CD38 deficient mice are not protected from atherosclerosis.

CD38 is a multifunctional enzyme implicated in chemotaxis of myeloid cells and lymphocyte activation, but also expressed by resident cells such as endothelial and smooth muscle cells. CD38 is important for host defense against microbes. However, CD38's role in the pathogenesis of atherosclerosis is controversial with seemingly conflicting results reported so far. To clarify the discrepancy of current literature on the effect of CD38 ablation on atherosclerosis development, we implanted a shear stress modifier around the right carotid artery in CD38-/- and WT mice. Hypercholesterolemia was induced by human gain-of-function PCSK9 (D374Y), introduced using AAV vector (serotype 9), combined with an atherogenic diet for a total of 9 weeks. Atherosclerosis was assessed at the aortic root, aortic arch and the right carotid artery. The findings can be summarized as follows: i) CD38-/- and WT mice had a similar atherosclerotic burden in all three locations, ii) No significant differences in monocyte infiltration or macrophage content could be seen in the plaques, and iii) The amount of collagen deposition in the plaques were also similar between CD38-/- and WT mice. In conclusion, our data suggest that CD38-/- mice are neither protected against nor prone to atherosclerosis compared to WT mice.

The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study.

BACKGROUND: Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture. METHODS: Individual-level data on medications dispensed from pharmacies (2005-2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006-2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model. RESULTS: During 2006-2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1-5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21-25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51-65 years. CONCLUSIONS: Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

Periodontitis is associated with decreased experimental pressure pain tolerance: The Tromsø Study 2015-2016.

AIM: To assess the relationship between periodontitis and experimental pain tolerance. MATERIALS AND METHODS: Participants from the population-based seventh survey of the Tromsø Study with data on periodontitis were included (n = 3666, 40-84 years old, 51.6% women). Pain tolerance was assessed through (i) pressure pain tolerance (PPT) test with a computerized cuff pressure algometry on the leg, and (ii) cold-pressor tolerance (CPT) test where one hand was placed in circulating 3°C water. Cox proportional hazard regression was used to assess the association between periodontitis and pain tolerance adjusted for age, sex, education, smoking and obesity. RESULTS: In the fully adjusted model using the 2012 Centers for Disease Control/American Academy of Periodntology case definitions for surveillance of periodontitis, moderate (hazard ratio [HR] = 1.09; 95% confidence interval [CI]: 1.01, 1.18) and severe (HR = 1.25, 95% CI: 1.11, 1.42) periodontitis were associated with decreased PPT. Using the 2018 classification of periodontitis, having Stage II/III/IV periodontitis was significantly associated with decreased PPT (HR = 1.09; 95% CI: 1.01, 1.18) compared with having no or stage I periodontitis. There were no significant associations between periodontitis and CPT in fully adjusted models. CONCLUSIONS: Moderate and severe periodontitis was associated with experimental PPT.

The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

BACKGROUND: Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON. METHODS: This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set. RESULTS: The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72-0.92). The model attained an accuracy of 76.2% (95% CI, 68.4-83.1), a sensitivity of 74.2% (95% CI, 55.9-87.4) and a specificity of 76.9% (95% CI, 67.6-85.0) in classifying images as non-MS-related ON. CONCLUSION: This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.

Circulating sex-steroids and Staphylococcus aureus nasal carriage in a general male population.

Male sex is associated with higher risk of both colonisation and infection with Staphylococcus aureus (S. aureus). However, the role of sex-steroids in colonisation among men is largely unknown. Thus, the aim of this study was to investigate possible associations between circulating sex-steroids and nasal carriage of S. aureus in a general male population. The population-based Tromsø6 study (2007-2008) included 752 males aged 31-87 years with serum sex-steroids measured by liquid chromatography tandem mass spectrometry and two nasal swab samples for the assessment of S. aureus carriage. Multivariable logistic regression models were used to study the association between sex-steroid concentrations and S. aureus persistent nasal carriage (two positive swabs vs. others), while adjusting for potential confounding factors.S. aureus persistent nasal carriage prevalence was 32%. Among men aged 55 years and above (median age 65 years), there was an inverse dose-response relationship between serum concentration of testosterone and persistent nasal carriage, and carriers had significantly lower mean levels of testosterone (P = 0.028, OR = 0.94 per nmol/l change in testosterone; 95% CI = 0.90-0.98). This association was attenuated when adjusting for body mass index and age (OR = 0.96 per nmol/l change in testosterone; 95% CI = 0.91-1.01). There was no association in the total population. This large population-based study suggests that testosterone levels may be inversely related to S. aureus persistent nasal carriage in older men. Future studies addressing biological mechanisms underlying the male predisposition to S. aureus colonisation and infection may foster preventive interventions that take sex-differences into account.

