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Background Pregnancy increases a woman’s risk of severe dengue. To the best of our knowledge, the moderation effect of the dengue serotype among pregnant women has not been studied in Mexico. This study explores how pregnancy interacted with the dengue serotype from 2012 to 2020 in Mexico. Method Information from 2469 notifying health units in Mexican municipalities was used for this cross-sectional analysis. Multiple logistic regression with interaction effects was chosen as the final model and sensitivity analysis was done to assess potential exposure misclassification of pregnancy status. Results Pregnant women were found to have higher odds of severe dengue [1.50 (95% CI 1.41, 1.59)]. The odds of dengue severity varied for pregnant women with DENV-1 [1.45, (95% CI 1.21, 1.74)], DENV-2 [1.33, (95% CI 1.18, 1.53)] and DENV-4 [3.78, (95% CI 1.14, 12.59)]. While the odds of severe dengue were generally higher for pregnant women compared with non-pregnant women with DENV-1 and DENV-2, the odds of disease severity were much higher for those infected with the DENV-4 serotype. Conclusion The effect of pregnancy on severe dengue is moderated by the dengue serotype. Future studies on genetic diversification may potentially elucidate this serotype-specific effect among pregnant women in Mexico.

Background The intensity of transmission of Aedes-borne viruses is heterogeneous, and multiple factors can contribute to variation at small spatial scales. Illuminating drivers of heterogeneity in prevalence over time and space would provide information for public health authorities. The objective of this study is to detect the spatiotemporal clusters and determine the risk factors of three major Aedes-borne diseases, Chikungunya virus (CHIKV), Dengue virus (DENV), and Zika virus (ZIKV) clusters in Mexico. Methods We present an integrated analysis of Aedes-borne diseases (ABDs), the local climate, and the socio-demographic profiles of 2469 municipalities in Mexico. We used SaTScan to detect spatial clusters and utilize the Pearson correlation coefficient, Randomized Dependence Coefficient, and SHapley Additive exPlanations to analyze the influence of socio-demographic and climatic factors on the prevalence of ABDs. We also compare six machine learning techniques, including XGBoost, decision tree, Support Vector Machine with Radial Basis Function kernel, K nearest neighbors, random forest, and neural network to predict risk factors of ABDs clusters. Results DENV is the most prevalent of the three diseases throughout Mexico, with nearly 60.6% of the municipalities reported having DENV cases. For some spatiotemporal clusters, the influence of socio-economic attributes is larger than the influence of climate attributes for predicting the prevalence of ABDs. XGBoost performs the best in terms of precision-measure for ABDs prevalence. Conclusions Both socio-demographic and climatic factors influence ABDs transmission in different regions of Mexico. Future studies should build predictive models supporting early warning systems to anticipate the time and location of ABDs outbreaks and determine the stand-alone influence of individual risk factors and establish causal mechanisms.

This study aimed to investigate time trends in diet quality and the consumption of major food groups and nutrients by race/ethnicity among adults in the United States. Dietary data from 19,192 adults aged ≥ 20 years from four National Health and Nutrition Survey (NHANES) cycles (2011–2018) were included. The Healthy Eating Index (HEI) 2015 scores (range: 0–100; higher scores indicate better diet quality) and dietary consumption of food groups and nutrients were estimated for each cycle. Linear regression was used to test trends. For the overall population, the estimated overall HEI-2015 scores significantly decreased (p for trend = 0.011). However, decreases were observed in the estimated consumption of added sugars and total carbohydrates, while the estimated consumption of soy products and polyunsaturated fatty acids was significantly increased. A significant decrease in overall HEI-2015 score was observed in the non-Hispanic white group, but not in other racial/ethnic groups. Decreases in added sugar intake were found in the non-Hispanic black and Hispanic groups; sodium intake significantly decreased in the non-Hispanic Asian group. From 2011 to 2018, there was a decrease in estimated overall diet quality in US adults; however, there were improvements in certain nutrients and dietary components. Nevertheless, disparities in diet quality exist among racial/ethnic groups.

BackgroundWe examined the human toll and subsequent humanitarian crisis resulting from the Russian invasion of Ukraine, which began on 24 February 2022.MethodWe extracted and analysed data resulting from Russian military attacks on Ukrainians between 24 February and 4 August 2022. The data tracked direct deaths and injuries, damage to healthcare infrastructure and the impact on health, the destruction of residences, infrastructure, communication systems, and utility services – all of which disrupted the lives of Ukrainians.ResultsAs of 4 August 2022, 5552 civilians were killed outright and 8513 injured in Ukraine as a result of Russian attacks. Local officials estimate as many as 24 328 people were also killed in mass atrocities, with Mariupol being the largest (n=22 000) such example. Aside from wide swaths of homes, schools, roads, and bridges destroyed, hospitals and health facilities from 21 cities across Ukraine came under attack. The disruption to water, gas, electricity, and internet services also extended to affect supplies of medications and other supplies owing to destroyed facilities or production that ceased due to the war. The data also show that Ukraine saw an increase in cases of HIV/AIDS, tuberculosis, and Coronavirus (COVID-19).ConclusionsThe 2022 Russia-Ukraine War not only resulted in deaths and injuries but also impacted the lives and safety of Ukrainians through destruction of healthcare facilities and disrupted delivery of healthcare and supplies. The war is an ongoing humanitarian crisis given the continuing destruction of infrastructure and services that directly impact the well-being of human lives. The devastation, trauma and human cost of war will impact generations of Ukrainians to come.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has had an unprecedented effect, especially among under-resourced minority communities. Surveillance of those at high risk is critical for preventing and controlling the pandemic. We must better understand the relationships between COVID-19-related cases or deaths and characteristics in our most vulnerable population that put them at risk to target COVID-19 prevention and management efforts. Population characteristics strongly related to United States (US) county-level data on COVID-19 cases and deaths during all stages of the pandemic were identified from the onset of the epidemic and included county-level socio-demographic and comorbidities data, as well as daily meteorological modeled observation data from the North American Regional Reanalysis (NARR), and the NARR high spatial resolution model to assess the environment. Advanced machine learning (ML) approaches were used to identify outbreaks (geographic clusters of COVID-19) and included spatiotemporal risk factors and COVID-19 vaccination efforts, especially among vulnerable and underserved communities. COVID-19 outcomes were found to be negatively associated with the number of people vaccinated and positively associated with age, the prevalence of cardiovascular disease, diabetes, and the minority population. There was also a strong positive correlation between unauthorized immigrants and the prevalence of COVID-19 cases and deaths. Meteorological variables were also investigated, but correlations with COVID-19 were relatively weak. Our findings suggest that COVID-19 has had a disproportionate impact across the US population among vulnerable and minority communities. Findings also emphasize the importance of vaccinations and tailored public health initiatives (e.g., mask mandates, vaccination) to reduce the spread of COVID-19 and the number of COVID-19 related deaths across all populations.

