Detection of delirium in older patients-A point prevalence study in surgical and non-surgical hospital wards.

AIMS AND OBJECTIVES: To (i) determine the prevalence of delirium and identify delirium subtypes in surgical and non-surgical patients aged ≥65 years, (ii) determine whether certain precipitating factors affect the prevalence of delirium and (iii) review patients' medical records for description of delirium symptoms and the presence of International Classification of Diseases (ICD-10) coding for delirium in discharge summaries. METHODOLOGICAL DESIGN AND JUSTIFICATIONS: Despite being a robust predictor of morbidity and mortality in older adults, delirium might be inadequately recognised and under-reported in patients' medical records and discharge summaries. A point prevalence study (24-h) of patients ≥65 years from surgical and non-surgical wards was therefore conducted in a tertiary university hospital. ETHICAL ISSUES AND APPROVAL: The study was approved by the Data Protection Officer at the university hospital (2018/3454). RESEARCH METHODS, INSTRUMENTS AND/OR INTERVENTIONS: Patients were assessed for delirium with 4AT and delirium subtypes with the Delirium Motor Subtype Scale. Information about room transfers, need and use of sensory aids and medical equipment was collected onsite. Patients' medical records were reviewed for description of delirium symptoms and of ICD-10 codes. RESULTS: Overall, 123 patients were screened (52% female). Delirium was identified in 27% of them. Prevalence was associated with advanced age (≥85 years). The uncharacterised delirium subtype was most common (36%), followed by hypoactive (30%), hyperactive (24%) and mixed (9%). There were significant associations between positive screening tests and the need and use of sensory aids. Delirium symptoms were described in 58% of the patients who tested positive for delirium and the ICD-10 code for delirium was registered in 12% of these patients' discharge summaries. CONCLUSIONS: The high prevalence of delirium and limited use of discharge codes highlight the need to improve the identification of delirium in hospital settings and at discharge. Increased awareness and detection of delirium in hospital settings are vital to improve patient care.

Renegotiating identity. A Nordic study of adolescent's experiences of living with a parent having heart disease.

AIM: To explore adolescents' experiences of having a parent with heart disease. DESIGN: This qualitative study was performed with semi-structured individual interviews. METHODS: Interviews were conducted with 33 adolescents between 13 and 19 years old, who either had a mother or father with one of these diagnoses: ischemic heart disease, arrhythmia, heart failure, cardiac arrest or heart valve disease. The parent had been ill for at least 6 months and up to 5 years. The study was carried out in Denmark, Norway and Sweden between 2019 and 2022. The analysis was inspired by Reflexive Methodology. RESULTS: Three central themes emerged: Response to parental heart disease; Growing up ahead of time; and Strategies in a changed life situation. For the adolescents, heart disease was experienced as an acute and lethal disease that put their parents' lives in danger. New routines and roles not only changed everyday life within the family but they also enhanced maturity and appreciation of life. To maintain a balance in life, the adolescents pursued normality and sought a safe space to have a normal youthful life. CONCLUSION: In a period known to be significant for development, life with parental heart disease appeared as a biographical disruption because adolescents renegotiated their identity to manage their new life situation. IMPACT: It is important to help younger family members adapt to parental heart disease by informing them about possible reactions and supporting them in how to adapt to their new life by seeking breaks and normality. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Genetic Characterization of Myoid Hamartoma of the Breast.

BACKGROUND/AIM: Myoid hamartoma of the breast is a very rare benign lesion of which only a few cases have been reported. The pathogenesis is unknown and nothing is known about its genetic constitution. We report here the genetic characterization of a myoid hamartoma of the breast. MATERIALS AND METHODS: Cytogenetic, fluorescence in situ hybridization (FISH), RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing analyses were performed on a myoid hamartoma of the breast. RESULTS: G-Banding analysis of short-term cultured tumor cells yielded the karyotype 46,XX,t(5;12)(p13;q14)[6]/46,XX[4]. FISH showed rearrangement of the high mobility group AT-hook 2 (HMGA2) gene. RNA sequencing detected fusion of HMGA2 (12q14) with a sequence from 5p13. RT-PCR together with Sanger sequencing verified the HMGA2-fusion transcript. CONCLUSION: Myoid hamartoma of the breast may be pathogenetically related to benign connective tissue tumors with HMGA2 rearrangements, such as pulmonary hamartomas, lipomas, myolipomas, and leiomyomas.

Cytogenetics of Spindle Cell/Pleomorphic Lipomas: Karyotyping and FISH Analysis of 31 Tumors.

BACKGROUND: Spindle cell/pleomorphic lipomas are benign tumors. Here, we present our cytogenetic data on 31 such tumors. MATERIALS AND METHODS: G-banding chromosome analysis and (in selected cases) fluorescence in situ hybridization (FISH) using probes for FOXO1, RB1, and HMGA2 were performed. RESULTS: Rearrangements of chromosome 13 were found in 58% of tumors. Chromosomes 6, 1, 12, and 11 were also involved in 42%, 26%, 26%, and 23% of tumors, respectively. FISH analysis showed heterozygous deletion of RB1 in seven samples with chromosome 13 aberrations. In four of them, FOXO1 was also deleted. In two tumors with 12q15 rearrangements, FISH confirmed that HMGA2 was targeted. CONCLUSION: Structural rearrangements of 13q or losses of an entire chromosome 13 are the most common cytogenetic aberrations in spindle cell/pleomorphic lipomas. However, cytogenetic variation exists similarly to what is found in other lipomas, suggesting that various pathways may be responsible for tumorigenesis.

PAN3-PSMA2 fusion resulting from a novel t(7;13)(p14;q12) chromosome translocation in a myelodysplastic syndrome that evolved into acute myeloid leukemia.

BACKGROUND: Acquired primary chromosomal changes in cancer are sometimes found as sole karyotypic abnormalities. They are specifically associated with particular types of neoplasia, essential in establishing the neoplasm, and they often lead to the generation of chimeric genes of pathogenetic, diagnostic, and prognostic importance. Thus, the report of new primary cancer-specific chromosomal aberrations is not only of scientific but also potentially of clinical interest, as is the detection of their gene-level consequences. CASE PRESENTATION: RNA-sequencing was performed on a bone marrow sample from a patient with myelodysplastic syndrome (MDS). The karyotype was 46,XX,t(7;13)(p14;q12)[2]/46,XX[23]. The MDS later evolved into acute myeloid leukemia (AML) at which point the bone marrow cells also contained additional, secondary aberrations. The 7;13-translocation resulted in fusion of the gene PAN3 from 13q12 with PSMA2 from 7p14 to generate an out-of-frame PAN3-PSMA2 fusion transcript whose presence was verified by RT-PCR together with Sanger sequencing. Interphase fluorescence in situ hybridization analysis confirmed the existence of the chimeric gene. CONCLUSIONS: The novel t(7;13)(p14;q12)/PAN3-PSMA2 in the neoplastic bone marrow cells could affect two key protein complex: (a) the PAN2/PAN3 complex (PAN3 rearrangement) which is responsible for deadenylation, the process of removing the poly(A) tail from RNA, and (b) the proteasome (PSMA2 rearrangement) which is responsible for degradation of intracellular proteins. The patient showed a favorable response to decitabine after treatment with 5-azacitidine and conventional intensive chemotherapy had failed. Whether this might represent a consistent feature of MDS/AML with this particular gene fusion, remains unknown.

Genetic heterogeneity in leiomyomas of deep soft tissue.

Leiomyoma of deep soft tissue is a rare type of benign smooth muscle tumor that mostly occurs in the retroperitoneum or abdominal cavity of women, and about which very little genetic information exists. In the present study, eight leiomyomas of deep soft tissue were genetically analyzed. G-banding showed that three tumors carried rearrangements of the long arm of chromosome 12, three others had 8q rearrangements, the 7th tumor had deletion of the long arm of chromosome 7, del(7)(q22), and the 8th had aberrations of chromosome bands 3q21~23 and 11q21~22. The target genes of the 12q and 8q aberrations were HMGA2 and PLAG1, respectively. In the leiomyomas with 12q rearrangements, both HMGA2 and PLAG1 were expressed whereas in the tumors with 8q aberrations, only PLAG1 was expressed. In the cases without 12q or 8q aberrations, the expression of HMGA2 was very low and PLAG1 was expressed only in the case with del(7)(q22). All eight leiomyomas of deep soft tissue expressed MED12 but none of them had mutation in exon 2 of that gene. In two tumors with 12q rearrangements, RPSAP52 on 12q14.3 was fused with non-coding RNA (accession number XR_944195) from 14q32.2 or ZFP36L1 from14q24.1. In a tumor with inv(12), exon 3 of HMGA2 was fused to a sequence in intron 1 of the CRADD gene from 12q22. The present data together with those of our two previous studies in which the fusions KAT6B-KANSL1 and EWSR1-PBX3 were described in two retroperitoneal leiomyomas carrying a t(10;17)(q22;q21) and a t(9;22)(q33;q12) translocation, respectively, show that leiomyomas of deep soft tissue are genetically heterogenous but have marked similarities to uterine leiomyomas.

Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma.

BACKGROUND: Pseudoangiomatous pleomorphic/spindle cell lipoma is a rare subtype of pleomorphic/spindle cell lipoma. Only approximately 20 such tumors have been described. Genetic information on pseudoangiomatous pleomorphic/spindle cell lipoma is restricted to a single case in which deletion of the forkhead box O1 (FOXO1) gene was found, using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: G-banding and FISH analyses were performed on a pseudoangiomatous pleomorphic/spindle cell lipoma. RESULTS: G-banding of tumor cells showed complex karyotypic changes including loss of chromosome 13. FISH analysis revealed that the deleted region contained the RB1 gene (13q14.2) and the part of chromosome arm 13q (q14.2-q14.3) in which spans the TRIM13 gene, the two non-coding RNA genes, DLEU1 and DLEU2, and the genetic markers RH44686 and D13S25. CONCLUSION: Several acquired genomic aberrations were found in the tumor. Among them was loss of chromosome 13 material. Results confirm the (cyto)genetic similarity between pseudoangiomatous pleomorphic/spindle cell lipoma and spindle cell lipomas.

Novel fusion genes and chimeric transcripts in ependymal tumors.

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.

Lost in translation: a case-study of the travel of lean thinking in a hospital.

BACKGROUND: Lean thinking as a quality improvement approach is introduced in hospitals worldwide, although evidence for its impact is scarce. Lean initiatives are social, complex and context-dependent. This calls for a shift from cause-effect to conditional attributions to understand how lean works. In this study, we bring attention to the transformative power of local translation, which creates different versions of lean in different contexts, and thereby affect the evidence for lean as well as the success of lean initiatives within and among hospitals. METHODS: We explored the travel of lean within a hospital in Norway by identifying local actors' perceptions of lean through their images of enablers for successful interventions. These attributions describe the characteristics of lean in use, i.e. the prevailing version of lean. Local actors' perceptions of enablers for lean interventions were collected through focus group interviews with three groups of stakeholders: managers, internal consultants and staff. A questionnaire was used to reveal the enablers relative importance. RESULTS: The enablers known from the literature were retrieved at the case hospital. The only exception was that external expert change agents were not believed to promote lean. In addition, the stakeholders added a number of new and supplementary enablers. Two-thirds of the most important enablers for success were novel, local ones. Among these were a problem, not method focus, a bottom-up approach, the need of internal consultants, credibility, realism and patience. The local actors told different stories about local enablers and had different images of lean depending on their hierarchical level. DISCUSSION: By comparing and analyzing the findings from the literature review, the focus groups and the survey, we deduced that the travel of lean within the hospital was affected by three principles of translation: the practical, the pragmatic, and the sceptical. Further, three logics of translation were in play: translation as a funnel, a conscious sell-in, and a wash-out. This resulted in various local versions of lean. CONCLUSIONS: We conclude that lean, introduced by the management, communicated by the internal consultants, and used by the staff, is transformed more than once within the hospital. Translation is part of the explanation for the lack of evidence for lean, and translation can be decisive for outcomes.

HMGA2 expression pattern and TERT mutations in tumors of the vulva.

Malignant tumors of the vulva account for only 5% of cancers of the female genital tract in the USA. The most frequent cancers of the vulva are squamous cell carcinoma (SCC) and malignant melanoma (MM). Little is known about the genetic aberrations carried by these tumors. We report a detailed study of 25 vulva tumors [22 SCC, 2 MM, 1 atypical squamous cell hyperplasia (AH)] analyzed for expression of the high-mobility group AT-hook family member genes HMGA2 and HMGA1, for mutations in the IDH1, IDH2 and TERT genes, and for methylation of the MGMT promoter. The RT-PCR and immunohistochemistry analyses showed that HMGA2 was expressed in the great majority of analyzed samples (20 out of 24; SCC as well as MM) but not in the normal controls. HMGA1, on the other hand, was expressed in both tumors and normal tissues. Five of the 24 tumors (all SCC) showed the C228T mutation in the TERT promoter. Our results showed that HMGA2 and TERT may be of importance in the genesis and/or the progression of tumors of the vulva.

Factors influencing the quality of postoperative epidural analgesia: an observational multicenter study.

BACKGROUND: Epidural analgesia (EDA) is used widely for postoperative pain treatment. However, studies have reported a failure rate of EDA of up to 30%. We aimed to evaluate the quality of postoperative EDA in patients undergoing a laparotomy in five Norwegian hospitals. METHODS: This was a multicenter observational study in patients undergoing a laparotomy with epidural-based postoperative analgesia. Data were registered at three time points. Technical aspects, infusion rates, pain intensity, assessment procedures, side effects, and satisfaction of patients and health personnel were recorded. The use of other pain medications and coanalgesics was registered. RESULTS: Three hundred and seventeen patients were included. Pain control at rest was satisfactory in 89% of patients at 24 hours and in 91% at 48 hours. Pain control when coughing was satisfactory in 62% at 24 hours and in 59% at 48 hours. The spread of hypoesthesia was consistent for each individual patient but varied between patients. The hypoesthetic area was not associated with pain intensity, and the precision of the EDA insertion point was not associated with the pain score. Few side effects were reported. EDA was regarded as effective and functioning well by 64% of health personnel. CONCLUSION: EDA was an effective method for postoperative pain relief at rest but did not give sufficient pain relief during mobilization. The use of cold stimulation to assess the spread of EDA had limited value as a clinical indicator of the efficacy of postoperative pain control. Validated tools for the control of EDA quality are needed.

Lean thinking in hospitals: is there a cure for the absence of evidence? A systematic review of reviews.

OBJECTIVE: Lean interventions aim to improve quality of healthcare by reducing waste and facilitate flow in work processes. There is conflicting evidence on the outcomes of lean thinking, with quantitative and qualitative studies often contradicting each other. We suggest that reviewing the literature within the approach of a new contextual framework can deepen our understanding of lean as a quality-improvement method. This article theorises the concept of context by establishing a two-dimensional conceptual framework acknowledging lean as complex social interventions, deployed in different organisational dimensions and domains. The specific aim of the study was to identify factors facilitating intended outcomes from lean interventions, and to understand when and how different facilitators contribute. DESIGN: A two-dimensional conceptual framework was developed by combining Shortell's Dimensions of capability with Walshes' Domains of an intervention. We then conducted a systematic review of lean review articles concerning hospitals, published in the period 2000-2012. The identified lean facilitators were categorised according to the intervention domains and dimensions of capability provided by the framework. RESULTS: We provide a framework emphasising context by relating facilitators to domains and dimensions of capability. 23 factors enabling a successful lean intervention in hospitals were identified in the systematic review, where management and a supportive culture, training, accurate data, physicians and team involvement were most frequent. CONCLUSIONS: In the absence of evidence, the two-dimensional framework, incorporating the context, may prove useful for future research on variation in outcomes from lean interventions. Findings from the review suggest that characteristics and local application of lean, in addition to strategic and cultural capability, should be given further attention in healthcare quality improvement.

Merging of three hospitals into one university hospital.

BACKGROUND: The merging of hospitals into health enterprises ensued from the Norwegian hospital reform of 2002. A complex restructuring process lasting from 2007 to 2009 resulted in the merger of three hospitals into the University Hospital of North Norway. MATERIAL AND METHOD: Clinical activities were reorganised into fewer and larger units (divisions) and changed from in-patient to day treatment. Leadership was established across geographic units, and a programme for improving patient care pathways was launched. The experience gained is described by means of activity data from January 2006 to April 2011. RESULTS: The number of patient contacts in the somatic sector was temporarily reduced by 7 % in 2009. The mean waiting period increased from 80 days in 2006 to 108 days in 2010, but fell to 85 days in 2011. In psychiatry and specialised cross-disciplinary addiction therapy, the number of patient contacts increased, and waits were unchanged or shortened. National quality indicators showed unchanged or improved results. The number of scientific publications increased by 62 %. Productivity (DRG points per employee-month) increased from 0.73 to 0.79. The annual financial outcome was improved by NOK 537 million (12 % of the 2006 budget). 81 % of the employees were satisfied with their jobs after the restructuring. INTERPRETATION: We maintained activity and the quality of patient treatment at a high level through the change period, and the hospital's financial position has improved. The methods used do not allow conclusions on possible causal relationships between the change process and the results achieved in core activities.

Genomic aberrations in borderline ovarian tumors.

BACKGROUND: According to the scientific literature, less than 30 borderline ovarian tumors have been karyotyped and less than 100 analyzed for genomic imbalances by CGH. METHODS: We report a series of borderline ovarian tumors (n = 23) analyzed by G-banding and karyotyping as well as high resolution CGH; in addition, the tumors were analyzed for microsatellite stability status and by FISH for possible 6q deletion. RESULTS: All informative tumors were microsatellite stable and none had a deletion in 6q27. All cases with an abnormal karyotype had simple chromosomal aberrations with +7 and +12 as the most common. In three tumors with single structural rearrangements, a common breakpoint in 3q13 was detected. The major copy number changes detected in the borderline tumors were gains from chromosome arms 2q, 6q, 8q, 9p, and 13q and losses from 1p, 12q, 14q, 15q, 16p, 17p, 17q, 19p, 19q, and 22q. The series included five pairs of bilateral tumors and, in two of these pairs, informative data were obtained as to their clonal relationship. In both pairs, similarities were found between the tumors from the right and left side, strongly indicating that bilaterality had occurred via a metastatic process. The bilateral tumors as a group showed more aberrations than did the unilateral ones, consistent with the view that bilaterality is a sign of more advanced disease. CONCLUSION: Because some of the imbalances found in borderline ovarian tumors seem to be similar to imbalances already known from the more extensively studied overt ovarian carcinomas, we speculate that the subset of borderline tumors with detectable imbalances or karyotypic aberrations may contain a smaller subset of tumors with a tendency to develop a more malignant phenotype. The group of borderline tumors with no imbalances would, in this line of thinking, have less or no propensity for clonal evolution and development to full-blown carcinomas.

t(3;21)(q22;q22) leading to truncation of the RYK gene in atypical chronic myeloid leukemia.

The analysis of a small number of patients with atypical chronic myeloid leukemia showing balanced chromosomal translocations has revealed diverse tyrosine kinase fusion genes, most commonly involving FGFR1, PDGFRA, PDGFRB, JAK2, and ABL. We present a case of aCML with a 3q22;21q22-translocation that led to truncation of the receptor-like tyrosine kinase (RYK) gene and its juxtaposition with sequences from chromosome 21 including the ATP5O gene coding for a mitochondrial ATP synthase. The resulting fusion was not in frame, however, which is why we speculate that an abrogated RYK gene product rather than a chimeric protein might be the leukemogenic result.