Variety of Fruit and Vegetables and Alcohol Intake are Associated with Gut Microbial Species and Gene Abundance in Colorectal Cancer Survivors.

BACKGROUND: Adherence to the American Cancer Society (ACS) guidelines of avoiding obesity, maintaining physical activity, and consuming a diet rich in fruits, vegetables, and whole grains is associated with longer survival in colorectal cancer (CRC) survivors. Dietary components of the ACS guidelines may act in part by changing the microbiome, which is implicated in CRC outcomes. OBJECTIVES: We conducted a pilot cross-sectional study to explore associations between ACS guidelines and the gut microbiome. METHODS: Stool samples and questionnaires were collected from 28 CRC survivors at the University of California, San Francisco from 2019 to 2020. ACS scores were calculated based on validated questionnaires. Gut microbial community structure from 16S amplicons and gene/pathway abundances from metagenomics were tested for associations with the ACS score and its components using ANOVA and general linear models. RESULTS: The overall ACS score was not significantly associated with variations in the fecal microbiota. However, fruit and vegetable intake and alcohol intake accounted for 19% (P = 0.005) and 13% (P = 0.01) of variation in the microbiota, respectively. Fruit/vegetable consumption was associated with increased microbial diversity, increased Firmicutes, decreased Bacteroidota, and changes to multiple genes and metabolic pathways, including enriched pathways for amino acid and short-chain fatty acid biosynthesis and plant-associated sugar degradation. In contrast, alcohol consumption was positively associated with overall microbial diversity, negatively associated with Bacteroidota abundance, and associated with changes to multiple genes and metabolic pathways. The other components of the ACS score were not statistically significantly associated with the fecal microbiota in our sample. CONCLUSIONS: These results guide future studies examining the impact of changes in the intake of fruits, vegetables, and alcoholic drinks on the gut microbiome of CRC survivors.

Assessing Unique Risk Factors for COVID-19 Complications Among Cancer Patients: A Multi-ethnic Cohort Study.

A myriad of organ-specific complications have been observed with COVID-19. While racial/ethnic minorities have been disproportionately burdened by this disease, our understanding of the unique risk factors for complications among a diverse population of cancer patients remains limited. This is a multi-institutional, multi-ethnic cohort study evaluating COVID-19 complications among cancer patients. Patients with an invasive cancer diagnosis and confirmed SARS-CoV-2 infection were identified from March to November 2020. Demographic and clinical data were obtained and a multivariate logistic regression was employed to evaluate the impact of demographic and clinical factors on COVID-19 complications. The study endpoints were evaluated independently and included any complication, sepsis, pulmonary complications and cardiac complications. A total of 303 patients were evaluated, of whom 48% were male, 79% had solid tumors, and 42% were Hispanic/Latinx (Hispanic). Malignant hematologic cancers were associated with a higher risk of sepsis (OR 3.93 (95% CI 1.58-9.81)). Male patients had a higher risk of sepsis (OR 4.42 (95% CI 1.63-11.96)) and cardiac complications (OR 2.02 (95% CI 1.05-3.89)). Hispanic patients had a higher odds of any complication (OR 2.31 (95% CI 1.18-4.51)) and other race was associated with a higher odds of cardiac complications (OR 2.41 (95% CI 1.01-5.73)). Clinically, fever, cough, and ≥2 co-morbidities were independently significantly associated with any complication. This analysis evaluated covariates that can significantly predict a myriad of complications among a multi-ethnic cohort of cancer patients. The conclusions drawn from this analysis elucidate a mechanistic understanding of differential illness severity from COVID-19.

Association between adherence to the American Cancer Society Nutrition and Physical Activity Guidelines and stool frequency among colon cancer survivors: a cohort study.

