Intrarater and Interrater Reliability of Radiographic Characteristics in Skeletally Immature Patients With Anterior Cruciate Ligament Tears: A PLUTO Study Group Reliability Study.

BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears. STUDY DESIGN: Cohort study (diagnosis). METHODS: Three fellowship-trained orthopaedic surgeons and 1 medical student performed 2 rounds of radiographic measurements on digital imaging (lateral knee radiographs and long-leg radiographs) of skeletally immature patients with ACL tears. Intrarater and interrater reliability for continuous radiographic measurements was assessed with intraclass correlation coefficients (ICCs) across 4 raters with 95% CIs for affected and unaffected side measurements. Interrater reliability analysis used an ICC (2, 4) structure and intrarater reliability analysis used an ICC (2, 1) structure. A weighted kappa coefficient was calculated for ordinal variables along with 95% CIs for both interrater and intrarater reliability. Agreement statistic interpretations are based on scales described by Fleiss, and Cicchetti and Sparrow: <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; and >0.74, excellent. RESULTS: Radiographs from a convenience sample of 43 patients were included. Intrarater reliability was excellent for nearly all measurements and raters. Interrater reliability was also excellent for nearly all reads for all measurements. CONCLUSION: Radiographic reliability of long-leg radiographs and lateral knee x-rays in skeletally immature children with ACL tears is excellent across nearly all measures and raters and can be obtained and interpreted as reliable and reproducible means to measure limb length and alignment. LEVEL OF EVIDENCE: Level III.

Clinical Assessment of Late Health Outcomes in Survivors of Wilms Tumor.

OBJECTIVES: We aimed to clinically characterize the health, neurocognitive, and physical function outcomes of curative treatment of Wilms tumor. METHODS: Survivors of Wilms tumor (n = 280) participating in the St. Jude Lifetime Cohort, a retrospective study with prospective follow-up of individuals treated for childhood cancer at St. Jude Children's Research Hospital, were clinically evaluated and compared to age and sex-matched controls (n = 625). Health conditions were graded per a modified version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Standardized neurocognitive testing was graded by using age-adjusted z-scores. Impaired physical function was defined by age- and sex-matched z-scores >1.5 SD below controls. Modified Poisson regression was used to compare the prevalence of conditions and multivariable logistic regression to examine treatment associations. RESULTS: Median age at evaluation was similar between survivors and controls (30.5 years [9.0-58.0] and 31.0 [12.0-70.0]). Therapies included nephrectomy (100%), vincristine (99.3%), dactinomycin (97.9%), doxorubicin (66.8%), and abdominal (59.3%) and/or chest radiation (25.0%). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI: 6.7-8.2) grade 2 to 4 health conditions, compared to 4.2 (CI: 3.9-4.6) and 2.3 (CI: 2.1-2.5), respectively, among controls. Grade 2 to 4 endocrine (53.9%), cardiovascular (26.4%), pulmonary (18.2%), neurologic (8.6%), neoplastic (7.9%), and kidney (7.2%) conditions were most prevalent. Survivors exhibited neurocognitive and physical performance impairments. CONCLUSIONS: Wilms tumor survivors experience a threefold higher burden of chronic health conditions compared to controls and late neurocognitive and physical function deficits. Individualized clinical management, counseling, and surveillance may improve long-term health maintenance.

Access to health services among sexual minority people in the United States.

Sexual minority people in the United States are less likely to have access to health services when compared to their heterosexual counterparts. Less is known about the within-group sociodemographic memberships among sexual minority people regarding access to health services. Using data from a nationally representative sample, a series of univariate and bivariate analyses were used to determine associations between sociodemographic group membership and access to health services. Results suggest there are significant differences in access to health services within the sexual minority population. Differences in access to health services when considering sex-at-birth, sexual identity, age, race/ethnicity, urbanicity, education level and income status were found. These findings offer insight into the role sociodemographic group membership has on the equity of access to health services. Specifically, results indicated that disproportionate access to health services among sexual minority people were more pronounced among those with group membership who experience social marginalisation. This was particularly true for sexual minority people who were bisexual, younger, Black and Latinx, lower-income earners and sexual minority people with less education attainment. Results from this study may be used to inform policies and practices aimed at improving access to health services including, but not limited to, the expansion of the Affordable Care Act and continued development of Federally Qualified Health Centers, while acknowledging the role of within-group differences among sexual minority people.

Assessment of Skeletal Maturity and Postoperative Growth Disturbance After Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: A Systematic Review.

