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Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months 总被引:1,自引:0,他引:1
Meghan B. Azad Theodore Konya Heather Maughan David S. Guttman Catherine J. Field Radha S. Chari Malcolm R. Sears Allan B. Becker James A. Scott Anita L. Kozyrskyj 《CMAJ》2013,185(5):385-394
Background:
The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.Methods:
We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.Results:
We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.Interpretation:
These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.The human body harbours trillions of microbes, known collectively as the “human microbiome.” By far the highest density of commensal bacteria is found in the digestive tract, where resident microbes outnumber host cells by at least 10 to 1. Gut bacteria play a fundamental role in human health by promoting intestinal homeostasis, stimulating development of the immune system, providing protection against pathogens, and contributing to the processing of nutrients and harvesting of energy.1,2 The disruption of the gut microbiota has been linked to an increasing number of diseases, including inflammatory bowel disease, necrotizing enterocolitis, diabetes, obesity, cancer, allergies and asthma.1 Despite this evidence and a growing appreciation for the integral role of the gut microbiota in lifelong health, relatively little is known about the acquisition and development of this complex microbial community during infancy.3Two of the best-studied determinants of the gut microbiota during infancy are mode of delivery and exposure to breast milk.4,5 Cesarean delivery perturbs normal colonization of the infant gut by preventing exposure to maternal microbes, whereas breastfeeding promotes a “healthy” gut microbiota by providing selective metabolic substrates for beneficial bacteria.3,5 Despite recommendations from the World Health Organization,6 the rate of cesarean delivery has continued to rise in developed countries and rates of breastfeeding decrease substantially within the first few months of life.7,8 In Canada, more than 1 in 4 newborns are born by cesarean delivery, and less than 15% of infants are exclusively breastfed for the recommended duration of 6 months.9,10 In some parts of the world, elective cesarean deliveries are performed by maternal request, often because of apprehension about pain during childbirth, and sometimes for patient–physician convenience.11The potential long-term consequences of decisions regarding mode of delivery and infant diet are not to be underestimated. Infants born by cesarean delivery are at increased risk of asthma, obesity and type 1 diabetes,12 whereas breastfeeding is variably protective against these and other disorders.13 These long-term health consequences may be partially attributable to disruption of the gut microbiota.12,14Historically, the gut microbiota has been studied with the use of culture-based methodologies to examine individual organisms. However, up to 80% of intestinal microbes cannot be grown in culture.3,15 New technology using culture-independent DNA sequencing enables comprehensive detection of intestinal microbes and permits simultaneous characterization of entire microbial communities. Multinational consortia have been established to characterize the “normal” adult microbiome using these exciting new methods;16 however, these methods have been underused in infant studies. Because early colonization may have long-lasting effects on health, infant studies are vital.3,4 Among the few studies of infant gut microbiota using DNA sequencing, most were conducted in restricted populations, such as infants delivered vaginally,17 infants born by cesarean delivery who were formula-fed18 or preterm infants with necrotizing enterocolitis.19Thus, the gut microbiota is essential to human health, yet the acquisition and development of this microbial community during infancy remains poorly understood.3 In the current study, we address this gap in knowledge using new sequencing technology and detailed exposure assessments20 of healthy Canadian infants selected from a national birth cohort to provide representative, comprehensive profiles of gut microbiota according to mode of delivery and infant diet. 相似文献4.
