Evaluation of consent forms for clinical practice in Spanish Public Hospitals.

OBJECTIVE: To evaluate the access, development, and quality of consents forms for clinical practice within the Spanish Public Hospitals. METHOD: A cross-sectional study was conducted in a two-stage process (January 2018-September 2021). In stage 1, A nationwide survey was undertaken across all public general hospitals (n=223) in the Spanish Healthcare System. In stage 2, Data was taken from the regional health services websites and Spanish regulations. Health Regional Departments were contacted to verify the accuracy of the findings. Data was analyzed using a descriptive and inferential statistics (frequencies, percentages, Chi-square & Fisher's exact tests). RESULTS: The response rate was 123 (55.16%) of Spanish Public Hospitals. The results revealed a range of hospital departments involved in the development of consent documents and the absence of a standardized approach to consent forms nationally. Consent audits are undertaken in 43.09% hospitals and translation of written consents into other languages is limited to a minority of hospitals (35.77%). The validation process of consent documentation is not in evidence in 13% of Spanish Hospitals. Regional Informed Consent Committees are not place in the majority (70.7%) of hospitals. Citizens can freely access to consent documents through the regional websites of Andalusia and Valencia only. CONCLUSION: Variability is found on access, development and quality of written consent across the Spanish Public Hospitals. This points to the need for a national informed consent strategy to establish policy, standards and an effective quality control system. National audits at regular intervals are necessary to improve the consistency and compliance of consent practice.

Multiplex immunoassay to measure antibody response to nine HPV vaccine types.

Well-characterized HPV serology assays are required to evaluate performance of biosimilar candidate vaccines, reduced dosing schedules and novel administration methods. We report characterization of an expanded assay, M9ELISA, that detects antibodies to HPV virus-like particles (VLP) of nine types using direct IgG ELISA on the Meso Scale Discovery (MSD) electrochemiluminescence platform. The method is based on the previously published M4ELISA which detects antibodies to HPV6,11,16, and 18. It has been modified to add detection of antibodies to HPV31,33,45,52 and 58, and to streamline assay and reduce background. The M9ELISA plates were prepared with purified type specific L1 + L2 VLPs coated on 10-spot/well standard MSD microplates. Results of ELISA on three serial dilutions of serum were read on MSD imager, and titers calculated using the parallel line method. Evaluations included dynamic range, assay reproducibility, and stability over time. We compared M9ELISA results to those from a pseudovirion-based neutralization assay in sera from a mixed cohort of unvaccinated and vaccinated individuals (n = ~116) and to competitive Luminex immunoassay (cLIA) results in sera from a predominantly unvaccinated cohort (n = 4426). The linear range of the assay extended over 5 logs, with inter-assay reproducibility coefficient of variation ≤25% for all types. The pre-coated plates were stable for at least 2 years. Spearman correlation of antibody titers showed excellent correlation with PBNA (r = 0.86-0.97) and moderate correlation (r = 0.52-0.68) with cLIA. Thus, the M9ELISA can serve as a useful platform for high-throughput, sensitive and simultaneous quantitation of the antibody responses to nine HPV vaccine types.

Comparison of traditional and molecular analytical methods for detecting biological agents in raw and drinking water following ultrafiltration.

AIMS: To compare the performance of traditional methods to quantitative polymerase chain reaction (qPCR) for detecting five biological agents in large-volume drinking-water samples concentrated by ultrafiltration (UF). METHODS AND RESULTS: Drinking-water samples (100 l) were seeded with Bacillus anthracis, Cryptospordium parvum, Francisella tularensis, Salmonella Typhi, and Vibrio cholerae and concentrated by UF. Recoveries by traditional methods were variable between samples and between some replicates; recoveries were not determined by qPCR. Francisella tularensis and V. cholerae were detected in all 14 samples after UF, B. anthracis was detected in 13, and C. parvum was detected in 9 out of 14 samples. Numbers found by qPCR after UF were significantly or nearly related to those found by traditional methods for all organisms except for C. parvum. A qPCR assay for S. Typhi was not available. CONCLUSIONS: qPCR can be used to rapidly detect biological agents after UF as well as traditional methods, but additional work is needed to improve qPCR assays for several biological agents, determine recoveries by qPCR, and expand the study to other areas. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first study to compare the use of traditional and qPCR methods to detect biological agents in large-volume drinking-water samples.

Rapid detection of Escherichia coli and enterococci in recreational water using an immunomagnetic separation/adenosine triphosphate technique.

