Phase Of Illness Research Articles

Observational study to assess the relationship between enteral nutrition delivery and nutritional biomarkers among mechanically ventilated critically ill patients

BackgroundBiochemical assessment is considered a useful tool in assessing the patient’s nutritional status and intake. However, during critical illness, nutritional biomarkers, such as albumin, and haemoglobin (HB) may reflect the severity of acute illness. The aim of this study is to assess the relationship between energy and protein delivery with the change in albumin, HB, “mean corpuscular volume”(MCV), and “mean corpuscular haemoglobin concentration” (MCHC) levels in critically ill patients. MethodIn this prospective observational study we monitored the intake of energy and protein in a group critically ill patients for 6 consecutive days. Biochemical data including albumin, HB, MCV and MCHC was measured on admission and on day 6 of the follow-up. The variation in the biomarkers between admission and day 6 was calculated as the follow-up reading minus the reading obtained upon admission to (Intensive Care Unit) ICU. ResultsThis study included 43 patients. There was a significant difference in the albumin and HB levels between admission and follow up readings. No statistical association was recorded between the intake and the changes in albumin, MCV and MCHC level during ICU stay. The results showed a significant association between the intake of energy (R = 0.393), and protein (R = 0.385), with the increase in HB level during hospitalisation. ConclusionOverall, this study showed that most nutritional biomarkers were not influenced by nutritional therapy during the acute phase of illness. These findings may directly undermine the usefulness of the serial measurements of these biomarkers in the early phase of ICU admission.

Mental health implications for aviators from COVID-19

Mental Health Implications for Aviators from COVID-19 The authors present aeromedical implications from COVID-19 disruptions on the civil aviation sector, consider mental health impacts on pilots, and discuss possible helpful responses to support pilot mental health. A multiple database review investigated articles from January 2002 to May 2021 on severe commercial aviation disruptions impacting pilot mental health and on pilot mental health coping or treatment. Fifteen papers were identified. During the COVID-19 pandemic, airline flights were severely reduced. By January 2021, airlines shed thousands of jobs and 24 airlines no longer existed. General population surveys found 13% of individuals had “serious distress” from the pandemic. In two aviation focused surveys, 40-66% of pilots agreed or strongly agreed that their mental health worsened since the COVID-19 pandemic. Compared to past Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) patients, more COVID-19 patients have mental health symptoms in the acute phase of illness; while about 10% of COVID-19 patients appear to have chronic or “long haul” symptoms. Mental Health treatment and coping strategies found helpful to pilots are discussed. Pilots remain at risk for mental health symptoms and illness due to the COVID-19 pandemic. For those who develop severe distress or mental illness from the effects of the pandemic (or COVID-19 infection), early treatment with psychotherapy and/or approved medications may be warranted. This may decrease the likelihood of persistent physical or cognitive or mental health symptoms that would delay a return to flying status.

Lithium and Valproate in Bipolar Disorder: From International Evidence-based Guidelines to Clinical Predictors.

Since decades, lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder. Different response patterns occur according to the phases of illness. At same time, individual pretreatment variables may concur to determine a specific drug-response. Our narrative review focuses on these two key clinical aspects to summarize the state of art. Information from i) clinical trials and ii) the most relevant international guidelines is collected to assess the clinical and preclinical factors that may guide the use of lithium rather than valproate. Lithium may be effective in treating acute mania, and lithium efficacy is maximized when used to prevent both manic and depressive episodes. Lithium may be a better treatment choice in patients with: positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, no comorbidities. Valproate may be more effective as antimanic rather than prophylactic agent. Valproate might be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities. Finally, neither lithium nor valproate are suggested for the treatment of acute mixed states or bipolar depression. To consider clinical and preclinical factors may thus be useful to select the best treatment strategy.

Chest CT findings in COVID 19 disease in relation with duration of illness: A study of two hundred cases.

