Osteogenesis Imperfecta: Skeletal and Non-skeletal Challenges in Adulthood.

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.

Effects of power training in older patients with multiple sclerosis on neurodegeneration, neuromuscular function, and physical function. A study protocol for the "power training in older multiple sclerosis patients (PoTOMS) randomized control trial.

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.

Hyperthyroidism and the risk of non-thyroid cancer: a Danish register-based long-term follow-up study.

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.

Prevalence and consequences of spinal pain among people with type 1 and type 2 diabetes mellitus in Denmark.

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.

Prevalence and consequences of musculoskeletal pain in the upper and lower extremities: A cross-sectional analysis of patients with type 1 and type 2 diabetes in Denmark.

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.

Key4OI Recommendations for Lung Function Guidance in Osteogenesis Imperfecta: Based on an Internationally Performed Comprehensive International Consortium for Health Outcomes Measurement Procedure.

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.

The risk of fragility fractures following initiation of gabapentin and pregabalin-A Danish, nationwide, high-dimensional propensity score-matched cohort study.

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.

Long-Term Selenium-Yeast Supplementation Does Not Affect Bone Turnover Markers: A Randomized Placebo-Controlled Trial.

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).

The Effect of Laser Thermal Ablation on Quality of Life: Improvements in Patients with Solid-Cystic Thyroid Nodules.

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.

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

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 cm2 (95% CI, -0.09 to 0.12 cm2; 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.

Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation.

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.

Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue disorder with considerable clinical and genetic heterogeneity. The clinical hallmark of OI is liability to fractures due to reduced bone strength. Pregnancy and lactation are periods of increased calcium demand resulting in a decrease in maternal bone mineral density (BMD). This self-controlled case series evaluates fracture risk 12- and 19-months prior to conception compared to a period of 12- and 19 months following childbirth in women with OI. This study is based on data from the Danish National Patient Register collected between 1995 and 2018. Modified Poisson models were fitted to estimate Incidence Rate Ratio in the post/pre-pregnancy period/s, adjusted by parity and age. The 12-month observation group included 111 women with 205 pregnancies, and the 19-month observation 108 women with 197 pregnancies. We calculated fracture rates (IR) of 48.78 [95%CI 18.55-79.01] per 1000 person years 12 months prior to conception, and of 27.87 [95%CI 10.60-45.14] in the 12 months post-delivery. Comparing pre- and post-pregnancy period we found an incidence rate ratio (IRR) of 1.00 [95%CI 0.42-2.40]. When adjusting for parity and age at delivery no significant change in the IRR was noted. In the 19 months observation-period, the IR per 1000 person years prior to conception was 74.84 [95%CI 44.25-105.43] and the IR postpartum was 36.86 [95%CI 17.55-56.17], leading to an IRR of 0.61 [95%CI 0.31-1.18]. We could not identify any increased risk of fractures when comparing fracture rates during pregnancy and 12 or 19 months postpartum to fracture rates 12 or 19 months prior to conception.

Osteoarthritis in osteogenesis imperfecta: A nationwide register-based cohort study.

BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic disease characterized by skeletal fragility. Collagen type 1 is found in many tissues and collagen abnormalities may result in organ specific symptomatology. Musculoskeletal pain is a known issue for patients with OI, osteoarthritis (OA) can be a likely cause. Only few studies have investigated the relationship between OI and OA but demonstrated a greater propensity in OI patients to develop rapidly progressing OA. Therefore, we wanted to investigate if OA is more frequent in patients with OI compared to the general population. OBJECTIVE: To evaluate the risk of osteoarthritis in patients with OI. DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study. PARTICIPANTS: From 1977 to 2019, all patients registered with an OI diagnosis and a reference population matched on age and sex 5:1. MEASUREMENTS: Sub-hazard ratios for any, hip, and knee osteoarthritis comparing the OI cohort to the reference population. RESULTS: We identified 907 patients with OI (493 women) and included 4535 patients in the reference population (2465 women). The Sub Hazard Ratio was 2.20 [95% CI 1.73-2.79] for any osteoarthritis with 11.4% of the OI population and 5.4% of the reference population being registered. We found lower incidences of upper extremity joint OA compared to lower joint OA, but upper extremity joint OA was significantly more frequent in the OI population 2.1% vs 0.6%, SHR 3.19 [95% CI 1.78-5.70]. CONCLUSION: Patients with OI have a higher risk of OA than the reference population. MINIABSTRACT: Osteogenesis Imperfecta (OI) is a hereditary connective tissue disorder with skeletal fragility and extraskeletal manifestations. Osteoarthritis is a frequent joint disease and the incidence increases with age. In a population-register-based study, the risk of osteoarthritis was higher in patients with OI at an earlier age compared to a reference population.

Risk of eye diseases in osteogenesis imperfecta - A nationwide, register-based cohort study.

BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary disease caused by affected collagen type 1. Collagen type 1 is an important structural component of the eye. Ocular manifestations in OI are described in literature, but little is known about the risk of eye diseases in OI. OBJECTIVE: To investigate the risk of eye diseases in OI. DESIGN: A Danish nationwide register-based cohort study based on data from the Danish National Patient Register. PARTICIPANTS: All patients registered with an OI diagnosis between January 1977 and December 2018 matched 1:5 with a reference population on gender and birth month and birth year. MEASUREMENTS: Incidence rates (IR) per 1000 patient years and sub-hazard ratio (SHR) for any eye disease, corneal diseases, cataract, refraction disorders, vitreous haemorrhage, retinal detachment, retinopathy, angiopathy, retinal haemorrhage, retinal degeneration, retinal changes, optic nerve disorders, and traumatic eye lesions. RESULTS: We identified 907 OI patients (493 women) and 4535 persons (2465 women) in the reference population. The IR for any eye disease was 4.07 [95% CI 3.41-4.85] in the OI cohort and 1.96 [95% CI 1.89-2.12] in the reference cohort. The two diseases with highest incidence was cataract (2.41 [95%CI 1.93-3.03] vs 1.29 [95% CI 1.12-1.47], SHR 1.76 [95% CI 1.34-2.33]) and glaucoma (1.08 [95% CI 0.77-1.51] vs 0.42 [95% CI 0.33-0.54], SHR 2.33 [95% CI 1.55-3.53]). The absolute risk of most other eye diseases was low, but the SHR indicated a higher risk in the OI cohort compared to the reference group showing statistically increased risk of refractive disorders, vitreous haemorrhage, retinal detachment or ruptures, other retinal diseases (i.e., retinopathy, angiopathy, retinal haemorrhage, degeneration, retinal changes), and optic nerve disorders. Corneal diseases and traumatic eye lesions were not statistically significantly increased in OI-patients. CONCLUSION: Patients with OI have a higher risk of cataract, refractive disorders, glaucoma, vitreous haemorrhages, retinal detachment/ruptures, retinal diseases, and optic nerve disorders.

The Danish Diabetes Musculoskeletal Cohort: Non-Responder Analysis of an Electronic Survey Using Registry Data.

PURPOSE: 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.

Nationwide study on trends in unplanned hospital attendance and deaths during the 7 weeks after the onset of the COVID-19 pandemic in Denmark.

BACKGROUND: The impact of a pandemic on unplanned hospital attendance has not been extensively examined. The aim of this study is to report the nationwide consequences of the COVID-19 pandemic on unplanned hospital attendances in Denmark for 7 weeks after a 'shelter at home' order was issued. METHODS: We merged data from national registries (Civil Registration System and Patient Registry) to conduct a study of unplanned (excluding outpatient visits and elective surgery) hospital-based healthcare and mortality of all Danes. Using data for 7 weeks after the 'shelter at home' order, the incidence rate of unplanned hospital attendances per week in 2020 was compared with corresponding weeks in 2017-2019. The main outcome was hospital attendances per week as incidence rate ratios. Secondary outcomes were general population mortality and risk of death in-hospital, reported as weekly mortality rate ratios (MRRs). RESULTS: From 2 438 286 attendances in the study period, overall unplanned attendances decreased by up to 21%; attendances excluding COVID-19 were reduced by 31%; non-psychiatric by 31% and psychiatric by 30%. Out of the five most common diagnoses expected to remain stable, only schizophrenia and myocardial infarction remained stable, while chronic obstructive pulmonary disease exacerbation, hip fracture and urinary tract infection fell significantly. The nationwide general population MRR rose in six of the recorded weeks, while MRR excluding patients who were COVID-19 positive only increased in two. CONCLUSION: The COVID-19 pandemic and a governmental national 'shelter at home' order was associated with a marked reduction in unplanned hospital attendances with an increase in MRR for the general population in two of 7 weeks, despite exclusion of patients with COVID-19. The findings should be taken into consideration when planning for public information campaigns.

Pseudohyponatraemia caused by acute pancreatitis-derived hypertriglyceridaemia.

We report a case of pseudohyponatraemia due to severe hypertriglyceridaemia-induced acute pancreatitis, stemming from unknown diabetes. A woman in her late 30s was admitted to the local hospital by her general practitioner due to severe hyponatraemia (116 mmol/L) and upper abdominal pain. At admission to the hospital, there was a discrepancy of 19 mmol/L between arterial and venous sodium, along with severe hypertriglyceridaemia and hypercholesterolaemia. Pancreatitis was diagnosed using a CT scan. The patient received plasmapheresis which significantly reduced triglycerides, and venous plasma sodium was normalised indicating pseudohyponatraemia at admission. Finally, a haemoglobin A1c of 83 mmol/mol was found. Diabetes was diagnosed, and insulin was initiated.

A standard set of outcome measures for the comprehensive assessment of osteogenesis imperfecta.

BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic disorder also known as 'brittle bone disease'. The clinical manifestation of OI shows a wide variation. Therefore, care for patients with OI requires an interdisciplinary approach. The effectiveness of particular interventions and treatment protocols of interdisciplinary teams is not clear due to a non-standardized and wide variation of patient outcomes thus making the comparison of outcome measures available in the literature difficult. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of OI that comparisons across interdisciplinary treatment centers for OI will be possible in the future. METHODS: The Key4OI international interdisciplinary working group of 27 members used a consensus-driven modified Delphi approach to develop a set of global outcome measures for patients with OI. The International Classification of Functioning, Disability and Health (ICF), was used to define domains and organize the outcomes from the literature search. After reviewing the outcomes extracted from the literature, trials and registries, the working group agreed on a final selection of domains and their definition (ICF definition as well as a lay description). These domains were then presented to the focus groups who prioritized the outcome domains by taking into account the items important to the OI community. All content was collected and analyzed and final domains were determined. A consensus of appropriate measuring instruments for each domain was reached with Delphi rounds. The entire approach was in line with the International Consortium for Health Outcomes Measurement ICHOM methodology. RESULTS: More than 400 different outcome measures were identified in our literature search. After three Delphi rounds, 24 domains were selected. After the focus group sessions, the number of domains were reduced to 15. A consensus was reached on the measuring instruments to cover these domains for both children and adults. CONCLUSION: The Key4OI project resulted in standard set of outcome measures focused on the needs and wishes of individuals with OI and their families. This outcome set will enable healthcare teams and systems to compare and to improve their care pathways and quality of care worldwide. Further studies are needed to evaluate the implementation of this standardized outcome set.