‘Intensive care unit survivorship’ - a constructivist grounded theory of surviving critical illness

Aims & objectiveTo theorise ICU survivorship after a critical illness based on longitudinal qualitative data.BackgroundIncreasingly patients survive episodes of critical illness. However, the short and long term impact of critical illness include physical, psychological, social and economic challenges long after hospital discharge. An appreciation is emerging that care needs to extend beyond critical illness to enable patients to reclaim their lives post-discharge with the term ‘Survivorship’ being increasingly used in this context. What constitutes critical illness survivorship has, to date, not been theoretically explored.DesignLongitudinal-qualitative and constructivist Grounded Theory. Interviews (n = 46) with 17 participants were conducted at four time points: (1) before discharge from hospital, (2) 4-6 weeks post-discharge, (3) 6 months and (4) 12 months post-discharge across two adult intensive care setting.MethodIndividual face-to-face interviews. Data analysis followed the principles of Charmaz's Constructivist Grounded Theory. ‘ICU survivorship’ emerged as the core category and was theorised using concepts such as Status Passages, Liminality and Temporality to understand the various transitions participants made post-critical illness.FindingsIntensive care survivorship describes the unscheduled status passage of falling critically ill and being taken to the threshold of life and the journey to a life post-critical illness. Surviving critical illness goes beyond recovery; surviving means ‘moving on’ to life post-critical illness. ‘Moving on’ incorporates a re-definition of self that incorporates any lingering intensive care legacies and being in control of one's life again.Relevance to clinical practiceFor healthcare professionals and policy makers it is important to realise that recovery and transitioning through to survivorship happens within an individual's time frame, not a schedule imposed by the healthcare system. Currently there are no care pathways or policies in place for critical illness survivors that would support ICU survivors and their families in the transitions to survivorship

A longitudinal qualitative exploration of healthcare and informal support needs among survivors of critical illness: the RELINQUISH protocol

Introduction and background: Survival following critical illness is associated with a significant burden of physical, emotional and psychosocial morbidity. Recovery can be protracted and incomplete, with important and sustained effects upon everyday life, including family life, social participation and return to work. In stark contrast with other critically ill patient groups (eg, those following cardiothoracic surgery), there are comparatively few interventional studies of rehabilitation among the general intensive care unit patient population. This paper outlines the protocol for a sub study of the RECOVER study: a randomised controlled trial evaluating a complex intervention of enhanced ward-based rehabilitation for patients following discharge from intensive care. Methods and analysis: The RELINQUISH study is a nested longitudinal, qualitative study of family support and perceived healthcare needs among RECOVER participants at key stages of the recovery process and at up to 1 year following hospital discharge. Its central premise is that recovery is a dynamic process wherein patients’ needs evolve over time. RELINQUISH is novel in that we will incorporate two parallel strategies into our data analysis: (1) a pragmatic health services-oriented approach, using an a priori analytical construct, the ‘Timing it Right’ framework and (2) a constructivist grounded theory approach which allows the emergence of new themes and theoretical understandings from the data. We will subsequently use Qualitative Health Needs Assessment methodology to inform the development of timely and responsive healthcare interventionsthroughout the recovery process.Ethics and dissemination: The protocol has been approved by the Lothian Research Ethics Committee (protocol number HSRU011). The study has been added to the UK Clinical Research Network Database(study ID. 9986). The authors will disseminate the findings in peer reviewed publications and to relevant critical care stakeholder groups

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study

Introduction: Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life.Methods and analysis: The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of lifeand survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers.Ethics and dissemination: Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed accordingto a predefined analysis plan

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial.

