Use of human embryonic stem cells and umbilical cord blood stem cells for research and therapy: a prospective survey among health care professionals and patients in Switzerland

BACKGROUND: Scientific progress in the biology of hematopoietic stem cells (HSCs) provides opportunities for advances in therapy for different diseases. While stem cell sources such as umbilical cord blood (UCB) are unproblematic, other sources such as human embryonic stem cells (hESCs) raise ethical concerns. STUDY DESIGN AND METHODS: In a prospective survey we established the ethical acceptability of collection, research, and therapy with UCB HSCs versus hESCs among health care professionals, pregnant women, patients undergoing in vitro fertilization therapy, parents, and HSC donors and recipients in Switzerland. RESULTS: There was overall agreement about an ethical justification for the collection of UCB for research and therapy in the majority of participants (82%). In contrast, research and therapy with hESCs was acceptable only by a minority (38% of all responders). The collection of hESCs solely created for HSC collection purposes met overall with the lowest approval rates. Hematologists displayed among the participants the highest acceptance rates for the use of hESCs with 55% for collection, 63% for research, and 73% for therapy. CONCLUSIONS: This is the first study assessing the perception of hESCs for research and therapy in comparison with UCB HSCs in different target groups that are exposed directly, indirectly, or not at all to stem cell-based medicine. Our study shows that the debate over the legitimacy of embryo-destructive transplantation medicine is far from over as particularly hESC research continues to present an ethical problem to an overwhelming majority among laypersons and even among health care professionals.

Management, feeding, production, reproduction and udder health on organic and conventional Swiss dairy farms

Organic dairy farms (OP; n=60) and conventional dairy farms (integrated production, IP; n=60), matched in size, location, and agricultural zone (altitude), were studied for possible differences in management, feeding, production, reproduction and udder health. OP and IP farms were similar in size (17.7 and 16.9 ha), milk quota (65900 and 70,000 kg/year), cow number (14 and 15), cow age (5.3 and 5.2 years), housing of cows of the Simmental x Red Holstein or Holstein breeds (87 and 75%; 45 and 60%), but differed significantly with respect to loose housing systems (18 and 7%), outside paddocks (98 and 75%), energy-corrected 305-d milk yield (5,695 and 6,059 kg), milk protein content (31.8 and 32.7 g/kg), use of bucket milking systems (73 and 33%), observance of regular (12-h) milking intervals (47 and 68%), routine application of the California-Mastitis-Test (10 and 28%), teat dipping after milking (25 and 43%) and blanket dry cow treatments (0 and 45%). Milk somatic cell counts on OP and IP farms (119 000 and 117,000/mL) and reproduction data were similar and there were no significant differences between OP and IP farms as concerns available feeds, planning and management of feeding. Alternative veterinary treatments were used more often on OP than IP farms (55 and 17%). Main causes for cow replacements on OP and IP farms were fertility disorders (both 45%), age (40 and 42%), sale (30 and 37%) and udder health (35 and 13%).Between OP and IP Swiss dairy farms thus relatively few larger differences were found.

Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial

OBJECTIVE: To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. DESIGN: H pylori screening programme followed by randomised placebo controlled trial of eradication. SETTING: Seven general practices in southwest England. PARTICIPANTS: 10,537 unselected people aged 20-59 years were screened for H pylori infection (13C urea breath test); 1558 of the 1636 participants who tested positive were randomised to H pylori eradication treatment or placebo, and 1539 (99%) were followed up for two years. INTERVENTION: Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. MAIN OUTCOME MEASURES: Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. RESULTS: In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were 84.70 pounds sterling (74.90 pounds sterling to 93.91 pounds sterling) greater per participant in the eradication group over two years, of which 83.40 pounds sterling (146 dollars; 121 euro) was the cost of eradication treatment. No difference in quality of life existed between the two groups. CONCLUSIONS: Community screening and eradication of H pylori is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.