BACKGROUND: Growth disturbance is an uncommon but potentially serious complication after anterior cruciate ligament (ACL) reconstruction in skeletally immature patients. PURPOSE: To describe how the pediatric ACL literature has assessed preoperative skeletal maturity and the amount of growth remaining and to comprehensively review the incidence, reporting, and monitoring of postoperative growth disturbance. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: This review included studies reporting original research of clinical outcomes of skeletally immature patients after ACL reconstruction. Patient characteristics, surgical techniques, preoperative assessments of skeletal maturity or growth remaining, and postoperative assessments of growth disturbances were extracted. RESULTS: A total of 100 studies met inclusion criteria. All studies reported chronological age, and 28 studies (28%) assessed skeletal age. A total of 44 studies (44%) used Tanner staging, and 12 studies (12%) obtained standing hip-to-ankle radiographs preoperatively. In total, 42 patients (2.1%) demonstrated a leg length discrepancy (LLD) >10 mm postoperatively, including 9 patients (0.5%) with LLD >20 mm; furthermore, 11 patients (0.6%) with LLD underwent growth modulation. Shortening was the most common deformity overall, but overgrowth was reported more frequently in patients who had undergone all-epiphyseal techniques. Most LLDs involved the femur (83%). A total of 26 patients (1.3%) demonstrated a postoperative angular deformity ≥5°, and 9 of these patients underwent growth modulation. The most common deformities were femoral valgus (41%), tibial recurvatum (33%), and tibial varus (22%). Although standing hip-to-ankle radiographs were the most common radiographic assessment of growth disturbance, most studies inadequately reported the clinical and radiographic methods of assessment for growth disturbance. Additionally, only 35% of studies explicitly followed patients to skeletal maturity. CONCLUSION: This systematic review described significant variability in the reporting and monitoring of growth-related complications after ACL reconstruction in skeletally immature patients. The incidence of LLD and angular deformity appeared to be low, but the quality of research was not comprehensive enough for accurate assessment. REGISTRATION: CRD42019136059 (PROSPERO).

Does Insurance Status Affect Treatment of Children With Tibial Spine Fractures?

BACKGROUND: Previous studies have reported disparities in orthopaedic care resulting from demographic factors, including insurance status. However, the effect of insurance on pediatric tibial spine fractures (TSFs), an uncommon but significant injury, is unknown. PURPOSE: To assess the effect of insurance status on the evaluation and treatment of TSFs in children and adolescents. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We performed a retrospective cohort study of TSFs treated at 10 institutions between 2000 and 2019. Demographic data were collected, as was information regarding pre-, intra-, and postoperative treatment, with attention to delays in management and differences in care. Surgical and nonsurgical fractures were included, but a separate analysis of surgical patients was performed. Univariate analysis was followed by purposeful entry multivariate regression to adjust for confounding factors. RESULTS: Data were collected on 434 patients (mean ± SD age, 11.7 ± 3.0 years) of which 61.1% had private (commercial) insurance. Magnetic resonance imaging (MRI) was obtained at similar rates for children with public and private insurance (41.4% vs 41.9%, respectively; P≥ .999). However, multivariate analysis revealed that those with MRI performed ≥21 days after injury were 5.3 times more likely to have public insurance (95% CI, 1.3-21.7; P = .02). Of the 434 patients included, 365 required surgery. Similar to the overall cohort, those in the surgical subgroup with MRI ≥21 days from injury were 4.8 times more likely to have public insurance (95% CI, 1.2-19.6; P = .03). Children who underwent surgery ≥21 days after injury were 2.5 times more likely to have public insurance (95% CI, 1.1-6.1; P = .04). However, there were no differences in the nature of the surgery or findings at surgery. Those who were publicly insured were 4.1 times more likely to be immobilized in a cast rather than a brace postoperatively (95% CI, 2.3-7.4; P < .001). CONCLUSION: Children with public insurance and a TSF were more likely to experience delays with MRI and surgical treatment than those with private insurance. However, there were no differences in the nature of the surgery or findings at surgery. Additionally, patients with public insurance were more likely to undergo postoperative casting rather than bracing.

Quantitative assessment of the vascularity of the skeletally immature patella: a cadaveric study using MRI.

