Many Intensive Care (ICU) survivors experience long lasting impairments in physical and psychological health as well as social functioning. The objective of our study was to evaluate these effects up ...to 10 years after ICU discharge. We performed a long-term prospective cohort study in patients admitted for longer than 48 h in a medical-surgical ICU. We evaluated health-related quality of life (HRQOL) before ICU admission using the Short-form-36 (SF-36), at ICU discharge, at hospital discharge and at 1, 2, 5 and 10 years follow up (all by patients). Changes in HRQOL were assessed based on linear mixed modeling. We included a total of 749 patients (from 2000 to 2008). During 10 years 475 (63.4%) patients had died, 125 (16.7%) patients were lost to follow up and 149 (19.9%) patients could be evaluated. The mean scores of four HRQOL dimensions (i.e., physical functioning (p < 0.001; mean 54, SD 32, effect size 0.77, 95% CI 0.54-1.0), role-physical (p < 0.001; mean 44, SD 47, effect size 0.65, 95% CI 0.41-0.68 general health (p < 0.001; mean 52, SD 27, effect size 0.48; 95% CI 0.25-0.71) and social functioning (p < 0.001; mean 72, SD 32, effect size 0.41, 95% CI 0.19-0.64) were still lower 10 years after ICU discharge compared with pre-admission levels (n = 149) and with an age reference population. Almost all SF-36 dimensions changed significantly over time from ICU discharge up to 10 years after ICU discharge. Over the 10 year follow up physical functioning of medical-surgical ICU survivors remains impaired compared with their pre-admission values and an age reference population. However, effect sizes showed no significant differences suggesting that surviving patients largely regained their age-specific HRQOL at 10 years.
Purpose
Delirium during intensive care unit (ICU) stay may be related to premorbid mental illness. In addition, delirium during ICU stay may also negatively affect long-term health-related quality of ...life. The aim of our study was to investigate if delirium in the ICU is related to premorbid mental quality of life and affects long-term mental quality of life after ICU stay.
Methods
We performed a prospective cohort study in 1021 patients admitted for longer than 48 h in a medical-surgical ICU. We evaluated mental and physical quality of life using the Short-form-12 before ICU admission, at hospital discharge, and 3, 6 and 12 months after hospital discharge. Mixed model and logistic regression models were used to analyze the data.
Results
Patients who experienced a delirium during ICU stay reported a worse pre-admission mental quality of life than those without delirium (
p
< 0.001). Furthermore, patients who suffered from delirium during their ICU stay exhibited a significant decrease in mental quality of life over time relative to patients without delirium (
p
= 0.035).
Conclusion
In this large follow-up study, we demonstrated that ICU survivors who experienced a delirium during ICU stay reported a significantly worse pre-admission mental health-related quality of life and a significant decrease in mental health-related quality of life in the year after hospital discharge compared with patients without delirium.
Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven ...early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned 1:1 using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 0·6% of 866 neonates in the procalcitonin group vs 4 0·5% of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 0·7% of 745 neonates in the procalcitonin group vs 4 0·6% of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
Severe sepsis is frequently complicated by organ failure and accompanied by high mortality. Patients surviving severe sepsis can have impaired health-related quality of life (HRQOL). The time course ...of changes in HRQOL in severe sepsis survivors after discharge from the intensive care unit (ICU) and during a general ward stay have not been studied.
We performed a long-term prospective study in a medical-surgical ICU. Patients with severe sepsis (n = 170) admitted for >48 h were included in the study. We used the Short-form 36 to evaluate the HRQOL of severe sepsis patients before ICU and hospital stay and at 3 and 6 mo after ICU discharge. Furthermore, we compared the results for ICU admission and 6 mo after ICU discharge with those of an age-matched general Dutch population.