Low social acceptance among peers increases the risk of persistent musculoskeletal pain in adolescents. Prospective data from the Fit Futures Study.

BACKGROUND: Musculoskeletal pain has a high prevalence in adolescence and causes huge consequences for the individuals and the society. Little knowledge exists on social risk factors for musculoskeletal pain in adolescents. This study aimed to investigate if low social acceptance among peers during the first year of upper secondary school was associated with persistent and severe persistent musculoskeletal pain 2 years later and if psychological distress modified this association. METHODS: Longitudinal data from the Norwegian Fit Futures Study was used. Students in the first year of upper secondary school answered an electronic questionnaire, covering health status, pain, social acceptance among peers, and psychological distress. Persistent musculoskeletal pain was measured 2 years later. Multiple logistic regression analyses and moderation analyses were conducted adjusting for sex and chronic diseases. Main analyses were conducted on participants without persistent musculoskeletal pain at baseline, and secondary analyses were conducted on all participants with and without persistent musculoskeletal pain at baseline. RESULTS: Of 775 participants (52% females), 556 (71.7%) were pain-free at baseline and included in the main analyses. Significant associations between low social acceptance among peers and persistent musculoskeletal pain 2 years later were found in crude (Odds ratio (OR) = 1.8, 95%CI [1.0-3.1]) and adjusted analyses (OR = 1.8, 95%CI [1.0-3.2]). No statistically significant effect modification of psychological distress (p = 0.89) on this association was found. A significant association between low social acceptance and persistent musculoskeletal pain was found in adjusted secondary analyses of all the students (n = 692) (OR = 1.6, 95%CI [1.0-2.3]). CONCLUSIONS: Our results indicate that low social acceptance among peers increases the risk of future persistent musculoskeletal pain in adolescents. Thus, interventions strengthening adolescent's social arenas may be helpful to prevent persistent musculoskeletal pain. TRIAL REGISTRATION: Retrospective registered at clinicaltrials.org NCT04526522 .

Predicting complete heart block after alcohol septal ablation for hypertrophic cardiomyopathy using a risk stratification model and clinical tool.

BACKGROUND: Alcohol septal ablation (ASA) is a proven method of septal reduction for patients with drug refractory, symptomatic hypertrophic obstructive cardiomyopathy (HOCM). This procedure is associated with a 6.5-11% risk of complete heart block (CHB). OBJECTIVE: The aim of this study is to determine factors that predict CHB and to develop a clinical tool for risk stratification of patients. METHODS: Patients were enrolled into an ongoing ASA study. A total of 636 patient procedures were included, 527 of whom were used in the development of the prediction tool, and 109 of whom were used for independent validation. Multivariate analysis was performed with odds ratios used to develop the clinical prediction tool. This was then internally and externally validated. RESULTS: Of the 527 in the prediction cohort, 46 developed CHB. The predictors of CHB were age ≥50 years, pre-ASA left bundle branch block (LBBB), transient procedural high-grade block, post-ASA PR prolongation ≥68 ms, and new bifascicular block. An 11-point clinical prediction tool was developed to classify these factors. Internal validation using a receiver operating characteristic curve revealed an area under the curve of 0.88 for the clinical prediction tool. External validation using 109 contemporary patients revealed a 98% negative predictive value, 24% positive predictive value, 75% sensitivity, and 81% specificity in high-risk patients. CONCLUSION: Among patients undergoing ASA, the risk of CHB can be predicted with easily obtained clinical and electrocardiographic factors. This clinical prediction tool allows identification of high-risk patients who may benefit from additional monitoring and therapy.