Copper and human health: biochemistry, genetics, and strategies for modeling dose-response relationships

Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Valuing the Health States Associated with Chlamydia trachomatis Infections and Their Sequelae: A Systematic Review of Economic Evaluations and Primary Studies

OBJECTIVES Economic evaluations of interventions to prevent and control sexually transmitted infections such as Chlamydia trachomatis are increasingly required to present their outcomes in terms of quality-adjusted life-years using preference-based measurements of relevant health states. The objectives of this study were to critically evaluate how published cost-effectiveness studies have conceptualized and valued health states associated with chlamydia and to examine the primary evidence available to inform health state utility values (HSUVs). METHODS A systematic review was conducted, with searches of six electronic databases up to December 2012. Data on study characteristics, methods, and main results were extracted by using a standard template. RESULTS Nineteen economic evaluations of relevant interventions were included. Individual studies considered different health states and assigned different values and durations. Eleven studies cited the same source for HSUVs. Only five primary studies valued relevant health states. The methods and viewpoints adopted varied, and different values for health states were generated. CONCLUSIONS Limitations in the information available about HSUVs associated with chlamydia and its complications have implications for the robustness of economic evaluations in this area. None of the primary studies could be used without reservation to inform cost-effectiveness analyses in the United Kingdom. Future debate should consider appropriate methods for valuing health states for infectious diseases, because recommended approaches may not be suitable. Unless we adequately tackle the challenges associated with measuring and valuing health-related quality of life for patients with chlamydia and other infectious diseases, evaluating the cost-effectiveness of interventions in this area will remain problematic.

Towards a new model of care: integrating mental health, substance use, and somatic care

Although research and clinical interventions for patients with dual disorders have been described since as early as the 1980s, the day-to-day treatment of these patients remains problematic and challenging in many countries. Throughout this book, many approaches and possible pathways have been outlined. Based upon these experiences, some key points can be extracted in order to guide to future developments. (1) New diagnostic approaches are warranted when dealing with patients who have multiple problems, given the limitations of the current categorical systems. (2) Greater emphasis should be placed on secondary prevention and early intervention for children and adolescents at an increased risk of later-life dual disorders. (3) Mental, addiction, and somatic care systems can be integrated, adopting a patient-focused approach to care delivery. (4) Recovery should be taken into consideration when defining treatment intervention and outcome goals. (5) It is important to reduce societal risk factors, such as poverty and early childhood adversity. (6) More resources are needed to provide adequate mental health care in the various countries. The development of European guidance initiatives would provide benefits in many of these areas, making it possible to ensure a more harmonized standard of care for patients with dual disorders.

Privacy Preserving Probabilistic Record Linkage (P3RL): a novel method for linking existing health-related data and maintaining participant confidentiality.

BACKGROUND Record linkage of existing individual health care data is an efficient way to answer important epidemiological research questions. Reuse of individual health-related data faces several problems: Either a unique personal identifier, like social security number, is not available or non-unique person identifiable information, like names, are privacy protected and cannot be accessed. A solution to protect privacy in probabilistic record linkages is to encrypt these sensitive information. Unfortunately, encrypted hash codes of two names differ completely if the plain names differ only by a single character. Therefore, standard encryption methods cannot be applied. To overcome these challenges, we developed the Privacy Preserving Probabilistic Record Linkage (P3RL) method. METHODS In this Privacy Preserving Probabilistic Record Linkage method we apply a three-party protocol, with two sites collecting individual data and an independent trusted linkage center as the third partner. Our method consists of three main steps: pre-processing, encryption and probabilistic record linkage. Data pre-processing and encryption are done at the sites by local personnel. To guarantee similar quality and format of variables and identical encryption procedure at each site, the linkage center generates semi-automated pre-processing and encryption templates. To retrieve information (i.e. data structure) for the creation of templates without ever accessing plain person identifiable information, we introduced a novel method of data masking. Sensitive string variables are encrypted using Bloom filters, which enables calculation of similarity coefficients. For date variables, we developed special encryption procedures to handle the most common date errors. The linkage center performs probabilistic record linkage with encrypted person identifiable information and plain non-sensitive variables. RESULTS In this paper we describe step by step how to link existing health-related data using encryption methods to preserve privacy of persons in the study. CONCLUSION Privacy Preserving Probabilistic Record linkage expands record linkage facilities in settings where a unique identifier is unavailable and/or regulations restrict access to the non-unique person identifiable information needed to link existing health-related data sets. Automated pre-processing and encryption fully protect sensitive information ensuring participant confidentiality. This method is suitable not just for epidemiological research but also for any setting with similar challenges.