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1.
Artigo em Inglês | MEDLINE | ID: mdl-31666286

RESUMO

BACKGROUND: We hypothesized that the risk of CRC in night-shift workers might be different according to insulin receptor substrates status. METHODS: Among 77,470 eligible women having night work assessed in the Nurses' Health Study, we documented a total of 1,397 CRC cases, of which 304 or 308 had available data on IRS1 and IRS2, respectively. We used duplication method Cox proportional hazards regression analysis for competing risks to calculate HRs and 95% CIs for each CRC subtype. We measured tumor IRS1 or IRS2 expression by immunohistochemistry. RESULTS: Compared with women who never worked night-shifts, those working ≥ 15 years night-shifts had a marginal trend of increased overall risk of CRC (Ptrend = 0.06, multivariable HR = 1.20, 95% CI, 0.99 to 1.45). Longer duration of night-shift work was associated with a higher risk of IRS2-positive tumors (multivariable HR = 2.69, 95% CI 1.48 to 4.89, Ptrend = 0.001, ≥ 15 years night-shifts vs. never) but not with IRS2-negative tumors (multivariable HR = 0.90, 95% CI 0.54 to 1.51, Ptrend = 0.72, Pheterogeneity for IRS2 = 0.008). Similarly, the corresponding multivariable HRs were 1.81 for IRS1-positive tumors (95% CI 0.94 to 3.48, Ptrend = 0.06) and 1.13 for IRS1-negative tumors (95% CI 0.71 to 1.80, Ptrend = 0.56, Pheterogeneity for IRS1 = 0.02). CONCLUSIONS: Our molecular pathological epidemiology data suggest a potential role of IRS in mediating carcinogenesis induced by night-shift work. IMPACT: Although these findings need validation, rotating night-shift might increase CRC risk in women with abnormal insulin receptor pathway.

2.
Neurosurgery ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625568

RESUMO

BACKGROUND: There is a paucity of investigation on the impact of spondylolisthesis surgery on back pain-related sexual inactivity. OBJECTIVE: To investigate predictors of improved sex life postoperatively by utilizing the prospective Quality Outcomes Database (QOD) registry. METHODS: A total of 218 patients who underwent surgery for grade 1 degenerative lumbar spondylolisthesis were included who were sexually active. Sex life was assessed by Oswestry Disability Index item 8 at baseline and 24-mo follow-up. RESULTS: Mean age was 58.0 ± 11.0 yr, and 108 (49.5%) patients were women. At baseline, 178 patients (81.7%) had sex life impairment. At 24 mo, 130 patients (73.0% of the 178 impaired) had an improved sex life. Those with improved sex lives noted higher satisfaction with surgery (84.5% vs 64.6% would undergo surgery again, P = .002). In multivariate analyses, lower body mass index (BMI) was associated with improved sex life (OR = 1.14; 95% CI [1.05-1.20]; P < .001). In the younger patients (age < 57 yr), lower BMI remained the sole significant predictor of improvement (OR = 1.12; 95% CI [1.03-1.23]; P = .01). In the older patients (age ≥ 57 yr)-in addition to lower BMI (OR = 1.12; 95% CI [1.02-1.27]; P = .02)-lower American Society of Anesthesiologists (ASA) grades (1 or 2) (OR = 3.7; 95% CI [1.2-12.0]; P = .02) and ≥4 yr of college education (OR = 3.9; 95% CI [1.2-15.1]; P = .03) were predictive of improvement. CONCLUSION: Over 80% of patients who present for surgery for degenerative lumbar spondylolisthesis report a negative effect of the disease on sex life. However, most patients (73%) report improvement postoperatively. Sex life improvement was associated with greater satisfaction with surgery. Lower BMI was predictive of improved sex life. In older patients-in addition to lower BMI-lower ASA grade and higher education were predictive of improvement.

3.
Science ; 365(6460): 1466-1469, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31604276

RESUMO

Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.

4.
Gastroenterology ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31586566

RESUMO

Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31663416

RESUMO

Introduction: Obstructive sleep apnea (OSA) is a chronic condition which requires a comprehensive chronic disease management model, rather than a device-focused approach, so as to achieve the best possible health outcomes. Oral appliances are the main alternative to continuous positive airway pressure (CPAP) for the treatment of OSA. There has been an expansion of the research evidence to support the use of oral appliances in clinical practice and the clinical use of oral appliances for the treatment of OSA has become a mainstream practice.Areas covered: This review summarizes the evidence base for the use of oral appliances for the treatment of OSA. The types of oral appliances; their mechanism of action and clinical efficacy for the treatment of OSA; adverse effects, and the impact on patient acceptability and treatment adherence; and clinical effectiveness and health outcomes are discussed.Expert opinion: Personalization of treatment is vitally important in OSA and is a pre-requisite for optimising adherence with treatment which, in turn, is a key determinant of clinical effectiveness. Treatment of OSA with mandibular advancement splints could provide an equivalent health benefit to CPAP despite not achieving a complete normalization of polysomnographic indices, mediated by differences in adherence profiles.

