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ObjectiveTo evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.DesignPooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.SettingPopulation-based.Patient(s)We included 8,500 women with ovarian cancer, 13,592 control women.Intervention(s)Ten well-established ovarian cancer risk factors.Main outcome measure(s)Risk of ovarian cancer for women with and without endometriosis.Result(s)Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-

Abstract Background In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer’s disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer’s disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. Methods A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. Results No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value

Climate reconstructions of the last millennium rely on networks of high-resolution and well-dated proxy records. This study presents age-at-depth data and preliminary results from the new Mount Brown South (MBS) ice cores, collected at an elevation of 2084 m on the boundary of Princess Elizabeth Land and Kaiser Wilhelm II Land in East Antarctica. We show an initial analysis of the site meteorology, mean annual chemical species concentrations and seasonal cycles, including the identification of a seasonal cycle in fluoride concentrations. The annually resolved chronologies were developed from the chemistry data using a site-specific layer-counting methodology that employed seasonally varying trace chemical species and stable water isotopic ratios, combined with alignment to known volcanic horizons. The uncertainty in the determination of annual horizons via layer counting was also quantified. The chronologies developed include the “Main” 295 m record spanning 1137 years (873–2009 CE) and three surface cores spanning the most recent 39–52 years up to the surface age at the time of drilling (austral summer 2017/2018). Mean annual trace chemical concentrations are compared to the Law Dome ice core (located 1130 km east of the Mount Brown South site) and discussed in terms of atmospheric transport. The MBS chronologies presented here – named MBS2023 – will underpin the development of new palaeoclimate records spanning the past millennium from this under-represented region of East Antarctica.

Abstract Background Long-term strength deficits are common after Achilles tendon ruptures. Early use of progressive resistance exercises may help reduce strength deficits, but the feasibility of this approach is unknown. The aim was to investigate the feasibility of early progressive resistance exercises regarding patient acceptability and compliance with the intervention. Methods We recruited patients with an acute Achilles tendon rupture treated non-surgically. During 9 weeks of immobilisation with a walking boot, participants attended weekly supervised physiotherapy sessions of progressive resistance exercises and performed home exercises, consisting of isometric ankle plantarflexion, seated heel-rise, and elastic band exercises. Acceptability was evaluated using a 7-point Likert scale (1 = very unacceptable and 7 = very acceptable) with feasibility threshold at 80% of the participants rating ≥ 4. Adherence to the exercises was defined as 80% of the participants performing at least 50% of the home exercises. During the intervention, tendon healing and adverse events were monitored. Results Sixteen participants (mean age 46 (range 28–61), male/female = 13/3) completed the intervention. Pre-injury Achilles tendon total rupture score was 98 (SD 8). All participants rated the acceptability of the exercises ≥ 5 (moderate acceptable to very acceptable) at 9- and 13-week follow-up and 9/16 rated 7 points (very acceptable). Participants performed 74% (range 4–117) of the total prescribed home exercises and 15/16 performed > 50%. One participant was not compliant with the home exercises due to feeling uncomfortable performing these independently. There were no re-ruptures, but one case of deep venous thrombosis. Conclusions The early progressive resistance exercise program for treatment of non-surgically treated Achilles tendon rupture was feasible. Future studies should investigate the efficacy of the progressive intervention. Trial registration The study was registered at Clinical Trials (NCT04121377) on 29 September 2019. ClinicalTrials: NCT04121377 .

Abstract Background On average, older patients use five or more medications daily, increasing the risk of adverse drug reactions, interactions, or medication errors. Healthcare sector transitions increase the risk of information loss, misunderstandings, unclear treatment responsibilities, and medication errors. Therefore, it is crucial to identify possible solutions to decrease these risks. Patients, relatives, and healthcare professionals were asked to design the solution they need. Methods We conducted a participatory design approach to collect information from patients, relatives, and healthcare professionals. The informants were asked to design their take on a tool ensuring that patients received the correct medication after discharge from the hospital. We included two patients using five or more medications daily, one relative, three general practitioners, four nurses from different healthcare sectors, two hospital physicians, and three pharmacists. Results The patients’ solution was a physical location providing a medication overview, including side effects and interactions. Healthcare professionals suggested different solutions, including targeted and timely information that provided an overview of the patient’s diagnoses, treatment and medication. The common themes identified across all sub-groups were: (1) Overview of medications, side effects, and diagnoses, (2) Sharing knowledge among healthcare professionals, (3) Timely discharge letters, (4) Does the shared medication record and existing communication platforms provide relevant information to the patient or healthcare professional? Conclusion All study participants describe the need for a more concise, relevant overview of information. This study describes elements for further elaboration in future participatory design processes aimed at creating a tool to ensure older patients receive the correct medication at the correct time.