PURPOSE: While predominant blood supply to the adult patella enters inferomedially, little is known about skeletally immature patellar perfusion. Improved knowledge of immature patella vascularity can further understanding of osteochondritis dissecans, dorsal defects of the patella and bipartite patella, and help ensure safe surgical approaches. We hypothesized that the immature patella would exhibit more uniform blood flow. The study purpose was to quantify immature patella regional perfusion in comparison with adults. METHODS: Ten cadaveric knees were utilized (five immature, five mature). The superficial femoral artery was cannulated proximally. Signal enhancement increases were compared from pre- to post-contrast MRI to assess relative arterial contributions to patella regions (quadrants, anterior/posterior, superior/inferior, medial/lateral, and outer/inner). RESULTS: Quantitative-MRI analysis revealed similar distribution of enhancement between the immature and mature patella. The inferior pole exhibited significantly higher arterial contribution versus superior pole in both immature and mature groups (p = 0.009; both groups), while the inferomedial quadrant had the highest arterial contribution of all quadrants in both groups. The superolateral quadrant demonstrated the lowest arterial contribution in the immature group and second lowest in the adult group. The patella outer periphery had significantly greater arterial contribution than the inner central region in both immature (p = 0.009) and mature (p = 0.009) groups. CONCLUSION: Distribution of arterial contributions between the immature and mature patella was similar. Our results highlight the importance of inferior and inferomedial blood supply in both immature and mature patellas. These findings have implications for paediatric and adult patients; surgical damage to inferior patellar vessels should be avoided to prevent associated complications.

Mental Health and Health Risk Behaviors of Active Duty Sexual Minority and Transgender Service Members in the United States Military.

Purpose: The aim of this study was to examine health risk behaviors and mental health outcomes among sexual minority and transgender active duty military service members and their heterosexual and cisgender counterparts. Methods: Participants (N = 544) were recruited by using respondent-driven sampling between August 2017 and March 2018 and completed an online survey by using validated measures of cigarette smoking, alcohol use, anxiety, depression, post-traumatic stress disorder (PTSD), and suicidality. Bayesian random intercept multiple logistic regressions were used to understand differences between sexual minority participants and heterosexual participants as well as between transgender participants and both their cisgender sexual minority and cisgender heterosexual peers. Results: Cisgender sexual minority women service members were more likely to meet criteria for problematic alcohol use (adjusted odds ratio [aOR] = 10.11) and cigarette smoking (aOR = 7.12) than cisgender heterosexual women. Cisgender sexual minority men had greater odds of suicidality (aOR = 4.73) than their cisgender heterosexual counterparts. Transgender service members had greater odds of anxiety, PTSD, depression, and suicidality than their cisgender peers. Conclusion: Military researchers and policymakers who seek to improve the overall health and well-being of sexual minority and transgender service members should consider programs and policies that are tailored to specific health outcomes and unique sexual minority and transgender subgroups.

Assessment of cerebrovascular responses to physiological stimuli in identical twins using multimodal imaging and computational fluid dynamics.

There is acknowledged variability in the Circle of Willis (CoW) in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. We aimed to demonstrate the feasibility of combining high-resolution imaging techniques and computational fluid dynamics (CFD) to describe cerebrovascular structure and function in vivo. We tested our methodology by examining the null hypothesis that monozygotic twins (18-30 yr) would exhibit similar CoW structure and function. Six twin pairs underwent 3T magnetic resonance angiography of the head and neck and B-mode Doppler ultrasound for velocity and diameter recordings in the vertebral and internal carotid arteries under three conditions (rest, hypercapnia, and exercise). Artery diameter, length, tortuosity, and bifurcation angle were assessed in regions of interest of the CoW. We simulated hemodynamics to determine the cardiac-cycle time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). We observed low and insignificant intraclass correlations (ICC) between twins in all regions for diameter (ICC range 0.000-0.657, P > 0.05), two of four regions for length (ICC range 0.355-0.368, P > 0.05), all regions for tortuosity (ICC range 0.270-0.505, P > 0.05), and all bifurcation angles (ICC range 0.000-0.547, P > 0.05). Similarly, no significant correlations were apparent for cerebral blood flow or CFD-derived measures of TAWSS, OSI, and RRT, at rest or in response to hypercapnia or exercise. Therefore, differences exist in CoW structure and associated shear stress in response to physiological stimulation. These data suggest that the structure, function, and health of cerebrovascular arteries are not primarily genetically dependent.NEW & NOTEWORTHY There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. Using a combination of magnetic resonance imaging, high-resolution Doppler ultrasound, and computational fluid dynamic modeling, we show that monozygotic twins exhibit differences in cerebrovascular structure and function when exposed to physiological stimuli. These data suggest that the morphology, function, and health of cerebrovascular arteries are not primarily genetically determined.

The Epidemiology of Back Pain in American Children and Adolescents.

