Selective inhibition of cyclooxygenase-2 (COX-2) may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis. We report on the ...cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term, multicenter, randomized, placebo-controlled, double-blind trial designed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas.
A total of 2586 patients with a history of colorectal adenomas underwent randomization: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo. All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee.
A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008). The increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups. The results primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group. There was earlier separation (at approximately five months) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure (hazard ratio for the comparison of the rofecoxib group with the placebo group, 4.61; 95 percent confidence interval, 1.50 to 18.83). Overall and cardiovascular mortality was similar in the two groups.
Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.
Summary
Background
Patients with inflammatory bowel disease (IBD) on certain immunosuppressants have increased herpes zoster (HZ) risk.
Aim
To determine the risk of HZ in IBD and how antitumour ...necrosis factor‐alpha (anti‐TNF) agents affect this risk.
Methods
We performed a retrospective cohort and nested case–control study using administrative data from IMS LifeLink® Information Assets‐Health Plan Claims Database. In the cohort, we identified IBD patients <age 64 by diagnosis codes; matched to four individuals without IBD. HZ risk was evaluated by incidence rate ratio (IRR) and adjusted Cox proportional hazards models (HR). In the nested case–control analysis, 2659 IBD patients with HZ were each matched to four IBD patients without HZ. We determined associations between medications and HZ using conditional logistic regression.
Results
The cohort included 50 932 patients with Crohn's disease (CD), 56 403 patients with ulcerative colitis (UC) and 1269 with unspecified IBD, matched to 434 416 individuals without IBD. The IBD cohort had increased HZ risk compared with non‐IBD (IRR: 1.68, 95% CI: 1.60–1.76). After adjustment, IBD patients had a higher risk of HZ than non‐IBD (HR: 1.49, 95% CI: 1.42–1.57). In the nested case–control multivariate‐adjusted analyses, anti‐TNF medications (OR: 1.81, 95% CI: 1.48–2.21), corticosteroids (OR: 1.73, 95% CI: 1.51–1.99) and thiopurines (OR: 1.85, 95% CI: 1.61–2.13) were independently associated with HZ. Risk of HZ was highest with combination anti‐TNF and thiopurine therapy (OR: 3.29, 95% CI: 2.33–4.65).
Conclusions
Patients with inflammatory bowel disease are at increased risk for herpes zoster. Use of thiopurines, anti‐TNF agents, combination therapy and corticosteroids increases herpes zoster risk.
Summary
Background
Azathioprine (AZA), a pro‐drug metabolised to the active metabolites 6‐tioguanine nucleotides (6TGN), is a steroid‐sparing therapy for Crohn's disease (CD).
Aim
To investigate ...whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations.
Methods
This multicentre, double‐blind, randomised controlled trial compared the efficacy and safety of weight‐based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid‐treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight‐based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250–400 pmol/8 × 108 red blood cells (RBC), or to a maximal dose of 4 mg/kg/day.
Results
After randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention‐to‐treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight‐based arm (P = 0.11). In per‐protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight‐based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 × 108 RBC respectively (P = 0.07).
Conclusions
Despite trends favouring individualised over weight‐based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. Clinicaltrials.Gov Identifier Nct00113503.
•Quantitative assessment of blood loss (QBL) systems are available.•Introduction of a QBL system suggested differences compared with simple estimation of blood loss.•Differences were in the timing ...and volume of peripartum blood loss.•Recognition of postpartum haemorrhage was enhanced but blood loss lower.•Differences in outcomes associated with QBL varied according to mode of delivery.
Imprecise visual estimates of blood loss contribute to morbidity from postpartum hemorrhage. We examined the impact of quantitative assessment of postpartum blood loss on clinical practice and outcomes.
An observational study comparing blood loss, management and outcomes between two historical cohorts (August 2016 to January 2017 and August 2017 to January 2018) at an academic tertiary care center. Patients in the intervention group (second period) had blood loss quantified compared with visual estimation for controls.
We included 7618 deliveries (intervention group n=3807; control group n=3811). There was an increase in the incidence of hemorrhage (blood loss >1 L) in the intervention group for both vaginal (2.2% vs 0.5%, P <0.001) and cesarean delivery (12.6% vs 6.4%, P <0.001). There was also a difference in median blood loss for vaginal (258 mL 151–384 vs 300 mL 300–350, P <0.001); and for cesarean delivery (702 mL 501–857 vs 800 mL 800–900, P <0.001). The median red blood cell units transfused was different in the intervention group having cesarean delivery (2 units 1–2 vs 2 units 2–2, P=0.043). Secondary uterotonic usage was greater in the intervention group for vaginal (22% vs 17.3%, P <0.001) but not cesarean delivery (7.0% vs 6.0%, P=0.177). Laboratory costs were different, but not the re-admission rate or length of stay.
Quantifying blood loss may result in increased vigilance for vaginal and cesarean delivery. We identified an association between quantifying blood loss and improved identification of postpartum hemorrhage, patient management steps and cost savings.
Background & Aims: The published risk of adenocarcinoma in the setting of Barrett's esophagus (BE) varies. Publication bias, the selective reporting of studies featuring positive or extreme results, ...may result in overestimation of this cancer risk in the literature. The aim of this study was to assess those publications reporting a cancer risk in BE for evidence of publication bias. Methods: A MEDLINE search for all published estimates between 1966 and 1998 of cancer risk in BE was performed. All studies reporting a cancer risk expressible in cancers per patient-year of follow-up were retrieved. Bibliographies of these studies were surveyed for additional estimates. All publications that required an initial endoscopy with histologic confirmation of BE and any cancer were included. The relationship of reported cancer risk to size of the study was assessed. Multivariable regression controlling for differences in definition of BE, as well as other study characteristics, was performed. The data were also analyzed by means of a funnel diagram, an epidemiologic method to assess publication bias. Results: Five hundred fifty-four abstracts were reviewed. Twenty-seven publications met the stated criteria for inclusion. There was a strong correlation between cancer risk and the size of the study, with small studies reporting much higher risks of cancer than larger studies. This association persisted when differences in the definition of BE, retrospective vs. prospective nature of the study, surveillance interval, and the effect of cancer detected in the first year were considered. The funnel diagram analysis suggested publication bias. Conclusions: The cancer risk in BE may be overestimated in the literature due to publication bias.
GASTROENTEROLOGY 2000;119:333-338
Nuclear mass measurements of isotopes are key to improving our understanding of nuclear structure across the chart of nuclides, in particular, for the determination of the appearance or disappearance ...of nuclear shell closures. We present high-precision mass measurements of neutron-rich Ca, Ti, and V isotopes performed at TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN) and the Low Energy Beam and Ion Trap (LEBIT) facilities. These measurements were made using the TITAN multiple-reflection time-of-flight mass spectrometer (MR-ToF-MS) and the LEBIT 9.4T Penning trap mass spectrometer. In total, 13 masses were measured, 8 of which represent increases in precision over previous measurements. These measurements refine trends in the mass surface around N=32 and N=34, and support the disappearance of the N=32 shell closure with increasing proton number. Additionally, our data do not support the presence of a shell closure at N=34.
We report high-precision mass measurements of ^{50-55}Sc isotopes performed at the LEBIT facility at NSCL and at the TITAN facility at TRIUMF. Our results provide a substantial reduction of their ...uncertainties and indicate significant deviations, up to 0.7 MeV, from the previously recommended mass values for ^{53-55}Sc. The results of this work provide an important update to the description of emerging closed-shell phenomena at neutron numbers N=32 and N=34 above proton-magic Z=20. In particular, they finally enable a complete and precise characterization of the trends in ground state binding energies along the N=32 isotone, confirming that the empirical neutron shell gap energies peak at the doubly magic ^{52}Ca. Moreover, our data, combined with other recent measurements, do not support the existence of a closed neutron shell in ^{55}Sc at N=34. The results were compared to predictions from both ab initio and phenomenological nuclear theories, which all had success describing N=32 neutron shell gap energies but were highly disparate in the description of the N=34 isotone.
Among the wide energy range of
β
decays, there can exist decays with
Q
values as low as a few hundred eV. These decays can occur when the parent decays to a excited state in the daughter nucleus. ...Such decays have been called “ultra-low”
Q
value
β
decays. Their application is mainly twofold: (1) they are of interest as potential candidates for neutrino mass determination experiments, and (2) they provide a testing ground for theoretical studies of atomic interference effects in the nuclear decay process. In this work we have identified a number of such potential candidates by analyzing the most recent atomic mass and nuclear energy level data. To determine if an ultra-low
Q
value
β
decay branch is energetically allowed for these candidates, more precise and accurate data for the
Q
value of the ultra-low decay branch is needed. In most cases, this requires more precise atomic mass measurements for the parent and/or daughter atoms. These requirements can be met using Penning trap mass spectrometry.
The development of problem-solving skills — particularly with stoichiometry concepts — is paramount for succeeding in a general chemistry sequence. Key concepts related to problem solving and ...stoichiometry were analyzed and reported in this paper. The study analyzed retention of stoichiometry concepts over two consecutive quarters, the correlations between metacognition and success, and the correlations between the COSINE (Coding System for Investigating Subproblems and the Network) codes with the categories measured by the Metacognitive Awareness Inventory (MAI). Two cohorts, identified as the general and focus groups, were evaluated in the study. The general group (n = 39) took MAI in the Fall quarter and completed one multi-step question as a part of their regular exam. Concurrently, the focus group (n = 20) participated in a think-aloud session in which they solved six stoichiometry questions. Using a 95% confidence level, statistical differences between the fall and winter problem-solving performances were observed with the focus group. Furthermore, statistically significant correlations (using a 95% level of confidence) were observed between the MAI categories and the COSINE codes.
The authors examined the association between colon cancer and meat intake categorized by level of doneness, cooking method, and estimated levels of heterocyclic amines (HCAs), benzoapyrene, and ...mutagenicity. Data were collected as part of a population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 that included 701 African-American (274 cases, 427 controls) and 957 White (346 cases, 611 controls) participants. Odds ratios were calculated by using unconditional logistic regression, comparing the fifth to the first quintile levels of intake or exposure. Intake of red meat was positively associated with colon cancer (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). Associations with meat intake by cooking method were strongest for pan-fried red meat (OR = 2.0, 95% CI: 1.4, 3.0). Associations with meat intake by doneness were strongest for well-/very well done red meat (OR = 1.7, 95% CI: 1.2, 2.5). The strongest association for individual HCAs was reported for 2-amino-3,4,8-trimethylimidazo4,5-fquinoxaline (DiMeIQx) across all levels of exposure, with odds ratios of 1.8–2.0. Overall, sophisticated exposure measures were used to report modest, positive associations between red meat intake and colon cancer consistent with the hypothesis that HCAs may be among the etiologically relevant compounds in red meat.
PDF
