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Importance: Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain. Observations: Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching). Conclusions and Relevance: Knee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management. This review summarizes current evidence regarding the diagnosis and treatment of knee osteoarthritis, patellofemoral pain, and meniscal tears. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does a weight loss and exercise program in community settings lead to improvement in knee pain in patients with osteoarthritis and overweight or obesity? Findings: This randomized clinical trial included 823 patients with knee osteoarthritis and overweight or obesity treated with diet and exercise vs an attention control. After 18 months, the adjusted mean difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (range, 0-20) was −0.6, a difference that met statistical significance. Meaning: In patients with knee osteoarthritis and overweight or obesity, an 18-month program of weight loss and exercise based in community settings, compared with an attention control group, led to a small difference in knee pain of uncertain clinical importance. Importance: Some weight loss and exercise programs that have been successful in academic center–based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, −0.6; 95% CI, −1.0 to −0.1; P =.02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was −7.7 kg (8%) in the diet and exercise group (n = 289) and −1.7 kg (2%) in the attention control group (n = 273) (mean difference, −6.0 kg; 95% CI, −7.3 kg to −4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549 This randomized clinical trial assesses the effect of a diet and exercise intervention vs an attention control condition on knee pain at 18-month follow-up among individuals aged 50 years or older with knee osteoarthritis and overweight or obesity. [ABSTRACT FROM AUTHOR]

The association between dietary fiber intake and risk of colorectal cancer is evaluated. Results reveal that dietary fiber intake is inversely associated with risk of colorectal cancer in age-adjusted analyses.

Epstein-Barr virus infection may increase a person's risk of developing multiple sclerosis, according to a study of 144 women with multiple sclerosis and 288 healthy women. Epstein-Barr virus causes mononucleosis., Context: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). Objective: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2) and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. Design Setting, and Subjects: Prospective, nested case-control study. Of 62439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 19891990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. Main Outcome Measure: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. Results: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P=.03), EBNA-2 (GMT, 91 vs 40; P=.01), and EA-D (15.9 vs 5.9; P=.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.73.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8(95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. Conclusions: Our results support a role of EBV in the etiology of MS.

Women with irregular menstrual cycles are twice as likely to develop type 2, or adult-onset, diabetes, according to a study of 101,073 women participating in the Nurses' Health Study II. The increased risk of type 2 diabetes was even evident in women who were not obese, although obese women had a greater risk than non-obese women., Context Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM). Objective To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles. Design and Setting The Nurses' Health Study II, a prospective observational cohort study. Participants A total of 101073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire. Main Outcome Measure Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories). Results During 564333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of Conclusion Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.

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]

Women who drink alcohol may want to limit their intake in order to reduce their risk of breast cancer. Researchers reviewed six studies covering 322,647 women that analyzed the link between food intake and breast cancer. Women who drank two to five drinks a day had a 40% greater risk of breast cancer than non-drinkers. Intakes above that amount do not seem to increase the risk. The type of alcoholic beverage consumed had no effect on risk., Objective.--To assess the risk of invasive breast cancer associated with Total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. Data Sources.--We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322 647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. Data Extraction.--Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. Data Synthesis.--For alcohol intakes less than 60 g/d (reported by [is greater than] 99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. Conclusions.--Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk. JAMA. 1998;279:535-540

Weight gain in adulthood may increase a woman's risk of developing breast cancer after menopause. This was one conclusion of a 16-year follow-up of 95,256 women participating in the Nurses' Health Study. During that time, 2,517 women developed breast cancer and 60% were postmenopausal. Weight gain during adulthood did not increase the risk of premenopausal breast cancer but increased the risk of postmenopausal breast cancer two-fold in women who did not use hormone therapy. Weight gain and hormone use combined were linked to one-third of postmenopausal breast cancer cases., Context.--Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease. Objective.--To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality. Design.--Cohort study. Setting.--A cohort of 95 256 US female nurses aged 30 to 55 years who were followed up for 16 years. Main Outcome Measure.--Incident and fatal breast cancer. Results.--During 1 203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m[sup.2] vs is less than or equal to 20 kg/m[sup.2]; 95% confidence interval, 1.09-2.32; P for trend Conclusions.--Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones. JAMA. 1997;278:1407-1411

Many of the same risk factors for diabetes appear to increase a woman's risk of gestational diabetes as well. Gestational diabetes is diabetes that is diagnosed for the first time during pregnancy. Of the 14,613 women enrolled in the Nurses' Health Study, 772 developed gestational diabetes during pregnancy. Older age, family history of diabetes, increased weight before pregnancy and cigarette smoking were all associated with an increased risk of gestational diabetes. Non-white women also had an increased risk. Women who exercised regularly before pregnancy had a slightly lower risk., Context. -- Gestational diabetes mellitus (GDM) affects 3% to 5% of pregnancies. Knowledge of risk factors for GDM is needed to identify possible preventive strategies. Objective. -- To assess whether recognized determinants of non -- insulin-dependent diabetes mellitus also may be markers for increased risk of GDM. Design. -- Prospective cohort study. Setting. -- The Nurses' Health Study II, which involves female US nurses aged 25 to 42 years at entry. Participants. -- The analyses included 14 613 women without previous GDM or other known diabetes who reported a singleton pregnancy between 1990 and 1994. Of these women, 722 (4.9%) reported a new diagnosis of GDM. Main Outcome Measure: Self-report of GDM, validated by medical record review in a subset. Results. -- In multivariate analyses including age, pregravid body mass index (BMI), and other GDM risk factors, the risk for GDM increased significantly with increasing maternal age (P for trend, [is less than].01) and family history of diabetes mellitus (relative risk, 1.68; 95% confidence interval [CI], 1.39-2.04). Relative risks for GDM were 2.13 (95% CI, 1.65-2.74) for pregravid BMI of 25 to 29.9 kg/[m.sup.2] and 2.90 (95% CI, 2.15-3.91) for BMI of 30 kg/[m.sup.2] or more (vs BMI of [is less than]20 kg/[m.sup.2]). Risk for GDM increased with greater weight gain in early adulthood, and it also increased among nonwhite women. Pregravid current smokers had a relative risk for GDM of 1.43 (95% CI, 1.14-1.80), and pregravid vigorous exercise was associated with a non-significant reduction in GDM risk. Conclusions. -- Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk. These observations may facilitate the identification of women at particular risk for GDM and suggest potential strategies for reducing this risk even before a woman becomes pregnant, such as avoiding substantial weight gain and smoking.

Women who have a tubal ligation may have a lower risk of developing ovarian cancer than those who do not. A tubal ligation is a sterilization procedure that involves closing off the fallopian tubes by surgical tieing off. Among 77,544 female nurses who were premenopausal in 1976, 14% had a tubal ligation and 10% had a hysterectomy. The risk of ovarian cancer for those who had had a tubal ligation was about one-fourth that of those who had not. Their lower risk did not appear to be caused by screening of the ovaries at the time of the tubal ligation. Researchers also examined the effect of having a hysterectomy on the risk of developing ovarian cancer in premenopausal and postmenopausal female nurses. Women who had had a hysterectomy were slightly less likely to develop ovarian cancer. Their risk was about two-thirds that of women who had not had a hysterectomy., Objective.--To assess whether tubal ligation and hysterectomy affect subsequent risk of ovarian cancer. Design.--Prospective cohort study with 12 years of follow-up. Setting.--United States, multistate. Participants.--A total of 121 700 female registered nurses who were 30 to 55 years of age in 1976; the follow-up rate was 90% as of 1988. Main Outcome Measure.--Ovarian cancer of epithelial origin confirmed by medical record review. Results.--We observed a strong inverse association between tubal ligation and ovarian cancer, which persisted after adjustment for age, oral contraceptive use, parity, and other ovarian cancer risk factors (multivariate relative risk [RR], 0.33; 95% confidence interval [CI], 0.16 to 0.64). The association was similar when we assessed tubal ligation status at the baseline questionnaire and excluded cases in the first 4 years to eliminate any possible short-term decrease in risk due to screening of the ovaries during ligation surgery. We noted a weaker inverse association between simple hysterectomy and ovarian cancer (RR, 0.67; 95% CI, 0.45 to 1.00). Neither vasectomy nor condom use by a partner was associated with risk of ovarian cancer. Conclusions.--These data indicate that tubal ligation, and perhaps hysterectomy, may substantially reduce risk of epithelial ovarian cancer.

Women may have a higher risk of developing breast cancer if their mother or sister have had the disease. The increase in risk associated with a family history of breast cancer may be smaller than previously thought. Among 117,988 women between 30 and 55 years old in 1976 who were followed until 1988, 2,389 developed invasive breast cancer. The highest risk of breast cancer occurred among women whose mother was diagnosed with breast cancer before the age of 40. These women had twice the risk of developing breast cancer as women with no maternal history of breast cancer. The risk of breast cancer was also higher among women whose mother was diagnosed with breast cancer after the age of 70 or whose sister had breast cancer. However, only 2.5% of the women diagnosed with breast cancer had a family history of the disease., Objective.-To examine the risk of breast cancer as influenced by a maternal history of breast cancer, the mother's age of diagnosis, or a sister's history of breast cancer. Design.-Prospective cohort study with biennial follow-up. Setting/Participants.-117 988 women in the Nurses' Health Study aged 30 to 55 years in 1976, followed up through 1988 (1.3 million person-years of follow-up). Results.-We identified 2389 incident cases of invasive breast cancer. Compared with women without a maternal history of breast cancer, the age-adjusted relative risk (RR) of breast cancer was highest among women whose mother was diagnosed before the age of 40 years (RR, 2.1 [95% confidence interval, 1.6 to 2.8]). The RR decreased with advancing maternal age at time of diagnosis to 1.5 (95% confidence interval, 1.1 to 2.2) for maternal diagnosis after the age of 70 years. Having a sister with a history of breast cancer also was related to increased risk; for women with one sister with breast cancer compared with those with one sister without such a history, the age-adjusted RR was 2.3 (95% confidence interval, 1.6 to 3.4). Women whose mother and sister both had a history of breast cancer had an RR of 2.5 (95% confidence interval, 1.5 to 4.2) compared with those without a family history. These associations did not differ appreciably when stratified by age; menopausal status; history of benign breast disease; body mass index; age at menarche; or parity or age at first birth of the women at risk. The results remained unchanged when we controlled for these risk factors in multivariate models. despite slightly greater mammography surveillance and earlier detection of tumors among women with a family history of breast cancer, detection bias is unlike to account for more than a small part of the observed association. Conclusions.--Risk of breast cancer is approximately doubled among women whose mother had breast cancer diagnosed before the age of 40 years or who have a sister with breast cancer, and remains elevated even for those whose mothers were diagnosed with breast cancer at the age of 70 years or older. However, the risk associated with a mother or sister history of breast cancer is smaller than suggested by earlier retrospective studies. Overall, within this population of middle-aged women, only 2.5% of breast cancer cases are attributable to a positive family history. (JAMA. 1993;270:338-343)

Women who reduce their fat intake may not necessarily reduce their risk of developing breast cancer. During an eight-year follow-up of 89,494 women in the Nurses' Health Study, 1,439 women developed breast cancer. There was no association between fat intake and the risk of developing breast cancer. This was true even in women who were postmenopausal. Women who consumed more than half their calories as fat were no more likely to develop breast cancer than those who consumed less than one-third their calories as fat. There was no association between the type of fat eaten and the risk of developing breast cancer. There was also no association between dietary fiber and the risk of developing breast cancer. Epidemiological studies have found low incidences of breast cancer in countries with low fat intake, but other dietary and life-style factors could be involved., Objective. -- To address the hypotheses that dietary fat increases and fiber decreases the risk of breast cancer. Design. -- Prospective cohort study with dietary assessment at baseline, using a balidated, self-administered food frequently questionnaire. Setting/Participants. -- 89 494 women in the Nurses' Health Study who were 34 through 59 years of age in 1980 and who were followed up for 8 years (>95% complete). Results. -- 1439 incident cases of breast cancer were diagnosed, including 774 among postmenopausal women. After adjustment for age, established risk factors, and total energy intake, we observed no evidence of any positive association between total fat intake and breast cancer incidence (relative risks [RRs] for increasing quintiles of fat intake were 1.0, 0.85, 0.96, 0.91, and 0.90; 95% confidence interval for highest vs lowest quintile, 0.77 to 1.07). Among postmenopausal women alone, corresponding RRs were 1.0, 0.89, 1.00, 0.95, and 0.91. Comparing extreme deciles of total fat intake (is greater than 49% vs Conclusions. -- These data provide evidence against both an adverse influence of fat intake and a protective effect of fiber consumption, by middle-aged women on breast cancer incidence over 8 years. Nevertheless, the positive association between intake of animal fat and risk of colon cancer observed in many studies provides ample reason to limit this source of energy.

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]

Fruit and vegetable consumption does not appear to substantially reduce the risk of breast cancer, according to eight studies that followed 351,825 women altogether. The rate of breast cancer was no different between women with the highest levels of fruit and vegetable consumption versus those with the lowest.

A study describes the magnitude of susceptibility to age-related macular degeneration (AMD) due to common variants in the gene for complement factor H (CFH) and the predicted gene LOC3877715. The rapid dissection of the genetic risks of AMD underscores the growing power of genomics in unraveling complex diseases, making AMD the paradigm for the success of genomic research.

Women who drink alcohol can reduce their risk of breast cancer by getting adequate dietary folate. Among 88,818 women in the Nurses' Health Study, 3,483 developed breast cancer during 16 years of follow-up. Dietary surveys completed by the women revealed that among those who drank alcohol every day, the risk of breast cancer was highest in those who consumed the lowest amounts of folate. Increasing folate intake from 300 to 600 micrograms per day lowered the risk of breast cancer 50%. There was no link between folate levels and breast cancer in women who did not drink alcohol.

Eating a low-fat diet may not necessarily protect women from breast cancer. Researchers followed 88,795 women participating in the Nurses' Health Study for up to 14 years. Over that time period, 2,956 of the women developed breast cancer. Women eating diets with 20% fat or less were just as likely to get breast cancer as those eating diets with 30% to 35% fat. It made no difference whether the dietary fat was saturated, polyunsaturated, or monounsaturated or animal or vegetable in origin.

Importance: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity.Objective: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone.Design, Setting, and Participants: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA.Interventions: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise.Main Outcomes and Measures: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100).Results: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005).Conclusions and Relevance: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group.Trial Registration: clinicaltrials.gov Identifier: NCT00381290. [ABSTRACT FROM AUTHOR]

Objectives: The retinoic acid receptor (RAR)-related orphan receptor α gene (RORA) is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and 2 clinic-based cross sectional studies. We aimed to determine if common variants in RORA predict future risk of neovascular AMD. Methods: We measured genotypes for 18 variants in intron 1 of the RORA gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective, nested, case-control study within the Nurses' Health Study and the Health Professionals Follow- up Study.Wedetermined the incidence rate ratios and 95%confidence intervals (CI) for neovascular AMD for each variant and examined interactions with other AMD associated variants and modifiable risk factors. Results: We identified one single-nucleotide polymorphism (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with 1 and 2 copies of the G allele were 1.73 (CI,1.32-2.27) and 2.99 (CI,1.74-5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the G allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD(CI,10.1-164; P=.017). Cigarette smokers who carried 2 copies of the G allele had a 9.89-fold risk of neovascular AMD but the interaction was not significant (P=.08). We identified a significant AMD-associated haplotype block containing the single-nucleotide polymorphisms rs730754, rs8034864, and rs12900948, with P values for ACA=1.16×10-9, ACG=5.85×10-12, and GAA=.0001 when compared with all other haplotypes. Conclusions: Common variants and haplotypes within the RORA gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. [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.

The article presents insights on reports about the approach to the future of public health education. Topics covered include the report released by William Welch of Johns Hopkins School of Medicine and educator Wickliffe Rose which addressed the need for training of professionals in public health, the differences in underlying philosophies of the Welch-Rose report and that of professor Milton J. Rosenau's report and the emphasis placed on practical instruction in the Rosenau report.

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.'

Importance: An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention., Objective: To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors., Design, Setting, and Participants: Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality., Exposures: Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors., Main Outcomes and Measures: Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking)., Results: The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population., Conclusions and Relevance: This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.