Managing Circadian Disruption due to Hospitalization: A Pilot Randomized Controlled Trial of the CircadianCare Inpatient Management System.

The objective of the present study was to test the effects of an inpatient management system (CircadianCare) aimed at limiting the negative impact of hospitalization on sleep by enhancing circadian rhythmicity. Fifty inpatients were randomized to either CircadianCare (n = 25; 18 males, 62.4 ± 1.9 years) or standard of care (n = 25; 14 males, 64.5 ± 2.3 years). On admission, all underwent a full sleep-wake evaluation; they then completed daily sleep diaries and wore an actigraph for the whole length of hospitalization. On days 1 (T0), 7 (T1), and 14 (T2, if still hospitalized), salivary melatonin for dim light melatonin onset (DLMO) and 24-h skin temperature were recorded. In addition, environmental noise, temperature, and illuminance were monitored. Patients in the CircadianCare arm followed 1 of 3 schedules for light/dark, meal, and physical activity timings, based on their diurnal preference/habits. They wore short-wavelength-enriched light-emitting glasses for 45 min after awakening and short-wavelength light filter shades from 18:00 h until sleep onset. While the first, primary registered outcome (reduced sleep-onset latency on actigraphy or diary) was not met, based on sleep diaries, there was a trend (0.05 < p < 0.1) toward an advance in bedtime for CircadianCare compared to standard of care patients between T0 and T1. Similarly, DLMO time significantly advanced in the small group of patients for whom it could be computed on both occasions, with untreated ones starting from earlier baseline values. Patients sleeping near the window had significantly higher sleep efficiency, regardless of treatment arm. As noise fluctuation increased, so did the number of night awakenings, regardless of treatment arm. In conclusion, the CircadianCare management system showed positive results in terms of advancing sleep timing and the circadian rhythm of melatonin. Furthermore, our study identified a combination of environmental noise and lighting indices, which could be easily modulated to prevent hospitalization-related insomnia.

VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study.

AIM: A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose. MATERIALS & METHODS: The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age. RESULTS: The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25-45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series. CONCLUSION: The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.

Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats.

OBJECTIVES: Long-Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu-induced liver damage was studied in 5-week-old LEC rats (n=52). METHODS: Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment. RESULTS: Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short- and long-term experiments. 8-hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats. CONCLUSIONS: Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism.