Using self-reported data on the social determinants of health in primary care to identify cancer screening disparities: opportunities and challenges.

BACKGROUND: Data on the social determinants of health can help primary care practices target improvement efforts, yet relevant data are rarely available. Our family practice located in Toronto, Ontario routinely collects patient-level sociodemographic data via a pilot-tested survey developed by a multi-organizational steering committee. We sought to use these data to assess the relationship between the social determinants and colorectal, cervical and breast cancer screening, and to describe the opportunities and challenges of using data on social determinants from a self-administered patient survey. METHODS: Patients of the family practice eligible for at least one of the three cancer screening types, based on age and screening guidelines as of June 30, 2015 and who had answered at least one question on a socio-demographic survey were included in the study. We linked self-reported data from the sociodemographic survey conducted in the waiting room with patients' electronic medical record data and cancer screening records. We created an individual-level income variable (low-income cut-off) that defined a poverty threshold and took household size into account. The sociodemographic characteristics of patients who were overdue for screening were compared to those who were up-to-date for screening for each cancer type using chi-squared tests. RESULTS: We analysed data for 5766 patients for whom we had survey data. Survey participants had significantly higher screening rates (72.9, 78.7, 74.4% for colorectal, cervical and breast cancer screening respectively) than the 13, 036 patients for whom we did not have survey data (59.2, 65.3, 58.9% respectively). Foreign-born patients were significantly more likely to be up-to-date on colorectal screening than their Canadian-born peers but showed no significant differences in breast or cervical cancer screening. We found a significant association between the low-income cut-off variable and cancer screening; neighbourhood income quintile was not significantly associated with cancer screening. Housing status was also significantly associated with colorectal, cervical and breast cancer screening. There was a large amount of missing data for the low-income cut-off variable, approximately 25% across the three cohorts. CONCLUSION: While we were able to show that neighbourhood income might under-estimate income-related disparities in screening, individual-level income was also the most challenging variable to collect. Future work in this area should target the income disparity in cancer screening and simultaneously explore how best to collect measures of poverty.

Health care providers' and parents' attitudes toward administration of new infant vaccines--a multinational survey.

The New Vaccinations of Infants in Practice online survey in seven countries evaluated vaccination-related attitudes and concerns of parents of infants and health care providers (HCPs) who provide pediatric medical care. The survey showed that HCPs and parents were open to adding new vaccines to the immunization schedule, even if it requires co-administration with current vaccines or introduction of new office visits. Parental disease awareness campaigns would be helpful to achieve widespread acceptance of changes to vaccination schedules. In addition, HCPs would ideally provide disease education to parents to accompany recommendations for a new vaccine.

Atrial pacing leads following open heart surgery: active or passive fixation?

The right atrial appendage is often amputated at the time of cardiopulmonary bypass. Because of concerns regarding lead displacement, use of active fixation atrial leads has been recommended in patients who require permanent atrial or dual chamber pacing after open heart surgery. We evaluated the acute and chronic performance of active and passive fixation atrial leads implanted at our institution between 1985 and 1993 in patients with previous open heart surgery. Of 78 consecutive patients, 38 had an active fixation atrial lead, 28 had a passive fixation steroid-eluting lead, and 12 had a passive fixation lead without steroid-eluting properties. At implantation, sensed P wave amplitudes were similar in the three groups, but lead impedance and threshold were significantly higher for active fixation leads compared to all passive fixation leads. During follow-up, atrial pacing thresholds were significantly higher, and sensed P wave amplitudes significantly lower, in the patients with active fixation leads compared to those with passive fixation leads. Loss of sensing occurred in 6 of 38 (16%) patients with active fixation leads and 1 of 40 (2.5%) patients with a passive fixation lead (P = 0.027). Atrial lead displacement occurred in two patients with active fixation leads and one with a passive fixation lead. Comparison with a parallel group of patients without previous open heart surgery demonstrated that atrial lead performance was similar in the two groups. We conclude that, when permanent atrial or dual chamber pacing is necessary in patients with prior open heart surgery, it is appropriate to implant a passive fixation atrial lead except on the infrequent occasions when a stable atrial position cannot be obtained.

