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A letter to the editor is presented in response to the article "Health care rationing," by C. Ham in the June 10, 1995;310 issue.

Presents a response by David J. Hunter, Meir J. Stampfer, Graham A. Colditz, Frank E. Speizer, Walter C. Willett and J. Steven Morris to a letter to the editor about their article 'A Prospective Study of Selenium Status and Breast Cancer Risk,' in the 1990 issue of the 'Journal of the American Medical Association.'

Striking differences exist in outcomes for cancer between developed countries with comparable healthcare systems. We compare the healthcare systems of 3 countries (Denmark, Norway, Sweden), 3 UK jurisdictions (England, Wales and Northern Ireland), 3 Canadian provinces (British Columbia, Manitoba, Ontario) and 2 Australian states (New South Wales, Victoria) using a framework which assesses the possible contribution of primary care systems to a range of health outcomes, drawing on key characteristics influencing population health. For many of the characteristics we investigated there are no significant differences between those countries with poorer cancer outcomes (England and Denmark) and the rest. In particular, regulation, financing, the existence of patient lists, the GP gatekeeping role, direct access to secondary care, the degree of comprehensiveness of primary care services, the level of cost sharing and the type of primary care providers within healthcare systems were not specifically and consistently associated with differences between countries. Factors that could have an influence on patient and professional behaviour, and consequently contribute to delays in cancer diagnosis and poorer cancer outcomes in some countries, include centralisation of services, free movement of patients between primary care providers, access to secondary care, and the existence of patient list systems. It was not possible to establish a causal correlation between healthcare system characteristics and cancer outcomes. Further studies should explore in greater depth the associations between single health system factors and cancer outcomes, recognising that in complex systems where context is all-important, it will be difficult to establish causal relationships. Better understanding of the interaction between healthcare system variables and patient and professional behaviour may generate new hypotheses for further research. [ABSTRACT FROM AUTHOR]

Background: Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Despite some clinical guidelines also recommending weight loss for hip OA, there is no evidence from randomised controlled trials (RCT) to substantiate these recommendations. This superiority, 2-group, parallel RCT will compare a combined diet and exercise program to an exercise only program, over 6 months.Methods: One hundred people with symptomatic and radiographic hip OA will be recruited from the community. Following baseline assessment, participants will be randomly allocated to either, i) diet and exercise or; ii) exercise only. Participants in the diet and exercise group will have six consultations with a dietitian and five consultations with a physiotherapist via videoconferencing over 6 months. The exercise only group will have five consultations with a physiotherapist via videoconferencing over 6 months. The exercise program for both groups will include prescription of strengthening exercise and a physical activity plan, advice about OA management and additional educational resources. The diet intervention includes prescription of a ketogenic very low-calorie diet with meal replacements and educational resources to support weight loss and healthy eating. Primary outcome is self-reported hip pain via an 11-point numeric rating scale (0 = 'no pain' and 10 = 'worst pain possible') at 6 months. Secondary outcomes include self-reported body weight (at 0, 6 and 12 months) and body mass index (at 0, 6 and 12 months), visceral fat (measured using dual energy x-ray absorptiometry at 0 and 6 months), pain, physical function, quality of life (all measured using subscales of the Hip Osteoarthritis Outcome Scale at 0, 6 and 12 months), and change in pain and physical activity (measured using 7-point global rating of change Likert scale at 6 and 12 months). Additional measures include adherence, adverse events and cost-effectiveness.Discussion: This study will determine whether a diet intervention in addition to exercise provides greater hip pain-relief, compared to exercise alone. Findings will assist clinicians in providing evidence-based advice regarding the effect of a dietary intervention on hip OA pain.Trial Registration: ClinicalTrials.gov . Identifier: NCT04825483 . Registered 31st March 2021. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome is a major health problem worldwide associated with obesity, thus drawing attention to its relation to osteoarthritis (OA). However, it is still uncertain whether metabolic syndrome or body fat distribution is associated with knee OA. The aim of this longitudinal study was to elucidate the association between metabolic obesity and adverse structural changes of knee OA assessed by magnetic resonance imaging (MRI). Methods: Participants were recruited from the Hallym Aging Study cohort in Korea. Knee MRI scans, along with dual‐energy X‐ray absorptiometry, were assessed in 226 participants at baseline and after 3 years. The structural progression in the tibiofemoral joint was evaluated using the semi‐quantitative Whole‐Organ MRI Score (WORMS) for cartilage morphology and bone marrow lesions (BML). Logistic regression with generalized estimating equation was performed for associations of metabolic risk factors with worsening of WORMS scores at the subregional level. Results: In the medial compartment, fat mass in women was associated with cartilage loss, but the statistical significance disappeared after adjusting for body mass index. Metabolic syndrome and each of its components were not associated with cartilage loss or increase of BML. On the other hand, the interaction effects of metabolic syndrome on the association between obesity and knee OA progression were not significant. Conclusion: In this cohort, metabolic effects of obesity on knee cartilage damage and BML were not demonstrated. Further large‐scale studies are required to prove the causal relationship between metabolic obesity and knee OA. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of ultrasound and radiographic features of thumb‐base osteoarthritis (OA) with thumb‐base pain and hand function at baseline and 12 weeks. Method: Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb‐base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self‐reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12‐week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors. Results: A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound‐detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks. Conclusion: This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb‐base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb‐base OA. [ABSTRACT FROM AUTHOR]

