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Purpose: Cancer treatments can paradoxically appear to reduce the risk of noncancer mortality in observational studies, due to residual confounding. Here we introduce a method, Bias Reduction through Analysis of Competing Events (BRACE), to reduce bias in the presence of residual confounding. Experimental Design: BRACE is a novel method for adjusting for bias from residual confounding in proportional hazards models. Using standard simulation methods, we compared BRACE with Cox proportional hazards regression in the presence of an unmeasured confounder. We examined estimator distributions, bias, mean squared error (MSE), and coverage probability. We then estimated treatment effects of high versus low intensity treatments in 36,630 prostate cancer, 4,069 lung cancer, and 7,117 head/neck cancer patients, using the Veterans Affairs database. We analyzed treatment effects on cancer-specific mortality (CSM), noncancer mortality (NCM), and overall survival (OS), using conventional multivariable Cox and propensity score (adjusted using inverse probability weighting) models, versus BRACE-adjusted estimates. Results: In simulations with residual confounding, BRACE uniformly reduced both bias and MSE. In the absence of bias, BRACE introduced bias toward the null, albeit with lower MSE. BRACE markedly improved coverage probability, but with a tendency toward overcorrection for effective but nontoxic treatments. For each clinical cohort, more intensive treatments were associated with significantly reduced hazards for CSM, NCM, and OS. BRACE attenuated OS estimates, yielding results more consistent with findings from randomized trials and meta-analyses. Conclusions: BRACE reduces bias and MSE when residual confounding is present and represents a novel approach to improve treatment effect estimation in nonrandomized studies.

In the last decade, the number of full-time registered dietitians (RDs) serving intercollegiate athletes in the United States has more than quadrupled. However, many student athletes may be at increased risk of nutrition-related problems that impact physical and academic performance, which include inadequate macronutrients, inadequate micronutrients, and excessive macronutrients. This narrative review reports the current literature to date on nutrition-related knowledge in collegiate athletes and the impact of sports RDs on student athletes’ nutrition knowledge and behaviors. To date, only observational and quasi-experimental studies have been published with regard to changes in nutrition knowledge and behaviors in NCAA athletes. While these studies report benefits of the RD as a member of the interdisciplinary student athlete support team, more well-designed randomized control trials are warranted to determine benefits related to health outcomes and sport-specific performance outcomes.

Background Zonulin is observed in animal models to regulate intestinal permeability and influenced by dietary intake, gut microbiota, and inflammation. We conducted a secondary analysis of a randomized controlled crossover trial (NCT03582306) in individuals with a BMI greater than 30 kg/m2 and high habitual red meat intake and low habitual green leafy vegetable (GLV) intake. Methods Participants were provided with frozen GLV during the first or last four weeks (immediate or delayed intervention) of the twelve-week trial. Biological and anthropometric measures were taken at the beginning and at each four-week interval. A subset of 20 participants was selected for this secondary analysis of the intestinal permeability and inflammation-related biomarkers: serum and fecal zonulin; serum lipopolysaccharide binding protein (LBP), Alpha-1-acid glycoprotein 1 (ORM-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and C-reactive protein; 8-hydroxy-2'-deoxyguanosine (8OHdG) and plasma Vitamin K1 as a marker of protocol adherence. Nutrient and food group intake from two-24-h dietary recalls collected at each time point were assessed. Fecal microbiota was measured by 16 s rRNA PCR sequencing. Changes in biological markers, dietary factors, and microbial taxa were assessed with Wilcoxon Sign Ranks Tests. Exploratory analyses of the relationship between changes in outcome variables were conducted with Spearman correlations. Results No changes in serum and fecal zonulin and serum LBP were observed. Plasma Vitamin K (p = 0.005) increased, while plasma 8OHdG (p = 0.023) decreased during the intervention compared to the control. The only dietary factors that changed significantly were increases during intervention in Vitamin K and Dark GLV (p p = 0.001) in females and Bifidobacterium (ρ = − 0.838, p = 0.009) and Bacteroidaceae (ρ = 0.871, p = 0.005) in men. Conclusions A high GLV dietary intervention increased serum zonulin levels and had no effect on fecal zonulin. Lack of concordance between several inflammation-associated biomarkers and zonulin corroborate recent reports of limited utility of zonulin in obese adults free of lower gastrointestinal disease. Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT03582306 (NCT03582306) registered on 07/11/2018.

Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) &gt, 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p &lt, 0.001) increased, while circulating 8OHdG (−8.52 ± 19.05 ng/mL, p &lt, 0.001), fecal 8OHdG (−6.78 ± 34.86 ng/mL, p &lt, 0.001), and TNFα (−16.95 ± 60.82 pg/mL, p &lt, 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted.