STUDY DESIGN: Cross-sectional survey. OBJECTIVE: To determine the prevalence of back pain in American children and adolescents, with a focus on anatomic region, duration, severity, and treatment patterns, and to investigate for any predictive variables. SUMMARY OF BACKGROUND DATA: No study has examined the prevalence of back pain in American children and adolescents in the last 15 years. Because the prevalence of back pain varies greatly by country and year of investigation, previous studies are not generalizable. METHODS: A United States epidemiologic cross-sectional survey-based investigation was performed in children and adolescents ages 10 and 18 years old, equally split by age and sex, and representing census-weighted distributions of state of residence, race/ethnicity, and health insurance status. Prevalence of back pain was evaluated and described. RESULTS: In total, 1236 (33.7%) participants reported experiencing back pain within the last year and 325 (8.9%) reported severe back pain within the last year. Prevalence of back pain increased with age and was significantly more common in females, P < 0.001 for both. Treatment for back pain was sought by 505 (40.9%) of the participants with pain, of which physical therapy was the most common. Invasive procedural treatment (e.g., injections, surgery) were rare and comprised only 61 (1.6%) of study participants. In addition, government insurance and lack of insurance coverage was associated with low treatment seeking behavior compared to private insurance users (P = 0.010 and P = 0.006, respectively). CONCLUSION: Despite how commonly it presents, the majority of young patients with back pain do not report procedural treatment such as injections or surgery. However, because many American children and adolescents seek treatment, future research on the etiology, treatment, and prevention of back pain in children and adolescents is essential to reducing a common and financially demanding problem. LEVEL OF EVIDENCE: 4.

Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology.

The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions.

Assessment of the human cutaneous microvasculature using optical coherence tomography: Proving Harvey's proof.

William Harvey proved the circulation of blood 400 years ago using a combination of ligature application and astute observation that presaged the existence of capillaries. Here we report findings, based on our development of a novel application of optical coherence tomography (OCT), that directly confirm the impact of cuff inflation on microvessels as small as ~30µm. By emulating Harvey's proofs, using cuff inflation at low pressure in the presence and absence of skin heating, we have imaged and quantified significant effects on microvascular diameter and density in humans in vivo. The application of cuff pressure significantly increased microvascular diameter (40.5 ± 4.6 vs 47.1 ± 3.9 µm, P = .01) and density (8.33 ± 4.3 vs 15.1 ± 4.9%, P < .01). These impacts were reversed by cuff deflation. Our study also showed the profound impacts of skin heating on microvessel diameter (46.7 ± 5.8 vs 70.6 ± 7.8 µm, P < .01) and density (14.2 ± 6.5 vs 43.2 ± 9%, P < .01) in vivo, which were further exacerbated by cuff inflation. Our approach to the direct visualization of the human skin microvasculature is non-invasive, safe, and easily applied. Future experiments might be directed at questions of microvascular physiology and pathophysiology, such as how different mammals thermoregulate and what impacts cardiovascular disease and diabetes have on microvascular structure and function.

Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans.

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes.

Novel Noninvasive Assessment of Microvascular Structure and Function in Humans.

INTRODUCTION: Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 µm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF). METHODS: Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C-44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days. RESULTS: Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 µm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 µm·s), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland-Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux. CONCLUSIONS: Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.

Age Cohort and Health Service Utilization Among Gay Men.

Gay men report unique health disparities and service utilization trends compared to their heterosexual peers including a lack of health-care participation which may lead to chronic health conditions. Limited research has been conducted analyzing group differences among gay men such as the influence of one's age cohort on disparities. The aim of this study was to examine the association age cohort has on health service utilization among gay men. A sample of 383 self-identified gay men was collected by the San Francisco Department of Public Health. Older men were less likely to have visited a medical provider in the past 12 months compared to middle-aged men (OR = 0.10; 95% CI [2.47, 39.8]) and younger men (OR = 0.35; 95% CI [1.28, 10.42]). However, older men were more likely to have a usual source of medical care compared to younger men (OR = 4.0; 95% CI [.05, .84]). Age cohort differences in health-care service utilization appear to exist among gay men. This study highlights additional areas for exploration including the impact HIV and socioeconomic status have on health-seeking behavior and health service utilization.

Cost-Utility Analysis of Routine Anxiety and Depression Screening in Patients Consulting for Osteoarthritis: Results From a Clinical, Randomized Controlled Trial.

