and to wait for better evidence before adopting less stringent therapeutic limits.</p

'The guy might not even be able to remember why he's here and what he's in here for and why he's locked in': residents and prison staff experiences of living and working alongside people with dementia who are serving prison sentences for a sexual offence

Prison staff and residents with sexual convictions, from two UK prisons, were interviewed to explore their understanding and experiences of dementia. The aim was to explore understanding and experiences of dementia in response to Governor-identified needs in the prisons. Semi-structured interviews were conducted with thirteen prisoners and seventeen prison staff across both prisons, all of whom had direct prisoner contact. Transcripts of the interviews were created and thematic analysis was carried out. Four superordinate themes emerged from the data. The first theme, 'Balancing act', explored the way that individuals with dementia should be encouraged to be independent whilst still meeting their need for support in some tasks and areas of functioning. The second theme, 'Challenges and confusion' explored the way that dementia symptoms might be masked in prison settings, how they can be misinterpreted and the impact and understanding of inappropriate behaviour in a prison for those with sexual convictions. 'What works and what doesn't' in a prison setting formed the basis of the third theme, with the final theme, 'Who to tell?' exploring the transfer of information and the sources of support available in the prisons. Practical suggestions for caring for individuals with dementia in prison are made

Hypnosis for hot flashes among postmenopausal women study: A study protocol of an ongoing randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Hot flashes are a highly prevalent problem associated with menopause and breast cancer treatments. The recent findings from the Women's Health Initiative have important implications for the significance of a non-hormonal, mind-body intervention for hot flashes in breast cancer survivors. Women who take hormone therapy long-term may have a 1.2 to 2.0 fold increased risk of developing breast cancer. In addition, it is now known that hormone therapy with estrogen and progestin is associated with increased risk of cardiovascular disease and stroke. Currently there are limited options to hormone replacement therapy as non-hormonal pharmacological agents are associated with only modest activity and many adverse side effects. Because of this there is a need for more alternative, non-hormonal therapies. Hypnosis is a mind-body intervention that has been shown to reduce self-reported hot flashes by up to 68% among breast cancer survivors, however, the use of hypnosis for hot flashes among post-menopausal women has not been adequately explored and the efficacy of hypnosis in reducing physiologically measured hot flashes has not yet been determined.</p> <p>Methods/design</p> <p>A sample of 180 post-menopausal women will be randomly assigned to either a 5-session Hypnosis Intervention or 5-session structured-attention control with 12 week follow-up. The present study will compare hypnosis to a structured-attention control in reducing hot flashes (perceived and physiologically monitored) in post-menopausal women in a randomized clinical trial. Outcomes will be hot flashes (self-report daily diaries; physiological monitoring; Hot Flash Related Daily Interference Scale), anxiety (State-Trait Anxiety Inventory; Hospital Anxiety and Depression Scale (HADS); anxiety visual analog scale (VAS rating); depression (Center for Epidemiologic Studies Depression Scale), sexual functioning (Sexual Activity Questionnaire), sleep quality (Pittsburgh Sleep Quality Index) and cortisol.</p> <p>Discussion</p> <p>This study will be the first full scale test of hypnosis for hot flashes; one of the first studies to examine both perceived impact and physiologically measured impact of a mind-body intervention for hot flashes using state-of-the-art 24 hour ambulatory physiological monitoring; the first study to examine the effect of hypnosis for hot flashes on cortisol; and the first investigation of the role of cognitive expectancies in treatment of hot flashes in comparison to a Structured-Attention Control.</p> <p>Trial Registration</p> <p>This clinical trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health, ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01293695">NCT01293695</a>.</p

First Randomized, Multicenter, Placebo-Controlled Study of Self-Administered Intranasal Etripamil for Acute Conversion of Spontaneous Paroxysmal Supraventricular Tachycardia (NODE-301).

BACKGROUND: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT. METHODS: NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration. RESULTS: NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P=0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes (P<0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P=0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events. CONCLUSIONS: Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03464019

Portraits of life: Patterns of events over the lifespan

This explorative content-analytic study completes earlier studies on the lifespan distributions of number and affect of past and future life-events, collected by means of the Life-line Interview Method (LIM), for three age groups of men and women (young, middle and late adulthood). LIM events were classified into 40 subcategories divided over 9 categories: Relations, School, Work, Health, Growth, Home, Birth, Death and Other. Compression of the full data set by age group, gender, affect, decade, and time perspective, disclosed various patterns of events underlying the human life-course, e.g., the ‘bump,’ ‘rosy view’ and ‘gender phase contrast’ patterns. The compressed data set provided detailed material for the composition of three written group portraits of life, reflecting the modal life story of young, middle-aged and older men and women. Patterns and portraits show a content shift of past memories and future expectations over the lifespan, supporting a more dynamic view on the human life-course