The regulation of intestinal bicarbonate secretion by marine teleost fish

In seawater, drinking is a fundamental part of the osmoregulatory strategy for teleost fish, and presents a unique challenge. The intestine has an established role in osmoregulation, and its ability to effectively absorb fluid from imbibed seawater is crucial to compensating for water losses to the surrounding hyperosmotic environment. Alongside solute-linked water transport (driven by NaCl cotransport), intestinal bicarbonate (HCO3-) secretion also benefits fluid absorption directly (via apical Cl-/HCO3- exchange), and indirectly through the formation of calcium carbonate (CaCO3) thus removing the osmotic influence of Ca2+ within the gut fluid. For the European flounder (Platichthys flesus), elevated luminal Ca2+ has proven to be a specific, potent stimulator of HCO3- secretion both in vitro and in vivo where these actions are presumably modulated by an extracellular Ca2+-sensing receptor (CaR). The focus of this work was to learn more about how intestinal HCO3- secretion is regulated, the role of Ca2+, and more specifically the CaR. To achieve this, in vitro ‘gut sac’ experiments investigated how luminal Ca2+ influenced HCO3- secretion, and associated ion and fluid transport. Contrary to expectation, increasing Ca2+ from 5 to 20 mM did not stimulate HCO3- secretion. In an attempt to elucidate the role of CaCO3 precipitation in fluid absorption, and further explore the physiological implications of HCO3- secretion, the intestine was perfused in vivo with salines containing varying concentrations of Ca2+ (10, 40 and 90 mM). The production and secretion of HCO3-, in addition to CaCO3 formation increased accordingly with Ca2+, and was associated with a dramatic 25 % rise in the fraction of fluid absorbed by the gut. Additional in vitro experiments, utilising the Ussing chamber, helped establish some of the characteristics of intestinal HCO3- secretion by the euryhaline killifish (Fundulus heteroclitus), but was unresponsive to elevated mucosal Ca2+. Further attempts to potentiate the activity of the CaR, and application of the receptor agonists gadolinium (Gd3+) and neomycin, failed to produce responses consistent with the effect of Ca2+ observed previously, either in vitro or in vivo. With no evidence supporting a direct role for an extracellular, intestinal CaR in HCO3- secretion it was argued that secretion would be principally regulated by two factors, the ability of the epithelia to generate high levels of intracellular HCO3- and the rate of CaCO3 formation.BBSR

Measuring intestinal fluid transport in vitro: Gravimetric method versus non-absorbable marker

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The gut sac is a long-standing, widely used in vitro preparation for studying solute and water transport, and calculation of these fluxes requires an accurate assessment of volume. This is commonly determined gravimetrically by measuring the change in mass over time. While convenient this likely under-estimates actual net water flux (Jv) due to tissue edema. We evaluated whether the popular in vivo volume marker [(14)C]-PEG 4000, offers a more representative measure of Jvin vitro. We directly compared these two methods in five teleost species (toadfish, flounder, rainbow trout, killifish and tilapia). Net fluid absorption by the toadfish intestine based on PEG was significantly higher, by almost 4-fold, compared to gravimetric measurements, compatible with the latter under-estimating Jv. Despite this, PEG proved inconsistent for all of the other species frequently resulting in calculation of net secretion, in contrast to absorption seen gravimetrically. Such poor parallelism could not be explained by the absorption of [(14)C]-PEG (typically <1%). We identified a number of factors impacting the effectiveness of PEG. One was adsorption to the surface of sample tubes. While it was possible to circumvent this using unlabelled PEG 4000, this had a deleterious effect on PEG-based Jv. We also found sequestration of PEG within the intestinal mucus. In conclusion, the short-comings associated with the accurate representation of Jv by gut sac preparations are not overcome by [(14)C]-PEG. The gravimetric method therefore remains the most reliable measure of Jv and we urge caution in the use of PEG as a volume marker.We are grateful to Ian and Tony McClure, the local fishermen of Flookburgh, Cumbria (U.K.) for collecting the flounder used in this study, and to Jan Shears for assistance with fish husbandry at Exeter (U.K.). We thank Ray Hurley and Debbie Fretz in Miami (U.S.A.) for supplying the toadfish. This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grants BBS/S/A/2004/11078 and BB/F009364/1 to R.W.W., and National Science Foundation (NSF) grants IAB0743903 and 1146695 to M.G

