Changes In Illness Severity Research Articles

Application of national early warning score in assessing postoperative illness severity in elderly patients with gastrointestinal illnesses.

Population aging is a social problem that is being faced in most countries. To apply the National Early Warning Score (NEWS) for an early warning on the vital signs and consciousness of elderly patients who are hospitalized in the gastrointestinal surgical department and to provide a reference for early detection of changes in illness severity in elderly patients by studying the correlation between NEWS value and changes in illness severity. We enrolled 528 elderly patients who were hospitalized in the gastrointestinal surgical department of a tertiary grade A hospital in Guizhou Province between June 2020 and May 2021, to analyze how NEWS max value correlates with illness severity and obtain the optimal NEWS cutoff value for both potentially critically ill and critically ill elderly patients using the receiver operating characteristic (ROC) curve. There were statistically significant differences in NEWS values between elderly patients with various illness severities (P< 0.05). NEWS values correlated positively with illness severity (r= 0.605, P< 0.001). Based on the ROC curve, early warning trigger values for NEWS to identify potentially critically ill, critically ill and terminally ill elderly patients were 6, 7 and 8, respectively. The area under the curve (AUC) for potentially critically ill, critically ill and terminally ill elderly patients was 0.907, 0.921 and 0.939, respectively. NEWS performed better in detecting patient illness severity than Modified Early Warning Score (MEWS) in AUC, sensitivity, specificity, and Youden's index, with statistically significant differences (P< 0.05). An early warning on the vital signs and consciousness of hospitalized elderly patients using NEWS can facilitate advanced detection of changes in illness severity of elderly patients by medical staff and enable timely treatment, thus significantly lowering the risks of illness deterioration.

Escalation of care in children at high risk of clinical deterioration in a tertiary care children’s hospital using the Bedside Pediatric Early Warning System

BackgroundEscalation and de-escalation are a routine part of high-quality care that should be matched with clinical needs. The aim of this study was to describe escalation of care in relation to the occurrence and timing of Pediatric Intensive Care Unit (PICU) admission in a cohort of pediatric inpatients with acute worsening of their clinical condition.MethodsA monocentric, observational cohort study was performed from January to December 2018. Eligible patients were children: 1) admitted to one of the inpatient wards other than ICU; 2) under the age of 18 years at the time of admission; 3) with two or more Bedside-Paediatric-Early-Warning-System (BedsidePEWS) scores ≥ 7 recorded at a distance of at least one hour and for a period of 4 h during admission. The main outcome -the 24-h disposition – was defined as admission to PICU within 24-h of enrolment or staying in the inpatient ward. Escalation of care was measured using an eight-point scale—the Escalation Index (EI), developed by the authors. The EI was calculated every 6 h, starting from the moment the patient was considered eligible. Analyses used multivariate quantile and logistic regression models.ResultsThe 228 episodes included 574 EI calculated scores. The 24-h disposition was the ward in 129 (57%) and the PICU in 99 (43%) episodes. Patients who were admitted to PICU within 24-h had higher top EI scores [median (IQR) 6 (5–7) vs 4 (3–5), p < 0.001]; higher initial BedsidePEWS scores [median (IQR) 10(8–13) vs. 9 (8–11), p = 0.02], were less likely to have a chronic disease [n = 62 (63%) vs. n = 127 (98%), p < 0.0001], and were rated by physicians as being at a higher risk of having a cardiac arrest (p = 0.01) than patients remaining on the ward. The EI increased over 24 h before urgent admission to PICU or cardiac arrest by 0.53 every 6-h interval (CI 0.37–0.70, p < 0.001), while it decreased by 0.25 every 6-h interval (CI -0.36–0.15, p < 0.001) in patients who stayed on the wards.ConclusionEscalation of care was related to temporal changes in severity of illness, patient background and environmental factors. The EI index can improve responses to evolving critical illness.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

