Mette Dahl Bendtsen

Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study

Essentials Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15–17 years. A TE‐associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment.

Normal Value Ranges for Central Retinal Thickness Asymmetry in Healthy Caucasian Adults Measured by SPECTRALIS SD-OCT Posterior Pole Asymmetry Analysis.

PURPOSE To determine the normal variation in central retinal thickness asymmetry in healthy Caucasian adults using the posterior pole asymmetry analysis (PPAA) of a SPECTRALIS spectral-domain optical coherence tomography (SD-OCT) device. METHODS Healthy Caucasian individuals aged between 18 and 45 years with a visual acuity of minimum 20/20 and a spherical equivalent between -1.5 and +1.5 diopters were recruited. Retinal thickness and retinal nerve fiber layer thickness (RNFL) were using measured SPECTRALIS SD-OCT. Inter- and intraocular differences in central retinal thickness were calculated using the PPAA. The association between age, sex, and interocular asymmetry was evaluated by a linear model with Gaussian correlation structure. RESULTS A total of 105 individuals, 30 men and 75 women, were studied. The mean age ± SD was 28.8 ± 7.87 years. The grand mean interocular retinal thickness asymmetry was 5.6 μm (95% confidence interval [CI]: 4.6-6.5) and the grand mean intraocular retinal thickness asymmetry was 8.3 μm (95% CI: 6.8-9.9) in the right eye and 8.4 μm (95% CI: 6.7-10.0) in the left eye. The highest local asymmetries were found in the nasal corners of macula were the posterior pole thickness map overlaps the temporal vascular arches. A slight general age and sex effect on the mean interocular retinal thickness asymmetry was found to be respectively 0.04 μm/year (95% CI: 0.02-0.06 μm) and 0.54 μm (95% CI: 0.19-0.88 μm) for men compared with women. CONCLUSIONS Statistically significant physiological asymmetries in inter- and intraocular central retinal thickness exist. This must be considered when early signs of glaucoma or other pathologies are evaluated based on the retinal thickness asymmetry. (http://www.controlled-trials.com/isrctn/ number, ISRCTN09017572.).

Early chest tube removal following cardiac surgery is associated with pleural and/or pericardial effusions requiring invasive treatment.

OBJECTIVES Different opinions exist as to when chest tube removal should be performed following cardiac surgery. The aim of this study was to compare early chest tube removal with removal of the tubes in the morning day 1 postoperatively. Primary combined end point was the risk of postoperative accumulation of fluid in the pericardial and/or pleural cavities requiring invasive treatment. METHODS A retrospective observational cohort study was performed among patients undergoing coronary artery bypass grafting (CABG) and/or conventional valve surgery between July 2010 and June 2013. Patients in whom chest tube output was <150 ml around midnight during the last 4 h were included in the study. These patients were divided into two groups: Group 1 had their chest tubes removed around midnight on the day of surgery, whereas Group 2 kept their tubes until next morning. Using Poisson regression, we estimated crude and adjusted relative risks (RRs) for developing postoperative pleural and/or pericardial effusion within 14 days requiring interventional treatment. RESULTS A total of 1232 patients underwent CABG, conventional valve or combined surgery during the study period. Of these, 782 patients fulfilled the criteria for early chest tube removal, which was performed in 385 of the patients. A total of 76 patients in Group 1 (20%) and 51 patients in Group 2 (13%) developed postoperative pleural and/or pericardial effusions requiring invasive treatment (P = 0.011). A positive association between early chest tube removal and the development of pleural and/or pericardial effusions was seen [crude RR: 1.54 (95% CI: 1.11-2.13); adjusted RR: 1.70 (95% CI: 1.24-2.33)]. The association became stronger investigating pleural effusions alone (adjusted RR = 1.77; 95% CI: 1.27-2.46), whereas the association with pericardial effusions was less clear. CONCLUSIONS Removal of all chest tubes around midnight on the day of surgery is associated with an increased risk of postoperative pleural and/or pericardial effusions requiring invasive treatment even if chest tube output during the last 4 h is <150 ml compared with removal of the tubes next morning.

