Towards tailored radiopeptide therapy.

PURPOSE Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. METHODS Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination. RESULTS (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. CONCLUSIONS Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.

Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland

The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.

Twenty years' experience with the Swiss data registry for assisted reproductive medicine: outcomes, key trends and recommendations for improved practice.

QUESTIONS UNDER STUDY The impact of assisted reproductive technology (ART) on Swiss demography was quantified. From 1993 to 2012 the number of deliveries, including multiples, generated by ART was compared with overall delivery numbers. Swiss experts in ART collaborated in a consensus to increase successful outcomes, to reduce the incidence of complications of ART and to validate recommendations through statistical review of available data. METHODS Data generated between 1993 and 2012 and published by the Federal Office of Statistics (BfS) were compared with the Swiss database on ART (FIVNAT-CH) as organised by the Swiss Society of Reproductive Medicine (SGRM). From these analyses a panel of Swiss experts in ART extracted recommendations to improve current practice, to prevent complications related to ART and to recommend changes in current Swiss legislation dealing with ART. RESULTS Since 1993 the age of women giving birth rose together with the number of women asking for ART. This demographic trend was reflected in a rise in the number of deliveries generated by ART (in 2012: 2.2%) and the proportion of multiple births (in 2012: 17.6%). The outcome of ART was most negatively influenced by the age of the treated patient. The number of retrieved oocytes decisively impacted the likelihood of delivery, the risk of multiple births and the incidence of ovarian hyperstimulation syndrome. CONCLUSIONS Optimal ovarian stimulation should be designed for the retrieval of 10 to 15 oocytes per treatment. Swiss legislation should enable and stimulate a policy of elective single embryo transfer to avoid multiple births.

EMAS recommendations for conditions in the workplace for menopausal women.

Women form a large part of many workforces throughout Europe. Many will be working throughout their menopausal years. Whilst the menopause may cause no significant problems for some, for others it is known to present considerable difficulties in both their personal and working lives. During the menopausal transition women report that fatigue and difficulties with memory and concentration can have a negative impact on their working lives. Furthermore, hot flushes can be a source of embarrassment and distress. Some consider that these symptoms can impact on their performance. Greater awareness among employers, together with sensitive and flexible management can be helpful for women at this time. Particular strategies might include: fostering a culture whereby employees feel comfortable disclosing health problems, allowing flexible working, reducing sources of work-related stress, providing easy access to cold drinking water and toilets, and reviewing workplace temperature and ventilation.

Increasing Scientific Confidence in Adverse Outcome Pathways: Application of Tailored Bradford-Hill Considerations for Evaluating Weight of Evidence.

Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and level of confidence in an AOP, methodologies and tools are still being formalized. The Organization for Economic Co-operation and Development (OECD) Users' Handbook Supplement to the Guidance Document for Developing and Assessing AOPs (OECD 2014a; hereafter referred to as the OECD AOP Handbook) provides tailored Bradford-Hill (BH) considerations for systematic assessment of confidence in a given AOP. These considerations include (1) biological plausibility and (2) empirical support (dose-response, temporality, and incidence) for Key Event Relationships (KERs), and (3) essentiality of key events (KEs). Here, we test the application of these tailored BH considerations and the guidance outlined in the OECD AOP Handbook using a number of case examples to increase experience in more transparently documenting rationales for assigned levels of confidence to KEs and KERs, and to promote consistency in evaluation within and across AOPs. The major lessons learned from experience are documented, and taken together with the case examples, should contribute to better common understanding of the nature and form of documentation required to increase confidence in the application of AOPs for specific uses. Based on the tailored BH considerations and defining questions, a prototype quantitative model for assessing the WoE of an AOP using tools of multi-criteria decision analysis (MCDA) is described. The applicability of the approach is also demonstrated using the case example aromatase inhibition leading to reproductive dysfunction in fish. Following the acquisition of additional experience in the development and assessment of AOPs, further refinement of parameterization of the model through expert elicitation is recommended. Overall, the application of quantitative WoE approaches hold promise to enhance the rigor, transparency and reproducibility for AOP WoE determinations and may play an important role in delineating areas where research would have the greatest impact on improving the overall confidence in the AOP.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Clinical Practice Recommendations For The Management And Prevention Of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field; (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment and management of cisplatin-induced hearing loss in children and adults; and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin based chemotherapy.