As the world tries to cope with the devastating effects of the COVID-19 pandemic and emerging variants of the virus, COVID-19 vaccination has become an even more critical tool toward normalcy. The effectiveness of the vaccination program and specifically vaccine uptake and coverage, however, is a function of an individual’s knowledge and individual opinion about the disease and available vaccines. This study investigated the knowledge, attitudes, and resulting community practice(s) associated with the new COVID-19 variants and vaccines in Bangladesh, Colombia, India, Malaysia, Zimbabwe, and the USA. A cross-sectional web-based Knowledge, Attitudes, and Practices (KAP) survey was administered to respondents living in six different countries using a structured and multi-item questionnaire. Survey questions were translated into English, Spanish, and Malay to accommodate the local language in each country. Associations between KAP and a range of explanatory variables were assessed using univariate and multiple logistic regression. A total of 781 responses were included in the final analysis. The Knowledge score mean was 24 (out of 46), Attitude score 28.9 (out of 55), and Practice score 7.3 (out of 11). Almost 65% of the respondents reported being knowledgeable about COVID-19 variants and vaccination, 55% reported a positive attitude toward available COVID-19 vaccines, and 85% reported engaging in practices that supported COVID-19 vaccination. From the multiple logistic models, we found post-graduate education (AOR = 1.83, 95% CI: 1.23–2.74) and an age range 45–54 years (AOR = 5.81, 95% CI: 2.30–14.69) to be significantly associated with reported COVID-19 knowledge. In addition, positive Attitude scores were associated with respondents living in Zimbabwe (AOR = 4.49, 95% CI: 2.04–9.90) and positive Practice scores were found to be associated with people from India (AOR = 3.68, 95% CI: 1.15–11.74) and high school education (AOR = 2.16, 95% CI: 1.07–4.38). This study contributes to the identification of socio-demographic factors associated with poor knowledge, attitudes, and practices relating to COVID-19 variants and vaccines. It presents an opportunity for collaboration with diverse communities to address COVID-19 misinformation and common sources of vaccine hesitancy (i.e., knowledge, attitudes, and practices).

Background Objectives were first to evaluate by education level one-year trajectories of pain, function and general health, as well as hospital resource and medication needs in patients undergoing primary total hip arthroplasty (THA); and second, to evaluate whether outcome differences are related to existing baseline differences in health and disease severity. Methods We included all primary THAs from a public hospital-based prospective arthroplasty registry, performed in a high-income country 2010 to 2017. Education was classified in three levels: ≤8years of schooling (low), 9-12years (medium), and ≥13years (high). Pain and function prior to and one-year after surgery were assessed with the Western Ontario McMaster Universities score (WOMAC) and general health with the 12-item short-form health survey (SF-12). Results Overall 963 patients were included, 340 (35.3%) with low, 306 (31.8%) with medium, and 317 (32.9%) with high education. With increasing educational level preoperative scores for pain, function and SF-12 mental health component increased. One year after surgery improvement was observed in all education categories for WOMAC pain and function, SF-12 mental and physical component. However, absolute postoperative scores remained lower in all four domains for the low education group. After adjustment for baseline characteristics differences were much attenuated and no longer significant. There was also greater resource need in low educated patients. Conclusions The inferior absolute results one year after surgery in less educated patients were largely due to older age, worse preoperative health and greater symptom severity calling for greater attention to timely and equal management, for more targeted perioperative care and increased support for the lower education group.

The intensity of transmission ofWe present an integrated analysis ofDENV is the most prevalent of the three diseases throughout Mexico, with nearly 60.6% of the municipalities reported having DENV cases. For some spatiotemporal clusters, the influence of socio-economic attributes is larger than the influence of climate attributes for predicting the prevalence of ABDs. XGBoost performs the best in terms of precision-measure for ABDs prevalence.Both socio-demographic and climatic factors influence ABDs transmission in different regions of Mexico. Future studies should build predictive models supporting early warning systems to anticipate the time and location of ABDs outbreaks and determine the stand-alone influence of individual risk factors and establish causal mechanisms.

As the COVID-19 pandemic continues to affect all countries across the globe, this study seeks to investigate the relationship between nations’ governance, COVID-19 national data, and nation-level COVID-19 vaccination coverage. National-level governance indicators (corruption index, voice and accountability, political stability, and absence of violence/terrorism), officially reported COVID-19 national data (cases, death, and tests per one million population), and COVID-19 vaccination coverage was considered for this study to predict COVID-19 morbidity and mortality. Results indicate a strong relationship between nations’ governance and officially reported COVID-19 data. Countries were grouped into three clusters using only the governance data: politically stable countries, average countries or “less corrupt countries,” and corrupt countries or “more corrupt countries.” The clusters were then tested for significant differences in reporting various aspects of the COVID-19 data. According to multinomial regression, countries in the cluster of politically stable nations reported significantly more deaths, tests per one million, total cases per one million, and higher vaccination coverage compared with nations both in the clusters of corrupt countries and average countries. The countries in the cluster of average nations reported more tests per one million and higher vaccination coverage than countries in the cluster of corrupt nations. Countries included in the corrupt cluster reported a lower death rate and morbidity, particularly compared with the politically stable nations cluster, a trend that can be attributed to poor governance and inaccurate COVID-19 data reporting. The epidemic evaluation indices of the COVID-19 cases demonstrate that the pandemic is still evolving on a global level.

Additional file 1. Supplemental table for measurement model fit indices and diagrams for measurement models and latent growth curve models.

Background: Social support is a well-known protective factor against depression and substance use problems, but very few studies have examined its protective effects among Permanent Supportive Housing (PSH) residents. We utilized unconditional latent growth curve models (LGCMs) and parallel process growth models to describe univariate trajectories of social support, depression, and substance use problems, and to examine their longitudinal associations in a large sample of adults residing in PSH.Methods: Participants were 653 adult PSH residents in North Texas (56% female; 57% Black, 35% White, 8% other; mean age: 51 years) who participated in a monthly health coaching program from 2014 to 2017. Their health behaviors were assessed at baseline and tracked every six months at three follow-up visits.Results: Unconditional LGCMs indicated that over time, social support increased, whereas depressive symptoms and substance use problems decreased. However, their rates of change slowed over time. Further, in parallel process growth models, we found that at baseline, individuals with greater social support tended to have less severe depression and substance use problems (coefficients: –0.67, pConclusions: This study suggests that increases in social support, though slowing over time, still positively impact depression and substance use problems among PSH residents. Future PSH programs could emphasize social support as an early component as it may contribute to clients’ overall health.

ObjectivesSmoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox.MethodsUsing 1995–2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders.ResultsOf 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9).ConclusionsIn this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis.