Background: increasing numbers of patients are surviving critical illness, but survival may be associated with aconstellation of physical and psychological sequelae that can cause on going disability and reduced health-relatedquality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitationprogrammes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period. This paper describes the construct development for a complex rehabilitationintervention intended to promote physical recovery following critical illness. The intervention is currently beingevaluated in a randomised trial (ISRCTN09412438; funder Chief Scientists Office, Scotland).Methods: the intervention was developed using the Medical Research Council (MRC) framework for developingcomplex healthcare interventions. We ensured representation from a wide variety of stakeholders includingcontent experts from multiple specialties, methodologists, and patient representation. The intervention constructwas initially based on literature review, local observational and audit work, qualitative studies with ICU survivors,and brainstorming activities. Iterative refinement was aided by the publication of a National Institute for Healthand Care Excellence guideline (No. 83), publicly available patient stories (Healthtalkonline), a stakeholder event incollaboration with the James Lind Alliance, and local piloting. Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant (GRA) role. Several rounds of external peer review during successive funding applications also contributed to development.Results: the final construct for the complex intervention involved a dedicated GRA trained to pre-definedcompetencies across multiple rehabilitation domains (physiotherapy, dietetics, occupational therapy, and speech/language therapy), with specific training in post-critical illness issues. The intervention was from ICU discharge to 3 months post-discharge, including inpatient and post-hospital discharge elements. Clear strategies to provide information to patients/families were included. A detailed taxonomy was developed to define and describe the processes undertaken, and capture them during the trial. The detailed process measure description, together with a range of patient, health service, and economic outcomes were successfully mapped on to the modifiedCONSORT recommendations for reporting non-pharmacologic trial interventions.Conclusions: the MRC complex intervention framework was an effective guide to developing a novel post-ICUrehabilitation intervention. Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting. These data will be useful when interpreting the results of the randomised trial, will increase internal and external trial validity, and help others implement the intervention if the intervention proves clinically and cost effective

Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit Discharge: The RECOVER Randomized Clinical Trial

Importance: critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain.Objective: to evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post–intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities.Design, Setting, and Participants: a parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation. Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013; for the 6- and 12-month outcomes and the health economic evaluation, between March and April 2014.Interventions: during the post-ICU hospital stay, both groups received physiotherapy and dietetic, occupational, and speech/language therapy, but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2- to 3-fold, increased dietetic assessment and treatment, used individualized goal setting, and provided greater illness-specific information. Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner.Main Outcomes and Measures: the Rivermead Mobility Index (RMI) (range 0-15) at 3 months; higher scores indicate greater mobility. Secondary outcomes included HRQOL, psychological outcomes, self-reported symptoms, patient experience, and cost-effectiveness during a 12-month follow-up (completed in February 2014).Results: median RMI at randomization was 3 (interquartile range [IQR], 1-6) and at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean difference, −0.2 [95% CI, −1.3 to 0.9; P = .71]). The HRQOL scores were unchanged by the intervention (mean difference in the Physical Component Summary score, −0.1 [95% CI, −3.3 to 3.1; P = .96]; and in the Mental Component Summary score, 0.2 [95% CI, −3.4 to 3.8; P = .91]). No differences were found for self-reported symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels of anxiety, depression, and posttraumatic stress were similar, as were hand grip strength and the timed Up & Go test. No differences were found at the 6- or 12-month follow-up for any outcome measures. However, patients in the intervention group reported greater satisfaction with physiotherapy, nutritional support, coordination of care, and information provision.Conclusions and Relevance: post-ICU hospital-based rehabilitation, including increased physical and nutritional therapy plus information provision, did not improve physical recovery or HRQOL, but improved patient satisfaction with many aspects of recovery

Nipple aspiration and ductal lavage in women with a germline BRCA1 or BRCA2 mutation