Investigation of the mechanism underlying the variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia.

The Islington Diabetes Survey identified two groups of non-diabetic individuals, low and high glycators, who remained consistently classified 4.4 +/- 0.2 years after the original study. To investigate the mechanism for this grouping, 12 original subjects, 5 with low and 7 with high levels of glycated haemoglobin relative to their 2 h blood glucose, were studied. Glycated albumin and fructosamine measurements gave comparable classifications, with three individuals being misclassified for each measurement; in addition glycated albumin was positively correlated with mean blood-glucose concentration (r = 0.53; P < 0.05). Fasting plasma glucose concentration was greater than the intra-erythrocyte concentration (P < 0.05), but their ratio was reduced in low compared to high glycators (0.77 +/- 0.12 and 0.94 +/- 0.13, P < 0.0001). No differences between groups were found for plasma insulin, urea or non-esterified fatty acids; plasma or intra-erythrocyte inorganic phosphate or vitamin C; nor plasma, erythrocyte or urinary total amino acids. Erythrocyte 2,3-diphosphoglycerate, a catalyst of glycation, was elevated in high compared to low glycators (5.61 +/- 0.26 and 4.81 +/- 0.24 mmol/l, P < 0.001). Mean centile glycated haemoglobin was positively correlated with intra-erythrocyte pH (r = 0.55; P < 0.05) and negatively with plasma total amino acids (r = -0.57, P < 0.05). These data indicate that the intra-erythrocyte environment of high glycators favours glycation of haemoglobin. This could have important consequences for diabetic patients in terms of monitoring their glycaemic control and in the progression of those complications related to non-enzymic glycation of intracellular proteins.

The zone of vulnerability to T wave shocks in humans.

INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. METHODS AND RESULTS: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P < 0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05). CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.

Comparative reproducibility of defibrillation threshold and upper limit of vulnerability.

The upper limit of vulnerability (ULV) is the strength at or above which VF is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. Previous studies have demonstrated a statistically significant correlation between the ULV and the defibrillation threshold (DFT) in groups of patients. However, the correlation between ULV and DFT may not be close in individual patients. This imperfect correlation may be due to physiological factors or to limitations of the measurement methods. The reproducibility of either DFT or ULV has not been studied critically. The purpose of this study was to compare the reproducibility of clinically applicable methods for determination of DFT and ULV. We prospectively studied 25 patients with a transvenous implantable cardioverter defibrillator (Medtronic 7219D) at postoperative electrophysiological study. DFT was defined as the lowest energy that defibrillated after 10 seconds of VF. The ULV was defined as the lowest energy that did not induce VF with three shocks at 0, 20, and 40 ms before the peak of the T wave in ventricular paced rhythm at a cycle length of 500 ms. Both the DFT and the ULV were determined twice for biphasic pulses using a three-step, midpoint protocol. There was no significant difference between the two determinations of DFT (10.1 +/- 5.9 J vs 10.4 +/- 5.8 J), the two determinations of ULV (13.4 +/- 6.8 J vs 13.8 +/- 6.6) or the DFT-ULV Pearson correlation coefficients for each determination (0.84, P < 0.001 vs 0.75, P < 0.001). To analyze reproducibility, Lin concordance coefficients for second determination versus first determination were constructed for both ULV and DFT. This coefficient is similar to the Pearson correlation coefficient, but measures closeness to the line of identity rather than the line of regression. The Lin concordance coefficient for ULV was higher than that for DFT (0.93, 95% CI 0.85-0.97 vs 0.64, 95% CI 0.33-0.82; P < 0.01). For paired comparison of defibrillation efficacy under different experimental conditions, the sample sizes required to detect differences of 2 J, 3 J, and 4 J (80% power, P < 0.05) were 52, 24, and 15 for DFT versus 15, 8, and 6 for ULV. We conclude that a simple, clinically applicable method for determination of ULV is more reproducible than the single point DFT. Measured correlations between the ULV and single point are limited by the reproducibility of the DFT measurement.

