Prevalence of concerns about falling in people with knee or hip osteoarthritis and the association with pain, function, and psychological factors-a cross-sectional study of 7442 patients treated in primary care.

BACKGROUND: Concerns about falling (CaF) are common in older people and can lead to avoidance of activities, social isolation and reduced physical function. However, there is limited knowledge about CaF in people with osteoarthritis (OA); yet, symptoms may increase CaF. We aimed to evaluate the prevalence of CaF and associated factors in people with knee or hip OA. METHODS: This cross-sectional study used data from the Good Life with osteoArthritis in Denmark registry including patients with OA treated in primary care. CaF was assessed with the Short Falls Efficacy Scale International (Short FES-I, range 7-28, low to high). Associations between CaF and pain, function and psychological factors were evaluated using multivariable linear Tobit regression. RESULTS: In total, 7442 patients were included [mean age 67 years (SD: 9.6), 67% females]. Mean Short FES-I was 9.8 [95% confidence interval (CI): 9.7; 9.8]. Moderate CaF was observed in 48.1% (95% CI: 46.7; 48.9) of participants, whilst 11.3% (95% CI: 10.7; 12.1) had a high level of CaF. CaF was more prevalent in the oldest participants and in females. Pain intensity [ß-value (95% CI): 0.52 (0.48; 0.55)], chair stand test [-0.21 (-0.22; -0.19)] and fear of movement [1.38 (1.19; 1.56)] were significantly associated with increased CaF across age groups and sex. CONCLUSIONS: CaF is common in people with OA, especially in the oldest participants and in females. Higher pain, lower function and psychological distress are associated with CaF; yet, the causality of the associations remain to be determined. Integrating CaF assessments and interventions into OA management in primary care seems highly relevant.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Prevalence of type 2 diabetes in psychiatric disorders: an umbrella review with meta-analysis of 245 observational studies from 32 systematic reviews.

AIMS/HYPOTHESIS: Estimates of the global prevalence of type 2 diabetes vary between 6% and 9%. The prevalence of type 2 diabetes has been investigated in psychiatric populations but a critical appraisal of the existing evidence is lacking, and an overview is needed. This umbrella review summarises existing systematic reviews of observational studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. METHODS: We searched PubMed, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews from inception to 17 January 2021 and screened reference lists of included systematic reviews. On the basis of prespecified criteria, we included systematic reviews investigating the prevalence of type 2 diabetes in adults (aged ≥18 years) with a psychiatric disorder. Titles and abstracts of 5155 identified records and full texts of 431 selected studies were screened by two independent reviewers, based on predefined eligibility criteria and an a priori developed extraction form, following the PRISMA and MOOSE guidelines. Risk of bias was assessed with the ROBIS instrument. Data extracted from primary studies were synthesised using random-effects meta-analyses. RESULTS: A total of 32 systematic reviews with 245 unique primary studies were identified and met inclusion criteria. Twelve had low risk of bias. They reported type 2 diabetes prevalence estimates ranging from 5% to 22% depending on the specific psychiatric disorder. We meta-analysed data for ten categories of psychiatric disorders and found the following prevalence estimates of type 2 diabetes: in people with a sleep disorder: 40%; binge eating disorder: 21%; substance use disorder: 16%; anxiety disorder: 14%; bipolar disorder: 11%; psychosis: 11%; schizophrenia: 10%; a mixed group of psychiatric disorders: 10%; depression: 9%; and in people with an intellectual disability 8%. All meta-analyses revealed high levels of heterogeneity. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is a common comorbidity in people with a psychiatric disorder. Future research should investigate whether routine screening for type 2 diabetes and subsequent prevention initiatives for these people are warranted. PROSPERO registration no. CRD42020159870.

The COVIDPregDK Study: A national survey on pregnancy during the early COVID-19 pandemic in Denmark.

AIM: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark. METHODS: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic. COHORT CHARACTERISTICS: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous. CONCLUSIONS: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Prevalence of long-term opioid therapy in spine center outpatients the spinal pain opioid cohort (SPOC).

PURPOSE: No reference material exists on the scope of long-term problems in novel spinal pain opioid users. In this study, we evaluate the prevalence and long-term use of prescribed opioids in patients of the Spinal Pain Opioid Cohort. METHODS: The setting was an outpatient healthcare entity (Spine Center). Prospective variables include demographics, clinical data collected in SpineData, and The Danish National Prescription Registry. Patients with a new spinal pain episode lasting for more than two months, aged between 18 and 65 years, who had their first outpatient visit. Based on the prescription of opioids from 4 years before the first spine center visit to 5 years after, six or more opioid prescriptions in a single 1-year interval fulfilled the main outcome criteria Long-Term Opioid Therapy (LTOT). RESULTS: Overall, of 8356 patients included in the cohort, 4409 (53%) had one or more opioid prescriptions in the registered nine years period. Of opioid users, 2261 (27%) were NaiveStarters receiving their first opioid prescription after a new acute pain episode; 2148(26%) PreStarters had previously received opioids. The prevalence of LTOT in PreStarters/NaiveStarters was 17.2%/11.2% in their first outpatient year. Similar differences between groups were seen in all follow-up intervals. In the last follow-up year, LTOT prevalence in Prestarters/NaiveStarters was 12.5%/7.0%. CONCLUSIONS: Previous opioid treatment-i.e., before a new acute spinal pain episode and referral to a Spine Center-doubled the risk of LTOT 5 years later. The results underscore clinicians' obligation to carefully and individually weigh the benefits against the risks of prescribing opioid therapy. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Validation of a comorbidity index for use in obstetric patients: A nationwide cohort study.

INTRODUCTION: A previously developed Obstetric Comorbidity Index has been validated in highly selected cohorts. Validation of the index in an unselected population as well as in other health registers is, however, of high importance to determine external validity. MATERIAL AND METHODS: Using nationwide registers, we formed a nationwide cohort including completed pregnancies (both live- and stillborn) in Denmark from 2000 through 2014. Maternal age and 20 comorbid conditions were assessed and weighted. Outcomes were maternal end-organ injury or death within 30 days postpartum. The index's predictive and discriminative ability was estimated by Brier score and the area under the receiver operating characteristic curve (AUC), respectively. Logistic regression analysis was used to estimate odds ratios (OR) with 95% confidence interval (CI). RESULTS: In 876 496 completed pregnancies by 527 079 women, 1.40% (n = 12 314) experienced an outcome. The majority of women (64.1%) did not have any record of a condition included in the index and only 0.3% (n = 3044) had a score >6. The incidence of an outcome increased with increasing comorbidity score from 0.9% (95% CI 0.8-0.9) in women scoring 0% to 10.4% (95% CI 7.6-13.9) in women scoring 9-10. Compared with women scoring 0, a score of 1-2 yielded an OR of 2.34 (95% CI 2.25-2.44), 3-4 an OR of 5.16 (95% CI 4.81-5.54), 5-6 an OR of 4.84 (95% CI 4.31-5.44), and 8-9 an OR of 7.97 (95% CI 6.54-9.72) for experiencing the outcome. The index had a Brier score of 0.01 and an AUC of 0.64. CONCLUSIONS: Despite potential weaknesses in the outcome definition, the Obstetric Comorbidity Index showed a moderate ability to discriminate and predict end-organ injury and death in a nationwide cohort in Denmark, in accordance with previous findings. These results suggest that the index may be a useful tool to control for confounding in health research and clinically to identify women at high risk for adverse maternal outcomes.

Socioeconomic status in Danish women with polycystic ovary syndrome: A register-based cohort study.