PURPOSE: We sought to determine whether adherence to the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines was associated with better bowel function among colon cancer survivors. METHODS: This prospective cohort study included patients surgically treated for stage I-IV colon cancer enrolled in the Lifestyle and Outcomes after Gastrointestinal Cancer (LOGIC) study between February 2017 and May 2021. Participants were assigned an ACS score (0-6 points) at enrollment. Stool frequency (SF) was assessed every 6 months using the EORTC QLQ-CR29. Higher SF is an indication of bowel function impairment. ACS score at enrollment was examined in relation to SF at enrollment and over a 3-year period. Secondarily, we examined associations between the ACS score components (body mass index, dietary factors, and physical activity) and SF. Multivariable models were adjusted for demographic and surgical characteristics. RESULTS: A total of 112 people with colon cancer (59% women, mean age 59.5 years) were included. Cross-sectionally, for every point increase in ACS score at enrollment, the odds of having frequent stools at enrollment decreased by 43% (CI 0.42-0.79; p < 0.01). Findings were similar when we examined SF as an ordinal variable and change in SF over a 3-year period. Lower consumption of red/processed meats and consuming a higher number of unique fruits and vegetables were associated with lower SF (better bowel function) at enrollment. CONCLUSIONS: Colon cancer survivors who more closely followed the ACS nutrition and physical activity guidelines had lower SF, an indication of better bowel function. IMPLICATIONS FOR CANCER SURVIVORS: Our findings highlight the value of interventions that support health behavior modification as part of survivorship care for long-term colon cancer survivors.

COVID-19 Outcomes Among Patients With Cancer: Observations From the University of California Cancer Consortium COVID-19 Project Outcomes Registry.

BACKGROUND: The risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer. METHODS: Clinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality. FINDINGS: Among all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44]). INTERPRETATION: This study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis.

Magnetic Resonance Imaging-Assessed Subchondral Cysts and Incident Knee Pain and Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. METHODS: We used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. RESULTS: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. CONCLUSION: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.

Magnetic Resonance Imaging-Defined Osteoarthritis Features and Anterior Knee Pain in Individuals With, or at Risk for, Knee Osteoarthritis: A Multicenter Study on Osteoarthritis.

OBJECTIVE: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. METHODS: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. RESULTS: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP. CONCLUSION: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP.

The Association of Parity with Greater Dynamic Pronation of the Feet.

BACKGROUND: Postpartum women are at increased risk for lower limb musculoskeletal disorders. Foot arch collapse following pregnancy has been reported as a mechanism for this increased risk. However, dynamic changes during gait in postpartum women have not been reported. Therefore, we assessed the association between parity and dynamic foot pronation during gait. OBJECTIVE: To determine (1) if there is an association between parity and dynamic foot pronation (center of pressure excursion index, CPEI) during gait; and (2) the extent to which there is a dose-effect of parity on foot pronation. DESIGN: The Multicenter Osteoarthritis Study (MOST) Study is a longitudinal cohort study of adults with or at risk for knee osteoarthritis (OA). SETTING: Two communities in the United States, Birmingham, Alabama and Iowa City, Iowa. INTERVENTIONS: Not applicable PARTICIPANTS: A population-based sample of 1177 MOST participants who were female, had complete CPEI and parity data and completed the baseline, 30- and 60-month visits. MAIN OUTCOME MEASURES: Odds of a one quintile decrease in CPEI by parity group and mean CPEI by parity group. RESULTS: In 1177 women, mean age was 67.7 years and mean body mass index (BMI) was 30.6 kg/m2 . As parity increased, there was significantly greater foot pronation, lower mean CPEI: 19.1 (18.2-20.1), 18.9 (18.4-19.4), 18 (17.5-18.6) to 17.5 (16.4-18.6) in the 0 to 4 and >5 children groups, respectively; (P = .002), which remained significant after adjusting for race and clinic site (P = .005). There was a positive linear trend (ß = 1.08, 1.03-1.14) in odds ratios of a one quintile decrease in CPEI (greater pronation) with increasing parity level (P = .004), which remained significant after adjusting for race and clinic site (P = .01). After adjusting for age and BMI, these two associations were no longer statistically significant. CONCLUSIONS: This study indicates a positive correlation between parity and greater dynamic pronation of the feet.

Phenylalanine Is a Novel Marker for Radiographic Knee Osteoarthritis Progression: The MOST Study.

OBJECTIVE: To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach. METHODS: Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis. RESULTS: There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women (P = 0.0002) but not in men. CONCLUSION: Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.

Cross-sectional and longitudinal reliability of semiquantitative osteoarthritis assessment at 1.0T extremity MRI: Multi-reader data from the MOST study.

Objective: To determine reliability among four experienced and calibrated readers in cross-sectional and longitudinal semi-quantitative MRI assessments of knee osteoarthritis (OA) in the Multicenter Osteoarthritis (MOST) study. Design: From all MOST participants with at least one knee with readable 60-month and 84-month paired knee MRIs (1.0 â€‹T extremity systems), we selected 10 subjects having a spectrum of baseline disease severity of cartilage, bone marrow lesions, and meniscal damage and a spectrum of longitudinal changes in severity at 24 months follow-up. MRIs were independently assessed using the WORMS grading system by four musculoskeletal radiologists with the chronological sequence known to the readers. Kappa statistics were used to determine agreement between each pair of readers and Kendall's coefficient of concordance to determine average agreement across readers. Results: For most features, cross-sectional reliability was substantial to almost perfect. Regarding longitudinal reliability (detection of longitudinal change), inter-reader reliability as weighted kappa values ranged from 0.62 to 0.78 for cartilage damage, 0.75-0.88 for bone marrow lesions, 0.75-0.92 for meniscal tears, 0.67-0.95 for meniscal extrusion, 0.51-0.77 for bone attrition, 0.43-0.76 for osteophytes, 0.31-0.70 for Hoffa-synovitis, and 0.47-0.85 for effusion-synovitis. Kendall's coefficient ranged from 0.65 to 0.98. Conclusion: High levels of cross-sectional reliability and moderate to high longitudinal reliability was achieved using four experienced readers in semiquantitative MRI-assessment of most knee OA features.

Relation of Patellofemoral Joint Alignment, Morphology, and Radiographic Osteoarthritis to Frequent Anterior Knee Pain: Data from the Multicenter Osteoarthritis Study.

OBJECTIVE: Patellofemoral (PF) alignment and trochlear morphology are associated with PF osteoarthritis (OA) and knee pain, but whether they are associated with localized anterior knee pain is unknown, which is believed to be a symptom specific to PF joint pathology. We therefore aimed to evaluate the relation of PF alignment and morphology, as well as PFOA and tibiofemoral OA, to anterior knee pain. METHODS: The Multicenter Osteoarthritis Study is a cohort study of individuals with, or at risk for, knee OA. We evaluated cross-sectional associations of PF alignment, trochlear morphology, and PF and tibiofemoral radiographic OA, with localized anterior knee pain (defined with a pain map). We used 2 approaches: a within-person knee-matched evaluation of participants with unilateral anterior knee pain (conditional logistic regression), and a cohort approach comparing those with anterior knee pain to those without (binomial regression). RESULTS: With the within-person knee-matched approach (n = 110; 64% women, mean age 70 years, body mass index [BMI] 30.9), PF alignment, morphology, and tibiofemoral OA were not associated with unilateral anterior knee pain. Radiographic PFOA was associated with pain, odds ratio 5.3 (95% confidence interval [95% CI] 1.6-18.3). Using the cohort approach (n = 1,818; 7% of knees with anterior knee pain, 59% women, mean age 68 years, BMI 30.4), results were similar: only PFOA was associated with pain, with a prevalence ratio of 2.2 (95% CI 1.4-3.4). CONCLUSION: PF alignment and trochlear morphology were not associated with anterior knee pain in individuals with, or at risk for, knee OA. Radiographic PFOA, however, was associated with pain, suggesting that features of OA, more so than mechanical features, may contribute to localized symptoms.

