A new method for scoring financial conflicts of interest.

BACKGROUND: There is a large and consistent body of evidence showing that research sponsored by for-profit industries tends to have pro-industry conclusions in comparison with similar research or re-analyses not funded by industry. Disclosure of financial conflicts via statements is presently the standard method for notification of potential biases. However, many journals are not consistent in publishing financial conflicts of interest (FCoI) statements. Furthermore, even when divulged, disclosure merely shifts the burden of evaluating conflicts to readers and the general public. Moreover, there has been an absence of a means of quantifying FCoI. OBJECTIVES: To propose a solution for the question: What are we doing about FCoI that continue to compromise the integrity of the scientific enterprise? METHODS: The FCoI Scale was developed for scoring and comparing FCoI and describing potential biases. RESULTS: The FCoI Scale consists of a score that may be expressed in whole numbers and decimal fractions, correlated to descriptive terms for potential biases and examples of financial conflicts at 11 levels. CONCLUSIONS: The FCoI score (FCoIS) provides a means for a more uniform and concise method of disclosure compared to statements, while at the same time permitting flexibility. It encourages the disclosure of relevant information and transparency in the reporting of financial conflicts. The FCoI Scale has the potential to become the standard basis for measuring, reporting, and comparing financial conflicts, suitable for disciplines in science, medicine, and beyond.

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer that has a lethality of nearly 100%. INTRODUCTION: One of the many factors that have been proposed to play an etiological role in BEN is exposure to organic compounds from Pliocene lignite coal deposits via the drinking water in endemic areas. OBJECTIVES: The objective of this study was to systematically evaluate the role of the tenets of the Pliocene lignite hypothesis in the etiology of BEN in order to provide an improved understanding of the hypothesis for colleagues and patients alike. METHODS: A comprehensive compilation of the possible limitations of the hypothesis, with each limitation addressed in turn is presented. RESULTS: The Pliocene lignite hypothesis can best account for, is consistent with, or has the potential to explain the evidence associated with the myriad of factors related to BEN. CONCLUSIONS: Residents of endemic areas are exposed to complex mixtures containing hundreds of organic compounds at varying doses and their potentially more toxic (including nephrotoxic) and/or carcinogenic metabolites; however, a multifactorial etiology of BEN appears most likely.

Organic compounds in water extracts of coal: links to Balkan endemic nephropathy.

The Pliocene lignite hypothesis is an environmental hypothesis that has been proposed to explain the etiology of Balkan endemic nephropathy (BEN). Aqueous leaching experiments were conducted on a variety of coal samples in order to simulate groundwater leaching of organic compounds, and to further test the role of the Pliocene lignite hypothesis in the etiology of BEN. Experiments were performed on lignite coal samples from endemic BEN areas in Romania and Serbia, and lignite and bituminous coals from nonendemic regions in Romania and the USA. Room temperature, hot water bath, and Soxhlet aqueous extraction experiments were conducted between 25 and 80 °C, and from 5 to 128 days in duration. A greater number of organic compounds and in higher concentrations were present in all three types of leaching experiments involving endemic area Pliocene lignite samples compared to all other coals examined. A BEN causing molecule or molecules may be among phenols, PAHs, benzenes, and/or lignin degradation compounds. The proposed transport pathway of the Pliocene lignite hypothesis for organic compound exposure from endemic area Pliocene lignite coals to well and spring drinking water, is likely. Aromatic compounds leached by groundwater from Pliocene lignite deposits in the vicinity of endemic BEN areas may play a role in the etiology of the disease. A better understanding of organic compounds leached by groundwater from Pliocene lignite deposits may potentially lead to the identification and implementation of effective strategies for the prevention of exposure to the causative agent(s) for BEN, and in turn, prevention of the disease.

Prosthetic mammoplasty sensitivity syndrome: a case for causation.