6.
J Neurosurg Spine ; : 1-8, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628295

RESUMO

OBJECTIVE: Understanding what influences pain and disability following anterior cervical discectomy and fusion (ACDF) in patients with degenerative cervical spine disease is critical. This study examines the timing of clinical improvement and identifies factors (including spinal alignment) associated with worse outcomes. METHODS: Consecutive adult patients were enrolled in a prospective outcomes database from two academic centers participating in the Quality Outcomes Database from 2013 to 2016. Demographics, surgical details, radiographic data, arm and neck pain (visual analog scale [VAS] scores), and disability (Neck Disability Index [NDI] and EQ-5D scores) were reviewed. Multivariate analysis was used. RESULTS: A total of 186 patients were included, and 48.4% were male. Their mean age was 55.4 years, and 45.7% had myelopathy. Preoperative cervical sagittal vertical axis (cSVA), cervical lordosis (CL), and T1 slope values were 24.9 mm (range 0-55 mm), 10.4° (range -6.0° to 44°), and 28.3° (range 14.0°-51.0°), respectively. ACDF was performed at 1, 2, and 3 levels in 47.8%, 42.0%, and 10.2% of patients, respectively. Preoperative neck and arm VAS scores were 5.7 and 5.4, respectively. NDI and EQ-5D scores were 22.1 and 0.5, respectively. There was significant improvement in all outcomes at 3 months (p < 0.001) and 12 months (p < 0.001). At 3 months, neck VAS (3.0), arm VAS (2.2), NDI (12.7), and EQ-5D (0.7) scores were improved, and at 12 months, neck VAS (2.8), arm VAS (2.3), NDI (11.7), and EQ-5D (0.8) score improvements were sustained. Improvements occurred within the first 3-month period; there was no significant difference in outcomes between the 3-month and 12-month mark. There was no correlation among cSVA, CL, or T1 slope with any outcome endpoint. The most consistent independent preoperative factors associated with worse outcomes were high neck and arm VAS scores and a severe NDI result (p < 0.001). Similar findings were seen with worse NDI and EQ-5D scores (p < 0.001). A significant linear trend of worse NDI and EQ-5D scores at 3 and 12 months was associated with worse baseline scores. Of the 186 patients, 171 (91.9%) had 3-month follow-up data, and 162 (87.1%) had 12-month follow-up data. CONCLUSIONS: ACDF is effective in improving pain and disability, and improvement occurs within 3 months of surgery. cSVA, CL, and T1 slope do not appear to influence outcomes following ACDF surgery in the population with degenerative cervical disease. Therefore, in patients with relatively normal cervical parameters, augmenting alignment or lordosis is likely unnecessary. Worse preoperative pain and disability were independently associated with worse outcomes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31639113

RESUMO

OBJECTIVE: The objective of this review is to synthesize the best available evidence on the outcomes of mandibular fibular free flap (MFFF) reconstructions using computer-assisted techniques versus traditional freehand techniques. INTRODUCTION: Fibular free flaps are the most commonly used free flap for mandible reconstruction and are considered best practice for mandible reconstructions following resection of head and neck cancers. There are several reported advantages of computer-assisted MFFF reconstructions, including increased accuracy, decreased operation time, decreased ischemia time, decreased overall cost and improved patient outcomes. It is important to assess the advantages and potential harms of these techniques in a systematic review. INCLUSION CRITERIA: Eligible studies will consider patients of all ages undergoing MFFF reconstruction. Studies will compare computer-assisted techniques to traditional freehand techniques for the primary outcomes of flap failure, patient-reported outcomes and bony resection margin status. Studies published in English from 2008 to the present will be included. Experimental, quasi-experimental, prospective and retrospective cohort, case-control and analytical cross-sectional studies will be considered. METHODS: MEDLINE, Embase, Scopus and the Cochrane Central Register of Controlled Trials will be searched. Gray literature sources will include Google Scholar and the World Health Organization International Clinical Trials Registry Platform. Two independent reviewers will screen titles and abstracts, assess full-text papers against the inclusion criteria, evaluate methodological quality using standardized critical appraisal instruments and extract data using a customized form. If possible, data will be pooled for statistical meta-analysis, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be presented.