Objective: To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Methods: Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. Results: The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10–1.50], 1.52 [1.30–1.78], 1.50 [1.27–1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03–1.42], 1.27 [1.07–1.52], 1.37 [1.15–1.62], respectively) were significantly associated with incident ROA. Conclusions: PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. Key Points: • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA. [ABSTRACT FROM AUTHOR]

Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.Design, Setting, and Participants: This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.Interventions: Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).Main Outcomes and Measures: The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.Results: Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.Conclusions and Relevance: Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347. [ABSTRACT FROM AUTHOR]

Motivation: Inference of ancestry using genetic data is motivated by applications in genetic association studies, population genetics and personal genomics. Here, we provide methods and software for improved ancestry inference using genome-wide single nucleotide polymorphism (SNP) weights from external reference panels. This approach makes it possible to leverage the rich ancestry information that is available from large external reference panels, without the administrative and computational complexities of re-analyzing the raw genotype data from the reference panel in subsequent studies.Results: We extensively validate our approach in multiple African American, Latino American and European American datasets, making use of genome-wide SNP weights derived from large reference panels, including HapMap 3 populations and 6546 European Americans from the Framingham Heart Study. We show empirically that our approach provides much greater accuracy than either the prevailing ancestry-informative marker (AIM) approach or the analysis of genome-wide target genotypes without a reference panel. For example, in an independent set of 1636 European American genome-wide association study samples, we attained prediction accuracy (R2) of 1.000 and 0.994 for the first two principal components using our method, compared with 0.418 and 0.407 using 150 published AIMs or 0.955 and 0.003 by applying principal component analysis directly to the target samples. We finally show that the higher accuracy in inferring ancestry using our method leads to more effective correction for population stratification in association studies.Availability: The SNPweights software is available online at http://www.hsph.harvard.edu/faculty/alkes-price/software/.Contact: aprice@hsph.harvard.edu or cychen@mail.harvard.edu.Supplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint disorder and a leading cause of disability. Due to an aging population and increasing obesity, the incidence of OA is rising. The etiology of OA is multifactorial and complex; thus prevention of OA remains challenging. Risk factors can be divided into person-level factors such as age, sex, obesity, genetics, race/ethnicity, and diet, and joint-level factors including injury, malalignment, and abnormal loading of the joints. This review provides a brief overview of the person-level risk factors and a more in-depth analysis of those at the joint level. It is only through an improved understanding of risk factors for the disease that we may be able to intervene meaningfully and prevent its occurrence. [ABSTRACT FROM AUTHOR]

Common polymorphisms in the N-acetyltransferase 2 gene (NAT2) modify the association between cigarette smoking and bladder cancer and have been hypothesized to determine whether active cigarette smoking increases breast cancer risk. The authors sought to replicate the latter hypothesis in a prospective analysis of 6,900 breast cancer cases and 9,903 matched controls drawn from 6 cohorts (1989–2006) in the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium. Standardized methods were used to genotype the 3 most common polymorphisms that define NAT2 acetylation phenotype (rs1799930, rs1799931, and rs1801280). In unconditional logistic regression analyses, breast cancer risk was higher in women with more than 20 pack-years of active cigarette smoking than in never smokers (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17, 1.39), after controlling for established risk factors other than alcohol consumption and physical inactivity. However, associations were similar for the slow (OR = 1.25, 95% CI: 1.11, 1.39) and rapid/intermediate (OR = 1.24, 95% CI: 1.08, 1.42) acetylation phenotypes, with no evidence of interaction (P = 0.87). These results provide some support for the hypothesis that long-term cigarette smoking may be causally associated with breast cancer risk but underscore the need for caution when interpreting sparse data on gene-environment interactions. [ABSTRACT FROM PUBLISHER]

Abstract: Background context: Few studies have directly evaluated the association of lumbar lordosis and segmental wedging of the vertebral bodies and intervertebral discs with the prevalence of spinal degenerative features. Purpose: To evaluate the association of computed tomography (CT)–evaluated lumbar lordosis as well as segmental wedging of the vertebral bodies and that of the intervertebral discs with various spinal degenerative features. Study design: This cross-sectional study was a nested project to the Framingham Heart Study. Patient Sample: A random consecutive subset of 191 participants chosen from the 3,590 participants enrolled in the Framingham Heart Study who underwent multidetector CT to assess aortic calcification. Outcome measures: Dichotomous variables indicating the presence of intervertebral disc narrowing, facet joint osteoarthritis, spondylolysis, spondylolisthesis and spinal stenosis, and density (in Hounsfield units) of multifidus and erector spinae muscles were evaluated on supine CT, as well as the lordosis angle (LA) and the wedging of the vertebral bodies and intervertebral discs. The sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were used in the analyses. Methods: Mean values (±standard deviation [SD]) of LA, ΣB, and ΣD were calculated in males and females and compared using the t test. Mean values (±SD) of LA, ΣB, and ΣD in four age groups (<40, 40–49, 50–59, and 60+ years) were calculated. We tested the linear relationship between LA, ΣB, and ΣD and age groups. We evaluated the association between each spinal degenerative feature and LA, ΣB, and ΣD using multiple logistic regression analysis where studied degenerative features were the dependent variable and all LA, ΣB, and ΣD (separately) as well as age, sex, and body mass index were independent predictors. Results: Lordosis angle was slightly lower than the normal range for standing individuals, and no difference was found between males and females (p=.4107). However, the sex differences in sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were statistically significant (.0001 and .001, respectively). Females exhibit more dorsal wedging of the vertebral bodies and less dorsal wedging of the intervertebral discs than do males. All these parameters showed no association (p>.05) with increasing age. Lordosis angle showed statistically significant association with the presence of spondylolysis (odds ratio [95% confidence interval]: 1.08 [1.02–1.14]) and with the density of multifidus (1.06 [1.01–1.11]) as well as a marginally significant association with isthmic spondylolisthesis (1.07 [1.00–1.14]). ΣB showed a positive association with degenerative spondylolisthesis and disc narrowing (1.14 [1.06–1.23] and 1.04 [1.00–1.08], correspondingly), whereas ΣD showed a negative one (0.93 [0.87–0.98] and 0.93 [0.89–0.97], correspondingly). Conclusions: Significant associations were found between lumbar lordosis evaluated in supine position and segmental wedging of the vertebral bodies and intervertebral discs and the prevalence of spondylolysis and spondylolisthesis. Additional studies are needed to evaluate the association between spondylolysis, isthmic and degenerative spondylolisthesis and vertebral and disc wedging at the segmental level. [Copyright &y& Elsevier]

The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses’ Health Study (NHS) aged 34–59 years (1980–2006) and 100,547 women from Nurses’ Health Study II (NHS II) aged 26–46 years (1991–2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)2) at age 18 years. Relative risks of T2DM across age-at-menarche categories (≤11, 12, 13, 14, and ≥15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI. [ABSTRACT FROM PUBLISHER]

Vitamin A supplementation starting at 6 months of age is an important child survival intervention; however, not much is known about the association between vitamin A status before 6 months and mortality among children born to HIV-infected women. Plasma concentrations of vitamins A and B-12 were available at 6 weeks of age (n = 576 and 529, respectively) for children born to HIV-infected women and they were followed up for morbidity and survival status until 24 months after birth. Children in the highest quartile of vitamin A had a 49% lower risk of death by 24 months of age compared to the lowest quartile (HR: 0.51, 95% CI: 0.29–0.90; P-value for trend = 0.01). Higher vitamin A levels were protective in the sub-groups of HIV-infected and un-infected children but this was statistically significant only in the HIV-uninfected subgroup. Higher vitamin A concentrations in plasma are protective against mortality in children born to HIV-infected women. [ABSTRACT FROM PUBLISHER]

To assess prospectively the relation between body mass index, weight gain, repeated intentional weight losses, and the risk of self-reported hypertension, the authors studied 46, 224 women who were participants in the Nurses Health Study II, who were free of hypertension in 1993, and who completed questions on intentional weight losses between 1989 and 1993. Women who reported they had intentionally lost ≥20 lbs (9 kg) ≥3 times were classified as severe weight cyclers. Women who had intentionally lost ≥10 lbs (4.5 kg) ≥3 times, but who did not meet the criteria for severe weight cycling, were classified as mild weight cyclers. Between 1993 and 1995, 1, 107 incident cases of diagnosed hypertension were reported. Body mass index and weight gain, but not weight cycler status, were independently associated with the development of hypertension. For each 10 Ib (4.5 kg) gain in weight between 1989 and 1993, the risk of hypertension increased 20% (odds ratio (OR) = 1.20, 95% confidence interval (Cl) 1.15, 1.24). After adjustment for body mass index and weight gain, the risks associated with mild weight cycling (OR = 1.15, 95% Cl 1.00, 1.33) and severe weight cycling (OR = 1.13, 95% Cl 0.79, 1.61) were small and not significant. Thus, the results of this study offer support for the current weight guidelines and provide further evidence of the health risks associated with excessive weight and weight gain. However, these data do not suggest an independent effect of weight cycling on risk of hypertension. Am J Epidemiol 1999; 150: 573-9. [ABSTRACT FROM PUBLISHER]

Objective Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. Methods We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren–Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. Results Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s. d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b  = −0.042, 95% CI −0.08, −0.0004). No other associations were observed. Conclusions In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications. [ABSTRACT FROM AUTHOR]

Objectives Emerging evidence suggests a potential link between OA and gout; however, the association between serum uric acid (UA) itself and knee OA remains uncertain due to a lack of longitudinal studies. Here, we investigated the association between serum UA and knee OA according to cartilage status in elderly community residents without gout. Methods In this longitudinal study, participants without a history of gout were recruited from among the Korean cohort of the Hallym Aging Study (n  = 296 for radiography study and n  = 223 for MRI study). Weight-bearing knee radiographs and 1.5-T MRI scans, along with blood collection for analysis of serum UA, were performed at baseline and after 3 years. The severity and structural progression of knee OA were evaluated using the Kellgren–Lawrence grading system and the Whole-Organ MRI Score (WORMS) cartilage scoring method. Multivariable logistic regression analysis was conducted using generalized estimating equation (GEE) models. Results Serum UA levels were not associated with radiographic progression after adjusting for age, sex and BMI. There was no significant association between serum UA and tibiofemoral cartilage loss on MRI. However, baseline serum UA levels were negatively associated with patellofemoral cartilage loss over 3 years (adjusted odd ratio 0.70 per 1 mg/dl increase, 95% CI: 0.49, 0.98). Conclusion In this population-based cohort, serum UA was not a risk factor for knee OA progression. Further large-scale longitudinal studies in other populations are needed to validate the effects of UA on cartilage damage. [ABSTRACT FROM AUTHOR]

Background: Results of several case-control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer. Methods: We conducted a pooled analysis of 13 prospective studies that included 530469 women and 244483 men and had follow-up times of up to 7-20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer. All participants had completed a validated food frequency questionnaire at study entry. Using the primary data from each study, we calculated the study-specific relative risks (RRs) for renal cell cancer by using Cox proportional hazards models and then pooled these RRs by using a random-effects model. All statistical tests were two-sided. Results: A total of 1478 incident cases of renal cell cancer were identified (709 in women and 769 in men). We observed statistically significant positive associations or trends in pooled age-adjusted models for intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, total protein, and animal protein. However, these associations were attenuated and no longer statistically significant after adjusting for body mass index, fruit and vegetable intake, and alcohol intake. For example, the pooled age-adjusted RR of renal cell cancer for the highest vs the lowest quintile of intake for total fat was 1.30 (95% confidence interval [Cl] = 1.08 to 1.56; Ptrend = .001) and for total protein was 1.17 (95% Cl = 0.99 to 1.38; Ptrend = .02). By comparison, the pooled multivariable RR for the highest vs the lowest quintile of total fat intake was 1.10 (95% Cl = 0.92 to 1.32; Ptrend = .31) and of total protein intake was 1.06 (95% Cl = 0.89 to 1.26; Ptrend = .37). Intakes of red meat, processed meat, poultry, or seafood were not associated with the risk of renal cell cancer. Conclusions: Intakes of fat and protein or their subtypes, red meat, processed meat, poultry, and seafood are not associated with risk of renal cell cancer. [ABSTRACT FROM AUTHOR]

The article presents medical research that investigated the relation between HIV infection stage, child malnutrition, and child mortality among children of HIV-positive mothers in Tanzania. Results indicate that advanced disease progression during pregnancy is associated with an increased risk of child mortality until 24 months of age.

BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp3l2Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (C1), 0.9-3.7]. For XPD, having variation at both loci (3l2Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% Cl, 0.6-1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% Cl, 1.0-5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p <0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp3l2Asn and Lys75lGln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study on the association of red meat consumption and risk of breast cancer among premenopausal women aged 26-46 participating in the Nurses' Health Study II. A 12-year follow-up of the 90,659 participants documented 1,021 cases of invasive breast carcinoma. Greater red meat intake was strongly related to higher risk of breast cancers that were estrogen and progesterone receptor positive, but not with progesterone and estrogen negative.

Emerging evidence indicates that variation in the transcription factor 7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2 diabetes. In a prospective, nested, case-control study (n = 3,520) within the Nurses' Health Study (687 type 2 diabetic case and 1,051 control subjects) and the Health Professionals Follow-up Study (886 case and 896 control subjects), we examined the association of a common variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk among Caucasians. Frequencies of the T-allele were significantly higher among case than control subjects; each copy of the T-allele was associated with a 1.32-fold (P = 0.0002) and 1.53-fold (P < 0.0001) increased type 2 diabetes risk in women and men, respectively. The odds ratios (95% CI) associated with homozygous carriers of the T-allele were 1.86 (1.30-2.67) and 2.15 (1.48-3.13) in women and men, respectively. Population-attributable risks for diabetes associated with the T-allele were 14.8 and 22.3% for women and men, respectively. In a meta-analysis of 3,347 case and 3,947 control sujects, each copy of the T-allele was associated with a 1.48-fold increased risk (P < 10-16). Our findings confirm that the TCF7L2 gene represents an important locus for predicting inherited susceptibility to type 2 diabetes. Diabetes 55:2645-2648, 2006 [ABSTRACT FROM AUTHOR]

Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [-786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects. Genotype distributions of -786T>C and Glu298Asp polymorphisms were not significantly different between case and control subjects. CHD risk was significantly higher among men with the variant allele at the rs1541861 locus (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence interval 1.1-2.1]). Moreover, among control subjects, plasma soluble vascular cell adhesion molecule concentrations were significantly higher among carriers of this allele (P 0.019) and carriers of the variant allele of the -786T>C (P 0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In conclusion, our data suggested that -786T>C, Glu298Asp, and an intron 8 polymorphism of the eNOS gene are potentially involved in the atherogenic pathway among U.S. diabetic men. Diabetes 55: 2140-2147, 2006 [ABSTRACT FROM AUTHOR]

Objective: To examine disclosure of sexual orientation and response rates in a pilot study of questions on sexual orientation and gender of sexual partners in the Nurses' Health Study II. Methods: A pilot questionnaire was mailed to random samples of 350 women from each of three marital status strata: never married, previously married, and currently married. We estimated prevalence of each category of sexual orientation in the pilot study. Response rates to the sexual orientation question for the pilot questionnaire and the 1995 cohort questionnaire were compared. Results: The overall response rate to the pilot study was 78%. In the pilot study, 98% of women reported a sexual orientation of heterosexual, 0. 1% bisexual, and 0.9% lesbian, with 0.7% either declining to answer, leaving the question blank, or categorizing themselves as none of the above, weighted for stratified sampling by marital status. The distribution of sexual orientation in the cohort study (N = 91,654) was similar. Asking women to participate in the pilot study of sexual orientation questions did not appear to cause participants to drop out of the cohort. Concordance between reported sexual orientation on the pilot study and the cohort study was high. Conclusions: Based on our experience, researchers may be encouraged to add questions on sexual orientation to large studies of women. [ABSTRACT FROM AUTHOR]

The erbB2 (HER2/neu) gene is found amplified in tumours. A single nucleotide polymorphism at codon 655 (Ile655Val) has been studied in a number of case-control studies with respect to breast cancer risk, with conflicting results. The aim of the present study was to examine the association between this polymorphism and breast cancer risk in a prospective, predominantly Caucasian cohort of women, the Nurses' Health Study. We genotyped the Ile655Val single nucleotide polymorphism (rs1801200) in 1271 incident breast cancer cases, and 1667 controls who were selected from the Nurses' Health Study blood cohort. Controls were matched to cases on age, menopausal status, fasting status and postmenopausal hormone use at blood draw. An inverse association was observed between the Val/Val genotype and breast cancer risk (Val/Val versus Ile/Ile odds ratio=0.68, 95% confidence interval 0.47-0.98). We conclude that this polymorphism is not associated with an increase in breast cancer risk, and may in fact be associated with a modest decrease in risk. [ABSTRACT FROM AUTHOR]

Objectives: To examine associations between sexual orientation and breast cancer risk factors, cardiovascular disease (CVD) risk factors, mental health status, and health-related functioning. Methods: We compared participants in the Nurses' Health Study II (NHSII) reporting a lesbian or bisexual orientation with those reporting a heterosexual orientation, with heterosexuals serving as the reference group for all comparisons. Prevalence of health behaviors and conditions was adjusted for differences in the distribution of age, ancestry, and region of residence by standardizing to the distribution of the overall cohort. Multivariate prevalence ratios were calculated to compare lesbians and bisexuals with heterosexuals using binomial regression with the log link function. Means of health conditions were measured using continuous scales standardized to the distribution of the overall cohort. Differences in means comparing lesbians and bisexuals with heterosexuals were tested by multivariate linear regression. All comparisons were adjusted for age, ancestry, and region of residence. Results: Based on information from 90,823 women aged 32-51 in 1995, those reporting a sexual orientation of lesbian (n = 694) had a higher prevalence of risk factors for breast cancer, including nulliparity and high daily alcohol intake, compared with heterosexual women. Lesbians also had a higher prevalence of several risk factors for CVD, including higher body mass index (BMI) and elevated prevalence of current smoking. Lesbians were more likely to report depression and the use of antidepressants. Key results for health risk factors were similar for lesbians and bisexual women (n = 317). Conclusions: Lesbian and bisexual women were found to have a higher prevalence of several important risk factors for breast cancer, CVD, and poor mental health and functioning outcomes. Most of these risk factors are modifiable, and appropriate interventions could play an important role in improving the health status of lesbian and bisexual women. [ABSTRACT FROM AUTHOR]

Background: In the general population, the risk of developing ovarian cancer is reduced in women who have undergone tubal ligation, hysterectomy, or oophorectomy, although peritoneal cancer can arise after bilateral oophorectomy. In studies from genetic screening clinics, women with mutations in the breast and ovarian susceptibility genes BRCA1 and BRCA2 have been found to have a low risk of peritoneal carcinoma in the first years after bilateral oophorectomy. We assessed the level and persistence of reduction of ovarian (including peritoneal) cancer risk after gynecologic surgeries for women who carry BRCA1/2 mutations but were not selected from high-risk clinics. Methods: We identified 1124 Israeli women with incident ovarian cancer or primary peritoneal cancer and tested 847 of them for the three Ashkenazi founder mutations. We compared gynecologic surgery history among all case patients, BRCA1 (n = 187) and BRCA2 (n = 64) carrier case patients, and the non-carrier case patients (n = 598) with that in control subjects drawn from a population registry (n = 2396). We estimated ovarian cancer risk (odds ratios [ORs] with 95% confidence intervals [CIs]) after gynecologic surgery in mutation carriers and noncarriers with logistic regression models. Results: Eight women with primary peritoneal cancer and 128 control subjects reported a previous bilateral oophorectomy (OR = 0.12, 95% CI = 0.06 to 0.24). Other gynecologic surgeries were associated with a 30%-50% reduced risk of ovarian cancer, depending on the type of surgery, with surgery to remove some ovarian tissue associated with the most risk reduction (OR = 0.34, 95% CI = 0.16 to 0.74). Reduced risks were seen in BRCA1/2 carriers and non-carriers. Age at surgery and years since surgery did not affect risk reductions. Conclusion: Both BRCA1/2 mutation carriers and non-carriers have reduced risk of ovarian or peritoneal cancer after gynecologic surgery. The magnitude of the reduction depends upon the type and... [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants.Methods: Twenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone.Results: Participants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3).Conclusions: There are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA. [ABSTRACT FROM AUTHOR]

The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24–60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren–Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle α), sagittal inclination angle (angle β), fibular contacting area (S), load‐bearing area (Sτ), lateral stress‐bolstering area (Sφ), and posterior stress‐bolstering area (Sυ) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR (T0) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty‐three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline and T0 time point. While baseline angle α was positively associated with TKR risk, other measures at baseline and all measures at T0 were not significantly associated with TKR risk. Changes in S, Sτ, and Sυ were significantly and negatively associated with the risk of TKR (ΔS, odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19–0.76; ΔSτ, OR = 0.37, 95% CI: 0.16–0.87; ΔSυ, OR = 0.22, 95% CI: 0.08–0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the association between psychological factors and pain exacerbations in people with hip OA. Methods Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perceived they were experiencing a hip pain exacerbation. Hip pain exacerbation was defined as an increase of 2 points in pain intensity compared with baseline on an 11-point numeric rating scale (0–10). The Depression, Anxiety and Stress Scale–21 Items, Positive and Negative Affect Schedule, Pain Catastrophizing Scale and Pain Self-Efficacy Questionnaire were used to evaluate psychological factors. The associations of these with risk of hip pain exacerbation were examined by conditional logistic regression. Results Of 252 participants recruited, 131 (52.0%) contributed both case and control period data and were included in the analysis. A significant association was found between Pain Catastrophizing Scale overall score (1 point increase) with hip pain exacerbations (odds ratio: 1.07, 95% CI: 1.04, 1.11). An increase of a minimal important change (5.5 points) of Pain Self-Efficacy Questionnaire score was associated with a lower odds of pain exacerbations (odds ratio: 0.74, 95% CI: 0.65, 0.85). No significant associations were found between Depression, Anxiety and Stress Scale–21 Items or Positive and Negative Affect Schedule scores with hip pain exacerbations. Conclusion Both pain catastrophizing and pain self-efficacy beliefs were associated with pain exacerbations in people with hip OA, but other psychological factors including depression, anxiety and stress or positive and negative affects, were not associated with pain exacerbations. [ABSTRACT FROM AUTHOR]

Importance: Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms.Objective: To determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis.Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017.Interventions: Participants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124).Main Outcomes and Measures: Primary outcomes at the 18-month follow-up were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) knee pain (0 best-20 worst; minimally clinically important difference [MCID, 2]) and knee joint compressive force, defined as the maximal tibiofemoral contact force exerted along the long axis of the tibia during walking (MCID, unknown).Results: Among 377 randomized participants (mean age, 65 years; 151 women [40%]), 320 (85%) completed the trial. Mean adjusted (sex, baseline BMI, baseline outcome values) WOMAC pain scores at the 18-month follow-up were not statistically significantly different between the high-intensity group and the control group (5.1 vs 4.9; adjusted difference, 0.2; 95% CI, -0.6 to 1.1; P = .61) or between the high-intensity and low-intensity groups (5.1 vs 4.4; adjusted difference, 0.7; 95% CI, -0.1 to 1.6; P = .08). Mean knee joint compressive forces were not statistically significantly different between the high-intensity group and the control group (2453 N vs 2512 N; adjusted difference, -58; 95% CI, -282 to 165 N; P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, -21; 95% CI, -235 to 193 N; P = .85). There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5).Conclusions and Relevance: Among patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis.Trial Registration: ClinicalTrials.gov Identifier: NCT01489462. [ABSTRACT FROM AUTHOR]

Presents a study which examined the association between physical activity and breast cancer in young women. Information on how physical activity has been described as a means of primary breast cancer prevention; Assessment of methods for measuring intensity and duration of activity; Methodological approach used in this study; What the findings of the study indicated.

Our studies on interactions of a folate-metabolizing gene polymorphism and dietary intake in colorectal tumorigenesis demonstrate the potential importance of studying interactions between genotype and environmental exposure in relation to cancer risk. We observed an inverse association of a polymorphism (667C --> T, ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with colorectal cancer but not with colorectal adenomas. The inverse association of methionine and adverse association of alcohol with colorectal cancer were stronger among val/val individuals. These interactions were not present in studies of colorectal adenomas. Our studies illustrate that studying gene-environment interactions in relation to cancer can be of importance in clarifying cancer etiology as well as pointing to preventive dietary modifications. [ABSTRACT FROM AUTHOR]

Focuses on the social inequalities on health in Australia. Development of national goals and target for health; Demand for medical services; Effectivity of health care delivery.

Background: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.Methods: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling.Discussion: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.Trial Registration: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019. [ABSTRACT FROM AUTHOR]

Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits.Methods: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity.Results: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed.Conclusions: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk. [ABSTRACT FROM AUTHOR]

Introduction. Hypertension is a leading risk factor for cardiovascular mortality and an emerging public health concern in sub-Saharan Africa. Few studies have examined performance on the management of hypertension in this region, where the context may be distinct from other developing regions. Objectives. We aimed to determine the prevalence and correlates of hypertension, awareness, treatment, and control among adults in Botswana, a middle-income African country undergoing rapid demographic transition and with high HIV burden. Methods. In this 2014 cross-sectional survey of adults aged 15–69 years, information on sociodemographic characteristics, lifestyle behavior, and medical history was collected through in-person interviews and physical measurements (body mass index and triplicate blood pressure (BP)). Hypertension was defined as self-report of use of antihypertensives in the previous two weeks and/or having elevated BP (≥140/90 mmHg). Multivariable logistic regression was employed to explore factors associated with hypertension, awareness (report of previous diagnosis), treatment (antihypertensives), and control (BP < 140/90). Results. Our analysis (N = 4,007) yielded an age-standardized hypertension prevalence of 30% (95% CI: 28%–32%, N = 1,393). Among hypertensives, 54% (50–58%) were unaware of their condition, 45% (40–50%) of those aware were untreated, and 63% (55–70%) of those on medications were suboptimally treated (BP ≥ 140/90 mmHg). A fifth of hypertensives who were diagnosed but not on medications had BP ≥ 180/110 mmHg. Diabetes was the strongest correlate of hypertension and awareness (aOR 4.00, 1.86–8.59; aOR 3.30, 1.44–7.55, respectively). Males were less likely to be aware (aOR 0.62, 0.41–0.94) or controlled (aOR 0.36, 0.16–0.83). Obese individuals were more likely to be treated (aOR 2.17, 1.12–4.22), yet less likely to be controlled (aOR 0.32, 0.15–0.66). Conclusions. We report the first nationally representative estimates of the hypertension care cascade performance in Botswana, which will support planning and future policy evaluations. Findings contribute to the relatively sparse evidence on this subject and may inform development of innovations that improve quality of hypertension management and adherence support in similar settings. [ABSTRACT FROM AUTHOR]

Introduction. Hypertension is a leading risk factor for cardiovascular mortality and an emerging public health concern in sub-Saharan Africa. Few studies have examined performance on the management of hypertension in this region, where the context may be distinct from other developing regions. Objectives. We aimed to determine the prevalence and correlates of hypertension, awareness, treatment, and control among adults in Botswana, a middle-income African country undergoing rapid demographic transition and with high HIV burden. Methods. In this 2014 cross-sectional survey of adults aged 15–69 years, information on sociodemographic characteristics, lifestyle behavior, and medical history was collected through in-person interviews and physical measurements (body mass index and triplicate blood pressure (BP)). Hypertension was defined as self-report of use of antihypertensives in the previous two weeks and/or having elevated BP (≥140/90 mmHg). Multivariable logistic regression was employed to explore factors associated with hypertension, awareness (report of previous diagnosis), treatment (antihypertensives), and control (BP < 140/90). Results. Our analysis (N = 4,007) yielded an age-standardized hypertension prevalence of 30% (95% CI: 28%–32%, N = 1,393). Among hypertensives, 54% (50–58%) were unaware of their condition, 45% (40–50%) of those aware were untreated, and 63% (55–70%) of those on medications were suboptimally treated (BP ≥ 140/90 mmHg). A fifth of hypertensives who were diagnosed but not on medications had BP ≥ 180/110 mmHg. Diabetes was the strongest correlate of hypertension and awareness (aOR 4.00, 1.86–8.59; aOR 3.30, 1.44–7.55, respectively). Males were less likely to be aware (aOR 0.62, 0.41–0.94) or controlled (aOR 0.36, 0.16–0.83). Obese individuals were more likely to be treated (aOR 2.17, 1.12–4.22), yet less likely to be controlled (aOR 0.32, 0.15–0.66). Conclusions. We report the first nationally representative estimates of the hypertension care cascade performance in Botswana, which will support planning and future policy evaluations. Findings contribute to the relatively sparse evidence on this subject and may inform development of innovations that improve quality of hypertension management and adherence support in similar settings. [ABSTRACT FROM AUTHOR]

Introduction: Symptomatic osteoarthritis (OA) in the knee is defined as the presence of OA radiographic features in combination with knee symptoms. Pain has not been shown to correlate meaningfully to radiographic severity. We aimed to determine the relationship between a tear of the anterior cruciate ligament (ACL) with knee symptoms and radiographic OA. Methods: A within‐person, between‐knee cross‐sectional study of 37 participants from the Osteoarthritis Initiative (OAI) with a complete or partial ACL tear detected on magnetic resonance imaging in 1 knee (index knee) were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and radiographs of both knees, 1 with an ACL tear and one without (control knee) were scored for OA severity (Kellgren‐Lawrence Grading) and symptoms. A generalized estimating equation with linear regression was used to compare symptom scores within individuals as well as to radiographic severity. Results: Thirty‐seven individuals (40% female, average age = 60.7years, body mass index = 31.0 kg/m2) reported no difference in knee symptoms (WOMAC pain odds ratio [OR] =1.92, 95%CI 0.699‐5.248, P =.21; KOOS symptoms OR = 2.12, 95%CI 0.740‐6.065, P =.09), stiffness (OR = 1.67, 95%CI 0.653‐5.583, P =.35) or functional disability (OR = 1 0.97, 95%CI 0.515‐7.508, P =.32) in the knee that exhibited an ACL tear compared to the control knee. Only knee function and disability (WOMAC Disability OR = 1.12, 95%CI 1.003‐1.249, P =.04) were associated with radiographic severity between index and control knees. Conclusion: Individuals did not report an increase in knee pain, stiffness or disability in their ACL‐deficient knee. Only disability was associated with worsening severity of radiographic OA in ACL‐deficient knees. [ABSTRACT FROM AUTHOR]

