Virtual reality for the treatment of postoperative pain after laparoscopic hysterectomy for benign Indications: A randomized controlled trial.

OBJECTIVE: The primary objective of this study was to determine if immediate post-operative use of virtual reality impacts pain scores or opioid consumption following hysterectomy. STUDY DESIGN: A randomized controlled trial was performed at a university associated tertiary referral hospital in the United States among patients undergoing laparoscopic hysterectomy for benign indications. Prior to surgery, participants were randomized to use a VR program versus routine care postoperatively in the post anesthesia care unit. Postoperative pain was measured using visual analogue scale, and morphine milligram equivalent to quantify narcotic usage. Patient satisfaction was assessed with a survey. A total of 15 patients were randomized to the virtual reality intervention and 15 to the standard care group. The test statistic was a one-sided T-test, with a significance level targeted of 0.05. Categorical variables were analyzed using chi-square analysis and t-test for continuous variables. Pain score differences between the virtual reality and standard care groups at each time assessment were compared using the Wilcoxon Rank Sum test. RESULTS: The use of virtual reality did not significantly affect pain scores or postoperative narcotics required; however, it did have a positive impact on the subject's perception of their postoperative course. No adverse events were reported. CONCLUSION: Although virtual reality use following hysterectomy did not improve pain scores or decrease narcotic usage, it was well received by patients.

Investigating racial disparities in quality-of-life years after pediatric hematopoietic stem cell transplant.

BACKGROUND: While racial disparities in the clinical outcomes of hematopoietic stem cell transplant (HSCT) patients have been explored, racial disparities in quality of life (QoL) during the re-adjustment phase after transplant are yet to be investigated in pediatric patients. The objective of this study was to examine the role of patient race in QoL at least 2 years after pediatric HSCT. PROCEDURE: We conducted a retrospective chart review of patients under 21 years of age at diagnosis who received an allogeneic transplant at our institution between January 2007 and December 2017. Patient QoL was assessed using the Pediatric Quality-of-Life Inventory Generic Score Scales (PedsQL TM 4.0) at least 2 years post transplant. Patient demographic, treatment, and transplant outcome data were obtained for subsequent analysis, where patient race was categorized as either Black, White, Hispanic, or Native American. RESULTS: Data were collected on 86 pediatric patients who underwent HSCT. Forty patients (46.5%) were non-Hispanic White, 29 (33.7%) Hispanic, 10 (11.6%) Black, and seven (8.1%) Native American. Where preliminary analyses indicated a difference in QoL by patient race, there were no significant differences in physical, emotional, social, and school functioning by patient race after adjusting for transplant characteristics (age at transplant, sex, diagnosis, donor type, and conditioning regimen) and determinants of socioeconomic status (insurance type, estimated household income). CONCLUSIONS: Pediatric patients had comparable QoL, regardless of race, at a median of 3 years after HSCT in our study cohort.

Ultrasound is superior to palpation for thyroid cancer detection in high-risk childhood cancer and BMT survivors.

PURPOSE: Thyroid cancer is a common subsequent malignant neoplasm in childhood cancer survivors (CCS). Patients who received radiotherapy (RT) to the head, neck, upper thorax, or total body irradiation (TBI) are considered to be at risk for subsequent thyroid cancer. Current Children's Oncology Group screening guidelines recommend annual neck palpation. Our objective was to determine if ultrasound (US) is more sensitive and specific than palpation to detect thyroid cancer in high-risk CCS and bone marrow transplant (BMT) survivors. METHODS: Electronic medical records of patients followed in a longitudinal survivorship clinic from January 1, 2010 to December 31, 2017 were reviewed. Inclusion criteria included history of RT to the head, neck, upper thorax, or TBI for primary therapy or preparation for BMT prior to the age of 20 years. RESULTS: Two hundred and twenty-five patients had documented palpation and 144 (64%) also had US evaluation. Mean radiation dose was 28.6 Gy. Sixteen of 225 patients (7.1%) developed a subsequent thyroid cancer at a mean of 9.7 years from the completion of RT. Sensitivity of US was 100% compared with 12.5% for palpation. US demonstrated higher accuracy, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.87 versus 0.56 for palpation (P < 0.0001). CONCLUSION: Routine screening with US was more sensitive than palpation for detection of subsequent thyroid cancer after high-risk RT in CCS and BMT survivors. Screening US may lead to earlier detection of thyroid cancer in this population. Earlier diagnosis has the potential to decrease operative complexity, and earlier definitive therapy reduces the likelihood of metastatic disease.