Shift work, low-grade inflammation, and chronic pain: a 7-year prospective study.

OBJECTIVES: We investigated prospective associations of shift work with chronic pain and C-reactive protein (CRP), an indicator of inflammation. Furthermore, we elucidated CRP as a possible mediator and/or moderator of effects of shift work on pain. METHODS: Data from a 7 years follow-up study were analyzed (N = 2323). Shift work and chronic pain of "neck/shoulder", "arm/hand", "upper back", "low back", "hip/leg/feet", and "other regions" were measured by questionnaires. "Chronic widespread pain", "number of chronic pain sites", and "any chronic pain" were computed. CRP was measured in serum samples. Logistic and Poisson regressions were conducted. Mediation was assessed by casual mediation analyses and moderation by the Relative Excess Risk due to Interaction (RERI). RESULTS: Shift work was not associated with any chronic pain variable and no mediation was detected. CRP was associated with low back pain, hip/leg pain, and "number of pain sites", and also with the combination of shift work and CRP of 1-2.99 mg/L (compared to: no shiftwork and CRP < 1). Additionally, shiftwork and CRP 1-2.99 mg/L was associated with risk of "any chronic pain" (OR: 1.76, 95% CI: 1.12, 2.85), which was not associated with CRP alone. Moderation analyses suggested the risks for "any chronic pain" and "number of pain regions" increased when individuals with elevated CRP worked shifts-beyond what the separate effects of CRP and shift would suggest. CONCLUSIONS: We found no evidence of shift work in general affecting CRP or chronic pain. However, shift work and elevated CRP combined may influence chronic pain.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A Phase 2, Randomized, Sham-Controlled Trial.

BACKGROUND: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%. METHODS: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise. RESULTS: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). CONCLUSIONS: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234.

Change in physical activity is not associated with change in mental distress among adolescents: the Tromsø study: Fit Futures.

BACKGROUND: Previous research shows that physical activity has a protective effect on mental distress in adults, but the relationship is less researched and seems more ambiguous for adolescents. Studies in this field have typically been cross-sectional by design and based on self-reported physical activity measures, which are known to be vulnerable to response bias. The aim of this study was to investigate the relationship between change in objectively assessed physical activity as measured by accelerometer and change in mental distress among adolescents using longitudinal data from The Tromsø Study: Fit Futures. METHOD: This study was based on data from 676 upper-secondary school students (mean age 16.23 years at baseline, 45.26% boys) from The Tromsø Study: Fit Futures. Physical activity, mental distress and covariates were measured at baseline (T1) and follow-up (T2) 2 years later. Physical activity was objectively measured with an ActiGraph GT3X accelerometer over 7 days. Mental distress was measured with the Hopkins Symptom Checklist-10 (HSCL-10). Change score variables were computed as the difference between T1 and T2 in number of steps, number of minutes of moderate to vigorous physical activity (MVPA) and mental distress between T1 and T2, and analyzed using linear regression analysis. RESULTS: Changes in steps per day were not associated with changes in mental distress in neither the crude, partially, nor fully adjusted model. Neither was changes in minutes of MVPA per day. Interaction effects between change in both steps per day and minutes of MVPA and gender were also not statistically significant, nor was the interaction effects between baseline levels of mental distress and physical activity. CONCLUSION: The results of our study indicate that for adolescents in the sample, change in physical activity is unrelated to change in mental distress over a two-year period.

Cross-sectional study of the differences between measured, perceived and desired body size and their relations with self-perceived health in young adults: The Tromsø Study - Fit Futures 2.

