Search

Background: The 500-rule for the insulin to carbohydrate ratio (ICR) and 100-rule for insulin sensitivity factor (ISF) are easy to use but unfortunately do not provide good ratio estimates for many patients. Analysis of downloaded CGM and pump data can give good estimates but require a lot of experience from the user and is time consuming. We have developed an algorithm (Diassist), based on clinical experience and signal processing, which automatically estimates ICR and ISF, and investigated this method in a clinical context. Methods: Pump and CGM downloads over 2 weeks were used for analysis. The physician interpreted these and compared with the Diassist results. Diassist calculated only valid meals and corrections, i.e., when blood glucose and carbohydrates had been entered by the patient. 8 patients with poor glucose control participated with 3-5 visits over 2-8 months. Mean (±SD) age was 12.7 ± 1.8 (range 10.4-16.5) years, diabetes duration 8.0±1.1 years. Insulin dose was 0.78±0.17 (0.6-1.1) units/kg/24 hours (% basal 40.8±13.0 (23-58)). The tool estimated ICR and ISF over 2 weeks and proposed to increase or decrease the settings based on actual glucose excursions. To validate the robustness of the method, cross validation with two data sets was used. Data was divided into 2 sets per patient; running Diassist on the two sets and comparing the results. Results: The physician followed the Diassist recommendations for ICR titration in 73% of the time slots (4-5/day, 58 out of 79), increasing or decreasing by 10-25%. In one occasion the ICR was changed in the opposite direction to the recommendation. In 98%, the ICR was lowered (more insulin for the meal), in 2% it was increased. HbA1c was not changed (61±4.4 vs. 57±6.3 mmol/mol, 7.7±0.4 vs. 7.4±0.6%). The quota of carbohydrate and boluses used in analysis were 67% and 58% of the logged data. Conclusions: Compared to methods used today, Diassist decreased both time and complexity of the estimation task. The proposed method shows promising results for usability, robustness and safety. Disclosure H. Svensson: Stock/Shareholder; Self; Diassist Technology AB. R. Hanas: Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; AstraZeneca.

NXY-059 is a novel free-radical trapping neuroprotectant. Digoxin treatment is common in acute ischaemic stroke, the intended patient population for NXY-059. Since both digoxin and NXY-059 are eliminated primarily renally, with a substantial contribution by active renal secretion, and because digoxin has a narrow therapeutic window, this open, randomised, crossover, two-period study investigated whether NXY-059 affects the pharmacokinetics (PK) of digoxin.Twenty-two healthy subjects received 0.5 mg oral digoxin 2 h after the start of 60-h intravenous infusions of NXY-059 and placebo separated by a 14-day washout. Blood and urine were collected for 60 h. Digoxin concentrations were measured by a novel liquid chromatography-mass spectrometry assay.The ratio of the geometric mean (90% confidence interval) between NXY-059 and placebo for the digoxin area under the concentration-versus-time curve was 0.91 (0.83-0.99) and was within the predefined range for no interaction (0.80-1.25). No safety concerns were raised in the study. No serious adverse events were recorded. The most common adverse event was headache with similar frequencies in the two treatments.NXY-059 had no clinically significant effect on the PK of digoxin.

The authors investigated the association of smoking and smoking cessation with the incidence of cataract extraction in a population-based prospective cohort study. A total of 34,595 women aged 49-83 years in the Swedish Mammography Cohort were followed from September 1997 through June 2002. Information on smoking, diet, and other lifestyle factors was collected through a self-administered questionnaire. A total of 2,128 cases of age-related cataract extraction were identified. Relative risks were estimated as rate ratios using Cox proportional hazards models. The authors observed a significant dose-response association between intensity of smoking and risk of cataract extraction (among current smokers, p for trend = 0.02; among past smokers, p for trend = 0.0002). After cessation of smoking, the risk decreased with time. Among women with a moderate lifetime smoking intensity (6-10 cigarettes/day), the relative risk was not significantly different from the risk among never smokers 10 years after smoking cessation. Among women who had smoked more intensively (> 10 cigarettes/day), after 20 years of nonsmoking the increased risk became small and no longer statistically significant in comparison with never smokers (for trend over time, p < 0.0001). This prospective study confirmed smoking as a risk factor for cataract, with a dose response for smoking intensity. Smoking cessation predicts reduced risk over time, but a longer period of time is needed with a higher smoking intensity.

Objective To evaluate whether the gold standard of 24-hour urine collection for measuring albumin excretion in pre-eclamptic women could be substituted by shorter collection periods. Design Prospective study. Setting Fetal maternity ward, university hospital. Participants Thirty women with pre-eclampsia and a positive urinary test strip for protein of at least 2+. Methods From each woman, within a 25-hour period, three spot, two 12-hour (day and night) and one 24-hour urine sample were collected. Urine albumin concentrations in milligrammes per litre were analysed by rate nephelometry on a Beckman Array protein system. The urinary albumin concentrations in the spot and the 12-hour samples were compared with the concentration in the 24-hour urine collection. Main outcome measures Urinary albumin concentrations in spot and 12-hour samples measured against the standard 24-hour albumin excretion. Results Albumin concentrations in the day and night collection fitted closely with the concentrations of the 24-hour collection. The median difference between the 24-hour and the day collection was −3 mg/L (interquartile range −264 to 116 mg/L). The median difference between the 24-hour and the night collection was 17 mg/L (interquartile range −186 to 210 mg/L). The association of urinary albumin concentration in the 24-hour collection and the spot samples was much weaker. Of the spot urine samples, the albumin concentration in the sample taken on the morning after admission to hospital was closest to the 24-hour urinary albumin excretion, with a median difference of −62 mg/L (interquartile range −1131 to 285 mg/L). Conclusion The gold standard of 24-hour urinary excretion for assessment of albuminuria in pre-eclamptic women can be substituted with a 12-hour collection. Spot urine samples were inaccurate and are therefore not recommended for quantification of albumin excretion.

A randomized, double-blind, three-period cross-over study was performed to characterize the sensory phenotype and pain demographics in patients with Morton neuroma ( n = 27) and to explore the effects of local administration (2 mL) of placebo and lidocaine (1 and 10 mg/mL) around the neuroma. Using the pain quality assessment scale (PQAS), the highest rating was seen for unpleasant pain and intensity of deep pain and the lowest for sensitive skin. Ongoing pain was reported in 32% of patients. Patients reported mild to moderate average pain, and that pain had interfered with sleep only marginally. Quantitative sensory testing (QST) measurements in the innervation territory showed hypophenomena or hyperphenomena in all patients, indicating that all had neuropathy. There was no particular QST modality that appeared to be specifically affected. Even the high-dose lidocaine resulted in limited effects on nerve-impulse conduction as judged by the effect on QST variables. However, both doses of lidocaine significantly reduced pain after step-ups, compared to placebo, indicating that lidocaine in this setting affected predominantly impulse generation and not impulse conduction. Following placebo treatment, pain after step-ups was similar in patients with and without hyperalgesia, indicating that the presence of hyperalgesia does not affect the pain intensity evoked by step-ups or walking. This pain model in patients with Morton neuroma allows investigation of drugs in a cross-over design and provides an opportunity to explore drug effects on both pain and QST variables. Commonly, neuromas are surgically removed and can be characterized in depth in vitro, thereby allowing close links to be established between pathophysiology and drug effect.

Objective The objective of this study was to assess the safety and tolerability of extended-release quetiapine fumarate (quetiapine XR) compared with quetiapine immediate-release (quetiapine IR) in older patients with Alzheimer's disease with symptoms of psychosis and/or agitation. Methods This was a 6-week, double-blind, double-dummy, randomised study. Of the 109 patients screened, 100 were randomised to receive quetiapine XR (n = 68) or quetiapine IR (n = 32), at doses of 50 and 25 mg/day, respectively. Treatment was escalated to 100 mg/day by Day 4. At Day 8, a flexible-dose (50-300 mg/day) period began when dose adjustment was made at the investigator's discretion. The primary variable was incidence and type of adverse events (AEs). Secondary variables included efficacy and other safety assessments. Results Mean daily doses were 143.6 and 142.0 mg in the quetiapine XR and quetiapine IR groups, respectively. Ninety patients completed the study; only one withdrew (in the quetiapine XR group) because of an AE. Laboratory evaluations identified severe neutropaenia (one patient), mild neutropaenia (three patients) and eosinophilia (five patients); however, these were not reported, as AEs and confounding factors, such as patient age, concomitant illness and medication, made it difficult to determine any relationship to quetiapine treatment. Numerical improvements from baseline were seen across both treatment groups in Neuropsychiatric Inventory frequency × severity total, Neuropsychiatric Inventory-Nursing Home version, Cohen–Mansfield Agitation Inventory, Clinical Global Impression-Severity of Illness and Clinical Global Impression-Improvement scores. Conclusion Quetiapine XR dosed up to 300 mg/day was generally well tolerated, with a similar profile to that of quetiapine IR. Copyright © 2011 John Wiley & Sons, Ltd.