Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?

INTRODUCTION: The effects of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) on cerebrovascular disease remain unsettled. However, most studies have focused on marine sourced n-3 PUFA rather than total n-3 PUFA, of which the majority in the American diet is plant derived. This study therefore intended to investigate these effects in a cohort for which the vegetarian diet was more prevalent than the general public. METHODS: Cox proportional hazards with fatal stroke as the outcome was performed on the approximately 96,000 subject Adventist Health Study 2 prospective cohort. Stratification by race and sex was performed on models with a priori covariables, comparing 90th to 10th percentile daily intakes of energy-adjusted total n-3 PUFA, total n-6 PUFA, and the n-6 / n-3 PUFA ratio as variables of interest. RESULTS: For the main analytical group (78,335 subjects), the hazard ratio (95% confidence interval) for total n-3 PUFA was 0.65 (0.51-0.83), and for total n-6 PUFA was 1.37 (1.02-1.82), while adjusting for both fatty acids in the model. The n-6 / n-3 PUFA ratio was harmful with a HR of 1.40 (1.16-1.69), whereas the inclusion of total n-3 PUFA slightly attenuated the HR to 1.33(1.02-1.74). Effects were similar for the non-black sex-combined and sex-specific analyses. CONCLUSION: In most analytic groups, subjects with greater total n-3 PUFA intakes have lower risk of fatal stroke, and those with a higher n-6 / n-3 PUFA ratio had higher risk. However, the n-6 / n-3 PUFA ratio remains statistically significant even after adjusting for total n-3 PUFA or total n-6 PUFA, suggesting that the ratio is of epidemiologic interest for cerebrovascular disease research.

Dietary patterns and hip fracture in the Adventist Health Study 2: combined vitamin D and calcium supplementation mitigate increased hip fracture risk among vegans.

BACKGROUND: Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue. OBJECTIVES: We aimed to explore the influence of 5 previously defined dietary patterns on hip fracture risk and whether this association is modified by concomitant calcium and vitamin D supplementation. METHODS: The Adventist Health Study 2 is a prospective cohort study in which participants were enrolled during 2002-2007; proportional hazards regression analyses were used to estimate fracture risk. Participants reside throughout the United States and Canada. A total of 34,542 non-Hispanic white peri- and postmenopausal women and men 45 y and older responded to the biennial hospital history form and were followed for a median of 8.4 y. RESULTS: The study identified 679 incident hip fractures during 249,186 person-years of follow-up. Fracture risk varied according to dietary pattern, with a clear effect modification by concurrent supplementation with both vitamin D and calcium. In multivariable models, including adjustment for calcium and vitamin D supplementation, female vegans had 55% higher risk of hip fracture (HR: 1.55; 95% CI: 1.06, 2.26) than nonvegetarians (NVEGs), whereas there was no association between diet pattern and hip fracture risk in men. When further stratifying females on supplement use with both vitamin D and calcium, vegans taking both supplements were at no greater risk of hip fracture than the subjects with other dietary patterns including the NVEGs. CONCLUSIONS: Without combined supplementation of both vitamin D and calcium, female vegans are at high risk of hip fracture. However, with supplementation the excessive risk associated with vegans disappeared. Further research is needed to confirm the adequacy of a vegan diet supplemented with calcium and vitamin D with respect to risk of fracture.

Quality of life and psychological outcomes of body-weight supported locomotor training in spinal cord injured persons with long-standing incomplete lesions.

STUDY DESIGN: Health-related quality of life (HRQOL) data from two parallel independent single-blinded controlled randomized studies of manual (Study 1) and robotic (Study 2) locomotor training were combined (ClinicalTrials.gov #NCT00854555). OBJECTIVE: To assess effects of body-weight supported locomotor training (BWSLT) programs on HRQOL in persons with long-standing motor incomplete spinal cord injury and poor walking function. SETTINGS: Two inpatient rehabilitation facilities and one outpatient clinic in Norway. METHODS: Data were merged into intervention (locomotor training 60 days) or control group ("usual care"). Participants completed questionnaires before randomization and 2-4 weeks after the study period, including demographic characteristics, HRQOL (36-Item Short-Form Health Status Survey, SF-36), physical activity (The International Physical Activity Questionnaire Short Form, IPAQ-SF), exercise barrier self-efficacy (EBSE), and motivation for training (Behavioral Regulation in Exercise Questionnaire, BREQ). Physical outcomes i.e., Lower extremity motor score (LEMS) was assessed. The main outcome was change in HRQOL. Secondary outcomes included changes in IPAQ-SF, EBSE, BREQ, and physical outcomes. RESULTS: We recruited 37 of 60 predetermined participants. They were autonomously motivated with high baseline physical activity. BWSLT with manual or robot assistance did not improve HRQOL, though LEMS increased in the BWSLT group compared with control group. CONCLUSIONS: The study was underpowered due to recruitment problems. The training programs seem to benefit LEMS, but not other physical outcomes, and had minimal effects on HRQOL, EBSE, and motivation. Autonomous motivation and high physical activity prior to the study possibly limited the attainable outcome benefits, in addition to limitations due to poor baseline physical function.

Red and Processed Meat and Mortality in a Low Meat Intake Population.

Associations of low-to-moderate consumption of red and processed meat with mortality would add to the evidence of possible adverse effects of these common foods. This study aims to investigate the association of red and processed meat intake with mortality. The Adventist Health Study-2 (AHS-2) is a prospective cohort study of ~96,000 Seventh-day Adventist men and women recruited in the US and Canada between 2002 and 2007. The final analytic sample after exclusions was 72,149. Cox proportional hazards regression was used and hazard ratios (HR) and confidence intervals (CI) were obtained. Diet was assessed by a validated quantitative food frequency questionnaire (FFQ), calibrated using six 24-h dietary recalls. Mortality outcome data were obtained from the National Death Index. During a mean follow-up of 11.8 years, there were 7961 total deaths, of which 2598 were Cardiovascular diseases (CVD) deaths and 1873 were cancer deaths. Unprocessed red meat was associated with risk of all-cause mortality (HR: 1.18; 95% CI: 1.07⁻1.31) and CVD mortality (HR: 1.26; 95% CI: 1.05⁻1.50). Processed meat alone was not significantly associated with risk of mortality. The combined intake of red and processed meat was associated with all-cause mortality (HR: 1.23; 95% CI: 1.11⁻1.36) and CVD mortality (HR: 1.34; 95% CI: 1.12⁻1.60). These findings suggest moderately higher risks of all-cause and CVD mortality associated with red and processed meat in a low meat intake population.

Robot-assisted locomotor training did not improve walking function in patients with chronic incomplete spinal cord injury: A randomized clinical trial.

OBJECTIVE: To assess the effects of robot-assisted locomotor training in patients with chronic incomplete spinal cord injury. DESIGN: Randomized single-blind controlled clinical trial. SETTING: The intervention site was an outpatient clinic, and pre- and post-evaluations were performed in a rehabilitation hospital. PATIENTS: A total of 24 subjects with American Spinal Injury Association Impairment Scale grades C or D, >?2 years post-injury. INTERVENTIONS: Subjects were randomized to 60 days of robot-assisted locomotor training, or to usual care. METHODS: Walking function, lower extremity muscle strength and balance were assessed single-blinded pre- and post-intervention. RESULTS: After a 9-year recruitment period, only 24 of the planned 30 subjects had been enrolled (mean time since injury 17 (standard deviation (SD) 20) years for all subjects). Walking function, lower extremity muscle strength and balance improved modestly in both groups, with no statistically significant group difference in walking function or muscle strength, whereas postural control declined significantly in the intervention group, compared with controls (p?=?0.03). CONCLUSION: Late-onset robot-assisted locomotor training did not re-establish independent walking function. A modest, but non-significant, effect was seen on muscle strength and balance. However, significant between-group differences were found only in postural control in the control group.

Manually assisted body-weight supported locomotor training does not re-establish walking in non-walking subjects with chronic incomplete spinal cord injury: A randomized clinical trial.

OBJECTIVE: To assess the effects of manually assisted body-weight supported locomotor training in subjects with chronic incomplete spinal cord injury. DESIGN: Randomized controlled clinical trial. SUBJECTS: Twenty subjects with American Spinal Injury Association Impairment Scale grades C or D and > 2 years post-injury. METHODS: Random allocation to 60 days of body-weight supported locomotor training, or usual care, which might include over-ground walking. Walking function, lower extremity muscle strength and balance were blindly evaluated pre-/post-intervention. RESULTS: A small, non-significant improvement in walking function was observed (0.1 m/s (95% confidence interval (95% CI) -0.2, 0.4)), but subjects without baseline gait function, did not re-establish walking. The effect on lower extremity muscle strength was 2.7 points (95% CI -1.4, 6.8). No difference was observed in balance measures. CONCLUSION: Subjects with chronic incomplete spinal cord injury without baseline walking function were unable to re-establish gait with manually assisted body-weight supported locomotor training. A modest, non-significant, improvement was found in strength and walking speed. However, due to study recruitment problems, an effect size that was smaller than anticipated, and large functional heterogeneity among study subjects, the effect of late-onset body-weight supported locomotor training is not clear. Future studies should include larger numbers of subjects with less functional loss and greater functional homogeneity. Intensive training should probably start earlier post-injury.

The association between ambient fine particulate matter and incident adenocarcinoma subtype of lung cancer.

BACKGROUND: Adenocarcinoma (AC) is the most common lung cancer among non-smokers, but few studies have assessed the effect of PM2.5 on AC among never smokers. The purpose of this study was to assess the association between ambient PM2.5 and incident lung AC in the Adventist Health and Smog Study-2 (AHSMOG-2), a cohort of 80,044 non-smokers (81% never smokers) followed for 7.5 years (597,177 person-years) (2002-2011). METHODS: Incident lung AC was identified through linkage with U.S. state cancer registries. Ambient PM2.5 levels at subjects' residences were estimated for the years 2000 and 2001, immediately prior to study start. RESULTS: A total of 164 incident lung AC occurred during follow-up. Each 10 µg/m3 increment in PM2.5 was associated with an increase in the hazard rate of lung AC [HR = 1.31 (95% confidence interval (CI) 0.87-1.97)] in the single-pollutant model. Excluding those with prevalent non-melanoma skin cancer (NMSC) strengthened the association with lung AC (HR = 1.62 (95% CI, 1.11-2.36) for each 10 µg/m3 PM2.5 increment. Also, limiting the analyses to subjects who spent more than 1 h/day outdoors, increased the estimate (HR = 1.55, 95% CI: 1.05, 2.30). CONCLUSIONS: Increased risk of AC was observed for each 10 µg/m3 increment in ambient PM2.5 concentrations. The risk was higher among those without prevalent NMSC and those who spent more than 1 h/day outdoors.

The Association between Ambient Fine Particulate Air Pollution and Lung Cancer Incidence: Results from the AHSMOG-2 Study.

BACKGROUND: There is a positive association between ambient fine particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) and incidence and mortality of lung cancer (LC), but few studies have assessed the relationship between ambient PM2.5 and LC among never smokers. OBJECTIVES: We assessed the association between PM2.5 and risk of LC using the Adventist Health and Smog Study-2 (AHSMOG-2), a cohort of health conscious nonsmokers where 81% have never smoked. METHODS: A total of 80,285 AHSMOG-2 participants were followed for an average of 7.5 years with respect to incident LC identified through linkage with U.S. state cancer registries. Estimates of ambient air pollution levels at participants' residences were obtained for 2000 and 2001, the years immediately prior to the start of the study. RESULTS: A total of 250 incident LC cases occurred during 598,927 person-years of follow-up. For each 10-µg/m3 increment in PM2.5, adjusted hazard ratio (HR) with 95% confidence interval (CI) for LC incidence was 1.43 (95% CI: 1.11, 1.84) in the two-pollutant multivariable model with ozone. Among those who spent > 1 hr/day outdoors or who had lived 5 or more years at their enrollment address, the HR was 1.68 (95% CI: 1.28, 2.22) and 1.54 (95% CI: 1.17, 2.04), respectively. CONCLUSION: Increased risk estimates of LC were observed for each 10-µg/m3 increment in ambient PM2.5 concentration. The estimate was higher among those with longer residence at enrollment address and those who spent > 1 hr/day outdoors. Citation: Gharibvand L, Shavlik D, Ghamsary M, Beeson WL, Soret S, Knutsen R, Knutsen SF. 2017. The association between ambient fine particulate air pollution and lung cancer incidence: results from the AHSMOG-2 study. Environ Health Perspect 125:378-384; http://dx.doi.org/10.1289/EHP124.

