To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old).
A ...retrospective cohort study of internal medicine patients visiting the emergency department between September 1st 2010 and August 31st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as ≥75th percentile of ED-LOS in the study population, which was 208 minutes.
Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3-4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16-1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0-8.8 and OR 2.3, 95% CI 1.4-3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4-4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients.
Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED-LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way.
Emergency department (ED) crowding leads to prolonged emergency department length of stay (ED-LOS) and adverse patient outcomes. No uniform definition of ED crowding exists. Several scores have been ...developed to quantify ED crowding; the best known is the Emergency Department Work Index (EDWIN). Research on the EDWIN is often applied to limited settings and conducted over a short period of time.
To explore whether the EDWIN as a measure can track occupancy at a Dutch ED over the course of one year and to identify fluctuations in ED occupancy per hour, day, and month. Secondary objective is to investigate the discriminatory value of the EDWIN in detecting crowding, as compared with the occupancy rate and prolonged ED-LOS.
A retrospective cohort study of all ED visits during the period from September 2010 to August 2011 was performed in one hospital in the Netherlands. The EDWIN incorporates the number of patients per triage level, physicians, treatment beds and admitted patients to quantify ED crowding. The EDWIN was adjusted to emergency care in the Netherlands: modified EDWIN (mEDWIN). ED crowding was defined as the 75th percentile of mEDWIN per hour, which was ≥0.28.
In total, 28,220 ED visits were included in the analysis. The median mEDWIN per hour was 0.15 (Interquartile range (IQR) 0.05-0.28); median mEDWIN per patient was 0.25 (IQR 0.15-0.39). The EDWIN was higher on Wednesday (0.16) than on other days (0.14-0.16, p<0.001), and a peak in both mEDWIN (0.30-0.33) and ED crowding (52.9-63.4%) was found between 13:00-18:00 h. A comparison of the mEDWIN with the occupancy rate revealed an area under the curve (AUC) of 0.86 (95%CI 0.85-0.87). The AUC of mEDWIN compared with a prolonged ED-LOS (≥4 hours) was 0.50 (95%CI 0.40-0.60).
The mEDWIN was applicable at a Dutch ED. The mEDWIN was able to identify fluctuations in ED occupancy. In addition, the mEDWIN had high discriminatory power for identification of a busy ED, when compared with the occupancy rate.
RAS genes are mutated in approximately 30% of all human cancers. Interestingly, there exists a strong bias in favor of mutation of only one of the three major RAS genes in tumors of different ...cellular origins. NRAS mutations occur in approximately 20% of human melanomas, whereas HRAS and KRAS mutations are rare in this disease. To define the mechanism(s) responsible for this preference in melanocytes, we compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. Although both NRAS and KRAS activate mitogen-activated protein kinase signaling, only NRAS enhances MYC activity in these cells. Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma. In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways.
Radiological examination may unexpectedly reveal an adrenal mass. Current algorithms for differentiating between benign and malignant lesions mainly rely on size and densitometry on unenhanced CT, ...which have limited specificity. We examined the diagnostic value of urinary steroid profiling by gas chromatography/mass-spectrometry (GC/MS) in differentiating between benign and malignant adrenal tumors. A retrospective study in two referral centers for patients with adrenal disease was performed. All urinary steroid profiles ordered for evaluation of an adrenal tumor between January 2000 and November 2011 were examined. Patients were diagnosed with adrenal cortical carcinoma (ACC), adrenal cortical adenoma (ACA), or other adrenal mass. Results of hormonal measurements, imaging studies, pathology reports, and clinical outcome were retrieved from medical records. The diagnostic value of individual urinary steroid metabolites was determined by receiver operating characteristics analysis. Cut-off values were compared to reference values from an age and gender-standardized population of healthy controls. Eighteen steroid metabolites were excreted in significantly higher concentrations in patients with ACC (
n
= 27) compared to patients with ACA (
n
= 107) or other adrenal conditions (
n
= 18). Tetrahydro-11-deoxycortisol (THS) at a cut-off value of 2.35 μmol/24 h differentiated ACC from other adrenal disorders with 100 % sensitivity and 99 % specificity. Elevated urinary excretion of THS was associated with a very high sensitivity and specificity to differentiate between an ACC and a benign adrenal mass. Urinary steroid profiling might be a useful diagnostic test for the evaluation of patients with an adrenal incidentaloma.
