Reallocating time spent in sleep, sedentary behavior and physical activity and its association with pain: a pilot sleep study from the Osteoarthritis Initiative.

OBJECTIVE: Being physically active has broad health benefits for people with osteoarthritis (OA), including pain relief. Increasing physical activity (PA) requires reducing time in other behaviors within a fixed 24-h day. We examined the potential benefits in relation to pain from trading time in one type of wake or sleep behavior for another. METHOD: In this cross-sectional study, we used isotemporal logistic regression models to examine the estimated effect on pain from replacing time in one behavior with equal time in another, controlling for sociodemographic and health factors. Stratified analysis was conducted by the report of restless sleep. Sleep and wake behaviors [sedentary behavior (SB), light PA, moderate PA] were monitored by accelerometer in a pilot study of 185 Osteoarthritis Initiative (OAI) participants. Outcomes were bodily pain interference and knee pain. RESULTS: Moderate PA substituted for an equivalent time in sleep or other types of wake behaviors was most strongly associated with lower odds of pain (bodily pain interference odds reduced 21-25%, knee pain odds reduced 17-20% per 10-min exchange). These beneficial associations were particularly pronounced in individuals without restless sleep, but not in those with restless sleep, especially for bodily pain interference. CONCLUSION: Interventions promoting moderate physical activities may be most beneficial to address pain among people with or at high risk for knee OA. In addition to encouraging moderate-intensity PA, pain management strategies may also include the identification and treatment of sleep problems.

Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort.

OBJECTIVE: To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. DESIGN: This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data identified THR and TKR. Hs-CRP and genotyping data were collected at baseline. Three CRP GRS were constructed: 1) a 4-SNP GRS comprised of genetic variants representing variation in the CRP gene among European populations; 2) a multilocus 18-SNP GRS of genetic variants significantly associated with CRP levels in a meta-analysis of genome-wide association studies; and 3) a 5-SNP GRS of genetic variants significantly associated with CRP levels among African American women. RESULTS: In analyses conducted separately among each race and ethnic group, there were no significant associations of ln hs-CRP with risk of THR or TKR, after adjusting for age, body mass index, lifestyle characteristics, chronic diseases, hormone therapy use, and non-steroidal anti-inflammatory drug use. CRP GRS were not associated with risk of THR or TKR in any ethnic group. CONCLUSIONS: Serum levels of ln hs-CRP and genetically-predicted CRP levels were not associated with risk of THR or TKR for OA among a diverse cohort of women.

Class II composite resin restorations: faster, easier, predictable.

Composite resin continues to displace amalgam as the preferred direct restorative material in developed countries. Even though composite materials have evolved to include nanoparticles with high physical properties and low shrinkage stress, dentists have been challenged to efficiently create quality, long lasting, predictable restorations. Unlike amalgam, composite resin cannot be condensed making the establishment of a predictable, proper contact more difficult. In addition, composite requires an understanding of adhesives and an appreciation for their exacting application. These facts combined with the precise adaptation and light-curing of multiple layers makes placement of quality Class II composite restorations tedious and time-consuming. For private practicing dentists, it can also have an effect on economic productivity. Clinicians have always wanted an easier, efficient placement technique for posterior composite restorations that rivals that for amalgam. It appears that advances in instrumentation, materials and technology have finally delivered it.

Lay public's use of a support group for general dental problems.

OBJECTIVE: To categorize and tabulate layperson inquiries made to an Internet dental health support site to identify oral conditions and associated behaviors of concern. METHODS: A retrospective tabulation of wall postings was made from an established dental health support website hosted by WebMD over a 2-year period (April 2013-April 2015). A mixed method approach of content and thematic analysis was used. Content analysis identified content of oral health concerns, while thematic analysis using grounded theory identified themes and beliefs concerning associated behaviors. RESULTS: The presence of non-descript growths on the tongue and swelling and/or discoloration of the lips elicited the most inquires. These were often self-diagnosed as oral candidiasis, a STD or a carcinoma, provoking high levels of self-concern. Unprotected sexual activity, excessive ingestion of soft and hard beverages, smoking and overexposure to the sun were the most frequently self-reported behaviors associated with their concerns. Many questions focused upon "normal" healing, including the amount of edema and discomfort that could occur following oral surgery or other dental procedures. Information concerning alternative treatments was often solicited, and many alluded that they had not been provided sufficient information to make informed decisions prior to dental treatment. CONCLUSIONS: Laypersons have many oral health concerns particularly in relationship to the development of undiagnosed pathologies in conjunction with a history of volitional behaviors. The dental community should monitor these sites to provide advice and links to information about common oral health concerns and their possible association with detrimental behaviors.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.

SUMMARY: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. INTRODUCTION: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. METHODS: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. CONCLUSION: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Cognitive function and retinal and ischemic brain changes: the Women's Health Initiative.

OBJECTIVE: To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women. METHODS: This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000-2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996-2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia. RESULTS: Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy. CONCLUSIONS: The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes.

Renal function and nonvertebral fracture risk in multiethnic women: the Women's Health Initiative (WHI).

UNLABELLED: To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION: The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS: A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS: Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNFα soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION: Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery.

The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community.

Semi-automated segmentation to assess the lateral meniscus in normal and osteoarthritic knees.

OBJECTIVE: The goal of this study was to develop an algorithm to semi-automatically segment the meniscus in a series of magnetic resonance (MR) images to use for normal knees and those with moderate osteoarthritis (OA). METHOD: The segmentation method was developed then evaluated on 10 baseline MR images obtained from subjects with no evidence, symptoms, or risk factors of knee (OA), and 14 from subjects with established knee OA enrolled in the Osteoarthritis Initiative (OAI). After manually choosing a seed point within the meniscus, a threshold level was calculated through a Gaussian fit model. Under anatomical, intensity, and range constraints, a threshold operation was completed followed by conditional dilation and post-processing. The post-processing operation reevaluates the pixels included and excluded in the area surrounding the meniscus to improve accuracy. The developed method was evaluated for both normal and degenerative menisci by comparing the segmentation algorithm results with manual segmentations from five human readers. RESULTS: The semi-automated segmentation method produces results similar to those of trained observers, with an average similarity index over 0.80 for normal participants and 0.75, 0.67, and 0.64 for participants with established knee OA with Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) scores of 0, one, and two respectively. CONCLUSION: The semi-automatic segmentation method produced accurate and consistent segmentations of the meniscus when compared to manual segmentations in the assessment of normal menisci in mild to moderate OA. Future studies will examine the change in volume, thickness, and intensity characteristics at different stages of OA.

Incidence of fractures compared to cardiovascular disease and breast cancer: the Women's Health Initiative Observational Study.

UNLABELLED: To compare the absolute risk of fracture to the risk of other conditions by race/ethnicity, we studied 83,724 women, aged 70-79. The projected number of fractures was similar to or exceeded the combined number of cardiovascular events and breast cancers. Osteoporosis prevention efforts should target women of all ethnicities. INTRODUCTION: The relative risk of fracture is lower in non-white compared to white women but the absolute risk of fracture in comparison to other common chronic conditions is uncertain. METHODS: We performed a prospective cohort study of 83,724 women, age 50-79 years. Cardiovascular disease (CVD), invasive breast cancer and all fractures were identified over an average of 7.7 +/- 2.6 years. RESULTS: The incidence of fracture, breast cancer, stroke and CVD varied across ethnicity. The annualized (%) incidence of fracture was greatest in whites (2.4%) and American Indians (2.8%) and lowest among blacks (1.3%). The majority of hip fractures occurred in white women. The projected number of women who will experience a fracture in one year exceeded the combined number of women who would experience invasive breast cancer or a broad category of CVD events in all ethnic groups except blacks. In 10,000 black women, an estimated 153 women would experience CVD, and 35 women, breast cancer compared to 126 women expected to fracture in one year. CONCLUSION: The annual risk of suffering a fracture is substantial in women of all ethnicities. Osteoporosis prevention efforts should target all women irrespective of their race/ethnic backgrounds.

Aesthetic inlays and onlays: the coming of age.

There are many prominent teaching clinicians who feel that inlays and onlays (of whatever colour) are a grossly under-utilised restoration and that crowns are an over-utilised restoration. I think it is worthwhile to examine some of the possible reasons for this unfortunate situation (for our patients) and see if the reasons for dentists' reluctance to incorporate these restorations into their routine services are really valid today.

Two year longitudinal change and test-retest-precision of knee cartilage morphology in a pilot study for the osteoarthritis initiative.

OBJECTIVE: Fast low angle shot (FLASH) and double echo steady state (DESS) magnetic resonance imaging (MRI) acquisitions were recently cross-calibrated for quantification of cartilage morphology at 3T. In this pilot study for the osteoarthritis (OA) initiative we compare their test-retest-precision and sensitivity to longitudinal change. METHOD: Nine participants with mild to moderate clinical OA were imaged twice each at baseline, year 1 (Y1) and year 2 (Y2). Coronal 1.5mm FLASH and sagittal 0.7mm DESS sequences were acquired; 1.5mm coronal multiplanar reformats (MPR) were obtained from the DESS. Patellar, femoral and tibial cartilage plates were quantified in a paired fashion, with blinding to time point. RESULTS: In the weight-bearing femorotibial joint, average precision errors across plates were 1.8% for FLASH, 2.6% for DESS, and 3.0% for MPR-DESS. Volume loss at Y1 was not significant; at Y2 the average change across the femorotibial cartilage plates was -1.7% for FLASH, -2.8% for DESS, and -0.3% for MPR-DESS. Volume change in the lateral tibia (-5.5%; P<0.03), and in the medial (-2.9%; P<0.04) and lateral femorotibial compartments (-3.8%; P<0.03) were significant for DESS. CONCLUSIONS: FLASH, DESS and MPR-DESS all displayed adequate test-retest precision. Although the comparison between protocols is limited by the small number of participants and by the relatively small longitudinal change in cartilage morphology in this pilot study, the data suggest that significant change can be detected with MRI in a small sample of OA subjects over 2 years.