Background Mental health has been shown to improve after total hip arthroplasty (THA). Little is known about the role of pain and function in this context. We assessed whether change in mental health was associated with improvement in pain and function 1 year post-surgery. Methods This prospective study included patients enrolled in a THA registry from 2010 to 2014. We examined the mental component score (MCS) before and 1 year post-surgery, and 1-year change, in association with Western Ontario McMaster Universities (WOMAC) pain and function scores. All scores were normalized, ranging from 0 to 100 (larger score indicating better outcome). Analyses were adjusted for potential confounders. Results Our study included 610 participants, of which 53% were women. Descriptive statistics are as follows: the average (SD) for age (years) was 68.5 (11.8), and for BMI was 26.9 (4.9). In addition, the MCS average (SD) at baseline was 44.7 (11.2), and at 1-year after THA was 47.5 (10.5). The average change from baseline to 1-year post-THA in MCS was 2.8 (95% CI: 1.9, 3.6), for an effect size of 0.26. As for the WOMAC pain score, the average change from baseline to 1-year post-THA was 44.2 (95%CI: 42.4, 46.0), for an effect size of 2.5. The equivalent change in WOMAC function was 38.1 (95% CI: 36.2, 40.0), for an effect size of 2.0. Results from multivariable analysis controlling for covariates showed that an improvement of 10 points in the 1-year change in pain score resulted in a 0.78 point (95%: CI 0.40, 1.26) increase in the 1-year change in MCS, whereas a 10-point improvement in the 1-year change in function was associated with a 0.94 point (95% CI: 0.56, 1.32) increase. Conclusions Mental health significantly improved from baseline to 1-year post-THA. Greater improvement in pain and function was associated with greater improvement in mental health 1 year post-THA.

Objective To examine neuromuscular factors that predict the incidence and progression of knee instability symptoms in older adults with or at high risk of knee osteoarthritis (OA). Methods At the 60-month clinic visit, participants in the Multicenter Osteoarthritis Study underwent evaluation of quantitative vibratory sense at the knee and isokinetic quadriceps muscle strength. At this 60-month visit, participants were also asked about knee buckling and sensations of knee shifting or slipping without buckling in the past 3 months and then were asked the same questions at the 72- and 84-month follow-up visits. We performed a person-based analysis using Poisson regression analysis with robust error variance to estimate adjusted relative risks (RRs) for the association of vibratory sense and muscle strength with the incidence and worsening of knee slipping/shifting, buckling, and overall knee instability symptoms (either buckling or knee shifting/slipping), with adjustment for relevant confounders. Results A total of 1,803 participants (61% women) were included. Approximately one-third of the participants reported incident or worsening of instability symptoms over the study period. After adjustment for relevant confounders, better vibratory acuity (adjusted RR 0.78, 95% confidence interval [95% CI] 0.56–1.09), P = 0.020 for trend) and greater quadriceps strength (adjusted RR 0.53, 95% CI 0.38–0.75, P

OBJECTIVES: 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 to 84 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: 1,842 subjects (59% women, mean [SD] age= 66.9 [7.8] and BMI= 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 two 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. This article is protected by copyright. All rights reserved.

Globalization has altered the way we live our lives and earn a livelihood. Consequently, trade and travel have been recognized as significant determinants of the spread of disease. Additionally, rise in urbanization and the closer integration of the world economy has facilitated global interconnectedness. Therefore, globalization has emerged as an essential mechanism of disease transmission. This paper aims to examine the potential impacts of COVID-19 on globalization and global health in terms of mobility, trade, travel, and countries most impacted. The effect of globalization was operationalized in terms of mobility, economy, and healthcare systems. The mobility of individuals and its magnitude was assessed using airline and seaport trade data and travel information. The economic impact was measured based on the workforce, event cancellations, food and agriculture, academic institutions, and supply chain. The healthcare capacity was assessed by consideration of healthcare systems indicators and preparedness of countries. Utilizing a technique for order of preference by similarity to ideal solution (TOPSIS) we calculated a pandemic vulnerability index (PVI) creating a quantitative measure of the potential global health. The pandemic has placed an unprecedented burden on the world's economy, healthcare, and globalization through the travel, events cancellation, employment workforce, food chain, academia, and healthcare capacity. Based on PVI results, certain countries are more vulnerable than others. In Africa, more vulnerable countries include South Africa and Egypt; in Europe, they are Russia, Germany, and Italy; in Asia and Oceania, they are India, Iran, Pakistan, Saudi Arabia, and Turkey; and for the Americas, they are Brazil, USA, Chile, Mexico, and Peru. The impact on mobility, economy, and healthcare systems has only started to manifest. The findings of this study may help in the planning and implementation of strategies at the country level to help ease this emerging burden.

The validity of research into risk factors for the development of rheumatic conditions and their sequelae can be threatened by selection bias. In this Review, the authors outline potentially major selection bias issues in rheumatic disease research and suggest approaches which could be used to help limit the impact of these biases on future research. The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias—a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic—in key areas of rheumatic disease research. We present index event bias (a type of selection bias) as one of the potentially unifying reasons behind some unexpected findings, such as the 'risk factor paradox'—a phenomenon exemplified by the discrepant effects of certain risk factors on the development versus the progression of osteoarthritis (OA) or rheumatoid arthritis (RA). We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research.

Objective Obesity is strongly associated with incident gout risk, but its association with the risk of recurrent gout attacks has been null or weak, constituting an obesity paradox. We sought to demonstrate and overcome the methodologic issues associated with the obesity paradox for risk of recurrent gout attacks. Methods Using the Multiple Risk Factor Intervention Trial database, we decomposed the total effect of obesity into its direct and indirect (i.e., mediated) effects using marginal structural models. We also estimated the total effect of body mass index (BMI) change from baseline among incident gout patients. Results Of 11,816 gout-free subjects at baseline, we documented 408 incident gout cases, with 132 developing recurrent gout attacks over a 7-year followup period. The adjusted odds ratio (OR) for incident gout among obese individuals was 2.6, whereas that for recurrent gout attacks among gout patients was 0.98 (i.e., the obesity paradox). These ORs correlated well with the ORs for the indirect and direct effects of obesity on the risk of recurrent gout attacks (2.83 and 0.98, respectively). Compared with no BMI change, the OR of increasing versus decreasing >5% of baseline BMI was 0.61 and 1.60 for recurrent gout attacks, respectively (P for trend

Objective: We investigated whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality. Methods: We identified an incident RA cohort in the Nurses' Health Study (NHS, 1976-2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within four years of RA/index date. We used Cox regression to obtain HRs for mortality, comparing sustained smoking cessation to continued smoking. Results: Among 121,701 women in the NHS, we identified 938 with incident RA matched to 8,951 non-RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period compared to 36.1% of comparators (OR for sustained cessation 1.18, 95%CI 0.88-1.58). There were 313 (33.4%) deaths in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58, 95%CI 0.33-1.01) and comparison (HR 0.47, 95%CI 0.39-0.58) cohorts. Women with RA had higher mortality for >5 post-RA pack-years (HR 3.67, 95%CI 2.80-4.81) than comparators with >5 post-index pack-years (HR 1.88, 95%CI 1.62-2.17; pinteraction5 pack-years after RA diagnosis significantly increased mortality beyond the risk of non-RA comparators. This article is protected by copyright. All rights reserved.

Background Although 25-hydroxyvitamin D (25[OH]D) is commonly used to define vitamin D status, there is no consensus on the cutoff levels for vitamin D deficiency and insufficiency. In this study, we aimed to identify the 25(OH)D threshold that maximally suppressed parathyroid hormone (PTH) in Hong Kong Chinese population. Methods The study included 5276 participants (70% female) of the Hong Kong Osteoporosis Study aged 20 or above who had total 25(OH)D measured. Three-phase segmented regression was used to identify the optimal break-point between 25(OH)D and PTH. Results The prevalence of vitamin D deficiency observed was 43.8% and the prevalence of insufficient ( 2 of 0.048, whereas the estimated first and second break-point of 25(OH)D were 27 nmol/L (95% CI: 24–30) and 47 nmol/L (95% CI: 37–56) after adjusting for factors affecting bone and mineral metabolism. In addition, the relationship between 25(OH)D and PTH significantly differed by sex and age. Conclusion The threshold for 25OHD at the point of maximal suppression of PTH estimated in this study was lower than the suggested threshold of vitamin D deficiency in the literature, perhaps due to race or assay differences, and the relationship between vitamin D and PTH changed with sex and age. Standardization in the methodology of searching for the optimal break-point is desirable so that a consensus on cutoff points can be obtained.

The prevalence of chronic diseases has risen along with increased longevity. Co-occurrence of two or more chronic diseases in an individual (multimorbidity) is prevalent and poses a huge burden to individuals and the society. However, determinants of multimorbidity are largely unknown. Handgrip strength is a general indicator of muscle strength and linked with premature mortality. However, its role in multimorbidity has never been evaluated. To investigate the relationships between handgrip strength and multiple chronic diseases and multimorbidity, and to assess the usefulness of age and handgrip as a marker of chronic diseases and multimorbidity in a community dwelling sample of men and women, we analyzed a cross-sectional cohort with 1,145 subjects (748 men and 397 women) aged 50 years and older living in Hong Kong. Low handgrip strength was significantly associated with increased odds of having five and three chronic diseases in men and women, respectively, after controlling for age, body mass index, history of smoking, educational level, marital level and comorbidity. Multivariable-adjusted handgrip strength was significantly decreased with the number of chronic diseases in men (trend, P = 0.001), but the trend in women was marginal (trend, P = 0.06). Conversely, multivariable-adjusted age was significantly increased with the number of chronic diseases in women (trend, P = 0.033), but not in men (trend, P = 0.118). In conclusion, handgrip strength is associated with multiple chronic diseases and multimorbidity in men and women after adjustment of confounding factors. It shows a linear trend of association with the number of chronic diseases in men, but not in women. Since handgrip strength is a biomarker of multiple physiological systems, its augmentation may be a feasible strategy to improve general health and decrease likelihood of having multiple chronic diseases and hence, premature mortality. © 2012 The Author(s)., published_or_final_version, Springer Open Choice, 25 May 2012

OBJECTIVES: To identify risk factors for indoor and outdoor falls. DESIGN: Prospective cohort study. SETTING: The MOBILIZE Boston Study, a study of falls etiology in community-dwelling older individuals. PARTICIPANTS: Seven hundred sixty-five women and men, mainly aged 70 and older, from randomly sampled households in the Boston, Massachusetts, area. MEASUREMENTS: Baseline data were collected by questionnaire and comprehensive clinic examination. During follow-up, participants recorded falls on daily calendars. The location and circumstances of each fall were asked during telephone interviews. RESULTS: Five hundred ninety-eight indoor and 524 outdoor falls were reported over a median follow-up of 21.7 months. Risk factors for indoor falls included older age, being female, and various indicators of poor health. Risk factors for outdoor falls included younger age, being male, and being relatively physically active and healthy. For instance, the age- and sex-adjusted rate ratio for having much difficulty or inability to perform activities of daily living relative to no difficulty was 2.57 (95% confidence interval (CI)=1.69-3.90) for indoor falls but 0.27 (95% CI=0.13-0.56) for outdoor falls. The rate ratio for gait speed of less than 0.68 m/s relative to a speed of greater than 1.33 m/s was 1.48 (95% CI=0.81-2.68) for indoor falls but 0.27 (95% CI=0.15-0.50) for outdoor falls. CONCLUSION: Risk factors for indoor and outdoor falls differ. Combining these falls, as is done in many studies, masks important information. Prevention recommendations for noninstitutionalized older people would probably be more effective if targeted differently for frail, inactive older people at high risk for indoor falls and relatively active, healthy people at high risk for outdoor falls. Language: en

BACKGROUND: Whether certain types of footwear, such as slippers, socks without shoes, and going barefoot, increase the risk for falls among the elderly is uncertain. Our purpose was to examine the relationship between footwear and falls within the home in MOBILIZE Boston, a prospective cohort study of falls etiology among non-institutionalized women and men, mainly aged 70 years and older, from the Boston MA, USA area. METHODS: The 765 participants were from households randomly selected from town lists. They were followed for a median of 27.5 months. At baseline, participants were administered a questionnaire that included questions on footwear usually worn, and were given a comprehensive examination that included measurement of many risk factors for falls. During follow-up participants were asked to record each day whether they had fallen; those reporting falls were asked about their footwear when they fell. RESULTS: At the time of in-home falls, 51.9% of people were barefoot, wearing socks without shoes, or wearing slippers; 10.1% of people reported that their usual footwear was one of these types. Among those who fell in their own home, the adjusted odds ratio for a serious injury among those who were shoeless or wearing slippers compared to those who were wearing other shoes at the time of the fall was 2.27 (95% confidence interval 1.21-4.24). CONCLUSIONS: It may be advisable for older individuals to wear shoes in their home whenever possible to minimize the risk of falling. Further research is needed to identify optimal footwear for falls prevention.

Many podiatric clinicians note that foot problems are common in older persons 1, 2, yet very little epidemiologic information exists on foot pain, especially in relation to shoewear, in older persons. National data reveal that foot and toe symptoms are among the top twenty reasons for physician office visits among those aged 65–74 years3. Prior research indicates that not enough attention has been given to foot pain and other foot disorders since historically these factors have not been regarded as important health risks1. Women are more likely to have foot pain than men4, 5, but it is unknown whether this is due to a higher prevalence of foot deformities, underlying disease, shoewear or other lifestyle choices. Foot pain and foot disorders are serious burdens for many older individuals, especially those with rheumatic diseases6–8. While foot pain is considered to be a very common musculoskeletal complaint in the U.S. adult population, relatively little is known of the prevalence or cause of foot pain in older Americans in a population-based sample. Examining the association between shoewear and foot pain may lead to a greater understanding of this relationship, which is important when considering strategies to prevent sequelae due to foot pain in older adults. Previous studies have examined the influence of footwear on foot problems and other diseases in older adults but have focused on small numbers of older adults or diseased patients. A 1993 study by Frey et al9 presented descriptive information on shoe trends and their effect on the development of foot deformities and pain in 356 women, aged 20–60. They observed that the majority of women wore shoes that were too small for their feet and had foot pain. However, no statistical analysis was presented in this paper. In a 2005 study by Menz and Morris, the relationship between footwear characteristics (length, width and area) and the prevalence of common forefoot problems were examined in 176 older adults residing in a retirement community10. Similar to the study by Frey, it was found that incorrectly fitting footwear is common and associated with forefoot disease and foot pain. Menz et al have also examined the relationship between footwear characteristics and the risk of indoor and outdoor falls in the same cohort of older adults. They found that there was no association between the type of shoe and the risk of falling either inside or outside the home11. Harrison et al reported an assessment of the fit of footwear in 100 patients with diabetes in 2007 and found that many diabetics wear shoes that are too narrow for their feet12. Garrow et al conducted a population-based foot pain and disability survey in 3417 adults, which examined age- and sex-differences in a variety of foot symptoms, but did not have any information on shoewear13. In addition, the preventative effects of footwear, like plantar pressure relief, have been shown to be important in previous studies. Lobman et al studied the effect of preventative footwear on foot pressure in 81 older diabetic patients14. This type of footwear was shown to be successful in reducing plantar pressure. Also, Burnfield et al found that, in 20 healthy, older adults, faster walking speed and walking barefoot result in higher foot pressures15. To evaluate the relationship between foot pain and shoewear in a large, population-based cross-sectional study, we collected information on major type of shoe worn currently and in the past, along with self-report of foot pain, by men and women of the Framingham Study. In addition to the aforementioned information, the Framingham Study has extensive data collected on many clinical and other factors, notably medical conditions, comorbidities and other potential confounders. The purpose of this study was to evaluate the relationship between type of shoe worn and foot pain, accounting for other possible risk factors, in men and women of the Framingham cohort.