Trends in diagnostic patterns and mortality in emergency ambulance service patients in 2007−2014: a population-based cohort study from the North Denmark Region

Objective Demand for ambulances is growing. Nevertheless, knowledge is limited regarding diagnoses and outcomes in patients receiving emergency ambulances. This study aims to examine time trends in diagnoses and mortality among patients transported with emergency ambulance to hospital. Design Population-based cohort study with linkage of Danish national registries. Setting The North Denmark Region in 2007–2014. Participants Cohort of 148 757 patients transported to hospital by ambulance after calling emergency services. Main outcome measures The number of emergency ambulance service patients, distribution of their age, sex, hospital diagnoses, comorbidity, and 1-day and 30-day mortality were assessed by calendar year. Poisson regression with robust variance estimation was used to estimate both age-and sex-adjusted relative risk of death and prevalence ratios for Charlson Comorbidity Index (CCI) to allow comparison by year, with 2007 as reference year. Results The annual number of emergency ambulance service patients increased from 24.3 in 2007 to 40.2 in 2014 per 1000 inhabitants. The proportions of women increased from 43.1% to 46.4% and of patients aged 60+ years from 39.9% to 48.6%, respectively. The proportion of injuries gradually declined, non-specific diagnoses increased, especially the last year. Proportion of patients with high comorbidity (CCI≥3) increased from 6.4% in 2007 to 9.4% in 2014, corresponding to an age- and sex-adjusted prevalence ratio of 1.27 (95% CI 1.16 to 1.39). The 1-day and 30 day mortality decreased from 2.40% to 1.21% and from 5.01% to 4.36%, respectively, from 2007 to 2014, corresponding to age-adjusted and sex-adjusted relative risk of 0.43 (95% CI 0.37 to 0.50) and 0.72 (95% CI 0.66 to 0.79), respectively. Conclusion During the 8-year period, the incidence of emergency ambulance service patients, the proportion of women, elderly, and non-specific diagnoses increased. The level of comorbidity increased substantially, whereas the 1-day and 30-day mortality decreased.

Changes in Weight and Body Composition Among Women With Breast Cancer During and After Adjuvant Treatment: A Prospective Follow-up Study

Background: Antineoplastic adjuvant treatment for breast cancer can cause changes in women’s weight and body composition and influence their general health and survival. Objective: The aim of this study is to investigate the extent and patterns of change in weight and body composition after current standard adjuvant antineoplastic treatment for breast cancer. Methods: Data on weight and body composition from 95 women with breast cancer Stage I to III were obtained during 18 months on a bioelectric impedance analyzer. Changes and odds ratio (OR) were calculated by a linear mixed model and logistic regression. Results: At 18 months, there was an increase in weight of 0.9 kg (95% confidence interval [CI], 0.3–1.5; P = .003) and an average positive association of 0.35 kg/cm increased waist circumference (95% CI, 0.29–0.42 kg; P < .0001). Relative weight changes ranged from −12.7% to 20.5%. Weight gains related to increased body fat were observed mainly in premenopausal women receiving chemotherapy (1.4 kg; 95% CI, 0.4–2.4; P = .007). For menopausal status, OR was 2.9 (95% CI, 1.14–7.1; P = .025), and for chemotherapy, OR was 2.6 (95% CI, 1.03–6.41; P = .043). The OR for weight loss in Stage III breast cancer was 12.5 (95% CI, 1.21–128.84; P = .034) and 4.3 (CI, 1.07–17.24; P = .40) for comorbidity. Conclusions: Results demonstrate that weight changes in a pooled sample are overestimated. However, premenopausal women receiving anthracycline-based chemotherapy show a tendency toward a body composition with increasing fat mass. Implications for Practice: A scheduled assessment of changes in weight and body composition is relevant at 18 months after treatment. To compare future studies, common measuring and cutoff points are needed.

Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin’s Lymphoma Risk and Survival

Background Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. Methods We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin’s lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included. Results We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02–0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center. Conclusions The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

Incidence of venous thromboembolism in patients with diffuse large B-cell lymphoma

Abstract Venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL) is an important complication. We aimed to asses the risk of VTE and the quality of VTE discharge diagnosis in a cohort of DLBCL patients. Objective confirmed VTE events during two years of follow-up were identified by the review of medical records of consecutive patients with DLBCL at Aalborg University Hospital from 2007 until 2013. Information on baseline disease stage, lifestyle factors, and anticoagulant therapy were registered. Cox regression was used to assess VTE risk factors. The data quality on VTE discharge diagnosis was evaluated by comparing data on VTE discharge diagnosis from the Danish National Registry of Patients with information from the medical records. Eleven percent of patients were diagnosed with VTE. Prior VTE, performance status, and Ann Arbor stage were associated with VTE. The positive predictive value of a VTE discharge diagnosis was 85% and the sensitivity 53%.