Short biphasic pulses from 90 microfarad capacitors lower defibrillation threshold.

For defibrillation between right ventricular and retropectoral patch electrodes using truncated exponential pulses, the stored energy defibrillation threshold (DFT) is lower for short pulses from small 60-microF capacitors than for conventional pulses from 120-microF capacitors, but 60-microF pulses frequently require higher voltages than are currently used. The goal of this study was to determine if DFT could be reduced by intermediate size 90-microF capacitors. This study compared biphasic waveform DFTs for 120 microF-65% tilt pulses, 90 microF-65% tilt pulses, and 90 microF-50% tilt pulses in 20 patients at defibrillator implantation. The 90 microF-50% tilt pulses were selected because their duration is half that of 120 microF-65% tilt pulses. The stored energy DFT for 90 microF-50% tilt pulses (9.1 +/- 4.3 J) was less than both the DFT for 120 microF-65% tilt pulses (12.0 +/- 5.5 J, P < 0.005) and the DFT for 90 microF-65% tilt pulses (11.6 +/- 5.8 J, P < 0.005). There was no significant difference between the latter two values. The voltage DFTs for 90 microF-50% pulses (436 +/- 113 V) and 120 microF-65% tilt pulses (436 +/- 104 V) were not statistically different; the voltage DFT for 90 microF-65% tilt pulses was higher than for either of the other two pulses (490 +/- 131, P < 0.005). The DFT was 20 J or greater in three patients for both 120 microF-65% tilt pulses and 90 microF-65% tilt pulses, but it was 16 J or less in all patients for 90 microF-50% tilt pulses. When pathways were dichotomized by the median resistance of 71 omega, 90 microF-50% tilt pulses significantly reduced DFTs compared to 120 microF-65% tilt pulses for higher resistance pathways (9.2 +/- 4.0 J vs 13.0 +/- 6.2 J, P = 0.002), but not lower resistance pathways (9.0 +/- 4.8 J vs 10.9 +/- 4.6 J, P = NS). For the electrode configuration tested, biphasic 90 microF-50% tilt pulses reduce stored energy DFT in comparison with 120 microF-65% tilt pulses without increasing voltage DFT. However, 90 microF-65% tilt pulses provide no benefit.

Upper limit of vulnerability is a good estimator of shock strength associated with 90% probability of successful defibrillation in humans with transvenous implantable cardioverter-defibrillators.

OBJECTIVES: The goals of this study were to determine the probability of successful defibrillation at the upper limit of vulnerability and to evaluate a minimal safety margin for implantable cardioverter-defibrillator first shocks based solely on the upper limit of vulnerability. BACKGROUND: The upper limit of vulnerability is the strength at or above which ventricular fibrillation is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It has been proposed as an estimate of defibrillation efficacy because it correlates with the defibrillation threshold and can be determined with a single episode of fibrillation. METHODS: We studied 40 patients prospectively at implantation of transvenous cardioverter-defibrillators. Defibrillation threshold was defined as the weakest biphasic shock that defibrillated after 10 s of ventricular fibrillation. The upper limit of vulnerability was defined as the weakest biphasic shock that did not induce ventricular fibrillation when given at 0, 20 and 40 ms before the peak of the T wave in ventricular paced rhythm at cycle length 500 ms. After determination of the upper limit of vulnerability and defibrillation threshold, patients underwent six additional fibrillation-defibrillation episodes. The strength of five of the defibrillation shocks was equal to the upper limit of vulnerability; the strength of one of the six shocks was randomly selected to be equal to the upper limit of vulnerability plus 3 J. The implantable cardioverter-defibrillator was tested at the upper limit of vulnerability plus 3 J in 28 patients. RESULTS: The defibrillation threshold was 8.8 +/- 5.0 J (mean +/- SD), and upper limit of vulnerability was 11.3 +/- 4.6 J; the defibrillation threshold and upper limit of vulnerability were highly correlated (r = 0.89, p < 0.001). The success rate for the 200 defibrillation shocks with strength equal to the upper limit of vulnerability was 90% (95% confidence intervals based on proportion of successes in 40 patients: 86% to 94%). All five defibrillation test shocks at the upper limit of vulnerability were successful in 24 patients (60%); four of five were successful in 12 patients (30%); and three of five were successful in 4 patients (10%). All 40 test shocks and 28 implantable cardioverter-defibrillator shocks with a strength equal to the upper limit of vulnerability plus 3 J were successful. CONCLUSIONS: The upper limit of vulnerability is a good estimator of the shock strength associated with 90% probability of successful defibrillation (DFT90). A strength of 3 J above the upper limit of vulnerability is a good estimate of the minimal acute safety margin for implantable cardioverter-defibrillator first shocks.

Optimal electrode configuration for pectoral transvenous implantable defibrillator without an active can.

A new 83 cm3 implantable cardioverter-defibrillator (ICD) designed for pectoral implantation has been implanted most frequently using right ventricular and superior vena cava (RV-->SVC) electrodes; a patch electrode (RV-->patch + SVC) has been added when necessary to decrease the defibrillation threshold (DFT). The goal of this prospective study was to compare biphasic waveform DFTs for 3 electrode configurations: RV-->patch, RV-->SVC, and RV-->patch + SVC in 25 consecutive patients. The patch was positioned in a left retro-pectoral pocket, and the SVC electrode was positioned with the tip at the junction of the SVC and innominate vein. In the first 15 patients, all 3 electrode configurations were tested in random order; in the last 10 patients, only the RV-->patch and RV-->patch + SVC configurations were tested. In the first 15 patients, the stored-energy DFT for the RV-->SVC configuration (15.2 +/- 7.7 J) was higher (p < 0.001) than the DFT for the RV-->patch configuration (11.3 +/- 6.2 J) and the RV-->patch + SVC configuration (10.0 +/- 5.8 J). For all 25 patients, the DFT was lower for the RV-->patch + SVC configuration (9.7 +/- 5.1 J) than for the RV-->patch configuration (12.4 +/- 6.6 J, p = 0.005). The pathway resistance was highest for the RV-->patch configuration (72 +/- 9 omega), lower for the RV-->SVC configuration (63 +/- 6 omega, p < 0.01), and lowest for the RV-->patch + SVC configuration (46 +/- 3 omega, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological variation in glycated proteins.

The high degree of individuality in the fructosamine assay has been ascribed to non-specific interferences in the assay. To investigate this, we measured the biological variability of 10 non-diabetic subjects using the fructosamine assay, the new fructosamine plus assay, glycated albumin and glycated total plasma proteins by affinity chromatography. The total variation of the two fructosamine assays was half that of the affinity chromatography assays. This was mainly due to the greater analytical imprecision of the affinity chromatography assays. The resulting high index of heterogeneity for both affinity methods makes it difficult to assess the significance of changes in serial results. The within-subject variation made a small contribution to the total variation for all the assays, and was particularly low for the fructosamine assays. This suggests that any non-specific component makes a constant contribution to the measured fructosamine activity in non-diabetic subjects. The fructosamine assays therefore have significant advantages over the affinity chromatography methods as indices of medium-term glycaemic control.

Effect of vitamin C on glycosylation of proteins.

Twelve nondiabetic subjects consumed 1 g/day vitamin C for 3 mo. A fasting blood sample was taken at the start of the study and at the end of each month for the measurement of plasma and intraerythrocyte glucose, vitamin C, glycosylated hemoglobin (affinity chromatography and electrophoresis), and glycosylated albumin (affinity chromatography). Although there were no significant changes in fasting glycemia, glycosylated hemoglobin (affinity chromatography) decreased 18%, from 6.18 +/- 0.48% (mean +/- SD) at the start to 5.05 +/- 0.50% (P less than 0.0001) after 3 mo, whereas, HbA1 measured by electrophoresis increased 16%, from 6.17 +/- 0.61 to 7.16 +/- 0.59% (P less than 0.0001) in this period. Glycosylated albumin decreased 33%, from 1.56 +/- 0.24 to 1.04 +/- 1.01% (P less than 0.0001) after 3 mo. This discrepancy between glycosylated hemoglobin measured by electrophoresis and affinity chromatography was due to methodological differences between the two techniques, with affinity chromatography measuring "true" glycosylated hemoglobin. The greater decrease found with glycosylated albumin was probably due to the different distribution of vitamin C between plasma and within the erythrocyte, levels after 1 mo of supplementation being 109 +/- 19 and 59 +/- 9 microM, respectively (P less than 0.001). This indicates that administration of oral vitamin C may inhibit the glycosylation of proteins in vivo by a competitive mechanism.

A study of the effect of diet on glycosylated haemoglobin and albumin levels and glucose tolerance in normal subjects.

As factors other than the degree of glucose tolerance or ambient blood glucose may determine glycosylated haemoglobin levels, we have investigated the effects of dietary glucose and soluble fibre supplementation on glucose tolerance, glycosylated haemoglobin and glycosylated albumin in non-diabetic subjects. Eleven non-diabetic subjects (7 M, 4 F; age 26.5 +/- 6.5 (+/- SD) yr; BMI 21.6 +/- 3.1 kg m-2) followed a high-soluble-fibre (5 g guar gum thrice daily)/low-glucose diet, or a low-soluble-fibre/high-glucose (500 ml glucose drink providing 100 g glucose per day) diet, each for 6 weeks, in randomized order. A 75 g oral glucose tolerance test was performed at recruitment and after each diet period, and fasting blood was assayed for glycosylated albumin by affinity chromatography, and glycosylated haemoglobin by four different methods. Adherence to guar and glucose supplementation was assessed at 89.5 +/- 7.5% and 97.1 +/- 3.5%, respectively. There was no significant effect of either diet on mean fasting, 1-h or 2-h plasma glucose concentration, or glycosylated haemoglobin levels by any assay. Glycosylated albumin was 1.71 +/- 0.35% at entry, fell to 1.33 +/- 0.30% (p less than 0.01) with high-fibre and rose to 1.95 +/- 0.23% (p less than 0.02) after a high-glucose diet. Insulin, total- and HDL-cholesterol and triglyceride levels were unaffected by either diet. A high-glucose diet increases, and a high-soluble-fibre diet decreases, levels of glycosylated albumin without effects on glucose tolerance or glycosylated haemoglobin.

Unexplained variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia.

We have studied levels of glycated haemoglobin in a sample of 223 people aged over 40 years without known diabetes mellitus screened in a community study. Each had a glucose tolerance test and glycated haemoglobin measured by four methods - agar gel electrophoresis with and without removal of Schiff base, affinity chromatography and isoelectric focusing. The correlation coefficients between 2 h blood glucose and levels of glycated haemoglobin were between 0.43 and 0.64. This poor correlation was not explained on the basis of assay or biological variability of either 2 h blood glucose or glycated haemoglobin. Multiple regression analysis showed that other assays of glycated haemoglobin contributed to the variance of any single glycated haemoglobin value by 0.1%-52.9% (median 12.8%) compared to the variance of 18.6%-41.4% (median 30.8%) explained by 2 h blood glucose alone, suggesting that in a non-diabetic population, the degree of glucose intolerance may explain only one third of the variance of glycated haemoglobin levels, but other factors operate to produce consistent changes in levels of glycated haemoglobin. Investigation of 42 subjects with consistently high (20 subjects) or low (22 subjects) levels of glycated haemoglobin relative to their 2 h blood glucose level showed no difference in age, gender, body mass index, haemoglobin levels or smoking, although 50% of low glycators had impaired glucose tolerance. Neither ambient blood-glucose levels, as estimated on two five-point blood-glucose profiles, nor dietary intake of carbohydrate, starch, sugars, fibre or alcohol, explained the difference between high and low glycators. The determinants of the consistent interindividual differences in levels of glycated haemoglobin in non-diabetic subjects remain to be determined.