Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Low-dose naltrexone is used to treat fibromyalgia despite minimal evidence for its efficacy. This trial aimed to investigate whether 12-week treatment with 6 mg low-dose naltrexone was superior to placebo for reducing pain in women with fibromyalgia. METHODS: We did a single-centre, randomised, double-blind, placebo-controlled trial in Denmark. We enrolled women aged 18-64 years who were diagnosed with fibromyalgia. Participants were randomly assigned 1:1 to receive low-dose naltrexone (6 mg) or an identical-appearing placebo, using a computerised algorithm with no stratifications applied. Participants, investigators, outcome assessors, and statistical analysts were all masked to treatment allocation. The primary outcome was change in pain intensity on an 11-point numeric rating scale from baseline to week 12, in the intention-to-treat population. Safety was assessed in participants in the intention-to-treat population who received at least one dose of their allocated intervention. This trial was registered with ClincalTrials.gov (NCT04270877) and EudraCT (2019-000702-30). FINDINGS: We screened 158 participants for eligibility from Jan 6, 2021, to Dec 27, 2022, and 99 patients were randomly assigned to low-dose naltrexone (n=49) or placebo (n=50). The mean age was 50·6 years (SD 8·8), one (1%) of 99 participants was Arctic Asian and 98 (99%) were White. No participants were lost to follow-up. The mean change in pain intensity was -1·3 points (95% CI -1·7 to -0·8) in the low-dose naltrexone group and -0·9 (-1·4 to -0·5) in the placebo group, corresponding to a between-group difference of -0·34 (-0·95 to 0·27; p=0·27, Cohen's d 0·23). Discontinuations due to adverse events were four (8%) of 49 in the low-dose naltrexone group and three (6%) of 50 in the placebo group. 41 (84%) of 49 patients in the low-dose naltrexone group had an adverse event versus 43 (86%) of 50 in the placebo group. One serious adverse event occurred in the placebo group and no deaths occurred. INTERPRETATION: This study did not show that treatment with low-dose naltrexone was superior to placebo in relieving pain. Our results indicate that low-dose naltrexone might improve memory problems associated with fibromyalgia, and we suggest that future trials investigate this further. FUNDING: The Danish Rheumatism Association, Odense University Hospital, Danielsen's Foundation, and the Oak Foundation.

Factors influencing the immune response over 15 months after SARS-CoV-2 infection: A longitudinal population-wide study in the Faroe Islands.

BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay  and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.

The left upper lobe challenge in video-assisted thoracoscopic surgery-use of a composite score to improve the assessment of simulated lobectomy.

AIM: The aim of this study is to develop a reliable composite score based on simulator metrics to assess competency in virtual reality video-assisted thoracoscopic surgery lobectomy and explore the benefits of combining it with expert rater assessments. METHODS: Standardized objective assessments (time, bleeding, economy of movement) and subjective expert rater assessments from 2 previous studies were combined. A linear mixed model including experience level, lobe and the number of previous simulated procedures was applied for the repeated measurements. Reliability for each of the 4 assessments was calculated using Cronbach's alpha. The Nelder-Mead numerical optimization algorithm was used for optimal weighting of scores. A pass-fail standard for the composite score was determined using the contrasting groups' method. RESULTS: In total, 123 virtual reality video-assisted thoracoscopic surgery lobectomies were included. Across the 4 different assessments, there were significant effects (P < 0.01) of experience, lobe, and simulator experience, but not for simulator attempts on bleeding (P = 0.98). The left upper lobe was significantly more difficult compared to other lobes (P = 0.02). A maximum reliability of 0.92 could be achieved by combining the standardized simulator metrics with standardized expert rater scores. The pass/fail level for the composite score when including 1 expert rater was 0.33. CONCLUSIONS: Combining simulator metrics with 1 or 2 raters increases reliability and can serve as a more objective method for assessing surgical trainees. The composite score may be used to implement a standardized and feasible simulation-based mastery training program in video-assisted thoracoscopic surgery lobectomy.

Assessing VATS competence based on simulated lobectomies of all five lung lobes.

OBJECTIVES: To determine the number of procedures and expert raters necessary to provide a reliable assessment of competence in Video-Assisted Thoracoscopic Surgery (VATS) lobectomy. METHODS: Three randomly selected VATS lobectomies were performed on a virtual reality simulator by participants with varying experience in VATS. Video recordings of the procedures were independently rated by three blinded VATS experts using a modified VATS lobectomy assessment tool (VATSAT). The unitary framework of validity was used to describe validity evidence, and generalizability theory was used to explore the reliability of different assessment options. RESULTS: Forty-one participants (22 novices, 10 intermediates, and 9 experienced) performed a total of 123 lobectomies. Internal consistency reliability, inter-rater reliability, and test-retest reliability were 0.94, 0.85, and 0.90, respectively. Generalizability theory found that a minimum of two procedures and four raters or three procedures and three raters were needed to ensure the overall reliability of 0.8. ANOVA showed significant differences in test scores between the three groups (P < 0.001). A pass/fail level of 19 out of 25 points was established using the contrasting groups' standard setting method, leaving one false positive (one novice passed) and zero false negatives (all experienced passed). CONCLUSION: We demonstrated validity evidence for a VR simulator test with different lung lobes, and a credible pass/fail level was identified. Our results can be used to implement a standardized mastery learning training program for trainees in VATS lobectomies that ensures that everyone reaches basic competency before performing supervised operations on patients.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

Effects of shared mental models in teams performing video-assisted thoracoscopic surgery lobectomy.

BACKGROUND: Important non-technical skills enable operating teams to establish shared mental models (SMMs). The importance of SMMs in regards to surgical performance and peri-operative outcomes remains to be investigated. The aim of this study was to explore whether shared mental models (SMMs) of team resources and the current situation, respectively, were predictive of technical skills, duration of surgery, and amount of intra-operative bleeding in video-assisted thoracoscopic surgery (VATS). METHODS: A prospective multi-center observational study was conducted at four tertiary academic hospitals during VATS lobectomy procedures. Data included pre-operative and post-operative questionnaires answered by each of the six team members to measure the SMMs; thoracoscopic video recordings assessed using the previously validated VATS lobectomy Assessment Tool (VATSAT); surgery-related time stamps; and amount (volume) of intra-operative bleeding. Linear regression analyses were conducted to adjust for confounders. RESULTS: Fifty-eight lobectomy procedures were included. Median (interquartile range) VATSAT score was 33.3 (scale 8-40) duration of surgery 101 min (88-123), and amount of intra-operative bleeding 100 ml (20-150). The mean (± SD) of teams' SMMs of the current situation was 20 (± 5). They were not predictive of the surgeons' technical skills, but every one point increase in SMM score significantly predicted a 1 min 52 s decrease in duration of surgery and an 11% decrease in amount of bleeding. The SMMs of team resources were not predictive of any outcomes. CONCLUSION: VATS teams' superior SMMs of the current situation related to significantly shorter duration of surgery and decreased intra-operative bleeding, indicating an effect on team performance and patient care. TRIAL REGISTRATION: NCT02999113 at http://www. CLINICALTRIALS: gov .

[Graves' orbitopathy]. / Endokrine Orbitopathie.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune orbital disease which is mostly associated with Graves' disease and requires good interdisciplinary cooperation. To minimize irreversible damages a stage-adapted anti-inflammatory therapy is of great importance. MATERIAL AND METHODS: Discussion of the latest results of new findings of the pathogenesis, randomized controlled trials on anti-inflammatory treatments for Graves' orbitopathy and novel therapeutic concepts. RESULTS: In all patients with GO achieving euthyroidism, as well as cessation of smoking is very important to avoid prolongated diseases. Mild cases of GO can be treated with selenium supplementation and artificial tears. The moderate-to-severe, active form of GO requires primarily i. v. steroids in combination with orbital irradiation in case of impaired motility. In patients with insufficient therapeutic response after 6 weeks, treatment should be switched to other immunosuppressive agents. In severe sight-threatening cases even high-dose i. v. steroid treatments are often ineffective and bony orbital decompression is necessary. As latest research data have improved our understanding of the pathophysiology of GO, targeted therapies have been developed for GO. Teprotumumab, an IGF-1 receptor antibody, was shown effective in treating GO patients in a phase III trial and should soon be awarded approval for Europe. Inactive patients, who suffer from disturbing exophthalmos should be also treated with bony decompression before eye muscle or lid surgery. CONCLUSION: The current concept for Graves' orbitopathy is as follows: first anti-inflammatory therapy then surgical correction of the permanent defects. This might be modified in the future, due to the promising effects of targeted therapies.

