The panorama of future sick-leave diagnoses among young adults initially long-term sickness absent due to neck, shoulder, or back diagnoses. An 11-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Little is known about future sick-leave diagnoses among individuals on long-term sickness absence. The aim of this study was to describe the panorama of sick-leave diagnoses over time among young adults initially sick-listed for ≥ 28 days due to back, neck, or shoulder diagnoses</p> <p>Methods</p> <p>An 11-year prospective population-based cohort study including all 213 individuals in a Swedish municipality who, in 1985, were aged 25–34 years and had a new sick-leave spell ≥ 28 days due to neck, shoulder, or back diagnoses.</p> <p>Results</p> <p>Over the 11-year period, the young adults in this cohort had 176,825 sick-leave days in 7,878 sick-leave periods (in 4,610 sick-leave spells) due to disorders in 17 of the 18 ICD-8 diagnostic categories (International Classification of Diseases, Revision 8). Musculoskeletal or mental diagnoses accounted for most of the sick-leave days, whereas most of the sick-leave periods were due to musculoskeletal, respiratory, or infectious disorders, or to unclassified symptoms. Most cohort members had had four to eight different sick-leave diagnoses over the 11 years, although some had had up to 11 diagnoses. Only two individuals (1%) had been sickness absent solely due to musculoskeletal diagnoses.</p> <p>Conclusion</p> <p>Although the young adults initially were sick listed with back, neck, or shoulder diagnoses, their sickness absence during the follow up were due to a wide variety of other medical diagnoses. It might be that the ill-health content of sickness absence due to back pain is greater than usually assumed. More research on prognoses of sick-leave diagnoses among long-term sick listed is warranted.</p

Physicians' messages in problematic sickness certification: a narrative analysis of case reports

<p>Abstract</p> <p>Background</p> <p>Many physicians find sickness certification tasks problematic. There is some knowledge about situations that are experienced as problematic, whereas less is understood about how physicians respond to the problems they face. One way to acquire such knowledge is to consider "reflection-in-action", aspects of which are expressed in the physician's interpretation of the patient's story. The aim of this study was to gain knowledge about the meaning content of case reports about problematic sickness certification. Specifically, we looked for possible messages to the colleagues intended to read the reports.</p> <p>Methods</p> <p>A narrative approach was used to analyse reports about problematic sickness certification cases that had been written by GPs and occupational health service physicians as part of a sickness insurance course. The analysis included elements from both thematic and structural analysis. Nineteen case reports were used in the actual analysis and 25 in the validation of the results. Main narrative qualities and structural features of the written case reports were explored.</p> <p>Results</p> <p>Five types of messages were identified in the case reports, here classified as "a call for help", "a call for understanding", "hidden worries", "in my opinion", and "appearing neutral". In the reports, the physicians tried to achieve neutrality in their writing, and the patients' stories tended to be interpreted within a traditional biomedical framework. In some cases there was an open request for help, in others it was not obvious that the physician had any problems. Overall, the messages were about having problems as such, rather than the specific features of the problems.</p> <p>Conclusions</p> <p>The case reports clearly demonstrated different ways of writing about problems that arise during sickness certification, from being neutral and not mentioning the problems to being emotionally involved and asking for help. The general character of the messages suggests that they are also relevant for case reports in problematic areas other than sickness certification. If pertinent relationships can be found between reflection-in-practice and the narrative writing about practice, they will provide an approach to further research concerning consultations perceived as problematic and also to medical education.</p

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.Patrik Johansson, Cecilia Krona and Soumi Kundu share first authorship</p

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3

Medico-legal reasoning in disability assessment: A focus group and validation study

<p>Abstract</p> <p>Background</p> <p>Decisions on disability pensions are based, among others, on medical reports. The way these medical assessments are performed is largely unclear. The aim of the study was to determine which grounds are used by social insurance physicians (SIPs) in these assessments and to determine if the identification of these grounds can help improve the quality of assessments in social insurance practice. The article describes a focus group study and a questionnaire study with SIPs in four different countries.</p> <p>Method</p> <p>Using focus group discussions of SIPs discussing the same case in Belgium, the Netherlands, Norway and Slovenia (N = 29) we determined the arguments and underlying grounds as used by the SIP's. We used a questionnaire study among other SIPs (N = 60) in the same countries to establish a first validation of these grounds.</p> <p>Results</p> <p>Grounds in the focus groups were comparable between the countries studied. The grounds were also recognized by SIPs who had not participated in the focus groups. SIPs agreed most on grounds with regard to the claimant's health condition, and about the claimant's duty to explore rehabilitation and work resumption, but less on accepting permanent incapacity when all options for treatment were exhausted.</p> <p>Conclusion</p> <p>Grounds that SIPs use refer to a limited group of key elements of disability evaluation. SIPs interpret disability in social insurance according to the handicapped role and strive at making their evaluation fair trials. ICF is relevant with regard to the health condition and to the process of evaluation. Identification of grounds is a valuable instrument for controlling the quality of disability evaluation. The grounds also appear to be internationally comparable which may enhance scientific study in this area.</p