Genetic Testing and Hospital Length of Stay in Neonates With Epilepsy

BackgroundWe evaluated changes in genetic testing for neonatal-onset epilepsy and associated short-term outcomes over an 8-year period among a cohort of patients in the neonatal intensive care unit (NICU) at a single institution before and after the introduction of sponsored genetic epilepsy testing in January 2018. MethodsOur primary outcome was a change in length of stay (LOS) after 2018. We also ascertained severity of illness with the Neonatal Sequential Organ Failure Assessment (nSOFA), type and result of genetic testing, turnaround time to molecular diagnosis (TAT), LOS, antiseizure medications (ASMs), and use of technology at discharge. We compared outcomes using nonparametric tests and difference-in-difference analysis. ResultsFifty-three infants with genetic testing were included; 20 infants were tested after 2018. A total of 4160 infants in the NICU without genetic testing were used as reference. In the genetic testing group, LOS was 25 days (interquartile range [IQR] 5, 49) pre-2018 and 19 days (IQR 6, 19) post-2018 (P < 0.001 when compared with the reference population in the difference-in-difference analysis). TAT decreased from 51 days to 17 days after 2018 (P = 0.003). ASM number decreased from 4 (IQR 2, 5) to 2 post-2018 (IQR 1, 3) (P = 0.02). Over the same time periods there was no significant change in birth weight, maximum nSOFA score, or technology dependence. ConclusionsIn this cohort, changes in genetic testing for neonatal-onset epilepsy were associated with shorter LOS that was not explained by changes in severity of illness, birth weight, or the average LOS in the NICU over time. Validation of these results in a larger, multicenter sample size is warranted.

The indirect impact of COVID-19 pandemic on the utilization of the emergency medical services

BackgroundFear of contracting COVID-19 and the large-scale preventing measures may have influenced health service utilization. The aim of the study was to assess the indirect impact of COVID-19 pandemic on the utilization of the emergency medical services (EMS) of Tuscany Region (Italy).MethodsThe study was carried out on administrative data from the public healthcare system of Tuscany (38 general hospitals and 4 university teaching hospitals). Variations in the utilization of out-of-hospital (i.e. calls for emergency medical assistance and dispatch of mobile medical care units) and in-hospitals (emergency department(ED) visits and hospitalizations from the ED) EMS during the first pandemic wave were analyzed (February - July 2020) in relation with corresponding periods of the previous three years. Furthermore, in order to understand changes in illness severity of patients using the EMS, standardized ratios for hospitalizations requiring ICU and in-hospital mortality were analyzed.ResultsSignificant decreases in the expected volumes of utilizations were observed in each of the considered EMS starting from the week in which the first case of COVID-19 was confirmed in Italy till the last week of the first wave. In particular, during the peak period of COVID-19 pandemic wave a reduction of 73,041 (-67%, 95%CI -69%; -66%) in ED admissions and of 682 (-38% 95%CI -55%; -43%) in hospitalization from ED were observed. Significant decreases in hospitalizations for life threatening medical conditions were observed. No significant differences were found between the observed and the expected in-hospital mortality and hospitalizations requiring ICU during the COVID-19 epidemic peak period (SR 1.1 95%CI 0.72-1.90; SR 1.0 95%CI 0.83-1.23).ConclusionsA large and generalized decrease in EMS utilization was observed during the first wave of COVID-19 pandemic. Furthermore, findings suggest that seriously ill patients avoid seeking care as less seriously ill patients did.Key messages The falling in the utilization of emergency medical services during pandemic could portend substantial harm to public health, and not simply the absence of real health need.The preparedness of the healthcare delivery system should not focus solely on confronting the pandemic disease, but also on ensuring access to high quality emergency care for other diseases.