Ian Williamson Jane Vennik Anthony Harnden Merryn Voysey Rafael Perera Sadie Kelly Guiqing Yao James Raftery David Mant Paul Little 《CMAJ》2015,187(13):961-969
Background:Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting.Methods:We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom. Children aged 4–11 years with a recent history of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by tympanometry, were allocated to receive either autoinflation 3 times daily for 1–3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1 and 3 months was assessed by experts masked to allocation.Results:Of 320 children enrolled, those receiving autoinflation were more likely than controls to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132]; adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). Autoinflation produced greater improvements in ear-related quality of life (adjusted between-group difference in change from baseline in OMQ-14 [an ear-related measure of quality of life] score −0.42, 95% CI −0.63 to −0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse events were mild, infrequent and comparable between groups.Interpretation:Autoinflation in children aged 4–11 years with otitis media with effusion is feasible in primary care and effective both in clearing effusions and improving symptoms and ear-related child and parent quality of life. Trial registration: ISRCTN, No. 55208702.Otitis media with effusion, also known as glue ear, is an accumulation of fluid in the middle ear, without symptoms or signs of an acute ear infection. It is often associated with viral infection.1–3 The prevalence rises to 46% in children aged 4–5 years,4 when hearing difficulty, other ear-related symptoms and broader developmental concerns often bring the condition to medical attention.3,5,6 Middle-ear fluid is associated with conductive hearing losses of about 15–45 dB HL.7 Resolution is clinically unpredictable,8–10 with about a third of cases showing recurrence.11 In the United Kingdom, about 200 000 children with the condition are seen annually in primary care.12,13 Research suggests some children seen in primary care are as badly affected as those seen in hospital.7,9,14,15 In the United States, there were 2.2 million diagnosed episodes in 2004, costing an estimated $4.0 billion.16 Rates of ventilation tube surgery show variability between countries,17–19 with a declining trend in the UK.20Initial clinical management consists of reasonable temporizing or delay before considering surgery.13 Unfortunately, all available medical treatments for otitis media with effusion such as antibiotics, antihistamines, decongestants and intranasal steroids are ineffective and have unwanted effects, and therefore cannot be recommended.21–23 Not only are antibiotics ineffective, but resistance to them poses a major threat to public health.24,25 Although surgery is effective for a carefully selected minority,13,26,27 a simple low-cost, nonsurgical treatment option could benefit a much larger group of symptomatic children, with the purpose of addressing legitimate clinical concerns without incurring excessive delays.Autoinflation using a nasal balloon device is a low-cost intervention with the potential to be used more widely in primary care, but current evidence of its effectiveness is limited to several small hospital-based trials28 that found a higher rate of tympanometric resolution of ear fluid at 1 month.29–31 Evidence of feasibility and effectiveness of autoinflation to inform wider clinical use is lacking.13,28 Thus we report here the findings of a large pragmatic trial of the clinical effectiveness of nasal balloon autoinflation in a spectrum of children with clinically confirmed otitis media with effusion identified from primary care. 相似文献
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Hazel J. Jenkins Mark J. Hancock Simon D. French Chris G. Maher Roger M. Engel John S. Magnussen 《CMAJ》2015,187(6):401-408
Background:Rates of imaging for low-back pain are high and are associated with increased health care costs and radiation exposure as well as potentially poorer patient outcomes. We conducted a systematic review to investigate the effectiveness of interventions aimed at reducing the use of imaging for low-back pain.Methods:We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from the earliest records to June 23, 2014. We included randomized controlled trials, controlled clinical trials and interrupted time series studies that assessed interventions designed to reduce the use of imaging in any clinical setting, including primary, emergency and specialist care. Two independent reviewers extracted data and assessed risk of bias. We used raw data on imaging rates to calculate summary statistics. Study heterogeneity prevented meta-analysis.Results:A total of 8500 records were identified through the literature search. Of the 54 potentially eligible studies reviewed in full, 7 were included in our review. Clinical decision support involving a modified referral form in a hospital setting reduced imaging by 36.8% (95% confidence interval [CI] 33.2% to 40.5%). Targeted reminders to primary care physicians of appropriate indications for imaging reduced referrals for imaging by 22.5% (95% CI 8.4% to 36.8%). Interventions that used practitioner audits and feedback, practitioner education or guideline dissemination did not significantly reduce imaging rates. Lack of power within some of the included studies resulted in lack of statistical significance despite potentially clinically important effects.Interpretation:Clinical decision support in a hospital setting and targeted reminders to primary care doctors were effective interventions in reducing