Surgical Equipment Price Awareness Amongst Obstetrician-Gynecologists.

BACKGROUND AND OBJECTIVES: Physicians typically have little information of surgical device pricing, although this trend has not been studied in the field of obstetrics and gynecology. We therefore aimed to determine how accurately obstetrician-gynecologists estimate surgical device prices, and to identify factors associated with accuracy. METHODS: An anonymous survey was emailed to all obstetrician-gynecologist attendings, fellows, and residents at 3 teaching hospitals in a single healthcare system in Arizona. We obtained demographic data, perceptions of price transparency and self-rated price knowledge, and price estimates for 31 surgical devices. RESULTS: After participants provided consent and demographics, they then estimated the purchasing price of 31 devices. We defined price accuracy as being within ±10% of the hospital's purchasing price. Fifty-six of the 170 (32.9%) invitees completed the survey and 48 (28.2%) provided price estimates. On average, participants identified 1.9 items correctly (6.1%; range, 0-7 items) out of 31 with no difference in accuracy based on seniority, surgical volume, physician reimbursement structure, nor subspecialty practice-focus. All (100%) respondents felt pricing should be transparent, and only 1.8% felt it is at least somewhat transparent. CONCLUSION: We found that price-estimate accuracy was very low and had no association with any of the demographics. Also notable was the perception that pricing is not transparent despite a unanimous desire for transparency. Although physicians reported a preference for using less-expensive surgical devices, we conclude that physicians are unequipped to make cost-conscious decisions highlighting a large potential for education.

ATF6α Activation Enhances Survival against Chemotherapy and Serves as a Prognostic Indicator in Osteosarcoma.

Patients with metastatic or relapsed/refractory osteosarcoma (OS) have a 5-year survival rate of <30%. This has remained unchanged over several decades. One of the factors contributing to lack of improvement in survival is the development of chemoresistance. Hence, elucidating and targeting the mechanisms that promote survival against chemotherapy and lead to chemoresistance is pivotal to improving outcomes for these patients. We identified that endoplasmic reticulum (ER) stress-activated transcription factor, ATF6α, is essential for the survival of OS cells against chemotherapy induced cell death. ATF6α cleavage and activity were enhanced in OS cells compared to normal osteoblasts and knockdown of ATF6α expression enhanced sensitivity of OS cells against chemotherapy induced cell death. This was in part due to increased Bax activation. Pharmacologic inhibition or knock-down of downstream targets of ATF6α, protein disulfide isomerases (PDI) and ERO1ß, a thiol oxidase that is involved in the re-oxidation of PDIs also independently induced pronounced killing of OS cells following chemotherapy. Analysis of primary tumors from OS patients reveals that patients with high levels of nuclear ATF6α: (1) also had increased expression of its downstream targets the chaperone BiP and enzyme PDI, (2) had a significant likelihood of developing metastasis at diagnosis, (3) had significantly poorer overall and progression free survival, and (4) had poorer response to chemotherapy. These findings suggest that targeting survival signaling by the ATF6α pathway in OS cells may favor eradication of refractory OS tumor cells and ATF6α could be a useful predictor for chemo-responsiveness and prognosis.

Selenium supplementation and insulin resistance in a randomized, clinical trial.