Preclinical and observational research suggests green leafy vegetables (GLVs) may reduce the risk of red meat (RM)-induced colonic DNA damage and colon cancer (CC). We sought to determine the feasibility of a high GLV dietary intervention in adults with an increased risk of CC (NCT03582306) via a 12-week randomized controlled crossover trial. Participants were randomized to immediate or delayed (post-4-week washout) intervention groups. During the 4-week intervention period, participants were given frozen GLVs and counseled to consume one cooked cup equivalent daily. The primary outcomes were: accrual&mdash, recruiting 50 adults in 9 months, retention&mdash, retaining 80% of participants at completion, and adherence&mdash, meeting GLV intake goals on 90% of days. Adherence data were collected twice weekly and 24-h dietary recalls at each time point provided nutrient and food group measures. The Food Acceptability Questionnaire (FAQ) was completed to determine acceptability. On each of the four study visits, anthropometrics, stool, saliva, and blood were obtained. Fifty adults were recruited in 44 days. Participants were 48 &plusmn, 13 years of age, 62% female, and 80% Caucasian, with an average BMI at screening of 35.9 &plusmn, 5.1. Forty-eight (96%) participants were retained and completed the study. During the intervention phase, participants consumed GLVs on 88.8% of days, the adherence goal of one cup was met on 73.2% of days. Dietary recall-derived Vitamin K and GLVs significantly increased for all participants during the intervention periods. Overall satisfaction did not differ between intervention and control periods (p = 0.214). This feasibility trial achieved accrual, retention and acceptability goals, but fell slightly short of the benchmark for adherence. The analysis of biological specimens will determine the effects of GLVs on gut microbiota, oxidative DNA damage, and inflammatory cytokines.

Background: Vildagliptin is a selective inhibitor of dipeptidyl peptidase IV (DPP-4) that improves glycemic control and pancreatic β-cell function in patients with Type 2 diabetes. Vildagliptin may be an appropriate agent to combine with other antihyperglycemic agents in patients requiring combination therapy to achieve optimal glycemic control. Two studies were performed to determine the potential for pharmacokinetic and pharmacodynamic interactions between vildagliptin and the sulfonylurea, glyburide, or pioglitazone in patients with Type 2 diabetes. Methods: Two open-label, multiple-dose, 3-period, randomized, crossover studies in patients with Type 2 diabetes were carried out. Steady state drug pharmacokinetics and postprandial plasma glucose and insulin responses were assessed during treatment with vildagliptin 100 mg b.i.d. alone and in combination with glyburide 10 mg q.d. (n = 17) or with vildagliptin 100 mg q.d. alone or in combination with pioglitazone 45 mg q.d. (n = 15). Results: Coadministration of vildagliptin with either glyburide or pioglitazone had no clinically significant effect on the pharmacokinetics of any of the 3 drugs. Changes in AUC and C max during combination treatment were small (≤ 15%), and 90% confidence intervals for the geometric mean ratios (drug coadministration/monotherapy) were generally contained within the acceptance range for bioequivalence (0.80 - 1.25). Vildagliptin/glyburide coadministration significantly reduced the area under the plasma glucose-time curve compared with glyburide alone (AUE 0-5h reduced by 12% (p = 0.005) and AUE 0-15h by 13% (p = 0.003)), and increased the area under the plasma insulin-time curve (AUE 0-15h increased by 12% (p = 0.041)). Vildagliptin/pioglitazone coadministration also significantly reduced postprandial glucose exposure compared with pioglitazone alone (AUE 0.5-5.5h reduced by 11% (p - 0.029) and AUE 0-15.5h by 10% (p = 0.019)). Vildagliptin was generally well tolerated whether administered alone or in combination with glyburide or pioglitazone, and was not associated with hypoglycemia. Conclusions: Coadministration of vildagliptin with either glyburide or pioglitazone in patients with Type 2 diabetes improves postprandial glycemic control without notable effects on drug pharmacokinetics.

Imatinib at 400 mg daily is standard treatment for chronic myeloid leukemia in chronic phase. We here describe the correlation of imatinib trough plasma concentrations (Cmins) with clinical responses, event-free survival (EFS), and adverse events (AEs). Trough level plasma samples were obtained on day 29 (steady state, n = 351). Plasma concentrations of imatinib and its metabolite CGP74588 were determined by liquid chromatography/mass spectrometry. The overall mean (± SD, CV%) steady-state Cmin for imatinib and CGP74588 were 979 ng/mL (± 530 ng/mL, 54.1%) and 242 ng/mL (± 106 ng/mL, 43.6%), respectively. Cumulative estimated complete cytogenetic response (CCyR) and major molecular response (MMR) rates differed among the quartiles of imatinib trough levels (P = .01 for CCyR, P = .02 for MMR). Cmin of imatinib was significantly higher in patients who achieved CCyR (1009 ± 544 ng/mL vs 812 ± 409 ng/mL, P = .01). Patients with high imatinib exposure had better rates of CCyR and MMR and EFS. An exploratory analysis demonstrated that imatinib trough levels were predictive of higher CCyR independently of Sokal risk group. AE rates were similar among the imatinib quartile categories except fluid retention, rash, myalgia, and anemia, which were more common at higher imatinib concentrations. These results suggest that an adequate plasma concentration of imatinib is important for a good clinical response. This study is registered at http://clinicaltrials.gov as NCT00333840.

The author proposes that the subject chosen for psychoanalytical investigation bears a relationship to autobiographical experiences. Aspects of the life of the British psychoanalyst, Joan Riviere (1883-1962), are examined and related to her investigation into a form of pathological femininity presented in her paper 'Womanliness as a masquerade'. Information about her formative years is gained from a diary kept by her mother that gives details of Joan Riviere's early months and years as well as further information about her as a young adult. Riviere's own diary, which lists events and activities in which she took part throughout more than a decade before she became a psychoanalyst, gives valuable insights into her life at that time. The author examines the descriptions of the patient in Riviere's paper and relates it to many facets of the latter's life. The defensive femininity shown by her patient is characterised by appeasement and denial of intellectual and professional attributes to escape detection and the retribution feared as a consequence of having, in phantasy, stolen potency from men. It is suggested that Riviere's own life experiences, particularly in relation to men, are represented in her paper.

Two cases of infra renal vena cava leiomyosarcoma are reported. Their locoregional extension resulted in a joint resection of the aorta and the vena cava. The follow-up of the two cases is of respectively 34 months and 32 months. We think that large resections are necessary, due to the microscopic characteristics of such tumors in order to try to improve the prognosis.

Inflammatory aneurysms of the abdominal aorta raise particular problems, as they are often detected as a result of their complications. In the light of one case presenting with anuria, the authors discuss the various treatment options and the value of preoperative corticosteroids.

The difficult insertion of a right subclavian catheter in a 63-year-old patient resulted in a pseudoaneurysm of the brachiocephalic artery requiring a resection-suture. The preventive measures of that complication are reminded.

A series of letters that Freud wrote to Joan Riviere in the period from 12-8-1921 to 22-1-1939 has been transcribed, translated into French and published here for the first time in the original text. They were given by Joan Riviere to the Sigmund Freud Archives and deposited at the Library of Congress in Washington where access to them had been restricted. Through the efforts of Dr. Harold Blum, the present Executive Director of the Freud Archives, the restriction was lifted. The letters concern arrangements that Freud made for his analysis of Joan Riviere; his (and her) relationship to Ernest Jones; the translation into English and the publication of his works in England. They also concern Freud's reaction to the reception in England of Anna Freud's book on The Technique of Child Analysis (1927) and his view of Melanie Klein's approach to the theory and practice of child analysis.

Clomiphene citrate, 50 mg/day, was administered to 105 patients with idiopathic azoospermia or oligoasthenospermia. Plasma FSH, LH, testosterone, and in a few cases estradiol were evaluated on day 0 and day 15 of therapy. Twelve other patients with no treatment were assayed in the same way. Statistical analysis demonstrated that, as a group, the infertile male population responds normally to clomiphene administration. On the other hand, three types of individual responses were recorded: complete positive response, dissociated positive response, and negative response. Sixty-nine patients were randomly selected for clomiphene therapy, 50 mg/day for 100 days; however, of 54 who completed the treatment schedule, only 11 showed elevated sperm counts. A study of correlations between hormonal and semen responses to clomiphene indicates that a complete or dissociated endocrine response is not an accurate predictor of possible semen amelioration on long-term therapy; on the other hand, sperm characteristics did not improve in those patients who did not demonstrate a positive hormonal response, mainly testosterone, on the 15th day of therapy.

During the beta 1-24 corticotropin stimulation test, it appears the increase of Aldosterone Blood level is more important (170,91% +/- 35,89 (S. E.)) and more significant (alpha less than 0,001) than for cortisol (+/- 54,47% +/- 9,45 (S. E.) - alpha less than 0,10). The authors suggest aldosterone assays have to be done in order to obtain a better estimation on adrenal response to synthetic A.C.T.H.

The authors report a case of giant diverticulum of the sigmoid colon, a very rare complication of diverticulosis of the colon, since only 38 cases have been reported in the literature. The diverticulum was seen at barium enema in a 66-year-old man complaining of digestive symptoms consisting of lower abdominal pain, tenesmus, diarrhea and fever. Segmental resection of the sigmoid colon including the site of implantation of the diverticulum with end-to-end anastomosis at the same operative stage led to definitive cure. On the basis of a study of the literature, the authors define the clinical, diagnostic and pathogenic characteristics of the condition.

In graves' disease small amounts of radioactive iodine administered repeatedly on a monthly basis depending on the progress of the disease is a method whose effectiveness we have studied on 192 cases over a period of 3 to 7 years. Relapses (4 %), failures (11 %) permanent hypothyroidism (24 % after 7 years) and the duration of the active stage have been collated with different clinical or biological parameters in order better to define the main factors that determine the course and prognosis. The size of the goitre and the presence of antithyroglobulin antibodies are among the most significant.

In three patients suffering from Cushing's disease, exploration revealed an enclosed pituitary adenoma in one case and a microadenoma in two cases. Selective excision via a transphenoidal approach resulted in cure of Cushing's disease as reflected by complete regression of clinical signs and the restoration of circadian rythm of cortisol. Regular follow-up over a period of more than two years showed the persistence of normal regulation of the corticotrophic sector of the pituitary.