the use of imaging for low-back pain. These are potentially low-cost interventions that would substantially decrease medical expenditures associated with the management of low-back pain.Current evidence-based clinical practice guidelines recommend against the routine use of imaging in patients presenting with low-back pain.1–3 Despite this, imaging rates remain high,4,5 which indicates poor concordance with these guidelines.6,7Unnecessary imaging for low-back pain has been associated with poorer patient outcomes, increased radiation exposure and higher health care costs.8 No short- or long-term clinical benefits have been shown with routine imaging of the low back, and the diagnostic value of incidental imaging findings remains uncertain.9–12 A 2008 systematic review found that imaging accounted for 7% of direct costs associated with low-back pain, which in 1998 translated to more than US$6 billion in the United States and £114 million in the United Kingdom.13 Current costs are likely to be substantially higher, with an estimated 65% increase in spine-related expenditures between 1997 and 2005.14Various interventions have been tried for reducing imaging rates among people with low-back pain. These include strategies targeted at the practitioner such as guideline dissemination,15–17 education workshops,18,19 audit and feedback of imaging use,7,20,21 ongoing reminders7 and clinical decision support.22–24 It is unclear which, if any, of these strategies are effective.25 We conducted a systematic review to investigate the effectiveness of interventions designed to reduce imaging rates for the management of low-back pain. 相似文献
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Background:
Many hospitals have adopted smoke-free policies on their property. We examined the consequences of such polices at two Canadian tertiary acute-care hospitals.Methods:
We conducted a qualitative study using ethnographic techniques over a six-month period. Participants (n = 186) shared their perspectives on and experiences with tobacco dependence and managing the use of tobacco, as well as their impressions of the smoke-free policy. We interviewed inpatients individually from eight wards (n = 82), key policy-makers (n = 9) and support staff (n = 14) and held 16 focus groups with health care providers and ward staff (n = 81). We also reviewed ward documents relating to tobacco dependence and looked at smoking-related activities on hospital property.Results:
Noncompliance with the policy and exposure to secondhand smoke were ongoing concerns. Peoples’ impressions of the use of tobacco varied, including divergent opinions as to whether such use was a bad habit or an addiction. Treatment for tobacco dependence and the management of symptoms of withdrawal were offered inconsistently. Participants voiced concerns over patient safety and leaving the ward to smoke.Interpretation:
Policies mandating smoke-free hospital property have important consequences beyond noncompliance, including concerns over patient safety and disruptions to care. Without adequately available and accessible support for withdrawal from tobacco, patients will continue to face personal risk when they leave hospital property to smoke.Canadian cities and provinces have passed smoking bans with the goal of reducing people’s exposure to secondhand smoke in workplaces, public spaces and on the property adjacent to public buildings.1,2 In response, Canadian health authorities and hospitals began implementing policies mandating smoke-free hospital property, with the goals of reducing the exposure of workers, patients and visitors to tobacco smoke while delivering a public health message about the dangers of smoking.2–5 An additional anticipated outcome was the reduced use of tobacco among patients and staff. The impetuses for adopting smoke-free policies include public support for such legislation and the potential for litigation for exposure to second-hand smoke.2,4Tobacco use is a modifiable risk factor associated with a variety of cancers, cardiovascular diseases and respiratory conditions.6–11 Patients in hospital who use tobacco tend to have more surgical complications and exacerbations of acute and chronic health conditions than patients who do not use tobacco.6–11 Any policy aimed at reducing exposure to tobacco in hospitals is well supported by evidence, as is the integration of interventions targetting tobacco dependence.12 Unfortunately, most of the nearly five million Canadians who smoke will receive suboptimal treatment,13 as the routine provision of interventions for tobacco dependence in hospital settings is not a practice norm.14–16 In smoke-free hospitals, two studies suggest minimal support is offered for withdrawal, 17,18 and one reports an increased use of nicotine-replacement therapy after the implementation of the smoke-free policy.19Assessments of the effectiveness of smoke-free policies for hospital property tend to focus on noncompliance and related issues of enforcement.17,20,21 Although evidence of noncompliance and litter on hospital property2,17,20 implies ongoing exposure to tobacco smoke, half of the participating hospital sites in one study reported less exposure to tobacco smoke within hospital buildings and on the property.18 In addition, there is evidence to suggest some decline in smoking among staff.18,19,21,22We sought to determine the consequences of policies mandating smoke-free hospital property in two Canadian acute-care hospitals by eliciting lived experiences of the people faced with enacting the policies: patients and health care providers. In addition, we elicited stories from hospital support staff and administrators regarding the policies. 相似文献9.
