Foundation model-driven distributed learning for enhanced retinal age prediction.

OBJECTIVES: The retinal age gap (RAG) is emerging as a potential biomarker for various diseases of the human body, yet its utility depends on machine learning models capable of accurately predicting biological retinal age from fundus images. However, training generalizable models is hindered by potential shortages of diverse training data. To overcome these obstacles, this work develops a novel and computationally efficient distributed learning framework for retinal age prediction. MATERIALS AND METHODS: The proposed framework employs a memory-efficient 8-bit quantized version of RETFound, a cutting-edge foundation model for retinal image analysis, to extract features from fundus images. These features are then used to train an efficient linear regression head model for predicting retinal age. The framework explores federated learning (FL) as well as traveling model (TM) approaches for distributed training of the linear regression head. To evaluate this framework, we simulate a client network using fundus image data from the UK Biobank. Additionally, data from patients with type 1 diabetes from the UK Biobank and the Brazilian Multilabel Ophthalmological Dataset (BRSET) were utilized to explore the clinical utility of the developed methods. RESULTS: Our findings reveal that the developed distributed learning framework achieves retinal age prediction performance on par with centralized methods, with FL and TM providing similar performance (mean absolute error of 3.57 ± 0.18 years for centralized learning, 3.60 ± 0.16 years for TM, and 3.63 ± 0.19 years for FL). Notably, the TM was found to converge with fewer local updates than FL. Moreover, patients with type 1 diabetes exhibited significantly higher RAG values than healthy controls in all models, for both the UK Biobank and BRSET datasets (P < .001). DISCUSSION: The high computational and memory efficiency of the developed distributed learning framework makes it well suited for resource-constrained environments. CONCLUSION: The capacity of this framework to integrate data from underrepresented populations for training of retinal age prediction models could significantly enhance the accessibility of the RAG as an important disease biomarker.

The physical activity paradox; exploring the relationship with pain outcomes. The Tromsø Study 2015-2016.

ABSTRACT: Paradoxical associations have been observed for leisure-time physical activity (LTPA) and occupational physical activity (OPA) and several health-related outcomes. Typically, higher LTPA is associated with health benefits and high OPA with health hazards. Using data from the Tromsø Study (2015-2016), we assessed how questionnaire-based LTPA and OPA (n = 21,083) and accelerometer-measured physical activity (PA) (n = 6778) relate to pain outcomes. Leisure-time physical activity and OPA were categorized as inactive PA, low PA, and moderate-to-vigorous PA and then aggregated into 9 levels, eg, inactive LTPA/inactive OPA. Accelerometer-measured PA included counts/minute, steps/day, and WHO PA recommendations from 2010 to 2020. Three binary pain outcomes (any pain, any chronic pain, and moderate-to-severe chronic pain) were constructed based on pain location, intensity, duration, and impact on daily activities. By using Poisson regression to estimate absolute and relative associations, we found that high LTPA was associated with lower pain prevalence and vice versa for OPA. Compared to inactive LTPA, prevalence ratio (PR) with 95% confidence intervals was lowest for moderate-to-vigorous LTPA, 0.93 (0.89-0.96) for any pain, 0.88 (0.84-0.93) for any chronic pain, and 0.66 (0.59-0.75) for moderate-to-severe chronic pain. Compared to sedentary OPA, the ratio was highest for moderate-to-vigorous OPA, 1.04 (1.01-1.07) for any pain, 1.06 (1.02-1.10) for any chronic pain, and 1.33 (1.21-1.46) for moderate-to-severe chronic pain. Aggregated LTPA and OPA showed lower outcomes for moderate-to-vigorous LTPA combined with lower levels of OPA. Higher levels of accelerometer-measured PA were associated with less pain. To summarize, we found inverse associations for LTPA and OPA. Benefits from LTPA seem to depend on low levels of OPA.

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.

Acquisition of peak bone mass in a Norwegian youth cohort: longitudinal findings from the Fit Futures study 2010-2022.