Effects of glycosylated hemoglobin levels on neutrophilic phagocytic functions.

It is well established that diabetic patients with poor glycemic control have increased susceptibility to infections, but glucose levels have not been directly associated with this increase. The assessment of the effects of glycosylated hemoglobin (A1 c) on the body's ability to fight infections may be useful directly in establishing a link between elevated blood sugar and the risk of infections. A total of 127 subjects in Heart Pilot Study (HPS), sub-study of the Adventist Health Study 2 (AHS-2) completed a lifestyle, medical and food frequency questionnaire (FFQ) at baseline between 2013 and 2014. The A1 c and phagocytic index (PI) were measured in the same blood sample and their associations were assessed using linear regression. Mean blood glucose (MBG) was estimated based on A1 c levels using a standard formula. Three levels of MBG were used to compare prediabetic and diabetic ranges to the normal range. The PI is the average number of bacteria in the cytoplasm of 50 neutrophils, manually counted under a light microscope after the whole blood was briefly exposed to a standard dose of bacteria and stained. In multivariable analysis, we found that MBG in the prediabetic (117 to137 mg/dL) and diabetic (>137 mg/dL) ranges were associated with 12.9% (ß= -0.129, 95% Cl: -0.30, 0.05) and 20.4% decrease in PI (ß= -0.204, 95% Cl: -0.592, 0.184) compared to that, observed among those with normal MBG (p for trend=0.119). Elevated MBG levels contribute a decrease in the PI among those in the prediabetic and diabetic range compared to the normal range. Although our findings were not quite statistically significant due to low power which are clinically relevant in line with observations of an increased infections among diabetics. Further research on larger populations is needed.

Are strict vegetarians protected against prostate cancer?

BACKGROUND: According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. OBJECTIVE: This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. DESIGN: In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. RESULTS: In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). CONCLUSION: Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null.

Non-sedentary Lifestyle Can Reduce Hip Fracture Risk among Older Caucasians Adults: The Adventist Health Study-2.

AIMS: The beneficial effect of physical activity on reducing hip fracture risk has been supported in many previous studies. The present cohort study explores the relationship between total daily physical activity expressed as MET-hour/day and hip fracture risk among men over 50 years of age and postmenopausal women (n=22,836). METHODOLOGY: Associations between self-reported hip fracture incidence and total daily physical activity and selected lifestyle factors were assessed using Cox proportional hazard regression. RESULTS: In gender-specific multivariable models, total activity above average (≥ 51 MET-hours per day for men, ≥ 48 MET-hours per day for women) compared to those with sedentary lifestyle (< 40 MET-hours per day) reduced the risk of hip fracture by 60% among men (HR=0.40, 95%CI: 0.23-0.70) (Ptrend=0.002) and 48% among women (HR=0.52, 95%CI: 0.32-0.84) (Ptrend=0.01). CONCLUSION: Our findings suggest that a moderate level of physical activity and avoiding a sedentary lifestyle can reduce the risk of hip fracture among the elderly.

Impact of Walking and Running on the Heel bone: the Adventist Health Study-2.

AIMS: Physical activity is well recognized for its bone health benefit. We examined the benefit of walk/run/jog on bone health using broadband ultrasound attenuation (BUA) of the calcaneus. METHODOLOGY: Caucasian and African American males (n=593) and females (n=1,106) had their calcaneal BUA measured two years later after enrollment into the AHS-2. The association between calcaneal BUA (dB/Mhz) and the distance of walk/run/ jog level per week (miles) was assessed using multiple linear regression. RESULTS: In a multivariable model adjusted for important covariates, BUA was positively associated with BMI (P < .001), total calcium intake (P =0.31), total protein intake (P =0.38) and inversely associated with age (P < .001) and smoking (P < .05). Compared to women who did not walk/ run/ jog, women walking 10 or more miles per week had an increase in BUA by 4.08 (dB/Mhz) (P trend=0.03). Similarly, compared to men who did not walk/ run/ jog, men walking 10 or more miles per week had an increase in BUA by 5.97 (dB/Mhz) (P trend=0.01). CONCLUSIONS: We concluded that BUA is positively associated with walk/ run/jog after accounting for age, BMI, smoking status, calcium intake, protein intake and estrogen usage.

Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2.

OBJECTIVE: In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. DESIGN: A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. SETTING: Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. SUBJECTS: Respondents (n 33,208) to a baseline and a follow-up questionnaire. RESULTS: In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio = 0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio = 0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49 % reduced risk of hip fracture (hazard ratio = 0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. CONCLUSIONS: Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture.

Outcomes of multimodality therapies for patients with stage II or III rectal cancer in California, 1994-2009.

BACKGROUND: Perioperative chemoradiotherapy is being used for the treatment of locally advanced rectal cancer to improve survival and reduce recurrence. Although several studies have prompted these changes, the survival benefits of additional chemoradiotherapy have not been adequately tested in a large-scale, population-based setting. OBJECTIVE: The purpose of this study was to evaluate survival differences between perioperative chemoradiotherapy and surgery alone for the treatment of rectal cancer. DESIGN: : This was a nonconcurrent cohort study of patients treated for rectal cancer stages II and III between 1994 and 2009. SETTING: The study was conducted through the California Cancer Registry. PATIENTS: Eligible patients were those with rectal cancer stage II or III who received either radical surgery alone (N = 2988) or perioperative chemoradiotherapy (N = 8852) during the study period. MAIN OUTCOME MEASURES: Cox proportional hazards regression was used to assess the risk of mortality associated with perioperative chemoradiotherapy versus surgery alone, adjusting for age, sex, race/ethnicity, socioeconomic status, tumor stage, month/year of surgery, and hospital factors. RESULTS: In multivariable binomial log-linear regression, the adjusted prevalence ratio (PR) for receiving perioperative chemoradiotherapy was lower among patients in the older age groups, especially among those ≥75 years of age (PR = 0.52 [95% CI, 0.49-0.55]), and increased monotonically from lowest (PR = 0.92 [95% CI, 0.89-0.95]) to highest socioeconomic status group (referent). Multivariable Cox proportional hazards regression analysis, adjusting for demographic factors, tumor stage, and hospital identification number, showed that perioperative chemoradiotherapy, relative to surgery alone, was associated with lower mortality during the entire study period, with survival benefit increasing over time (1994-1997: HR = 0.76 [95% CI, 0.66-0.88]; 1998-2001: HR = 0.71 [95% CI, 0.64-0.79]; 2002-2005: HR = 0.63 [95% CI, 0.55-0.71]; 2006-2008: HR = 0.47 [95% CI, 0.39-0.56]). LIMITATIONS: No information was available on comorbidities or specific surgeon factors, which could contribute to survival differences. CONCLUSIONS: Perioperative chemoradiotherapy, compared with surgery alone, was associated with significantly improved survival during the entire study period, with increasing benefit among those treated during the latter years of our studied time period. (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A120).

The association between incident self-reported fibromyalgia and nonpsychiatric factors: 25-years follow-up of the Adventist Health Study.

UNLABELLED: The purpose of the study was to investigate the association between incident self-reported fibromyalgia (FM) and prior somatic diseases, lifestyle factors, and health behaviors among 3,136 women who participated in 2 cohort studies 25 to 26 years apart (the Adventist Health Study 1 and 2). The women completed a comprehensive lifestyle and medical history questionnaire at baseline in 1976. Information on new diagnosis of doctor-told FM was obtained at the second survey in 2002. A total of 136 women reported a diagnosis of FM during 25 years of follow-up, giving a period incidence of 43/1,000 or 1.72/1000 per year. In multivariable logistic regression analyses, a significant, dose-response association was found with number of allergies with OR of 1.61 (95% CI: .92-2.83) and 3.99 (95% CI: 2.31-6.88), (P[trend] < .0001), respectively, for 1 and 2 or more allergies versus none. A history of hyperemesis gravidarum was also associated with FM with OR of 1.32 (95% CI: .75-2.32) and 1.73 (95% CI: .99-3.03), (P[trend] < .05), respectively, for some or all pregnancies versus none. A positive association with smoking was also found with OR of 2.37 (95% CI: 1.33-4.23) for ever smokers versus never smokers. No significant association was found with number of surgeries, history of peptic ulcer, or taking medications to control various symptoms. PERSPECTIVE: Smoking as well as prevalent allergies, and a history of hyperemesis gravidarum, seem to predict development of FM in women during 25 years of follow-up. This information may help in identifying persons at high risk of developing FM and thus initiate effective prevention strategies.