Treatment of patients experiencing adverse health effects following prosthetic mammoplasty has suffered from a lack of an acknowledgment of a causal relationship to their breast prosthetic devices. Case reports and case series showing an association between adverse health effects and breast implants have been routinely dismissed as anecdotal, and epidemiological studies have been considered necessary to prove causality. We show that epidemiological research is not necessary for establishing a causal relationship, and one properly documented case can be, in fact, all that is needed to show causation. Presently in the peer-reviewed literature there exists a substantial scientifically sound body of data showing an association between breast implants and adverse health effects. Ample evidence has shown that exposure to the five common types of breast implants outlined, i.e., silicone gel filled, saline filled, double lumen, polyurethane coated, and cohesive silicone, has caused adverse health effects in humans. Prosthetic mammoplasty sensitivity syndrome (PMSS) is the proposed term to describe the disease processes documented in the literature that has a causal relationship to breast implants.

Assessment of the FDA backgrounder on platinum in silicone breast implants: implications for public health policy.

A recent report by the U.S. Food and Drug Administration reviewed the literature on the subject of platinum in silicone gel-filled breast implants. In this study the author evaluates the FDA report for scientific accuracy and impartiality, and provides relevant discussions on financial conflicts of interest, an Institute of Medicine report, and public health policy. The study suggests that the FDA used discredited scientific practices in compiling its report. Reports by regulatory agencies should be scientifically accurate, with no partiality to industry. The current policy of one-way information flow from the FDA directly to those being informed needs to be revised. Greater importance should be placed on studies in which authors have no financial conflicts of interest.

Exposure dose and significance of platinum and platinum salts in breast implants.

The objectives of this study were to illustrate and inform key scientific issues, as determined from the peer-reviewed literature, that are critical to developing an accurate understanding of the current state of knowledge regarding platinum (Pt) in medical devices (ie, breast implants). The author identified most studies for inclusion via a PubMed database search; she extracted descriptive statistics from the studies. The author calculated Pt and Pt salt exposure doses for environmental and occupationally related samples. She observed that a number of samples elicited biological effects over a wide range of concentrations. A single silicone breast implant may be expected to contain higher Pt and Pt salt doses than have produced adverse health effects in humans. The author posits a biologically plausible rationale for Pt salt-related health problems in women that have been exposed to silicone breast implants.

Total platinum concentration and platinum oxidation states in body fluids, tissue, and explants from women exposed to silicone and saline breast implants by IC-ICPMS.

Ion chromatography-inductively coupled plasma-mass spectrometry was used to determine the total platinum concentration and platinum oxidation states in samples from women exposed to silicone and saline breast implants. Samples included the following: whole blood, urine, hair, nails, sweat, brain tissue, breast milk, and explants. Mean Pt concentration in samples from women exposed to silicone breast implants were as follows: whole blood, 568.1 +/- 74.77 pmol/L (n = 9); urine, 1.77 +/- 0.847 mug/g of creatinine (n = 10); hair, 2.13 +/- 2.984 ng/g (n = 9); nails, 0.88 +/- 0.335 ng/g (n = 9); sweat, 1.90 +/- 1.691 ng/g (n = 9); breast milk, 1.09 +/- 0.316 mug/L (n = 6). Pt in explanted silicone breast implant gel (n = 9) occurred mainly in the +2, +4, and +6 oxidation states. Pt in whole blood (n = 7) and breast milk samples (n = 6) from women exposed to silicone breast implants occurred mainly in the +2 and +4 oxidation states. Saline breast implant fluid (n = 2) did not contain detectable levels of Pt. This is the most comprehensive report, to date, to show that women exposed to silicone breast implants have Pt levels that exceed that of the general population, and the first report, to date, to document the various Pt oxidation states present in samples from women exposed to silicone breast implants.

Platinum concentration in silicone breast implant material and capsular tissue by ICP-MS.

Inductively coupled plasma-mass spectrometry (ICP-MS) was used to determine the concentration of platinum (Pt) in silicone breast implant gel (range, 0.26-48.90 microg g(-1) Pt; n=15), elastomer (range, 3.05-28.78 microg g(-1) Pt; n=7), double lumen (range, 5.79-125.27 microg g(-1) Pt; n=7), foam (range, 5.79-8.36 microg g(-1) Pt; n=2), and capsular tissue (range, 0.003-0.272 microg g(-1) Pt; n=15). The results show that very high levels of Pt are present in the encasing elastomer, double lumen, and foam envelope materials. Silicone breast implants can be a source of significant Pt exposure for individuals with these implants.