In a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass. PURPOSE: To examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood. METHOD: In a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16-19 years into adulthood (age of 26-29) on three occasions: 2010-2011 (Fit Futures 1 (FF1)), 2012-2013 (FF2), and 2021-2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3. RESULTS: From the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059-1.082) to 1.076 (1.065-1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029-1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091-1.116); 27 years, 1.063 (1.050-1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133-1.148); 27 years, 1.204 (1.196-1.212), p < 0.001; males: 16 years, 1.179 (1.170-1.188); 27 years, 1.310 (1.296-1.315), p < 0.001). CONCLUSION: BMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.

How is age at menopause and reproductive lifespan associated with chronic pain outcomes in postmenopausal women?

ABSTRACT: Female sex is a prominent risk factor for chronic pain, although the underlying mechanisms are not fully understood. This cross-sectional study aimed to investigate the relationship between age at menopause, reproductive lifespan, and chronic pain in a sample of postmenopausal women aged 40 to 93 years. Data were collected from the Tromsø study conducted in Norway between 2015 and 2016 (Tromsø7). Chronic pain was assessed using a single question, which formed a sample size of 5741 participants. Chronic widespread pain was evaluated using the more comprehensive Graphical Index of Pain, resulting in a sample size of 5920 women. Premenopausal women and those who experienced menstrual cessation due to chemotherapy/radiation or hormonal intrauterine devices were excluded from the analysis. Adjusted relative risk ratios with 95% confidence intervals were calculated to determine associations. The results showed that early menopause was associated with a 1% increase in the prevalence of chronic pain for each year of earlier onset at menopause (0.992, CI 95% 0.985-0.998). This association was also observed in women who experienced natural menopause only. However, the association between menopause and chronic widespread pain did not reach statistical significance in the fully adjusted analysis (0.996, CI 95% 0.975-1.017). There were no significant associations found between reproductive lifespan and either outcome. In conclusion, the findings suggest that early menopause in postmenopausal women is linked to a higher prevalence of chronic pain. However, reproductive lifespan does not appear to have a significant impact on chronic pain or chronic widespread pain.

Distal Lumbar Lordosis is Associated With Reoperation for Adjacent Segment Disease After Lumbar Fusion for Degenerative Conditions.

STUDY DESIGN: A single centre retrospective review. OBJECTIVE: Recent studies have suggested that distal lordosis (L4-S1, DL) remains constant across all pelvic incidence (PI) subgroups, whilst proximal lordosis (L1-L4, PL) varies. We sought to investigate the impact of post-operative DL on adjacent segment disease (ASD) requiring reoperation in patients undergoing lumbar fusion for degenerative conditions. METHODS: Patients undergoing 1-3 level lumbar fusion with the two senior authors between 2007-16 were included. Demographic and radiographic data were recorded. Univariate, multivariate binary logistic regression, and Kaplan Meier survivorship analyses were performed. RESULTS: 335 patients were included in the final analysis. Most had single (67%) or two (31%) level fusions. The mean follow-up was 64-month. Fifty-seven patients (17%) underwent reoperation for ASD at an average of 78-month post-operatively (R group). The R group had a significantly lower mean post-operative DL (27.3 vs 31.1 deg, P < .001) and mean PI (55.5 vs 59.2 deg, P < .05). On univariate analysis, patients with a post-operative DL of <35 deg had higher odds of reoperation for ASD than those with a post-operative DL of ≥35 deg (OR 2.7, P = .016). In the multivariate model, post-operative DL, low/average PI, and spondylolisthesis were all significantly associated with reoperation for ASD. CONCLUSION: This study provides preliminary support to an association between post-operative distal lumbar lordosis and risk of reoperation for ASD in patients undergoing fusions for degenerative conditions. Further multicentre prospective study is needed to independently confirm this association and identify the impact of restoration of physiological distal lumbar lordosis on long term patient outcomes.

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.

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.

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.