Objective is to examine the effect of epidural analgesia in first stage of labor on occurrence of cesarean and operative vaginal deliveries in nulliparous women and multiparous women without a previous cesarean delivery. Design of the Prospective cohort study. Prenatal care was received at 12 free-standing health centers, 7 private physician offices, or 2 hospital-based clinics; babies were delivered at a free standing birth center or at 3 hospitals, all in San Diego, CA. This study of 2,052 women used data from the San Diego Birth Center Study that enrolled women between 1994 and 1996 to compare the birthing management of the collaborative Certified Nurse Midwife-Medical Doctor Model with that of the traditional Medical Doctor Model. Main Outcome Measures of the Cesarean or operative vaginal deliveries. After adjusting for differences between women who used and those who did not use epidural analgesia in 1st stage of labor, epidural use was associated with a 2.5 relative risk (95% CI: 1.8, 3.4) for operative vaginal delivery in nulliparous women, and a 5.9 relative risk (95% CI: 3.2, 11.1) in multiparous women. Epidural use was associated with a 2.4 relative risk (95% CI: 1.5, 3.7) for cesarean delivery in nulliparous women, and a 1.8 relative risk (95% CI: 0.6, 5.3) in multiparous women. Epidural anesthesia increases the risk for operative vaginal deliveries in both nulliparous and multiparous women, and increases risk for cesarean deliveries in nulliparous more so than in multiparous women.

Objective. To describe trajectories of functional decline over 84 months and study associated risk factors among adults initially without limitation who had or were at risk of knee OA. Methods. We used annual measures of WOMAC physical function over 84 months from the OA Initiative. We included knees with no functional limitation (i.e. WOMAC = 0) at baseline. Knee-based trajectories of functional decline from WOMAC were identified from a group-based trajectory model (PROC TRAJ). Results. We identified five trajectories from 2110 knees (1055 participants, age 61.0 ± 9.3, BMI 27.1 ± 4.4, 52% women). Half of the knees (54%) remained free of limitation over 84 months, 26% slowly declined to a WOMAC of 1.5, 9% were limitation free for the first 36 months and declined to a WOMAC of 11.3, 6% rapidly declined over the first 12 months and gradually recovered to a WOMAC of 3.3 and 5% steadily declined to a WOMAC of 13.2. Baseline radiographic disease, knee pain, obesity and depressive symptoms at baseline were associated with trajectories of worse functional decline. Conclusion. Five per cent of our sample initially without limitation was on a trajectory of progressive functional decline over 84 months later. We found worse disease and health status at baseline to be associated with faster decline over time.

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.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.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.Interventions that reduce knee buckling may help prevent falls, fall-related injuries, and adverse psychological consequences of falls in persons with knee OA.

Objective. We compared outcomes, safety, and resource utilization in a collaborative management birth center model of perinatal care versus traditional physician-based care. Methods. We studied 2957 low-risk, low-income women: 1808 receiving collaborative care and 1149 receiving traditional care. Results. Major antepartum (adjusted risk difference [RD] = ‐0.5%; 95% confidence interval [CI] = ‐2.5, 1.5), intrapartum (adjusted RD = 0.8%; 95% CI = ‐2.4, 4.0), and neonatal (adjusted RD = ‐1.8%; 95% CI = ‐3.8, 0.1) complications were similar, as were neonatal intensive care unit admissions (adjusted RD= ‐1.3%; 95% CI = ‐3.8, 1.1). Collaborative care had a greater number of normal spontaneous vaginal deliveries (adjusted RD = 14.9%; 95% CI = 11.5, 18.3) and less use of epidural anesthesia (adjusted RD = ‐35.7%; 95% CI = ‐39.5, ‐31.8). Conclusions. For low-risk women, both scenarios result in safe outcomes for mothers and babies. However, fewer operative deliveries and medical resources were used in collaborative care. (Am J Public Health. 2003;93:999‐1006) at a freestanding birth center (The BirthPlace, located in San Diego, Calif) for women who remained at low perinatal risk. These components were integrated within the health care delivery system, which included private medical offices, neighborhood health centers, and community and tertiary hospitals. In the collaborative care model, obstetricians and CNMs were part of the same practice. CNMs provided 95% of prenatal care at 12 clinic sites. During antepartum care, 30% of participants saw only CNMs, 65% were collaboratively managed through consultation or necessary visits with an obstetrician, and 5% required exclusive antepartum management by an obstetrician. 10 In the intrapartum setting, women who remained at low risk and who delivered their babies at the freestanding birth center were managed (or co-managed) by CNMs, whereas women referred to the hospital were managed and delivered by collaborating obstetricians. Medically eligible women were given the option to enroll in the birth center program at the beginning of prenatal care, with the majority (65%‐75%) choosing birth center de

We thank Lee and Song1 for their interest in our extended report on the smoking paradox in the development of psoriatic arthritis among patients with psoriasis.2 Please note that the point of our paper was indeed to demonstrate how …

ObjectiveKnee buckling, in which a knee gives way during weight-bearing, is common in people with knee pain and knee osteoarthritis (OA), but little is known about the prevalence of sensations of knee instability, slipping or shifting in which the knee does not actually buckle, or of the psychosocial and physical consequences of these symptoms.DesignWe asked participants in the Multicenter Osteoarthritis Study (MOST) separately about episodes of knee buckling and sensations of knee instability without buckling in the past 3 months, and assessed fear of falling, poor balance confidence (Activities-specific Balance Confidence (ABC) Scale≤67/100), activity limitation due to concern about buckling, and poor physical function (Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function≥28/68). We used Poisson regression to estimate prevalence ratios (PRs) for cross-sectional associations of buckling and sensations of instability without buckling with these outcomes, adjusting for confounders.ResultsOf 2120 participants (60% female, 40%≥65 years, mean Body mass index (BMI): 31kg/m258), 18% reported buckling, 27% had sensations of knee instability without buckling, and 9% reported both symptoms. Buckling and sensations of instability without buckling were each significantly associated with fear of falling, poor balance confidence, activity limitations, and poor WOMAC physical function. Subjects who reported both buckling and instability without buckling and those with at least two buckling episodes (15%) had the strongest association with poor outcomes.ConclusionsKnee buckling and especially sensations of knee instability without buckling were common and each was significantly associated with fear of falling, poor balance confidence, activity limitations, and poor physical function.