8.
Abdom Radiol (NY) ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31555846

RESUMO

PURPOSE: To assess guideline compliance and quality of hepatocellular carcinoma, (HCC) diagnostic imaging within community hospitals (CH) and their Tertiary referral center (TRC) in a moderately high incidence region. METHODS: Initial diagnostic workup CT/MRI scans of 251 patients (122 CH, 112 TRC, 17 Non-TRC academic) with HCC over a 15-month period were assessed for Liver reporting and Data System (LI-RADS) guideline compliance. 269 scans (182 CT, 87 MRI) were qualitatively evaluated by 2 independent blinded radiologists for arterial timing, overall image quality, noise and sharpness, with quantification of interobserver variability. The contrast enhancement ratio (CER) for the largest HCC on each scan was calculated using pre- and post-contrast images. RESULTS: 103/104 (99%) of TRC and 44/78 (56%) of CH CTs adhered to LI-RADS imaging guidelines (P < 0.0001). Lack of delayed phase accounted for 32/34 (94%) of noncompliant CH CTs. Regarding MRI, 19/19 (100%) of TRC and 60/68 (88%) of CH scans were adherent (P = 0.12). For both modalities, overall image quality, noise and sharpness were rated significantly higher for TRC than CH. There was moderate interobserver agreement with intraclass correlation coefficient of 0.73, 0.70 and 0.63, respectively. Arterial-phase timing was rated adequate for CT in 75/104 TRC (72%) and 10/68 (14%) CH scans (P < 0.0001) and for MRI in 8/19 (42%) TRC and 23/68 (33%) CH scans (P = 0.17). The CER was significantly higher for TRC versus CH (2.9 vs. 1.9, P < 0.001) and MRI (0.9 vs. 0.7, P = 0.03). CONCLUSIONS: Community hospital HCC diagnostic scans significantly lag in critical quality parameters of tumor enhancement, arterial phase timing, perceived image quality, and LI-RADS CT technique compliance compared to a TRC.

9.
Carcinogenesis ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556446

RESUMO

Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case-control study of 324 female cases and 658 matched controls nested within the Nurses' Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative PCR-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the 4th quartile, multivariable-adjusted OR (95% CI) was 1.10 (0.69, 1.76) for the 3rd quartile, 1.40 (0.89, 2.19) for the 2nd quartile, and 2.19 (1.43, 3.35) for the 1st quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest vs. highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years' follow-up, and marginally significant among those with ≥ 10 years' follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis.

11.
MBio ; 10(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551328

RESUMO

Flavonoids are a group of polyphenolic dietary compounds found in many different plant-based foods. There is increasing evidence that higher flavonoid intake may be causally linked to a reduced risk of cardiovascular disease and other chronic diseases. The bioactivity and bioavailability of many dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. However, the role that habitual flavonoid intake plays in shaping the human gut microbiome is poorly understood. We describe an application of an ecosystem-based analytic approach to nutritional, microbiome, and questionnaire data from a cohort of more than 240 generally healthy adult males to assess the role of dietary flavonoid compounds in driving patterns of microbial community assembly. We identified six subclass-specific microbial communities (SMCs) uniquely and independently associated with intakes of the six flavonoid subclasses. Eggerthela lenta was positively associated with intakes of flavonol and flavanone, and Adlercreutzia equolifaciens was positively associated with intakes of flavonols and flavanol monomers. In contrast, for nearly all flavonoid subclasses, Flavonifractor plautii was inversely associated with subclass consumption. Consuming tea at least once per week explained 10.4% of the total variance in assembly of the 20 species comprising the flavanol monomer SMC. The novel methodology employed, necessitated by multidimensional microbiome data that consist of nonindependent features that exhibit a wide range of distributions and mean values, addresses a major challenge in our ability to understand associations of the microbiome in a wide range of clinical and epidemiologic settings.IMPORTANCE Dietary flavonoids, which have been implicated in lowering chronic disease risk and improving blood pressure, represent a diverse group of polyphenolic compounds found in many commonly consumed foods such as tea, red wine, apples, and berries. The bioactivity and bioavailability of more dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. With demonstrated prebiotic and antimicrobial effects in in vitro and in animal models, it is surprising that there are not many human studies investigating the role dietary flavonoids play in shaping the gastrointestinal microbiome. Our analysis revealed patterns of community assembly that uniquely and independently characterize an individual's exposure to various flavonoid compounds. Furthermore, this study confirmed, independent from effects of other dietary and lifestyle factors included in the multivariate-adjusted model, that flavonoid intake is associated with microbial community assembly.

12.
Lancet Oncol ; 20(11): 1531-1543, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31540791

RESUMO

BACKGROUND: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. METHODS: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing. FINDINGS: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred. INTERPRETATION: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. FUNDING: Accuray and National Institute of Health Research.

13.
Mucosal Immunol ; 12(6): 1336-1347, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31501515

RESUMO

Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.

14.
Am J Gastroenterol ; 114(9): 1531-1538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397679

RESUMO

OBJECTIVES: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women. METHODS: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records. RESULTS: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day. DISCUSSION: Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk.

15.
BMJ Open ; 9(7): e022877, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31371282

RESUMO

OBJECTIVE: We tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI). DESIGN: Three FADS variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies. SETTING: Population based study. PARTICIPANTS: 11 323 women from the Nurses' Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women's Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS). MAIN OUTCOMES: Long-term (~10 years) changes in BMI and body weight. RESULTS: In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the FADS rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the FADS rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the FADS rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2 per g, p=3×10-5) than the rs174570 non-T carriers (beta=0.16 kg/m2 per g, p=0.08). Similar results were observed for fish intake. CONCLUSIONS: Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the FADS variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31387969

RESUMO

BACKGROUND: Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. METHODS: We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. RESULTS: There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). CONCLUSIONS: Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. IMPACT: Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

17.
Mult Scler ; : 1352458518823955, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31456464

RESUMO

BACKGROUND: Diagnosing multiple sclerosis (MS) early is crucial to avoid future disability. However, potentially preventable delays in the diagnostic cascade from contact with a physician to definite diagnosis still occur and their causes are still unclear. OBJECTIVE: To identify the possible causes of delays in the diagnostic process. METHODS: We analyzed the data of the Swiss MS Registry. With logistic regression, we modeled the time from the first contact to the first consultation (contact-to-evaluation time, ⩽1 month/>1 month) and the evaluation-to-diagnosis time (⩽6 months/>6 months). Potential factors were health system characteristics, sociodemographic variables, first symptoms, and MS type. RESULTS: We included 522 participants. Mostly, general practitioners (67%) were contacted first, without delaying the diagnosis. In contrast, first symptoms and MS type were the major contributors to delays: gait problems were associated with longer contact-to-evaluation times, depression as a concomitant symptom with longer evaluation-to-diagnosis times, and having primary progressive MS prolonged both phases. In addition, living in mountainous areas was associated with longer contact-to-evaluation times, whereas diagnosis after 2000 was associated with faster diagnoses. CONCLUSION: For a quicker diagnosis, awareness of MS as a differential diagnosis of gait disorders and the co-occurrence of depression at onset should be raised, and these symptoms should be attentively followed.

18.
JBI Database System Rev Implement Rep ; 17(10): 2136-2151, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31403550

RESUMO

OBJECTIVE: The objective of this review is to synthesize the best available evidence on the outcomes of mandibular fibular free flap (MFFF) reconstructions using computer-assisted techniques versus traditional freehand techniques. INTRODUCTION: Fibular free flaps are the most commonly used free flap for mandible reconstruction and are considered best practice for mandible reconstructions following resection of head and neck cancers. There are several reported advantages of computer-assisted MFFF reconstructions, including increased accuracy, decreased operation time, decreased ischemia time, decreased overall cost and improved patient outcomes. It is important to assess the advantages and potential harms of these techniques in a systematic review. INCLUSION CRITERIA: Eligible studies will consider patients of all ages undergoing MFFF reconstruction. Studies will compare computer-assisted techniques to traditional freehand techniques for the primary outcomes of flap failure, patient-reported outcomes and bony resection margin status. Studies published in English from 2008 will be included. Experimental, quasi-experimental, prospective and retrospective cohort, case-control and analytical cross-sectional studies will be considered. METHODS: MEDLINE, Embase, Scopus and the Cochrane Central Register of Controlled Trials will be searched. Gray literature sources will include Google Scholar and the World Health Organization International Clinical Trials Registry Platform. Two independent reviewers will screen titles and abstracts, assess full-text papers against the inclusion criteria, evaluate methodological quality using standardized critical appraisal instruments and extract data using a customized form. If possible, data will be pooled for statistical meta-analysis, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be presented.

20.
Gastroenterology ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31302144

RESUMO

BACKGROUND & AIMS: Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance. METHODS: We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or non-advanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (< 10 mm). We used Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors. RESULTS: After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared to participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% CI, 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI, 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with non-advanced adenomas (HR, 1.21; 95% CI, 0.68-2.16, P=.52) or small serrated polyps (HR, 1.25; 95% CI, 0.76-2.08; P=.38). CONCLUSIONS: These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with non-advanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.

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