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Elucidating the temporal order of silencing 总被引:1,自引:0,他引:1
Izaurralde E 《EMBO reports》2012,13(8):662-663
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Gilaad G. Kaplan Elijah Dixon Remo Panaccione Andrew Fong Li Chen Mieczyslaw Szyszkowicz Amanda Wheeler Anthony MacLean W. Donald Buie Terry Leung Steven J. Heitman Paul J. Villeneuve 《CMAJ》2009,181(9):591-597
Background
The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis.Methods
We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season.Results
An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24).Interpretation
Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.Appendicitis was introduced into the medical vernacular in 1886.1 Since then, the prevailing theory of its pathogenesis implicated an obstruction of the appendiceal orifice by a fecalith or lymphoid hyperplasia.2 However, this notion does not completely account for variations in incidence observed by age,3,4 sex,3,4 ethnic background,3,4 family history,5 temporal–spatial clustering6 and seasonality,3,4 nor does it completely explain the trends in incidence of appendicitis in developed and developing nations.3,7,8The incidence of appendicitis increased dramatically in industrialized nations in the 19th century and in the early part of the 20th century.1 Without explanation, it decreased in the middle and latter part of the 20th century.3 The decrease coincided with legislation to improve air quality. For example, after the United States Clean Air Act was passed in 1970,9 the incidence of appendicitis decreased by 14.6% from 1970 to 1984.3 Likewise, a 36% drop in incidence was reported in the United Kingdom between 1975 and 199410 after legislation was passed in 1956 and 1968 to improve air quality and in the 1970s to control industrial sources of air pollution. Furthermore, appendicitis is less common in developing nations; however, as these countries become more industrialized, the incidence of appendicitis has been increasing.7Air pollution is known to be a risk factor for multiple conditions, to exacerbate disease states and to increase all-cause mortality.11 It has a direct effect on pulmonary diseases such as asthma11 and on nonpulmonary diseases including myocardial infarction, stroke and cancer.11–13 Inflammation induced by exposure to air pollution contributes to some adverse health effects.14–17 Similar to the effects of air pollution, a proinflammatory response has been associated with appendicitis.18–20We conducted a case–crossover study involving a population-based cohort of patients admitted to hospital with appendicitis to determine whether short-term increases in concentrations of selected air pollutants were associated with hospital admission because of appendicitis. 相似文献12.
Manon Choinière Judy Watt-Watson J. Charles Victor Roger J.F. Baskett Jean S. Bussières Michel Carrier Jennifer Cogan Judy Costello Christopher Feindel Marie-Claude Guertin Mélanie Racine Marie-Christine Taillefer 《CMAJ》2014,186(7):E213-E223
Background:
Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.Methods:
We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.Results:
A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.Interpretation:
Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.Postoperative pain that persists beyond the normal time for tissue healing (> 3 mo) is increasingly recognized as an important complication after various types of surgery and can have serious consequences on patients’ daily living.1–3 Cardiac surgeries, such as coronary artery bypass grafting (CABG) and valve replacement, rank among the most frequently performed interventions worldwide.4 They aim to improve survival and quality of life by reducing symptoms, including anginal pain. However, persistent postoperative pain of nonanginal origin has been reported in 7% to 60% of patients following these surgeries.5–23 Such variability is common in other types of major surgery and is due mainly to differences in the definition of persistent postoperative pain, study design, data collection methods and duration of follow-up.1–3,24Few prospective cohort studies have examined the exact time course of persistent postoperative pain after cardiac surgery, and follow-up has always been limited to a year or less.9,14,25 Factors that put patients at risk of this type of problem are poorly understood.26 Studies have reported inconsistent results regarding the contribution of age, sex, body mass index, preoperative angina, surgical technique, grafting site, postoperative complications or level of opioid consumption after surgery.5–7,9,13,14,16–19,21–23,25,27 Only 1 study investigated the role of chronic nonanginal pain before surgery as a contributing factor;21 5 others prospectively assessed the association between persistent postoperative pain and acute pain intensity in the first postoperative week but reported conflicting results.13,14,21,22,25 All of the above studies were carried out in a single hospital and included relatively small samples. None of the studies examined the contribution of psychological factors such as levels of anxiety and depression before cardiac surgery, although these factors have been shown to influence acute or persistent postoperative pain in other types of surgery.1,24,28,29We conducted a prospective multicentre cohort study (the CARD-PAIN study) to determine the prevalence of persistent postoperative pain of nonanginal origin up to 24 months after cardiac surgery and to identify risk factors for the presence and severity of the condition. 相似文献13.
Nancy Babio Estefanía Toledo Ramón Estruch Emilio Ros Miguel A. Martínez-González Olga Casta?er Mònica Bulló Dolores Corella Fernando Arós Enrique Gómez-Gracia Valentina Ruiz-Gutiérrez Miquel Fiol José Lapetra Rosa M. Lamuela-Raventos Lluís Serra-Majem Xavier Pintó Josep Basora José V. Sorlí Jordi Salas-Salvadó 《CMAJ》2014,186(17):E649-E657
Background:
Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome.Methods:
We performed a secondary analysis of the PREDIMED trial — a multicentre, randomized trial done between October 2003 and December 2010 that involved men and women (age 55–80 yr) at high risk for cardiovascular disease. Participants were randomly assigned to 1 of 3 dietary interventions: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts or advice on following a low-fat diet (the control group). The interventions did not include increased physical activity or weight loss as a goal. We analyzed available data from 5801 participants. We determined the effect of diet on incidence and reversion of metabolic syndrome using Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results:
Over 4.8 years of follow-up, metabolic syndrome developed in 960 (50.0%) of the 1919 participants who did not have the condition at baseline. The risk of developing metabolic syndrome did not differ between participants assigned to the control diet and those assigned to either of the Mediterranean diets (control v. olive oil HR 1.10, 95% CI 0.94–1.30, p = 0.231; control v. nuts HR 1.08, 95% CI 0.92–1.27, p = 0.3). Reversion occurred in 958 (28.2%) of the 3392 participants who had metabolic syndrome at baseline. Compared with the control group, participants on either Mediterranean diet were more likely to undergo reversion (control v. olive oil HR 1.35, 95% CI 1.15–1.58, p < 0.001; control v. nuts HR 1.28, 95% CI 1.08–1.51, p < 0.001). Participants in the group receiving olive oil supplementation showed significant decreases in both central obesity and high fasting glucose (p = 0.02); participants in the group supplemented with nuts showed a significant decrease in central obesity.Interpretation:
A Mediterranean diet supplemented with either extra virgin olive oil or nuts is not associated with the onset of metabolic syndrome, but such diets are more likely to cause reversion of the condition. An energy-unrestricted Mediterranean diet may be useful in reducing the risks of central obesity and hyperglycemia in people at high risk of cardiovascular disease. Trial registration: ClinicalTrials.gov, no. ISRCTN35739639.Metabolic syndrome is a cluster of 3 or more related cardiometabolic risk factors: central obesity (determined by waist circumference), hypertension, hypertriglyceridemia, low plasma high-density lipoprotein (HDL) cholesterol levels and hyperglycemia. Having the syndrome increases a person’s risk for type 2 diabetes and cardiovascular disease.1,2 In addition, the condition is associated with increased morbidity and all-cause mortality.1,3–5 The worldwide prevalence of metabolic syndrome in adults approaches 25%6–8 and increases with age,7 especially among women,8,9 making it an important public health issue.Several studies have shown that lifestyle modifications,10 such as increased physical activity,11 adherence to a healthy diet12,13 or weight loss,14–16 are associated with reversion of the metabolic syndrome and its components. However, little information exists as to whether changes in the overall dietary pattern without weight loss might also be effective in preventing and managing the condition.The Mediterranean diet is recognized as one of the healthiest dietary patterns. It has shown benefits in patients with cardiovascular disease17,18 and in the prevention and treatment of related conditions, such as diabetes,19–21 