Search

From 20 April through 13 May 1992, 9 children were hospitalized with hemolytic-uremic syndrome in Lombardia, Italy, where only 14 cases of this syndrome had occurred in the preceding 4 years. Cases were scattered in a large area encompassing five provinces, and the source of the outbreak was not identified. Eight patients needed dialysis, and there was 1 death. Seven of the 9 cases were examined for evidence of infection by Vero cytotoxin (VT)-producing Escherichia coli (VTEC). Six children had serum antibodies to the lipopolysaccharide of E. coli O111, and a VT-producing E. coli O111:NM was isolated from stool in 1 case. This is the first outbreak of VTEC infection recognized in Italy and the first associated with an E. coli serotype other than O157:H7. [ABSTRACT FROM AUTHOR]

Abstract Background The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract was designed to assess the impact of a multivitamin-mineral supplement on age-related cataract. Trial results showed evidence of a beneficial effect of the supplement on all types of cataract combined, opposite effects on two of the three types of cataract (beneficial for nuclear opacities and harmful for posterior sub-capsular opacities) and no statistically significant effect on cortical opacities. No treatment recommendations were made. A post-trial survey was conducted on 817 surviving elderly participants to assess their satisfaction, their understanding of treatment assignment to supplement or placebo and the success of masking. Methods Trial results were communicated by letter and the level of satisfaction and of understanding of the results was assessed by a questionnaire. Participants were offered the option of being unmasked: a second questionnaire was administered to this subset to assess their understanding of the randomisation process and the success of masking. Results 610 participants (74.7%) responded to the survey: 94.6% thought the description of the results was "very clear" or "quite clear", 5.4% "not clear" or "do not know"; 89.8% considered the results "very interesting" or "quite interesting", 10.2% "not interesting" or "do not know"; 60.3% expressed "satisfaction", 17.2% "both satisfaction and concern", 2.6% "concern", 19.9% "indifference" or "do not know". 480 participants (78.7%) accepted the offer to be unmasked to their treatment assignment: 395 (82.3%) recalled/understood the possibility of assignment to vitamins or placebo, 85 (17.7%) did not. 68 participants (17.2%) thought they had taken vitamins (79.4% were correct; p = 0.0006), 47 (11.9%) thought they had taken placebo (59.6% were correct; p = 0.46) and 280 (70.9%) declared they did not know. Conclusions The results were made difficult to explain to study participants by the qualitatively different effect of treatment on the two most visually significant types of cataract. Although the study did not lead to a recommendation to use the dietary supplement, the vast majority of participants reported satisfaction after they received the results but almost 20% of the participants expressed some concern. Masking to treatment assignment was successful in the majority of participants.

Biochemical confirmation of ovulation typically involves measuring serum progesterone levels during the mid-luteal phase. Alternatively, this information could be obtained by monitoring urinary excretion of conjugated metabolites of ovarian steroids such as pregnanediol 3-glucuronide (PDG) using immunoassay techniques that have methodological limitations. The aim of the present study was to develop a mass spectrometry (MS)-based method for the rapid and accurate measurement of urinary PDG levels in spot urine samples. A "dilute and shoot" ultra-high-performance liquid cromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for measuring PDG urinary concentration with a 6-min analysis time. The method underwent validation in accordance with ISO 17025 documentation for quantitative methods, proving an efficient separation of PDG from other structurally similar glucuro-conjugated steroid metabolites and ensuring a sufficient sensitivity for detecting the target analyte at concentrations as low as 0.01 μg/mL. The validation protocol yielded satisfactory results in terms of accuracy, repeatability, intermediate precision, and combined uncertainty. Additionally, the stability of both the samples and calibration curves was also conducted. The application to real urine samples confirmed the method's capability to measure PDG levels throughout an entire menstrual cycle and detecting ovulation. The rapidity of the analytical platform would therefore enable high throughput analysis, which is advantageous for large cohort clinical studies., (© 2024 The Author(s). Biomedical Chromatography published by John Wiley & Sons Ltd.)

Study Question: Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)?, Summary Answer: Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories., What Is Known Already: Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting., Study Design, Size, Duration: This case-control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021., Participants/materials, Setting, Methods: Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp., Main Results and the Role of Chance: REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9 kcal/kgFFM·day, P < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number., Limitations, Reasons for Caution: Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS., Wider Implications of the Findings: A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon., Study Funding/competing Interest(s): This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

After an overview of the evolution of ethics laws for medical activities, we suggest a possible classification of documents regarding the ethical conduct of scientific research with human beings. The authors outline the necessity to define formal criteria for the development and the implementation of ethics standards.

Background: The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract was designed to assess the impact of a multivitamin-mineral supplement on age-related cataract. Trial results showed evidence of a beneficial effect of the supplement on all types of cataract combined, opposite effects on two of the three types of cataract (beneficial for nuclear opacities and harmful for posterior sub-capsular opacities) and no statistically significant effect on cortical opacities. No treatment recommendations were made. A post-trial survey was conducted on 817 surviving elderly participants to assess their satisfaction, their understanding of treatment assignment to supplement or placebo and the success of masking., Methods: Trial results were communicated by letter and the level of satisfaction and of understanding of the results was assessed by a questionnaire. Participants were offered the option of being unmasked: a second questionnaire was administered to this subset to assess their understanding of the randomisation process and the success of masking., Results: 610 participants (74.7%) responded to the survey:94.6% thought the description of the results was "very clear" or "quite clear", 5.4% "not clear" or "do not know"; 89.8% considered the results "very interesting" or "quite interesting", 10.2% "not interesting" or "do not know"; 60.3% expressed "satisfaction", 17.2% "both satisfaction and concern", 2.6% "concern", 19.9% "indifference" or "do not know".480 participants (78.7%) accepted the offer to be unmasked to their treatment assignment: 395 (82.3%) recalled/understood the possibility of assignment to vitamins or placebo, 85 (17.7%) did not. 68 participants (17.2%) thought they had taken vitamins (79.4% were correct; p = 0.0006), 47 (11.9%) thought they had taken placebo (59.6% were correct; p = 0.46) and 280 (70.9%) declared they did not know., Conclusions: The results were made difficult to explain to study participants by the qualitatively different effect of treatment on the two most visually significant types of cataract. Although the study did not lead to a recommendation to use the dietary supplement, the vast majority of participants reported satisfaction after they received the results but almost 20% of the participants expressed some concern. Masking to treatment assignment was successful in the majority of participants.