New surgical techniques and technology have simplified laparoscopic hysterectomy and have enhanced the safety of this procedure. However, the surgical colpotomy step has not been addressed. This ...study evaluates the surgical colpotomy step in laparoscopic hysterectomy with respect to difficulty and duration. Furthermore, it proposes an alternative route that may simplify this step in laparoscopic hysterectomy. A structured interview, a prospective cohort study, and a problem analysis were performed regarding experienced difficulty and duration of surgical colpotomy in laparoscopic hysterectomy. Sixteen experts in minimally invasive gynecologic surgery from 12 hospitals participated in the structured interview using a 5-point Likert scale. The colpotomy in LH received the highest scores for complexity (2.8 ± 1.2), compared to AH and VH. Colpotomy in LH was estimated as more difficult than in AH (2.8 vs 1.4,
p
< .001). In the cohort study, 107 patients undergoing LH were included. Sixteen percent of the total procedure time was spent on colpotomy (SD 7.8 %). BMI was positively correlated with colpotomy time, even after correcting for longer operation time. No relation was found between colpotomy time and blood loss or uterine weight. The surgical colpotomy step in laparoscopic hysterectomy should be simplified as this study demonstrates that it is time consuming and is considered to be more difficult than in other hysterectomy procedures. A vaginal approach to the colpotomy is proposed to achieve this simplification.
Structural and functional alterations of the brain in persons genetically at-risk for Alzheimer's disease (AD) are crucial in unravelling AD development. Filippini et al. found that the default mode ...network (DMN) is already affected in young APOE ε4-carriers, with increased co-activation of the DMN during rest and increased hippocampal task activation. We aimed to replicate the early findings of Filippini et al, using the APOE gene, still the principal AD risk gene, and extended this with a polygenic risk score (PRS) analysis for AD, using the Human Connectome Project dataset (HCP). We included participants from the HCP S1200 dataset (age range: 22-36 years). We studied morphometric features, functional DMN co-activation and functional task activation of recollection performance. Permutation Analysis of Linear Models (PALM) was used to test for group differences between APOE ε4-carriers and non-carriers, and to test the association with PRS. PALM controls for biases induced by the family structure of the HCP sample. Results were family-wise error rate corrected at p < 0.05. Our primary analysis did not replicate the early findings of Filippini et al. (2009). However, compared with non-carriers, APOE ε4-carriers showed increased functional activation during the encoding of subsequently recollected items in areas related to facial recognition (p<0.05, t>756.11). This increased functional activation was also positively associated with PRS (APOE variants included) (p<0.05, t>647.55). Our results are supportive for none to limited genetic effects on brain structure and function in young adults. Taking the methodological considerations of replication studies into account, the true effect of APOE ε4-carriership is likely smaller than indicated in the Filippini paper. However, it still holds that we may not yet be able to detect already present measurable effects decades before a clinical expression of AD. Since the mechanistic pathway of AD is likely to encompass many different factors, further research should be focused on the interactions of genetic risk, biomarkers, aging and lifestyle factors over the life course. Sensitive functional neuroimaging as used here may help disentangling these complex interactions.
The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed ...to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).
This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.
The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).
In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.