hypertension22,23 and metabolic syndrome.24Several cross-sectional25–29 and prospective30–32 epidemiologic studies have suggested an inverse association between adherence to the Mediterranean diet and the prevalence or incidence of metabolic syndrome. Evidence from clinical trials has shown that an energy-restricted Mediterranean diet33 or adopting a Mediterranean diet after weight loss34 has a beneficial effect on metabolic syndrome. However, these studies did not determine whether the effect could be attributed to the weight loss or to the diets themselves.Seminal data from the PREDIMED (PREvención con DIeta MEDiterránea) study suggested that adherence to a Mediterranean diet supplemented with nuts reversed metabolic syndrome more so than advice to follow a low-fat diet.35 However, the report was based on data from only 1224 participants followed for 1 year. We have analyzed the data from the final PREDIMED cohort after a median follow-up of 4.8 years to determine the long-term effects of a Mediterranean diet on metabolic syndrome. 相似文献14.
Chun-Sick Eom Christie Y. Jeon Ju-Won Lim Eun-Geol Cho Sang Min Park Kang-Sook Lee 《CMAJ》2011,183(3):310-319
Background
Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a systematic review and meta-analysis to summarize this association.Methods
We searched three electronic databases (MEDLINE [PubMed], Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect.Results
We identified 31 studies: five case–control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.11–1.46, I2 90.5%) and histamine2 receptor antagonists (adjusted OR 1.22, 95% CI 1.09–1.36, I2 0.0%). In the randomized controlled trials, use of histamine2 receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01–1.48, I2 30.6%).Interpretation
Use of a proton pump inhibitor or histamine2 receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.Recently, the medical literature has paid considerable attention to unrecognized adverse effects of commonly used medications and their potential public health impact.1 One group of medications in widespread use is acid-suppressive drugs, which represent the second leading category of medication worldwide, with sales totalling US$26.9 billion in 2005.2Over the past 40 years, the development of potent acid-suppressive drugs, including proton pump inhibitors, has led to considerable improvements in the treatment of acid-related disorders of the upper gastrointestinal tract.3 Experts have generally viewed proton pump inhibitors as safe.4 However, potential complications such as gastrointestinal neoplasia, malabsorption of nutrients and increased susceptibility to infection have caused concern.5Of special interest is the possibility that acid-suppressive drugs could increase susceptibility to respiratory infections because these drugs increase gastric pH, thus allowing bacterial colonization.6,7 Several previous studies have shown that treatment with acid-suppressive drugs might be associated with an increased risk of respiratory tract infections8 and community-acquired pneumonia in adults6,7 and children.9 However, the association between use of acid-suppressive drugs and risk of pneumonia has been inconsistent.10–13Given the widespread use of proton pump inhibitors and histamine2 receptor antagonists, clarifying the potential impact of acid-suppressive therapy on the risk of pneumonia is of great importance to public health.14 Previous meta-analyses have focused on the role of acid-suppressive drugs in preventing stress ulcer,11,13,15 but none have examined pneumonia as the primary outcome.The aim of this study was to summarize the association between the use of acid-suppressive drugs and the risk of pneumonia in observational studies and randomized controlled trials. 相似文献15.
