Composition of gut microbiota and its association with body mass index and lifestyle factors in a cohort of 7-18 years old children from the American Gut Project.

BACKGROUND: The association between the gut microbiota and obesity in young children and adolescents is not fully studied. OBJECTIVES: This study investigated the associations between the gut microbiota and body mass index (BMI) level (underweight, normal, overweight, obese) and lifestyles (diet type and exercise frequency), controlling for demographic and clinical factors among children aged 7-18 years. METHODS: A cohort study was conducted on 267 children aged 7-18 years from the American Gut Project. 16S rRNA sequences were analysed by QIIME 2™. Composition of gut microbiota and its associations with BMI level, weight change and lifestyles were analysed using linear decomposition model. RESULTS: Significant factors affecting the gut microbiota were BMI level (p = 0.009), exercise frequency (p = 0.003) and diet type (p = 0.01), controlling for age, sex and use of antibiotics and probiotics. More bacterial operational taxonomic units (OTUs) were associated with BMI level (120 OTUs) and diet type (122 OTUs) than exercise frequency (67 OTUs). Actinobacteria phylum had significantly depleted OTUs for BMI level, diet type and exercise frequency; Proteobacteria phylum had significantly enriched OTUs for higher BMI level and Firmicutes phylum had significantly enriched OTUs for more frequent exercise. CONCLUSIONS: Significant associations were found between the gut microbiota composition and BMI level and lifestyles controlling for demographic and clinical factors in children aged 7-18 years.

Impact of sildenafil on marital and sexual adjustment in patients and their wives after radiotherapy and short-term androgen suppression for prostate cancer: analysis of RTOG 0215.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) 0215 investigated the efficacy of sildenafil in improving erectile dysfunction following radiotherapy and neoadjuvant/concurrent androgen deprivation therapy among prostate cancer patients and found a significant improvement on drug but only in 21% of study participants. This paper reports on a secondary aim to investigate the effect of sildenafil on overall sexual and marital adjustment among both patients and their wives. METHODS: RTOG 0215 was a placebo-controlled, double-blind, crossover trial of sildenafil. Participation of wives was optional. Twenty-four married heterosexual couples (33% of heterosexual couples in study) completed the Sexual Adjustment Questionnaire and Locke's Marital Adjustment Test. Treatment differences in mean change scores were evaluated by paired t-tests, and the proportion of patients achieving a clinically meaningful change was evaluated using chi-square tests. Spearman's correlation coefficients were used to determine the association of adjustment between patients and wives. RESULTS: There was no significant change in either sexual or marital adjustment for patients. For wives, there was a trend for improvement in sexual adjustment but no significant change in marital adjustment. Change in marital adjustment between patients and wives was weakly related (r(s) = 0.15, p = 0.48), and for sexual adjustment, there was a moderate, but nonsignificant relationship (r(s) = 0.40, p = 0.09). CONCLUSIONS: Larger studies are warranted to further examine possible differences in sexual experiences and treatment needs between prostate cancer patients and their wives, as well as to assess predictors of sildenafil response.

Patterns of missing mini mental status exam (MMSE) in radiation therapy oncology group (RTOG) brain cancer trials.