Novel fast semi-automated software to segment cartilage for knee MR acquisitions.

OBJECTIVE: Validation of a new fast software technique to segment the cartilage on knee magnetic resonance (MR) acquisitions. Large studies of knee osteoarthritis (OA) will require fast and reproducible methods to quantify cartilage changes for knee MR data. In this report we document and measure the reproducibility and reader time of a software-based technique to quantify the volume and thickness of articular cartilage on knee MR images. METHODS: The software was tested on a set of duplicate sagittal three-dimensional (3D) dual echo steady state (DESS) acquisitions from 15 (8 OA, 7 normal) subjects. The repositioning, inter-reader, and intra-reader reproducibility of the cartilage volume (VC) and thickness (ThC) were measured independently as well as the reader time for each cartilage plate. The root-mean square coefficient of variation (RMSCoV) was used as metric to quantify the reproducibility of VC and mean ThC. RESULTS: The repositioning RMSCoV was as follows: VC=2.0% and ThC=1.2% (femur), VC=2.9% and ThC=1.6% (medial tibial plateau), VC=5.5% and ThC=2.4% (lateral tibial plateau), and VC=4.6% and ThC=2.3% (patella). RMSCoV values were higher for the inter-reader reproducibility (VC: 2.5-8.6%) (ThC: 1.9-5.2%) and lower for the intra-reader reproducibility (VC: 1.6-2.5%) (ThC: 1.2-1.9%). The method required an average of 75.4min per knee. CONCLUSIONS: We have documented a fast reproducible semi-automated software method to segment articular cartilage on knee MR acquisitions.

The significance of platelet counts in coagulation studies.

Traditionally, the platelet count recommended for coagulation studies has been less than 10 x 10(9)/L, but the documentation for this is obscure. In the present study, platelet rich plasma (PRPs) and platelet poor plasmas (PPPs) were prepared from the same blood specimen to determine prothrombin times (PTs), International Normalized Ratios (INRs), partial thromboplastin times (PTTs), and their results compared. The measurements of all three of these parameters are not statistically or clinically significant in 100 paired comparisons. Incremented platelet count studies, selected by the number of platelets in the PRPs, showed that platelet counts of at least 199 x 10(9)/L, or perhaps even higher, did not compromise the results of PTs, INRs or PTTs. Such increased platelet counts, however, cannot be tolerated in the various studies for antiphospholipid antibodies, the Lupus Anticoagulant (LAC), or when monitoring heparin therapy with PTTs. Here, the < 10 x 10(9)/L platelet levels must be respected; otherwise the tests would be compromised by platelet-liberated phospholipid (Triplett, Brand et al., 1983) or by Platelet Factor 4, respectively.

The new posterior resins and a simplified placement technique.

BACKGROUND: New heavy-body (packable) composites have been developed for use in posterior direct resin restorations. These materials are promoted as having better handling characteristics and higher physical properties than previous microhybrid composites. METHODS: The authors describe an incremental layering technique that takes advantage of the improved handling characteristics and proposed reduced shrinkage and greater depth of cure. CLINICAL IMPLICATIONS: When this new technique is used with one-bottle adhesives and improved instrumentation, posterior heavy-body composites can be placed faster, easier and possibly more predictably than when medium-body resins and previous techniques are used.

Involving minority and underrepresented women in clinical trials: the National Centers of Excellence in Women's Health.

Recent attention to reducing health disparities among population groups has focused on the need to include in clinical studies, especially clinical trials, participants who represent the diversity of the populations to which study results will be applied. While scientists generally applaud the goal of broadening the characteristics of participants in clinical trials, they are faced with multiple challenges as they seek to include historically underrepresented populations in their research. This article examines the historical and sociocultural context of participation by underrepresented groups, especially women and minorities, in clinical trials, identifies major barriers and challenges facing researchers, and suggests strategies for meeting these challenges. The article draws upon the experiences of the investigators affiliated with the National Centers of Excellence of Women's Health (CoEs).

Dental caries diagnosis.

As with any disease process, the early initiation of therapy for dental caries is often the most effective means to ensure resolution. However, for any therapy to be effective, early diagnosis is paramount to success. Unfortunately, current tools used in dental caries detection are not sensitive enough to diagnose the disease process in its early stages and, frequently, once a diagnosis is made restoration is the only effective means of treatment. Quantitative light-induced fluorescence, electrical conductance measurements, direct digital radiography, and direct fiber optic transillumination are methods that may offer promise as effective tools in diagnosing early dental caries. This article describes some of the research that has been performed to make these methods a reality.