Chest CT scans of 200 symptomatic patients infected with COVID 19 from different health facilities and home were reviewed for common CT findings in relationship with their clinical symptoms, comorbidities and the time between symptom onset and the initial CT scan was studied in this cross-sectional study. Cases were categorized into three groups according to the timing of HRCT, 10 cases were in early (0-2days), 56 cases in intermediate (3-5days) and 110 cases were in late (6-12days) groups. Chest CT scan images showed bilateral peripheral ground glass opacities 96.63%, pulmonary consolidations 15.9%. Notably 29.54% patient had normal CT scan chest and 60% of them were imaged at early phase. With a longer duration of symptoms, chest CT findings were more typical including GGO, consolidation with greater total lung involvement. Bilateral peripheral GGO was observed in 20% patients at early phase while 53.57% and 64.54% were observed at intermediate and late phase of illness. Among the symptoms cough and dyspnea were observed more related with typical CT changes (95%). Diabetes and Hypertension (58% of patients) were the leading comorbidities that were found related with GGO and other typical CT findings. Mean time duration between symptom onset and positive RT PCR, CT scan changes were 4.79 and 7.55 respectively.
 Central Medical College Journal Vol 5 No 2 Jul 2021 PP 70-75

Discovery of novel drugs for Chagas disease: is carbonic anhydrase a target for antiprotozoal drugs?

ABSTRACT Introduction Carbonic anhydrase (CA) arose significant interest as a potential new target for Chagas disease since its discovery in Trypanosoma cruzi in 2013. Benznidazole and Nifurtimox have been used for Chagas disease treatment for 60 years despite all efforts done for obtaining more efficient treatments, acting in the acute and chronic phases of illness, with fewer side effects and resistance induction. Areas covered We discuss the positive and negative aspects of T. cruzi CA (TcCA) studies as a target for developing new drugs. The current research discoveries and the classes of TcCA inhibitors are reviewed. The sulfonamides and their derivatives are the main inhibitor classes, but hydroxamates and the thiols, were investigated too. These compounds inhibited the growth of the evolutive forms of the parasite. A comparative analysis was done with CAs from other Trypanosomatids and protozoans. Expert opinion The search for new targets and drugs is a significant challenge worldwide, and TcCA is a potential candidate for developing new drugs. Several studied inhibitors were active against Trypanosoma cruzi, but their penetration and toxicity problems emerged. New approaches are in progress to obtain inhibitors with desired properties, allowing further steps such as tests using an adequate animal model and subsequent developments for the preclinical testing.

Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents

The postacute sequelae of SARS-CoV-2 infection (PASC) has emerged as a long-term complication in adults, but current understanding of the clinical presentation of PASC in children is limited. To identify diagnosed symptoms, diagnosed health conditions, and medications associated with PASC in children. This retrospective cohort study used electronic health records from 9 US children's hospitals for individuals younger than 21 years who underwent antigen or reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 between March 1, 2020, and October 31, 2021, and had at least 1 encounter in the 3 years before testing. SARS-CoV-2 positivity by viral test (antigen or RT-PCR). Syndromic (symptoms), systemic (conditions), and medication PASC features were identified in the 28 to 179 days following the initial test date. Adjusted hazard ratios (aHRs) were obtained for 151 clinically predicted PASC features by contrasting viral test-positive groups with viral test-negative groups using proportional hazards models, adjusting for site, age, sex, testing location, race and ethnicity, and time period of cohort entrance. The incidence proportion for any syndromic, systemic, or medication PASC feature was estimated in the 2 groups to obtain a burden of PASC estimate. Among 659 286 children in the study sample, 348 091 (52.8%) were male, and the mean (SD) age was 8.1 (5.7) years. A total of 59 893 (9.1%) tested positive by viral test for SARS-CoV-2, and 599 393 (90.9%) tested negative. Most were tested in outpatient testing facility settings (322 813 [50.3%]) or office settings (162 138 [24.6%]). The most common syndromic, systemic, and medication features were loss of taste or smell (aHR, 1.96; 95% CI, 1.16-3.32), myocarditis (aHR, 3.10; 95% CI, 1.94-4.96), and cough and cold preparations (aHR, 1.52; 95% CI, 1.18-1.96), respectively. The incidence of at least 1 systemic, syndromic, or medication feature of PASC was 41.9% (95% CI, 41.4-42.4) among viral test-positive children vs 38.2% (95% CI, 38.1-38.4) among viral test-negative children, with an incidence proportion difference of 3.7% (95% CI, 3.2-4.2). A higher strength of association for PASC was identified in those cared for in the intensive care unit during the acute illness phase, children younger than 5 years, and individuals with complex chronic conditions. In this large-scale, exploratory study, the burden of pediatric PASC that presented to health systems was low. Myocarditis was the most commonly diagnosed PASC-associated condition. Acute illness severity, young age, and comorbid complex chronic disease increased the risk of PASC.

Maoism and mental illness: psychiatric institutionalization during the Chinese Cultural Revolution.

This article offers a preliminary analysis of psychiatric treatment during the Chinese Cultural Revolution on the basis of interviews and rare case records obtained from ‘F Hospital’ in southern China. In contrast to the prevailing view of psychiatry during this time, which highlights either rampant patient abuse or revolutionary ideology, we show that psychiatric treatment at this facility was not radically altered by the politics of the Maoist period. Instead, treatments were informed by a predominantly biomedical understanding of mental illness, one that derived from the prior training of the facility’s lead physicians. Although political education was nominally incorporated into patient rehabilitation and outpatient care, it was not a constitutive element of inpatient treatment during the acute phase of illness.

Cardiac Assessment in Children with MIS-C: Late Magnetic Resonance Imaging Features.

Multisystem Inflammatory Syndrome (MIS-C) is a new entity that emerges 2–4 weeks after the SARS-CoV-2 infection in children. MIS-C can affect all systems, the most severe of which is cardiac involvement. The duration of the cardiac symptoms is still uncertain and may be persistent or prolonged. The American College of Rheumatology Clinical Guidelines recommends cardiac magnetic resonance imaging (MRI) 2–6 months after the diagnosis of MIS-C in patients presenting with significant transient left ventricular (LV) dysfunction in the acute phase of illness (LV ejection fraction 50%) or persistent LV dysfunction. There are a few studies investigating cardiac MRI findings in MIS-C patients. In this study, we aimed to evaluate cardiac MRI findings, at the earliest 3 months after diagnosis, and compare these findings with the echocardiograms in children with MIS-C. A retrospective study including 34 MIS-C patients was conducted at a tertiary-level University Hospital between June 2020 and July 2021. Centers for Disease Control and Prevention criteria were used in the diagnosis of MIS-C. Cardiac MRI was performed at least 3 months after MIS-C diagnosis. The study included 17 (50%) boys and 17 (50%) girls with a mean age of 9.31 ± 4.72 years. Initial echocardiographic evaluation revealed cardiac abnormality in 13 (38.2) patients; 4 (11.8%) pericardial effusion, 4 (11.8%) left ventricular ejection fraction (LVEF) < 55%, and 5 (14.7%) coronary artery dilatation. Echocardiography showed normal LV systolic function in all patients during follow-up; coronary dilatation persisted in 2 of 5 (40%) patients at the 6th-month visit. Cardiac MRI was performed in 31 (91.2%) patients, and myocardial hyperemia was not detected in any patients (T1 relaxation time was < 1044 ms in all children). However, 9 (29%) patients’ MRI showed isolated elevated T2 levels, and 19 (61.3%) revealed at least one of the following findings: pericardial effusion, right ventricular dysfunction, or LVEF abnormality. In patients with MIS-C, a high rate of cardiac involvement, particularly pericardial effusion was determined by cardiac MRI performed at the earliest 2–6 months after diagnosis. Even if echocardiography does not reveal any abnormality in the initial phase, cardiac MRI should be suggested in MIS-C patients in the late period. This is the first study reporting cardiac MRI findings in the late period of MIS-C patients.

Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection.

Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) – that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness. Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors. The sample included 484 subjects (51% female, median age 32, IQR 19–44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34–0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30–0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery. Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71–2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.

Coronavirus Disease: Subacute to Chronic Neuroimaging Findings.

Several neurologic disorders are associated with coronavirus disease 2019 (COVID-19). In this article, clinical syndromes typically occurring in the subacute to chronic phase of illness and their neuroimaging findings are described with discussion of their COVID-19 specific features and prognosis. Proposed pathogenic mechanisms of these neuroimaging findings and challenges in determining etiology are reviewed.

Nutrition in Pediatric Intensive Care: A Narrative Review.

Nutrition support in pediatric intensive care is an integral part of a complex approach to treating critically ill children. Smaller energy reserves with higher metabolic demands (a higher basal metabolism rate) compared to adults makes children more vulnerable to starvation. The nutrition supportive therapy should be initiated immediately after intensive care admission and initial vital sign stabilization. In absence of contraindications (unresolving/decompensated shock, gut ischemia, critical gut stenosis, etc.), the preferred type of enteral nutrition is oral or via a gastric tube. In the acute phase of critical illness, due to gluconeogenesis and muscle breakdown with proteolysis, the need for high protein delivery should be emphasized. After patient condition stabilization, the acute phase with predominant catabolism converts to the anabolic phase and intensive rehabilitation, where high energy demands are the keystone of a positive outcome.

Setting the River on Fire: A Study of Genius, Mania, and Character

Setting the River on Fire: A Study of Genius, Mania, and Character

Olanzapine Use in Schizophrenia and the Modulation of Its Response by Genetic Variations

Schizophrenia is a chronic disease with diverse psychopathology and multiple phases of illness. Consequently, numerous factors must be considered when assessing the benefits of a given treatment over short- and long-term periods. Olanzapine is an atypical antipsychotic reported to be effective without producing many of the disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Despite the fact that olanzapine is still associated with a known risk of metabolic side effects, including weight gain, many clinicians continue to prescribe olanzapine for the treatment of schizophrenia with the expectation of additional therapeutic antipsychotic efficacy relative to other first-line atypical antipsychotics. This review focuses on the epidemiology, pathogenesis, and treatment of schizophrenia with special emphasis on the role of olanzapine in the treatment of schizophrenia. Genetic variants associated with the therapeutic efficacy and adverse effects of olanzapine are reviewed and those with the potential to act as a clinical predictor of therapeutic response and/or adverse effects are discussed. Recommendations are made for the use of some of these genetic variants in clinical medicine.

Fine-Humor Producing Materia Medica in Persian Medicine

According to Persian Medicine (PM), humors that can replace the consumed body compounds, while contributing to health maintenance, is called ‘fine humor’ (khelt-e saleh). However, a limited number of foods and beverages have been mentioned as the producers of fine humor. These substances are particularly important in maintaining health in vulnerable populations including pregnant women, lactating mothers, the elderly, infants and children. They also play an important role in certain treatment plans during illness and injury and after recovery. The present study was designed to investigate properties of fine-humor producing materia medica, as described by PM resources. Based on the search performed in PM textbooks, 63 substances were found to have this property. The most frequent Mizaj types were hot-wet (33.34%), hot-dry (19.05%), and cold-wet (17.47%). The highest organ tropism belonged to kidneys and bladder, brain, liver, sex organs, stomach and lungs respectively. Examining drug actions indicated obesogenous (53.97%), enhancing sperm production and sexual potency (42.86%), laxative (39.69%), and tonic (33.34%) actions to be the most prevalent effects of these substances in the body. By integrating these substances into diets, health promotion for children, the elderly, and mothers during nursing and pregnancy may be achieved. Additionally, patients can benefit from a fine-humor producing nutrition both for 1) prevention of chronic diseases and 2) during disease recovery, acute phases of illness, anemia, and metabolic illnesses. Further studies are recommended to analyze the components and nutritional value, and the use of PM capability in culinary medicine.

Strengthening Community End-of-Life Care through Implementing Measurement-Based Palliative Care.

The increasing demand for palliative care in New Zealand presents a potential threat to the quality of service delivery. One strategy to overcome this is through the implementation of valid and reliable patient-reported outcome measures. This mixed-methods study aimed to (1) implement measurement-based palliative care (MBPC) in a community palliative care service in Auckland, New Zealand; (2) evaluate the clinical utility of MBPC perceived by clinicians; (3) describe patient characteristics as measured by the Integrated Palliative Care Outcome Scale (IPOS), the Australasian Modified Karnofsky Performance Scale (AKPS), and Phase of Illness (POI); and (4) evaluate the internal consistency of the IPOS. Participants were over 18 years of age from a community outpatient palliative care service. In a phased approach to implementation, healthcare staff were educated on each instrument used for patient assessment. Uptake and internal consistency were evaluated through descriptive statistics. An interpretive descriptive methodology was used to explore the clinical utility of MBPC through semi-structured interviews with seven clinical staff members. Individual patient assessments (n = 1507) were undertaken predominantly on admission, with decreasing frequency as patients advanced through to the terminal phase of their care. Mean total IPOS scores were 17.97 (SD = 10.39, α = 0.78). The POI showed that 65% of patients were in the stable phase, 20% were in the unstable phase, 9% were in the deteriorating phase, and 2% were in the terminal phase. Clinicians reported that MBPC facilitated holistic and comprehensive assessments, as well as the development of a common interdisciplinary language. Clinicians expressed discomfort using the psychosocial and spiritual items. Measurement-based palliative care was only partially implemented but it was valued by staff and perceived to increase the quality of service delivery. Future research should determine the optimal timing of assessments, cultural responsivity for Māori and Pacific patients, and the role of MBPC in decision support for clinicians.

Treatment and Epidemiology of Third-Generation Cephalosporin-Resistant Urinary Tract Infections.

Limited data are available on the contemporary epidemiology, clinical management, and health care utilization for pediatric urinary tract infection (UTI) due to third-generation cephalosporin-resistant Enterobacterales (G3CR) in the United States. The objective is to describe the epidemiology, antimicrobial treatment and response, and health care utilization associated with G3CR UTI. Multisite, matched cohort-control study including children with G3CR UTI versus non-G3CR UTI. UTI was defined as per American Academy of Pediatrics guidelines, and G3CR as resistance to ceftriaxone, cefotaxime, or ceftazidime. We collected data from the acute phase of illness to 6 months thereafter. Among 107 children with G3CR UTI and 206 non-G3CR UTI with documented assessment of response, the proportion with significant improvement on initial therapy was similar (52% vs 57%; odds ratio [OR], 0.81; 95% confidence interval [CI], 0.44-1.50). Patients with G3CR were more frequently hospitalized at presentation (38% vs 17%; OR, 3.03; 95% CI, 1.77-5.19). In the follow-up period, more patients with G3CR had urine cultures (75% vs 53%; OR, 2.61; 95% CI, 1.33-5.24), antimicrobial treatment of any indication (53% vs 29%; OR, 2.82; 95% CI, 1.47-5.39), and subspecialty consultation (23% vs 6%; OR, 4.52; 95% CI, 2.10-10.09). In multivariate analysis, previous systemic antimicrobial therapy remained a significant risk factor for G3CR UTI (adjusted OR, 1.91; 95% CI, 1.06-3.44). We did not observe a significant difference in response to therapy between G3CR and susceptible UTI, but subsequent health care utilization was significantly increased.

Immune-mediated inflammatory markers in acute and transient psychotic disorders-comparison with schizophrenia: An exploratory comparative study.

Considering Acute and Transient psychotic disorders (ATPDs) to be a close entity to Schizophrenia (SZ) with a completely different course and outcome, studies evaluating the immunological abnormalities are scarce in ATPDs. We analysed immune-mediated inflammatory marker levels [Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-17 (IL-17) and Tumour necrosis factor-alpha (TNF-α)] in patients with ATPDs (in the acute phase and after remission), and compared these with patients with SZ in remission and with healthy controls. Ninteen subjects with ATPDs in acute phase of illness were age-/gender-matched with healthy controls and patients with schizophrenia in remission; recruited through purposive sampling. Clinical assessment and immune-marker levels were carried out in all the three groups. Follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured. Immune-marker levels were compared across the three groups. Patients with ATPDs had elevated levels of the pro-inflammatory cytokines IL-6 and IL-17 and low levels of IL-8 in the acute phase and low levels of IL-6 and elevated levels of IL-8 during the remission phase. Compared to patients with SZ in remission, patients with ATPD in remission had low levels of all the three pro-inflammatory cytokines (with significantly low IL-6 levels and non-significant, yet low levels of IL-8 and IL-17) and had significantly low and high levels of IL-6 and IL-8 respectively than healthy controls. These findings suggest that there existed immunological abnormalities in the acute and remission phase of illness in patients with ATPDs compared to both patients with SZ in remission and healthy controls.

Early taurine administration as a means for halting the cytokine storm progression in COVID-19 patients

Around the world, more than 6.2 million individuals have died as a result of coronavirus disease 2019 (COVID-19). According to a recent survey conducted among immunologists, epidemiologists, and virologists, this disease is expected to become endemic. This implies that the disease could have a continuous presence and/or normal frequency in the population. Pharmacological interventions to prevent infection, as well as to treat the patients at an early phase of illness to avoid hospitalization are essential additions to the vaccines. Taurine is known to inhibit the generation of all inflammatory mediators linked to the cytokine storm. It can also protect against lung injury by suppressing increased oxidants production and promoting the resolution of the inflammatory process. Neutrophil lactoferrin degranulation stimulated by taurine may have antiviral effects against SARS-CoV-2, limiting viral replication. It is hypothesized that if taurine is administered early in the onset of COVID-19 disease, it may stop the cytokine storm from progressing, lowering morbidity and mortality.

The association between phase of illness and resource utilisation—a potential model for demonstrating clinical efficiency?

Background: Healthcare efficiency involves demonstrating flexible inter-relationships between resource utilisation and patient need. In palliative care, five phases of patient illness have been identified: stable, unstable, deteriorating, terminal and bereaved. Evaluating the association between phase of illness and nursing activities could demonstrate clinical efficiency. Aim: The aim of this study was to evaluate the association between the phase of illness and the intensity of nursing care in a specialist palliative care unit. Methods: This was a prospective, observational cohort study of consecutive admissions (n=400) to a specialist palliative care unit. Patient phase of illness was documented on admission and daily thereafter. A nursing activity tool was developed, which scored daily nursing interventions (physical, psychological, family care and symptom control). This score was called the nursing total score (NTS) and reflected the intensity of nursing activities. Data were entered into SPSS and descriptive statistics weregenerated. Results: A total of 342 (85%) patients had full data recorded on admission. Stable, unstable, deteriorating and terminal phases were associated with progressively increasing median NTSs on days 1, 2, 3 and 4 (all P<0.01). Phase stabilisation from the unstable to the stable phase during this timeframe resulted in reductions in physical care (p=0.038), symptom management (p=0.007) and near-significant reductions in family support (p=0.06). Conclusion: A significant association was demonstrated between phase of illness and intensity of nursing activities, which were sensitive to phase changes, from unstable to stable. This demonstrates technically efficient resource utilisation and identifies a potential efficiency model for future evaluations of inpatient palliative care.

Novel insights in endocrine and metabolic pathways in sepsis and gaps for future research.

Sepsis is defined as any life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains an important cause of critical illness and has considerable short- and long-term morbidity and mortality. In the last decades, preclinical and clinical research has revealed a biphasic pattern in the (neuro-)endocrine responses to sepsis as to other forms of critical illness, contributing to development of severe metabolic alterations. Immediately after the critical illness-inducing insult, fasting- and stress-induced neuroendocrine and cellular responses evoke a catabolic state in order to provide energy substrates for vital tissues, and to concomitantly activate cellular repair pathways while energy-consuming anabolism is postponed. Large randomized controlled trials have shown that providing early full feeding in this acute phase induced harm and reversed some of the neuro-endocrine alterations, which suggested that the acute fasting- and stress-induced responses to critical illness are likely interlinked and benefical. However, it remains unclear whether, in the context of accepting virtual fasting in the acute phase of illness, metabolic alterations such as hyperglycemia are harmful or beneficial. When patients enter a prolonged phase of critical illness, a central suppression of most neuroendocrine axes follows. Prolonged fasting and central neuroendocrine suppression may no longer be beneficial. Although pilot studies have suggested benefit of fasting-mimicking diets and interventions that reactivate the central neuroendocrine suppression selectively in the prolonged phase of illness, further study is needed to investigate patient-oriented outcomes in larger randomized trials.