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Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.
Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, et al
Gut. 2018;67(2):237-243
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Intravenous steroids are the first-line therapy for ulcerative colitis (UC) patients who are hospitalised during a severe UC flare-up. In the 40% of patients who don’t respond to steroids, the drugs ciclosporin and infliximab have been found to be efficient in preventing surgery to remove part or all of the colon, but there is a lack of data on the long-term outcomes of using these medications in UC patients. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. Between 2007 and 2010, 115 patients with UC that did not respond to steroids were randomised to receive ciclosporin or infliximab in association with azathioprine. Patients were followed to January 2015 or death. After a median follow-up of 5.4 years, colectomy-free survival rates at 1 and 5 years were, respectively, 70.9% and 61.5% in patients who received ciclosporin and 69.1% and 65.1% in those who received infliximab. Long-term colectomy-free survival was independent from initial treatment. However, a higher proportion of patients initially treated with ciclosporin needed a new treatment compared with those who received infliximab first. The researchers concluded that these results further confirm a similar efficacy and good safety profiles of both drugs.
Abstract
OBJECTIVE Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
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Comparison of the construct validity and reproducibility of four different types of patient-reported outcome measures (PROMs) in patients with rheumatoid arthritis.
Renskers, L, van Uden, RJJC, Huis, AMP, Rongen, SAA, Teerenstra, S, van Riel, PLCM
Clinical rheumatology. 2018;37(12):3191-3199
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Rheumatoid arthritis is an inflammatory autoimmune disease characterised by chronic joint inflammation, which leads to pain, stiffness, function loss, and fatigue. During outpatient visits, patient-reported outcome measures (PROMs) are taking a more central place because they directly apply to the patients’ personal perception and can identify key concerns that need to be addressed. The objective of this study was to measure and compare construct validity of four scale types of PROMs within four different domains. The study is a prospective longitudinal study which recruited adult patients with rheumatoid arthritis. Two-hundred eleven patients were included for the construct validity assessment and one hundred fifty-three patients for the reproducibility assessment. Results showed that within the construct validity assessment, the differences between the four scale types were small and appeared not different. On the other hand, the assessment on reproducibility of the scales was moderate to high. The exception was for the domain of general well-being, as correlations both for construct validity as well as for reproducibility were lower compared to the other domains. Authors conclude that the numerical rating scale is the preferred PROM scale for patients with rheumatoid arthritis.
Abstract
Patient-reported outcome measures (PROMs) are increasingly used in the assessment of patients with rheumatoid arthritis (RA). The aim of this study was to assess the construct validity and reproducibility of four types of PROMs (numerical rating scale (NRS), visual analogue scale (VAS), verbal rating scale (VRS), and Likert scale). In addition, patients' preference for one of these PROMs was measured. Patients with stable RA and no change in pain medication or steroid medication (n = 211) were asked to complete a questionnaire directly following, and 5 days after their outpatient visit. The questionnaire measured the validity of the PROMs in four domains (pain, fatigue, experienced disease activity, and general well-being). To assess construct validity, Pearson correlation coefficients were calculated using the Disease Activity Score-3. To assess reproducibility, intraclass correlation coefficients (ICCs) were calculated. Correlation coefficients between the different PROMs within each domain were compared. There were no differences regarding construct validity between the different PROM scale types. Regarding reproducibility, VAS and NRS scored better in the domains pain and experienced disease activity. Patients chose NRS as preferred measurement method, with the VAS in second place. The four scale types of PROMs appeared to be equally valid to assess pain, fatigue, experienced disease activity, and general well-being. VAS and NRS appeared to be more reliable for measuring pain and experienced disease activity. The patients favoured NRS. In combination with other practical advantages of NRS over VAS, we do advise the NRS as the preferred scale type for PROMs.
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Micronutrient Gaps in Three Commercial Weight-Loss Diet Plans.
G Engel, M, J Kern, H, Brenna, JT, H Mitmesser, S
Nutrients. 2018;10(1)
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Globally, around 39% of adults are overweight and 13% obese, and more than one third of American adults are obese. Being overweight or obese is associated with many chronic conditions, such as heart disease, high blood pressure and type 2 diabetes. Weight loss, even at moderate level, can reduce the risk of these obesity-related chronic conditions. Commercial weight-loss diet plans can vary greatly, not only in energy content but also in macronutrient and micronutrient composition. Most plans restrict calories or certain macronutrients, particularly carbohydrate or fat, and in doing so, often overlook micronutrient, i.e. vitamin and mineral, content. Previous studies have shown that many weight-loss plans do not provide adequate amounts of all micronutrients, and in order to reach the reference daily intakes for various vitamins and minerals, dieters would need to increase their calorie intake significantly and often unrealistically. The authors of this paper analysed seven single-day menus of three select commercial diet plans to determine their micronutrient sufficiency. The diet plans included were Eat to Live-Vegan, Aggressive Weight Loss (ETL-VAWL), Fast Metabolism Diet (FMD), and Eat, Drink and Be Healthy (EDH). ETL-VAWL diet provided less than 90% of recommended amounts for B12, B3, D, E, calcium, selenium and zinc. The FMD diet was low in B1, D, E, calcium, magnesium and potassium, while EDH diet didn’t meet the recommended amounts for vitamin D, calcium and potassium. Even after adjusting all the plans to an intake of 2000 kcal/day, several micronutrients were found to remain inadequate (vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets). The authors conclude that, in order to reduce the risk of micronutrient deficiencies, more attention needs to be paid to micronutrient rich foods when designing commercial diet plans. Alternatively, these nutrient gaps should be filled in other ways, e.g. using appropriate dietary supplements.
Abstract
Weight-loss diets restrict intakes of energy and macronutrients but overlook micronutrient profiles. Commercial diet plans may provide insufficient micronutrients. We analyzed nutrient profiles of three plans and compared their micronutrient sufficiency to Dietary Reference Intakes (DRIs) for male U.S. adults. Hypocaloric vegan (Eat to Live-Vegan, Aggressive Weight Loss; ETL-VAWL), high-animal-protein low-carbohydrate (Fast Metabolism Diet; FMD) and weight maintenance (Eat, Drink and Be Healthy; EDH) diets were evaluated. Seven single-day menus were sampled per diet (n = 21 menus, 7 menus/diet) and analyzed for 20 micronutrients with the online nutrient tracker CRON-O-Meter. Without adjustment for energy intake, the ETL-VAWL diet failed to provide 90% of recommended amounts for B12, B₃, D, E, calcium, selenium and zinc. The FMD diet was low (<90% DRI) in B₁, D, E, calcium, magnesium and potassium. The EDH diet met >90% DRIs for all but vitamin D, calcium and potassium. Several micronutrients remained inadequate after adjustment to 2000 kcal/day: vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets. Consistent with previous work, micronutrient deficits are prevalent in weight-loss diet plans. Special attention to micronutrient rich foods is required to reduce risk of micronutrient deficiency in design of commercial diets.
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Does adapted physical activity‑based rehabilitation improve mental and physical functioning? A randomized trial.
Røe, C, Preede, L, Dalen, H, Bautz-Holter, E, Nyquist, A, Sandvik, L, Saebu, M
European journal of physical and rehabilitation medicine. 2018;54(3):419-427
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Physical and mental functioning is reduced in people with chronic disability. Adapted physical activity (APA) programmes have been developed to facilitate physical activity in this population, but the mental effects have not yet been addressed. The aim of this study was to determine both the physical and mental effects of an APA programme in 202 patients with chronic disability. Participants were randomised to either join an in-patient APA rehabilitation programme or a waitlist control group. Those in the APA programme received 2-5 hours of guided activity every day for 6 days a week, as well as 1-3 hours of a social or cultural activities. Various questionnaires were completed at baseline and at the end of the intervention. This study found participants receiving the APA rehabilitation programme showed improvements in physical functioning, motivation, self-efficacy (a feeling that 'I can do' an action), pain and fatigue compared with the waitlist group. Based on these results, the authors conclude physical activity should be considered during the development of rehabilitation strategies for people with chronic disabilities.