OBJECTIVES: This study characterized ethnic disparities for children in demographics, health status, and use of services; explored whether ethnic subgroups (Puerto Rican, Cuban, and Mexican) have additional distinctive differences; and determined whether disparities are explained by differences in family income and parental education. METHODS: Bivariate and multivariate analyses of data on 99,268 children from the 1989-91 National Health Interview Surveys were conducted. RESULTS: Native American, Black, and Hispanic children are poorest (35%, 41% below poverty level vs 10% of Whites), least healthy (66%-74% in excellent or very good health vs 85% of Whites), and have the least well educated parents. Compared with Whites, non-White children average fewer doctor visits and are more likely to have excessive intervals between visits. Hispanic subgroup differences in demographics, health, and use of services equal or surpass differences among major ethnic groups. In multivariate analyses, almost all ethnic group disparities persisted after adjustment for family income, parental education, and other relevant covariates. CONCLUSIONS: Major ethnic groups and subgroups of children differ strikingly in demographics, health, and use of services; subgroup differences are easily overlooked; and most disparities persist even after adjustment for family income and parental education.

Background Total knee arthroplasty (TKA) is an effective treatment to relieve pain and restore function in patients with advanced knee osteoarthritis. TKA utilization is growing rapidly, and the appropriateness of current TKA use is of great interest. We examined patient-reported preoperative pain and function profiles to understand symptom severity at the time of TKA decision. Methods Data were from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. We included patients undergoing primary, unilateral TKAs between 2011 and 2014 for osteoarthritis and had data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and Short-Form 36-item Physical Component Summary (PCS) score. We compared patient profiles across groupings by symptoms: (1) little pain and high function (KOOS ≥70, PCS ≥40); (2) little pain but poor function (KOOS ≥70, PCS Results Of 6936 patients, 77% had high pain and poor function (group 4), 19% had high pain "or" poor function (groups 2-3), and 5% had little pain and high function before TKA (group 1). In group 1, 86% were constantly aware of their knee problem, 48% reported pain daily yet 5% experienced severe or extreme pain on stairs, and 1% pain in bed. Over half had a lot of limitations in vigorous activities. Compared with group 4, group 1 were older, less obese, more educated, and included more men and people reporting being healthy, less disabled, and happy ( P Conclusion Most patients undergoing TKAs had significant pain and/or poor function. Our results provide critical information given the current debate of potentially inappropriate TKA utilization in the United States.

Objective: To evaluate the effect of calcium supplementation on blood pressure in children. Design: Randomized, double-masked, placebo-controlled trial. Setting and participants: One hundred one fifth-grade students in one inner-city school. Intervention: Each child consumed 480 ml of juice beverages, containing either no calcium or 600 mg calcium (as calcium citrate malate) daily for 12 weeks. Measurements: At baseline we obtained nutrient data from three sets of 2-day food records on each subject. We measured blood pressure four times on each of three weekly sittings at baseline and at follow-up. Using multiple linear regression analysis, we compared mean blood pressure change in the intervention group with that in the placebo group. Results: There were 50 girls and 51 boys; 61 subjects were black. At baseline, mean age was 11.0 years, systolic and diastolic blood pressures were 101.7 and 57.7 mm Hg, daily total energy intake was 1966 kcal, and calcium intake was 827 mg. With control for age, height, hours of television watched, and baseline blood pressure, systolic blood pressure increased 1.0 mm Hg in the intervention group and 2.8 mm Hg in the placebo group (effect estimate = –1.8 mm Hg; 95% confidence interval –4.0, 0.3). In black subjects the intervention effect estimate was –2.0 mm Hg (95% confidence interval –4.4, 0.4). From lowest to highest quartile of baseline calcium intake (per 1000 kcal), the intervention effect estimates were –3.5, –2.8, –1.3, and 0.0 mm Hg ( p for trend = 0.009). There was little effect on diastolic blood pressure. Conclusion: These data suggest a blood pressure–lowering effect of calcium supplementation in children, especially in subjects with low baseline calcium intake. (J P EDIATR 1995;127:186-92)

Purpose. Total hip arthroplasty (THA) effectively restores function and alleviates pain in patients with end-stage hip osteoarthritis. Pain affects mood through its effect on disability and fatigue. Few studies have examined mental health as a consequence of pain or function after THA. We assessed change in mental health 1-year post-surgery, and examined whether change in pain and function predict change in mental health. Methods. We used data from a prospective THA registry that began in 1996 at a large public Geneva University hospital. We included surgeries performed 2010 and 2012-2014, with demographic information, body mass index (BMI), co-morbidities, baseline and 1-year post-surgery WOMAC pain and function scores, and the SF-12 mental health component score (MCS). The pain, function, and MCS scores were normalized and ranged from 0-100; increasing score indicating better outcome. We calculated descriptive statistics, and used multivariable linear regression to predict 1-year change in MCS. Results. Of 610 participants, mean (SD) age was 68.5 (11.8) years and BMI of 26.9 (4.9), 53% were women. Mean MCS was 44.7 (11.2) at baseline and 47.5 (10.5) at 1-year post surgery; average 1-year change was 2.8 (95% CI 1.9-3.6). WOMAC pain score was 39.6 (18.3) at baseline and 83.8 (20.4) at 1-year post surgery; 1-year change was 44.2 (95% CI 42.4-46.0). Corresponding WOMAC function was 40.2 (18.8) and 78.3 (22.1); 1-year change was 38.1 (95% CIs 36.2-40.0). On average, a 10-point increase in 1-year change in pain score was associated with a 0.7 point increase in the adjusted 1-year change in MCS (95% CI 0.2-1.1). The change in function was associated with a 0.9 point increase in 1-year change in MCS (95% CI 0.5-1.4). Conclusion. Mental health significantly improved from baseline to 1-year post-surgery. Patients whose pain and function scores improved the most had also the greatest improvement in mental health.

It is known that impaired balance is associated with falls in older adults; however, there is no accepted gold standard on how balance should be measured. Few studies have examined measures of postural sway and clinical balance concurrently in large samples of community-dwelling older adults. We examined the associations among 4 types of measures of laboratory- and clinic-based balance in a large population-based cohort of older adults.We evaluated balance measures in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly Boston Study (276 men and 489 women ages 64-97 years). The measures included laboratory-based anteroposterior (AP) path length and mean sway speed, mediolateral (ML) mean sway and root mean square, and area of ellipse postural sway; the Short Physical Performance Battery (SPPB); the Berg Balance Scale; and the one-leg stand test. Spearman's rank correlation coefficients were assessed among the balance measures.The area of ellipse sway was highly correlated with the ML sway measures (r =0.91, P0.0001) and sway speed was highly correlated with AP sway (r = 0.97, P0.0001). The Berg Balance Scale was highly correlated with the SPPB (r = 0.74, P0.001) and the one-leg stand test (r = 0.82, P0.001). Correlations between the laboratory- and clinic-based balance measures were low but statistically significant (-0.29 ≤ r ≤ -0.16, P0.0001).Clinic-based balance measures, and laboratory-based measures comparing area of ellipse with ML sways or sway speed with AP sway, are highly correlated. There is less correlation between the clinic- and laboratory-based measures. Since both laboratory- and clinic-based measures inform balance in older adults, but are not highly correlated with each other, future work should investigate the differences.

Indirect immunofluorescence microscopy has been used to investigate the coordinated reorganization of microtubules, microfilaments, and keratin intermediate filaments in cultured human epidermal keratinocytes following a switch from low-Ca++ (0.15 mM) medium to high-Ca++ (1.05 mM) medium. A dramatic reorganization occurs concurrently in the three major cytoskeletal components shortly after the calcium switch. The most prominent features are the alignment of keratin filaments at the plasma membranes of apposed cells, the induction of microfilament rings, the restriction of microtubules to the area within the boundaries of the microfilament rings, and the alignment of actin bundles at cell borders. Additional changes are observed in terminally differentiated cells. This is the first report that describes simultaneous changes in the organization of the three major cytoskeletal components of epidermal keratinocytes. Cytochalasin D and demecolcine (colcemid) studies were performed to determine whether the organization of microtubules, microfilaments, and keratin filaments, as well as the calcium-induced reorganization of these cytoskeletal elements, may be dependent on the existence of structural relationships between them. These studies demonstrate that the disruption of microfilaments results in the formation of a latticelike keratin network, with a close association of actin and keratin being maintained. The formation of keratin filament alignments occurs even in the absence of intact microfilaments. In addition, it was found that the Ca(++)-induced reorganization of microfilaments and keratin filaments is not dependent on an intact microtubule network. Furthermore, the reorganization of actin into concentric rings can be dissociated from changes in the organization of keratin filaments.

We read with great interest the letter from Banack and Kaufman recently published in Epidemiology.1 The authors cited research by Curtis et al.2 who found that, among persons with heart disease, those who were overweight or obese had a lower risk of death than those with a normal weight. Banack and Kaufman proposed that such an “obesity paradox” was the result of collider stratification bias, and they demonstrated a method to correct for such bias. We posit that, even after correction for bias, this paradoxical phenomenon may persist in observational studies of the effect of obesity on mortality among patients with heart failure. Numerous studies conducted in the general population have shown that obesity is associated with an increased risk of mortality.3,4 We have depicted these studies using a causal diagram in Figure 1A. To simplify our discussion, we assume that obesity increases the risk of death through two causal pathways: one mediated through heart failure (i.e., obesity → heart failure → death [indirect effect]), and the other through a mechanism that does not include heart failure (i.e., obesity → death [direct effect]). The total effect of obesity on the risk of death is the net causal effect through both pathways after proper adjustment for potential confounders (CF1). Thus, the primary aim of these studies is to evaluate the total effect of obesity on the risk of death in the general population. Figure 1 Directed acyclic graph showing the effect of obesity on the risk of death. A. Direct effect, and indirect effect through heart failure. CF 1 indicates set of potential confounders. B. Same as part A, except restricted to patients with heart failure. CF ... Many studies have also evaluated whether the effect of obesity observed in the general population persists among high-risk populations, such as those with heart failure. These studies are depicted in Figure 1B, where restricting the study population to patients with heart failure is indicated by a box around “heart failure.” In these studies, obesity status (a known cause of heart failure) has often been assessed before or at the time of heart failure onset. Such a study design (restricting to heart failure patients) could not only introduce collider stratification bias by creating a spurious association pathway between obesity and death (i.e., obesity → heart failure ← CF2 → death), but also change the interpretation of the effect estimates of obesity on the risk of death. By restricting the study population to patients with heart failure, one can assess only the direct effect of obesity on the risk of death, as the indirect effect of obesity on the risk of death through heart failure has been blocked (by restriction). Correction of collider stratification bias would result in an unbiased estimate of the direct effect of obesity, but would not generate an estimate of the total effect of obesity on the risk of death among heart failure patients, which is the intended aim of these studies. Assuming that both the direct and indirect effects of obesity on the risk of death are in the same direction, one would expect the total effect of obesity to be larger than its direct effect. In an extreme scenario, if the effect of obesity on the risk of death is completely mediated through heart failure, one should expect a null direct effect of obesity on risk of death among heart failure patients. Nevertheless, because the direct effect of obesity on the risk of death is different from its total effect, this would not constitute a true “obesity paradox.” In practice, it is challenging to assess the total effect of obesity on the risk of death among patients with heart failure. One approach would be to conduct a randomized clinical trial of a weight loss intervention (e.g., exercise, weight loss diet, medication, or surgical intervention) among obese patients with heart failure to determine whether weight loss is associated with reduced risk of death. However, to obtain an unbiased estimate of the total effect of weight loss on the risk of death, the weight-loss intervention itself should have no direct effect on risk of death, or such an effect should be appropriately controlled, if present. Alternatively, in observational study settings, if there were sufficient changes in obesity status after heart failure, one would be able to assess the total effect of obesity on mortality, assuming appropriate adjustment for all potential confounders. If the total effect of obesity on the risk of death among patients with heart failure were different from the total effect in the general population, one could claim that an “obesity paradox” does exist. We agree with Banack and Kaufman1 that “paradoxes” should be met with skepticism. We postulate that the “obesity paradox” could have resulted from confusion between the direct (estimated) and total (intended) effect. Incorrect interpretations of the results, and the ensuing debate about the paradoxical phenomena from studies restricted to people with a condition that is an intermediate in the causal pathway, can undermine scientific knowledge and evidence-based clinical recommendations. To avoid these issues, the investigators should carefully specify the research question of interest, clarify the time sequence of exposure, mediators, and outcome variables, employ appropriate design and analysis, and exercise proper inference. Failure in any of these steps could potentially lead to incorrect causal inference.

Background.While primary prevention of adult cardiovascular diseases should begin early, there are problems in identifying children at increased risk of future disease. Methods.We did a follow-up study in 1991–1992 of 100 male former students at a boarding high school who had blood cholesterol measured in 1970–1971 both prior to and following a school-wide, reduced-fat dietary intervention. We compared adult cholesterol levels of the 50 subjects whose cholesterol decreased ≥16.5% (the median decrease) following the 1970–1971 intervention (Diet-Sensitive) with the 50 whose response was 20 mg/dl lower than Non-Diet-Sensitive adults on a similar diet (180.1 vs 202.1 mg/dl, respectively). Conclusions.Degree of response to a low-fat, low-cholesterol diet during adolescence may identify male subjects who will have differing patterns of cholesterol change over time.

Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest.Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest.For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation.High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.

