Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion.

Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].

Parent and child perceptions of gambling promotions in Australian sport.

Gambling is recognized as a significant public health problem. However, there is little research exploring community attitudes towards gambling and the development of advocacy initiatives. Engaging adults and young people in advocacy efforts is recognized as being beneficial to the successful implementation of harm prevention and reduction strategies. This study explored the attitudes of young people and their parents towards the alignment of gambling with sport, and the strategies they perceive could be used to prevent and reduce gambling related harm. Using a Constructivist Grounded Theory approach, 30 family groups from Melbourne, Australia participated in semi-structured interviews. Parents and young people were asked about gambling and its promotion, alignment with sporting codes, the potential impact on young people and strategies that may prevent or reduce gambling harm. Thematic analysis was undertaken to interpret the data. The sample comprised 29 parents, one grandparent and 48 young people. Themes emerging from the data related to the use of imagery and appeal strategies in advertisements, the normalization of betting in advertisements and the alignment of betting with sport. Parents and young people also identified a number of potential gambling harm prevention and reduction initiatives. Parents and young people were able to describe a range of strategies used by gambling companies to promote their products, understand the potential impact of these strategies, and recommend strategies to reduce harm. Given this level of understanding there is clearly an opportunity to engage young people and stakeholders in advocacy initiatives aimed at reducing and preventing gambling harm.

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

PURPOSE: Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). METHODS: Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. RESULTS: Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67). CONCLUSION: More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

How Many Lymph Nodes Are Enough? Assessing the Adequacy of Lymph Node Yield for Papillary Thyroid Cancer.

PURPOSE: Patients who undergo surgery for papillary thyroid cancer with only a limited lymph node examination are thought to be at risk for potentially harboring occult disease. However, this risk has not been objectively quantified and may have implications for subsequent management and surveillance. METHODS: Data from the National Cancer Database (1998 to 2012) were used to characterize the distribution of nodal positivity of adult patients diagnosed with localized ≥ 1-cm papillary thyroid cancer who underwent thyroidectomy with one or more lymph nodes (LNs) examined. A ß-binomial distribution was used to estimate the probability of occult nodal disease as a function of total number of LNs examined and pathologic tumor stage. RESULTS: A total of 78,724 patients met study criteria; 38,653 patients had node-positive disease. The probability of falsely identifying a patient as node negative was estimated to be 53% for patients with a single node examined and decreased to less than 10% when more than six LNs were examined. To rule out occult nodal disease with 90% confidence, six, nine, and 18 nodes would need to be examined for patients with T1b, T2, and T3 disease, respectively. Sensitivity analyses limited to patients likely undergoing prophylactic central neck dissection resulted in three, four, and eight nodes needed to provide comparable adequacy of LN evaluation. CONCLUSION: To our knowledge, our study provides the first empirically based estimates of occult nodal disease risk in patients after surgery for papillary thyroid cancer as a function of primary tumor stage and number of LNs examined. Our estimates provide an objective guideline for evaluating adequacy of LN yield for surgeons and pathologists in the treatment of papillary thyroid cancer, and especially intermediate-risk disease, for which use of adjuvant radioactive iodine and surveillance intensity are not currently standardized.

Lymphovascular invasion is associated with survival for papillary thyroid cancer.

Data are limited regarding the association between tumor lymphovascular invasion and survival for patients with papillary thyroid cancer (PTC). This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing thyroid resection. The National Cancer Data Base (2010-2011) was queried for patients with PTC who underwent total thyroidectomy or lobectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical and pathological features were evaluated for all patients. A Cox proportional hazards model was utilized to identify factors associated with survival. Results show that 45,415 patients met inclusion criteria; 11.6% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8cm vs 1.5cm, P<0.01), metastatic lymph nodes (74.1% vs 32.5%, P<0.01), and distant metastases (3.0% vs 0.5%, P<0.01). They were also more likely to receive radioactive iodine (69.3% vs 44.9%, P<0.01). Unadjusted overall 5-year survival was lower for patients who had tumors with lymphovascular invasion (86.6% vs 94.5%) (log-rank P<0.01). After adjustment, increasing patient age (HR=1.06, P<0.01), male gender (HR=1.68, P<0.01), presence of metastatic lymph nodes (HR=1.77, P<0.01), distant metastases (HR=3.49, P<0.01), and lymphovascular invasion (HR=1.88, P<0.01) were associated with compromised survival. For patients with lymphovascular invasion, treatment with RAI was associated with reduced mortality (HR=0.43, P<0.01). The presence of lymphovascular invasion among patients with PTC is independently associated with compromised survival. Patients who have PTC with lymphovascular invasion should be considered higher risk, and adjuvant RAI should be more strongly considered.

Therapeutic bronchoscopy improves spirometry, quality of life, and survival in central airway obstruction.

BACKGROUND: Central airway obstruction (CAO) occurs in patients with primary or metastatic lung malignancy and nonmalignant pulmonary disorders and results in significant adverse effects on respiratory function and quality of life. OBJECTIVES: The objective of this study was to assess the effect of therapeutic bronchoscopic interventions on spirometry, dyspnea, quality of life, and survival in patients with CAO. METHODS: We prospectively studied patients who underwent therapeutic rigid bronchoscopy for CAO. Spirometry, San Diego Shortness of Breath questionnaire (SOBQ), and SF-36 questionnaire responses were obtained before the procedure and at follow-up 6-8 weeks after the procedure. RESULTS: Fifty-three patients (24 malignant and 29 nonmalignant CAO), who underwent successful rigid bronchoscopic intervention, were enrolled. Airway stent placement and various debulking techniques including mechanical debridement and heat therapy were used. After bronchoscopy, there was a significant increase in forced vital capacity (2.2 ± 0.91 l before, 2.7 ± 0.80 l after, p = 0.009) and forced expiratory volume at 1 s (1.4 ± 0.60 l before, 1.8 ± 0.67 l after, p = 0.002). The SOBQ score improved from 55.8 ± 30.1 before the procedure to 37.9 ± 27.25 after the procedure (p = 0.002). In the SF-36, there was an improvement in almost all domains, with statistically significant improvement seen in several domains. Benefits were seen independent of the etiology of CAO, site of intervention or stent placement. The patients with malignant CAO, in whom airway patency could not be achieved, had a poor survival. CONCLUSIONS: Alleviation of CAO with therapeutic rigid bronchoscopy results in improvement in spirometry, shortness of breath, quality of life, and survival.

Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer.

CONTEXT: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. OBJECTIVE: The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. DESIGN/SETTING: Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. PATIENTS: Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. MAIN OUTCOME MEASURES: Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. RESULTS: A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). CONCLUSION: This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.

Parent and child interactions with two contrasting anti-obesity advertising campaigns: a qualitative analysis.

BACKGROUND: Social marketing has been proposed as a framework that may be effectively used to encourage behaviour change relating to obesity. Social advertising (or mass media campaigning) is the most commonly used social marketing strategy to address the issue of obesity. While social advertising has the potential to effectively communicate information about obesity, some argue that the current framing and delivery of these campaigns are ineffective, and may cause more harm than good. METHODS: We used a qualitative advertising reception study. 150 family groups (comprised of 159 parents and 184 children) were shown two Australian government anti-obesity advertisements: Measure Up (focused on problems associated with obesity) and Swap It (focused on solutions for obesity). Families were engaged in a discussion about the visual appeals, verbal messages and their perceptions about the impact of the advertisements on behavioural change. Open coding techniques and a constant comparative method of analysis was used to interpret the data. RESULTS: Many parents had strong personal resonance with the visual imagery within the campaigns. While Swap It had strong 'likeability' with children, many children believed that the messages about overweight and obesity were less personally relevant because they did not perceive themselves to be overweight. The content and delivery style of the verbal messages (the serious risk focused message in Measure Up compared to the upbeat, fun practical message in Swap It) influenced how different audiences (parents and children) interpreted the information that was presented. Parents assimilated practical and instructive messages, while children assimilated messages about weight loss and weight gain. Parents and children recognised that the campaigns were asking individuals to take personal responsibility for their weight status, and were at times critical that the campaigns did not tackle the broader issues associated with the causes and consequences of obesity. The lack of practical tools to encourage behavioural change was a key barrier for obese parents. CONCLUSIONS: Well-funded, targeted social marketing campaigns will play an important role in the prevention and management of obesity. It is important that these campaigns are comprehensively evaluated and are backed up with structural supports to enable and encourage population subgroups to act upon messages.

Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.