At 6 mo after ICU discharge, 95 patients could be evaluated (eight patients were lost to follow-up, 67 died). HRQOL showed a multidimensional decline during the ICU stay and gradual improvement over the 6 mo after ICU discharge for the social functioning, vitality, role-emotional, and mental health dimensions. However, 6 mo after ICU discharge, scores for the physical functioning, role-physical, and general health dimensions were still significantly lower than preadmission values. Physical and Mental Component Scores changed significantly over time. In particular, the Mental Component Score showed a small decline at ICU discharge but recovered rapidly, and at 6 mo after ICU discharge had improved to near normal values. In addition, Short-form 36 scores were lower than those in a matched general population in six of the eight dimensions, with the exception of social functioning and bodily pain. Interestingly, the preadmission HRQOL in surviving patients was already lower in three of the eight dimensions (role-physical, mental health, and vitality) when compared with the general population.
Severe sepsis patients demonstrate a sharp decline of HRQOL during ICU stay and a gradual improvement during the 6 mo after ICU discharge. Recovery begins after ICU discharge to the general ward. Nevertheless, recovery is incomplete in the physical functioning, role-physical, and general health dimensions at 6 mo after ICU discharge compared with preadmission status.
Purpose
Severe critical illness requiring treatment in the intensive care unit (ICU) may have a serious impact on patients and their families. However, optimal follow-up periods are not defined and ...data on health-related quality of life (HRQOL) before ICU admission as well as those beyond 2 years follow-up are limited. The aim of our study was to assess the impact of ICU stay up to 5 years after ICU discharge.
Methods
We performed a long-term prospective cohort study in patients admitted for longer than 48 h in a medical-surgical ICU. The Short-Form 36 was used to evaluate HRQOL before admission (by proxy within 48 h after admission of the patient), at ICU discharge, and at 1, 2, and 5 years following ICU discharge (all by patients). Changes in HRQOL were assessed using linear mixed modeling.
Results
We included a total of 749 patients (from 2000 to 2007). At 5 years after ICU discharge 234 patients could be evaluated. After correction for natural decline in HRQOL, the mean scores of four dimensions—physical functioning (
p
< 0.001), role-physical (
p
< 0.001), general health (
p
< 0.001), and social functioning (
p
= 0.003)—were still significantly lower 5 years after ICU discharge compared with their pre-admission levels, although effect sizes were small (<0.5).
Conclusions
After correction for natural decline, the effect sizes of decreases in HRQOL were small, suggesting that patients regain their age-specific HRQOL 5 years after their ICU stay.
Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for ...malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
Pain is a common problem for critically ill patients treated in the intensive care unit (ICU) and can have serious consequences. For this reason, the appropriate recognition and treatment of pain is ...of extreme importance. However, pain assessment in critically ill patients can be challenging because these patients are often unable to self-report. To identify attitudes and practices regarding the assessment and management of pain in ICU patients unable to self-report, we surveyed all adult ICUs in the Netherlands.
A multicenter, exploratory survey was sent by mail to all adult ICUs in the Netherlands.
Eighty-four of 107 ICUs returned the questionnaire for a response rate of 79%. In patients able to self-report, 94% (n = 79; 95% confidence interval CI, 86.7%-98%) of the ICUs used a standardized pain score. Visual Analog Scale and Numerical Rating Scale were used in 57% (n = 48; 99.3% CI, 41%-72%) and 48% (n = 40; 99.3% CI, 33%-64%), respectively. Nonteaching hospitals used pain assessment tools more often than teaching hospitals (P = 0.012). In patients not able to self-report, pain assessment tools were used in 19% (n = 16) of the ICUs. In the ICUs that used behaviorally based scoring systems, the Critical Care Pain Observation Tool and Behavioral Pain Scale (BPS) were used in 6% (n = 5; 99.5% CI, 1.1%-17%) and 5% (n = 4; 99.5% CI, 0.1%-15%), respectively. Among Dutch nurses, nursing opinion was considered the gold standard assessment in 36% (n = 30; 98.8% CI, 23%-50%) of the respondents, even when a patient was able to self-report and pain scales were used. In patients unable to self-report, nurses judged themselves to be more accurate than a behavioral pain assessment tool in 98% (n = 82; 98.8% CI, 89.7%-99.9%) of the patients.