The Mini Mental Status Exam (MMSE) instrument has been commonly used in the Radiation Therapy Oncology Group (RTOG) to assess mental status in brain cancer patients. Evaluating patient factors in relation to patterns of incomplete MMSE assessments can provide insight into predictors of missingness and optimal MMSE collection schedules in brain cancer clinical trials. This study examined eight RTOG brain cancer trials with ten treatment arms and 1,957 eligible patients. Patient data compliance patterns were categorized as: (1) evaluated at all time points (Complete), (2) not evaluated from a given time point or any subsequent time points but evaluated at all the previous time points (Monotone drop-out), (3) not evaluated at any time point (All missing), and (4) all other patterns (Mixed). Patient characteristics and reasons for missingness were summarized and compared among the missing pattern groups. Baseline MMSE scores and change scores after radiation therapy (RT) were compared between these groups, adjusting for differences in other characteristics. There were significant differences in frequency of missing patterns by age, treatment type, education, and Zubrod performance status (ZPS; P < 0.001). Ninety-two percent of patients were evaluated at least once: seven percent of patients were complete pattern, 49% were Monotone pattern, and 36% were mixed pattern. Patients who received RT only regimens were evaluated at a higher rate than patients who received RT + other treatments (49-64% vs. 27-45%). Institutional error and request to not be contacted were the most frequent known reasons for missing data, but most often, reasons for missing MMSE was unspecified. Differences in baseline mean MMSE scores by missing pattern (Complete, Monotone dropout, Mixed) were statistically significant (P < 0.001) but differences were small (<1.5 points) and significance did not persist after adjustment for age, ZPS, and other factors related to missingness. Post-RT change scores did not differ significantly by missing pattern. While baseline and change scores did not differ widely by missing pattern for available measurements, incomplete data was common and of unknown reason, and has potential to substantially bias conclusions. Higher compliance rates may be achievable by addressing institutional compliance with assessment schedules and patient refusal issues, and further exploration of how educational and health status barriers influence compliance with MMSE and other tools used in modern neurocognitive batteries.

Body shape in American and British adults: between-country and inter-ethnic comparisons.

BACKGROUND: Recent studies indicate differences between British and American white adults, and between income and ethnic groups within the United States, in the population distribution of lifestyle diseases. Differential prevalence of obesity has been suggested as a contributing factor; however, the conventional approach to categorizing obesity, body mass index, is confounded by ethnic variability in physique. OBJECTIVE: To compare indices of shape between white British and American adults, and between white, African and Hispanic American adults. DESIGN: Analysis of two large National Sizing Surveys, using identical study design and three-dimensional (3D) body-scanning instrumentation, on adults aged 17+ years from the UK (3907M and 4710F white), and from the USA (1744M and 3329F white, 709M and 1106F African and 639M and 839F Hispanic). OUTCOME MEASURES: Weight, height, body circumferences. RESULTS: In the United States, socio-economic status was associated with increasing height and decreasing waist girth in white and Hispanic, but not African Americans. Compared to white British, white Americans had larger weight and girths, especially waist girth in men. Relative to white Americans, African Americans had smaller relative waist girth, but larger thigh girth, whereas Hispanic Americans had larger relative waist girth. CONCLUSIONS: Body shape of white American adults differs from that of their UK counterparts. Within Americans, ethnic differences in body shape closely track reported differences in prevalence of the metabolic syndrome, implicating variability in central abdominal fat as a key contributing factor. 3D photonic scanning offers a novel approach for categorizing risk of the metabolic syndrome and monitoring treatment success.

Measurement of vaginal length: Reliability of the vaginal sound--a Gynecologic Oncology Group study.

A decrease in vaginal length associated with treatments for gynecological malignancies, particularly pelvic radiotherapy, negatively impacts sexuality. Research into this important problem has been hampered by a lack of instrumentation to measure vaginal length. The Gynecologic Oncology Group recently evaluated the reliability of an instrument, the "vaginal sound," designed to measure vaginal length. Eighty-eight physicians and nurses attended a training session in the use of the vaginal sound that included a clinical practicum with live models. Reliability was assessed at the time of the practicum. The instrument performed well, with vaginal lengths in models without cancer in the upper range of normal as documented by Masters and Johnson. The vaginal sound also appeared to be sensitive to hypothesized changes in vaginal length. Interrater reliability was high with intraclass correlation coefficients of 0.88 among instructors and 0.76 among trainees. In conclusion, the vaginal sound is a simple, yet reproducible measure and adds methodologic rigor to studies of vaginal length.

Differences in ornithine decarboxylase and androgen receptor allele frequencies among ethnic groups.

Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined ODC allele frequencies and distribution of AR alleles in American Caucasians, African-Americans, Hispanics, Europeans, and Africans. The frequency of the ODC A allele varied from 0.183 (Hispanics, Europeans) to 0.415 (Africans) with American Caucasian and African-Americans having intermediate values. The mean number of CAG repeats in the AR gene varied from 19.8 (African-Americans) to 25.1 (Hispanics). It is possible that ethnic differences in risk alleles for ODC and AR may account for some of the ethnic variation in prostate cancer risk.