AIMS: The aim of this study was to examine a rapid method for detecting Escherichia coli and enterococci in recreational water. METHODS AND RESULTS: Water samples were assayed for E. coli and enterococci by traditional and immunomagnetic separation/adenosine triphosphate (IMS/ATP) methods. Three sample treatments were evaluated for the IMS/ATP method: double filtration, single filtration, and direct analysis. Pearson's correlation analysis showed strong, significant, linear relations between IMS/ATP and traditional methods for all sample treatments; strongest linear correlations were with the direct analysis (r = 0.62 and 0.77 for E. coli and enterococci, respectively). Additionally, simple linear regression was used to estimate bacteria concentrations as a function of IMS/ATP results. The correct classification of water-quality criteria was 67% for E. coli and 80% for enterococci. CONCLUSIONS: The IMS/ATP method is a viable alternative to traditional methods for faecal-indicator bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The IMS/ATP method addresses critical public health needs for the rapid detection of faecal-indicator contamination and has potential for satisfying US legislative mandates requiring methods to detect bathing water contamination in 2 h or less. Moreover, IMS/ATP equipment is considerably less costly and more portable than that for molecular methods, making the method suitable for field applications.

The involvement, understanding and attitudes of dietitians towards research and audit.

AIM: To investigate the involvement of dietitians in research and audit and to assess their understanding of and attitudes towards these activities. METHODS: A postal questionnaire was used to investigate the knowledge, attitude towards and involvement in research and audit of State Registered Dietitians practising in the National Health Service (NHS) in the UK. RESULTS: A response rate of 64% was achieved. Few respondents (15%) were currently involved in research, although more (65%) were currently involved in audit. Involvement in audit rose significantly with increasing grade and managerial responsibility. Dietitians qualifying more recently were more likely to believe that their college training prepared them to undertake research, but felt less confident about undertaking audit. Experience of audit made respondents more confident about auditing their work and improved their belief that they understood audit terminology. Higher grade dietitians were more likely to see audit as an important part of their role than were their more junior colleagues. Understanding of the terms 'research' and 'audit' was poor, although 48% of respondents identified the link between the two activities. Perceived constraints to involvement in research and audit were identified. CONCLUSION: The present level of involvement of dietitians in research and audit activities falls below that recommended in the BDA's (1997a) National Professional Standards for Dietitians Practising in Healthcare. This study identifies factors that influence dietitians' involvement in, understanding of and attitudes towards research and audit and recommends ways of increasing their involvement in these activities.

The oral administration of polysorbate 80 to the immature female rat does not increase uterine weight.

Some xenobiotics display estrogenic activity in in vitro and/or in vivo systems. Previous studies by Gajdova et al. have shown that polysorbate 80 (also known as Tween 80) administered by intraperitoneal injection to neonatal female rats on days 4-7 after birth produced estrogenic effects including earlier vaginal opening, prolongation of the estrus cycle and persistent vaginal estrus. Some of these effects were evident many weeks after cessation of administration of polysorbate 80. The present study has evaluated the estrogenic properties of polysorbate 80 following oral administration, a route of exposure which is more relevant for the consideration of human health hazard. The effects of polysorbate 80 at oral gavage doses of up to 5 g/kg/day for 3 consecutive days on uterine growth of immature female rats, a commonly used in vivo mammalian assay for estrogenic activity, have been determined. Estradiol benzoate administered subcutaneously was used as a positive control and significantly increased uterine weight in this age and strain of female rat (21-23 days, Alpk:APfSD Wistar derived) by up to 4.5-fold above vehicle control values. Polysorbate 80 administered orally to rats had no effect on uterine weight. Thus, intrinsic estrogenic effects of polysorbate 80 reported following its intraperitoneal injection to neonatal 4-day-old female rats are not manifest when it is administered by oral gavage to immature 20- to 22-day-old female rats. This latter route of exposure is of more relevance to human exposure scenarios and these data are, therefore, important in assessing hazard/risk of polysorbate 80 to man.

Rationale and perspectives on the development of fungicides.