The diagnosis, prevalence and prognosis of delirium in an older hospital population

Delirium is a syndrome which is characterised by a change in cognition, attentional difficulties and alterations to the sleep-wake cycle. In most cases it is caused by the onset of a physical illness. Delirium is more commonly found in older people aged 65 years or older, with prevalence in hospital being as high as 42%. Delirium is associated with negative outcomes such as increased length of hospital admissions, institutionalisation and mortality. There are tools which can identify and measure delirium and its associated symptoms. The Delirium Rating Scale-Revised-98 is claimed to be a valid tool, but its use in older patients in general hospital has not been fully investigated and there is limited research to support its validity in such a population. A cohort study of older people with mental health problems admitted to general hospital was used to establish whether the DRS–R–98 was able to distinguish delirium from other mental health problems, to examine the association between DRS-R-98 scores, demographic variables and health problems and to study outcomes associated with delirium. 250 patients over 70 years admitted to hospital as an emergency and likely to have a mental health problem on the basis of screening were recruited and 249 completed a battery of questionnaires including the DRS-R-98 at baseline. 180 days later 121 participants completed a follow-up questionnaire. 128 participants were lost to follow-up due to refusal of the outcomes questionnaire, ill-health, withdrawal, mortality or being un-contactable after the baseline questionnaire. Delirium was common in the study population (43%).The odds of having delirium increased with the presence of dementia (odds ratio=6.7) and functional disability (odds ratio=4.5). It was not significantly associated with mortality or length of stay in hospital. It was associated with recoverable cognitive impairment. The DRS-R-98 has reasonable content, concurrent and predictive validity but compared with clinician diagnosis the sensitivity and specificity of the DRS-R-98 were modest (about 0.75). The validity of the DRS-R-98 was not as strongly supported as in other research, which reported sensitivity and specificity as high as 0.98 and 0.77 respectively. This could be due to the differences in participant populations, as the participants of this study were all older patients with mental health problems on general hospital wards. In view of its ability to discriminate groups the DRS-R-98 is sufficiently valid for use in epidemiological research, but its moderate sensitivity and specificity make it unsuitable for use alone in clinical practice on individual patients, especially in populations where co-morbid dementia is prevalent

Caring for cognitively impaired older patients in the general hospital: A qualitative analysis of similarities and differences between a specialist Medical and Mental Health Unit and standard care wards

Background: Around half of people aged over 70 admitted as an emergency to general hospital have dementia, delirium or both. Dissatisfaction is often expressed about the quality of hospital care. A medical and mental health unit was developed to provide best practice care to cognitively impaired older patients. The Unit was evaluated by randomised controlled trial compared to standard care wards. Part of this evaluation involved structured non-participant observations of a random sub-sample of participants and the recording of field notes. Objectives: The aim of this paper is to compare and contrast the behaviours of staff and patients on the Medical and Mental Health Unit and standard care wards and to provide a narrative account that helps to explain the link between structure, process and reported outcomes. Design: Field notes were analysed using the constant comparison method. Setting: A large hospital within the East Midlands region of the United Kingdom. Participants: Patient participants were aged over 65, and identified by Admissions Unit physicians as being ‘confused’. Most patients had delirium or dementia. Results: Sixty observations (360 hours) were made between March and December 2011. Cognitively impaired older patients had high physical and psychological needs, and were cared for in environments which were crowded, noisy and lacked privacy. Staff mostly prioritised physical over psychological needs. Person-centred care on the Medical and Mental Health Unit was mostly delivered during activity sessions or meal times by activities coordinators. Patients on this unit were able to walk around more freely than on other wards. Mental health needs were addressed more often on the Medical and Mental Health Unit than on standard care wards but most staff time was still taken up delivering physical care. More patients called out repetitively on the Unit and staff were not always able to meet the high needs of these patients. Conclusion: Care provided on the Medical and Mental Health Unit was distinctly different from standard care wards. Improvements were worthwhile, but care remained challenging and consistent good practice was difficult to maintain. Disruptive vocalisation may have been provoked by concentrating cognitively impaired patients on one ward

