Cord-Blood Derived Chemistry Reference Values in Preterm Infants for Sodium, Chloride, Potassium, Glucose, and Creatinine.

OBJECTIVES: International guidelines recommend that preterm infants should be supported to maintain their serum electrolytes within "normal" ranges. In term babies, cord blood values differed in pathological pregnancies from healthy ones. STUDY DESIGN: We examined cord blood sodium, chloride, potassium, glucose, and creatinine to derive maturity-related reference intervals. We examined associations with gestational age, delivery mode, singleton versus multiple, and prenatal maternal adverse conditions. We compared preterm cord values to term, and to adult reference ranges. RESULTS: There were 591 infants, 537 preterm and 54 term. Preterm cord glucose levels were steady (3.7 ± 1.1 mmol/L), while sodium, chloride, and creatinine increased over GA by 0.17, 0.14 mmol/L/week, and 1.07 µmol/L/week, respectively (p < 0.003). Average preterm cord potassium and chloride were higher than the term (p < 0.05). Compared with adult reference intervals, cord preterm reference intervals were higher for chloride (100-111 vs. 98-106 mmol/L), lower for creatinine (29-84 vs. 62-115 µmol/L), and more variable for potassium (2.7-7.9 vs. 3.5-5.0 mmol/L) and sodium (130-141 vs. 136-145 mmol/L). Cesarean section was associated with higher potassium and lower glucose, multiple births with higher chloride and creatinine and lower glucose, and SGA with lower glucose. CONCLUSIONS: Cord blood values varied across the GA range with increases in sodium, chloride, and creatinine, while glucose remained steady. Average preterm reference values were higher than term values for potassium and chloride. Preterm reference values differed from published adults' reference values. The changes across GA and by delivery mode, SGA, and being a multiple, which may have direct implications for neonatal care and fluid management. KEY POINTS: · Cord blood electrolyte, creatinine, and glucose values vary across neonatal gestational age.. · Average preterm cord values of potassium and chloride were higher than term values.. · Cord reference values differ by delivery mode, growth, and multiple impacting neonatal care decisions..

Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in North American Chronic HBV Carriers.

INTRODUCTION: Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response. MATERIAL AND METHODS: In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort. RESULTS: 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In the untreated group (44%), 8% were classified as immune tolerant, 10% immune clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were 4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR 2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68% tenofovir, 4% lamivudine), no significant change in qHBsAg levels occured with time. However, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL. CONCLUSION: qHBsAg titers were associated with CHB phase and remained stable in those on long-term NA. A significant number of treated patients had low-level qHBsAg, of which some may be eligible for treatment discontinuation without risk of flare.

Risk and Protective Factors for Late Talking: An Epidemiologic Investigation.

OBJECTIVE: To identify risk and protective factors for late talking in toddlers between 24 and 30 months of age in a large community-based cohort. STUDY DESIGN: A prospective, longitudinal pregnancy cohort of 1023 mother-infant pairs in metropolitan Calgary, Canada, were followed across 5 time points: before 25 weeks gestation, between 34-36 weeks gestation, and at 4, 12, and 24 months postpartum. Toddlers who scored ≤10th percentile on The MacArthur-Bates Communicative Development Inventories: Words and Sentences between 24 and 30 months of age were identified as late talkers. Thirty-four candidate characteristics theoretically and/or empirically linked to language development and/or language impairment were collected using survey methodology. RESULTS: The prevalence of late talking was 12.6%. Risk factors for late talking in the multivariable model included: male sex (P = .017) and a family history of late talking and/or diagnosed speech or language delay (P = .002). Toddlers were significantly less likely to be late talkers if they engaged in informal play opportunities (P = .013), were read to or shown picture books daily (P < .001), or cared for primarily in child care centers (P = .001). CONCLUSIONS: Both biological and environmental factors were associated with the development of late talking. Biological factors placed toddlers at risk for late talking, and facets of the environment played a protective role. Enveloping infants and toddlers in language-rich milieus that promote opportunities for playing, reading, and sharing books daily may decrease risk for delayed early vocabulary.

Evaluation of E-cadherin, ß-catenin and vimentin protein expression using quantitative immunohistochemistry in nasopharyngeal carcinoma patients.