Urodynamic and questionnaire findings in urinary incontinent women with and without diabetes. Data from a health study.

INTRODUCTION AND HYPOTHESIS: Our aim was to compare urodynamic findings in urinary incontinent (UI) women with and without diabetes. METHODS: In the extensive Lolland-Falster Health Study, women with lower urinary tract symptoms were offered urodynamic testing. After excluding 6 women with incomplete urodynamic testing and 88 women without UI, our analysis ended up including 417 women (31 with and 386 without diabetes). Student's t-test and chi-squared test were used to compare differences of urodynamic findings. Urodynamic testing consisted of a 2-day bladder diary, post-void residual urine volume, filling cystometry, pressure-flow study, cough stress test, and uroflowmetry. Three experienced physicians in urogynecology evaluated all urodynamic findings leading to an overall conclusion of the test results. RESULTS: Self-reported data showed that compared to incontinent women without diabetes, incontinent women with diabetes had more frequent leakage, a larger amount of leakage, and a higher ICIQ score. A positive ICS Uniform cough stress test was more prevalent in women with diabetes. There were no significant differences in other urodynamic findings or overall conclusion between the two groups. Controlling for age and BMI did not affect our findings. CONCLUSIONS: Women with diabetes complained more about UI, had a higher ICIQ score, and had a positive ICS Uniform cough stress test more often than women without diabetes. Based on these findings, we recommend to include the history of urinary incontinence in the care of women with diabetes. This sample consists of women from a comprehensive health study with different severity of UI. Therefore, it can serve as a reference cohort for future studies.

Hypothyroidism and urinary incontinence: Prevalence and association in a Danish, female sample from the Lolland-Falster Health study.

INTRODUCTION: We aimed to estimate the prevalence of urinary incontinence (UI) in women with hypothyroidism and subclinical hypothyroidism and to examine the association of hypothyroidism and UI. METHODS: This cross-sectional study was based on the population-based Lolland-Falster Health Study (LOFUS), Denmark. Data comprising a questionnaire, physical examination, and blood samples were collected between 2016 and 2020. Multiple logistic regression was used to estimate odds ratios (OR) and control for possible confounders: age, body mass index, diabetes, smoking, and education. RESULTS: Of 7,699 women included in the study, 7.9% had hypothyroidism, and 2.4% had subclinical hypothyroidism. The prevalence of any UI in women with hypothyroidism, subclinical hypothyroidism, and a control group (normal level of thyroid hormones) was 43.6%, 38.1%, and 39.3%, respectively. After controlling for confounders, no association between hypothyroidism and any UI (OR 1.01, 95% CI 0.85-1.20) or frequent UI (OR 1.05, 95% CI 0.84-1.32) were demonstrated. Additional, no association between subclinical hypothyroidism and any UI (OR 0.87, 95% CI 0.64-1.18) or frequent UI (OR 1.15, 95 CI 0.79-1.69) were demonstrated. CONCLUSIONS: In our female sample, the prevalence of UI was high regardless of the thyroid status. No association between hypothyroidism and any or frequent UI was demonstrated. The prevalence of hypothyroidism was 7.9%.

Prevalence of urinary incontinence among women with diabetes in the Lolland-Falster Health Study, Denmark.

AIMS: To investigate the prevalence of urinary incontinence (UI) and UI subtypes (stress, urgency, and mixed UI) in women with or without diabetes mellitus; and to investigate the association between diabetes and UI (any and subtypes). METHODS: A cross-sectional study based on the Lolland-Falster, Denmark population-based health study. From 2016 to 2020, clinical measurement, questionnaires, and blood tests were collected. A total of 8563 women aged 18 or older were enrolled. Data analysis included 7906 women. UI was defined as any involuntary leakage of urine during the previous 4 weeks. Multiple logistic regression was used to adjust for confounders: age, body mass index, parity, physical activity, previous gestational diabetes, education, and smoking. RESULTS: UI prevalence was 50.3% in women with diabetes and 39.3% in women without diabetes. The unadjusted and adjusted odds ratio (OR) for UI in women with diabetes was OR 1.56 (95% confidence interval [CI], 1.27-1.92) and 1.11 (95% CI, 0.88-1.38), respectively. Mixed UI was associated with diabetes after controlling for confounders. A subgroup analysis found women using multiple antidiabetic medications had increased odds of UI, 2.75 (95% CI, 1.38-5.48), after controlling for confounders. CONCLUSION: The prevalence of UI in women with diabetes was higher than in women without diabetes. The odds of UI was 56% higher in women with diabetes compared with women without diabetes but the effect was attenuated when controlling for confounders and statistically significance was not achieved. For a subgroup using multiple antidiabetic medications, the risk of UI was higher than in women without diabetes.