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

BACKGROUND: The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. METHODS: To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. RESULTS: This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. CONCLUSION: The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

Prevalence and patterns of self-initiated nutritional supplementation in men at high risk of prostate cancer.

OBJECTIVE: To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention. SUBJECTS AND METHODS: Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables. RESULTS: In all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk. CONCLUSIONS: A significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.

Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at increased risk of prostate cancer.

OBJECTIVES: To further investigate the relationship between the plasma levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone, testosterone, and demographic factors, particularly race, within a group of men at increased risk of prostate cancer development. METHODS: Enzyme-linked immunosorbent assays or an immunosorbent assay was used to quantitate the plasma levels of IGF-1, IGF-2, IGFBP-3, growth hormone, and testosterone. The study group consisted of 169 men (85 African-American, 84 white) aged 35 to 69 years, with no personal history of prostate cancer, but having at least one first-degree relative diagnosed with the disease, unless they were African-American. The relationships between the plasma levels and the categorical covariates were assessed using the nonparametric Wilcoxon test and between the continuous variables using Spearman's correlation coefficient. RESULTS: The mean plasma levels of IGFBP-3 were significantly lower in African-American (2657 ng/mL) than in white (2965 ng/mL) men (P = 0.0062). The plasma levels of IGF-2 were also lower in the African-American (503.5 ng/mL) than in the white (549.1 ng/mL) men (P = 0.0084). Overall, the IGF-1 plasma levels correlated positively with the IGF-2, IGFBP-3, and growth hormone levels and the IGF-2 plasma levels correlated negatively with the testosterone levels. CONCLUSIONS: Our results demonstrate that lower plasma levels of IGFBP-3 and IGF-2 are associated with race in a population of men at increased risk of developing prostate cancer. The ability of these markers to predict earlier disease onset is currently under investigation.

Psychological and screening profiles of first-degree relatives of prostate cancer patients.

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.

Quality of life study in prostate cancer patients treated with three-dimensional conformal radiation therapy: comparing late bowel and bladder quality of life symptoms to that of the normal population.

PURPOSE: The goals of this study were twofold. First, differences were quantified for symptoms that impact bowel and bladder quality of life (QOL) in prostate cancer patients treated with three-dimensional conformal radiotherapy (3DCRT) alone to the prostate vs. whole pelvis with prostate boost. Second, bowel and bladder QOL measures for these patients were compared to those of the normal population of men with a similar age distribution. MATERIAL AND METHODS: Two health status surveys evaluating bowel and bladder functioning, along with the AUA Symptom Problem Index and the BPH Impact Index, were mailed to 195 prostate cancer patients treated with 3DCRT between 12/92 and 11/95 at Fox Chase Cancer Center by a single clinician (GH). No patient received hormonal management as part of his treatment. Ninety-five patients had pretreatment PSA levels <10 ng/ml, T1/T2A tumors with Gleason scores 2-6, and no perineural invasion. They were treated to the prostate alone and are referred to as Group I. The remaining 100 patients had one or more of the following characteristics: pretreatment PSA levels > or =10 ng/ml, T2B/T3 tumors, Gleason scores 7-10, or perineural invasion. These patients were treated to the whole pelvis followed by a boost to the prostate and are referred to as Group II. Frequencies were tabulated, and differences in percentages for the two groups were evaluated using the two-tailed Fisher's Exact Test. Overall percentages were compared to those for equivalent measures reported by Litwin (1999) based on a normal population of men with a mean age of 73 years (range 47-86). Comparisons to the normal population were also evaluated using two-tailed Fisher's Exact p values. RESULTS: The mailing yielded a high response rate of 71% (n = 139, 66 in Group I and 73 in Group II). The mean age was 67 (range 49-82), and the median ICRU dose levels for Groups I and II were 73 and 76 Gy, respectively. Responses relating to bladder symptoms were similar for Groups I and II, except for the degree of bother associated with trouble in urination over the last month. Percentages for no bother at all were 66% and 56% for Groups I and II, respectively. Observed differences in bowel functioning related to rectal urgency over the past year (22% vs. 40% for Groups I and II, p = 0.03), the use of pads for protection against bowel incontinence (0% vs. 10% for Groups I and II, p = 0.01), and bowel satisfaction (88% vs. 72% for Groups I and II, p = 0.03). There was no significant difference in the degree of bother bladder symptoms cause men treated with radiotherapy as compared to men without cancer. Few patients reported bowel dysfunction bother as a big problem, but patients do tend to have more very small to moderate bother from bowel dysfunction than the normal population (55% vs. 33%, p < 0.001). CONCLUSION: This is the first long-term study of QOL in men treated with high-dose 3DCRT for prostate cancer. It demonstrates that these men enjoy QOL related to bladder function similar to that of the normal population. Few patients report bother from bowel symptoms as a big problem but tend to have more very small to moderate bother than the normal population. Treatment of prostate cancer patients to the whole pelvis may result in decreased QOL as defined by rectal urgency, the use of pads for bowel incontinence, and satisfaction with bowel functioning. However, regardless of field size, men are generally satisfied with their bowel and bladder functioning three to six years post treatment.

