Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is effective and cost-effective, but the potential national impact of widespread screening is uncertain. It is controversial whether screening colonoscopy can be offered widely and how emerging tests may impact health services demand. Our aim was to produce integrated, comprehensive estimates of the impact of widespread screening on national clinical and economic outcomes and health services demand. METHODS: We used a Markov model and census data to estimate the national consequences of screening 75% of the US population with conventional and emerging strategies. RESULTS: Screening decreased CRC incidence by 17%-54% to as few as 66,000 cases per year and CRC mortality by 28%-60% to as few as 23,000 deaths per year. With no screening, total annual national CRC-related expenditures were 8.4 US billion dollars. With screening, expenditures for CRC care decreased by 1.5-4.4 US billion dollars but total expenditures increased to 9.2-15.4 US billion dollars. Screening colonoscopy every 10 years required 8.1 million colonoscopies per year including surveillance, with other strategies requiring 17%-58% as many colonoscopies. With improved screening uptake, total colonoscopy demand increased in general, even assuming substantial use of virtual colonoscopy. CONCLUSIONS: Despite savings in CRC care, widespread screening is unlikely to be cost saving and may increase national expenditures by 0.8-2.8 US billion dollars per year with conventional tests. The current national endoscopic capacity, as recently estimated, may be adequate to support widespread use of screening colonoscopy in the steady state. The impact of emerging tests on colonoscopy demand will depend on the extent to which they replace screening colonoscopy or increase screening uptake in the population.     

Comparison of total-breath and single-breath diffusing capacity in healthy volunteers and COPD patients

BACKGROUND: The measurement of single-breath diffusing capacity (Dlco(SB)) assumes that diffusing capacity per liter of alveolar volume (Dlco/VA) determined in a 750-mL gas sample represents the diffusing capacity (Dlco) of the entire lung. Fast-responding gas analyzers provide the opportunity to verify this assumption because of the possibility to measure CO and CH(4) fractions continuously throughout the entire expiration. Continuous gas sampling provides more information per measurement, but this information cannot be expressed in the traditional parameters. Our goals were to find new parameters to express the extra information of the continuous gas sampling, and to compare these new parameters with the traditional parameters. METHODS: We compared a new method to determine Dlco with the traditional method in 62 healthy volunteers and 26 COPD patients. Traditionally, Dlco(SB) is determined by multiplying Dlco/VA with alveolar volume, both calculated from gas concentrations in a 750-mL gas sample. The new method calculates total-breath Dlco (Dlco(TB)) by integration of Dlco/VA against exhaled volume. RESULTS: In healthy volunteers, Dlco/VA shows a slight upward slope during exhalation, while in COPD patients Dlco/VA shows a horizontal line. Total-breath total lung capacity (TLC) is larger than single-breath TLC both in healthy volunteers and in COPD patients, leading to a Dlco(TB) that is significantly larger than Dlco(SB) in both groups (p < 0.001). CONCLUSION: The assumption that a 750-mL gas sample represents the entire lung seems to be correct for Dlco/VA but not for the CH(4) fraction in case of ventilation inhomogeneity.     

Lung function accurately predicts hypercapnia in patients with Duchenne muscular dystrophy

BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), implementation of mechanical ventilation depends on sleep investigation and measurement of CO2 tension. The objective of this cross-sectional study was to determine which noninvasive lung function parameter best predicts nocturnal hypercapnia and diurnal hypercapnia in these patients. METHODS: According to transcutaneous CO2 (TcCO2) measurement, 114 DMD patients were classified into three groups: nocturnal hypercapnia (n = 38) [group N], diurnal hypercapnia (n = 39), despite nocturnal ventilation (group D), and 24-h normocapnia and spontaneous breathing (n = 37) [group S] as control. TcCO2 tension and lung function variables included vital capacity (VC) and maximal inspiratory pressure (MIP), and breathing pattern variables included tidal volume (Vt) and respiratory rate (RR), measured at the time of group inclusion. The rapid and shallow breathing index (RSBI [RR/Vt]) and Vt/VC ratio were calculated. Areas under the curve from the receiver operating characteristic (ROC) were calculated for those parameters. RESULTS: Compared to group S, lung function was significantly worse in group N and group D. VC, RR, and RSBI distinguished group S from group N by ROC comparison. Cut-off values of VC < or = 680 mL (ROC, 0.968), MIP < or = 22 cm H2O (ROC, 0.928), and Vt/VC > 0.33 (ROC, 0.923) accurately discriminated group D from group N, but RSBI, RR, and Vt did not. CONCLUSIONS: Lung function is useful to predict nocturnal hypercapnia in patients with DMD. Moreover, VC < 680 mL is very sensitive to predict daytime hypercapnia.     

Influence of the NR3A subunit on NMDA receptor functions

Various combinations of subunits assemble to form the NMDA-type glutamate receptor (NMDAR), generating diversity in its functions. Here we review roles of the unique NMDAR subunit, NR3A, which acts in a dominant-negative manner to suppress receptor activity. NR3A-containing NMDARs display striking regional and temporal expression specificity, and, unlike most other NMDAR subtypes, they have a low conductance, are only modestly permeable to Ca²⁺, and pass current at hyperpolarized potentials in the presence of magnesium. While glutamate activates triheteromeric NMDARs composed of NR1/NR2/NR3A subunits, glycine is sufficient to activate diheteromeric NR1/NR3A-containing receptors. NR3A dysfunction may contribute to neurological disorders involving NMDARs, and the subunit offers an attractive therapeutic target given its distinct pharmacological and structural properties.     

Correlation between cardiac biomarkers and right ventricular enlargement on chest CT in non massive pulmonary embolism

BACKGROUND: Troponin I (cTnI), myoglobin, heart-type fatty acid binding protein (H-FABP), and natriuretic peptides (BNP, NTproBNP) were all reported to be elevated in patients with pulmonary embolism (PE). METHODS: To assess the correlation between the aforementioned markers and helical computed tomography (hCT) right ventricular dysfunction (RVD) in non massive PE, we performed this prospective pilot study on 50 patients. RESULTS: Patients with RVD had significant higher natriuretic peptides prevalence than cardiomyocytes damage-related markers (48% vs 20%, P=0.006). Significant prevalence differences were observed only for natriuretic peptides when patients with RVD and those without were compared (74% vs 33% for NT-pro BNP, P=0.005 and 65% vs 22% for BNP, P=0.003). Patients with RVD had significant higher biomarkers median plasmatic values than those without (BNP: 170 vs 36 pg/ml, P=0.0027; NT-proBNP: 1369 vs 170.7 pg/ml, P=0.0024; cTnI: 0.032 vs 0 ng/ml, P=0.0034; H-FABP: 4.32 vs 2.23 ng/ml, P=0.0032; myoglobin: 36.7 vs 28.2 ng/ml, P=0.03). Significant correlations were only obtained between RV/LV index and plasmatic natriuretic peptides (NT-proBNP: r=0.36, P=0.009; BNP r=0.28; P=0.047). CONCLUSIONS: Natriuretic peptides prevalence elevation and median values are significantly higher when RVD is present and significantly correlate with hCT RVD.     

The new ATS/ERS guidelines for assessing the spirometric severity of restrictive lung disease differ from previous standards

BACKGROUND AND OBJECTIVES: The ATS/ERS Task Force on Lung Function Testing recently proposed guidelines for the interpretation of pulmonary function tests and suggested that a reduction in FEV(1) be used for categorizing both obstructive and restrictive abnormalities. This changes the severity stratification algorithm of restrictive patterns diagnosed by spirometry, that are currently categorized based on reduction in VC. This study examined the level of agreement between these two categorization schemes. METHODS: Spirometry records of 2,527 adult patients evaluated over 1 year were retrieved; 361 of these patients showed a restrictive pattern. Severity of airway restriction was separately assessed in these patients using the indicative schemes provided in the new ATS/ERS and the earlier ATS guidelines. RESULTS: There were 212 (58.7%) patients with a restrictive pattern who had identical severity categorization using both guidelines. In most instances of discordance, the severity categorization differed only by a single stratum. Of 149 discordant results, 91 (60.1%) were placed in a better category, and 58 (39.9%) in a worse category, when using the new ATS/ERS recommendations. Overall weighted kappa estimate for agreement between the two schemes of categorization was 0.649. CONCLUSION: Based on spirometry results, the level of severity of restriction cannot be described interchangeably between the old and new guidelines for all patients. The new guidelines tend to give lower severity scores for restrictive lung diseases in up to 25% of patients.     

Severity of asthma in skin test-negative and skin test-positive patients

The standardized records of 144 asthmatic patients have been analyzed to determine whether the severity of their condition was correlated with the presence or absence of positive intradermal skin test reactions to a panel of seven allergen extracts (dust, feathers, Alternaria, Hormodendrum, mixed tree pollen, mixed grass pollen, and ragweed pollen). The skin tests were totally negative in 71 of the subjects, whereas in 73 subjects there was a strongly positive response to two or more allergens. The skin test-negative patients were older than the skin test-positive ones and had a shorter duration as well as a later onset of asthma. Also, they had lower serum-IgE levels and a lower frequency of a family history of atopic disease. Moreover, the skin test-negative group lost more time from their normal activities, required more visits to their doctor as a result of asthma, and were more frequently treated with oral corticosteroids. They additionally had greater air trapping on pulmonary function tests. However, when the groups were adjusted for the discordance in their age and duration of asthma, they tended to converge in the level of the variables that described the severity of their asthma. Thus the severity of asthma was found to be relatively similar in skin test-negative and skin test-positive patients.     

The immediate effects of cortisol on pulmonary function in normals and asthmatics

We investigated short-term effects of corticosteroids on airway caliber, measured by spirometry and body plethysmography, over a period of 6 hr after an intravenous bolus of cortisol (8 mg/kg) or saline placebo was administered in a double-blind crossover format comparing 10 normal and nine asymptomatic unmedicated asthmatics. After 6 hrs isoproterenol (240 μg) was administered to compare the effects of cortisol with a β-agonist bronchodilator. Serum cortisol levels remained >100 μg/dl after cortisol and normal after placebo. Cortisol had no effect on pulmonary function except for a trend of improved flows and decreasing ratios of residual volume to total lung capacity in asthmatics that was not significant at 6 hr. Isoproterenol resulted in immediate improvement in specific conductance and flows in both groups; no interaction with cortisol was seen. We conclude that cortisol had no short-term effect on airway caliber in normals, at best a slowly evolving effect in asymptomatic unmedicated asthmatics, and no interaction with the bronchodilator effects of a maximal dose of isoproterenol in these groups.     

对比分析显微镜与腹腔镜下精索静脉结扎术治疗精索静脉曲张的临床效果

目的:对比和分析显微镜与腹腔镜下精索静脉结扎术治疗精索静脉曲张的临床效果。方法:选择从2015年5月至2016年4月在我院接受治疗的120例精索静脉曲张患者,随机分成甲组和乙组,每组各60例。甲组行显微镜下精索静脉结扎术,乙组行腹腔镜下精索静脉结扎术。观察和对比两组的手术时间、住院时间、阴囊水肿发生率及精液参数。结果:甲组手术时间、阴囊水肿发生率均显著低于乙组,比较差异具有统计学意义(P0.05)。住院时间两组无比较差异(P0.05)。与术前相比,两组术后3个月精液参数明显改善,比较差异具有统计学意义(P0.05)。组间比较,术前及术后3个月精液参数均无显著差异(P0.05)。结论:在精索静脉曲张的治疗中,显微镜下精索静脉结扎术手术时间短、并发症少,且能达到同样的治疗效果,优于腹腔镜下精索静脉结扎术。     

Regulation of hemodynamics in major salivary glands by parasympathetic vasodilation

Background

Since salivary fluid is created from blood plasma, hemodynamics in the salivary glands play an important role in the production of saliva. Trigeminal sensory input induces both salivary secretion and reflex parasympathetic vasodilation in salivary glands. This glandular vasodilation is thought to be important for the regulation of glandular hemodynamics due to the rapidity with which blood flow is increased. This review article summarizes recent research on the involvement of parasympathetic vasodilation in regulating hemodynamics in the salivary gland.