Hua He Wei Li David Y. Tseng Shan Zhang Szu-Yu Chen Anthony J. Day Scheffer C. G. Tseng 《The Journal of biological chemistry》2009,284(30):20136-20146
Clinically, amniotic membrane (AM) suppresses inflammation, scarring, and angiogenesis. AM contains abundant hyaluronan (HA) but its function in exerting these therapeutic actions remains unclear. Herein, AM was extracted sequentially with buffers A, B, and C, or separately by phosphate-buffered saline (PBS) alone. Agarose gel electrophoresis showed that high molecular weight (HMW) HA (an average of ∼3000 kDa) was predominantly extracted in isotonic Extract A (70.1 ± 6.0%) and PBS (37.7 ± 3.2%). Western blot analysis of these extracts with hyaluronidase digestion or NaOH treatment revealed that HMW HA was covalently linked with the heavy chains (HCs) of inter-α-inhibitor (IαI) via a NaOH-sensitive bond, likely transferred by the tumor necrosis factor-α stimulated gene-6 protein (TSG-6). This HC·HA complex (nHC·HA) could be purified from Extract PBS by two rounds of CsCl/guanidine HCl ultracentrifugation as well as in vitro reconstituted (rcHC·HA) by mixing HMW HA, serum IαI, and recombinant TSG-6. Consistent with previous reports, Extract PBS suppressed transforming growth factor-β1 promoter activation in corneal fibroblasts and induced mac ro phage apo pto sis. However, these effects were abolished by hyaluronidase digestion or heat treatment. More importantly, the effects were retained in the nHC·HA or rcHC·HA. These data collectively suggest that the HC·HA complex is the active component in AM responsible in part for clinically observed anti-inflammatory and anti-scarring actions.Hyaluronan (HA)4 is widely distributed in extracellular matrices, tissues, body fluids, and even in intracellular compartments (reviewed in Refs. 1 and 2). The molecular weight of HA ranges from 200 to 10,000 kDa depending on the source (3), but can also exist as smaller fragments and oligosaccharides under certain physiological or pathological conditions (1). Investigations over the last 15 years have suggested that low Mr HA can induce the gene expression of proinflammatory mediators and proangiogenesis, whereas high molecular weight (HMW) HA inhibits these processes (4–7).Several proteins have been shown to bind to HA (8) such as aggrecan (9), cartilage link protein (10), versican (11), CD44 (12, 13), inter-α-inhibitor (IαI) (14, 15), and tumor necrosis factor-α stimulated gene-6 protein (TSG-6) (16, 17). IαI consists of two heavy chains (HCs) (HC1 and HC2), both of which are linked through ester bonds to a chondroitin sulfate chain that is attached to the light chain, i.e. bikunin. Among all HA-binding proteins, only the HCs of IαI have been clearly demonstrated to be covalently coupled to HA (14, 18). However, TSG-6 has also been reported to form stable, possibly covalent, complexes with HA, either alone (19, 20) or when associated with HC (21).The formation of covalent bonds between HCs and HA is mediated by TSG-6 (22–24) where its expression is often induced by inflammatory mediators such as tumor necrosis factor-α and interleukin-1 (25, 26). TSG-6 is also expressed in inflammatory-like processes, such as ovulation (21, 27, 28) and cervical ripening (29). TSG-6 interacts with both HA (17) and IαI (21, 24, 30–33), and is essential for covalently transferring HCs on to HA (22–24). The TSG-6-mediated formation of the HC·HA complex has been demonstrated to play a crucial role in female fertility in mice. The HC·HA complex is an integral part of an expanded extracellular “cumulus” matrix around the oocyte, which plays a critical role in successful ovulation and fertilization in vivo (22, 34). HC·HA complexes have also been found at sites of inflammation (35–38) where its pro- or anti-inflammatory role remain arguable (39, 40).Immunostaining reveals abundant HA in the avascular stromal matrix of the AM (41, 42).5 In ophthalmology, cryopreserved AM has been widely used as a surgical graft for ocular surface reconstruction and exerts clinically observable actions to promote epithelial wound healing and to suppress inflammation, scarring, and angiogenesis (for reviews see Refs. 43–45). However, it is not clear whether HA in AM forms HC·HA complex, and if so whether such an HC·HA complex exerts any of the above therapeutic actions. To address these questions, we extracted AM with buffers of increasing salt concentration. Because HMW HA was found to form the HC·HA complex and was mainly extractable by isotonic solutions, we further purified it from the isotonic AM extract and reconstituted it in vitro from three defined components, i.e. HMW HA, serum IαI, and recombinant TSG-6. Our results showed that the HC·HA complex is an active component in AM responsible for the suppression of TGF-β1 promoter activity, linkable to the scarring process noted before by AM (46–48) and by the AM soluble extract (49), as well as for the promotion of macrophage death, linkable to the inflammatory process noted by AM (50) and the AM soluble extract (51). 相似文献
16.