The association of the COVID-19 pandemic and short-term outcomes of non-COVID-19 critically ill patients: an observational cohort study in Brazilian ICUs

PurposeTo assess whether intensive care unit (ICU) outcomes for patients not affected by coronavirus disease 2019 (COVID-19) worsened during the COVID-19 pandemic.MethodsRetrospective cohort study including prospectively collected information of patients admitted to 165 ICUs in a hospital network in Brazil between 2011 and 2020. Association between admission in 2020 and worse hospital outcomes was performed using different techniques, including assessment of changes in illness severity of admitted patients, a variable life-adjusted display of mortality during 2020, a multivariate mixed regression model with admission year as both fixed effect and random slope adjusted for SAPS 3 score, an analysis of trends in performance using standardized mortality ratio (SMR) and standardized resource use (SRU), and perturbation analysis.ResultsA total of 644,644 admissions were considered. After excluding readmissions and patients with COVID-19, 514,219 patients were available for analysis. Non-COVID-19 patients admitted in 2020 had slightly lower age and SAPS 3 score but a higher mortality (6.4%) when compared with previous years (2019: 5.6%; 2018: 6.1%). Variable-adjusted life display (VLAD) in 2020 increased but started to decrease as the number of COVID-19 cases increased; this trend reversed as number of COVID cases reduced but recurred on the second wave. After logistic regression, being admitted in 2020 was associated with higher mortality when compared to previous years from 2016 and 2019. Individual ICUs standardized mortality ratio also increased during 2020 (higher SMR) while resource use remained constant, suggesting worsening performance. A perturbation analysis further confirmed changes in ICU outcomes for non-COVID-19 patients.ConclusionHospital outcomes of non-COVID-19 critically ill patients worsened during the pandemic in 2020, possibly resulting in an increased number of deaths in critically ill non-COVID patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-021-06528-6.

Characteristics and Outcomes of Clinic Visits Immediately Preceding Sepsis Hospitalization.

Existing sepsis quality improvement initiatives focus on recognition and treatment of sepsis upon hospital admission. Yet many patients are evaluated in the clinic within 1 day of sepsis hospitalization. To determine the circumstances of clinic visits that precede sepsis hospitalization, including illness severity, whether patients are referred to the hospital, and time lapse and change in illness severity between clinic and hospital evaluation. In a retrospective cohort study at a tertiary academic medical center, data from electronic medical records were collected for all adult patients evaluated in an outpatient clinic within 1 day of sepsis hospitalization in 2017. Of 1450 patients hospitalized with sepsis, 118 had an established outpatient provider and a clinic visit within 1 day of admission and thus were included. During the clinic visit, 47 patients (39.8%) had a quick Sequential Organ Failure Assessment (qSOFA) score ≥1, and 59 (50.0%) had vital sign abnormalities. Most (74, 62.7%) were sent directly to the emergency department or hospital. Upon emergency department/hospital presentation, 62 patients (52.5%) had a worsening qSOFA score and/ or vital signs and 27 (22.9%) had worsening of multiple parameters. Median time lapse from clinic to emergency department/hospital evaluation was 3.2 hours. One in 10 patients hospitalized for sepsis had been evaluated in a clinic within 1 day of admission. At that clinic visit, most patients had an elevated qSOFA score or abnormal vital signs and a majority were sent directly to the emergency department/hospital. Half experienced clinical deterioration between the clinic visit and arrival in the emergency department/hospital.

557: The Association Between PICU to ED Telemedicine Consultations on Changes in Severity of Illness

INTRODUCTION: Children and adolescents transferring from emergency departments (EDs) with video telemedicine programs have been associated with lower severity of illness (SOI) on admission to Pediatric Intensive Care Units (PICUs) compared to patients transferred from EDs without telemedicine programs Very little is known about the relationship between telemedicine use and SOI in the ED We hypothesize telemedicine will be used on patients with higher SOI in comparison to telephone consultations METHODS: A prospective crossover-cluster randomized controlled trial was conducted to compare telemedicine and telephone consultations conducted on critically ill children Patients age 0-14 from 15 participating EDs with established telemedicine programs were included if they were transferred to the regional PICU Patients were randomized to either telemedicine or telephone consultation based on four 6-month blocks Data was analyzed using 'intention to treat' analysis, as well as 'as treated' and 'per protocol' RePEAT (Revised Pediatric Emergency Assessment Tool) and PRISA (Pediatric Risk of Admission) scores were used to estimate SOI in the ED and Pediatric Index of Mortality (PIM) was used to assess SOI at the time of PICU admission RESULTS: This study enrolled 696 patients, 373 were admitted to the PICU Telemedicine and telephone cohorts were comparable by sex, age and race/ethnicity PIM-2/3 scores (median -4 97 telemed, -5 1 telephone, p = 0 95) and mean RePEAT scores (1 67 telemed, 1 71 telephone, p=0 61) were not statistically significant between the groups whether using the intention to treat or as treated analysis PRISA scores were similar in the intention to treat analysis, (19 5 telemed, 21 7 telephone, p=0 15) but were significantly higher in the telemedicine cohort (mean=22, SD=13 09) than in the telephone cohort (mean=19, SD=12 82), p= 0 039) in the as treated analysis CONCLUSIONS: Despite randomization of telemedicine and telephone consultations among patients presenting to 15 EDs as part of a multi-institutional trial, physicians did not adhere to telephone consultations when patients had higher SOI and instead preferentially used telemedicine More data is needed to understand the effect of telemedicine consultation on transfer rates, SOI, and optimal application in the post-COVID era