INTRODUCTION: The aim of this study was to collect serial samples of nipple aspirate (NA) and ductal lavage (DL) fluid from women with germline BRCA1/2 mutations in order to create a biorepository for use in identifying biomarkers of breast cancer risk. METHODS: Between March 2003 and February 2005, 52 women with germline BRCA1 or BRCA2 mutations (median age 43 years, range 27 to 65 years) were scheduled for six-monthly NA, DL and venesection. DL was attempted for all NA fluid-yielding (FY) and any non-FY ducts that could be located at each visit. RESULTS: Twenty-seven (52%) women were postmenopausal, predominantly (19/27) from risk reducing bilateral salpingo-oophorectomy (BSO). FY ducts were identified in 60% of all women, 76% of premenopausal women versus 44% of postmenopausal (P = 0.026). Eighty-five percent of women had successful DL. Success was most likely in women with FY ducts (FY 94% versus non-FY 71% (P = 0.049). DL samples were more likely to be cellular if collected from FY ducts (FY 68% versus non-FY 43%; P = 0.037). Total cell counts were associated with FY status (FY median cell count 30,996, range 0 to >1,000,000 versus non-FY median cell count 0, range 0 to 173,577; P = 0.002). Four women (8%) had ducts with severe atypia with or without additional ducts with mild epithelial atypia; seven others had ducts with mild atypia alone (11/52 (21%) in total). Median total cell count was greater from ducts with atypia (105,870, range 1920 to >1,000,000) than those with no atypia (174, 0 to >1,000,000; P ≤ 0.001). CONCLUSION: It is feasible to collect serial NA and DL samples from women at high genetic risk of breast cancer, and we are creating a unique, prospective collection of ductal samples that have the potential to be used for discovery of biomarkers of breast cancer risk and evaluate the ongoing effects of risk reducing BSO. DL cellular atypia was not predictive of a current breast cancer and longer follow up is needed to determine whether atypia is an additional marker of future breast cancer risk in this population already at high genetic risk of breast cancer

High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change

Early mobilisation in intensive care units in Australia and Scotland:A prospective, observational cohort study examining mobilisation practises and barriers

Introduction: Mobilisation of patients in the intensive care unit (ICU) is an area of growing research. Currently, there is\ud little data on baseline mobilisation practises and the barriers to them for patients of all admission diagnoses.\ud Methods: The objectives of the study were to (1) quantify and benchmark baseline levels of mobilisation in Australian\ud and Scottish ICUs, (2) compare mobilisation practises between Australian and Scottish ICUs and (3) identify barriers to\ud mobilisation in Australian and Scottish ICUs. We conducted a prospective, observational, cohort study with a 4-week\ud inception period. Patients were censored for follow-up upon ICU discharge or after 28 days, whichever occurred first.\ud Patients were included if they were >18 years of age, admitted to an ICU and received mechanical ventilation in the ICU.\ud Results: Ten tertiary ICUs in Australia and nine in Scotland participated in the study. The Australian cohort had a large\ud proportion of patients admitted for cardiothoracic surgery (43.3 %), whereas the Scottish cohort had none. Therefore,\ud comparison analysis was done after exclusion of patients admitted for cardiothoracic surgery. In total, 60.2 % of the 347\ud patients across 10 Australian ICUs and 40.1 % of the 167 patients across 9 Scottish ICUs mobilised during their ICU stay\ud (p < 0.001). Patients in the Australian cohort were more likely to mobilise than patients in the Scottish cohort (hazard\ud ratio 1.83, 95 % confidence interval 1.38–2.42). However, the percentage of episodes of mobilisation where patients\ud were receiving mechanical ventilation was higher in the Scottish cohort (41.1 % vs 16.3 %, p < 0.001). Sedation was the\ud most commonly reported barrier to mobilisation in both the Australian and Scottish cohorts. Physiological instability\ud and the presence of an endotracheal tube were also frequently reported barriers.\ud Conclusions: This is the first study to benchmark baseline practise of early mobilisation internationally, and it\ud demonstrates variation in early mobilisation practises between Australia and Scotland

Ochre, ground stone and wrapping the dead in the Late Epipalaeolithic (Natufian) Levant: revealing the funerary practices at Shubayqa 1, Jordan

The appearance of rich and diverse funerary practices is one of the hallmarks of the Late Epipalaeolithic Natufian in the Levant. Numerous burials at a number of sites excavated mostly in the Mediterranean zone of the southern Levant have fed into the interpretation of the Natufian as a sedentary society of complex hunter-gatherers. Here, we report on the human remains recovered from Shubayqa 1, a well-dated early to late Natufian site in northeast Jordan. The majority of the minimum of 23 individuals that are represented are perinates and infants, which represents an atypical population profile. Ground stone artifacts and traces of colourants are associated with some of these individuals, providing a rare insight into funerary treatment of subadults in Natufian contexts. We interpret the Shubayqa 1 evidence in the light of current and ongoing debates concerning Natufian burial practices and the issue of social complexity

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors