Accelerated telomere shortening in adrenal zona reticularis in patients with prolonged critical illness.

Background: The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging. However, the association between PCI and telomere lengths in human adrenal cells is poorly understood. In this study, we investigated this association to assess whether the burden of PCI could accelerate the aging process in adrenal cells. Methods: Adrenocortical tissues from patients who died after PCI usually show a diffuse pattern of intracellular cholesterol ester depletion (i.e., lipid depletion). This study examined near-normal adrenal glands obtained from autopsied patients who died suddenly (control group) and lipid-depleted adrenal glands obtained from autopsied patients who died after PCI (PCI group). The control group included 7 men aged 80 to 94 years (mean age: 85.3 years) and 7 women aged 84 to 94 years (mean age: 87.7 years). The PCI group included 10 men aged 71 to 88 years (mean age: 78.8 years) and 8 women aged 77 to 95 years (mean age: 85.6 years). By using quantitative fluorescence in situ hybridization, relative telomere lengths (RTLs) were determined in the parenchymal cells of the three adrenocortical zones (zona glomerulosa, zona fasciculata, and zona reticularis [ZR]) and in the chromaffin cells of the medulla. The number of adrenal parenchymal cells was determined by immunohistochemistry and digital image analysis. Results: RTLs in ZR cells were significantly shorter in the PCI group than in the control group for both men and women (P = 0.0001 for men and P = 0.0012 for women). However, RTLs in the remaining three types of adrenal cells did not differ between the control and PCI groups for both men and women. The number of ZR cells was higher in the PCI group than in the control group for both men and women (P < 0.0001 for both men and women). The proportion of the number of ZR cells to the total number of adrenocortical parenchymal cells was also higher in the PCI group than in the control group (P < 0.0001 for both men and women). The Ki-67 proliferation index in ZR cells was higher in the PCI group than in the control group (P = 0.0039 for men and P = 0.0063 for women). Conclusions: This study demonstrated ZR cell-specific telomere shortening in patients with adrenal lipid depletion who died after PCI. Our results suggest that the reactive proliferation of ZR cells accelerates the telomere shortening and aging process in ZR cells in these patients. The results of our study may contribute to the understanding of adrenal aging during PCI.

Hospital re-admission after critical care survival: a systematic review and meta-analysis.

Survivors of critical illness frequently require increased healthcare resources after hospital discharge. We undertook a systematic review and meta-analysis to assess hospital re-admission rates following critical care admission and to explore potential re-admission risk factors. We searched the MEDLINE, Embase and CINAHL databases on 05 March 2020. Our search strategy incorporated controlled vocabulary and text words for hospital re-admission and critical illness, limited to the English language. Two reviewers independently applied eligibility criteria and assessed quality using the Newcastle Ottawa Score checklist and extracted data. The primary outcome was acute hospital re-admission in the year after critical care discharge. Of the 8851 studies screened, 87 met inclusion criteria and 41 were used within the meta-analysis. The analysis incorporated data from 3,897,597 patients and 741,664 re-admission episodes. Pooled estimates for hospital re-admission after critical illness were 16.9% (95%CI: 13.3-21.2%) at 30 days; 31.0% (95%CI: 24.3-38.6%) at 90 days; 29.6% (95%CI: 24.5-35.2%) at six months; and 53.3% (95%CI: 44.4-62.0%) at 12 months. Significant heterogeneity was observed across included studies. Three risk factors were associated with excess acute care rehospitalisation one year after discharge: the presence of comorbidities; events during initial hospitalisation (e.g. the presence of delirium and duration of mechanical ventilation); and subsequent infection after hospital discharge. Hospital re-admission is common in survivors of critical illness. Careful attention to the management of pre-existing comorbidities during transitions of care may help reduce healthcare utilisation after critical care discharge. Future research should determine if targeted interventions for at-risk critical care survivors can reduce the risk of subsequent rehospitalisation.

Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a "reactivation" of the pituitary gland's pulsatile secretion of tropic hormones, or (b) the interruption of the "vicious circle" between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients-and the resulting positive metabolic effects-could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones-including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis-also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS.

Nurses' experiences of caring for patients during a prolonged critical illness.

BACKGROUND: The literature regarding nurses' experiences of caring for chronically critically ill (CCI) patients is scant, however, there are subtleties within the literature, identifying nurses are often challenged providing care to this patient group. This can lead to feeling frustrated, lack of control, and distress. AIMS AND OBJECTIVES: As part of a larger study, this paper reports nurses' experiences of caring for patients during a prolonged critical illness in the intensive care unit (ICU). DESIGN: A longitudinal, qualitative, instrumental, multi-case study consisting of six cases from four New Zealand ICUs was conducted. Theoretical underpinnings were informed by the Chronic Illness Trajectory Framework. The principles of consolidated criteria for reporting qualitative research were applied in reporting the methods and findings. METHODS: Patients, family members, nurses, and other health care professionals constituted the participant groups in the larger body of work. Data were collected from observations, conversations, interviews, and document review. Data were analysed by identifying themes, developing vignettes, and trajectory mapping. RESULTS: Nurses' experiences of caring for CCI patients in the ICU can be framed by a prolonged critical illness trajectory that is unpredictable, problematic, and prolonged. Nurses experienced distress in one of the phases in the trajectory because of uncertainty about a positive outcome for the patient related to multiple complications, with anxiety, delirium, and the suffering they witnessed. Nurses were frustrated and challenged to meet all the patient's needs because of the many tasks they needed to complete over the shift. CONCLUSION: Understanding the trajectory of a prolonged critical illness from the perspective of nurses, allows for challenges to be identified and is the first step in improving practice through the education of nurses. RELEVANCE TO CLINICAL PRACTICE: Understanding the challenges posed by caring for CCI patients will assist in improving their interactions and prioritizing their care for nurses.

Standardising care in the ICU: a protocol for a scoping review of tools used to improve care delivery.

BACKGROUND: Increasing numbers of critically ill patients experience a prolonged intensive care unit stay contributing to greater physical and psychological morbidity, strain on families and cost to health systems. Quality improvement tools such as checklists concisely articulate best practices with the aim of improving quality and safety; however, these tools have not been designed for the specific needs of patients with prolonged ICU stay. The primary objective of this review will be to determine the characteristics including format and content of multicomponent tools designed to standardise or improve ICU care. Secondary objectives are to describe the outcomes reported in these tools, the type of patients and settings studied, and to understand how these tools were developed and implemented in clinical practice. METHODS: We will search the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, PsycINFO, Web of Science, OpenGrey, NHS evidence and Trial Registries from January 2000 onwards. We will include primary research studies (e.g. experimental, quasi-experimental, observational and qualitative studies) recruiting more than 10 adult participants admitted to ICUs, high dependency units and weaning centres regardless of length of stay, describing quality improvement tools such as structured care plans or checklists designed to standardize more than one aspect of care delivery. We will extract data on study and patient characteristics, tool design and implementation strategies and measured outcomes. Two reviewers will independently screen citations for eligible studies and perform data extraction. Data will be synthesised with descriptive statistics; we will use a narrative synthesis to describe review findings. DISCUSSION: The findings will be used to guide development of tools for use with prolonged ICU stay patients. Our group will use experience-based co-design methods to identify the most important actionable processes of care to include in quality improvement tools these patients. Such tools are needed to standardise practice and thereby improve quality of care. Illustrating the development and implementation methods used for such tools will help to guide translation of similar tools into ICU clinical practice and future research. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on the Open Science Framework, https://osf.io/ , DOI https://doi.org/10.17605/OSF.IO/Z8MRE.