Association of Diabetes Mellitus and Biomarkers of Abnormal Glucose Metabolism With Incident Radiographic Knee Osteoarthritis.

OBJECTIVE: The association of diabetes mellitus (DM) with increased risk of knee osteoarthritis (OA) is uncertain. We evaluated associations of DM and biomarkers of abnormal glucose metabolism with incident radiographic knee OA, controlling for body mass index (BMI). METHODS: Participants (mean ± SD age 60.6 ± 7.8 years; mean ± SD body mass index [BMI] 29.1 ± 4.9 kg/m2 ) were from the Multicenter Osteoarthritis Study and did not have radiographic knee OA at baseline (Kellgren/Lawrence [K/L] grade <2 bilaterally). A random sample (n = 987) was selected and stratified by BMI. Baseline serum fasting glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) were measured. Participants were categorized as having DM based on self-report, use of medication, or fasting glucose ≥126 mg/dl. Incident radiographic knee OA (K/L grade ≥2 or knee replacement) was assessed at 3 follow-up visits (30, 60, and 84 months). Knee-level pooled logistic regression analysis was performed to obtain odds ratios (ORs) (95% confidence interval [95% CI]) for associations of DM status and biomarkers of abnormal glucose metabolism with incident radiographic knee OA. RESULTS: After adjustment for BMI, the odds of incident radiographic knee OA were not associated with baseline DM status nor with levels of fasting glucose and HOMA-IR, overall and in men. In women, HOMA-IR was inversely associated with odds of incident radiographic knee OA (adjusted OR 0.80 [95% CI 0.69-0.94], P = 0.005). CONCLUSION: DM and higher levels of biomarkers of abnormal glucose metabolism were not associated with increased odds of incident radiographic knee OA after adjusting for BMI in this cohort overall. A possible protective association of higher HOMA-IR with incident radiographic knee OA in women warrants further investigation.

Association of Varus Knee Thrust During Walking With Worsening Western Ontario and McMaster Universities Osteoarthritis Index Knee Pain: A Prospective Cohort Study.

OBJECTIVE: To investigate the 2-year association of varus knee thrust observed during walking to the odds of worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain in older adults with or at risk of osteoarthritis (OA). METHODS: Video recordings of self-paced walking trials of Multicenter Osteoarthritis Study participants were assessed for the presence of varus thrust at baseline. Knee pain was assessed using the WOMAC questionnaire at baseline and at 2 years. Logistic regression was used to estimate the odds of worsening knee pain (defined as either any increase in WOMAC score or as clinically important worsening), adjusting for age, sex, race, body mass index, clinic site, gait speed, and static knee alignment. Analyses were repeated, stratified by baseline radiographic OA status and among the subset of knees without baseline WOMAC pain. RESULTS: A total of 1,623 participants contributed 3,204 knees. Varus thrust was observed in 31.5% of knees. Knees with varus thrust had 1.44 times (95% confidence interval [95% CI] 1.19-1.73) the odds of any worsening and 1.37 times (95% CI 1.11-1.69) the odds of clinically important worsening WOMAC pain compared to knees without thrust. Knees with thrust without baseline WOMAC pain had 2.01 times (95% CI 1.47-2.74) the odds of incident total pain. CONCLUSION: Results indicate that varus thrust is a risk factor for worsening and incident knee pain. Targeting varus thrust through noninvasive therapies could prevent development or worsening of knee pain in older adults with or at risk for knee OA.

Brief Report: Leg Length Inequality and Hip Osteoarthritis in the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative.