Emergency department (ED) crowding leads to prolonged emergency department length of stay (ED-LOS) and adverse patient outcomes. No uniform definition of ED crowding exists. Several scores have been ...developed to quantify ED crowding; the best known is the Emergency Department Work Index (EDWIN). Research on the EDWIN is often applied to limited settings and conducted over a short period of time. To explore whether the EDWIN as a measure can track occupancy at a Dutch ED over the course of one year and to identify fluctuations in ED occupancy per hour, day, and month. Secondary objective is to investigate the discriminatory value of the EDWIN in detecting crowding, as compared with the occupancy rate and prolonged ED-LOS. A retrospective cohort study of all ED visits during the period from September 2010 to August 2011 was performed in one hospital in the Netherlands. The EDWIN incorporates the number of patients per triage level, physicians, treatment beds and admitted patients to quantify ED crowding. The EDWIN was adjusted to emergency care in the Netherlands: modified EDWIN (mEDWIN). ED crowding was defined as the 75.sup.th percentile of mEDWIN per hour, which was greater than or equal to0.28. In total, 28,220 ED visits were included in the analysis. The median mEDWIN per hour was 0.15 (Interquartile range (IQR) 0.05-0.28); median mEDWIN per patient was 0.25 (IQR 0.15-0.39). The EDWIN was higher on Wednesday (0.16) than on other days (0.14-0.16, p0.001), and a peak in both mEDWIN (0.30-0.33) and ED crowding (52.9-63.4%) was found between 13:00-18:00 h. A comparison of the mEDWIN with the occupancy rate revealed an area under the curve (AUC) of 0.86 (95%CI 0.85-0.87). The AUC of mEDWIN compared with a prolonged ED-LOS (greater than or equal to4 hours) was 0.50 (95%CI 0.40-0.60). The mEDWIN was applicable at a Dutch ED. The mEDWIN was able to identify fluctuations in ED occupancy. In addition, the mEDWIN had high discriminatory power for identification of a busy ED, when compared with the occupancy rate.
Simultaneous multiplex mutation of large gene families using Cas9 has the potential to revolutionize agriculture and plant sciences. The targeting of multiple genomic sites at once raises concerns ...about the efficiency and specificity in targeting. The model Arabidopsis thaliana is widely used in basic plant research. Previous work has suggested that the Cas9 off-target rate in Arabidopsis is undetectable. Here we use deep sequencing on pooled plants simultaneously targeting 14 distinct genomic loci to demonstrate that multiplex targeting in Arabidopsis is highly specific to on-target sites with no detectable off-target events. In addition, chromosomal translocations are extremely rare. The high specificity of Cas9 in Arabidopsis makes this a reliable method for clean mutant generation with no need to enhance specificity or adopt alternate Cas9 variants.
OBJECTIVETo evaluate the effect of chenodeoxycholic acid treatment on disease progression in cerebrotendinous xanthomatosis (CTX).
METHODSIn this retrospective cohort study, we report the clinical ...long-term follow-up characteristics of 56 Dutch patients with CTX. Age at diagnosis was correlated with clinical characteristics and with the course of modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS) scores at follow-up.
RESULTSMedian follow-up time was 8 years (6 months–31.5 years). Patients diagnosed and treated before the age of 24 years had a significantly better outcome at follow-up. When considering only patients with a good treatment adherence (n = 43), neurologic symptoms, if present, disappeared in all patients who were diagnosed before the age of 24 and treated since. Furthermore, treatment prevented the development of new neurologic symptoms during follow-up. In contrast, 61% of the patients diagnosed and treated after the age of 24 showed deterioration of the neurologic symptoms, with parkinsonism as a treatment-resistant feature. There was an improvement or stabilization in favor of patients diagnosed and treated before the age of 24 compared to those treated after the age of 24100% vs 58% for mRS scores and 100% vs 50% for EDSS scores, respectively.
CONCLUSIONSTreatment start at an early age can reverse and even prevent the development of neurologic symptoms in CTX. This study emphasizes the importance of early diagnosis in CTX and provides a rationale to include CTX in newborn screening programs.
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