How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS

A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

We propose a framework for the treatment, rehabilitation, and research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using a natural history of disease approach to outline the distinct disease stages, with an emphasis on cases following infection to provide insights into prevention. Moving away from the method of subtyping patients based on the various phenotypic presentations and instead reframing along the lines of disease progression could help with defining the distinct stages of disease, each of which would benefit from large prospective cohort studies to accurately describe the pathological mechanisms taking place therein. With a better understanding of these mechanisms, management and research can be tailored specifically for each disease stage. Pre-disease and early disease stages call for management strategies that may decrease the risk of long-term morbidity, by focusing on avoidance of further insults, adequate rest to enable recovery, and pacing of activities. Later disease stages require a more holistic and tailored management approach, with treatment-as this becomes available-targeting the alleviation of symptoms and multi-systemic dysfunction. More stringent and standardised use of case definitions in research is critical to improve generalisability of results and to create the strong evidence-based policies for management that are currently lacking in ME/CFS

Human factors and ergonomics to improve performance in intensive care units during the COVID-19 pandemic

The COVID-19 pandemic has tested the very elements of human factors and ergonomics (HFE) to their maximum. HFE is an established scientific discipline that studies the interrelationship between humans, equipment, and the work environment. HFE includes situation awareness, decision making, communication, team working, leadership, managing stress, and coping with fatigue, empathy, and resilience. The main objective of HF is to optimise the interaction of humans with their work environment and technical equipment in order to maximise patient safety and efficiency of care. This paper reviews the importance of HFE in helping intensivists and all the multidisciplinary ICU teams to deliver high-quality care to patients in crisis situations

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU—An International, Prospective, Bi-Center Observational Study (IDeAS)

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU—An International, Prospective, Bi-Center Observational Study (IDeAS)

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors “level of sedation” and “mechanical ventilation” impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/−1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/−1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs