Reflect Severity Of Illness Research Articles

Evaluating the Validity of the Responses to Illness Severity Quantification Score to Discriminate Illness Severity and Level of Care Transitions in Hospitalized Children with Severe Acute Malnutrition

To evaluate the validity of the Responses to Illness Severity Quantification (RISQ) score to discriminate illness severity and transitions between levels of care during hospitalization. A prospective observational study conducted in Maiduguri, Nigeria, enrolled inpatients aged 1-59months with severe acute malnutrition. The primary outcome was the RISQ score associated with the patient state. Heart and respiratory rate, oxygen saturation, respiratory effort, oxygen use, temperature, and level of consciousness are summed to calculate the RISQ score. Five states were defined by levels of care and hospital discharge outcome. The states were classified hierarchically, reflecting illness severity: hospital mortality was the most severe state, then intensive care unit (ICU), care in the stabilization phase (SP), care in the rehabilitation phase (RP), and lowest severity, survival at hospital discharge. A multistate statistical model examined performance of the RISQ score in predicting clinical states and transitions. Of 903 children enrolled (mean age, 14.6months), 63 (7%) died. Mean RISQ scores during care in each phase were 3.5 (n=2265) in the ICU, 1.7 (n=6301) in the SP, and 1.5 (n=2377) in the RP. Mean scores and HRs for a 3-point change in score at transitions: ICU to death, 6.9 (HR, 1.80); SP to ICU, 2.8 (HR, 2.00); ICU to SP, 2.0 (HR, 0.5); and RP to discharge, 1.4 (HR, 0.91). The RISQ score can discriminate between points of escalation or de-escalation of care and reflects illness severity in hospitalized children with severe acute malnutrition. Evaluation of clinical implementation and demonstration of benefit will be important before widespread adoption.

Increased serum pannexin-1 concentrations reflect illness severity and predict a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

BackgroundPannexin-1 is a nonselective, large pore and voltage gated channel protein, whose activation may aggravate acute brain injury. We ascertained the clinical significance of serum pannexin-1 as a prognostic biomarker of acute intracerebral hemorrhage (ICH). MethodsIn this prospective, observational study of 124 acute supratentorial ICH patients and 124 healthy controls, serum pannexin-1 concentrations were determined. Admission National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used for assessment of hemorrhagic severity, post-stroke 6-month modified Rankin scale (mRS) score was registered to reflect clinical outcome and early neurologic deterioration (END) and 6-month poor outcome (mRS score of 3–6) were regarded as the 2 prognostic parameters. Their associations with serum pannexin-1 concentrations were investigated using multivariate analysis. The predictive performance was evaluated in terms of area under receiver operating characteristic curve (AUC). ResultsIn comparison to controls, significantly increased serum pannexin-1 concentrations after ICH (median, 6.8 vs. 2.7 mg/ml) were independently correlative with NIHSS score (β, 0.193; 95% CI: 0.086–0.300), hematoma volume (β, 0.641; 95% CI: 0.423–0.859) and mRS score (β, 0.199; 95% CI: 0.065–0.174), were independently predictive of END (OR, 1.176; 95% CI: 1.081–1.280) and poor outcome (odds ratio, 1.218; 95% CI: 1.059–1.400), as well as were efficiently discriminative of END (AUC, 0.764; 95% CI: 0.663–0.864) and poor 6-month outcome (AUC, 0.790; 95% CI: 0.711–0.870). Serum pannexin-1 combined with NIHSS score and hematoma volume (AUC, 0.908; 95% CI: 0.857–0.960) displayed significantly higher predictive ability for poor 6-month outcome than NIHSS score and hematoma volume alone (both P < 0.05). ConclusionRising serum pannexin-1 concentrations following ICH, in strong correlation with hemorrhagic severity, independently distinguish the risk of END and 90-day poor outcome. Assumably, serum pannexin-1 may represent a valuable prognostic biomarker of ICH.

Prognostic and predictive significance of serum soluble scavenger receptor A in acute primary basal ganglia hemorrhage: A prospective cohort study

BackgroundScavenger receptor A (SRA) can regulate immune response and is involved in pathophysiological processes of acute brain injury. We analyzed the prognostic role of serum soluble SRA in intracerebral hemorrhage (ICH). MethodsIn this prospective cohort study of 110 healthy controls and 110 patients with acute basal ganglia hemorrhage, serum soluble SRA concentrations were detected. Univariate analyses, followed by multivariate logistic regression analyses, were utilized to explore the relationship between serum soluble SRA concentrations and early neurologic deterioration (END) plus post-stroke 3-month poor prognosis (modified Rankin Scale scores of 3–6). ResultsSerum soluble SRA concentrations of patients were significantly higher than those of controls (median, 3.6 vs 0.9 ng/ml; P < 0.001). Serum soluble SRA concentrations of patients were independently correlated with hematoma volume (β, 0.201; 95 % confidence interval (CI), 0.093–0.309; P = 0.001), National Institutes of Health Stroke Scale (NIHSS) scores (β, 0.118; 95 % CI, 0.024–0.213; P = 0.024), and 3-month modified Rankin Scale scores (β, 0.148; 95 % CI, 0.063–0.232; P = 0.001). Serum soluble SRA concentrations independently predicted END and poor 3-month prognosis with odds ratio values of 1.394 (95 % CI, 1.024–1.899; P = 0.035) and 1.441 (95 % CI, 1.016–2.044; P = 0.040) respectively. Serum soluble SRA concentrations were efficiently predictive of the development of END (ROC AUC 0.746; 95 % CI, 0.631–0.861) and poor 3-month prognosis (AUC, 0.773; 95 % CI, 0.685–0.861). Serum soluble SRA concentrations significantly improved AUCs of NIHSS score and hematoma volume to 0.889 (95 % CI, 0.829–0.948; P = 0.035) and 0.873 (95 % CI, 0.811–0.936; P = 0.036) for prognostic prediction. The END predictive ability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.900; 95 % CI, 0.835–0.965) was significantly superior to those of NIHSS score (P = 0.020) and hematoma volume (P = 0.022). The prognostic predictive capability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.907; 95 % CI, 0.852–0.962) substantially exceeded those of NIHSS score (P = 0.009) and hematoma volume (P = 0.005). ConclusionsSerum soluble SRA concentrations may reflect illness severity and neurologic function after ICH, indicating serum soluble SRA may serve as a promising prognostic biochemical marker of ICH.

Elevation in troponin associated with COVID-19 is associated with an adverse long-term outcome

Abstract Funding Acknowledgements Type of funding sources: None. Aim Elevated troponin levels have been shown to predict in-hospital outcomes in patients with COVID-19. However, whether this relates to or predicts longer-term outcomes is unknown. We aimed to investigate the effect of troponin elevation in patients with COVID-19, looking at resource utilisation post discharge, re-hospitalisation and outcomes. Methods This was a prospective study of 7650 patients admitted from December 2019 to July 2020 across a large university hospital trust. Patients were stratified according to COVID-19 status and troponin values (elevated = troponin T ≥15 ng/mL). The primary outcome assessed was all-cause mortality. Results 1005 patients were COVID-19 positive and had elevated troponin levels, with the remaining patients troponin positive but COVID-19 negative. COVID+ patients were more likely to be older, and less likely to be Caucasian (35.7% vs 46.6%, p&amp;lt;0.0001), however, peak troponin did not differ significantly between the groups {54 (28-125) vs 47 (25-130) ng/mL, p=0.121}. Mortality before first discharge was four times more likely in COVID+ than COVID- patients with elevated troponins {389 (39%) vs 359 (9.9%); p&amp;lt;0.001}. This mortality rate was also significantly higher than in COVID-19 positive patients who were troponin negative (p=6%, P&amp;lt;0.0001). Post-discharge over a follow-up period of 365 days, in the discharged COVID-19 positive troponin positive group, a minority of patients (13.2%) were investigated with outpatient cardiac investigations (echocardiography, CTCA, coronary angiography and cardiac MRI) compared to the COVID-19 negative group (34.5%). Post-discharge mortality was significantly higher among the COVID+ cohort {63 (10.2%) vs COVID-19 negative troponin positive 103 (3.1%); p&amp;lt;0.001}. COVID+ patients who died post discharge were more likely to be Caucasian (55.4% vs 35.2%, p&amp;lt;0.05) and more likely to be older (81 (72-87.5) vs 67 (57-79), p&amp;lt;0.05) than COVID+ patients who survived post discharge. Conclusion Elevated troponin levels in patients with COVID-19 is associated with long-term mortality. Patients were unlikely to undergo cardiac investigations and the troponin rise likely reflects illness severity. Further data is needed in this area.

712 Association between administration of hydroxycobalamin and acute kidney injury in patients with burn injury

IntroductionHydroxycobalamin (HC) is administered to patients with suspected hydrogen cyanide poisoning. Some reports suggest that this practice may be associated with acute kidney injury (AKI). We aimed to evaluate the association between HC administration and AKI after burn injury.MethodsWe conducted a retrospective matched cohort study. All adults admitted to a regional ABA-verified burn center within 24 hours of injury between 2015-2019 with >10% total body surface area (TBSA) flame burn injury were reviewed. We excluded patients who were palliated within 48 hours of admission, and those with pre-existing renal disease. Patients who received HC, either pre-hospital, in the emergency department, or the burn center, were matched on age (+/-2 years) and %TBSA (+/-5%) to up to 5 patients who did not receive HC. Rates of AKI within 7 days of admission, as defined by KDIGO criteria, were then compared. Secondary outcomes included receipt of renal replacement therapy, death, ventilator days, and discharge disposition.ResultsWe identified 10 patients who received HC; these patients were matched to 42 patients who did not receive HC. The median age of the HC group was 57 (IQR 43-66), compared to 65 in the non-HC group (IQR 57-65) (p= 0.98). The median %TBSA burn and %TBSA full thickness burn in the HC group and control was 16.5 (14-19) vs 13.5 (11-18) respectively (p= 0.22) and 3.5 vs 3.5 (0-9.5) respectively (p= 0.93). The incidence of inhalation injury in the HC group (n=8, 80%) was significantly higher than in the non-HC group (n=7, 17%)(p< 0.001). All HC patients were intubated within 24 hours of admission vs. only 48% of controls (p=0.003). The HC group also had significantly higher median SOFA scores on admission (9.5 vs 4, p< 0.001) and had a significantly higher admission creatinine [1.08 (0.95-1.26) vs 0.86 (0.71-1.02) mg/dl), p= 0.02]. The median 24-hour crystalloid fluid administered was 5911 mL/kg/%TBSA in the HC group vs 2774 mL/kg/%TBSA burn in controls (p= 0.004). All patients in the HC group developed AKI (n=10, 100%), compared to 64% (n=27) of non-HC patients (p=0.03). There was no significant difference in rates of death (20% vs 10%, p=0.35), Renal Replacement Therapy (20% vs 7%, p=0.21), discharge disposition, or ventilator days between groups.ConclusionsWe identified a small number of patients who received HC over a 5-year period at our burn center. There was an association between HC administration and development of AKI, but there were no differences in mortality, RRT, or ventilator days. HC administration is rare, and our data suggest that the sickest burn injured patients receive it. Larger studies are required to determine if HC administration is associated with AKI, or whether the increased rate of AKI in our study reflects illness severity.

Are point-of-care urine albumin–creatinine ratio measurements accurate in the critically ill?

BackgroundIn the critical care environment, elevated albuminuria values show capacity to reflect illness severity and predict mortality and hence assessing albumin/creatinine ratio (ACR) at the bedside has potential clinical benefit Point-of-care (POC) analysers offer rapid results but may be less accurate then laboratory analysis. MethodsCritically ill adult patients with a urinary catheter in situ had albumin, creatinine, and ACR measurements performed via laboratory and POC analysis. Data are presented as mean (standard deviation) or median [interquartile range]. Measurement agreement was assessed by Lin's concordance correlation coefficient, Bland Altman 95% limits of agreement, and classification by Cohen's kappa statistic. Results/FindingsAlbumin, creatinine, and ACR analysis was performed for 30 patients. Lin's correlation coefficient showed ‘substantial’ agreement for albumin and ACR and ‘almost perfect’ agreement for creatinine for POC vs laboratory analysis. POC vs laboratory analysis also showed poor agreement for identification of normal ACR (>1 mg/mmol) and mild urine ACR (1–3 mg/mmol) and ‘substantial’ agreement for moderately increased urine ACR (3–30 mg/mmol). ConclusionsACR POC values appear to provide an accurate and rapid method that has potential to provide an early indication of injury severity and mortality risk in the critically ill.

1424. Factors Associated with Failure to Clear Candidemia Infection: Surveillance Data from Eight States, 2017

BackgroundCandidemia is a bloodstream infection commonly associated with high morbidity and mortality. Failure to clear candidemia can lengthen hospitalization and treatment. Factors associated with candidemia clearance are unknown.MethodsWe analyzed 2017 candidemia surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program. Data from eight sites (counties in California, Colorado, Georgia, Minnesota, New Mexico, New York, Oregon, and Tennessee) were included. Clearance was defined as having a blood culture negative for Candida ≤30 days after initial culture date (ICD). Cases with unknown clearance, unknown survival outcome, or death ≤30 days of ICD were excluded. Demographic and clinical factors associated with clearance were assessed with bivariate analysis using chi-square tests and multivariable logistic regression to calculate adjusted odds ratios (aOR) using backward selection (p-value< 0.10).ResultsOf 1,024 candidemia cases, 737 were included and 582 (79%) demonstrated clearance, of which 79% had evidence of clearance ≤5 days after ICD. In bivariate analysis, clearance was associated with central venous catheter (CVC) ≤2 days before ICD, CVC removal ≤7 days after ICD, and systemic antifungal medication within 14 days before ICD. Clearance was inversely associated with black race and admission from another hospital. In multivariable analysis, only race and admission from another hospital were significant predictors; age, sex, and CVC presence and subsequent removal were also retained for their clinical relevance. In the final model, clearance was less likely among black patients (aOR 0.51, 95% confidence interval [CI] 0.29-0.91) and those admitted from another hospital (aOR 0.28, 95% CI 0.11-0.75).Table 1. Bivariate associations for select variables between individuals with documented candidemia clearance and those without documented clearance in eight Emerging Infections Program surveillance sites, 2017 ConclusionWe found failure to clear candidemia infection to be associated with black race and prior hospital exposure, but not other factors previously shown to be associated (e.g., comorbidities, CVC presence). These associations could reflect illness severity, access to care, or other obstacles to effective treatment. Additional research is needed to investigate these associations further and identify other factors (e.g., treatment type and timing) to improve outcomes.Disclosures All Authors: No reported disclosures

Relationships between abnormal neural activities and cognitive impairments in patients with drug-naive first-episode schizophrenia

BackgroundPrior resting state functional Magnetic Resonance Imaging studies (rs-fMRI) via the regional homogeneity (ReHo) method have demonstrated inconsistent and conflicting results because of several confounding factors, such as small sample size, medicinal influence, and illness duration. Relationships between ReHo measures and cognitive impairments in patients with drug-naive First-Episode Schizophrenia (dn-FES) are rarely reported. This study was conducted to explore the correlations between ReHo measures and cognitive deficits and clinical symptoms in patients with dn-FES.MethodsA total of 69 patients with dn-FES and 74 healthy controls were recruited. MATRICS Consensus Cognitive Battery (MCCB), Wechsler Adult Intelligence Scale (WAIS), and Positive And Negative Syndrome Scale (PANSS) were used to assess cognitive function, Intelligence Quotient (IQ), and clinical symptoms, respectively. The correlations between ReHo maps and cognitive deficits and the severity of symptoms were examined using strict correlation analysis.ResultsReHo values in right Middle Frontal Gyrus (MFG) and Superior Frontal Gyrus (SFG) increased in dn-FES group, whereas ReHo values in right cuneus decreased. Correlation analysis showed that the ReHo values in right MFG positively correlated with attention/vigilance impairments, social cognition deficits, and the severity of clinical manifestations.ConclusionsThese findings suggested that abnormal spontaneous activities in right MFG reflect illness severity and cognitive deficits, which also serve as a basis for establishing objective diagnostic markers and might be a clinical intervention target for treating patients with schizophrenia.

Providing clarity around ethical discussion: development of a neonatal intervention score.

To develop a Neonatal Intervention Score (NIS) to describe the clinical trajectory of a neonate throughout their neonatal intensive care unit (NICU) admission. The NIS was developed by modifying the Neonatal Therapeutic Intervention Scoring System (NTISS) to reflect illness severity, dependency on life-sustaining interventions and overall life trajectory on a longitudinal basis, rather than illness burden. Validity for longitudinal use within the NICU was tested by calculating the score for 99 preterm babies born less than 28weeks at predetermined time points throughout their admission to tertiary level care at two institutions. A total of 1333 NISs were analysed, ranging from 0 to 32.5 (mean 9.77, SD 5.4). Internal consistency (Cronbach alpha) reached 0.8. NIS moderately correlated to both SNAPPE-II and SNAP-II (Spearman's rho=0.47, p=<0.001) within the first 24hours. The NIS is a useful and reliable descriptive tool of relative illness severity and degree of medical interventions throughout a baby's admission. Integrating a longitudinal description of medical dependency of a patient may assist both clinical and ethical decision-making and empirical research by providing an objective account of a baby's clinical trajectory. Establishment of validity within individual institutions is required.

Editorial Volume Editorial Volume 15 Issue 2

Hospital mortality has been a hot topic in the medical and popular Press over recent years. Many readers will recall ‘scandals’ around hospitals whose mortality rates appeared higher than that which would be expected. The so-called ‘weekend effect’ whereby patients admitted to hospital between Friday and Monday appear more likely to die during their hospital stay has been regularly quoted in Parliament by the Secretary of State as justification for the Government’s manifesto pledge to create a ‘7 day NHS’. A number of recent publications have illustrated the complexity of this statistic, which – at least in part – is likely to reflect illness severity as much as organizational factors. The paper by Emma Mason in this edition further supports the concept that hospital mortality statistics may be hard to influence through structural or staffing changes. Those working in the acute medicine setting will not be surprised to read that almost half of those patients who die within 48 hours of arrival in hospital had solely palliative care needs at the time of admission. Many of these patients were elderly, frail and resident in a care home environment, but many also had undergone previous admissions within the months leading up to their death; the authors comment that this could have provided an opportunity to discuss end of life care plans, potentially enabling their final admission to hospital to have been avoided. Preventing ‘avoidable’ deaths in hospital from conditions such as sepsis and acute pulmonary embolism is a key component of the job of an acute physician. However, even when death in unavoidable we must do what we can to ensure patients die in the environment of their choice. Reducing deaths in hospital should not simply focus on those whose death can be prevented. Although mortality statistics may be misleading when interpreted in isolation, good quality data can be a powerful tool to influence changes in the acute medicine setting. By the time this edition is published, the 2016 Society for Acute Medicine Benchmarking Audit (SAMBA16) will already have take n place; previous years’ data were published in this journal and we hope to see a continued rise in the numbers of participating units this year. Tom Brougham and colleagues from Bristol have illustrated how an electronic system for data collection on their AMU enabled reorganization of their junior doctor rota, reducing waiting time for patients. Their data illustrate the problem which will be familiar to many acute physicians, whereby the surge in afternoon arrivals on the AMU often coincides with shift changeovers and reductions in junior doctor and other numbers. Matching staffing to workload can have significant benefits for patient care and may enable a reduced strain on the night shift team if patients are seen in a more timely fashion. Whether this can be linked to improved patient outcomes in the future will be interesting. Finally, I would like to welcome one more addition to the editorial board. Dr Nick Murch is an acute physician in the Royal Free hospital, with an interest in medical education and simulation skills training. With an increasing number of acute medicine trainees undertaking medical education as their specialist skill, I am keen to develop the training and education section of the journal over the coming years, and look forward to Nick’s input in this regard. We will continue to welcome submissions of research relating to acute medicine education and training, which we will consider for future publication in this section of the journal.

Behavioral activities collected through smartphones and the association with illness activity in bipolar disorder.

Smartphones are useful in symptom-monitoring in bipolar disorder (BD). Objective smartphone data reflecting illness activity could facilitate early treatment and act as outcome in efficacy trials. A total of 29 patients with BD presenting with moderate to severe levels of depressive and manic symptoms used a smartphone-based self-monitoring system during 12weeks. Objective smartphone data on behavioral activities were collected. Symptoms were clinically assessed every second week using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Objective smartphone data correlated with symptom severity. The more severe the depressive symptoms (1) the longer the smartphone's screen was "on"/day, (2) more received incoming calls/day, (3) fewer outgoing calls/day were made, (4) less answered incoming calls/day, (5) the patients moved less between cell towers IDs/day. Conversely, the more severe the manic symptoms (1) more outgoing text messages/day sent, (2) the phone calls/day were longer, (3) the fewer number of characters in incoming text messages/day, (4) the lower duration of outgoing calls/day, (5) the patients moved more between cell towers IDs/day. Further, objective smartphone data were able to discriminate between affective states. Objective smartphone data reflect illness severity, discriminates between affective states in BD and may facilitate the cooperation between patient and clinician. Copyright © 2016 John Wiley & Sons, Ltd.

Redefining massive transfusion when every second counts

The massive transfusion (MT) concept (>10-U packed red blood cells per 24 hours) is retrospective, arbitrary, and prone to survivor bias. Accounting for rate and timing is a more accurate conceptual framework. We redefined MT as a critical administration threshold (CAT) of 3 U/h, which is clinically pertinent and reflects hemorrhagic shock. The purpose of this study was to compare the traditional form of MT to a CAT definition in predicting mortality. Patients receiving transfusion in the first 24 hours were included. Precise transfusion times for each unit, in minutes, were calculated from time of injury. MT and CAT were compared to determine risk of death. Univariate and multivariate analyses were used to examine inpatient mortality. A total of 169 patients(70%, >10 New Injury Severity Score [NISS]) were studied; 46% were CAT+; 22% met the MT criteria. With logistic regression, a CAT of 3 U/h (CAT+) was more predictive of death compared with 2, 4, 5, or 6 U/h. CAT was met once (CAT 1), twice (CAT 2) or more than 3 times (CAT 3) in 21%, 14%, and 11%, respectively. Increasing CAT was associated with increased mortality. CAT identified 75% of all deaths; MT only identified 33% and failed to identify 42% of CAT+ deaths. CAT (relative risk [RR] 3.58; 95% confidence interval [CI] 1.80-7.15) had a stronger association with mortality compared with MT(RR, 1.82; 95% confidence interval, 1.02-3.26). The traditional definition of MT is inadequate to reflect illness severity. Using CATs allows prospective identification of critically ill trauma patients and eliminates survivor bias. CAT may serve as an activation trigger for transfusion protocols, allowing early identification of patients with critical transfusion requirements. Clinical trials involving transfusion strategies should consider CAT as an instrument for evaluating outcomes. Diagnostic/prognostic study, level II.

Frequency, duration and predictors of bronchiolitis episodes of care among infants ≥32 weeks gestation in a large integrated healthcare system: a retrospective cohort study

BackgroundBronchiolitis is common in the first two years of life and is the most frequent cause of hospitalization in this age group. No previous studies have used an episode-of-care analysis to describe the frequency, duration, and predictors of bronchiolitis episodes of care during the first two years.MethodsWe conducted a retrospective cohort study of 123,264 infants ≥32 weeks gestation born at 6 Northern California Kaiser Permanente hospitals between 1996 and 2002. We used electronic medical records to concatenate hospital, emergency department and outpatient health care encounters for bronchiolitis into discrete episodes of care. We used descriptive statistics to report frequency and duration of bronchiolitis episodes and used logistic regression to assess the effect of gestational age and other clinical and demographic predictors on the outcome of bronchiolitis episodes.ResultsAmong all infants, the rate of bronchiolitis episodes was 162 per 1000 children during the first 2 years of life; approximately 40% required >1 day of medical attention with a mean duration of 7.0 ± 5.9 days. Prematurity was associated with increased risk of bronchiolitis episodes and longer duration. Bronchiolitis episodes rates per 1000 infants were 246 for 32–33 weeks gestational age, 204 for 34–36 weeks, and 148–178 for >36 weeks. Male gender, African-American and Hispanic race/ethnicity, and parental history of asthma were associated with an increased risk of having a bronchiolitis episode and/or longer duration.ConclusionsBronchiolitis episodes of care are frequent during the first two years of life and the duration ranges from 1 to 27 days. Prematurity was associated with more frequent and longer duration of bronchiolitis episodes of care, which may reflect illness severity and/or perceived vulnerability.

Size and Shape of the Corpus Callosum in Adult Niemann-Pick Type C Reflects State and Trait Illness Variables

Variable alterations to the structure of the corpus callosum have been described in adults with NPC, a neurometabolic disorder known to result in both white and gray matter pathology. This study sought to examine the structure of the callosum in a group of adult patients with NPC and compared callosal structure with a group of matched controls, and to relate callosal structure with state and trait illness variables. Nine adult patients with NPC were matched to control subjects (n = 26) on age and sex. The corpus callosum was segmented from the midsagittal section of T1-weighted images on all subjects, and total area, length, bending angle, and mean thickness were calculated. In addition, 39 regional thickness measures were derived by using a previously published method. All measures were compared between groups, and analyzed alongside symptom measures, biochemical parameters, and ocular-motor measures. The callosal area and mean thickness were significantly reduced in the patient group, and regional thickness differences were greatest in the genu, posterior body, isthmus, and anterior splenium. Global callosal measures correlated significantly with duration of illness and symptom score, and at trend level with degree of filipin staining. Measures of reflexive saccadic peak velocity and gain, and self-paced saccades, correlated strongly with total callosal area. Callosal structure and size reflect both state and trait markers in adult NPC, and they may be useful biomarkers to index both white and gray matter changes that reflect illness severity and progression.

Latent viral infections in critically ill patients

A key message of Osawa and Singh's review of cytomegalovirus infection in critically ill patients is that the infection occurred in 25% of patients and was associated with worse outcome [1]. Emphasis was placed on the lack of proof of causality between infection and outcome, and reactivation may reflect illness severity. The herpesvirus family all cause latent infections in humans, and similar rates of infection, morbidity and mortality have also been reported in comparable patients with herpes simplex virus [2,3]. Nevertheless, although infection rates with latent herpesviruses appear high, the majority of seropositive patients do not suffer reactivation. Acquisition of herpesviruses in infancy results in trivial clinical illness, suggesting we have co-evolved effectively with these pathogens. Indeed a recent report highlighted how herpesviruses offer protection from bacterial infections [4]. Latent, but not acute, infection conferred a 100-fold to 1,000-fold reduction in bacterial burden due to IFNγ-dependent macrophage activation. Latency with all herpesviruses in humans is probably associated with frequent subclinical reactivation, which may lead to reticuloendothelial cell priming [5]. We suggest that the sequelae of latent infection may not be universally adverse in all patients, some of whom may be protected from developing septic shock and never enter the intensive care unit. Osawa and Singh suggested a study to determine the role of antiviral agents; until the mechanisms and significance of reactivation in different patient groups are elucidated, however, such studies will prove difficult to interpret. A pilot study of acyclovir in the prophylaxis of herpesvirus infections in critical care is already underway in the United Kingdom (ISRCTN29934637).