Predicting the Relapse of Hyperthyroidism in Treated Graves' Disease with Orbitopathy by Serial Measurements of TSH-Receptor Autoantibodies.

The aim of this study was to investigate the potential of the new TSH-receptor antibody (TRAb) assays to predict remission or relapse of hyperthyroidism in patients with Graves' disease (GD) and Graves' orbitopathy (GO). TRAbs were measured retrospectively in sera from a cohort of GD patients with GO (n=117; remission n=38 and relapse n=79-Essen GO biobank) with automated binding immunoassays: TRAb Elecsys (Cobas Roche) and TRAb bridge assay (IMMULITE, Siemens), and the TSAb (thyroid stimulating Ab) cell-based bioassay (Thyretain, Quidel Corp.). To identify relapse risk/remission of hyperthyroidism patients were followed up at least 10 months after the end of antithyroid drug therapy (ATD) therapy. ROC plot analysis was performed to calculate cut-off levels of TRAb and TSAb for prediction of relapse and remission of hyperthyroidism. Cut-off serum levels are provided for timepoints around 3, 6, 10, and 15 months after the beginning of ATD. Repeated measurements of TRAb increase the rate of relapses predictions to 60% (Elecsys), 70% (IMMULITE), and 55% (Thyretain). Patients with remission have consistently TRAb levels below the cut off for relapse in repeated measurements. The cell-based bioassay was the most sensitive - and continued to be positive during follow up [at 15 months: 90% vs. 70% (IMMULITE) and 65% (Elecsys)]. Identification of relapsing hyperthyroidism is possible with automated immunoassays and cell-based bioassay especially with serial TRAb measurements during the course of ATD therapy. Patient who need eye surgery may profit from an early decision towards definitive treatment.

Delayed massive haemothorax following thoracic trauma. / Forsinket pleuraeffusjon etter thoraxtraume.

BACKGROUND: Most cases of thoracic injury are the result of minor trauma, treated out of hospital. Approximately 10 % of patients with minor thoracic trauma develop delayed haemothorax, with risk of fibrosis and empyema. Traumatic diaphragmatic injury following blunt trauma can be difficult to diagnose, and is a rare condition associated with high-energy trauma. CASE PRESENTATION: A 63-year-old man with multiple rib fractures following a traffic accident was readmitted for chest tube drainage 19 days after trauma, due to delayed haemothorax. Four days later, the patient developed massive haemothorax due to pleural fibrinolysis. Video-assisted thoracic surgery confirmed lacerated diaphragm with protruding, bleeding omentum. INTERPRETATION: This case report describes an atypical presentation of a common complication following thoracic trauma. Identification and control of patients at risk of developing delayed haemothorax is of clinical importance to reduce the risk of long-term complications.

Diagnostic Electron Microscopy of Viruses With Low-voltage Electron Microscopes.

Diagnostic electron microscopy is a useful technique for the identification of viruses associated with human, animal, or plant diseases. The size of virus structures requires a high optical resolution (i.e., about 1 nm), which, for a long time, was only provided by transmission electron microscopes operated at 60 kV and above. During the last decade, low-voltage electron microscopy has been improved and potentially provides an alternative to the use of high-voltage electron microscopy for diagnostic electron microscopy of viruses. Therefore, we have compared the imaging capabilities of three low-voltage electron microscopes, a scanning electron microscope equipped with a scanning transmission detector and two low-voltage transmission electron microscopes, operated at 25 kV, with the imaging capabilities of a high-voltage transmission electron microscope using different viruses in samples prepared by negative staining and ultrathin sectioning. All of the microscopes provided sufficient optical resolution for a recognition of the viruses tested. In ultrathin sections, ultrastructural details of virus genesis could be revealed. Speed of imaging was fast enough to allow rapid screening of diagnostic samples at a reasonable throughput. In summary, the results suggest that low-voltage microscopes are a suitable alternative to high-voltage transmission electron microscopes for diagnostic electron microscopy of viruses.

Amphipathic Helices of Cellular Proteins Can Replace the Helix in M2 of Influenza A Virus with Only Small Effects on Virus Replication.