In the Netherlands, most ICUs used a standardized pain score in patients able to self-report. Nonteaching hospitals used pain assessment tools more often than teaching hospitals. In patients unable to self-report, pain is not routinely measured with a validated behavioral pain assessment tool. Almost all nurses in our survey felt that their assessment of patient pain was more accurate than behavioral pain assessment tools in patients unable to self-report. More research is needed to identify factors preventing more widespread acceptance of validated behavioral pain scores in patients unable to self-report.
The time course of changes in health-related quality of life (HRQOL) following discharge from the ICU and during a general ward stay has not been studied. We therefore studied the immediate impact of ...critical illness on HRQOL and its recovery over time.
In a prospective study, all patients admitted to the ICU for > 48 h who ultimately survived to follow-up at 6 months were included. The Medical Outcomes Study 36-item short form was used to measure HRQOL before ICU admission, at discharge from the ICU and hospital, and at 3 and 6 months following discharge from the ICU and hospital. An age-matched healthy Dutch population was used as a reference.
Of the 451 included patients, 252 could be evaluated at 6 months (40 were lost to follow-up, and 159 died). Pre-ICU admission HRQOL in survivors was significantly worse compared to the healthy population. Patients who died between ICU admission and long-term follow-up had significantly worse HRQOL in all dimensions already at ICU admission when compared to the long-term survivors. HRQOL decreased in all dimensions (p < 0.001) during ICU stay followed by a rapid improvement during hospital stay, gradually improving to near pre-ICU admission HRQOL at 6 months following ICU discharge. Physical functioning (PF), general health (GH), and social functioning (SF) remained significantly lower than pre-ICU admission values. Compared to the healthy Dutch population, ICU survivors had significantly lower HRQOL 6 months following ICU discharge (except for the bodily pain score).
A sharp multidimensional decline in HRQOL occurs during ICU admission where recovery already starts following ICU discharge to the general ward. Recovery is incomplete for PF, GH, and SF when compared to baseline values and the healthy population.
The purposes of the study were to provide richer context for families' quantitative assessments of the quality of ICU care, and to describe further quality areas of importance for family members.
...Free-text comments from 1077 family members of 920 patients focusing on family evaluation of ICU quality of care were analyzed using content analysis. Twenty-one Danish and Dutch ICUs participated from October 2014 to June 2015.
Four themes emerged as important to families: information, clinician skills, ICU environment, and discharge from the ICU. Families highlighted the importance of receiving information that was accessible, understandable and honest. They indicated that quality care was ensured by having clinicians who were both technically and interpersonally competent. The ICU environment and the circumstances of the transfer out of the ICU were described as contributing to quality of care. The comments identified room for improvement within all themes.
The study highlights the importance of including both technical and emotional care for patients and families and the consequent need to focus on clinicians' mastery of interpersonal skills.
•High quality ICU care includes meeting the needs of family members•Both technical and emotional care is needed.•Both aspects of care should be included in the ICU taff educational curriculum•ICU discharge plans should be discussed at an early stage•Using both qualitative and quantitative data enable a more complete picture of family experiences
Xeroderma pigmentosum patients with a defect in the nucleotide-excision repair gene XPA are characterized by, for example, a > 1,000-fold higher risk of developing sunlight-induced skin cancer. ...Nucleotide-excision repair (NER) is involved in the removal of a wide spectrum of DNA lesions. The XPA protein functions in a pre-incision step, the recognition of DNA damage. To permit the functional analysis of the XPA gene in vivo, we have generated XPA-deficient mice by gene targeting in embryonic stem cells. The XPA-/-mice appear normal, at least until the age of 13 months. XPA-/-mice are highly susceptible to ultraviolet (UV)-B-induced skin and eye tumours and to 7,12-dimethylbenzaanthracene (DMBA)-induced skin tumours. We conclude that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum.
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