Abstract Few non-surgical, longitudinal studies have evaluated the relations between spinal degeneration, lumbar multifidus muscle (LMM) quality, and clinical outcomes. None have assessed the potential mediating role of the LMM between degenerative pathology and 12-month clinical outcomes. This prospective cohort study used baseline and 12-month follow-up data from 569 patients conservatively managed for low back or back-related leg pain to estimate the effects of aggregate degenerative lumbar MRI findings and LMM quality on 12-month low back and leg pain intensity (0–10) and disability (0–23) outcomes, and explored the mediating role of LMM quality between degenerative findings and 12-month clinical outcomes. Adjusted mixed effects generalized linear models separately estimated the effect of aggregate spinal pathology and LMM quality. Mediation models estimated the direct and indirect effects of pathology on leg pain, and pathology and LMM quality on leg pain, respectively. Multivariable analysis identified a leg pain rating change of 0.99 [0.14; 1.84] (unstandardized beta coefficients [95% CI]) in the presence of ≥ 4 pathologies, and a disability rating change of − 0.65 [− 0.14; − 1.16] for each 10% increase in muscle quality, but no effect on back pain intensity. Muscle quality had a non-significant mediating role (13.4%) between pathology and leg pain intensity. The number of different pathologies present demonstrated a small effect on 12-month leg pain intensity outcomes, while higher LMM quality had a direct effect on 12-month disability ratings but no mediating effect between pathology and leg pain. The relations between degenerative pathology, LMM quality, and pain-related outcomes appear complex and may include independent pathways.

Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Abstract Background Recently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient’s synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid. Methods Using hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20–40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years. Results On the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5). Conclusions Severe osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA. Trial registration The study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 − 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Background: Approximately 15% of patients undergoing radical cystectomy (RC) develop benign ureteroenteric strictures. Of these strictures, the majority are located in the left ureter. To lower the rate of strictures, a retrosigmoid ileal conduit has been suggested. Objective: To investigate the feasibility and safety of a retrosigmoid ileal conduit during robot-assisted RC in bladder cancer patients. Design, setting, and participants: This randomized controlled trial included 303 patients from all five cystectomy centers in Denmark from May 2020 to August 2022. Participants were diagnosed with bladder cancer and scheduled for robot-assisted RC with an ileal conduit. Intervention: Intervention group: a retrosigmoid ileal conduit was constructed using approximately 25 cm of the terminal ileum and tunneled behind the sigmoid where the left ureter was anastomosed from end to side. Control group: the conventional ileal conduit ad modum Bricker with individual end-to-side anastomoses. Outcome measurements and statistical analysis: Patients were analyzed by the intention-to-treat approach. Complications within 90 d were categorized using the Clavien-Dindo grading system and compared using Fisher’s exact test. Wilcoxon’s test was used for pre- and postoperative renal function. Results and limitations: Of the 149 patients randomized for the retrosigmoid ileal conduit (MOSAIC), a total of 137 (92%) patients received the allocated conduit. Postoperative complications were distributed equally between the two groups. The relative risk of Clavien-Dindo complications of grade ≥III was 1.12 (95% confidence interval: 0.96–1.31) in the intervention group compared with the control group. Conclusions: The retrosigmoid ileal conduit with robot-assisted RC was technically feasible. Early postoperative complications were not significantly different when comparing the two groups. Further investigation of long-term complications, including strictures, is needed. Patient summary: We compared a conventional urinary diversion with a longer conduit to prevent constriction from developing in the ureters. The new conduit is feasible and safe within the first 90 d, with no differences in postoperative complications from those of the conventional diversion.