AIMS: The aim of this study was to explore the relationships between measured body size (body mass index (BMI)), perceived body size, weight change wishes and self-perceived health in young adults. METHODS: The participants were recruited from a school-based population study in Norway, the Tromsø Study: Fit Futures 2, carried out in 2012-2013. A total of 629 young women and men (aged 18-23 years) reported on the main variables. The data were collected through weight and height measurements and questionnaires. The analyses were performed with descriptive statistics, the χ2 test and Student's t-test. RESULTS: A total of 20% of the women and 28% of the men were overweight or obese. There were considerable discrepancies between the measured BMI and perceived body size in both sexes. A substantial number of participants wanted to change their weight. Among the 174 women who reported that they were trying to lose weight, as many as 57 (32.8%) had a low normal weight (BMI 18.5-21.9 kg/m2). Correspondingly, among the 66 men who reported that they wanted to gain weight, as many as 19 (28.8%) had a high normal weight (BMI 22-24.9 kg/m2). We found no relation between body size perceptions, weight change wishes and self-perceived health. CONCLUSIONS: Discrepancies between measured and perceived body size and weight change wishes are common findings in young adults. The lack of relation with self-perceived health found in our study is surprising and not easy to interpret. To gain more knowledge about these matters, further research, including both qualitative and quantitative studies, is needed.

Persistent analgesic use and the association with chronic pain and other risk factors in the population-a longitudinal study from the Tromsø Study and the Norwegian Prescription Database.

PURPOSE: Analgesics are commonly used drugs. The long-term effectiveness is mostly unproven, while the risk of several serious adverse effects is well established. We aimed to estimate the prevalence and incidence of persistent analgesic use and the association with chronic pain and sociodemographic and comorbid risk factors. METHODS: The Tromsø Study is an epidemiological, prospective study of health and diseases. We linked the sixth wave (Tromsø 6, 2007-08, n = 12,981) with the Norwegian Prescription Database (NorPD, 2004-13). Persistent analgesic use was defined as the use of analgesics, i.e., either non-steroidal anti-inflammatory drugs, opioids or paracetamol, for ≥90 days with proportion-of-days-covered ≥40 %. The study design provided both cross-sectional and longitudinal data; a cohort of 11,905 persons was followed for 4.5 years. RESULTS: The prevalence of persistent analgesic use was 4 % in general and 10 % among those reporting chronic pain. The incidence rate of persistent analgesic use was 21 per 1000 person-years in general. Baseline chronic pain doubled the risk of incident persistent analgesic use (HR = 2.05, 95 % CI 1.80-2.33). The risk increased with increasing chronic pain severity, as measured by chronic pain duration, frequency, intensity, and number of body locations. Sociodemographic risk factors were older age, female sex, lower education, and most likely lower physical activity. Psychological distress was not a statistical significant risk factor. CONCLUSIONS: This study showed a relatively low prevalence of persistent analgesic use and that the majority of persons reporting chronic pain do not use analgesics persistently.

Assessment of Receiver Signal Strength Sensing for Location Estimation Based on Fisher Information.

Currently there is almost ubiquitous availability of wireless signaling for data communications within commercial building complexes resulting in receiver signal strength (RSS) observables that are typically sufficient for generating viable location estimates of mobile wireless devices. However, while RSS observables are generally plentiful, achieving an accurate estimation of location is difficult due to several factors affecting the electromagnetic coupling between the mobile antenna and the building access points that are not modeled and hence contribute to the overall estimation uncertainty. Such uncertainty is typically mitigated with a moderate redundancy of RSS sensor observations in combination with other constraints imposed on the mobile trajectory. In this paper, the Fisher Information (FI) of a set of RSS sensor observations in the context of variables related to the mobile location is developed. This provides a practical method of determining the potential location accuracy for the given set of wireless signals available. Furthermore, the information value of individual RSS measurements can be quantified and the RSS observables weighted accordingly in estimation combining algorithms. The practical utility of using FI in this context was demonstrated experimentally with an extensive set of RSS measurements recorded in an office complex. The resulting deviation of the mobile location estimation based on application of weighted likelihood processing to the experimental RSS data was shown to agree closely with the Cramer Rao bound determined from the FI analysis.

The role of labor pain and overall birth experience in the development of posttraumatic stress symptoms: a longitudinal cohort study.