We compared the assessment of active synovitis in knee osteoarthritis (OA) by utilising superb microvascular imaging (SMI) and conventional power Doppler (cPD) techniques, and then correlated each technique with paients' symptoms, radiographic features and magnetic resonance imaging (MRI)-detected synovitis. A subgroup of participants with symptomatic knee OA underwent dynamic ultrasound assessment for semi-quantitative scores for SMI and cPD in the suprapatellar, medial and lateral parapatellar knee recesses. Knee pain and other symptoms were evaluated with the knee injury and osteoarthritis outcome score (KOOS). OA severity was assessed using the Kellgren and Lawrence grade (KLG) on radiograph and effusion-synovitis and Hoffa's synovitis score of MRI osteoarthritis knee score on non-contrast-enhanced MRI sequences. The χ2 test and κ statistics were conducted to compare detectability of SMI and cPD for low-grade inflammation, and the Spearman's correlation and Fisher's r to z transformation were conducted to compare correlations of both techniques with symptoms and imaging severity. A total of 89 participants were included in the analyses. SMI increased the detection rate by 25.5% for grade 0 cPD, by 35.4% for grade 1 cPD and by 9% for grade 2 cPD. SMI showed significant correlations with KOOS symptoms, KLG, MRI effusion-synovitis and Hoffa's synovitis scores (r = -0.24 [-0.45, -0.01]; r = 0.31 [0.10, 0.50]; r = 0.49 [0.33, 0.63]; and r = 0.54 [0.37, 0.68]). The cPD was significantly correlated with KOOS pain, other symptoms, MRI effusion-synovitis and Hoffa's synovitis (r = -0.23 [-0.44, -0.01]; r = -0.29 [-0.49, -0.06]; r = 0.46 [0.28, 61], r = 0.46 [0.25, 0.63]). However, no significant differences were detected in their extent of correlations. SMI can detect low-grade inflammation implicated in OA disease better than cPD and reveal a significant correlation with symptoms, radiographic features and MRI synovitis. The added clinical value of SMI over cPD is still not clear. [ABSTRACT FROM AUTHOR]

Background: Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive.Objective: To determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK.Methods: Between 1996 and 2001, approximately 1.3 million women in the UK, mean age 56 (standard deviation, 5) years, were recruited into the Million Women Study. Information on alcohol intake, lifestyle factors, and medical history was collected at recruitment by questionnaire. Information on incident cases of PD was ascertained by record linkage to national hospital admission records and death registrations. We estimated multivariable-adjusted relative risks and corresponding 95% confidence intervals using Cox proportional hazards models according to categories of alcohol intake.Results: During an average of 17.9 years of follow-up, 11,009 women had a new record of PD among 1,309,267 women. In drinkers, the multivariable-adjusted relative risk comparing women who drank more than 14 drinks of alcohol per week with women who drank 1 to 2 drinks of alcohol per week was 0.99 (95% confidence interval: 0.90, 1.10). Results did not materially change after excluding the first 10 years of follow-up (relative riskadjusted = 1.01; 95% confidence interval: 0.90, 1.13). There were no significant trends in alcohol-related PD risk among never smokers. Additionally, examining this association by type of alcohol intake also yielded null findings.Conclusion: These results do not support an association between alcohol intake and PD risk in women. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of the updated version of an evidence-based osteoarthritis (OA) resource and consumer hub, 'My Joint Pain' website, on health education and quality of care over 12 months.Methods: Using a classic quasi-experimental design, participants with symptomatic hip or knee OA were recruited across Australia to evaluate the 'My Joint Pain' website, compared to a control group of non-users from 12 to 24 months. Outcome measures included the Health Education Impact Questionnaire (HEIQ) and the OA Quality Indicator (OAQI) questionnaire. The changes from 12 to 24 months in the HEIQ were evaluated using a generalised linear model. The differences between users and non-users in the OAQI were evaluated using a chi-square test.Results: A total of 277 eligible participants with symptomatic hip or knee OA were recruited at baseline, and 122 participants completed the 24-month surveys (users: n = 35, non-users: n = 87). There was no significant difference between users and non-users for the HEIQ scores at 24 months after adjustments for age, sex and body mass index (BMI). Users had higher emotional distress scores than non-users in univariable analysis. When compared with non-users in the OAQI, users showed favourable changes in receiving information about "self-management" and "acetaminophen" and "non-steroidal anti-inflammatory drugs (NSAIDs)" from 12 to 24 months.Conclusion: The evaluation of the updated 'My Joint Pain' website didn't find significant improvements in terms of health education, but it may help delivering useful information about self-management and appropriate use of pharmacological treatments. More strategies are needed to facilitate the uptake of evidence-based self-management and education online resources for OA consumers. [ABSTRACT FROM AUTHOR]

Objective: To examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses' Health Study (NHS) data. Design: At baseline (1995–2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed. Setting and participants: 8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory. Measures: We estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension. Results: We confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score. Conclusions: Women with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension. [ABSTRACT FROM AUTHOR]