Fungicides continue to be essential for the effective control of plant diseases. New classes of fungicides with novel modes of action are being developed in the 1990s. These include the strobilurins, phenylpyrroles, anilinopyrimidines, phenoxyquinolines, and compounds that trigger defense mechanisms in the plant. For the foreseeable future, new toxophores will be identified through a process of random screening, with natural products representing a rich source of fungicide leads. Progress is being made in the development of high-throughput screens comprised of target enzyme sites or cell-based assays; these techniques will improve the probability of discovery. Following the identification of suitable leads, biorational design is used to optimize specific properties. In vivo glasshouse screens and field trials are expected to remain the dominant methods for characterizing new compounds. Low toxicity to humans and wildlife, low environmental impact, low residues in food, and compatibility with integrated pest management (IPM) programs are increasingly important considerations in the selection of fungicides for development.

Management of painful paraneoplastic syndromes.

The majority of patients with advanced malignant disease experience pain, so pain is commonly present in patients with paraneoplastic syndromes. It is rare, however, that the pain itself is a paraneoplastic manifestation of cancer. Usually, the pain in this context is associated with a paraneoplastic syndrome but is not a direct result of that syndrome. Three syndromes in which pain is part of the syndrome and a paraneoplastic manifestation of malignant disease--neuropathy, ganglionitis, and monolitis--have been described in the literature. These syndromes and their management are discussed in this article.

Effects of 2-[1-(ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone on hepatic haem biosynthesis: species differences in hepatic porphyria.

2-[1-(Ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone (ETC) is a novel alkyl ketone herbicide. Continuous administration of ETC to mice for 28 days resulted in marked liver enlargement and severe intrahepatic cholestasis. These effects have been shown to result directly from a rapid and marked accumulation of porphyrin in the liver. The porphyrin which accumulates in the liver has been identified as protoporphyrin IX and dose response and time course studies confirm prior inhibition of mitochondrial ferrochelatase as the causal lesion. ETC was a very potent porphyrinogenic compound in mice, with a no-effect level for a single oral dose of 1 mg/kg. Rats and hamsters were insensitive to this type of hepatotoxicity following single oral doses of up to 750 mg/kg or following repeated, and indeed prolonged administration. The sensitivity of different species to ETC-induced porphyria correlated with the effect of ETC on hepatic ferrochelatase activity. The inhibition of ferrochelatase activity and the hepatic porphyria in mice were both found to be readily reversible upon withdrawal of ETC.

The practice patterns of adult oncologists' care of pediatric oncology patients.

The role of the adult oncologists in the area of pediatric cancer treatment previously has been unmeasured. A questionnaire bearing regarding the practice of 447 adult oncologists was administered in June 1991. The membership list of the Association of Community Cancer Centers was used to identify contact oncologists. One hundred thirty-one questionnaires (29.3%) were returned for analysis. The data reveal that 204 patients younger than 21 years of age were treated during the last year in 63 adult oncology practices. Most of these patients were more than 15 years of age. Only a minority (53) were treated in rural practices. In addition, only a minority (27%) of these patients are reported to be enrolled in clinical trials. In addition, adult oncologists appear to regard physiologically mature adolescents (age 16-21 years) as adults. They do not seem to make a distinction between patients 16-21 years old and those older than 21 years.

Comparison of the effects of griseofulvin and dihydropyridines on ferrochelatase activity and porphyrin accumulation in primary cultures of mouse and rat hepatocytes.

The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethyl pyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse and rat hepatocytes was determined. Exposure of mouse hepatocytes to DDC, EDDC or griseofulvin (5-100 mum) for 4 days resulted in a marked inhibition of ferrochelatase activity (up to 95%). However, whereas exposure of rat hepatocytes to DDC or EDDC (5-100 mum) for 4 days also resulted in marked inhibition of ferrochelatase activity (up to 96%), exposure to griseofulvin (5-100 mum) had no effect. DDC, EDDC and griseofulvin induced porphyrin accumulation in both mouse and rat hepatocyte cultures. In mouse hepatocyte cultures exposed to each xenobiotic the porphyrin that accumulated was predominantly protoporphyrin. In rat hepatocyte cultures exposed to DDC or EDDC the porphyrin that accumulated was also predominantly protoporphyrin, whereas following exposure to griseofulvin it was coproporphyrin. Time course studies confirmed that in rat hepatocyte cultures exposed to griseofulvin (25 or 100 mum) over a 4-day exposure period, ferrochelatase activity was not inhibited and coproporphyrin was always the predominant porphyrin accumulating (45-72% of total). Addition of 5-aminolaevulinic acid to mouse or rat hepatocyte cultures (10-1000 mum) also resulted in marked accumulation of porphyrin but whereas uroporphyrin accumulated in mouse hepatocyte cultures, coproporphyrin accumulated in rat hepatocyte cultures. These studies demonstrated that the hepatic porphyrias produced by the dihydropyridines and griseofulvin can be modelled in vitro in primary cultures of hepatocytes. Furthermore, the species differences in sensitivity of mouse and rat hepatocyte cultures in vitro to inhibition of ferrochelatase activity by griseofulvin mirrors, and therefore probably explains, the species differences in porphyria observed in vivo.