OBJECTIVE: To investigate the cost-effectiveness (cost-utility) of introducing general practitioner screening for anxiety and depression in patients consulting for osteoarthritis (OA). METHODS: A cluster-randomized trial-based economic evaluation to assess general practitioners screening for anxiety and depression symptoms in patients consulting for OA compared to usual care (screening for pain intensity) was undertaken over a 12-month period from a UK National Health Service and societal perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were estimated, and cost-effectiveness acceptability curves controlling for cluster-level data were constructed. The base-case analysis used the net benefit regressions approach. The 2-stage nonparametric sampling technique was explored in a sensitivity analysis. RESULTS: The base-case analysis demonstrated that the intervention was as costly as, and less effective than, the control (QALY differential -0.029 [95% confidence interval -0.062, 0.003]). In the base-case analyses, general practitioner screening for anxiety and depression was unlikely to be a cost-effective option (probability <5% at £20,000/QALY). Similar results were observed in all sensitivity analyses. CONCLUSION: Prompting general practitioners to routinely screen and manage comorbid anxiety and depression in patients presenting with OA is unlikely to be cost-effective. Further research is needed to explore clinically effective and cost-effective models of managing anxiety and depression in patients presenting with clinical OA.

Synchrotron imaging and Markov Chain Monte Carlo reveal tooth mineralization patterns.

The progressive character of tooth formation records aspects of mammalian life history, diet, seasonal behavior and climate. Tooth mineralization occurs in two stages: secretion and maturation, which overlap to some degree. Despite decades of study, the spatial and temporal pattern of elemental incorporation during enamel mineralization remains poorly characterized. Here we use synchrotron X-ray microtomography and Markov Chain Monte Carlo sampling to estimate mineralization patterns from an ontogenetic series of sheep molars (n = 45 M1s, 18 M2s). We adopt a Bayesian approach that posits a general pattern of maturation estimated from individual- and population-level mineral density variation over time. This approach converts static images of mineral density into a dynamic model of mineralization, and demonstrates that enamel secretion and maturation waves advance at nonlinear rates with distinct geometries. While enamel secretion is ordered, maturation geometry varies within a population and appears to be driven by diffusive processes. Our model yields concrete expectations for the integration of physiological and environmental signals, which is of particular significance for paleoseasonality research. This study also provides an avenue for characterizing mineralization patterns in other taxa. Our synchrotron imaging data and model are available for application to multiple disciplines, including health, material science, and paleontological research.

The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).

BACKGROUND: Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. METHODS: The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. FINDINGS: Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. INTERPRETATION: The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population. FUNDING: The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Economic Decision Model for First-Time Traumatic Patellar Dislocations in Adolescents.

BACKGROUND: The surgical management of traumatic patellar dislocations in adolescents is associated with a lower rate of recurrent dislocations compared with nonoperative care. However, the attendant cost of surgery and the quality-of-life benefit of a surgical treatment strategy are unclear. PURPOSE: To compare the cost-utility of 3 management strategies for acute first-time patellar dislocations in adolescents: (1) nonoperative treatment only, (2) initial nonoperative treatment with surgery only for recurrent dislocations, and (3) immediate surgery. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: A 10-year state-transition Markov model was constructed to compare the cost-utility of the 3 index treatment protocols. Utilities used to define health states were derived from a telephone interview of 60 adolescents with a history of acute patellar dislocations. The probability of transition between each health state was informed by the available literature. Direct costs were estimated using a statewide ambulatory surgery database, and indirect costs were estimated based on parental lost productivity. Effectiveness was expressed in quality-adjusted life years (QALYs). The principal outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS: In the base case for our model, nonoperative treatment only was the least costly ($7300) but also the least effective (5.30 QALYs); initial nonoperative treatment with delayed surgery cost $10,500 for a 5.93 QALY benefit, while immediate surgical treatment cost $17,100 and provided 6.32 QALY benefits. Compared with nonoperative treatment only, initial nonoperative treatment with delayed surgery was associated with an ICER of $5100 per QALY. When immediate surgery was compared with a strategy of delayed surgery, immediate surgery provided incremental benefits at an ICER of $17,000 per QALY. The model was sensitive to the probability of surgical versus nonoperative treatment to achieve a full return to preinjury activity versus an intermediate lower state. When the probability of achieving a full return to preinjury activity with initial nonoperative treatment exceeds 47.5% (compared with 34.2% in the base case), then initial nonoperative treatment with delayed surgery is preferred to immediate surgery. Similarly, when the probability of achieving a full return to full preinjury activity with surgery falls below 51% (compared with 64% in the base case), then delayed surgery after initial nonoperative treatment is preferred. CONCLUSION: Immediate surgery and delayed surgical treatment are both cost-effective treatment options; however, immediate surgical treatment provides the highest QALY gains within a 10-year time horizon. Our model sensitivity analysis highlights the role of optimizing functional and quality-of-life benefits in the treatment of acute traumatic patellar dislocations. These findings have implications for clinical guidelines and policy decisions relating to adolescent patellar dislocations.