Objective: While controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic ß-cell function and insulin sensitivity. Research design and methods: In a subset of 400 individuals participating in a randomized, placebo-controlled trial of Se at 200 µg/day for colorectal adenomatous polyps, fasting plasma glucose and insulin were measured before randomization and within 6 months of completing intervention. Change in the homeostasis model assessment-ß cell function (HOMA2-%ß) and insulin sensitivity (HOMA2-%S) were compared between arms. A subgroup of 175 (79 Se and 96 placebo) participants underwent a modified oral glucose tolerance test (mOGTT) at the end of intervention and change in glucose values was assessed. Results: No statistically significant differences were observed for changes in HOMA2-%ß or HOMA2-%S between those who received Se compared with placebo. After a mean of 2.9 years on study, mean HOMA2-%ß values were 3.1±24.0 and 3.1±29.8 for the Se and placebo groups, respectively (p=0.99). For HOMA2-%S, the values were -0.5±223.2 and 80.9±1530.9 for the Se and placebo groups, respectively (p=1.00). Stratification by sex or age did not reveal any statistically significant effects on insulin sensitivity by treatment group. For mOGTT, mean baseline fasting blood glucose concentrations were significantly higher among participants in the placebo group compared with the Se group (96.6±14.6 and 92.3±12.0, respectively; p=0.04), a trend which remained through the 20 min assessment. Conclusions: These findings do not support a significant adverse effect of daily Se supplementation with 200 µg/day of selenized yeast on ß-cell function or insulin sensitivity as an explanation for previously reported associations between Se and T2D. Further clarification of longer term effects of Se is needed. Clinical trial registry: NIH Clinical Trials.gov number NCT00078897.

Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers.

Background. The level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6) is linked to an increased risk for cardiovascular diseases (CVD) and cancer. Methods. We recruited 154 current and former smokers between 40 and 80 years of age with 25 or more pack-years of smoking history to study the relationship between inflammatory markers (CRP and IL-6) and smoking status. Results. Our results show that male smokers had significantly higher levels of serum IL-6 compared to male former smokers. We did not find any gender specific differences for smoking and CRP levels but the IL-6 levels were slightly lower in females compared to males. Additionally, our results show that CRP is significantly associated with IL-6 regardless of smoking status. Modelling indicates that the significant predictors of CRP levels were biomarkers of the metabolic syndrome while the significant predictors of IL-6 levels were age and plasma triglycerides among former smokers and the numbers of smoked packs of cigarettes per year among smokers. Conclusions. In conclusion, our study showed that CRP levels were not associated with markers of smoking intensity. However, IL-6 levels were significantly associated with smoking especially among current smokers.

Brief questions highlight the need for melanoma information campaigns.

Melanoma awareness was briefly assessed at walk/runs held simultaneously in Philadelphia PA, Phoenix AZ, and Seattle WA. Of the participants, 75 % (1521) answered short questions during event registration. Among 1,036 respondents aged 14 years and older, 66 % reported knowing melanoma warning signs. Significantly more respondents with melanoma family history reported having a physician-administered skin exam and knowing warning signs. More than one third of walk/run participants reported no definitive melanoma warning sign knowledge. Self-reported melanoma awareness and detection indices were lowest among Phoenix participants; the event city with the greatest annual sun exposure. Educational efforts for melanoma awareness are critically needed. Selected results of this project were presented in a poster forum at the 2006 Congress for Epidemiology meeting held in Seattle, WA (June 2006).

Dose response of retinol and isotretinoin in the prevention of nonmelanoma skin cancer recurrence.

Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin vs. placebo on recurrence of nonmelanoma skin cancer in high-risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose-response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, whereas only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC, hazard ratios (HRs) for the first quartile were as follows: HR = 2.92, 95% confidence interval (CI) = 1.67-5.10 crude; HR = 1.95, 95% CI = 1.00-3.80 adjusted. For isotretinoin and SCC, HRs for the first quartile were as follows: HR = 2.38, 95% CI = 1.35-4.19 crude; HR = 1.69, 95% CI = 0.87-3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose.