The use of multivitamin-mineral supplements has become increasingly common, but whether the use of such supplements improves micronutrient status remains still unclear. The objective of this report is to investigate how a long-term vitamin-mineral supplementation following the US Recommended Daily Intake (RDI) affected the plasma levels of selected nutrients in a subset (No. = 407) of participants in the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS). The CTNS was a double-blind, single centre, controlled clinical trial of 1020 participants aged 55-75 years randomized to a daily tablet of Centrum(R) or placebo. A representative sample of 40% of the 1020 subjects, whom plasma level of selected vitamins was determined at the baseline, was retested throughout the treatment period that averaged 9.0 +/- 2.4 years. Participants assigned to Centrum(R) showed a significant increase (p < 0.005) in mean/median plasma levels of vitamin E, beta-carotene, folate, and vitamin B12, and an improved riboflavin status when compared with participants assigned to placebo. Differences concerning vitamin C were statistically less relevant and those concerning vitamin A were at a borderline level. In the treated group the effect of supplementation on plasma levels of vitamins A, E, and C, and on the glutathione reductase activation coefficient was significantly higher in participants with lower nutritional status at baseline.

Objective: To evaluate the effect of a multivitamin/mineral supplement on development or progression of age-related lens opacities., Design: Randomized, double-masked, single center, placebo-controlled clinical trial., Participants: One thousand twenty participants, 55 to 75 years old and with early or no cataract, were randomly assigned to a daily tablet of a multivitamin/mineral formulation or a placebo., Methods: Baseline and annual lens photographs were graded for severity of lens opacities according to a modification of the Age-Related Eye Disease Study system for classifying cataracts., Main Outcome Measures: The primary outcome was a prespecified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary outcomes included an increase in type-specific opacity grades, cataract surgery, and visual acuity (VA) loss from baseline > or =15 letters., Results: Participants were observed for an average of 9.0+/-2.4 years. There was a decrease in total lens events in participants assigned to the multivitamin/mineral formulation compared with those assigned to the placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.98; P = 0.03). Nuclear events were significantly less common (HR, 0.66; 95% CI, 0.50-0.88; P = 0.004) and PSC events significantly more common (HR, 2.00; 95% CI, 1.35-2.98; P<0.001) in participants taking the multivitamin/mineral formulation than in those assigned to the placebo. No statistically significant treatment effects were seen for cortical opacities, moderate VA loss, or cataract surgery., Conclusions: Lens events were less common in participants who took the multivitamin/mineral formulation, but treatment had opposite effects on the development or progression of nuclear and PSC opacities, the 2 most visually important opacity subtypes.

Principles promoting the protection of subjects involved in biomedical research are interpreted differently within the scientific community. The purpose of this paper is to describe the attitudes of researchers working at the Istituto Superiore di Sanità (ISS) regarding the ethical implications of studies involving human beings, with particular emphasis on aspects concerning informed consent (IC) and ethics committee (EC) review. In 2001, ISS researchers published a total of 733 articles, 93 (12.7%) of which were studies involving human beings. Nearly 2/3 (60/93) were epidemiological, while the remaining 35.5% were based on laboratory data. Half (47/93) reported physical or psychological interventions or treatments on study subjects. 40.9% of articles mentioned that informed consent had been obtained and only 12.9% that approval had been given by an ethics committee. The low proportion of articles on which a protocol had been submitted the EC was due in part to the type of studies, but also to the absence of an institutional EC prior to 2001. Ethical procedures were more present in laboratory than in epidemiologic studies (IC: 69.7% vs 25.0%, p < 0.001) (EC: 27.3% vs 5.0% p = 0.004). Those differences were more likely due to the less interventionist nature of the epidemiologic studies rather than in poor ethical awareness on the part of epidemiologists. Further efforts are needed to develop and enforce clear institutional policies regarding ethical procedures.

We described the indications of laws and the commitment of researchers on the decision to submit two projects regarding observational studies to the ethics committee. Out of the two studies, the first one shows problems on data confidentiality and privacy, while the other one entails a risk, even though minimum, of physical damage for the study subjects. In Italy, the laws foreseeing the submission of research projects to the ethical committee are the Code for Personal Data Protection (Dlgs 196/2003), and the Good Clinical Practice regulations for the protection of research subjects (DM 15 luglio 1997); other provisions tied to such basic laws are also mentioned in the article. The laws on the protection of personal data tend to simplify prescriptions when the research relates to public health issues; the laws on the protection of the research subject do not almost totally pertain observational studies. We concluded that the researchers are free to submit or not both projects to the ethics committee. We underlined that the sensitivity of researchers on the endorsement of the same ethical principles can be different. We would think convenient also for epidemiological research, as well for clinic research, to establish an uniform approach. The recent issuing of the Additional Protocol on biomedical research to the Oviedo Convention may provide an opportunity.