Risk characterization of N-nitrosodimethylamine in pharmaceuticals.

Since 2018, N-nitrosodimethylamine (NDMA) has been a reported contaminant in numerous pharmaceutical products. To guide the pharmaceutical industry, FDA identified an acceptable intake (AI) of 96 ng/day NDMA. The approach assumed a linear extrapolation from the Carcinogenic Potency Database (CPDB) harmonic-mean TD50 identified in chronic studies in rats. Although NDMA has been thought to act as a mutagenic carcinogen in experimental animals, it has not been classified as a known human carcinogen by any regulatory agency. Humans are exposed to high daily exogenous and endogenous doses of NDMA. Due to the likelihood of a threshold dose for NDMA-related tumors in animals, we believe that there is ample scientific basis to utilize the threshold-based benchmark dose or point-of-departure (POD) approach when estimating a Permissible Daily Exposure limit (PDE) for NDMA. We estimated that 29,000 ng/kg/day was an appropriate POD for calculating a PDE. Assuming an average bodyweight of 50 kg, we expect that human exposures to NDMA at doses below 5800 ng/day in pharmaceuticals would not result in an increased risk of liver cancer, and that there is little, if any, risk for any other type of cancer, when accounting for the mode-of-action in humans.

Providing diabetes patients with personalized written clinical information in the diabetes outpatient clinic: a pilot study.

AIM: To explore the impact of sharing personalized written clinical information with diabetes outpatients on patient involvement in the clinical consultation. METHODS: One hundred and six patients attending diabetes outpatient clinics for a review visit were allocated to receive either a patient information sheet containing personalized clinical information (prior to their consultation) or no information sheet. Both groups were compared by observing the number of patients raising any of the 17 topics included on the patient information sheet, the number of topics raised by each individual and the proportion of the total consultation time in which the patient was involved in conversation. A mean patient score was calculated by summing the number of topics raised by each patient. RESULTS: Patients in the intervention group were more likely to initiate a conversation on all 17 topics during the consultation than those in the control group. These differences were significant for all topics except glycated haemoglobin (HbA(1c)) and diabetes complications. The mean patient score was significantly higher in the intervention group (5 vs. 1, P < 0.005), with the highest patient score in the intervention group being 14 compared with 4 in the control group. The mean patient conversation time for the intervention group was significantly longer than for the control group (6.34 vs. 3.34 min, P < 0.01). The overall consultation time did not significantly differ between groups. CONCLUSIONS: Providing patients with personalized clinical information in a routine clinical setting can increase patients' involvement in the consultation without significantly increasing the length of the consultation.

Decisions about treatment: interpretations of two measures of control by women having a hysterectomy.

A number of authors have developed sets of role descriptions that have been used to classify patients' roles in decisions about their health care as either active, collaborative or passive. We explored the validity of two such measures. Twenty women who had recently had a hysterectomy described their experiences of treatment decision-making in their own words and picked role descriptions from the Control Preferences Scale (Degner, Sloan, J. Clin. Epidemiol. 45 (1992) 941) and Patient Preferences for Control measure (Bradley et al.. Fam. Med. 28 (1996) 496), both phrased in the past tense to assess roles played. The women explained why they had picked particular role descriptions. We compared the women's selections from the two measures and considered the relationship between their narrative descriptions and the role descriptors they picked. Several women found it hard to find an appropriate role description among those they were offered. Some picked apparently conflicting statements from the two measures. The role classifications that would be made on the basis of the women's chosen role descriptions did not always seem appropriate when compared with their narrative descriptions of how treatment decisions were reached. Women gave a range of explanations for choosing the role descriptors that they did, and some women who picked different role descriptions gave similar explanations for doing so. These findings suggest that there are problems with the validity of some currently used measures of patients' participation in health care decision-making. Researchers need to pay more attention to the key features of participation in decision-making and develop measures that can distinguish between these.