Chemoprevention of human actinic keratoses by topical DL-alpha-tocopherol.

Prior research shows that topical application of free, nonfatty acid-conjugated vitamin E (DL-alpha-tocopherol) prevents skin cancer in mice, as well as immunosuppression induced by UVB radiation. This study investigated the chemopreventive potential of DL-alpha-tocopherol in humans through monitoring surrogate end point biomarkers in sun-damaged skin. Contralateral arms of healthy human volunteers with actinic keratoses (AK) were randomly assigned to receive either 12.5% DL-alpha-tocopherol or placebo in a crème base for 6 months. Changes in number of AKs, levels of p53 protein expression, proliferating cell nuclear antigen, and polyamines were assessed along with skin and systemic vitamin E levels. Following treatment, plasma concentration levels of DL-alpha-tocopherol were unchanged, but skin levels were highly elevated (P < 0.001). Levels of p53 and proliferating cell nuclear antigen did not change significantly, whereas number of AKs declined insignificantly in both placebo and treatment arms. Regression models showed significant decreases in putrescine, spermidine, spermine, and total polyamine concentrations following treatment. Topically applied DL-alpha-tocopherol was substantially absorbed in skin, but the 6-month application did not significantly reduce numbers of preexisting AKs on moderately to severely sun-damaged forearms. Increases in polyamine synthesis are expected during tumor initiation and promotion; conversely, the significant reductions in polyamine levels resulting from the topical DL-alpha-tocopherol application are consistent with reductions in tumorigenesis potential. Topical tocopherol did not normalize established sun-induced lesions, but DL-alpha-tocopherol-induced reductions in polyamine metabolism are consistent with the inhibition of skin squamous cell carcinogenesis as seen in previous human trials and animal models.

Effect of non-steroidal anti-inflammatory drugs on non-melanoma skin cancer incidence in the SKICAP-AK trial.

Recent studies link the prostaglandin metabolic pathway to skin carcinogenesis expanding possibilities that cyclooxygenase (COX) inhibitors may be utilized in non-melanoma skin cancer (NMSC) chemoprevention. Using data from a study of the efficacy of retinol supplementation on incidence of NMSC, we sought to determine the role of non-steroidal anti-inflammatory drugs (NSAIDs) in NMSC development. Cox proportional hazards models describe the relationship between NSAID use and time to first squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) among participants categorized by use pattern: continuous users (use for length of study duration), new users (use for less than study duration), and non-users. For SCC and BCC, there was a statistically significant protective effect for participants who reported use for less than the study duration (HR = 0.49, 95%CI 0.28-0.87 and HR = 0.43, 95%CI 0.25-0.73, respectively). Categorical examination of NSAIDs (aspirin (ASA) vs. non-ASA NSAIDs) showed significant effects for BCC among those using non-ASA NSAIDs for less than the study duration (HR = 0.33, 95%CI 0.13-0.80). For SCC and BCC, NSAID use of shorter duration and potentially more recent, was more protective than longer duration of use. These results are counter to the idea that longer duration of NSAID use is more protective. Additional investigations are needed into the role NSAIDs play in the chemoprevention of NMSC.

Vitamin D insufficiency in southern Arizona.