Enhancement of cognitive insight and higher-order neurocognitive function by fronto-temporal transcranial direct current stimulation (tDCS) in patients with schizophrenia

No studies have examined the effects of fronto-temporal transcranial direct current stimulation (tDCS) on cognitive insight and neurocognitive function in schizophrenia patients and the dynamic interplay between tDCS-induced changes in these two outcomes. In this double-blind, randomized, sham-controlled study, we investigated the effects of fronto-temporal tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5 days] on illness severity, psychosocial functioning, cognitive insight and neurocognitive function in schizophrenia patients (N = 60).The authors observed significant trends that tDCS ameliorated the severity of total and general psychopathology as measured by the Positive and Negative Syndrome Scale. No significant effects were observed for other psychopathological symptoms and psychosocial functioning. Cognitive insight as measured by the Beck Cognitive Insight Scale (BCIS) was rapidly enhanced by 10-session tDCS (F = 10.80, Cohen's d = 0.44, p = 0.002) but the beneficial effect became borderline significant 1 month after stimulation. A trend-level improvement with tDCS of planning ability (F = 6.40, Cohen's d = 0.339, p = 0.014) as measured by the accuracy in Tower of London task was also observed. In the active tDCS group, the change in cognitive insight from baseline to immediately after tDCS assessment was positively correlated with that in planning ability (r = 0.46, p = 0.015), which was independent of the corresponding change in illness severity. The promising results regarding the fast-acting beneficial effects of tDCS on cognitive insight and planning ability in schizophrenia require confirmation in future replication studies.

Linking the severity of illness and the weekend effect: a cohort study examining emergency department visits

BackgroundDespite extensive research on the “weekend effect” i.e., the increased mortality associated with hospital admission during weekend, knowledge about disease severity in previous studies is limited. The aim of this study is to examine patient characteristics, including disease severity, 30-day mortality, and length of stay (LOS), according to time of admission to an emergency department.MethodsOur study encompassed all patients admitted to a Danish emergency department in 2014–2015. Using data from electronic patient records, this study examines patient characteristics including age, gender, Charlson Comorbidity Index score, triage score, and primary diagnosis. Triage score and transfer to intensive care unit (ICU) were used as indicators of disease severity. LOS within the department and within the hospital was examined. Age- and sex-standardized 30-day mortality rates comparing patients with the same triage score admitted at daytime, evening, and nighttime on weekdays and on weekends were computed. To test differences, a Cox regression analysis was added.ResultsWe included 35,459 patient visits, of which 10,435 (32%) started on a weekend. There were no large differences in baseline characteristics between patients admitted on weekdays and those admitted on weekends. The relative risk (RR) for being triaged orange or red was 1.16 (95% confidence interval (CI) 1.06–1.28, P = 0.0017) for weekend admissions as compared with weekday admissions. Weekend admissions were twice as likely as weekday admissions to be transferred to the ICU (RR, 1.96; 95% CI 1.53–2.52, P = 0.0000). No significant changes were found in LOS. The 30-day mortality rate increased with disease severity regardless of time of admission. When comparing the 30-day mortality rate for patients with the same triage score, the trend was toward a higher mortality when admission occurred during the weekend. Increasing mortality rate was significant for patients admitted at evening on weekends with a hazard ratio of 1.32 (95% CI 1.03–1.70, P = 0.027) when compared with patients admitted on daytime on weekdays.ConclusionsWhen comparing weekday and weekend admissions, the 30-day mortality rate increased for patients admitted at evening on weekends after adjusting for comorbidity and triage score, indicating that the weekend effect was independent of changes in illness severity.