The diagnosis, prevalence and prognosis of delirium in an older hospital population

Delirium is a syndrome which is characterised by a change in cognition, attentional difficulties and alterations to the sleep-wake cycle. In most cases it is caused by the onset of a physical illness. Delirium is more commonly found in older people aged 65 years or older, with prevalence in hospital being as high as 42%. Delirium is associated with negative outcomes such as increased length of hospital admissions, institutionalisation and mortality. There are tools which can identify and measure delirium and its associated symptoms. The Delirium Rating Scale-Revised-98 is claimed to be a valid tool, but its use in older patients in general hospital has not been fully investigated and there is limited research to support its validity in such a population. A cohort study of older people with mental health problems admitted to general hospital was used to establish whether the DRS–R–98 was able to distinguish delirium from other mental health problems, to examine the association between DRS-R-98 scores, demographic variables and health problems and to study outcomes associated with delirium. 250 patients over 70 years admitted to hospital as an emergency and likely to have a mental health problem on the basis of screening were recruited and 249 completed a battery of questionnaires including the DRS-R-98 at baseline. 180 days later 121 participants completed a follow-up questionnaire. 128 participants were lost to follow-up due to refusal of the outcomes questionnaire, ill-health, withdrawal, mortality or being un-contactable after the baseline questionnaire. Delirium was common in the study population (43%).The odds of having delirium increased with the presence of dementia (odds ratio=6.7) and functional disability (odds ratio=4.5). It was not significantly associated with mortality or length of stay in hospital. It was associated with recoverable cognitive impairment. The DRS-R-98 has reasonable content, concurrent and predictive validity but compared with clinician diagnosis the sensitivity and specificity of the DRS-R-98 were modest (about 0.75). The validity of the DRS-R-98 was not as strongly supported as in other research, which reported sensitivity and specificity as high as 0.98 and 0.77 respectively. This could be due to the differences in participant populations, as the participants of this study were all older patients with mental health problems on general hospital wards. In view of its ability to discriminate groups the DRS-R-98 is sufficiently valid for use in epidemiological research, but its moderate sensitivity and specificity make it unsuitable for use alone in clinical practice on individual patients, especially in populations where co-morbid dementia is prevalent

Risk of Injury in Royal Air Force Training: Does Sex Really Matter?

IntroductionMusculoskeletal injuries are common during military and other occupational physical training programs. Employers have a duty of care to reduce employees’ injury risk, where females tend to be at greater risk than males. However, quantification of principle co-factors influencing the sex–injury association, and their relative importance, remain poorly defined. Injury risk co-factors were investigated during Royal Air Force (RAF) recruit training to inform the strategic prioritization of mitigation strategies.Material and MethodsA cohort of 1,193 (males n = 990 (83%); females n = 203 (17%)) recruits, undertaking Phase-1 military training, were prospectively monitored for injury occurrence. The primary independent variable was sex, and potential confounders (fitness, smoking, anthropometric measures, education attainment) were assessed pre-training. Generalized linear models were used to assess associations between sex and injury.ResultsIn total, 31% of recruits (28% males; 49% females) presented at least one injury during training. Females had a two-fold greater unadjusted risk of injury during training than males (RR = 1.77; 95% CI 1.49–2.10). After anthropometric, lifestyle and education measures were included in the model, the excess risk decreased by 34%, but the associations continued to be statistically significant. In contrast, when aerobic fitness was adjusted, an inverse association was identified; the injury risk was 40% lower in females compared with males (RR = 0.59; 95% CI: 0.42–0.83).ConclusionsPhysical fitness was the most important confounder with respect to differences in males’ and females’ injury risk, rather than sex alone. Mitigation to reduce this risk should, therefore, focus upon physical training, complemented by healthy lifestyle interventions