Abstract
BACKGROUND Persons with chronic disabilities face a wide variety of problems with functioning that affect their level of physical activity and participation. We have limited knowledge about the effect of adapted physical activity (APA)-based rehabilitation on perceived mental and physical functioning. AIM: The main aim of this study was to evaluate the effect of APA‑based rehabilitation compared to waiting‑list on perceived mental and physical functioning. Secondly, we wanted to assess whether improvement in self‑efficacy, motivation, pain and fatigue during rehabilitation was related to the effect of the intervention. DESIGN Randomized controlled trial. SETTING In‑patient rehabilitation Center. POPULATION All subjects above 17 years who were referred by their physician to BHC between July 1, 2010 and August 1, 2012 without major cognitive or language problems were eligible for the study (N.=321). METHODS Persons above 17 years (men and women) with chronic disabilities who applied for a rehabilitation stay, were randomized to an adapted physical activity‑based rehabilitation intervention (N.=304) or waiting‑list with delayed rehabilitation. A total of 246 consented and were allocated to four week intervention or a waiting‑list control group. The main outcome was physical and mental functioning evaluated four weeks after rehabilitation using the Medical Outcomes Study 12-Item Short‑Form Health Survey (SF-12). RESULTS Compared to waiting‑list the adapted physical activity‑based intervention improved physical and mental functioning. Improvement in physical functioning during rehabilitation was related to reduced pain, improved motivation and self‑efficacy. CONCLUSIONS The results indicate that an adapted physical activity‑based rehabilitation program improves functioning. Improved efficacy for managing disability may mediate the improvement in mental functioning. CLINICAL REHABILITATION IMPACT Adapted physical activity‑based rehabilitation should be considered during the development of rehabilitation strategies for people with chronic disabilities. Motivational and self‑efficacy aspects must be addressed when organizing and evaluating rehabilitation programs.
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Comparison of Oropharyngeal Microbiota from Children with Asthma and Cystic Fibrosis.
Boutin, S, Depner, M, Stahl, M, Graeber, SY, Dittrich, SA, Legatzki, A, von Mutius, E, Mall, M, Dalpke, AH
Mediators of inflammation. 2017;2017:5047403
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The lungs are under constant exposure to microorganisms contained in inhaled air and the upper respiratory tract. In healthy subjects, the lower airways are colonized by bacteria. Changes in the microbiome are found in several lung diseases associated with chronic airway inflammation including chronic obstructive pulmonary disease, asthma and cystic fibrosis. The aim of the study was to find out whether the throat microbiota of children with asthma and cystic fibrosis differ from healthy children. Another aim was to find out whether the throat microbiota of children with asthma differ from those with cystic fibrosis. The study compared the throat microbiota of healthy school-aged children with that of age-matched children with asthma and cystic fibrosis. Results indicate that the microbiota of cystic fibrosis, asthmatic, and healthy children show high levels of similarities with a strong core microbiota. The cystic fibrosis group show a decrease in both diversity and total bacterial load in the throat in comparison to asthmatic and control children. The cystic fibrosis group also showed a significant increase in typical pathogens in the throat. Based on the results, the authors conclude that the three patient groups had a core microbiome and a host regulation that favours the growth of commensals.
Abstract
A genuine microbiota resides in the lungs which emanates from the colonization by the oropharyngeal microbiota. Changes in the oropharyngeal microbiota might be the source of dysbiosis observed in the lower airways in patients suffering from asthma or cystic fibrosis (CF). To examine this hypothesis, we compared the throat microbiota from healthy children (n = 62) and that from children with asthma (n = 27) and CF (n = 57) aged 6 to 12 years using 16S rRNA amplicon sequencing. Our results show high levels of similarities between healthy controls and children with asthma and CF revealing the existence of a core microbiome represented by Prevotella, Streptococcus, Neisseria, Veillonella, and Haemophilus. However, in CF, the global diversity, the bacterial load, and abundances of 53 OTUs were significantly reduced, whereas abundances of 6 OTUs representing opportunistic pathogens such as Pseudomonas, Staphylococcus, and Streptococcus were increased compared to those in healthy controls controls and asthmatics. Our data reveal a core microbiome in the throat of healthy children that persists in asthma and CF indicating shared host regulation favoring growth of commensals. Furthermore, we provide evidence for dysbiosis with a decrease in diversity and biomass associated with the presence of known pathogens consistent with impaired host defense in children with CF.
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Integrated Evaluation of the Potential Health Benefits of Einkorn-Based Breads.