INTRODUCTION: Low socioeconomic status (SES) may be associated with increased risk of polycystic ovary syndrome (PCOS) and vice versa. Possible associations between SES, obesity and ethnicity in PCOS are undetermined. MATERIAL AND METHODS: National register-based study including women with PCOS aged 25 years or above (PCOS Denmark and an embedded cohort; PCOS Odense University Hospital [OUH]) and one control population. PCOS Denmark (n = 13 891) included women with PCOS in the Danish National Patient Register. Women in PCOS OUH underwent clinical examination (n = 814). Three age-matched controls were included per patient (n = 41 584). The main outcome measure was SES (personal income, occupational status and education). RESULTS: The median (Q1; Q3) age of women in PCOS Denmark and controls was 33 (29; 39) years. Women with personal income in the lower tertile had a higher probability of a PCOS diagnosis than women in the high-income tertile (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.4-1.6). Women who were unemployed or on welfare payment (aOR 1.5, 95% CI 1.4-1.6), or who retired early (OR 1.8, 95% CI 1.7-2.0) had a higher probability of a PCOS diagnosis than women affiliated to the labor market. Women originating from the Middle East more often had PCOS (aOR 3.2, 95% CI 2.8-3.7) compared with women originating from Europe. In PCOS OUH, SES was lower in obese than in normal weight women. CONCLUSIONS: A diagnosis of PCOS was associated with lower SES. In PCOS, women of foreign origin and women with obesity more often had low SES.

Elevated risk of developing type 2 diabetes in people with a psychiatric disorder: What is the role of health behaviors and psychotropic medication?

AIMS: Several psychiatric disorders are linked with an increased risk of developing type 2 diabetes (T2D), but the mediating mechanisms are unclear. We aimed to investigate health behaviors, obesity, psychotropic medication use, and comorbidity as potential mediating mechanisms explaining these associations. METHODS: We combined data from a large population-based survey with register-based data and followed a sample of 250,013 Danes (≥16 years) for up to 8.9 years. We conducted mediation analyses investigating 10 potential mediators of the associations between psychiatric disorders and incident T2D. RESULTS: Individuals with a substance use disorder, schizophrenia, mood disorder, neurotic disorder, eating disorder, or a personality disorder had a significantly higher risk of developing T2D. Organic disorders, intellectual disabilities, developmental and behavioral disorders were not associated with T2D-risk. For all psychiatric disorders significantly associated with T2D, the use of antidepressant medication had the largest proportional mediating effect on the association (13-32 %). CONCLUSIONS: Use of antidepressant medication had the largest contribution to the associations between psychiatric disorders and incident T2D. Future epidemiological studies and prevention studies should focus on optimizing the use of antidepressant medication with minimal side effects, and the promotion of health behaviors in individuals with a psychiatric disorder to prevent T2D.

Developing and Validating a Lung Cancer Risk Prediction Model: A Nationwide Population-Based Study.

Lung cancer can be challenging to diagnose in the early stages, where treatment options are optimal. We aimed to develop 1-year prediction models for the individual risk of incident lung cancer for all individuals aged 40 or above living in Denmark on 1 January 2017. The study was conducted using population-based registers on health and sociodemographics from 2007-2016. We applied backward selection on all variables by logistic regression to develop a risk model for lung cancer and applied the models to the validation cohort, calculated receiver-operating characteristic curves, and estimated the corresponding areas under the curve (AUC). In the populations without and with previously confirmed cancer, 4274/2,826,249 (0.15%) and 482/172,513 (0.3%) individuals received a lung cancer diagnosis in 2017, respectively. For both populations, older age was a relevant predictor, and the most complex models, containing variables related to diagnoses, medication, general practitioner, and specialist contacts, as well as baseline sociodemographic characteristics, had the highest AUC. These models achieved a positive predictive value (PPV) of 0.0127 (0.006) and a negative predictive value (NPV) of 0.989 (0.997) with a 1% cut-off in the population without (with) previous cancer. This corresponds to 1.2% of the screened population experiencing a positive prediction, of which 1.3% would be incident with lung cancer. We have developed and tested a prediction model with a reasonable potential to support clinicians and healthcare planners in identifying patients at risk of lung cancer.

Can National Registries Contribute to Predict the Risk of Cancer? The Cancer Risk Assessment Model (CRAM).