Factors associated with family caregiver dissatisfaction with acute hospital care of older cognitively impaired relatives

Objectives To identify patient and caregiver characteristics associated with caregiver dissatisfaction with hospital care of cognitively impaired elderly adults. Design Secondary analysis of data from a randomized controlled trial. Setting An 1,800-bed general hospital in England providing the only emergency medical services in its area. Participants Cognitively impaired individuals aged 65 and older randomly assigned to a specialist unit or standard geriatric or internal medical wards (N = 600) and related caregivers (N = 488). Measurements Patient and caregiver health status was measured at baseline, including delirium, cognitive impairment, behavioral and psychological symptoms, activities of daily living, and caregiver strain. Caregiver satisfaction with quality of care was ascertained after hospital discharge or death. Results Four hundred sixty-two caregivers completed satisfaction questionnaires. Regardless of assignment, 54% of caregivers were dissatisfied with some aspects of care, but overall 87% were satisfied with care. The main areas of dissatisfaction were communication, discharge planning, and medical management. Dissatisfaction was associated with high levels of patient behavioral and psychological symptoms on admission, caregiver strain and poor psychological well-being at admission, a diagnosis of delirium, and the relationship between the caregiver and the patient. There was less dissatisfaction from caregivers of patients managed on the specialist Medical and Mental Health Unit than those on standard wards, after controlling for multiple factors. Conclusion Dissatisfaction was associated with patient behavioral and psychological symptoms and caregiver strain but was not immutable to efforts to improve care

Diagnoses, problems and healthcare interventions amongst older people with an unscheduled hospital admission who have concurrent mental health problems: a prevalence study

Background Frail older people with mental health problems including delirium, dementia and depression are often admitted to general hospitals. However, hospital admission may cause distress, and can be associated with complications. Some commentators suggest that their healthcare needs could be better met elsewhere. Methods We studied consecutive patients aged 70 or older admitted for emergency medical or trauma care to an 1800 bed general hospital which provided sole emergency medical and trauma services for its local population. Patients were screened for mental health problems, and those screening positive were invited to take part. 250 participants were recruited and a sub-sample of 53 patients was assessed by a geriatrician for diagnoses, impairments and disabilities, healthcare interventions and outstanding needs. Results Median age was 86 years, median Mini-Mental State Examination score at admission was 16/30, and 45% had delirium. 19% lived in a care home prior to admission. All the patients were complex. A wide range of main admission diagnoses was recorded, and these were usually complicated by falls, immobility, pain, delirium, dehydration or incontinence. There was a median of six active diagnoses, and eight active problems. One quarter of problems was unexplained. A median of 13 interventions was recorded, and a median of a further four interventions suggested by the geriatrician. Those with more severe cognitive impairment had no less medical need. Conclusions This patient group, admitted to hospital in the United Kingdom, had numerous healthcare problems, and by implication, extensive healthcare needs. Patients with simpler conditions were not identified, but may have already been rapidly discharged or redirected to non-hospital services by the time assessments were made. To meet the needs of this group outside the hospital would need considerable investment in medical, nursing, therapy and diagnostic facilities. In the meantime, acute hospitals should adapt to deliver comprehensive geriatric assessment, and provide for their mental health needs

Non‐pharmacological interventions for preventing delirium in hospitalised non‐ICU patients

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness of non‐pharmacological interventions designed to prevent delirium in hospitalised non‐intensive care unit (ICU) patients