PURPOSE: Aberrant expression of proteins involved in epithelial-to-mesenchymal transition have been described in various cancers. In this retrospective study, we sought to evaluate E-cadherin, ß-catenin and vimentin protein expression in non-metastatic nasopharyngeal (NPC) patients treated with curative intent, examine their relationship with each other, and with clinical outcome measures. METHODS: Pre-treatment formalin-fixed paraffin-embedded biopsies of 140 patients treated between January 2000 and December 2007 were assembled into a tissue microarray (TMA). Automated quantitative immunohistochemistry (AQUA®) was performed on sequential TMA sections stained with fluorescent-labeled antibodies against E-cadherin, ß-catenin and vimentin. Cox proportional hazards regression was used to estimate the effect of cytoplasmic vimentin, cytoplasmic E-cadherin, ß-catenin nuclear/cytoplasmic ratio expression on overall survival and disease-free survival. RESULTS: The average age of the patients was 51.7 years (SD=12.1; range 18-85), 66% were male, 71% had a KPS ≥ 90% at the start of treatment and 65% had stage III/IV disease. After adjusting for performance status, WHO and stage, high E-cadherin levels over the 75th percentile were found to produce a significantly increased risk for both a worse overall survival (HR = 2.53, 95% CI 1.21, 5.27) and disease free survival (DFS; HR = 2.14, 95%CI 1.28, 3.59). Vimentin levels over the first quartile produced an increased risk for a worse DFS (HR = 2.21, 95% CI 1.11, 4.38). No association was seen between ß-catenin and survival. CONCLUSION: In this cohort of NPC patients, higher levels of E-cadherin and higher levels of vimentin were associated with worse outcomes. Further work is needed to understand the role of these epithelial mesenchymal transition proteins in NPC.

An examination of the effectiveness of Handwriting Without Tears instruction.

BACKGROUND: Handwriting is an important childhood occupation, and implications of poor handwriting may have significant long-term effects. PURPOSE: The purpose of this study was to determine the effectiveness of Handwriting Without Tears (HWT) on Grade I students' handwriting and perception of skills. METHODS: A cross-over design was used. Repeated measures, at three points, included the Minnesota Handwriting Assessment (MHA) and performance rating scales. FINDINGS: Eighty-three boys and 66 girls with an average age of 6.2 years participated in the study. Students receiving HWT achieved significantly higher improvements compared to students with teacher-designed instruction in MHA Total Test Score and in MHA components of form, size, space, and alignment (all p < .05). Students had higher average performance ratings when receiving HWT in the first half of the school year. IMPLICATIONS: Instruction using HWT improves students' perception and skill in handwriting performance.

Social equity in Human Papillomavirus vaccination: a natural experiment in Calgary Canada.

BACKGROUND: The Alberta Immunization Program offers a vaccine against the Human Papillomavirus (HPV) free of charge to all girls in Grades 5 and 9. The vaccine is provided in two different service delivery models depending upon the acceptance of the program by the local school board. Vaccinations may be provided "in-school" or in "community" through appointments at Public Health Clinics. The purpose of this study was to determine whether there was a difference in vaccine uptake in Calgary between the two service delivery models, "in-school" and "community", and to examine if socioeconomic status (SES) was a contributing factor. METHODS: Individual data from the Calgary Zone Public Health vaccination database for all grade 5 and 9 girls in Calgary for school years 2008-2011 were analyzed using descriptive statistics. These data included vaccination records for 35,592 girls. Logistic regression was used to examine the effect of delivery system and SES status on being vaccinated, controlling for school type. RESULTS: HPV vaccination completion rates were 75% (95% confidence interval = 74.7%, 75.8%) for girls with an "in-school" compared to 36% (95% confidence interval = 35.3%, 37.2%) for girls in schools with a "community" service delivery model. A girl's neighbourhood SES was related to the likelihood of being HPV vaccinated depending on the service delivery model available to her. For girls attending a Public school with an "in-school" delivery model, the proportion completing vaccination increased as SES decreased (high SES = 79%; medium SES = 79%; low SES = 83%; p-value<0.001). For girls attending Calgary Catholic School District schools with the "community" delivery model there was a decrease in immunization rates from high and mid to low SES (high SES = 41%; medium SES = 42%; low SES = 34%; p-value<0.001). These results show that those with lower SES were differentially disadvantaged by not having access to an "in-school" vaccination delivery model. CONCLUSION: Service delivery models make a difference in HPV vaccination completion rates and create inequities for health protection and disease prevention based on socioeconomic status.

Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.

BACKGROUND: Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. METHODS AND RESULTS: The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). CONCLUSIONS: In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational age-specific reference intervals for preterm infants.

BACKGROUND: The objective was to determine the influence of gestational age, maternal, and neonatal variables on reference intervals for cord blood bone minerals (calcium, phosphate, magnesium) and related laboratory tests (alkaline phosphatase, and albumin-adjusted calcium), and to develop gestational age specific reference intervals based on infants without influential pathological conditions. METHODS: Cross-sectional study. 702 babies were identified as candidates for this study in a regional referral neonatal unit. After exclusions (for anomalies, asphyxia, maternal magnesium sulfate administration, and death), relationships were examined between cord blood serum laboratory analytes (calcium, phosphate, magnesium, alkaline phosphatase, and albumin-adjusted calcium) with gestation age and also with maternal and neonatal variables using multiple linear regression. Infants with influential pathological conditions were omitted from the development of gestational age specific reference intervals for the following categories: 23-27, 28-31, 32-34, 35-36 and > 36 weeks. RESULTS: Among the 506 preterm and 54 terms infants included in the sample. Phosphate, magnesium, and alkaline phosphatase in cord blood serum decreased with gestational age, calcium increased with gestational age. Those who were triplets, small for gestational age, and those whose mother had pregnancy-induced hypertension were influential for most of the analytes. The reference ranges for the preterm infants ≥ 36 weeks were: phosphate 1.5 to 2.6 mmol/L (4.5 to 8.0 mg/dL), calcium: 2.1 to 3.1 mmol/L (8.3 to 12.4 mg/dL); albumin-adjusted calcium: 2.3 to 3.2 mmol/L (9.1 to 12.9 mg/dL); magnesium 0.6 to 1.0 mmol/L (1.4 to 2.3 mg/dL), and alkaline phosphatase 60 to 301 units/L. CONCLUSIONS: These data suggest that gestational age, as well as potentially pathogenic maternal and neonatal variables should be considered in the development of reference intervals for preterm infants.

Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden.

INTRODUCTION: accurate selection of patients for vasovagal syncope studies requires strong risk stratification and knowledge of the natural history of syncope. We aimed to test the hypothesis that recent history of vasovagal syncope compared to distant history better predicts subsequent recurrence of syncope. METHODS AND RESULTS: in all, 208 subjects with a positive tilt test and ≥ 3 lifetime syncope spells were followed for 1 year. Syncope episodes in the preceding year and total historical spells were compared for their ability to predict a syncope recurrence using the criteria of optimal statistical significance, best linear separation of risk populations, and impact on power calculations. The number of vasovagal syncope spells in the preceding year better predicted syncope recurrence when compared to total number of historical spells (likelihood ratio statistic 28.4, P < 0.0001; versus 20.4, P = 0.001), and showed a substantial effect as the number of syncope events increased. For example, syncope recurred in 22% of those with <2 spells in the previous year compared to 69% in those with >6 spells. A history of no syncope compared to any syncope in the preceding year was associated with a 1-year probability of 7% versus 46% for syncope recurrence. A study designed to detect a 50% decrease in syncope recurrence at P = 0.05 with 80% power would require 159 patients with at least 3 lifetime spells, and only 108 patients with at least 3 spells in the previous year. CONCLUSIONS: the number of syncope events in the year preceding clinical evaluation is the best predictor of syncope recurrence.

Beneficial effects of statin therapy for prevention of atrial fibrillation following DDDR pacemaker implantation.