OBJECTIVE: Studies suggest that persons with a leg length inequality (LLI) of ≥2 cm have an increased risk of developing knee osteoarthritis (OA) in that limb. The present study was undertaken to examine whether LLI also confers an increased risk of hip OA. METHODS: Using long limb radiographs from subjects in the Multicenter Arthritis Study (MOST) and the Osteoarthritis Initiative (OAI), we measured LLI and scored hip radiographs that were obtained at baseline and 3-5-year follow-up. The associations of LLI of ≥1 cm and LLI of ≥2 cm with radiographic hip OA were examined cross-sectionally and longitudinally, assessing risk in shorter limbs and longer limbs compared to limbs from subjects with no LLI. We carried out logistic regression analyses with generalized estimating equations and adjusted for age, sex, body mass index, height, and cohort of origin. RESULTS: There were 1,966 subjects from the MOST and 2,627 subjects from the OAI. Twelve percent had LLI of ≥1 cm and 1% had LLI of ≥2 cm. For LLI ≥1 cm, the adjusted odds ratio for prevalent hip OA in the shorter leg was 1.47 (95% confidence interval [95% CI] 1.07-2.02) and for LLI ≥2 cm, it was 2.15 (95% CI 0.87-5.34). For LLI ≥1 cm, the odds of incident hip OA in the shorter leg were 1.39 (95% CI 0.81-2.39) while for LLI ≥2 cm, they were 4.20 (95% CI 1.26-14.03). We found no increased risk of hip OA in longer limbs. CONCLUSION: Our findings suggest that, as with knee OA, legs that are at least 2 cm shorter than the contralateral leg are at increased risk of hip OA.

Symptoms of Knee Instability as Risk Factors for Recurrent Falls.

OBJECTIVE: Whether knee instability contributes to the increased risk of falls and fractures observed in persons with knee osteoarthritis (OA) has not been studied. We examined the association of knee buckling with the risk of falling and fall-related consequences in older adults with, or at high risk for, knee OA. METHODS: At the 60-month visit of the Multicenter Osteoarthritis Study, men and women ages 55-84 years were asked about knee buckling in the past 3 months and whether they fell when a knee buckled. Falls and fall-related injuries in the past 12 months and balance confidence were assessed at 60 and 84 months. Multivariate logistic regression was used to assess the association of knee buckling with falls and their consequences. RESULTS: A total of 1,842 subjects (59% women, mean ± SD age 66.9 ± 7.8 years, and body mass index 30.3 ± 5.7) were included. At 60 months 16.8% reported buckling and at 84 months 14.1% had recurrent (≥2) falls. Bucklers at 60 months had a 1.6- to 2.5-fold greater odds of recurrent falls, fear of falling, and poor balance confidence at 84 months. Those who fell when a knee buckled at baseline had a 4.5-fold, 2-fold, and 3-fold increased odds 2 years later of recurrent falls, significant fall injuries, and fall injuries that limited activity, respectively, and were 4 times more likely to have poor balance confidence. CONCLUSION: Interventions that reduce knee buckling may help prevent falls, fall-related injuries, and adverse psychological consequences of falls in persons with knee OA.

Association of hip pain with radiographic evidence of hip osteoarthritis: diagnostic test study.

STUDY QUESTION: Is there concordance between hip pain and radiographic hip osteoarthritis? METHODS: In this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test. STUDY ANSWER AND LIMITATIONS: In the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations. WHAT THIS STUDY ADDS: Hip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs. FUNDING, COMPETING INTERESTS, DATA SHARING: See the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu.

Risk adjustment for health care financing in chronic disease: what are we missing by failing to account for disease severity?

BACKGROUND: Adjustment for differing risks among patients is usually incorporated into newer payment approaches, and current risk models rely on age, sex, and diagnosis codes. It is unknown the extent to which controlling additionally for disease severity improves cost prediction. Failure to adjust for within-disease variation may create incentives to avoid sicker patients. We address this issue among patients with chronic obstructive pulmonary disease (COPD). METHODS: Cost and clinical data were collected prospectively from 1202 COPD patients at Kaiser Permanente. Baseline analysis included age, sex, and diagnosis codes (using the Diagnostic Cost Group Relative Risk Score) in a general linear model predicting total medical costs in the following year. We determined whether adding COPD severity measures-forced expiratory volume in 1 second, 6-Minute Walk Test, dyspnea score, body mass index, and BODE Index (composite of the other 4 measures)-improved predictions. Separately, we examined household income as a cost predictor. RESULTS: Mean costs were $12,334/y. Controlling for Relative Risk Score, each ½ SD worsening in COPD severity factor was associated with $629 to $1135 in increased annual costs (all P<0.01). The lowest stratum of forced expiratory volume in 1 second (<30% normal) predicted $4098 (95% confidence interval, $576-$8773) additional costs. Household income predicted excess costs when added to the baseline model (P=0.038), but this became nonsignificant when also incorporating the BODE Index. CONCLUSIONS: Disease severity measures explain significant cost variations beyond current risk models, and adding them to such models appears important to fairly compensate organizations that accept responsibility for sicker COPD patients. Appropriately controlling for disease severity also accounts for costs otherwise associated with lower socioeconomic status.

Vitamin K deficiency is associated with incident knee osteoarthritis.

BACKGROUND: Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K's role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI). METHODS: Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders. RESULTS: Among 1180 participants (62% women, mean age 62±8 years, mean body mass index 30.1±5.1 kg/m(2)), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08-2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05-5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54-10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01-1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively). CONCLUSION: In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.

Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts.

Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.

Socioeconomic status, race and COPD health outcomes.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is a common cause of death and disability, little is known about the effects of socioeconomic status (SES) and race-ethnicity on health outcomes. METHODS: The aim of this study is to determine the independent impacts of SES and race-ethnicity on COPD severity status, functional limitations and acute exacerbations of COPD among patients with access to healthcare. Data were used from the Function, Living, Outcomes and Work cohort study of 1202 Kaiser Permanente Northern California Medical Care Plan members with COPD. RESULTS: Lower educational attainment and household income were consistently related to greater disease severity, poorer lung function and greater physical functional limitations in cross-sectional analysis. Black race was associated with greater COPD severity, but these differences were no longer apparent after controlling for SES variables and other covariates (comorbidities, smoking, body mass index and occupational exposures). Lower education and lower income were independently related to a greater prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR 2.1; 95% CI 1.4 to 3.4, respectively). CONCLUSION: Low SES is a risk factor for a broad array of adverse COPD health outcomes. Clinicians and disease management programs should consider SES as a key patient-level marker of risk for poor outcomes.

Asthma and the prospective risk of anaphylactic shock and other allergy diagnoses in a large integrated health care delivery system.

BACKGROUND: The association between asthma and anaphylaxis remains poorly understood. OBJECTIVE: To ascertain, in a managed care organization in northern California, the association of asthma and asthma severity with future risk of anaphylactic shock and other selected allergy diagnoses. METHODS: Using electronic data and validated algorithms, we assembled a cohort of 526,406 patients who met the criteria for asthma between 1996 and 2006 and a referent cohort (with no utilization for asthma) individually matched on age, sex, and race/ethnicity. In each cohort, 54% of patients were female and 55% were white; their mean (SD) age was 24 (20) years. The main outcome measures were anaphylactic shock (caused by an adverse food reaction, caused by serum, or other/idiopathic), allergic urticaria, anaphylaxis after sting(s), and angioedema. RESULTS: The incidence of anaphylactic shock was 109.0 per 100,000 person-years in the asthma cohort and 19.9 per 100,000 person-years in the referent cohort. After adjustment for age, sex, race/ethnicity, comorbidities, and immunotherapy, asthma was associated with a 5.2-fold (95% confidence interval, 4.7- to 5.6-fold) increased hazard of anaphylactic shock. Asthma was also significantly associated with an increased risk of the 3 selected allergy diagnoses, with hazard ratios of 1.4 to 1.9. A significant trend by severity of asthma was apparent for food-related and other/idiopathic anaphylactic shock and for anaphylaxis after sting(s). CONCLUSIONS: In this insured population, asthma was prospectively associated with increased risk of anaphylactic shock and other allergy diagnoses. However, the effect of asthma severity was not consistent across outcome measures.