Does pain tolerance mediate the effect of physical activity on chronic pain in the general population? The Tromsø Study.

ABSTRACT: Knowledge is needed regarding mechanisms acting between physical activity (PA) and chronic pain. We investigated whether cold pain tolerance mediates an effect of leisure-time physical activity on the risk of chronic pain 7 to 8 years later using consecutive surveys of the population-based Tromsø Study. We included participants with information on baseline leisure-time PA (LTPA) and the level of cold pressor-assessed cold pain tolerance, who reported chronic pain status at follow-up as any of the following: chronic pain for ≥3 months, widespread chronic pain, moderate-to-severe chronic pain, or widespread moderate-to-severe chronic pain. We included 6834 participants (52% women; mean age, 55 years) in counterfactual mediation analyses. Prevalence decreased with severity, for example, 60% for chronic pain vs 5% for widespread moderate-to-severe chronic pain. People with one level higher LTPA rating (light to moderate or moderate to vigorous) at baseline had lower relative risk (RR) of 4 chronic pain states 7 to 8 years later. Total RR effect of a 1-level LTPA increase was 0.95 (0.91-1.00), that is, -5% decreased risk. Total effect RR for widespread chronic pain was 0.84 (0.73-0.97). Indirect effect for moderate-to-severe chronic pain was statistically significant at RR 0.993 (0.988-0.999); total effect RR was 0.91 (0.83-0.98). Statistically significantly mediated RR for widespread moderate-to-severe chronic pain was 0.988 (0.977-0.999); total effect RR was 0.77 (0.64-0.94). This shows small mediation of the effect of LTPA through pain tolerance on 2 moderate-to-severe chronic pain types. This suggests pain tolerance to be one possible mechanism through which PA modifies the risk of moderate-to-severe chronic pain types with and without widespread pain.

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 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.

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.

Local contamination is a major cause of early deep wound infections following open posterior lumbosacral fusions.

PURPOSE: Postoperative surgical site infection in patients treated with lumbosacral fusion has usually been thought to be caused by perioperative contamination. With the proximity of these incisions to the perineum, this study sought to determine if contamination by gastrointestinal and/or urogenital flora should be considered as a major cause of this complication. METHODS: We conducted a retrospective review of adults treated with open posterior lumbosacral fusions between 2014 and 2021 to identify common factors in deep postoperative infection and the nature of the infecting organisms. Cases of tumor, primary infection and minimally invasive surgery were excluded. RESULTS: 489 eligible patients were identified, 20 of which required debridement deep to the fascia (4.1%). Mean age, operative time, estimated blood loss and levels fused were similar between both groups. The infected group had a significantly higher BMI. The mean time from primary procedure to debridement was 40.8 days. Four patients showed no growth, 3 showed Staphylococcus sp. infection (Perioperative Inside-Out) requiring debridement at 63.5 days. Thirteen showed infection with intestinal or urogenital pathogens (Postoperative Outside-In) requiring debridement at 20.0 days. Postoperative Outside-In infections led to debridement 80.3 days earlier than Perioperative Inside-Out infections (p = 0.007). CONCLUSIONS: 65% of deep infections in patients undergoing open lumbosacral fusion were due to early contamination by pathogens associated with the gastrointestinal and/or urogenital tracts. These required earlier debridement than Staphylococcus sp. INFECTIONS: There should be renewed focus on keeping these pathogens away from the incision during the early stages of wound healing.

Pain tolerance after stroke: The Tromsø study.