AIMS: Data suggest that atrial pacing, statins, angiotensin-converting enzyme-inhibitors and angiotensin receptor blocking drugs prevent atrial tachycardia/atrial fibrillation (AT/AF) in some patients. The clinical predictors of at/af recurrence following dual-chamber pacemaker insertion were examined in 185 consecutive patients with paroxysmal AF. METHODS AND RESULTS: Predictors of AT/AF recurrence were evaluated in this observational cohort study. The time to first AT/AF recurrence and AT/AF burden (h/day) was retrieved at each follow-up visit by interrogating the pacemaker. AT/AF recurred following pacemaker implantation in 157 (85%) patients. At 1 year of follow-up, patients without recurrence were more likely to be on statin therapy (54%) when compared with patients without statin therapy (25%, chi = 12.31, P = 0.0004). Statin therapy was the only significant predictor of AT/AF recurrence in a multivariate logistic regression model (adjusted odds ratio 0.33, 95% confidence interval 0.14-0.74, P = 0.007). AT/AF burden was significantly lower in the group on statin therapy (median 0.10 h/day) when compared with the group not on statin therapy (median 0.39 h/day, P = 0.0059). CONCLUSION: AT/AF recurs frequently following pacemaker implantation in patients with sinus node disease. The progression to permanent AF remains low over time. Statin therapy was significantly associated with AT/AF suppression.

Genetic Association Study in Multigenerational Kindreds With Vasovagal Syncope: Evidence for Involvement of Sex-Specific Serotonin Signaling.

BACKGROUND: Several studies suggest that vasovagal syncope has a genetic origin, but this is unclear. We assessed whether plausible gene variants associate with vasovagal syncope. METHODS: We studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. The diagnosis was ascertained with the Calgary Syncope Score. Common genetic variants were genotyped for 12 genes for vascular signaling, potassium channels, the HTR1A(serotonin 5-HT1A receptor), SLC6A4(serotonin reuptake transporter), and COMT(catecholamine O-methyltransferase). Sex-specific associations between genotypes and phenotypes were tested. RESULTS: In 9 out of 12 variants, there was no significant association between genotype and phenotype. However, the HTR1A(-1019) G alleles associated with syncope in males, but not in females ( P=0.005). CC and GG males had 9% versus 77% likelihoods of syncope. The SLC6A4 promoter L alleles associated with decreased syncope in males but increased in females ( P=0.059). The LL and SS males had 25% and 47% syncope likelihoods, whereas females had 75% and 50% syncope likelihoods. The COMT c.472 A alleles associated with decreased syncope in males but increased in females ( P=0.017). The GG and AA males had 50% and 15% syncope likelihoods, whereas females had 52% and 73% syncope likelihoods. CONCLUSIONS: There is a sex-dependent effect of alleles of serotonin signaling and vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.

Sociodemographic predictors of sport injury in adolescents.

OBJECTIVE: To examine sociodemographic risk factors for sport injury in adolescents. METHODS: This is a cross-sectional survey design in which a random sample of high school students (ages 14-19) completed an in-class survey (N = 2721). Students were asked questions regarding sociodemographic factors, sport participation, and sport injury in the past year. RESULTS: The incidence proportion of self-reported and medically treated sports injury, adjusting for the clustering effect of school, was 67.5 (95% CI; 64.2-71.1) and 43.2 (95% CI; 40.4-46.3) per 100 adolescents per year, respectively. Students from small towns had a lower risk of injury than those in the larger urban center (ORadjusted = 0.76, 95% CI 0.63-0.92). Non-Caucasian students had a lower risk of injury than did Caucasian students (ORadjusted = 0.63 (95% CI 0.5-0.79) for all sport injury and 0.57 (95% CI 0.47 - 0.7) for medically treated sport injury. Students with BMI in the 50th-90th percentiles had the greatest risk of sport injury. The risk of injury increased with weekly hours of participation. CONCLUSIONS: Location of residence, weekly exposure (participation hours), ethnicity, and BMI were simultaneous predictors of sport injuries in adolescents.

Comparison of logistic EuroSCORE and EuroSCORE II in predicting operative mortality of 1125 total arterial operations.

OBJECTIVES: The purpose of this study was to compare effectiveness of the 1999 logistic EuroSCORE (LES) and of the 2012 EuroSCORE II (ESII) in a real-world patient population of 1125 patients undergoing total arterial grafting (TAG) coronary artery bypass graft (CABG) surgery. METHODS: The performance of the two risk scores was compared using (i) discrimination (accuracy of discriminating non-survivors from survivors), (ii) calibration (assessment of agreement between the predicted/observed outcomes) and (iii) agreement between the two scores. By averaging medians of LES and ESII and then sub-division into 10 equal groups, actual operative mortality rate was compared with the median LES and ESII within each risk group, the difference plotted against the average risk score (as in a Bland and Altman plot), and using the traditional risk groupings for EuroSCORE of low (0-2.99), medium (3-5.99) and high risk (6.0 and above), the reclassification rate of ESII was compared with that of LES. RESULTS: In 1125 consecutive total arterial CABG patients, demographics included: mean age 64.6 years, 79% males, 35% diabetic patients, 57% urgent/emergent patients, 37% off-pump and 77% bilateral mammary grafting. Overall operative mortality was 3.2% (36 patients). Comparison of the LES and ESII showed (i) good discrimination for both LES and ESII (area under the curve for LES was 0.85 and for ESII was 0.87); (ii) neither score was well calibrated: LES tended to overestimate and ESII underestimated risk. In general, the ESII provided a better estimate of risk in lower risk patients and LES was better for the highest risk group. (iii) In terms of agreement, in the lower four risk groups the risk was overestimated by both scores, in five of the higher six risk groups ESII underestimated risk and LES overestimated risk, and in the highest risk group LES was very close (17.2 cf. 17.7) compared with ESII (5.6 cf. 17.7). In addition, ESII downgraded risk in 96.8% of survivors and in 97.2% of non-survivors. CONCLUSIONS: In 1125 consecutive TAG CABG patients, neither LES nor ESII performed well enough to be used as a consistent risk stratification tool; LES overestimated risk but was highly accurate for the highest of 10 risk groups and ESII consistently underestimated risk in all patients.

Prenatal Maternal Anxiety as a Risk Factor for Preterm Birth and the Effects of Heterogeneity on This Relationship: A Systematic Review and Meta-Analysis.

Background. Systematic reviews (SR) and meta-analyses (MA) that previously explored the relationship between prenatal maternal anxiety (PMA) and preterm birth (PTB) have not been comprehensive in study inclusion, failing to account for effects of heterogeneity and disagree in their conclusions. Objectives. This SRMA provides a summary of the published evidence of the relationship between PMA and PTB while examining methodological and statistical sources of heterogeneity. Methods. Published studies from MEDLINE, CINAHL, PsycINFO, and EMBASE, until June 2015, were extracted and reviewed. Results. Of the 37 eligible studies, 31 were used in this MA; six more were subsequently excluded due to statistical issues, substantially reducing the heterogeneity. The odds ratio for PMA was 1.70 (95% CI 1.33, 2.18) for PTB and 1.67 (95% CI 1.35, 2.07) for spontaneous PTB comparing higher levels of anxiety to lower levels. Conclusions. Consistent findings indicate a significant association between PMA and PTB. Due to the statistical problem of including collinear variables in a single regression model, it is hard to distinguish the effect of the various types of psychosocial distress on PTB. However, a prenatal program aimed at addressing mental health issues could be designed and evaluated using a randomised controlled trial to assess the causal nature of different aspects of mental health on PTB.

ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent.

BACKGROUND: In advanced nasopharyngeal carcinoma (NPC), biomarkers may help predict survival. METHODS: Tumoral expression of ataxia-telangiectasia mutated (ATM), thymidylate synthetase (THMS), and ribonucleotide reductase subunit M1 (RRM1), was correlated with survival in patients with nonmetastatic NPC using quantitative fluorescence immunohistochemistry with automated quantitative digital image analysis. RESULTS: Of the 146 patients included, 58 patients (40%) received concurrent chemoradiation therapy; the remainder was treated with radiation. Overall survival (OS) at 5 years was 71% (95% confidence interval [CI], 62% to 78%); disease-free survival (DFS) was 48% (95% CI, 39% to 57%). OS worsened for increasing values of ATM (hazard ratio [HR], 2.83; 95% CI, 1.01-7.94; p = .049) for values greater than the 75th percentile compared to less than the 25th percentile, but improved for tumors with higher THMS levels (HR, 0.44; 95% CI, 0.20-0.94; p = .033) for values greater than the 25th percentile compared to less than or equal to the 25th percentile. RRM1 was not associated with OS (p = .748). No biomarkers were associated with DFS. CONCLUSION: In our cohort, relative overexpression of ATM and low THMS levels were associated with worse OS. © 2015 Wiley Periodicals, Inc. Head Neck 38: E384-E391, 2016.

Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial.

BACKGROUND: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope. OBJECTIVES: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction. METHODS: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope. RESULTS: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had ≥1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019). CONCLUSIONS: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482).

Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time.

INTRODUCTION: In patients with non-metastatic muscle-invasive bladder cancer (MIBC) fit for curative therapy, a multidisciplinary approach consisting is recommended. This approach includes local treatment (usually radical cystectomy), ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit with NACT, uptake remains low. We assessed NACT consultation in Alberta and examined associative factors, as well as the relationship to survival. METHODS: Patients with MIBC were identified through the Alberta Cancer Registry. Demographic and clinicopathologic information was collected from electronic medical records between 2007 and 2011. In addition to descriptive statistics, logistic regression was used to determine factors associated with receiving NACT consultation. Overall survival was described using a Kaplan-Meier estimate. RESULTS: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence interval [CI] 39.5, 50.8) received NACT consultation. Patients ≥80 years (odds ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR 0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT consultation. The rate of NACT consultation increased steadily from 2007 to 2011 (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median follow-up of 28.1 months (range: 14.6-50.3), median survival was 54.7 months for patients who received NACT consultation versus 31.2 months for those who did not (p = 0.030). CONCLUSIONS: NACT consultation in patients with MIBC undergoing radical cystectomy has improved over time; however, regional differences underscore the need for a standardized approach to NACT consultation, including common referral mechanisms.

Quicker yet safe: skeletonization of 1640 internal mammary arteries with harmonic technology in 965 patients.

OBJECTIVES: Skeletonization of the internal mammary artery (IMA) facilitates arterial grafting and has been shown to reduce deep sternal infection but is more time-consuming and tedious than pedicle harvest. We wished to determine if use of harmonic technology (HT) facilitates skeletonization of the IMA and is as safe as the conventional technique of skeletonization. METHODS: In a consecutive series of 1057 patients with isolated coronary artery bypass graft (CABG) surgery from 2003 to 2013, adverse events and recorded harvest times were compared between harmonic (965 patients) and non-harmonic patients (86 patients). RESULTS: HT was used to harvest 1640 IMAs in 965 (91%) of 1057 consecutive CABG patients and skeletonization with the traditional technique (use of an electrocautery tip as a dissector) was used to harvest 147 IMAs in 86 patients. Six patients had no IMA harvested with this surgery (4 patients had an IMA used from a previous CABG, 1 had no disease of the left anterior descending coronary artery and 1 patient was in cardiogenic shock precluding IMA use). Excluding patients with single-vessel disease, 730/987 (74%) of patients received bilateral IMAs. Demographics of patients with and without harmonic skeletonization, respectively, were the following: mean age: 64.7 vs 67.7 years; diabetes: 33 vs 34%; women: 21 vs 26% and median European System for Cardiac Operative Risk Evaluation: 2.9 vs 3.2. The mean harvest time for 77 non-harmonic skeletonized mammary arteries (49 surgeries) was 32.2 min (95% confidence interval (CI): 30.1, 34.3), for harmonic skeletonized arteries after 450 surgeries was 28.4 min, (95% CI: 27.8, 29.1) and in the last 100 IMAs harvested for the isolated harmonic device use/mammary was 15.4 min (95% CI: 14.0, 16.7). Major adverse events for patients with and without harmonic skeletonization, respectively, were: reoperation for bleeding: 2.7 vs 3.5% (difference = 0.8%, 95% CI: -3.2, 4.8); damaged mammaries: 0.4 vs 0.7% (difference = 0.3%, 95% CI: -1.0, 1.7); deep sternal infection: 1.6 vs 1.2% (difference = -0.4%, 95% CI: -2.8, 2.0) and perioperative infarction: 1.7 vs 2.3% (difference = 0.7%, 95% CI: -2.6, 4.0). CONCLUSION: In this largest series to date of harmonic IMA skeletonization, this technique results in rare damage, is quicker and with a comparable adverse event rate compared with the non-harmonic method.

Arterial grafts balance survival between incomplete and complete revascularization: a series of 1000 consecutive coronary artery bypass graft patients with 98% arterial grafts.

OBJECTIVE: Coronary artery bypass grafting (CABG) with incomplete revascularization (ICR) is thought to decrease survival. We studied the survival of patients with ICR undergoing total arterial grafting. METHODS: In a consecutive series of all-comer 1000 patients with isolated CABG, operative and midterm survival were assessed for patients undergoing complete versus ICR, with odds ratios and hazard ratios, adjusted for European System for Cardiac Operative Risk Evaluation category, CABG urgency, age, and comorbidities. RESULTS: In this series of 1000 patients with 98% arterial grafts (2922 arterial, 59 vein grafts), 73% of patients with multivessel disease received bilateral internal mammary artery grafts. ICR occurred in 140 patients (14%). Operative mortality was 3.8% overall, 8.6% for patients with ICR, and 3.2% for patients with complete revascularization (P = .008). For operative mortality using multivariable logistic regression, after controlling for European System for Cardiac Operative Risk Evaluation category (P < .001) and CABG urgency (P = .03), there was no evidence of a statistically significant increased risk of death due to ICR (odds ratio, 1.73; 95% confidence interval, 0.80-3.77). For midterm follow-up (median, 54 months [interquartile range, 27-85 months]), after controlling for European System for Cardiac Operative Risk Evaluation category (P < .001) and comorbidities (P = .017) there was a significant interaction between age ≥ 80 years and ICR (P = .017) in predicting mortality. The adjusted hazard ratio associated with ICR for patients older than age 80 years was 5.7 (95% confidence interval, 1.8-18.0) versus 1.2 (95% confidence interval, 0.7-2.1) for younger patients. CONCLUSIONS: This is the first study to suggest that ICR in patients with mostly arterial grafts is not associated with decreased survival perioperatively and at midterm in patients younger than age 80 years. Arterial grafting, because of longevity, may balance survival between complete revascularization and ICR.

Toward zero: deep sternal wound infection after 1001 consecutive coronary artery bypass procedures using arterial grafts: implications for diabetic patients.

OBJECTIVE: Coronary artery bypass graft (CABG) surgery with arterial conduits is considered optimal. A deterrent to bilateral internal thoracic artery (BITA) grafting is the risk of deep sternal wound infection (DSWI). We introduced infection prevention measures sequentially, attempting to reduce DSWIs. The aim was to determine (1) if the absence of DSWIs in the last 469 of 1001 consecutive operations was significant; (2) which measures explained the change; and (3) the impact of diabetes. METHODS: The measures included internal thoracic artery (ITA) skeletonization, no bone wax, wound irrigation, 1 observer per case, harmonic scalpel harvest of ITAs, vancomycin paste on sternal marrow, iodine-impregnated skin drapes, chlorhexidine-alcohol skin preparation, no BITA grafts in obese, diabetic women, more off-pump procedures, aseptic wound care, and marrow irrigation before sternal approximation. RESULTS: Mean age was 65±10.4 years, 78% were male, 34% had diabetes, and 34% were obese. The first 532 patients had 16 DSWIs (3%) and the subsequent 469 had none (P<.001). Analysis of the data suggested that the first 11 measures likely contributed to the absence of DSWI and less likely, the twelfth. Key measures were likely chlorhexidine-alcohol use and avoidance of BITAs in obese diabetic women who had a 10-fold higher DSWI rate than the other patients (21.4% vs 2.0%). Other diabetics, including obese men, had no increased risk of DSWI. CONCLUSIONS: The measures applied caused a substantial reduction in DSWIs. Key measures included the use of chlorhexidine-alcohol and avoidance of BITA grafting in obese diabetic females. These measures reduced DSWIs after BITA grafting in most diabetics.