Preferences for vaccines against children’s diarrheal illness among mothers in Poland and Hungary

PurposeAlthough the World Health Organization recommends universal rotavirus immunization, uptake of the vaccine is low in Poland and Hungary, where it is not covered by the National Immunization Program. This study aimed to quantify mothers’ preferences for vaccines preventing children’s diarrheal illness and to examine whether willingness to vaccinate varies with working status. MethodsMothers of children aged <3 years living in Poland and Hungary completed an online discrete-choice experiment survey. In each of 9 choice questions, respondents indicated whether they preferred no vaccination or one of two hypothetical vaccine profiles described in terms of 6 features. Vaccine preference parameters were estimated for working and non-working mothers using a random-parameter logit model and were used to calculate the relative importance of changes in vaccine features. Results350 mothers in Poland and 350 mothers in Hungary were surveyed. Of the attributes evaluated, changes in vaccine cost were most important in both countries, followed by changes in severity of illness prevented, vaccine effectiveness, mode of administration, duration of illness prevented, and number of doses. Mothers in both countries had a strong preference for vaccination versus no vaccination, which was more pronounced among working mothers. In Poland, working mothers placed less weight on effectiveness, illness severity, and cost than non-working mothers and were more likely to rate disruptions in work, child care, and routines as important reasons to vaccinate. In Hungary, working mothers were statistically significantly less likely to opt out of vaccination than non-working mothers. Preference for vaccination itself, relative to improving vaccine effectiveness (from 50% to 90% effective), was 7 times greater among working than among non-working mothers in Poland but was not considerably different between working and non-working mothers in Hungary. ConclusionsPolish and Hungarian working mothers are more likely to vaccinate children against diarrheal illness than non-working mothers.

Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial.

BackgroundDelayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT).MethodsThis randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time.FindingsBetween September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] −60 to −8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm.ConclusionsIn this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling.Trial registrationThis trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897.

Characteristics and Outcome of Cancer Patients Admitted to the ICU in England, Wales, and Northern Ireland and National Trends Between 1997 and 2013.

To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. Retrospective analysis. Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. None. In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for gastrointestinal (odds ratio, 1.12), respiratory (odds ratio, 1.48) or neurological (odds ratio, 1.65) reasons, and previous ICU admission (odds ratio, 1.18). In patients with a hematological malignancy admitted between 2009 and 2013, hospital mortality was 53.6%. Independent risk factors for hospital mortality were age (odds ratio, 1.02), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.90), Intensive Care National Audit & Research Centre Physiology Score (odds ratio, 1.12), admission for hematological (odds ratio, 1.48) or respiratory (odds ratio, 1.56) reasons, bone marrow transplant (odds ratio, 1.53), previous ICU admission (odds ratio, 1.43), and mechanical ventilation within 24 hours of admission (odds ratio, 1.33). Trend analysis showed a significant decrease in ICU and hospital mortality and length of stay between 1997 and 2013 despite little change in severity of illness during this time. Between 1997 and 2013, the outcome of cancer patients with an unplanned admission to ICU improved significantly. Among those admitted between 2009 and 2013, independent risk factors for hospital mortality were age, severity of illness, previous cardiopulmonary resuscitation, previous ICU admission, metastatic disease, and admission for respiratory reasons.

