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Eleanor Boyle,1 Lars Folkestad,2– 5 Erik Frafjord,6 Bart W Koes,1,7 Soren Thorgaard Skou,1,8 Jan Hartvigsen1,6 1Center for Muscle and Joint Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark; 2Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark; 3Department of Internal Medicine, Hospital of South West Denmark, Esbjerg, Denmark; 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Open Patient Exploratory Network, University of Southern Denmark, Odense, Denmark; 6Chiropractic Knowledge Hub, Odense, Denmark; 7Department of General Practice, Erasmus MC, Rotterdam, the Netherlands; 8The Research Unit PROgrez, Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Slagelse, DenmarkCorrespondence: Jan HartvigsenDepartment of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, Odense M, Odense, 5230, DenmarkTel +45 65504522Email jhartvigsen@health.sdu.dkPurpose: To conduct a non-responder analysis on a musculoskeletal (MSK) electronic questionnaire.Methods: Individuals aged 18 years and older, diagnosed with diabetes mellitus (DM), and attended an ambulatory DM clinic formed the sample frame. They were invited to complete an electronic musculoskeletal (MSK) conditions and symptoms questionnaire booklet using a secured electronic email system. Individuals whose secured email box was not active at the time were discarded. Using the Central Person Registry number, a unique number assigned to all Danish residents, we linked the sample frame to different registries to learn more about non-responders. Non-responders were either individuals who did not respond to a single question and those who responded “No” to the first question about willing to participate. We calculated descriptive statistics for each characteristic. Univariate logistic regression models were conducted to determine the relationship between each characteristic and non-responder status.Results: The response rate was 36% (n = 3812). Individuals with type 2 DM (OR 2.0 (95% CI 1.8– 2.2)), secondary DM (1.9 (1.3– 2.8)) or unspecified DM (2.1 (1.8– 2.4)) were more likely to be non-responders than individuals with Type 1 DM. Also, individuals aged 70– 79 (1.3 (1.1– 1.6)) and 80 years and older (5.9 (4.5– 7.7)) were more likely to be non-responders than 18– 29 years old individuals. However, individuals aged 40– 49 (1.5 (1.2– 1.8)), 50– 59 (1.5 (1.3– 1.8)) or 60– 69 (1.4 (1.1– 1.6)) were more likely to be responders than 18– 29 years old individuals. Individuals with Charlson Comorbidity Index (CCI) of 1 (2.0 (1.3.2.9) or CCI of 2 (1.7 (1.1– 2.5) were more likely to be responders than individuals with a CCI of 0. Lastly, individuals who were currently outside of the workforce (1.6 (2.4– 2.9) or had unknown/missing socioeconomic status (3.9 (2.8– 5.3) were more likely to be non-responders than individuals who were working.Conclusion: Although we did find a non-response bias, this cohort will be an important source to determine the prevalence and consequences of MSK conditions in a secondary care DM population.Keywords: diabetes, survey, non-participation analysis, musculoskeletal conditions

Summary: Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. Introduction: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. Methods: The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I ( n = 58), III ( n = 12), and IV ( n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset ( n = 67). Results: A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect ( p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD ( p < 0.005), thinner cortexes ( p < 0.001), and reduced trabecular number ( p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA. Conclusion: The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities. [ABSTRACT FROM AUTHOR]

Abstract Background Interruption in chest compressions during cardiopulmonary resuscitation can be characterized as no flow ratio (NFR) and the importance of minimizing these pauses in chest compression has been highlighted recently. Further, documentation of resuscitation performance has been reported to be insufficient and there is a lack of identification of important issues where future efforts might be beneficial. By implementing in situ simulation we created a model to evaluate resuscitation performance. The aims of the study were to evaluate the feasibility of the applied method, and to examine differences in the resuscitation performance between the first responders and the cardiac arrest team. Methods A prospective observational study of 16 unannounced simulated cardiopulmonary arrest scenarios was conducted. The participants of the study involved all health care personel on duty who responded to a cardiac arrest. We measured NFR and time to detection of initial rhythm on defibrillator and performed a comparison between the first responders and the cardiac arrest team. Results Data from 13 out of 16 simulations was used to evaluate the ability of generating resuscitation performance data in simulated cardiac arrest. The defibrillator arrived after median 214 seconds (180-254) and detected initial rhythm after median 311 seconds (283-349). A significant difference in no flow ratio (NFR) was observed between the first responders, median NFR 38% (32-46), and the resuscitation teams, median NFR 25% (19-29), p < 0.001. The difference was significant even after adjusting for pulse and rhythm check and shock delivery. Conclusion The main finding of this study was a significant difference between the first responders and the cardiac arrest team with the latter performing more adequate cardiopulmonary resuscitation with regards to NFR. Future research should focus on the educational potential for in-situ simulation in terms of improving skills of hospital staff and patient outcome.

Abstract Microgrants are a novel concept where small grants are used to facilitate research. The concept might have a place in developing emergency medicine research, especially in countries where emergency medicine is not established or in new areas of research. Two examples of the beneficial effects of microgrants in emergency medicine research are described. Emergency medicine interest groups and foundations should consider setting up microgrant schemes.

Abstract Background Patients referred to a medical admission unit (MAU) represent a broad spectrum of disease severity. In the interest of allocating resources to those who might potentially benefit most from clinical interventions, several scoring systems have been proposed as a triaging tool. Even though most scoring systems are not meant to be used on an individual level, they can support the more inexperienced doctors and nurses in assessing the risk of deterioration of their patients. We therefore performed a systematic review on the level of evidence of literature on scoring systems developed or validated in the MAU. We hypothesized that existing scoring systems would have a low level of evidence and only few systems would have been externally validated. Methods We conducted a systematic search using Medline, EMBASE and the Cochrane Library, according to the PRISMA guidelines, on scoring systems developed to assess medical patients at admission. The primary endpoints were in-hospital mortality or transfer to the intensive care unit. Studies derived for only a single or few diagnoses were excluded. The ability to identify patients at risk (discriminatory power) and agreement between observed and predicted outcome (calibration) along with the method of derivation and validation (application on a new cohort) were extracted. Results We identified 1,655 articles. Thirty were selected for further review and 10 were included in this review. Eight systems used vital signs as variables and two relied mostly on blood tests. Nine systems were derived using regression analysis and eight included patients admitted to a MAU. Six systems used in-hospital mortality as their primary endpoint. Discriminatory power was specified for eight of the scoring systems and was acceptable or better in five of these. The calibration was only specified for four scoring systems. In none of the studies impact analysis or inter-observer reliability were analyzed. None of the systems reached the highest level of evidence. Conclusions None of the 10 scoring systems presented in this article are perfect and all have their weaknesses. More research is needed before the use of scoring systems can be fully implemented to the risk assessment of acutely admitted medical patients.

Pain is a challenge in persons with OI and causes much concern in the Osteogenesis Imperfecta (OI) population. We aim to evaluate the usability of the Nordic Musculoskeletal Questionnaire (NMQ) to identify painful sites in adults with OI and to describe the occurrence of musculoskeletal (MSK) pain and its impact on their work and daily activities. This cross-sectional pilot study uses the OI-NMQ to study MSK pain prevalence in nine separate anatomical regions (neck, upper back, lower back, shoulder, elbow, hand/wrist, hip, knee, and ankle/foot) and its impact on regular work and daily activities in adults with OI. The questionnaire was distributed among participants of the 2023 annual meeting of The Danish OI Society. The response rate was 68%, and all participants considered the OI-NMQ helpful in assessing the presence of pain and its consequences. The analysis included 27 adults with OI type I, III, or IV above 18 years. Among all 27 participants, MSK pain was present in 15-56% of the 9 sites within the last 7 days and 33-89% of the nine anatomical regions during the last 12 months. In 7-48% of all the participants, their regular work and daily activities had been affected by the presence of MSK pain. The OI-NMQ was feasible in assessing MSK pain among adults with OI and displayed a high prevalence of MSK pain with a moderate impact on their regular work and daily activities in this OI population. A larger and repeated measurement of MSK pain in adults with OI is needed to confirm these results., (© 2024. The Author(s).)

Objective: Patients with Osteogenesis Imperfecta (OI) have varying degrees of bone fragility and increased fracture rates. There is a paucity of data related to complications to pregnancies in patients with OI and to their offspring. With this study we aim to evaluate the risk of complications to pregnancies, delivery, and offspring in pregnancies where the mother or father have OI., Design: Nationwide, register-based, cohort study., Setting: Danish health register-based data., Population: All pregnancies registered in the Danish health registers where one parent has OI and a reference population of all other pregnancies in the general population from 1997 to 2018., Methods: Descriptive epidemiology MAIN OUTCOME MEASURES: Pregnancy and delivery complications (e.g. prevalence of pre-eclampsia, eclampsia and perinatal haemorrhage), and complications in the offspring (e.g. prevalence of low birth weight, low Apgar Score, need of CPAP or NICU, prevalence of congenital malformations (using the EUROCAT classification), incidence of osteogenesis imperfecta, prevalence of birth related fractures and hospital contacts during the first year of life) from pregnancies with parental OI., Results: We identified 433 OI related pregnancies among 134 mothers with OI and 73 fathers with OI. The rates of pregnancy and delivery complications were similar between the OI cohorts and the reference population. More (31 % vs 19 %) children were delivered by caesarean section in the OI cohort than in the reference population., Conclusion: Pregnancies, where one parent have OI, result in live births to term with very few complications., Competing Interests: Declaration of competing interest All authors declare that they have no financial, personal, political, intellectual or religious conflicts of interests relevant to this study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Osteogenesis imperfecta (OI) is a rare hereditary disease mainly resulting in reduced or altered collagen type I. Collagen type I is a major constituent of the respiratory system, and normal collagen type I is vital for pulmonary tissue function., Research Question: Do patients with OI have increased admission rates resulting from pulmonary diseases compared with the general population?, Study Design and Methods: This was a register-based, nationwide cohort study, including all patients with OI in Denmark and a reference population. From January 1, 1995, through December 31, 2018, we evaluated the rates of admissions resulting from asthma, COPD, and pneumonia as well as the use of bronchodilator drugs and antibiotics comparing individuals with OI with the reference population., Results: We included 862 individuals with OI and 4,283 people from the reference population covering 15,952 and 79,471 person-years of observation, respectively, in the two cohorts. The admissions rate (incidence rate [IR]) was highest in women with OI 65 years of age or older, with 56.3 admissions per 1,000 person-years and 29.4 admissions per 1,000 person-years in the reference population (amounting to an admissions incident rate ratio [IRR] of 1.91 [95% CI, 1.38-2.70]). The highest admission rate in men with OI was found among participants 0 to 18 years of age, with an IR of 30.4 per 1,000 person-years compared with an IR of 7.7 per 1,000 person-years in the reference population (IRR, 4.92 [95% CI, 3.79-6.38]). We found a higher proportion of long-acting and short-acting bronchodilator drug users in the OI cohort, but no increased use of antibiotics., Interpretation: Overall, the admission rates for respiratory diseases were low in the OI cohort, but a higher relative risk of hospitalizations resulting from respiratory disease compared with the general population. Timely diagnosis and treatment of respiratory complications in individuals with OI is warranted., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64-5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62-40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21-5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age., (© 2024. The Author(s).)

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which involves not only the skeleton, but also the cardiopulmonary and gastrointestinal system, soft tissues, tendons, muscle, and joints, hearing, eyesight, dental health, and women's health in OI and potentially adds negative affect to health-related quality of life. We aim to guide clinicians as well as draw attention to obvious knowledge gaps and the need for further research in adult OI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Cancer is the second most common cause of death worldwide. It is currently debated whether thyroid dysfunction is a modifiable cancer risk factor. Our aim was to evaluate the risk of cancer in patients with hyperthyroidism., Methods: This is a register-based nationwide cohort study of individuals with a diagnosis of hyperthyroidism. Each hyperthyroid case was matched with four reference individuals according to age and sex. Using Fine and Gray competing risk regression models, we studied the association of hyperthyroidism and subsequent all-cause cancer diagnoses, adjusted for preexisting morbidity. Sub-analyses were stratified for cause of hyperthyroidism (Graves' disease and toxic nodular goiter, age when diagnosed with hyperthyroidism, sex, and cancer localization (lung, prostate, breast, and colorectal cancer))., Results: The cohort consisted of 95,469 patients with hyperthyroidism (followed for a median of 10.9 years (range: 5.2-17.2)), and 364,494 reference individuals (followed for a median of 11.2 years (range: 5.4-17.4)). Hyperthyroidism was associated with increased all-cause cancer risk (sub-distribution hazard ratio (SHR): 1.12; 95% CI: 1.10-1.14), as well as an increased risk of breast (SHR: 1.07; 95% CI: 1.02-1.13), lung (SHR: 1.20; 95% CI: 1.16-1.26), and prostate cancer (SHR: 1.10; 95% CI: 1.02-1.19), but not colorectal cancer (SHR: 1.04; 95% CI: 0.99-1.09). Sub-analyses stratified for age when diagnosed with hyperthyroidism and cause of hyperthyroidism yielded similar results., Conclusion: In this register-based study, patients with hyperthyroidism had an increased risk of cancer, in particular lung, prostate, and breast cancer. Whether a causal link exists remains to be proven.