BACKGROUND: Stroke lesions might alter pain processing and modulation by affecting the widely distributed network of brain regions involved. We aimed to compare pain tolerance in stroke survivors and stroke-free persons in the general population, with and without chronic pain. METHODS: We included all participants of the sixth and seventh wave of the population-based Tromsø Study who had been tested with the cold pressor test (hand in cold water bath, 3°C, maximum time 106 s in the sixth wave and 120 s in the seventh) and who had information on previous stroke status and covariates. Data on stroke status were obtained from the Tromsø Study Cardiovascular Disease Register and the Norwegian Stroke Register. Cox regression models were fitted using stroke prior to study attendance as the independent variable, cold pressor endurance time as time variable and hand withdrawal from cold water as event. Statistical adjustments were made for age, sex, diabetes, hypertension, hyperlipidaemia, body mass index and smoking. RESULTS: In total 21,837 participants were included, 311 of them with previous stroke. Stroke was associated with decreased cold pain tolerance time, with 28% increased hazard of hand withdrawal (hazard ratio [HR] 1.28, 95% CI 1.10-1.50). The effect was similar in participants with (HR 1.28, 95% CI 0.99-1.66) and without chronic pain (HR 1.29, 95% CI 1.04-1.59). CONCLUSIONS: Stroke survivors, with and without chronic pain, had lower cold pressor pain tolerance, with possible clinical implications for pain in this group. SIGNIFICANCE: We found lower pain tolerance in participants with previous stroke compared to stroke-free participants of a large, population-based study. The association was present both in those with and without chronic pain. The results may warrant increased awareness by health professionals towards pain experienced by stroke patients in response to injuries, diseases and procedures.

Longitudinal relationships between habitual physical activity and pain tolerance in the general population.

Physical activity (PA) might influence the risk or progression of chronic pain through pain tolerance. Hence, we aimed to assess whether habitual leisure-time PA level and PA change affects pain tolerance longitudinally in the population. Our sample (n = 10,732; 51% women) was gathered from the sixth (Tromsø6, 2007-08) and seventh (Tromsø7, 2015-16) waves of the prospective population-based Tromsø Study, Norway. Level of leisure-time PA (sedentary, light, moderate, or vigorous) was derived from questionnaires; experimental pain tolerance was measured by the cold-pressor test (CPT). We used ordinary, and multiple-adjusted mixed, Tobit regression to assess 1) the effect of longitudinal PA change on CPT tolerance at follow-up, and 2) whether a change in pain tolerance over time varied with level of LTPA. We found that participants with high consistent PA levels over the two surveys (Tromsø6 and Tromsø7) had significantly higher tolerance than those staying sedentary (20.4 s. (95% CI: 13.7, 27.1)). Repeated measurements show that light (6.7 s. (CI 3.4, 10.0)), moderate (CI 14.1 s. (9.9, 18.3)), and vigorous (16.3 s. (CI 6.0, 26.5)) PA groups had higher pain tolerance than sedentary, with non-significant interaction showed slightly falling effects of PA over time. In conclusion, being physically active at either of two time points measured 7-8 years apart was associated with higher pain tolerance compared to being sedentary at both time-points. Pain tolerance increased with higher total activity levels, and more for those who increased their activity level during follow-up. This indicates that not only total PA amount matters but also the direction of change. PA did not significantly moderate pain tolerance change over time, though estimates suggested a slightly falling effect possibly due to ageing. These results support increased PA levels as a possible non-pharmacological pathway towards reducing or preventing chronic pain.

Gray matter volume and pain tolerance in a general population: the Tromsø study.

ABSTRACT: As pain is processed by an extensive network of brain regions, the structural status of the brain may affect pain perception. We aimed to study the association between gray matter volume (GMV) and pain sensitivity in a general population. We used data from 1522 participants in the seventh wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120 seconds), undergone magnetic resonance imaging (MRI) of the brain, and had complete information on covariates. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume was the independent variable, and analyses were adjusted for intracranial volume, age, sex, education level, and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. FreeSurfer was used to estimate vertexwise cortical and subcortical gray matter volumes from the T1-weighted MR image. Post hoc analyses were performed on cortical and subcortical volume estimates. Standardized total GMV was associated with risk of hand withdrawal (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.93). The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72-0.97) or depression (HR 0.82, 95% CI 0.71-0.94). In post hoc analyses, positive associations between standardized GMV and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain. In conclusion, our findings indicate that larger GMV is associated with longer pain tolerance in the general population.

The Influence of Multilevel Spinal Deformity Surgery on the EuroQol 5 Dimensions' (EQ-5D) Questionnaire and Residential Status in the Elderly: A Prospective, Observational, Multicenter Study.

STUDY DESIGN: Multicenter, international prospective study. OBJECTIVE: This study investigated the clinical outcome up to 2 years after multi-level spinal deformity surgery in the elderly by reporting the minimal clinically important difference (MCID) of EuroQol 5-dimensions (EQ-5D), EQ-VAS, and residential status. METHODS: As an ancillary study of 219 patients ≥60 years with spinal deformity undergoing primary instrumented fusion surgery of ≥5 levels, this study focuses on EQ-5D (3-L) as the primary outcome and EQ-VAS and residential status as secondary outcomes. Data on EQ-5D were compared between pre-operatively and postoperatively at 10 weeks, 12 months, and 24 months. An anchor-based approach was used to calculate the MCID. RESULTS: The EQ-5D index and EQ-VAS, respectively, improved significantly at each time point compared to pre-operatively (from .53 (SD .21) and 55.6 (SD 23.0) pre-operatively to .64 (SD .18) and 65.8 (SD 18.7) at 10 weeks, .74 (SD .18) and 72.7 (SD 18.1) at 12 months, and .73 (SD .20) and 70.4 (SD 20.4) at 24 months). 217 (99.1%) patients lived at home pre-operatively, while 186 (88.6%), 184 (98.4%), and 172 (100%) did so at 10 weeks, 12 months, and 24 months, respectively. Our calculated MCID for the EQ-5D index at 1 year was .22 (95% CI .15-.29). CONCLUSIONS: The EQ-5D index significantly increased at each time point over 24 months after ≥5 level spinal deformity surgery in elderly patients. The MCID of the EQ-5D-3 L was .22. Patients living at home pre-operatively can expect to be able to live at home 2 years postoperatively.

The role of neuroticism and pain in dental anxiety: A twin study.

OBJECTIVES: Accumulating evidence has revealed that dental anxiety is robustly associated with dental care-related pain and discomfort, but also with the personality trait of neuroticism (i.e. the relatively stable disposition to experience the world as distressing, threatening and unsafe). However, there is a near absence of research on these risk factors in samples for which genetic information is available. With the aim of arriving at a more refined understanding of dental anxiety, this twin cohort study assessed genetic and environmental influences on neuroticism, dental care-related pain and dental anxiety, and the relation between these phenotypes. METHODS: Participants were recruited from the Norwegian Twin Registry, and data collections were carried out in 1992-98 (Time 1) and 2011 (Time 2). Well-validated questionnaires were used to assess the study variables, including Corah's Dental Anxiety Scale, the Numerical Pain Rating Scale, the NEO Personality Inventory Revised (Time 2) and Eysenck's Personality Questionnaire (Time 1). Pearson correlation analysis and generalized estimating equations (GEE) were used to investigate phenotypic associations. Analyses of genetic and environmental influences were performed using Cholesky modelling. RESULTS: A total of 746 monozygotic (MZ) and 770 dizygotic (DZ) twins in the age group of 50-65 participated in the study. Moderate estimates of heritability for dental anxiety (0.29), treatment-related pain (0.24) and neuroticism (0.45-0.54) were found. Cholesky modelling showed furthermore that neuroticism assessed at Time 1 and Time 2 was related to dental anxiety and pain via both genetic and individual-specific environmental pathways, albeit not very strongly. The particularly high phenotypic correlation observed between dental care-related pain and anxiety (r = .68) was explained by both overlapping genetic and individual-specific environmental influences (the genetic and environmental correlations were .84 and .63 respectively). CONCLUSIONS: The findings provide deeper insight into the aetiology of dental anxiety and confirm that while it is strongly linked to treatment-related pain experiences, this relation is to a considerable degree independent of general negative affectivity/neuroticism.