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Enfortumab vedotin is a novel antibody-drug conjugate (ADC) approved to treat urothelial carcinoma. One rarely reported adverse effect has been life-threatening diabetic ketoacidosis (DKA) driven by profound insulin resistance. We report a case of a 62-year-old nondiabetic woman with metastatic urothelial carcinoma who experienced DKA following her third dose of enfortumab vedotin, with extreme insulin requirements of > 1000 units daily, and full resolution of insulin requirement by day 7 of admission. Including this case, 3 of 9 reported patients with enfortumab vedotin–associated DKA have survived. Monomethyl auristatin E (MMAE), the cytotoxic component of enfortumab vedotin, is the likely cause, although the exact mechanism remains unclear. This rare clinical event challenges the usual protocols and practice surrounding insulin infusion administration, and this case provides evidence to assist in understanding the mechanism by which enfortumab vedotin causes ketoacidosis. [ABSTRACT FROM AUTHOR]

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1–0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors. [ABSTRACT FROM AUTHOR]

The market for conservation easements provides a way to ensure the continued existence of open space amenities where rural communities face development pressure. The object of this research is to identify factors affecting land trust agents’ preferences for conservation easements and to investigate preference heterogeneity among those potentially involved in easement acquisition. Stated choice surveys were sent to land trusts’ personnel (agents) across the Intermountain West. Models were segmented by attitudinal data from land trust agents regarding their organizations’ provision of ecosystem services versus their sense of place or place attachment when considering conservation easement choices. Four separate random utility models were estimated. Results indicated that preference heterogeneity for conservation easements exists across land trust agent segments. Such knowledge provides insights into factors which may affect potential demands for conservation easements in this evolvingmarket. These outcomes might help public policy makers allocate resources towards land conservation and land use planning.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60–84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely 'some or more pain impact' and 'presence of any bodily pain') to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year), the mean (sd) 25(OH)D concentrations were 77 (sd 25) and 115 (sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration >50 nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (−0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D3/month had negligible effect on bodily pain. [ABSTRACT FROM AUTHOR]