BACKGROUND: Vitamin D deficiency or insufficiency has been observed among populations in the northern United States. However, data on the prevalence of vitamin D deficiency in areas of high sun exposure, such as Arizona, are limited. OBJECTIVE: The purpose of this study was to analyze serum 25-hydroxyvitamin D [25(OH)D] concentrations in residents of southern Arizona and to evaluate predictors of 25(OH)D in this population. DESIGN: Cross-sectional analyses of serum from participants in a colorectal adenoma prevention study were conducted to determine rates of vitamin D deficiency. Participants were categorized into 4 groups on the basis of serum 25(OH)D concentrations: <10.0 ng/mL, > or =10.0 ng/mL and <20.0 ng/mL, > or =20.0 ng/mL and <30.0 ng/mL, and > or =30.0 ng/mL. RESULTS: The mean serum 25(OH)D concentration for the total population was 26.1 +/- 9.1 ng/mL. Of 637 participants, 22.3% had 25(OH)D concentrations >30 ng/mL, 25.4% had concentrations <20 ng/mL, and 2.0% had concentrations <10 ng/mL. Blacks (55.5%) and Hispanics (37.6%) were more likely to have deficient 25(OH)D concentrations (<20 ng/mL) than were non-Hispanic whites (22.7%). Sun exposure had a greater effect on 25(OH)D in whites than in blacks and Hispanics, whereas BMI appeared to be more important in the latter groups. CONCLUSION: Despite residing in a region with high chronic sun exposure, adults in southern Arizona are commonly deficient in vitamin D deficiency, particularly blacks and Hispanics.

Fatty acid composition of red blood cell membranes and risk of squamous cell carcinoma of the skin.

Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis that lower levels of arachidonic acid in RBC membranes were associated with decreased risk of skin squamous cell carcinoma (SCC; n = 335 SCC cases and 321 controls). Extracted and esterified RBC fatty acids were analyzed using capillary gas chromatography. Individual peaks for 14 fatty acids were measured as a percentage of total fatty acids. Logistic regression was used to estimate odds ratios (OR), adjusting for SCC risk factors (age, gender, actinic keratosis history, freckling, and tanning ability). Increased levels of arachidonic acid in RBC membranes were associated with increased risk of SCC [odds ratio (OR), 1.08 per mg/100 mL change; 95% confidence interval (95% CI), 1.02-1.15] and this association remained when controls with actinic keratosis precursor lesions were excluded. SCC risk was highest among the upper quartile of arachidonic acid (OR, 2.38; 95% CI, 1.37-4.12). In contrast, increasing proportions of palmitic acid (OR, 0.94; 95% CI, 0.89-1.00) and palmitoleicacid (OR, 0.49; 95% CI, 0.30-0.81) were associated with reduced SCC risk. More studies are needed to elucidate the function of RBC fatty acids so that recommendations can be made to alter the human diet for cancer prevention.

Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate.

Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.

Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin.

PURPOSE: Previously, we reported the results of a Phase III, placebo-controlled trial in 2297 randomized participants with moderately severe actinic keratoses wherein 25000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50000 or 75000 IU/day would be both safe and more efficacious in skin cancer chemoprevention. EXPERIMENTAL DESIGN: One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25000, 50000, or 75000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin. RESULTS: There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25000 IU/day, 50000 IU/day, and 75000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25000 and 50000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor alpha, retinoic acid receptor beta, and retinoid X receptor alpha at the 50000 IU/day vitamin A dose. CONCLUSIONS: The vitamin A doses of 50000 and 75000 IU/day for 1 year proved safe and equally more efficacious than the 25000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.

Factors associated with dietary supplement use among healthy adults of five ethnicities: the Multiethnic Cohort Study.

Participants of the Multiethnic Cohort Study in Hawaii and Los Angeles, California, a representative sample of African-American, Native Hawaiian, Latino, Japanese-American, and White adults, completed a baseline questionnaire in 1993-1996 assessing dietary supplement use during the past year as well as demographic, dietary, and other lifestyle factors. Factors associated with supplement use were examined among those who reported an absence of chronic disease (n = 100,196). Use of any of eight supplements at least once per week during the past year ranged from 44% among Hawaiian men to 75% among Japanese-American and White women. Multivitamins were the most frequently reported supplement; 48% of the men and 56% of the women reported regular use. Dietary supplement use was high across all ethnic groups, although levels and length of regular use varied. In all gender-specific ethnic groups, supplement use tended to increase with age, education, physical activity, fruit intake, and dietary fiber intake and to decrease with obesity, smoking, and dietary fat intake. Participants whose lifestyles were healthier were more likely to use dietary supplements. Therefore, it may be difficult to separate the effects of supplement use from other lifestyle factors when studying disease etiology.