Introduction: Approximately one-third of all persons with multiple sclerosis (pwMS) are older, i.e., having an age ≥60 years. Whilst ageing and MS separately elicit deteriorating effects on brain morphology, neuromuscular function, and physical function, the combination of ageing and MS may pose a particular challenge. To counteract such detrimental changes, power training (i.e., a type of resistance exercise focusing on moderate-to-high loading at maximal intended movement velocity) presents itself as a viable and highly effective solution. Power training is known to positively impact physical function, neuromuscular function, as well as brain morphology. Existing evidence is promising but limited to young and middle-aged pwMS, with the effects of power training remaining to be elucidated in older pwMS., Methods: The presented 'Power Training in Older MS patients (PoTOMS)' trial is a national, multi-center, parallel-group, randomized controlled trial. The trial compares 24 weeks of usual care(n = 30) to 24 weeks of usual care and power training (n = 30). The primary outcome is whole brain atrophy rate. The secondary outcomes include changes in brain micro and macro structures, neuromuscular function, physical function, cognitive function, bone health, and patient-reported outcomes., Ethics and Dissemination: The presented study is approved by The Regional Ethics Committee (reference number 1-10-72-222-20) and registered at the Danish Data Protection Agency (reference number 2016-051-000001). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences independent of the results. The www.clinicaltrials.gov identifier is NCT04762342., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: To describe 1-week and 1-year prevalence of spinal pain and its consequences in relation to leisure activity, work-life, and care-seeking in people with type 1 and 2 diabetes mellitus (DM)., Methods: A cross-sectional survey including adults diagnosed with DM from two Danish secondary care centres. Using the Standardised Nordic Questionnaire, spinal pain prevalence (cervical, thoracic, lumbar) and its consequences were evaluated (proportions, 95% confidence intervals) and compared to the general population., Results: Among 3767 people, 1-week and 1-year spinal pain prevalence were 11.6-32.4 and 18.5-49.6%, respectively, highest for lumbar pain (24.6-49.6%). The prevalence was similar between DM types for cervical and thoracic pain, but higher in type 2 for lumbar spine. Women had higher pain prevalence across spinal regions and DM types, while cervical and thoracic pain estimates were higher for age < 60 vs. ≥ 60. Within the past year, > 50% reported pain > 30 days, high proportions had reduced their activities (leisure time, 43.7-63.9%; work, 20.7-33.3%), 13.3-28.1% reported sick-leave > 30 days, and 44.3-48.5% had sought care due to spinal pain., Conclusion: Spinal pain is common in people with type 1 and 2 DM, resulting in considerable consequences for work/leisure activities, sick-leave, and healthcare utilisation as compared to the general population., (© 2023. The Author(s).)

Competing Interests: Declaration of competing interest All authors state that they have no conflict of interest.

Purpose: The present study aims to investigate how well CT images correlate to surgical findings in orbital floor fractures and to the presence of diplopia., Methods: In this cross-sectional study, 27 consecutive patients already selected for surgery due to an orbital floor fracture underwent a routine CT scan (axial, coronal, sagittal). An ophthalmologist established any presence of diplopia. Extent of fracture/injury seen on CT was compared to that discovered during surgery., Results: In the surgeons´ opinions CT-images were in concordance with surgical findings in 71% of the cases. Agreement for pure blow out fractures was high (92%). Tetrapod fractures as a cause of an orbital floor fracture was only identified as such by surgeons in three of 11 cases, all subjected to orbital exploration, not only a closed reduction. Diplopia showed a significant correlation to rounding of the inferior rectus muscle at coronal CT. "Rounding" significantly correlated with the presence of a floor defect, to herniation of soft tissues and to the volume of displaced tissue., Conclusions: The results imply that the joint professional interaction between neuroradiology and surgery is important and would benefit from the use of an easy and well-defined classification system of orbital floor fractures. In Sweden a national record to collect data on all zygomaticomaxillary complex fractures assessed is to be started aiming at making general statements possible by time., (© 2023. The Author(s).)