The identification and screening of men at high risk for developing prostate cancer.

It is estimated that the lifetime risk of being diagnosed with prostate cancer is 1 in 5. The identification of risk factors, including age, African-American ancestry, family history, and possibly diet and environmental factors, has allowed health care professionals the opportunity to identify, screen, and study men at the greatest risk of developing prostate cancer. The risk factors, current screening tools, and the informed consent process for men participating in a prostate cancer screening program are outlined.

Assessing women's sexuality after cancer therapy: checking assumptions with the focus group technique.

Cancer and cancer therapies impair sexual health in a multitude of ways. The promotion of sexual health is therefore vital for preserving quality of life and is an integral part of total or holistic cancer management. Nursing, to provide holistic care, requires research that is meaningful to patients as well as the profession to develop educational and interventional studies to promote sexual health and coping. To obtain meaningful research data instruments that are reliable, valid, and pertinent to patients' needs are required. Several sexual functioning instruments were reviewed for this study and found to be lacking in either a conceptual foundation or psychometric validation. Without a defined conceptual framework, authors of the instruments must have made certain assumptions regarding what women undergoing cancer therapy experience and what they perceive as important. To check these assumptions before assessing women's sexuality after cancer therapies in a larger study, a pilot study was designed to compare what women experience and perceive as important regarding their sexuality with what is assessed in several currently available research instruments, using the focus group technique. Based on the focus group findings, current sexual functioning questionnaires may be lacking in pertinent areas of concern for women treated for breast or gynecologic malignancies. Better conceptual foundations may help future questionnaire design. Self-regulation theory may provide an acceptable conceptual framework from which to develop a sexual functioning questionnaire.

Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer.

OBJECTIVES: To determine the overall plasma levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in a group of men at higher risk of prostate cancer development and to investigate the relationships between demographics and these levels, particularly with regard to race. METHODS: An enzyme-linked immunosorbant assay was used to quantitate plasma levels of IGF-1 and IGFBP-3. The study group consisted of 105 men (63 African American [AA], 42 white), aged 35 to 69 years, with no personal history of prostate cancer, but having at least one first-degree relative diagnosed with the disease, unless they were AA. Differences in plasma levels and categorical covariates were assessed using the nonparametric Wilcoxon test. Associations between plasma levels and the continuous variables were quantified using the nonparametric Spearman correlation coefficient. RESULTS: The mean plasma level of IGF-1 was not significantly different between AA (162.3 ng/mL) and white (172.1 ng/mL) men (P = 0.415). However, the mean plasma level of IGFBP-3 was lower in AA (2789 ng/mL) than in white (3216 ng/mL) men, and this decrease was highly significant (P = 0.0045). No correlation between IGFBP-3 plasma level and age was detected in the group as a whole, but an inverse relationship between IGF-1 plasma level and age was evident (P = 0.0079). CONCLUSIONS: Our results demonstrate that IGFBP-3 plasma levels are lower in AA men than in white men. Since IGFBP-3 can control IGF-1 bioavailability, the lowered IGFBP-3 could explain in part the increased risk of prostate cancer in AA men.

Prostate cancer risk assessment program. A model for the early detection of prostate cancer.

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.