Antognoni, F, Mandrioli, R, Bordoni, A, Di Nunzio, M, Viadel, B, Gallego, E, Villalba, MP, Tomás-Cobos, L, Taneyo Saa, DL, Gianotti, A
Nutrients. 2017;9(11)
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While health benefits of whole grains has been long established, recent findings suggest ancient grains may provide additional cardiovascular and anti-inflammatory benefits. Einkorn is an ancient crop that has a favourable biochemical makeup however very little research exists on its properties. The aim of this study was to evaluate the nutritional characteristics and health benefits of eikorn-based bread compared to wheat-based breads. Both types of grains were subject to either conventional fermentation with baker’s yeast or sourdough fermentation with lactic acid. Breads were digested in-vitro using the Dynamic Gastrointestinal Digestor, a controlled system that simulates the in vivo digestion process. Bread content was characterised before and after digestion, and the product of their digestion was used to evaluate anti-inflammatory effects. The primary finding of this study was a significantly higher carotenoid level in einkorn compared to modern wheat. Additionally, the use of sourdough fermentation aided to preserve these carotenoids, thus improving the availability and accessibility of nutrient absorption in the final product. Based on this study, the authors conclude einkorn is a good candidate to produce bakery products with enhanced nutritional properties.
Abstract
Nowadays the high nutritional value of whole grains is recognized, and there is an increasing interest in the ancient varieties for producing wholegrain food products with enhanced nutritional characteristics. Among ancient crops, einkorn could represent a valid alternative. In this work, einkorn flours were analyzed for their content in carotenoids and in free and bound phenolic acids, and compared to wheat flours. The most promising flours were used to produce conventional and sourdough fermented breads. Breads were in vitro digested, and characterized before and after digestion. The four breads having the best characteristics were selected, and the product of their digestion was used to evaluate their anti-inflammatory effect using Caco-2 cells. Our results confirm the higher carotenoid levels in einkorn than in modern wheats, and the effectiveness of sourdough fermentation in maintaining these levels, despite the longer exposure to atmospheric oxygen. Moreover, in cultured cells einkorn bread evidenced an anti-inflammatory effect, although masked by the effect of digestive fluid. This study represents the first integrated evaluation of the potential health benefit of einkorn-based bakery products compared to wheat-based ones, and contributes to our knowledge of ancient grains.
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An internet-based self-administered intervention for promoting healthy habits and weight loss in hypertensive people who are overweight or obese: a randomized controlled trial.
Banos, RM, Mensorio, MS, Cebolla, A, Rodilla, E, Palomar, G, Lisón, J, Botella, C
BMC cardiovascular disorders. 2015;15:83
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Overweight and obesity are chronic conditions that have been linked with an increased risk of developing hypertension. Healthy lifestyle habits around eating behaviour and physical activity are known to help counteract these conditions. The aim of this study will be to evaluate whether an self-administered internet-based programme targeting eating behaviour and physical activity levels can help improve disease markers in hypertensive obese patients. The internet-based programme consisted of nine modules designed to promote healthy eating and increased physical activity. A randomised trial will be conducted with 100 hypertensive patients and participants will be randomised to either receive the online programme or usual medical care for three months. Patients will be assessed at baseline, three months, six months and one year for blood pressure and body mass index, as well as quality of life measures. The authors conclude the current literature highlights the need for more studies on the benefits of using internet-based lifestyle interventions, and suggests this protocol will provide a starting point for developing cost-effective healthy lifestyle interventions.
Abstract
BACKGROUND The prevalence of overweight and obesity is on the rise worldwide with severe physical and psychosocial consequences. One of the most dangerous is hypertension. Lifestyle changes related to eating behaviour and physical activity are the critical components in the prevention and treatment of hypertension and obesity. Data indicates that the usual procedures to promote these healthy habits in health services are either insufficient or not efficient enough. Internet has been shown to be an effective tool for the implementation of lifestyle interventions based on this type of problem. This study aims to assess the efficacy of a totally self-administered online intervention programme versus the usual medical care for obese and overweight participants with hypertension (from the Spanish public health care system) to promote healthy lifestyles (eating behaviour and physical activity). METHOD A randomized controlled trial will be conducted with 100 patients recruited from the hypertension unit of a public hospital. Participants will be randomly assigned to one of two conditions: a) SII: a self-administered Internet-based intervention protocol; and b) MUC-medical usual care. The online intervention is an Internet-delivered, multimedia, interactive, self-administered programme, composed of nine modules designed to promote healthy eating habits and increase physical activity. The first five modules will be activated at a rate of one per week, and access for modules 5 to 9 will open every two weeks. Patients will be assessed at four points: before the intervention, after the intervention (3 months), and at 6 and 12 months (follow-up). The outcome variables will include blood pressure, and Body Mass Index, as primary outcome measures, and quality of life and other lifestyle and anthropometrical variables as secondary outcome measures. DISCUSSION The literature highlights the need for more studies on the benefits of using the Internet to promote lifestyle interventions. This study aims to investigate the efficiency of a totally self-administered Internet - +based programme for promoting healthy habits and improving the medical indicators of a hypertensive and overweight population. TRIAL REGISTRATION NCT02445833.
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Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis.
Chung, M, Ma, J, Patel, K, Berger, S, Lau, J, Lichtenstein, AH
The American journal of clinical nutrition. 2014;100(3):833-49
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There have been increasing concerns on the relationship between non-alcoholic fatty liver disease (NAFLD) and fructose or high-fructose corn syrup (HFCS). The objective of this systematic review was to assess the effect of dietary fructose in different forms on NAFLD and various biomarkers of liver health. This review included 21 published intervention studies and found a diet supplemented with fructose or glucose increases liver fat and aspartate aminotransferase (AST) concentrations when compared with a maintenance diet in healthy adults. Based on the available research, the authors point out the relationship between liver health markers and fructose, but also recognise this association may be confounded by excess energy intake. Due to the lack of robust findings, they conclude there is insufficient evidence on HFCS and NAFLD.
Abstract
BACKGROUND Concerns have been raised about the concurrent temporal trend between simple sugar intakes, especially of fructose or high-fructose corn syrup (HFCS), and rates of nonalcoholic fatty liver disease (NAFLD) in the United States. OBJECTIVE We examined the effect of different amounts and forms of dietary fructose on the incidence or prevalence of NAFLD and indexes of liver health in humans. DESIGN We conducted a systematic review of English-language, human studies of any design in children and adults with low to no alcohol intake and that reported at least one predetermined measure of liver health. The strength of the evidence was evaluated by considering risk of bias, consistency, directness, and precision. RESULTS Six observational studies and 21 intervention studies met the inclusion criteria. The overall strength of evidence for observational studies was rated insufficient because of high risk of biases and inconsistent study findings. Of 21 intervention studies, 19 studies were in adults without NAFLD (predominantly healthy, young men) and 1 study each in adults or children with NAFLD. We found a low level of evidence that a hypercaloric fructose diet (supplemented by pure fructose) increases liver fat and aspartate aminotransferase (AST) concentrations in healthy men compared with the consumption of a weight-maintenance diet. In addition, there was a low level of evidence that hypercaloric fructose and glucose diets have similar effects on liver fat and liver enzymes in healthy adults. There was insufficient evidence to draw a conclusion for effects of HFCS or sucrose on NAFLD. CONCLUSIONS On the basis of indirect comparisons across study findings, the apparent association between indexes of liver health (ie, liver fat, hepatic de novo lipogenesis, alanine aminotransferase, AST, and γ-glutamyl transpeptase) and fructose or sucrose intake appear to be confounded by excessive energy intake. Overall, the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose, HFCS, or sucrose consumption on NAFLD.
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Vegetarian dietary patterns and mortality in Adventist Health Study 2.
Orlich, MJ, Singh, PN, Sabaté, J, Jaceldo-Siegl, K, Fan, J, Knutsen, S, Beeson, WL, Fraser, GE
JAMA internal medicine. 2013;173(13):1230-8
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Vegetarian diets have been associated with reduced risk of several chronic cardiometabolic diseases. The aim of this cohort study was to evaluate the effect of vegetarian diets on mortality. The study followed 73,308 male and female Seventh-day Adventists for a mean of 5.79 years. At baseline, just under half were non-vegetarians. Vegetarians had a lower mortality than non-vegetarians: death rates (deaths per 1000 person-years) were 5.4 for vegans, 5.61 for ovo-lacto vegetarians and 5.33 for pesco-vegetarians, which were significantly lower than that of non-vegetarians (6.61). After adjustment for a variety of factors, the lowered hazard ratio seen with vegetarian diets only remained statistically significant in pesco-vegetarians (compared to non-vegetarians). The non-vegetarians had on average higher rates of other risk factors, such as smoking, they consumed more alcohol, exercised less and had lower educational level. The authors concluded that vegetarian dietary patterns were associated with lower mortality.
Abstract
IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality. DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.