BACKGROUND: The aim of this prospective study was to investigate the role of labor pain and overall birth experience in the development of posttraumatic stress symptoms in a comprehensive framework. METHODS: The study sample (N = 1893) comprised women with a vaginal delivery and was drawn from the Akershus Birth Cohort, which targeted all women scheduled to give birth at Akershus University Hospital in Norway. Questionnaires were given at three different stages: from pregnancy weeks 17 to 32, from the maternity ward, and from 8 weeks postpartum. Data were also obtained from the hospital's birth record. Using structural equation modeling, a prospective mediation model was tested. RESULTS: Posttraumatic stress symptoms were significantly related to both labor pain (r = 0.23) and overall birth experience (r = 0.39). A substantial portion (33%) of the effect of labor pain on posttraumatic stress symptoms was mediated by the overall birth experience. CONCLUSIONS: Although the results of this study showed that both labor pain and overall birth experience played a role in the development of posttraumatic stress symptoms after childbirth, overall birth experience appeared to be the central factor. The women's birth experience was not only related to posttraumatic stress symptoms directly but also mediated a substantial portion of the effect of labor pain on posttraumatic stress symptoms. Future work should address which areas of birth experience confer protective effects on women to improve clinical care.

Chronic pain and cardiovascular stress responses in a general population: the Tromsø Study.

We tested whether cardiovascular stress responsiveness is elevated in individuals experiencing chronic pain in a large general population sample. Blood pressure (BP) and heart rate (HR) were assessed at rest, during the cold pressor test, and during subsequent recovery in 554 individuals reporting daily chronic pain and 3,082 individuals free of chronic pain. After correcting for potential confounds, differences as a function of chronic pain status were noted for only 5 of 23 cardiovascular outcomes despite very high statistical power. Compared to the pain-free group, the chronic pain group displayed higher baseline HR/mean arterial pressure (MAP) ratio (p = .03), greater systolic BP (SBP) reactivity during the cold pressor test (p = .04), and higher HR/MAP ratio (p = .047) and significantly less SBP (p = .017) and MAP (p = .041) return to baseline during recovery. Findings suggest that changes in cardiovascular stress responsiveness associated with chronic pain are of limited clinical significance and unlikely to contribute to increased cardiovascular risk in the chronic pain population.

Vitamin D Status During Adolescence and the Impact of Lifestyle Changes: 2 Years' Follow-up From the Fit Futures Study.

CONTEXT: Longitudinal data regarding vitamin D status in adolescence is scarce. This study presents population-based data from an Arctic adolescent population (n = 589) at 16 and 18 years. OBJECTIVE: The aims of this study were to investigate changes in vitamin D status during 2 years in adolescence, and whether lifestyle changes were associated with serum 25-hydroxyvitamin D (s-25(OH)D) at follow-up. METHODS: Fit Futures is a longitudinal study at 69°N in Norway. Participants had their s-25(OH)D levels analyzed in their first and third year of upper secondary school (median age 16 and 18 years), in Fit Futures 1 (FF1) and Fit Futures 2 (FF2), respectively. Self-reported lifestyle habits were registered through questionnaires. The association between lifestyle changes and s-25(OH)D levels at follow-up were calculated by regression analyses, controlling for baseline s-25(OH)D levels. RESULTS: Longitudinal data were available for 309 girls and 280 boys. The proportion of adolescents with s-25(OH)D <50 nmol/L were 73.7% in FF1 and 77.1% in FF2, while the proportion <30 nmol/L constituted 35.7% in FF1 and 40.9% in FF2. Of those with s-25(OH)D <30 nmol/L (severe vitamin D deficiency) in FF1, 73.3% remained severely deficient in FF2. Among boys, an increase in UV exposure was significantly associated with higher s-25(OH)D levels in FF2 (beta; CI [nmol/L] 12.9; 9.1, 16.7). In girls, decreased vitamin/mineral supplement intake was significantly associated with lower s-25(OH)D at FF2 (-6.7; -10.2, -3.1), while increased UV (10.8; 7.0, 14.7) and combined hormonal contraceptive exposure (12.1; 6.0, 18.1) in FF2 was significantly associated with higher s-25(OH)D levels in FF2. CONCLUSION: Severe vitamin D deficiency was prevalent throughout adolescence. Lifestyle changes may alter s-25(OH)D levels in this age group.