Real-world paliperidone palmitate data from acute units: The SHADOW study

IntroductionThere is an increasing interest in understanding how antipsychotic treatments work in a real-world-setting. This is especially important with long-acting-antipsychotics, where explanatory trials may not always represent the real-world-population. Observational studies and pragmatic-clinical trials could provide additional information about new therapies, which could inform decision-making processes.ObjectivesTo assess the effectiveness of Paliperidone-Palmitate(PP) in an acute setting within real-world-conditions. Functionality, satisfaction with treatment and pattern of use were also evaluated.MethodsAn observational, prospective 6-week follow-up study was performed in acute units including adult patients with acute exacerbation of schizophrenia that started treatment with PP. Data were collected from initiation of PP until week-6 (or patient's discharge if earlier). Clinical-Global Inventory-Severity (CGI-S) was used to assess effectiveness as well as changes in illness severity. Other outcomes included total score on the Personal and Social Performance scale (PSP), patient-satisfaction with medication (MSQ) and tolerability. Student's-t tests were used to assess changes from baseline in CGI-S and PSP.ResultsTwo hundred and eighty patients were included in the analysis (mean age: 40.5 ± 12.2 [SD] years). A significant decrease in mean (SD) CGI-S score between baseline (4.7 [0.9]) and endpoint (3.3 [0.9]) (P &lt; 0.0001) was observed. (Note that 21% of patients were discharged on PP-monotherapy). Patient-functioning also significantly improved from baseline to endpoint (P &lt; 0.0001). Seventy-four percent of patients were satisfied (measured by MSQ) at the end of follow-up. Anticholinergic-treatment was less frequent for PP discharged on monotherapy vs. not monotherapy (12.5% vs 21.2% respectively). Overall, PP was well-tolerated. Twenty-five AEs were reported in 20 patients (incidence 7.1%). No serious AEs occurred.ConclusionsThese results support the effectiveness and tolerability of PP in an acute setting under daily-clinical-practice with good acceptance by patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Learning (predictive) risk scores in the presence of censoring due to interventions

A large and diverse set of measurements are regularly collected during a patient's hospital stay to monitor their health status. Tools for integrating these measurements into severity scores, that accurately track changes in illness severity, can improve clinicians' ability to provide timely interventions. Existing approaches for creating such scores either (1) rely on experts to fully specify the severity score, (2) infer a score using detailed models of disease progression, or (3) train a predictive score, using supervised learning, by regressing against a surrogate marker of severity such as the presence of downstream adverse events. The first approach does not extend to diseases where an accurate score cannot be elicited from experts. The second assumes that the progression of disease can be accurately modeled, limiting its application to populations with simple, well-understood disease dynamics. The third approach, also most commonly used, often produces scores that suffer from bias due to treatment-related censoring (Paxton et al. in AMIA annual symposium proceedings, American Medical Informatics Association, p 1109, 2013). Specifically, since the downstream outcomes used for their training are observed only noisily and are influenced by treatment administration patterns, these scores do not generalize well when treatment administration patterns change. We propose a novel ranking based framework for disease severity score learning (DSSL). DSSL exploits the following key observation: while it is challenging for experts to quantify the disease severity at any given time, it is often easy to compare the disease severity at two different times. Extending existing ranking algorithms, DSSL learns a function that maps a vector of patient's measurements to a scalar severity score subject to two constraints. First, the resulting score should be consistent with the expert's ranking of the disease severity state. Second, changes in score between consecutive periods should be smooth. We apply DSSL to the problem of learning a sepsis severity score using a large, real-world electronic health record dataset. The learned scores significantly outperform state-of-the-art clinical scores in ranking patient states by severity and in early detection of downstream adverse events. We also show that the learned disease severity trajectories are consistent with clinical expectations of disease evolution. Further, we simulate datasets containing different treatment administration patterns and show that DSSL shows better generalization performance to changes in treatment patterns compared to the above approaches.

Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients With Sepsis*

To assess the timing of appropriate antibiotic therapy as a determinant of postinfection hospital and ICU lengths of stay in patients with sepsis. Single-center retrospective cohort study (January 2008-December 2012). One thousand two hundred fifty-bed academic hospital. One thousand fifty-eight consecutive blood culture positive patients. We retrospectively identified adult patients with severe sepsis or septic shock. Timing of appropriate antibiotic therapy was determined from blood culture collection time to the administration of the first dose of antibiotic therapy with documented in vitro susceptibility against the identified pathogen. We constructed generalized linear models to examine the determinants of attributable lengths of stay. The median (interquartile range) time from blood culture collection to the administration of appropriate antibiotic therapy was 6.7 hours (0.0-23.3 hr). Linear regression analysis adjusting for severity of illness and comorbid conditions identified time to appropriate antibiotic therapy to be an independent determinant of postinfection ICU length of stay (0.095-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.057-0.132 d; p < 0.001) and postinfection hospital length of stay (0.134-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.074-0.194 d; p < 0.001). Other independent determinants associated with increasing ICU length of stay and hospital length of stay were mechanical ventilation (both ICU and hospital lengths of stay) and incremental peak WBC counts (hospital length of stay only). Incremental changes in severity of illness assessed by Acute Physiology and Chronic Health Evaluation II scores and comorbidity burden assessed by the Charlson comorbidity score were independently associated with decreases in ICU length of stay and hospital length of stay. We identified time to appropriate antibiotic therapy in patients with sepsis to be an independent determinant of postinfection ICU and hospital lengths of stay. Clinicians should implement local strategies aimed at timely delivery of appropriate antibiotic therapy to improve outcomes and reduce length of stay.

Using endophenotypes to examine molecules related to candidate genes as novel therapeutics: The “endophenotype-associated surrogate endpoint (EASE)” concept

In this article, a new concept of an “endophenotype-associated surrogate endpoint (EASE)” is proposed. To examine effect of a novel therapeutic molecule on a target phenotype of a genotype associated with the molecule, state-dependent aspect of an endophenotype can be used as a surrogate endpoint. Desired characteristics for EASE are (1) a close relationship to the endophenotype associated with therapeutics, (2) longitudinal changes in illness severity, while the original “endophenotype” is primarily state independent, (3) a physical sign or laboratory measurement that occurs in association with a pathological process and has putative diagnostic and/or prognostic utility, and (4) serves as a substitute for a clinically meaningful endpoint. Advantages are expected for both surrogate endpoints in drug development and endophenotypes in uncovering pathogenesis. EASE are closer to molecules than clinically meaningful endpoints and can respond to administration of the molecule in a more direct manner. Therefore, a statistically significant effect is likely to be observed in clinical trials with smaller sample sizes and shorter durations. As with endophenotypes, reduced heterogeneity might be expected especially in heterogeneous syndromes such as psychiatric disorders. Potential interactions (e.g., elucidating biological mechanisms underlying novel treatments) can be further expected.

Treatment of complicated grief in elderly persons: a randomized clinical trial.

Complicated grief (CG) is a debilitating condition, most prevalent in elderly persons. However, to our knowledge, no full-scale randomized clinical trial has studied CG in this population. To determine whether complicated grief treatment (CGT) produces greater improvement in CG and depressive symptoms than grief-focused interpersonal psychotherapy (IPT). Randomized clinical trial enrolling 151 individuals 50 years or older (mean [SD] age, 66.1 [8.9] years) scoring at least 30 on the Inventory of Complicated Grief (ICG). Participants were recruited from the New York metropolitan area from August 20, 2008, through January 7, 2013, and randomized to receive CGT or IPT. The main outcome was assessed at 20 weeks after baseline, with interim measures collected at 8, 12, and 16 weeks after baseline. Sixteen sessions of CGT (n = 74) or IPT (n = 77) delivered approximately weekly. Rate of treatment response, defined as a rating from an independent evaluator of much or very much improved on the Improvement subscale of the Clinical Global Impression Scale. Both treatments produced improvement in CG symptoms. Response rate for CGT (52 individuals [70.5%]) was more than twice that for IPT (24 [32.0%]) (relative risk, 2.20 [95% CI, 1.51-3.22]; P < .001), with the number needed to treat at 2.56. Secondary analyses of CG severity and CG symptom and impairment questionnaire measures confirmed that CGT conferred a significantly greater change in illness severity (22 individuals [35.2%] in the CGT group vs 41 [64.1%] in the IPT group were still at least moderately ill [P = .001]), rate of CG symptom reduction (1.05 ICG points per week for CGT vs 0.75 points per week for IPT [t633 = 3.85; P < .001]), and the rate of improvement in CG impairment (0.63 work and Social Adjustment Scale points per week with CGT and 0.39 points per week with IPT [t503 = 2.87; P = .004]). Results were not moderated by participant age. Complicated grief treatment produced clinically and statistically significantly greater response rates for CG symptoms than a proven efficacious treatment for depression (IPT). Results strongly support the need for physicians and other health care providers to distinguish CG from depression. Given the growing elderly population, the high prevalence of bereavement in aging individuals, and the marked physical and psychological impact of CG, clinicians need to know how to treat CG in older adults. clinicaltrials.gov Identifier: NCT01244295.