M2 of influenza virus functions as a proton channel during virus entry. In addition, an amphipathic helix in its cytoplasmic tail plays a role during budding. It targets M2 to the assembly site where it inserts into the inner membrane leaflet to induce curvature that causes virus scission. Since vesicularization of membranes can be performed by a variety of amphiphilic peptides, we used reverse genetics to investigate whether the peptides can substitute for M2's helix. Virus could not be generated if M2's helix was deleted or replaced by a peptide predicted not to form an amphiphilic helix. In contrast, viruses could be rescued if the M2 helix was exchanged by helices known to induce membrane curvature. Infectious virus titers were marginally reduced if M2 contains the helix of the amphipathic lipid packing sensor from the Epsin N-terminal homology domain or the nonnatural membrane inducer RW16. Transmission electron microscopy of infected cells did not reveal unequivocal evidence that virus budding or membrane scission was disturbed in any of the mutants. Instead, individual virus mutants exhibit other defects in M2, such as reduced surface expression, incorporation into virus particles, and ion channel activity. The protein composition and specific infectivity were also altered for mutant virions. We conclude that the presence of an amphiphilic helix in M2 is essential for virus replication but that other helices can replace its basic (curvature-inducing) function.IMPORTANCE Influenza virus is unique among enveloped viruses since it does not rely on the cellular ESCRT machinery for budding. Instead, viruses encode their own scission machine, the M2 protein. M2 is targeted to the edge of the viral assembly site, where it inserts an amphiphilic helix into the membrane to induce curvature. Cellular proteins utilize a similar mechanism for scission of vesicles. We show that the helix of M2 can be replaced by helices from cellular proteins with only small effects on virus replication. No evidence was obtained that budding is disturbed, but individual mutants exhibit other defects in M2 that explain the reduced virus titers. In contrast, no virus could be generated if the helix of M2 is deleted or replaced by irrelevant sequences. These experiments support the concept that M2 requires an amphiphilic helix to induce membrane curvature, but its biophysical properties are more important than the amino acid sequence.

Pelvic organ prolapse surgery after native tissue vault suspension at hysterectomy-A prospective cohort study.

OBJECTIVE: The effect of prophylactic vaginal vault suspension during hysterectomy in prevention of subsequent development of pelvic organ prolapse (POP) is unknown. We aimed to investigate incidences and risk of POP surgery in women who had undergone hysterectomy on benign indication with and without prophylactic suspension. STUDY DESIGN: We linked the national clinical Danish Hysterectomy and Hysteroscopy Database (DHHD) to administrative registries to assess data on all total hysterectomies (1 May 2012 to 31 December 2014), suspension methods, age, POP surgery, births, obstetric complications, prescriptions, socioeconomic- and vital status. Women undergoing total hysterectomy on non-prolapse and benign indication with no prior POP surgery were included and followed from hysterectomy to POP surgery, death/emigration or end of study period (maximum 2 years). Descriptive statistics, cumulative incidence curves and multivariable Cox proportional hazard models were fitted to assess the associated risk of POP in relation to prophylactic suspension. RESULTS: We included 7625 patients undergoing total hysterectomy; of these, 6538 (85.7%) were registered with prophylactic suspension during hysterectomy and 1087 (14.3%) women were specifically registered with no suspension in the DHHD. At baseline, women undergoing hysterectomy with suspension were on average 47.1 years of age (standard error SE 0.1) compared to 48.4 years (SE 0.3) in women with no suspension (p-value <0.0001). Moreover, women with suspension differed from their counterparts with no suspension with respect to geographical site of hysterectomy, hysterectomy method, parity and income. The cumulative risk of POP surgery after two years follow-up was 0.9% and 0.5% in the suspension group and the no suspension group, respectively. In the adjusted analysis, we found no association of prophylactic suspension and risk of POP surgery, hazard ratio (HR) = 2.1 (95% confidence interval (CI) 0.8-5.3, p-value 0.13). CONCLUSION: Of all women undergoing hysterectomy for benign indication, 0.84% (N = 64) were surgically treated for POP. At two-year follow-up, there was no association between prophylactic vaginal vault suspension at time of hysterectomy and subsequent POP surgery.

Feeling lucky: hierarchies of suffering and stories of endometrial cancer in a Danish context.