PURPOSE: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer. METHODS: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer during 2017 excluding nonmelanoma skin cancer. Diagnoses, medication, and contact with general practitioners in the exposure period (2007-2016) were considered for the predictive model. We applied backward selection to all variables by logistic regression to develop a risk model for cancer. We applied the models to the validation cohort, calculated the receiver operating characteristic curves, and estimated the corresponding areas under the curve (AUC). RESULTS: The study population consisted of 4.2 million persons; 32,447 (0.76%) were diagnosed with cancer in 2017. We identified 39 predictive risk factors in women and 42 in men, with age above 30 as the strongest predictor for cancer. Testing the model for cancer risk showed modest accuracy, with an AUC of 0.82 (95% CI 0.81-0.82) for men and 0.75 (95% CI 0.74-0.75) for women. CONCLUSION: We have developed and tested a model for identifying the individual risk of cancer through the use of administrative data. The models need to be further investigated before being applied to clinical practice.

Risk of Developing Type 2 Diabetes in Individuals With a Psychiatric Disorder: A Nationwide Register-Based Cohort Study.

OBJECTIVE: Previous studies have investigated the incidence of type 2 diabetes in individuals with psychiatric disorders, but most studies have focused on a specific psychiatric disorder or a selected sample. More population-based studies are needed to determine these associations in representative samples. We therefore aimed to determine these associations in a nationwide, register-based dynamic cohort study. RESEARCH DESIGN AND METHODS: We analyzed data from 5,005,612 adults living in Denmark between 1995 and 2018, without prior diabetes. We investigated 10 different categories of psychiatric disorders and a composite group with any psychiatric disorder. Individuals with a psychiatric disorder were compared with individuals without using multivariable-adjusted Poisson regression to estimate incidence rate ratios (IRR) of type 2 diabetes. We modeled age-specific incidence rates (IR) for individuals with and without the specific psychiatric disorder. All models were stratified by sex. RESULTS: In total, 334,739 individuals developed type 2 diabetes during follow-up. For all investigated categories of psychiatric disorders, we found increased IR of type 2 diabetes for individuals with versus those without a psychiatric disorder (IRR: men, 1.47 [95% CI 1.45-1.50]; women, 1.65 [95% CI 1.62-1.68]). When we examined age-specific IR, the largest differences were found in the younger population (<50 years). CONCLUSIONS: We found that the IR of type 2 diabetes was higher in individuals with a psychiatric disorder compared with individuals without a psychiatric disorder and particularly high in the younger people with a psychiatric disorder. New studies into the prevention and early detection of type 2 diabetes in these groups are warranted.

Inverse Cross-sectional and Longitudinal Relationships between Diabetic Retinopathy and Obstructive Sleep Apnea in Type 2 Diabetes: Results from a National Screening Program.

Purpose: In previous smaller studies, associations were demonstrated between diabetic retinopathy (DR) and obstructive sleep apnea (OSA), but longitudinal relationships have not been evaluated in larger cohorts. The aim of the present study was to assess the cross-sectional and prospective associations between DR and OSA in a national cohort of patients with type 2 diabetes. Design: Cross-sectional and 5-year longitudinal registry-based cohort study. Participants: For cases, we included 153 238 patients with type 2 diabetes who had attended diabetic eye screening and were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each of these were matched by 5 control participants without diabetes of the same age and gender (n = 746 148). Methods: Exposure and outcome data as well as systemic morbidity and use of medications were identified in national registers, including the DiaBase, the Danish National Patient Register, the Danish National Prescription Registry, and the Danish Civil Registration System. The index date was defined as the date of the first DR screening registered in DiaBase. Main Outcome Measures: Exposure was defined as present and level-specific DR, and main outcomes were crude, age- and gender-adjusted, and multivariable adjusted odds ratios (ORs) for prevalent OSA as well as hazard ratios (HR) for 5-year incident OSA and DR. Results: Patients with type 2 diabetes independently were more likely to have prevalent OSA (OR, 2.01; 95% confidence interval [CI], 1.95-2.08) and to develop OSA within 5 years (HR, 1.55; 95% CI, 1.46-1.64). Patients with type 2 diabetes and DR at baseline were less likely to have prevalent OSA (OR, 0.57; 95% CI, 0.52-0.62) or to demonstrate incident OSA (HR, 0.86; 95% CI, 0.74-0.99). Likewise, patients with OSA had a lower risk to develop DR (HR, 0.83; 95% CI, 0.74-0.92). Conclusions: In a registry-based national cohort study, patients with type 2 diabetes had a higher risk of OSA. However, a 43% decreased risk of prevalent OSA was demonstrated in patients with DR, and prospectively, OSA and DR both were related inversely with each other.

