METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.
RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.
CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.
AIM/OBJECTIVES: To explore how curricula contribute to health graduate capabilities and what factors contribute to the development of these capabilities.
METHODS: Using contribution analysis evaluation, a six-step iterative process, key stakeholders in the six selected courses were engaged in an iterative theory-driven evaluation. The researchers collectively developed a postulated theory-of-change. Then evidence from existing relevant documents were extracted using documentary analysis. Collated findings were presented to academic staff, industry representatives and graduates, where additional data was sought through focus group discussions - one for each discipline. The focus group data were used to validate the theory-of-change. Data analysis was conducted iteratively, refining the theory of change from one course to the next.
RESULTS: The complexity in teaching and learning, contributed by human, organizational and curriculum factors was highlighted. Advances in knowledge, skills, attitudes and graduate capabilities are non-linear and integrated into curriculum. Work integrated learning significantly contributes to knowledge consolidation and forming professional identities for health professional courses. Workplace culture and educators' passion impact on the quality of teaching and learning yet are rarely considered as evidence of impact.
DISCUSSION: Capturing the episodic and contextual learning moments is important to describe success and for reflection for improvement. Evidence of impact of elements of courses on future graduate capabilities was limited with the focus of evaluation data on satisfaction.
CONCLUSION: Contribution analysis has been a useful evaluation method to explore the complexity of the factors in learning and teaching that influence graduate capabilities in health-related courses.
METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
METHODS: Patients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.
RESULTS: There were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.
CONCLUSION: The incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.
METHODS: Review of prospectively collected data from a multicentre, randomised controlled trial comparing CLE and laser peripheral iridotomy. Eligible participants were ≥50 years old and newly diagnosed with (1) primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and refractive outcomes at 12 and 36 months postoperatively for those who underwent CLE.
RESULTS: Of the 419 participants, 208 were randomised to CLE. Mean baseline CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months. Fifty-nine per cent and 85% eyes were within ±0.5D and ±1.0D of predicted refraction, respectively, at 36 months.
CONCLUSIONS: Mean CDVA in patients undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study period. Refractive error was significantly reduced with surgery but refractive predictability was suboptimal.
TRIAL REGISTRATION NUMBER:
METHODS: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.
RESULTS: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.
CONCLUSION: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.
METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.
RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).
CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.