Assessing Nutritional Status in Chronically Critically Ill Adult Patients

Numerous methods are used to measure and assess nutritional status of chronically critically ill patients. To discuss the multiple methods used to assess nutritional status in chronically critically ill patients, describe the nutritional status of chronically critically ill patients, and assess the relationship between nutritional indicators and outcomes of mechanical ventilation. A descriptive, longitudinal design was used to collect weekly data on 360 adult patients who required more than 72 hours of mechanical ventilation and had a hospital stay of 7 days or more. Data on body mass index and biochemical markers of nutritional status were collected. Patients' nutritional intake compared with physicians' orders, dieticians' recommendations, and indirect calorimetry and physicians' orders compared with dieticians' recommendations were used to assess nutritional status. Relationships between nutritional indicators and variables of mechanical ventilation were determined. Inconsistencies among nurses' implementation, physicians' orders, and dieticians' recommendations resulted in wide variations in patients' calculated nutritional adequacy. Patients received a mean of 83% of the energy intake ordered by their physicians (SD 33%, range 0%-200%). Patients who required partial or total ventilator support upon discharge had a lower body mass index at admission than did patients with spontaneous respirations (Mann-Whitney U = 8441, P = .001). In this sample, the variability in weaning progression and outcomes most likely reflects illness severity and complexity rather than nutritional status or nutritional therapies. Further studies are needed to determine the best methods to define nutritional adequacy and to evaluate nutritional status.

Hyperglycemia and Nutrition Support: Theory and Practice

Hyperglycemia has long been known to portend a worse short-term prognosis than euglycemia in hospitalized patients. Hyperglycemia reflects illness severity and results in deleterious consequences for certain patient groups. In a surgical intensive care unit population, normalization of morning glucose values using insulin infusions improved mortality vs controls. Until additional studies in other patient groups are reported, practitioners of nutrition support must prevent excessive iatrogenic hyperglycemia, in particular when using parenteral feeding, and should choose aggressive glycemic goals that also avoid hypoglycemia.

Gut overgrowth with abnormal flora: the missing link in parenteral nutrition-related sepsis in surgical neonates.

Patients receiving parenteral nutrition are at risk of septicaemia. Intestinal dysmotility and impaired gut immunity due to parenteral nutrition promote bacterial overgrowth. Gut overgrowth with aerobic Gram-negative bacilli (AGNB) impairs systemic immunity. The aim of this study was to determine the potential role of gut overgrowth with AGNB in the pathogenesis of septicaemia related to parenteral nutrition. A prospective 5 y study of surgical infants less than 6 months of age was undertaken. Surveillance samples of the oropharynx and gut were obtained at the start of parenteral nutrition and thereafter twice weekly, to detect AGNB carriage. Blood cultures were taken on clinical indication only. Two-hundred and eight infants received parenteral nutrition for 6271 days (median 13 days, range 1-512 days). The incidence of AGNB carriage was 42%, whilst the septicaemia rate was 15%. Eighty-four percent of septicaemic infants carried AGNB, whilst 16% never carried AGNB (P<0.005). Carriage developed significantly earlier than septicaemia. The incidence of septicaemia was significantly greater in the subset of abnormal carriers. Although gut overgrowth with abnormal flora reflects illness severity, the fact that it preceded septicaemia implicates AGNB overgrowth, per se, as a contributory factor in the development of septicaemia related to parenteral nutrition. Prevention is unlikely to be successful if it ignores the abnormal flora.

Ethological assessment of the DSM‐III subtyping of unipolar depression

An ethological method was employed to validate the DSM-III subtyping of unipolar, nondelusional depression. The nonverbal behavior of 44 depressed outpatients was video-recorded during psychiatric interview. The DSM-III subtyping was not significantly associated with sex or level of education. Patients with major depression (with or without melancholia) were significantly older than those with dysthymic disorder. The Hamilton Rating Scale for Depression (HRSD) scores of the 3 diagnostic groups indicated a progressive increase in symptom severity across DSM-III subtypes (dysthymic disorder less than major depression without melancholia less than major depression with melancholia). Ethological assessment failed to find any evidence for the validity of the DSM-III subtyping of unipolar depression. Of the 8 behavioral categories analyzed in this study, none showed statistically significant differences between the 3 diagnostic groups. Our interpretation of these results is that, whereas the DSM-III subtyping primarily reflects illness severity, the ethological profile measures a dimension of depression largely independent from severity, as indicated by the lack of correlation between the HRSD score and the categories of nonverbal behavior.

Melancholic subtyping: a qualitative or quantitative distinction?

Melancholic depressed subjects scored significantly higher than did nonmelancholic subjects both on the depressive symptoms used and those not used for melancholic subtyping. The results suggest that DSM-III's melancholic criteria do not identify a qualitatively distinct subgroup, but instead reflect illness severity.