Indirect immunofluorescence microscopy has been used to investigate the ultraviolet (UV) radiation induced disruption of the organization of microfilaments, keratin intermediate filaments, and microtubules in cultured human epidermal keratinocytes. Following irradiation, concurrent changes in the organization of the three major cytoskeletal components were observed in cells incubated under low Ca2+ (0.15 mM) conditions. UV irradiation induced a dose-dependent condensation of keratin filaments into the perinuclear region. This collapse of the keratin network was accompanied by the reorganization of microfilaments into rings and a restricted distribution of microtubules, responses normally elicited by exposure to high Ca2+ (1.05 mM) medium. The UV induced alteration of the keratin network appears to disrupt the interactions between keratin and actin, permitting the reorganization of actin filaments in the absence of Ca2+ stimulation. In addition to the perinuclear condensation of keratin filaments, UV irradiation inhibits the Ca2+ induced formation of keratin alignments at the membrane of apposed cells if UV treatment precedes exposure to high Ca2+ medium. Incubation of keratinocytes in high Ca2+ medium for 24 hours prior to irradiation results in the stabilization of membrane associated keratin alignments and a reduced susceptibility of cytoplasmic keratin filaments to UV induced disruption. Unlike results from investigations with isogenic skin fibroblasts, no UV induced disassembly of microtubules was discernible in irradiated human keratinocytes. © 1992 Wiley-Liss, Inc.

Objective: The search for quality, cost-effective health care programs in the United States is now a major focus in the era of health care reform. New programs need to be evaluated as alternatives are developed in the health care system. The BirthPlace program provides comprehensive perinatal services with certified nurse-midwives and obstetricians working together in an integrated collaborative practice serving a primarily low-income population. Low-risk women are delivered by nurse-midwives in a freestanding birth center (The BirthPlace), which is one component of a larger integrated health network. All others are delivered by team obstetricians at the affiliated tertiary hospital. Wellness, preventive measures, early intervention, and family involvement are emphasized. The San Diego Birth Center Study is a 4-year research project funded by the U.S. Federal Agency for Health Care Policy and Research (#R01-HS07161) to evaluate this program. The National Birth Center Study (NEJM, 1989; 321(26): 1801-11) described the advantages and safety of freestanding birth centers. However, a prospective cohort study with a concurrent comparison group of comparable risk had not been conducted on a collaborative practice-freestanding birth center model to address questions of safety, cost, and patient satisfaction.Methods: The specific aims of this study are to compare this collaborative practice model to the traditional model of perinatal health care (physician providers and hospital delivery). A prospective cohort study comparing these two health care models was conducted with a final expected sample size of approximately 2,000 birth center and 1,350 traditional care subjects. Women were recruited from both the birth center and traditional care programs (private physicians offices and hospital based clinics) at the beginning of prenatal care and followed through the end of the perinatal period. Prenatal, intrapartum, postpartum and infant morbidity and mortality are being compared along with cost-effectiveness and acceptance of the model by patients. Data collection occurred primarily through medical record abstraction with the addition of two patient questionnaires. Comparability of the cohorts was established by using a validated methodology to determine medical/perinatal risk and birth center eligibility, which included assessment by two CNMs and an independent blind review by a perinatologist. The cost analysis uses a resource-utilization approach and new methodologies such as activity-based-costing to compare costs from both the perspective of the payor and the health care provider. Patient satisfaction was measured using a self-administered patient questionnaire.Results: Current preliminary results from approximately 38% of the final expected study sample are available. Crude and adjusted analysis have been conducted. Overall, the preliminary results suggest similar morbidity and mortality in the two groups. Fetal deaths are 0.75% in the index and 0.64% in the comparison group, with early neonatal deaths at 0.26% and 0.23%, respectively. The traditional care group showed adjusted rate differences of 5.83% more major maternal intrapartum complications and 9% more NICU admissions. While the birth center group showed adjusted rate differences of 5.5% more low birth weight and 0.95% more preterm birth. For other outcomes, the birth center group showed an adjusted rate difference of 22.34% more exclusive breastfeeding at discharge. Also, there was less utilization of cesarean section and assisted delivery in the birth center group as compared to the traditional care group. The adjusted rate difference for normal spontaneous vaginal deliveries in nulliparas was 10.23% more in the birth center group, with similar results in multiparas with and without history of cesarean (28.88% and 7.84%, respectively). Preliminary results also show that the average total cost for pregnancy-related services paid by California Medicaid was $4,550 for the birth center and $5,535 for the traditional care group. Final results based on the full study sample (full data available February 1998) details of payor costs such as provider, facility, NICU, and ancillary along with costs from the health care system perspective and patient satisfaction results will be presented.Conclusion: Current results suggest similar morbidity and mortality between the birth center program and traditional care groups, with less resource utilization translating to lower costs in the collaborative practice model. Results suggest that collaborative practice using a freestanding birth center as an adjunct to an integrated perinatal health care system may provide a quality, lower-cost alternative for the provision of perinatal services.

ObjectiveHamstring coactivation during quadriceps activation is necessary to counteract the quadriceps pull on the tibia, but coactivation can be elevated with symptomatic knee osteoarthritis (OA). To guide rehabilitation to attenuate risk for mobility limitations and falls, this study evaluated whether higher antagonistic open kinetic chain hamstring coactivation is associated with knee joint buckling (sudden loss of support) and shifting (a sensation that the knee might give way).DesignAt baseline, median hamstring coactivation was assessed during maximal isokinetic knee extensor strength testing and at baseline and 24-month follow-up, knee buckling and shifting was self-reported. Associations between tertiles of co-activation and knee (1) buckling, (2) shifting and (3) either buckling or shifting were assessed using logistic regression, adjusted for age, sex, knee OA and pain.Results1826 participants (1089 women) were included. Mean±SD age was 61.7±7.7 years, BMI was 30.3±5.5kg/m(2) and 38.2% of knees had OA. There were no consistent statistically significant associations between hamstring coactivation and ipsilateral prevalent or incident buckling or the combination of buckling and shifting. The odds ratios for incident shifting in the highest in comparison with the lowest tertile of coactivation had similar magnitudes in the combined and medial hamstrings, but only reached statistical significance for lateral hamstring coactivation, OR(95%CI) 1.53 (0.99, 2.36).ConclusionsHamstring coactivation during an open kinetic chain quadriceps exercise was not consistently associated with prevalent or incident self-reported knee buckling or shifting in older adults with or at risk for knee OA.

Summary Objective To examine potential risk factors for hallux valgus in community-dwelling elders. Method Data from 600 MOBILIZE Boston Study participants (386 women and 214 men) were analyzed. Hallux valgus was defined as >15° angular deviation of the hallux with respect to the first metatarsal bone toward the lesser toes. Associations of hallux valgus with age, body mass index (BMI), race, education, pes planus, foot pain, and in women, history of high heel shoe use, were assessed using sex-specific Poisson regression with robust variance estimation for risk ratios (RR) and 95% confidence intervals (CI). Results Hallux valgus was present in 58% of women and 25% of men. Higher BMI was inversely associated with presence of hallux valgus in women ( P trend=0.001), with the strongest inverse association observed in those with BMI of 30.0 or more compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually wore high-heeled shoes during ages 20–64 years compared to those who did not, had increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men, those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men without pes planus. Conclusion In women, hallux valgus was associated with lower BMI and high heel use during ages 20–64, while in men, associations were observed with higher BMI and pes planus. Our results suggest that the etiologic mechanisms for hallux valgus may differ between men and women.