Fostering collaboration by understanding physician behavior: the cancer program perspective.

To build collaborative relations with physicians, which are particularly desirable in cancer programs, hospital administrators must first understand the intrinsic differences between the ways physicians and hospital administrators operate. Administrators' failure to understand physicians' behavior can hamper the development of such programs. Relations between physicians and hospitals have traditionally been good, and while hospital administrators and physicians have approached health care from different perspectives, their activities have generally been mutually supportive. Over the last decade, however, health care payment reform has exacerbated differences in hospitals' and physicians' goals and expectations, and these differences have begun to threaten the traditional collaborative relationship between hospitals and physicians. This report is intended for hospital administrators who wish to strengthen their relationships with their physicians and thereby develop a more comprehensive approach to the delivery of cancer care services. It identifies specific physician behavioral tendencies and analyzes their potential impact on the delivery of patient-centered cancer care. It also examines the ways physicians' attitudes and behaviors develop, as well as the reasons physicians may find themselves in conflict with other health care providers. Finally, it reviews current factors affecting physician/hospital relations and suggests ways hospitals and their medical staffs can develop mutually supportive, collaborative activities.

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate and species differences in response.

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate (DEHA) has been achieved using primary hepatocyte cultures derived from different species and cyanide-insensitive fatty acyl CoA oxidase (PCO) as a marker enzyme for peroxisome proliferation. In rat and mouse hepatocytes, the parent compound (DEHA) had no effect on peroxisomal beta-oxidation, but primary metabolites of DEHA, mono (2-ethylhexyl) adipate (MEHA) and 2-ethylhexanol (EH), were approximately equipotent in PCO induction (5-fold at 0.5 mM final concentration). The secondary metabolite of DEHA, 2-ethylhexanoic acid (EHA), was in both species the most potent peroxisome proliferator (25- and 9-fold induction in mice and rats, respectively, at 1 mM final concentration). At 2 mM final concentration a tertiary metabolite of DEHA, 2-ethyl-5-hydroxyhexan-1-oic acid, was less effective in mouse and rat hepatocytes at inducing PCO (15- and 5-fold, respectively). 2-Ethyl-5-oxohexan-1-oic acid and 2-ethylhexan-1,6-dioic acid had little effect (2-3-fold in both rat and mouse hepatocytes). Thus, EHA was identified as the proximate peroxisome proliferator of DEHA and mouse hepatocytes were approximately twice as sensitive as rat hepatocytes to peroxisome proliferation due to MEHA, EH and EHA. We investigated further species differences in response to peroxisome proliferators by using guinea pig and marmoset primary hepatocyte culture. None of the chemicals studied stimulated peroxisomal beta-oxidation in these species up to a final concentration of 2 mM. Higher concentrations lead to cytotoxicity. This lack of sensitivity of guinea pig and marmoset hepatocytes is in agreement with previous studies with di (2-ethylhexyl) phthalate metabolites, suggesting the absence of a threat of hepatocarcinogenic damage to these species and confirming that primary hepatocytes cultures are useful models for investigating the phenomenon of peroxisome proliferation.

Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals.

The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse hepatocytes has been examined. Exposure of cultured mouse hepatocytes to DDC, EDDC or griseofulvin resulted in a marked inhibition of ferrochelatase which was sustained over the 4-day exposure period. Maximal concentrations of DDC (25 microM), EDDC (25 microM) and griseofulvin (25 microM) resulted in 14-fold, 30-fold and 9-fold increases, respectively, in total porphyrin in the culture medium. Analysis of the porphyrins accumulating indicated a predominance of protoporphyrin with all three xenobiotics. Addition of 5-aminolaevulinic acid (ALA) to mouse hepatocyte cultures (10-1000 microM) resulted in much larger increases (up to 164-fold) in porphyrin accumulation in the medium and the porphyrin accumulating was predominantly uroporphyrin. These studies have demonstrated that primary cultures of mouse hepatocytes provide a valid mechanism-based in vitro model of the hepatic porphyrias produced by the dihydropyridines and griseofulvin in mice.