Aims: To describe the one-week and 12-month prevalence of musculoskeletal pain in the upper and lower extremities and consequences in relation to care seeking, leisure time activity, and work life in patients with type 1 and 2 diabetes., Methods: A cross-sectional survey including adults diagnosed with type 1 and 2 diabetes from two Danish secondary care databases. Questions covered pain prevalence (shoulder, elbow, hand, hip, knee, ankle) and its consequences based on the Standardised Nordic Questionnaire. Data was presented using proportions (95 % confidence intervals)., Results: The analysis included 3767 patients. The one-week prevalence was 9.3-30.8 % and 12-month prevalence 13.9-41.8 %, highest for shoulder pain (30.8-41.8 %). The prevalence was similar between type 1 and 2 diabetes for the upper extremity, but higher in type 2 for the lower extremity. Women had a higher pain prevalence for any joint for both diabetes types, while estimates did not vary between age groups (<60 or ≥60 years). More than half of the patients had reduced their activities at work or leisure time, and more than one-third had sought care during the past year because of pain., Conclusions: Musculoskeletal pain in the upper and lower extremities is common in patients with type 1 and 2 diabetes from Denmark, with considerable consequences for work and leisure activities., Competing Interests: Competing interest The authors declare no conflicts of interest related to this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pulmonary involvement in Osteogenesis Imperfecta (OI) can be severe but may be overlooked in milder cases. The Care4BrittleBones Foundation initiated this project to develop a set of global outcome measures focusing on respiratory-related issues in patients with OI. The objective was to reach an international consensus for a standardized set of outcomes and associated measuring instruments for the pulmonary care of individuals with OI. Based on the initial tests and questionnaires, we suggest parameters for when pulmonologists should seek guidance from the growing literature on OI pulmonary care and/or recognized experts in the field., Study Design and Methods: The project team consisted of a multidisciplinary mix of 12 people from six countries, including an OI patient representative, and facilitated by the Care4BrittleBones Foundation director. The International Consortium for Health Outcomes Measurement (ICHOM) process was followed, which includes the Delphi method, used to collect the opinions of the expert team. Patient input was present in each meeting due to the inclusion of a patient representative. In addition, online focus groups were held. They consisted of adults with OI from different countries, and they determined which questions matter the most to the OI community worldwide., Results: After three Delphi rounds, the expert team reached a consensus on the final set of measuring instruments, which included pulmonary function testing and patient self-reporting of symptoms related to breathing and sleep. Two questionnaires were decided upon: St. George's Respiratory Questionnaire (shortened version) and four questions regarding sleep. Patients should be screened for a history of pneumonia. Advanced testing for select patients by a pulmonologist would include further pulmonary function tests and a chest radiograph., Conclusions: A standardized set of outcome measures related to pulmonary care of individuals with OI was determined based on what is important to both experts and patients. This included patient-reported outcome measures and basic pulmonary function testing. Using these outcome measures, it can be determined which patients are at high risk for pulmonary complications., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Gabapentin and pregabalin have been associated with an increased risk of fragility fractures. Due to differences in pharmacokinetics, we aimed to assess the fracture-risk difference between the two medicines. We performed a Danish nationwide new user, high-dimensional propensity score-matched cohort study to assess the 90-day risk of fragility fractures among adults, from January 1996 to December 2018. We applied a high-dimensional propensity score to match new users of gabapentin with new users of pregabalin in a 1:1 intention-to-treat approach. Hazard ratios (HRs), incidence rates (IRs) and incidence rate difference (IRD) were obtained. We identified 388 236 eligible patients of which 294 223 and 98 869 initiated gabapentin and pregabalin, respectively. We included 48 272 matched pairs for further analysis. The mean age was 56 (IQR 44-69) years, and the average follow-up was approximately 11 500 person-years (PY). The IRs of fragility fractures were 23.7 (95%CI 21.0-26.7) and 23.2 (95%CI 20.5-26.2) per 1000 PY for gabapentin and pregabalin-exposed patients, respectively. This yielded an HR of 1.02 (95%CI 0.86-1.21) when using gabapentin as the intervention drug and pregabalin as the reference drug. The IRD was estimated to 0.5 PY (95%CI -3.5-4.5). In conclusion, short-term risk of fragility fractures among gabapentin initiators was not different compared to those initiating pregabalin., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60-74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 μg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 μg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 μg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 μg/L for 100, 200, and 300 μg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Evidence of the efficacy of laser thermal ablation (LTA) in benign thyroid nodules is abundant. However, little is known about the effect on quality of life (QoL) of this treatment. Methods: Prospective cohort study investigating the effect of LTA before, three, and six months after LTA on QoL using the thyroid-specific patient-reported outcome (ThyPRO) measure. Patients receiving LTA (laser group [LG]) was compared with a well-characterized control group (CG) from the Danish civil registry. Results: The LG comprised 54 patients, with no age or sex differences compared with the CG ( n  = 739). Sixty-nine percent of the patients had a recurrent cystic thyroid nodule, 6% had a solid nodule, while the remaining 25% were of mixed character. The median nodule volume was 6.8 mL (interquartile range [IQR]: 4.0-11.1) before LTA, and 1.8 mL (IQR: 0.6-4.1) at 6 months post-LTA ( p  < 0.001), corresponding to a median reduction of 78%. All cystic fluid (median: 6 mL; IQR: 2.0-9.0) was aspirated before LTA. Median treatment time was 400 seconds (IQR: 300-600), applying a median energy of 823 J (IQR: 600-1200). At baseline and according to the ThyPRO scales, the LG differed significantly from the CG by having more goiter symptoms, hyperthyroid symptoms, tiredness, and cognitive complaints ( p  < 0.05 for all variables), but only the difference in the goiter symptom scale was of a clinically important magnitude. At three months, the LG experienced a large improvement in goiter symptoms (effect size [ES] = 1.05), a moderate improvement in cosmetic complaints (ES = 0.50), and a moderate improvement in the overall QoL (ES = 0.64). Only the improvements in the goiter symptom and the cosmetic complaint scales were clinically important. Six months after LTA, the anxiety scale showed further improvement of moderate size (ES = 0.52). At 6 months, the results above were maintained, and 79% of patients experienced a large and clinically important improvement in the goiter symptom scale and no clinically important differences were found between the LG and the CG. Conclusions: In this unblinded, prospective observational study, measures of disease-specific QoL were significantly improved compared with preprocedure levels, in patients with solid-cystic nodules.