Diabetic retinopathy as a potential marker of Parkinson's disease: a register-based cohort study.

Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, and an association between diabetic retinopathy and Parkinson's disease has been proposed. In this nationwide register-based cohort study, we investigated the prevalence and incidence of Parkinson's disease among patients screened for diabetic retinopathy in a Danish population-based cohort. Cases (n = 173 568) above 50 years of age with diabetes included in the Danish Registry of Diabetic Retinopathy between 2013 and 2018 were matched 1:5 by gender and birth year with a control population without diabetes (n = 843 781). At index date, the prevalence of Parkinson's disease was compared between cases and controls. To assess the longitudinal relationship between diabetic retinopathy and Parkinson's disease, a multivariable Cox proportional hazard model was estimated. The prevalence of Parkinson's disease was 0.28% and 0.44% among cases and controls, respectively. While diabetic retinopathy was not associated with present (adjusted odds ratio 0.93, 95% confidence interval 0.72-1.21) or incident Parkinson's disease (adjusted hazard ratio 0.77, 95% confidence interval 0.56-1.05), cases with diabetes were in general less likely to have or to develop Parkinson's disease compared to controls without diabetes (adjusted odds ratio 0.79, 95% confidence interval 0.71-0.87 and adjusted hazard ratio 0.88, 95% confidence interval 0.78-1.00). In a national cohort of more than 1 million persons, patients with diabetes were 21% and 12% were less likely to have prevalent and develop incident Parkinson's disease, respectively, compared to an age- and gender-matched control population without diabetes. We found no indication for diabetic retinopathy as an independent risk factor for incident Parkinson's disease.

Long-Term Opioid Therapy in Spine Center Outpatients: Protocol for the Spinal Pain Opioid Cohort (SPOC) Study.

BACKGROUND: Spinal pain is the leading cause of patient-years lived with chronic pain and disability worldwide. Although opioids are well documented as an effective short-term pain-relieving medication, more than a few weeks of treatment may result in a diminishing clinical effect as well as the development of addictive behavior. Despite recognition of opioid addiction in pain patients as a major problem commonly experienced in the clinic, no reference material exists on the scope of long-term problems in novel opioid users and the link to clinical outcomes. OBJECTIVE: The main aims of this study are to describe baseline and follow-up characteristics of the Spinal Pain Opioid Cohort (SPOC), to evaluate the general use of opioids in spinal pain when an acute pain episode occurs, and to demonstrate the prevalence of long-term opioid therapy (LTOT). METHODS: Prospective clinical registry data were collected from an outpatient spine center setting during 2012-2013 including patients with a new spinal pain episode lasting for more than 2 months, aged between 18 and 65 years who had their first outpatient visit in the center. Variables include demographics, clinical data collected in SpineData, the Danish National Patient Register, and The Danish National Prescription Registry. The primary outcome parameter is long-term prescription opioid use registered from 4 years before the first spine center visit to 5 years after. RESULTS: This is an ongoing survey. It is estimated that more than 8000 patients fulfill the SPOC inclusion criteria. In 2019, we began the intellectual process of identifying the most relevant supplementary data available from the wide range of existing national registries available in Denmark. We have now begun merging SpineData with relevant opioid data from Danish national registers and will continue to extract data up to 2021-2022. We will also be looking at data regarding somatic or psychiatric hospitalization patterns, patient usage of health care resources, as well as their working status and disability pensions. CONCLUSIONS: To our knowledge, this survey will be the first to document the scope of long-term problems regarding LTOT and opioid addiction following new spinal pain episodes and comparing descriptive follow-up data between substance users and nonusers. TRIAL REGISTRATION: ISRCTN Registry ISRCTN69685117; http://www.isrctn.com/ISRCTN69685117. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21380.

Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B-5) chronic kidney disease: an open cohort multivariable and propensity score analysis from Funen, Denmark.

Bisphosphonates are contraindicated in moderate-to-severe chronic kidney disease patients. However, they are used to prevent fragility fractures in patients with impaired kidney function, despite a lack of evidence on their effects on bone density in these patients. We demonstrated that Alendronate had a positive effect on bone in these patients. PURPOSE: This study aimed to assess the association between alendronate use and bone mineral density (BMD) change in subjects with moderate-severe chronic kidney disease (CKD). METHODS: We created a cohort of CKD stage 3B-5 patients by linking all DXA-based measurements in the Funen area, Denmark, to biochemistry, national health registries and filled prescriptions. Exposure was dispensation of alendronate and the outcome was annualized percentage change in BMD at the femoral neck, total hip and lumbar spine. Individuals were followed from first BMD to the latest of subsequent DXA measurements. Alendronate non-users were identified using incidence density sampling and matched groups were created using propensity scores. Linear regression was used to estimate average differences in the annualized BMD. RESULTS: Use of alendronate was rare in this group of patients: propensity score matching (PSM) resulted in 71 alendronate users and 142 non-users with stage 3B-5 CKD (as in the 1 year before DXA). Whilst alendronate users gained an average 1.07% femoral neck BMD per year, non-users lost an average of 1.59% per annum. The PSM mean differences in annualized BMD were + 2.65% (1.32%, 3.99%), + 3.01% (1.74%, 4.28%) and + 2.12% (0.98%, 3.25%) at the femoral neck, total hip and spine BMD, respectively, all in favour of alendronate users. CONCLUSION: In a real-world cohort of women with stage 3B-5 CKD, use of alendronate appears associated with a significant improvement of 2-3% per year in the femoral neck, total hip and spine BMD. More data are needed on the anti-fracture effectiveness and safety of bisphosphonate therapy in moderate-severe CKD.

Incidence and Predictors of Multiple Fractures Despite High Adherence to Oral Bisphosphonates: A Binational Population-Based Cohort Study.

Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of two or more fractures while on treatment (≥2 FWOT) among users with high adherence. Fractures were considered from 6 months after treatment initiation and up to 6 months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP; Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001, respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p- exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ≥2 FWOT among patients having persisted with treatment ≥6 months with overall medication possession ratio (MPR) ≥80%. Incidence of ≥2 FWOT was 2.4 (95% confidence interval [CI], 1.8 to 3.2) and 1.7 (95% CI, 1.2 to 2.2) per 1000 patient-years (PYs) within Catalonia and Denmark, respectively. Older age was predictive of ≥2 FWOT in both Catalonian and Danish cohorts: subhazard ratio (SHR) = 2.28 (95% CI, 1.11 to 4.68) and SHR = 2.61 (95% CI, 0.98 to 6.95), respectively, for 65 to <80 years; and SHR = 3.19 (95% CI, 1.33 to 7.69) and SHR = 4.88 (95% CI, 1.74 to 13.7), respectively, for ≥80 years. Further significant predictors of ≥2 FWOT identified within only one cohort were dementia, SHR = 4.46 (95% CI, 1.02 to 19.4) (SIDIAP); and history of recent or older fracture, SHR = 3.40 (95% CI, 1.50 to 7.68) and SHR = 2.08 (95% CI: 1.04-4.15), respectively (Denmark). Even among highly adherent users of oral BP therapy, a minority sustain multiple fractures while on treatment. Older age was predictive of increased risk within both study populations, as was history of recent/old fracture and dementia within one but not both populations. Additional and/or alternative strategies should be investigated for these patients.