Illness stories are a prime analytical way of understanding patient perspectives on cancer. Nevertheless, limited studies have focused on stories of endometrial cancer. An ethnographic study including participant observation and interviews among 18 Danish women with endometrial cancer was conducted to examine prevalent stories and the ways the women responded to them. In this article, the analysis focuses on two exemplary cases, which present a line of issues related to the kinds of experiences that suffering includes. Findings illustrate that feelings of luck were central to the experience of being diagnosed, treated and cured, which was related to the way health professionals framed endometrial cancer as favourable through notions of curable/incurable, trivial and gentle/invasive and brutal, and aggressive/non-aggressive. Drawing upon the concept of a 'hierarchy of suffering', we exemplify how women tended to scale own experiences of suffering against others', leading some to believe they were not in a legitimate position to draw attention to themselves nor seek help and support, despite adverse physical, psychosocial effects. Thus, feelings of being lucky were intertwined with a sense of ambivalence. We conclude by discussing how suffering arises within a moral context, suggesting that the ways we speak of cancer may make some experiences unspeakable. This calls for increased clinical attention to more diverse narratives of cancer.

Sulfurimonas subgroup GD17 cells accumulate polyphosphate under fluctuating redox conditions in the Baltic Sea: possible implications for their ecology.

The central Baltic Sea is characterized by a pelagic redox zone exhibiting high dark CO2 fixation rates below the chemocline. These rates are mainly driven by chemolithoautotrophic and denitrifying Sulfurimonas GD17 subgroup cells which are motile and fast-reacting r-strategists. Baltic Sea redox zones are unstable and a measurable overlap of nitrate and reduced sulfur, essential for chemosynthesis, is often only available on small scales and short times due to local mixing events. This raises the question of how GD17 cells gain access to electron donors or acceptors over longer term periods and under substrate deficiency. One possible answer is that GD17 cells store high-energy-containing polyphosphate during favorable nutrient conditions to survive periods of nutrient starvation. We used scanning electron microscopy with energy-dispersive X-ray spectroscopy to investigate potential substrate enrichments in single GD17 cells collected from Baltic Sea redox zones. More specific substrate enrichment features were identified in experiments using Sulfurimonas gotlandica GD1T, a GD17 representative. Sulfurimonas cells accumulated polyphosphate both in situ and in vitro. Combined genome and culture-dependent analyses suggest that polyphosphate serves as an energy reservoir to maintain cellular integrity at unfavorable substrate conditions. This redox-independent energy supply would be a precondition for sustaining the r-strategy lifestyle of GD17 and may represent a newly identified survival strategy for chemolithoautotrophic prokaryotes occupying eutrophic redox zones.

"But this is a good cancer:" Patient perceptions of endometrial cancer in Denmark.

AIMS AND OBJECTIVES: To explore endometrial cancer patients' perceptions of the disease and the influence of favourable prognoses on their experiences. BACKGROUND: Endometrial cancer is associated with favourable prognoses, which may imply that patients experience distress to a lesser extent than other cancer patients with less positive treatment outcomes. However, most people with cancer report reduced quality of life and, despite endometrial cancer being prevalent worldwide, experiences of the disease have been little explored. DESIGN: Ethnographic fieldwork with participant observations and interviews. METHODS: Observations during clinical consultations at two Danish hospitals and interviews with women with endometrial cancer (n = 18) over a period of 6 months. The article adheres to the COREQ guidelines for reporting qualitative research. RESULTS: We identify how patients consider cancer in general very likely to be fatal, while clinicians in contrast characterise endometrial cancer specifically as "good" because of favourable prognoses. We employ the concept of bricolage to illustrate how bits and pieces of biomedical knowledge and statistical evidence become intertwined with patients' past experiences and subjective ways of knowing, suggesting that patients' perceptions of endometrial cancer as a disease are somewhat dynamic. CONCLUSIONS: Public stories and everyday life experiences of cancer provide a central framework for illness perceptions. As a result, patients retain the idea of a close connection between cancer and death, while also adopting the notion of endometrial cancer as "good". This influenced how women responded to treatment and care. Framing endometrial cancer as "good" is not always helpful, as the impact of a cancer diagnosis per se is rarely favourable. RELEVANCE TO CLINICAL PRACTICE: In providing women with endometrial cancer with optimal support through diagnosis and treatment, clinicians should attend to the complexity of patients' illness understandings and be aware that assuring patients of a good prognosis not always has the expected impact.