Abstract The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics. We investigated NLR on mortality stratified by prevalent and incident MPN, essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), comorbidity burden (CCI-score), and the Triple-A risk score using hazard ratio (HR) and 95% confidence interval (95%CI). NLR 1–1.9 was the reference level. During a median follow-up of 11.2 years, 197,802 deaths were recorded. All-cause mortality increased for a stepwise increasing NLR with a HR (95%CI) for NLR ≥ 6 of 2.06(2.03–2.09) for the whole population and 2.93(2.44–3.50) in prevalent MPN. ET, PV, and MF had a HR (95%CI) for NLR ≥ 2 of 2.14(1.71–2.69), 2.19(1.89–2.54), and 2.31(1.91–2.80). Results were similar for incident MPN. Mortality was higher for stepwise increasing NLR and CCI-score(p interaction

Abstract Background Failing to comprehend risk communication might contribute to poor treatment adherence. Using hypertension as a case, we investigated how a risk communication tool for patients with an elevated risk of cardiovascular disease was perceived. Methods As part of a large project featuring a randomised controlled trial in a general practice setting in the Region of Southern Denmark, we conducted a semi-structured individual interview study. The study included patients with hypertension who had used an intervention comprising a visual and dynamic cardiovascular risk communication tool, along with receiving recurring emails providing advice on a healthy lifestyle. The analyses were based on Malterud’s Systematic Text Condensation. Results This article focuses solely on the results of the interview study, which comprised a total of 9 conducted and analysed interviews. The IT setup had a major impact on adherence to the intervention. A positive impact was found when the IT setup was perceived as easy to use and accessible, while a negative impact was noted when it malfunctioned. The intervention increased patients’ self-reported insight into risk of cardiovascular disease. Patients reported the intervention and their risk of cardiovascular disease to become less important to them when they had more severe comorbidities. The involved health professional was very important for treatment adherence when communicating risk visually. Patients expressed trust in their general practitioners, and the general practitioners’ attitudes toward the intervention affected patients’ perceptions of its usefulness. While the informants reported an increased awareness of their risk of cardiovascular disease, none of them felt more concerned. Conclusions Patients reported an increase in their perceived insight into the risk of cardiovascular disease but not an increased concern. Our findings align with previous studies emphasizing the importance of patients’ motivation as well as risk perception for adherence. General practitioners have an important role when implementing new tools for patients.

Abstract Background Rotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable. Methods A single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18–55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound. Discussion The results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of “exercising into pain” for this patient group, as there is currently no consensus. Trial registration ClinicalTrials.gov NCT05124769. Registered on August 11, 2021.

Abstract Background Age‐related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro‐myo‐tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species and sex. Methods Vastus lateralis muscle biopsies (n = 265) from 197 males and females, covering an age span of 20–97 years, were examined. The gastrocnemius and soleus muscles of 11 + 22‐month‐old male C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross‐sections were used to measure myofiber cross‐sectional area (CSA) and perimeter. From these, a shape factor index (SFI) was calculated in a fibre‐type‐specific manner (type I/II in humans; type I/IIa/IIx/IIb in mice), with higher values indicating increased deformity. Heavy resistance training (RT) was performed three times per week for 3–4 months by a subgroup (n = 59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development and specific force (MVC/muscle mass). Results In human muscle, SFI was positively correlated with age for both type I (R2 = 0.20) and II (R2 = 0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (4%, P 80) compared with old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofiber SFI was higher than that for type I myofiber (4–13%, P

Little is known about risk factors for progression of high-grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population-based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985-2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry and the Danish HIV Cohort Study for information on autoimmune disease, genital warts and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis and sex. The study population comprised 1222 individuals with AIN3 contributing 12 824 person-years of follow-up. Ninety-seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared to individuals without these conditions. People living with HIV had a higher progression rate than HIV-negative individuals (HR = 4.25; 95% CI: 1.87-9.65) with the highest progression rate among those with CD4 count ≤200 cells/μL. These associations may be caused by an interplay between HPV infection and immunosuppression.