Recommendations Regarding the Nomenclature of Systematic Botany

P. Ascherson. A. Engler

A survey of the implementation status of environmental management systems in U.S. colleges and universities, and, An environmental management system implementation model for U.S. colleges and universities

A census of 925 U.S. colleges and universities offering masters and doctorate degrees was conducted in order to study the number of elements of an environmental management system as defined by ISO 14001 possessed by small, medium and large institutions. A 30% response rate was received with 273 responses included in the final data analysis. Overall, the number of ISO 14001 elements implemented among the 273 institutions ranged from 0 to 16, with a median of 12. There was no significant association between the number of elements implemented among institutions and the size of the institution (p = 0.18; Kruskal-Wallis test) or among USEPA regions (p = 0.12; Kruskal-Wallis test). The proportion of U.S. colleges and universities that reported having implemented a structured, comprehensive environmental management system, defined by answering yes to all 16 elements, was 10% (95% C.I. 6.6%–14.1%); however 38% (95% C.I. 32.0%–43.8%) reported that they had implemented a structured, comprehensive environmental management system, while 30.0% (95% C.I. 24.7%–35.9%) are planning to implement a comprehensive environmental management system within the next five years. Stratified analyses were performed by institution size, Carnegie Classification and job title. ^ The Osnabruck model, and another under development by the South Carolina Sustainable Universities Initiative, are the only two environmental management system models that have been proposed specifically for colleges and universities, although several guides are now available. The Environmental Management System Implementation Model for U.S. Colleges and Universities developed is an adaptation of the ISO 14001 standard and USEPA recommendations and has been tailored to U.S. colleges and universities for use in streamlining the implementation process. In using this implementation model created for the U.S. research and academic setting, it is hoped that these highly specialized institutions will be provided with a clearer and more cost-effective path towards the implementation of an EMS and greater compliance with local, state and federal environmental legislation. ^

The relationship between oral contraceptives and pelvic inflammatory disease: Policy implications and recommendations

One of the most widely accepted noncontraceptive benefits of oral contraceptive use is the reduction in the development of pelvic inflammatory disease (PID) and its sequelae in users. While much of the research over the past forty years has found an association between oral contraceptive use and reduced rates of PID [Senanayake, 1980], more recent studies have qualified and even challenged this widely held belief. [Henry-Suchet, 1997; Ness 1997; Ness, 2001] PID, an infection in the upper genital tract causing infertility and ectopic pregnancy, affects over one million women in the United States each year, exacting an enormous toll on women's reproductive and emotional health, as well as our economy. [CDC Factsheet, 2007] This thesis examines the public health implications of pelvic inflammatory disease and the use of oral contraceptives. Sixteen original studies are reviewed and analyzed, thirteen of which found a protective benefit with oral contraceptive use against PID and three more recent studies which found no protective benefit or association between oral contraceptive use and PID. Analysis of the research findings suggests a need for additional research, provider and patient education, and an increased government role in addressing the ongoing and significant public health concerns raised by current rates of Chlamydia- and gonorrheal-PID. ^

Knowledge of exercise recommendations and energy intake from foods and beverages in relation to exercise behaviors within two Hispanic border communities

This research is a secondary analysis of the Qué Sabrosa Vida population-based cross-sectional study of two predominately Mexican American communities located along the Texas-Mexico border in 2000. There were two aims for this research. The first was to determine the relationship between knowledge of exercise and water recommendations, and exercise behavior and water consumption. The second was to determine the relationship between exercise behavior and percentage of energy consumption from beverages. Chi-square analysis revealed the majority of both populations had adequate knowledge about water and exercise recommendations, although significant percentages of the populations (>40%) did not consume water or exercise in adequate amounts. Knowledge was found to be a component of both behaviors, as it was more prevalent in the adults who exercised and consumed water in adequate amounts. Analysis of variance revealed no significant difference between overall beverage calorie percentage and exercise level (all p-values > 0.05); both regions and genders reported ∼18% of total caloric intake from beverages. There was no disproportionate influence of beverage calories on total caloric intake, after controlling for water consumption and independent of exercise behavior. These findings suggest that overall caloric intake, from both foods and beverages, may be the most influential factor to the energy imbalance contributing to the obesity crisis in these Hispanic border populations. ^

Food advertisements during children's television programming in 2007: Comparison with ads in 1994 and the 2005 dietary recommendations

