A RANDOMIZED TRIAL OF BILEVEL POSITIVE AIRWAY PRESSURE DEVICE AND HIGH FLOW OXYGEN FOR PERSISTENT DYSPNEA IN

Background: Dyspnea is a common and distressing symptom among patients with advanced cancer. The role of bilevel positive airway pressure (BIPAP) and Vapotherm in the relief of dyspnea have not been well defined. We aimed to determine and to compare the efficacy of BIPAP and VapoTherm for cancer related dyspnea. Methods: In this randomized, open-label, crossover study, we randomly assigned advanced cancer patients with persistent dyspnea >=3/10 to either Vapotherm for 2 hours followed by BiPAP for 2 hours, or BiPAP followed by Vaptherm. A variable washout period was instituted between interventions. The primary end point was change in numeric rating scale before and after each intervention. We planned to enroll 50 patients in total. Results: Among the 803 patients screened over the last 8 months, 62 (26%) were eligible, and 16 (2%) were enrolled so far. Five patients completed the entire study successfully, 4 discontinued the study prematurely due to prolonged relief of dyspnea, and 7 dropped out for various reasons, including inability to tolerate BiPAP (N=3), anxiety (N=2), fatigue (N=1) and pain requiring opioids (N=1). The median baseline numeric rating score for dyspnea was 7/10 (interquartile range (IQR) 5-8), and the median baseline Borg score was 4/10 (3-7). Interim analysis revealed that BiPAP was associated with a median change in numeric rating score of -3 (N=10, IQR -6.3 to -1, p=0.007) and modified Borg score of -1 (N=10, IQR -3 to 0.3, p=0.058), while Vapotherm was associated with a median change in numeric rating score of -2 (N=9, IQR -3 to -1, p=0.011) and modified Borg score of -2.5 (N=8, IQR -5.5 to -0.1, p=0.051). Among the 5 individuals who completed the entire study, 2 preferred Vapotherm, 2 favored BiPAP, and 1 liked both. The respiratory rate decreased and the oxygen saturation improved with both interventions. No significant toxicities were observed. Conclusions: We were successfully able to enroll patients onto this clinic trial. Our preliminary results suggest that BiPAP and Vapotherm are highly efficacious in providing relief for patients with persistent refractory dyspnea. A direct comparison of the two interventions will be done upon study completion. Further research is necessary to confirm our findings.

Contribution of the genes of the renin-angiotensin system to interindividual differences in blood pressure levels in Caucasians from Rochester, Minnesota

The Renin-Angiotensin system (RAS) regulates blood pressure through its effects on vascular tone, renal hemodynamics, and renal sodium and fluid balance. The genes encoding the four major components of the RAS, angiotensinogen, renin, angiotensin I-converting enzyme (ACE), and angiotensin II receptor type 1 (AT1), have been investigated as candidate genes in the pathogenesis of essential hypertension. However, studies have primarily focused on small samples of diseased individuals, and, therefore, have provided little information about the determinants of interindividual variation in blood pressure (BP) in the general population.^ Using data from a large population-based sample from Rochester, MN, I have evaluated the contribution of variation in the region of the RAS genes to interindividual variation in systolic, diastolic, and mean arterial pressure in the population-at-large. Marker genotype data from four polymorphisms located within or very near these genes were first collected on 3,974 individuals from 583 randomly ascertained three-generation pedigrees. Haseman-Elston regression and variance component methods of linkage analysis were then carried out to estimate the proportion of interindividual variance in BP attributable to the effects of variation at these four measured loci.^ A significant effect of the ACE locus on interindividual variation in mean arterial pressure (MAP) was detected in a sample of siblings belonging to the youngest generation. After allowing for measured covariates, this effect accounted for 15-25% of the interindividual variance in MAP, and was even greater in a subset with a positive family history of hypertension. When gender-specific analyses were carried out, this effect was significant in males but not in females. Extended pedigree analyses also provided evidence for an effect of the ACE locus on interindividual variation in MAP, but no difference between males and females was observed. Circumstantial evidence suggests that the ACE gene itself may be responsible for the observed effects on BP, although the possibility that other genes in the region may be at play cannot be excluded.^ No definitive evidence for an effect of the renin, angiotensinogen, or AT1 loci on interindividual variation in BP was obtained in this study, suggesting that the impact of these genes on BP may not be great in the Caucasian population-at-large. However, this does not preclude a larger effect of these genes in some subsets of individuals, especially among those with clinically manifest hypertension or coronary heart disease, or in other populations. ^

Effectiveness of dietary intervention in children and adolescents with elevated blood pressure