Controlling Placebo Response in Drug Development: Lessons Learned from Psychopharmacology

Placebo response impacts the development of treatments for central nervous system disorders. Despite significant attention in scientific literature, the magnitude of placebo response continues to increase. The present work reviews empirical and theoretical literature on associations of trial design features, patient selection, and investigative site selection with signal detection and placebo response. Trials with greater percentages of patients randomized to placebo had smaller average placebo responses and larger average drug–placebo differences in comprehensive meta-analyses of major depressive disorder and schizophrenia. Excluding patients with large responses during double-blind placebo lead-ins reduced placebo response and increased drug–placebo differences, but that advantage was nearly offset by the decrease in sample size. Core factor subscales of the Hamilton Rating Scale for Depression (HAMD) yielded larger drug–placebo differences than the HAMD total score. Theoretical considerations suggest that the number of sites and number of patients per site can influence power, with the optimal combination of the two being influenced by the correlation structure and therefore being situation dependent. Similar considerations apply to the number of countries and number of sites per country. Sequential parallel comparison and randomized withdrawal designs hold promise for improved signal detection. Patient selection and assessment of changes in illness severity may benefit from remote and independent evaluation as well as patient self-reports. Given the complexities of signal detection and placebo response, no single strategy will solve all the problems and combinations of approaches may be most useful.

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Introduction: Because hospital mortality rates of sepsis are widely reported, individual ICUs are tasked to reduce the mortality rate of patients with sepsis. However, factors outside the control of intensivists may undermine efforts to achieve mortality reductions. Methods: This is a retrospective single-center observational study in an academic MICU from January 2010 to June 2012 during refinement of sepsis bundles. We examined outcomes of MICU patients with ICD-9 codes for severe sepsis/septic shock and ICD-9 codes for infection and acute organ failure. Results: Per 6-month block, over the 30 months of the study, the number of cases of sepsis increased by 35% (327 to 469) and cases of infection with organ failure increased 28% (390 to 498). Mean age, gender and the likelihood of undergoing mechanical ventilation for both groups was unchanged. For patients coded with sepsis, mean ICU and hospital LOS decreased from 6.1 to 4.6 days (p<0.01) and 13.2 to 11.1 days (p< 0.01) respectively. For patients coded for infection and organ failure, ICU and hospital LOS decreased from 4.5 to 4 days (p<0.01) and 13.5 to 11.8 days (p<0.01). Mortality rates for sepsis decreased non-significantly from 37% to 31.6% (p 0.1) and for sepsis and organ failure from 14.9% to 11.3% (p 0.6). The observed to expected mortality ratio (O/E) decreased for sepsis (1.58 to 1.29) and for infection with organ failure (1.44 to 0.85). Conclusions: Because of relatively small numbers of sepsis cases seen in a single ICU, coding variability and changes in severity of illness, unadjusted mortality is an inadequate sole measurement of the clinical improvement achieved from adherence to sepsis bundles. While crude mortality rates did not statistically change, we found significant decreases in ICU and hospital LOS and substantial decreases in the O/E mortality for cases of sepsis and infection with organ failure. We confirmed previous findings that reliance on ICD-9 codes for sepsis may underestimate the true incidence of sepsis in the ICU.