Adam T. Hancock Christian D. Mallen Sara Muller John Belcher Edward Roddy Toby Helliwell Samantha L. Hider 《CMAJ》2014,186(13):E495-E501
Background:
Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults. Other inflammatory rheumatologic disorders are associated with an excess risk of vascular disease. We investigated whether polymyalgia rheumatica is associated with an increased risk of vascular events.Methods:
We used the General Practice Research Database to identify patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1, 1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up to 5 patients without polymyalgia rheumatica. Patients were followed until their first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or the end of available records (May 2011). All participants were free of vascular disease before the diagnosis of polymyalgia rheumatica (or matched date). We used Cox regression models to compare time to first vascular event in patients with and without polymyalgia rheumatica.Results:
A total of 3249 patients with polymyalgia rheumatica and 12 735 patients without were included in the final sample. Over a median follow-up period of 7.8 (interquartile range 3.3–12.4) years, the rate of vascular events was higher among patients with polymyalgia rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted hazard ratio 2.6, 95% confidence interval 2.4–2.9). The increased risk of a vascular event was similar for each vascular disease end point. The magnitude of risk was higher in early disease and in patients younger than 60 years at diagnosis.Interpretation:
Patients with polymyalgia rheumatica have an increased risk of vascular events. This risk is greatest in the youngest age groups. As with other forms of inflammatory arthritis, patients with polymyalgia rheumatica should have their vascular risk factors identified and actively managed to reduce this excess risk.Inflammatory rheumatologic disorders such as rheumatoid arthritis,1,2 systemic lupus erythematosus,2,3 gout,4 psoriatic arthritis2,5 and ankylosing spondylitis2,6 are associated with an increased risk of vascular disease, especially cardiovascular disease, leading to substantial morbidity and premature death.2–6 Recognition of this excess vascular risk has led to management guidelines advocating screening for and management of vascular risk factors.7–9Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults,10 with a lifetime risk of 2.4% for women and 1.7% for men.11 To date, evidence regarding the risk of vascular disease in patients with polymyalgia rheumatica is unclear. There are a number of biologically plausible mechanisms between polymyalgia rheumatica and vascular disease. These include the inflammatory burden of the disease,12,13 the association of the disease with giant cell arteritis (causing an inflammatory vasculopathy, which may lead to subclinical arteritis, stenosis or aneurysms),14 and the adverse effects of long-term corticosteroid treatment (e.g., diabetes, hypertension and dyslipidemia).15,16 Paradoxically, however, use of corticosteroids in patients with polymyalgia rheumatica may actually decrease vascular risk by controlling inflammation.17 A recent systematic review concluded that although some evidence exists to support an association between vascular disease and polymyalgia rheumatica,18 the existing literature presents conflicting results, with some studies reporting an excess risk of vascular disease19,20 and vascular death,21,22 and others reporting no association.23–26 Most current studies are limited by poor methodologic quality and small samples, and are based on secondary care cohorts, who may have more severe disease, yet most patients with polymyalgia rheumatica receive treatment exclusively in primary care.27The General Practice Research Database (GPRD), based in the United Kingdom, is a large electronic system for primary care records. It has been used as a data source for previous studies,28 including studies on the association of inflammatory conditions with vascular disease29 and on the epidemiology of polymyalgia rheumatica in the UK.30 The aim of the current study was to examine the association between polymyalgia rheumatica and vascular disease in a primary care population. 相似文献17.
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20.
Naveen Poonai Gina Bhullar Kangrui Lin Adam Papini David Mainprize Jocelyn Howard John Teefy Michelle Bale Cindy Langford Rodrick Lim Larry Stitt Michael J. Rieder Samina Ali 《CMAJ》2014,186(18):1358-1363