Hypertension is a known risk factor for cardiovascular disease in adults. Essential hypertension in children and adolescents is increasing in prevalence in the United States, and hypertension in children may track into adulthood. This increasing prevalence is attributed to the trends of increasing overweight and obese children and adolescents. Family history and being of African-American/black descent may predispose youth to elevated blood pressure. Interventions targeted to reduce and treat hypertension in youth include non-pharmaceutical interventions such as weight reduction, increased physical activity, and dietary changes and pharmaceutical treatment when indicated. The effectiveness of non-pharmaceutical interventions is well documented in adults, but there are limited studies with regards to children and adolescents, specifically in the arena of dietary interventions. Lifestyle modifications such as dietary interventions are the mainstay of recommended treatment for those children and adolescents with prehypertension or stage 1 hypertension. Given the association of being overweight and hypertension, efficacy of dietary interventions are of interest because of reduced cost, easy implementation and potential for multiple beneficial outcomes such as reduced weight and reduction of other metabolic or cardiovascular derangements. Barriers to dietary interventions often include socioeconomic status, ethnicity, personal, and external factors. The goal of this systematic review of the literature is to identify interventions targeted to children and adolescents that focus on recommended dietary changes related to blood pressure. Dietary interventions found for this review mostly focused on a particular nutrient or food group with the one notable exception that focused on the DASH pattern of eating. The effects of the interventions on blood pressure varied, but overall dietary modifications can be achieved in youth and can serve a role in producing positive outcomes on blood pressure. Increasing potassium and following a DASH diet seemed to provide the most clinically significant results. Further studies are still needed to evaluate long-term effectiveness and to contribute more supporting evidence for particular modifications in these age cohorts.^

Intensive care noise and mean arterial blood pressure in ELBW neonates

Objective. Loud noises in neonatal intensive care units (NICUs) may impede growth and development for extremely low birthweight (ELBW, < 1000 grams) newborns. The objective of this study was to measure the association between NICU sound levels and ELBW neonates' arterial blood pressure to determine whether these newborns experience noise-induced stress. ^ Methods. Noise and arterial blood pressure recordings were collected for 9 ELBW neonates during the first week of life. Sound levels were measured inside the incubator, and each subject's arterial blood pressures were simultaneously recorded for 15 minutes (at 1 sec intervals). Time series cross-correlation functions were calculated for NICU noise and mean arterial blood pressure (MABP) recordings for each subject. The grand mean noise-MABP cross-correlation was calculated for all subjects and for lower and higher birthweight groups for comparison. ^ Results. The grand mean noise-MABP cross-correlation for all subjects was mostly negative (through 300 sec lag time) and nearly reached significance at the 95% level at 111 sec lag (mean r = -0.062). Lower birthweight newborns (454-709 g) experienced significant decreases in blood pressure with increasing NICU noise after 145 sec lag (peak r = -0.074). Higher birthweight newborns had an immediate negative correlation with NICU sound levels (at 3 sec lag, r = -0.071), but arterial blood pressures increased to a positive correlation with noise levels at 197 sec lag (r = 0.075). ^ Conclusions. ELBW newborns' arterial blood pressure was influenced by NICU noise levels during the first week of life. Lower birthweight newborns may have experienced an orienting reflex to NICU sounds. Higher birthweight newborns experienced an immediate orienting reflex to increasing sound levels, but arterial blood pressure increased approximately 3 minutes after increases in noise levels. Increases in arterial blood pressure following increased NICU sound levels may result from a stress response to noise. ^

Type A behavior and blood pressure during adolescence

In The Woodlands, Texas, 346 students in grades 9-12, age 14-18 participated in a screening examination for cardiovascular risk factors. The relationships between blood pressure with Type-A-behavior and its components were evaluated. Type-A-behavior was measured using the Hunter-Wolf Type-A-behavior scale.^ The following results refer to the current 24-item version of the Hunter-Wolf Type-A-behavior scale and subscales derived in the Bogalusa study which thereafter were applied to The Woodlands population.^ No significant differences in blood pressure were observed among children in the highest vs. lowest quintile of the Type-A-behavior score or subscales scores. The correlation coefficients of blood pressure with the Type-A-behavior and its components were small and non-significant in both boys and girls. Multiple regression analyses conducted by sex, showed that after adjustment for age, weight and height, the addition of the total Type-A-behavior score or subscale scores did not increase significantly the amount of the variability explained for any of the blood pressure components.^ These analyses were repeated with results from the original 17-item version of the Hunter-Wolf Type-A-behavior scale and subscales derived in Bogalusa. Similarly, no relationship was observed between the 17-item Type-A-behavior score or subscales scores with blood pressure levels in The Woodlands population.^ Finally, it was important to determine whether subscales derived within The Woodlands population would differ from those described in Bogalusa and would relate differently to blood pressure among students in The Woodlands. The corresponding analyses showed that the subscales derived from the two studies were different, but in fact neither set of subscales was importantly related with blood pressure in The Woodlands population.^ The results of this study are largely consistent with those obtained by Hunter and Wolf in Bogalusa, who among the white population found only the factor "Eagerness-Energy" to be associated with fourth phase diastolic blood pressure among girls. Even this relationship which they observed was weak and inconsistent across sex-race groups and blood pressure components. This study does not support even this positive finding. In conclusion, evidence indicates that blood pressure is not associated with Type-A-behavior or its components as measured by the Hunter-Wolf Type-A-behavior scale among white adolescents. ^

Blood pressure and dietary factors in Mexican-Americans of Starr County, Texas

This study examined the cross-sectional associations between blood pressure, hypertension and dietary factors among 580 Mexican-American adults residing in Starr County, Texas. The data were collected as part of Gallbladder Disease Study between April, 1985 and December, 1986.^ Dietary intake was assessed for the month previous to the interview by means of a 38 food item quantified frequency questionnaire representing foods and mixed dishes commonly consumed in the community. From the dietary information intake of calcium, cholesterol, total kilocalories, and percent of kilocalories contributed by total fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, protein, carbohydrates were calculated. The effect of other factors associated with blood pressure, such as age, body mass index, body fat distribution, smoking, and drinking were controlled.^ Age was the most important predictor of both systolic and diastolic blood pressure and hypertension. For both males and females, systolic and diastolic blood pressure levels were consistently positively associated with body mass index but were not associated with waist hip ratio. However, a strong positive relationship between hypertension and waist hip ratio but not body mass index was observed.^ After controlling for age and body mass index it was noted that for males there were no significant associations between the dietary variables and systolic blood pressure. For diastolic blood pressure there were significant associations with percent fat, percent monounsaturated fatty acids, percent protein and percent carbohydrates.^ For females, there were significant associations between systolic blood pressure and percent protein, percent carbohydrates and cholesterol. There were no significant associations between dietary variables and diastolic blood pressure.^ After controlling for age and waist hip ratio significant associations between hypertension and percent fat, percent saturated fat, percent monounsaturated fatty acids, percent carbohydrate and percent protein were observed in males. Significant associations between hypertension and percent polyunsaturated fatty acids and percent protein were noted in females. ^

Low birthweight and the risk of developing subsequent high blood pressure and/or dyslipidemia in childhood

The association between birthweight and blood pressure (BP), and birthweight and serum lipid concentrations at age 7 through 11 years was examined in 1446 black and white children. The prevalence ratio (with 95% confidence interval) for being in the race-, sex- and age-specific upper decile of diastolic BP in children born with low birthweight (LBW, $<$2500 grams) versus children with birthweight $\geq$2500 grams was for black boys, 2.66 (1.24-5.70). In the other race-sex groups for diastolic BP, and in all race-sex groups for systolic BP this ratio did not differ from one. Among white boys with LBW, but not in the other race-sex groups, higher than expected percentages of subjects were in the highest decile group of triglyceride concentrations (0.01 $<$ p $<$ 0.05). The prevalence ratio was 2.42 (1.19-4.91). When prematures were excluded only more than expected white girls with LBW were in the highest decile group of triglyceride concentrations. The prevalence ratio was 3.23 (1.16-9.00). Prevalence ratios for triglyceride concentrations in black boys and girls, and for LDL/HDL-C ratio, cholesterol and VLDL-C concentrations in all race-sex groups were not different from one in analyses including and in those excluding prematures. Mean triglyceride concentrations stratified by tertiles of Quetelet Index, race and sex showed a strongly positive association between triglyceride concentrations and Quetelet Index, and in the upper tertile of the Quetelet Index an association between LBW and raised triglyceride concentrations. Multiple linear regression analyses showed that after adjusting for sex, race and age present Quetelet Index (p $<$ 0.001) is a much stronger predictor of systolic and diastolic BP, and also of LDL-C/HDL-C ratio and triglyceride concentrations in this age group than birthweight (p $>$ 0.05). Thus, an association between LBW and subsequent risk for elevated BP was confirmed for diastolic BP in black boys, but not for the other race-sex groups, and not for systolic BP in any group. This is the first study finding an association between LBW and elevated triglyceride concentrations in boys (white and black) and girls (white). A follow-up study to assess whether the findings can be confirmed at adult age is recommended. ^