The costs of chronic pain-Long-term estimates.

BACKGROUND: Chronic pain is a condition with severe impact on many aspects of life, including work, functional ability and quality of life, thereby reducing physical, mental and social well-being. Despite the high prevalence and burden of chronic pain, it has received disproportionally little attention in research and public policy and the societal costs of chronic pain remain largely unknown. This study aimed to describe the long-term healthcare and work absence costs of individuals with and without self-identified chronic pain. METHODS: The study population were participants in two Norwegian population health studies (HUNT3 and Tromsø6). Participants were defined as having chronic pain based on a self-reported answer to a question on chronic pain in the health studies in 2008. Individuals in the study population were linked to four national register databases on healthcare resource use and work absence. RESULTS: In our study, 36% (n = 63,782) self-reported to have chronic pain and the average years of age was 56.6. The accumulated difference in costs between those with and without chronic pain from 2010 to 2016 was €55,003 (CI: 54,414-55,592) per individual. Extrapolating this to the entire population suggests that chronic pain imposes a yearly burden of 4% of GDP. Eighty per cent of the costs were estimated to be productivity loss. CONCLUSION: Insights from this study can provide a greater understanding of the extent of healthcare use and productivity loss by those with chronic pain and serve as an important basis for improvements in rehabilitation and quality of care, and the education of the public on the burden of chronic pain. SIGNIFICANCE: This was the first study to estimate the economic burden associated with chronic pain in the general population using linked individual-level administrative data and self-reported survey answers. We provide calculations showing that annual costs of chronic pain may be as high as €12 billion or 4% of GDP. Findings from this study highlight the need for a greater understanding of the substantial healthcare use and productivity losses among individuals with chronic pain.

Performance, safety, and biocompatibility of a novel PFO closure device in a long-term porcine model.

BACKGROUND: As the catheter-based device closure of the patent foramen ovale (PFO) is expanding, novel devices aim to address the limitations of first-generation occluders (e.g. bulk, erosion, dislodgment). The second-generation device from Encore Medical (Eagan, MN, USA) features an articulating frame structure which allows the device to better conform to atrial anatomies, has lower disc thickness and metal mass/surface area, and is fully retrievable at any point in the procedure. The aim of the study was to evaluate the feasibility and safety of a novel low-profile, fully retrievable, Encore PFO closure device in the animal model. METHODS: Six swine underwent implantation of the novel PFO occluder under fluoroscopic and intra-cardiac echocardiography guidance and survived for 140 days. Interim transthoracic echocardiography (TTE) was conducted on Day 29. Following terminal angiography and TTE at 140 days, the hearts were subjected to gross and histopathologic analysis. RESULTS: All animals were successfully implanted and survived for 140 days. Interim TTE revealed proper device retention with no blood flow across the septum or thrombus in any of the animals. X-ray and pathology results showed preserved implant integrity with no fractures, and complete integration of the devices into the septum with complete re-endothelialization and nearly complete coverage by a mature, relatively thin neoendocardium. No surface fibrin deposition or thrombosis was reported. CONCLUSIONS: In the standard porcine model, device retention and biocompatibility remained favorable following structural and functional device modifications exemplified by the second-generation PFO occluder from Encore Medical, including marked reduction of metal mass.

Associations between cognitive test scores and pain tolerance: The Tromsø study.

OBJECTIVES: Previous studies have suggested that experimental pain sensitivity is associated with cognitive function. The aim of this study is to assess this relationship in a large population-based sample. METHODS: We included 5,753 participants (aged 40-84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom information on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12-word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain. RESULTS: In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12-word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90-0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89-0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90-0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94-0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89-0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95-1.00, p = 0.082). CONCLUSION: Lower pain tolerance was associated with poorer performance on cognitive tests.