Background: Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP., Methods: In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system., Results: Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p = 0.041)., Conclusions: BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis., Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events., Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P =0.64). The mean change in aortic valve area was 0.02 cm 2 (95% CI, -0.09 to 0.12 cm 2 ; P =0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P =0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P =0.99), all-cause death (1 versus 4 patients; P =0.37), or cardiovascular events (10 versus 10 patients; P =0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P <0.001)., Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03243890.

Background  The aim of this study was to assess patient-reported symptoms and health-related quality of life, 12 to 24 months after injury in patients with midfacial fractures. Methods  Patients diagnosed with midfacial fractures were assessed regarding symptoms related to the fracture as well as assessment of the patients overall health-related quality of life using the Gothenburg Trismus Questionnaire (GTQ), the Folkestad facial trauma questionnaire, and EuroQol five-dimensional (EQ-5D). Questionnaires were distributed to the study patients 12 to 24 months after the trauma. Medical records were retrospectively surveyed for age, gender, trauma etiology, date of injury, fracture classification, treatment regimen, and time of surgery. Results  Sixty-seven percent of the study group reports sensibility disturbance in the face 12 to 24 months after trauma and 52% reported cosmetic consequences related to the trauma. Numbness in the face was the symptom reported to be most disturbing for the patients. Few of the patients reported severe jaw-related problems, problems with muscular tension, or eating limitation according to the validated questionnaire GTQ. Conclusion  Sensibility disturbance remains a significant and common symptom 12 to 24 months after midfacial trauma. There is a need for a validated patient-reported outcome instrument for facial trauma that covers multiple aspects of facial trauma such as vision disturbance and diplopia, jaw-related problems, and facial pain as well as sensibility disturbance and cosmetic consequences., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)