Childhood overweight and obesity are two major public health problems that are of economic and medical concern in the world today (Lobstein, Baur, & Uauy, 2004). Overweight conditions in childhood are important because they are widely prevalent, serious, and carry lifetime consequences for health and well being (Lobstein et al., 2004). Several studies have shown an association between television viewing and obesity in all age groups (Caroli, Argentieri, Cardone, & Masi, 2004; Harper, 2006; Vandewater & Huang, 2006; Wiecha et al., 2006). One mechanism that potentially links television viewing to childhood obesity is food advertising (Story, 2003). ^ The purpose of this study was to examine the types of foods advertised on children's television programming and to determine if there have been any changes in the number and types of commercials over the last 13 years. In addition, the food content of the advertisements was compared to the 2005 Dietary Guidelines to determine if the foods targeted were consistent with the current recommendations. Finally, each television network was analyzed individually to determine any differences between advertising on cable and regular programming. ^ A descriptive analysis was conducted on the most commonly advertised commercials during children's television programming on Saturday morning from 7 a.m. to 10:30 a.m. A total of 10 major television networks were viewed on three different Saturday mornings during June and July 2007. Commercial advertising accounted for approximately 19% of children's total viewing time. Of the 3,185 commercials, 28.5% were for foods, 67.7% were for non-food items, and 3.8% were PSAs. On average, there were 30 commercial advertisements and PSAs per hour, of which approximately nine were for food. ^ Of the 907 food advertisements, 72.0% were for foods classified in the fats, oils, and sugar group. The next largest group (17.3%) was for restaurant food of which 15.3% were for unhealthy/fast food restaurant fare. The most frequently advertised food product on Saturday morning television was regular cereal, accounting for 43.9% of all food advertisements. ^ Cable and regular programming stations varied slightly in the amount, length, and category of commercials. Cable television had about 50% less commercials and PSAs (1098) than regular programming (2087), but only had approximately 150 minutes less total commercial and PSA time; therefore, cable, in general, had longer commercials than regular programming. Overall, cable programming had more advertisements encouraging increased physical activity and positive nutrition behavior with less commercials focusing on the fats, oils, and sugar groups, compared to regular programming. ^ During the last 13 years, food advertisements have not improved, despite the recent IOM report on marketing foods to children (Institute of Medicine-Committee on Food Marketing and the Diets of Children and Youth, 2005), although the frequency of food advertisements has improved slightly. Children are now viewing an average of one food advertisement every 7 minutes, compared to one food advertisement every 5 minutes in 1994 (Kotz & Story, 1994). Therefore, manufacturers are putting a greater emphasis on advertising other products to children. Despite the recent attention to the issue of marketing unhealthy foods to children through television advertisements, not much progress has been noted since 1994. Further advocacy and regulatory issues concerning the content of advertisements during Saturday morning TV need to be explored. ^

Uncertainty analysis of cost effectiveness in a tailored intervention to promote screening for colorectal cancer

Background. Screening for colorectal cancer (CRC) is considered cost effective but screening compliance in the US remains low. There have been very few studies on economic analyses of screening promotion strategies for colorectal cancer. The main aim of the current study is to conduct a cost effectiveness analysis (CEA) and examine the uncertainty involved in the results of the CEA of a tailored intervention to promote screening for CRC among patients of a multispeciality clinic in Houston, TX. ^ Methods. The two intervention arms received a PC based tailored program and web based educational information to promote CRC screening. The incremental cost of implementing a tailored PC based program was compared to the website based education and the status quo of no intervention for each unit of effect after 12 months of delivering the intervention. Uncertainty analysis in the point estimates of cost and effect was conducted using nonparametric bootstrapping. ^ Results. The cost of implementing a web based educational intervention was $36.00 per person and the cost of the tailored PC based interactive intervention was $43.00 per person. The additional cost per person screened for the web-based strategy was $2374 and the effect of the tailored intervention was negative. ^

Deployed military women: A second look at gender-specific infections

This descriptive, cross-sectional study addressed the relationship between variables of deployed military women and prevalence of gender-specific infections. The analysis of secondary data will look at the last deployment experience of 880 randomly selected U.S. military women who completed a mailed questionnaire (Deployed Female Health Practice Questionnaire (FHPQ)) in June 1998. The questionnaire contained 191 items with 80 data elements and one page for the subject's written comments. The broad categories of the questionnaire included: health practices, health promotion, disease prevention and treatment, reproduction, lifestyle management, military characteristics and demographics. The research questions are: (1) What is the prevalence of sexually transmitted diseases (STD), urinary tract infections (UTI) and vaginal infections (VI) related to demographic data, military characteristics, behavioral risk factors and health practices of military women during their last deployment? and (2) What are the differences between STD, UTI and VI related to the demographic data, military characteristics, behavioral risk factors and health practices of military women during their last deployment. The results showed that (1) STDs were found to be significantly associated with age and rank but not location of deployment or military branch; (2) UTI were found to be significantly associated with intrauterine device (IUD) use, prior UTI and type of items used for menses management, but not education or age; and (3) VI were significantly associated with age, rank and deployment location but not ethnicity or education. Although quantitative research exploring hygiene needs of deployed women continues, qualitative studies may uncover further “hidden” issues of importance. It cannot be said that the military has not made proactive changes for women, however, continued efforts to hone these changes are still encouraged. Mandatory debriefings of “seasoned” deployed women soldiers and their experiences would benefit leadership and newly deployed female soldiers with valuable “lessons learned.” Tailored hygiene education material, prevention education classes, easy access website with self-care algorithms, pre-deployment physicals, revision of military protocols for health care providers related to screening, diagnosing and treatment of gender-specific infections and process changes in military supply network of hygiene items for women are offered as recommendations. ^