Evaluating competency in video-assisted thoracoscopic surgery (VATS) lobectomy performance using a novel assessment tool and virtual reality simulation.

BACKGROUND: Competency-based training has gained ground in surgical training and with it assessment tools to ensure that training objectives are met. Very few assessment tools are available for evaluating performance in thoracoscopic procedures. Video recordings would provide the possibility of blinded assessment and limited rater bias. This study aimed to provide validity evidence for a newly developed and dedicated tool for assessing competency in Video-Assisted Thoracoscopic Surgery (VATS) lobectomy. METHODS: Participants with varying experience with VATS lobectomy were included from different countries. Video recordings from participants' performance of a VATS right upper lobe lobectomy on a virtual reality simulator were rated by three raters using a modified version of a newly developed VATS lobectomy assessment tool (the VATSAT) and analyzed in relation to the unitary framework (content, response process, internal structure, relation to other variables, and consequences of testing). RESULTS: Fifty-three participants performed two consecutive simulated VATS lobectomies on the virtual reality simulator, leaving a total of 106 videos. Content established in previously published studies. Response process Standardized data collection was ensured by using an instructional element, uniform data collection, a special rating program, and automatic generation of the results to a database. Raters were carefully instructed in using the VATSAT, and tryout ratings were carried out. Internal structure Inter-rater reliability was calculated as intra-class correlation coefficients, to 0.91 for average measures (p < 0.001). Test/re-test reliability was calculated as Pearson's r of 0.70 (p < 0.001). G-coefficient was calculated to be 0.79 with two procedures and three raters. By performing D-theory was found that either three procedures rated by two raters or five procedures rated by one rater were enough to reach an acceptable G-coefficient of ≥ 0.8. Relation to other variables Significant differences between groups were found (p < 0.001). The participants' VATS lobectomy experience correlated significantly to their VATSAT score (p = 0.016). Consequences of testing The pass/fail score was found to be 14.9 points by the contrasting groups' method, leaving five false positive (29%) and six false negatives (43%). CONCLUSION: Validity evidence was provided for the VATSAT according to the unitary framework. The VATSAT provides supervisors and assessors with a procedure-specific assessment tool for evaluating VATS lobectomy performance and aids with the decision of when the trainee is ready for unsupervised performance.

Assessment of competence in video-assisted thoracoscopic surgery lobectomy: A Danish nationwide study.

BACKGROUND: Competence in video-assisted thoracoscopic surgery lobectomy has previously been established on the basis of numbers of procedures performed, but this approach does not ensure competence. Specific assessment tools, such as the newly developed video-assisted thoracoscopic surgery lobectomy assessment tool, allow for structured and objective assessment of competence. Our aim was to provide validity evidence for the video-assisted thoracoscopic surgery lobectomy assessment tool. METHODS: Video recordings of 60 video-assisted thoracoscopic surgery lobectomies performed by 18 thoracic surgeons were rated using the video-assisted thoracoscopic surgery lobectomy assessment tool. All 4 centers of thoracic surgery in Denmark participated in the study. Two video-assisted thoracoscopic surgery experts rated the videos. They were blinded to surgeon and center. RESULTS: The total internal consistency reliability Cronbach's alpha was 0.93. Inter-rater reliability between the 2 raters was Pearson's r = 0.71 (P < .001). The mean video-assisted thoracoscopic surgery lobectomy assessment tool scores for the 10 procedures performed by beginners were 22.1 (standard deviation [SD], 8.6) for the 28 procedures performed by the intermediate surgeons, 31.2 (SD, 4.4), and for the 20 procedures performed by experts 35.9 (SD, 2.9) (P < .001). Bonferroni post hoc tests showed that experts were significantly better than intermediates (P < .008) and beginners (P < .001). Intermediates' mean scores were significantly better than beginners (P < .001). The pass/fail standard calculated using the contrasting group's method was 31 points. One of the beginners passed, and 2 experts failed the test. CONCLUSIONS: Validity evidence was provided for a newly developed assessment tool for video-assisted thoracoscopic surgery lobectomy (video-assisted thoracoscopic surgery lobectomy assessment tool) in a clinical setting. The discriminatory ability among expert surgeons, intermediate surgeons, and beginners proved highly significant. The video-assisted thoracoscopic surgery lobectomy assessment tool could be an important aid in the future training and certification of thoracic surgeons.