Early mobilisation of patients with community-acquired pneumonia reduce length of hospitalisation-a pilot study

[Purpose] To examine if length of stay was reduced following an early mobilisation programme in patients with community-acquired pneumonia, and secondary, if such a program influenced short-term rehospitalisation and mortality rates. [Participants and Methods] Ninety seven consecutive patients (51% men; over all mean ± SD age 71.9 ± 16.5 years) with community-acquired pneumonia were included in the intervention group, and compared with a historical control group of 97 patients, matching at case level. Early mobilisation was defined as more than 20 minutes out of bed within 24 hours of hospitalisation. [Results] Eighty out of 97 patients in the intervention group were mobilised within 24 hours and length of stay for all patients was reduced with an average of 1.5 (95%CI: −0.2; 3.2) days compared to the control group. There was no significant difference between the two groups according to 30-day rehospitalisation and mortality. [Conclusion] An early mobilisation program seem to reduce the length of stay for patients with community-acquired pneumonia, and without an increase in short-term mortality and re-hospitalisation rates.

Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia: a Danish population-based study

Stringent complete remission (sCR) of acute myeloid leukemia is defined as normal hematopoiesis after therapy. Less sCR, including non-sCR, was introduced as insufficient blood platelet, neutrophil, or erythrocyte recovery. These latter characteristics were defined retrospectively as postremission transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, <5% blasts in the postinduction bone marrow analysis). Individual patients were classified as having sCR (n = 360; 46.8%) or non-sCR (n = 409; 53.2%) based on data from our national laboratory and transfusion databases. Survival analysis revealed that patients achieving sCR had superior overall survival (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64) as well as relapse-free survival (HR, 1.25; 95% CI, 1.03-1.51) compared with those with non-sCR after adjusting for covariates. Cox regression analysis regarding the impact of the stringent criteria for blood cell recovery identified these as significant and independent variables. In conclusion, this real-life register study supports the international criteria for response evaluation on prognosis and, most importantly, documents each of the 3 lineage recovery criteria as contributing independently.

Prehospital intravenous fentanyl to patients with hip fracture: an observational cohort study of risk factors for analgesic non-treatment

BackgroundPatients with proximal femoral neck fracture have a high short-term mortality, a high risk of postoperative complications, and impaired quality of life. One of the challenges related to the prehospital treatment of these patients is to administer systemic opioids fast and properly. Effective analgesic prehospital treatment ought be initiated rapidly in order to alleviate the stress that follows acute pain, to facilitate transportation, and to improve quality of care. The objectives of this study were to explore the prevalence of prehospital administration of intravenous fentanyl to patients with proximal femoral neck fracture in the ambulances and to assess risk factors for analgesic non-treatment.MethodsThis was a register-based observational cohort study of patients with proximal femoral neck fracture from the North Denmark Region transported by ambulance. The patients were identified via the Danish Interdisciplinary Hip Fracture Registry over a 3-year period from 1 July 2011 to 30 June 2014. This hospital registry contains data on several patient characteristics used for the risk factor analysis. Data on prehospital treatment (intravenous fentanyl) and patient monitoring were registered in an electronic prehospital patient record. A modified Poisson regression with robust standard errors was carried out with intravenous fentanyl as the primary binary outcome and the following explanatory variables: age, sex, Charlson Comorbidity Index score, housing, body mass index, type of fracture, fracture displacement, prior consultation with general practitioner, dispatch triage level, and time with ambulance personnel.ResultsIn total, 2,140 patients with proximal femoral neck fracture were transported by ambulance, of which 584 (27.3%, 95% CI: 25.4-29.2) were treated with intravenous fentanyl. Risk factors for non-treatment were: older age, male sex (RR 0.77, 95% CI: 0.64-0.91), institutional housing (RR 0.72, 95% CI: 0.56-0.92), medial fracture (RR 0.74, 95% CI: 0.60-0.92), short time with ambulance personnel, Charlson Comorbidity Index score > 1, year of fracture (2011), low levels of urgency at dispatch, and if seen by general practitioners prior to transport.DiscussionEducation of ambulance personnel in assessing and treating patients with hip fracture seems to be required. Also, future studies should consider alternative or supportive pain treatment options with suitable analgesic effects and side effects.ConclusionsFew patients with proximal femoral neck fracture were treated with intravenous fentanyl, and several risk factors were associated with prehospital analgesic non-treatment. Future prospective studies should explore covariates of socioeconomic, cultural, and psychological origin to provide further insight into the multifactorial causes of non-treatment of acute pain.