The police, social services and psychiatry cooperation in Denmark--a new model of working practice between governmental sectors. A description of the concept, process, practice and experience.

In 2004 a new model of working practice between three public sectors, the local Police Department, Social Services and Psychiatry/Mental Health Services (PSP) was introduced in the municipality of Frederiksberg, Denmark. The aim of this cooperation was to enhance support to vulnerable citizens, who do not belong solely to one of the three sectors and thereby often get lost in the system. The PSP cooperation was introduced to ensure that relevant information concerning vulnerable citizens was shared between the three sectors and to improve collaboration between the sectors involved in order to provide the needed support to the individual citizen. Due to the success of the PSP cooperation in Frederiksberg, the PSP model was implemented by law in Denmark in 2009. In order to evaluate the model, a qualitative study based on structured interviews, focus group discussions and observations, was performed in four selected municipalities in Denmark: Frederiksberg, Odense, Amager and Esbjerg. The evaluation was undertaken by the Danish National Centre for Social Research. It is concluded that the PSP cooperation draws attention to marginalized groups of citizens and helps to prevent social downfall and crime. Participants of the PSP cooperations further highlight positive changes in the cooperation between the involved sectors, which is thought to further improve the support to vulnerable citizens and thereby enhance both prevention and follow up of cases. Furthermore, the recommendations drawn from the evaluation are to adapt PSP cooperations to local conditions, avoid unnecessary red-tape, keep a constant focus on citizens' ethics, as well as involve the frontline workers in the individual sectors, i.e. those who are actually in contact with marginalized citizens.

Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.

OBJECTIVE: Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. DESIGN: A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. SUBJECTS: A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909. RESULTS: From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. CONCLUSION: Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes.

AIM: Sulphonylureas (SUs) are often used as first-line treatments for type 2 diabetes in Japan, hence it is important to study new antidiabetic drugs in combination with SUs in Japanese patients. METHODS: The efficacy and safety of the once-daily human glucagon-like peptide-1 (GLP-1) analogue liraglutide were compared in 264 Japanese subjects [mean body mass index (BMI) 24.9 kg/m(2); mean glycated haemoglobin (HBA1c) 8.4%] randomized and exposed to receive liraglutide 0.6 mg/day (n = 88), 0.9 mg/day (n = 88) or placebo (n = 88) each added to SU monotherapy (glibenclamide, glicazide or glimeprimide) in a 24-week, double-blind, parallel-group trial. RESULTS: The mean change in HBA1c from baseline to week 24 (LOCF) was -1.56 (s.d. 0.84) and -1.46 (s.d. 0.95) with liraglutide 0.9 and 0.6 mg respectively, and -0.40 (s.d. 0.93) with placebo. HBA1c decreased in the placebo group from 8.45 to 8.06%, while liraglutide reduced HBA1c from 8.60 to 7.14%, and from 8.23 to 6.67% at the 0.6 and 0.9 mg doses respectively. Mean HBA1c at week 24 of the two liraglutide groups were significantly lower than the placebo group (p < 0.0001 for both). More subjects reached HBA1c < 7.0% with liraglutide (0.6 mg: 46.5%; 0.9 mg: 71.3%) vs. placebo (14.8%). Fasting plasma glucose (FPG) levels were significantly improved with liraglutide (difference -1.47 mmol/l and -1.80 mmol/l with 0.6 and 0.9 mg vs. placebo; p < 0.0001). Overall safety was similar between treatments: no major hypoglycaemic episodes were reported, while 84/77/38 minor hypoglycaemic episodes occurred in the 0.6 mg/0.9 mg and placebo treatment groups (all in combination with SU), reflecting lower ambient glucose levels. No relevant change in mean body weight occurred in subjects receiving liraglutide (0.6 mg: 0.06 kg; 0.9 mg: -0.37 kg), while mean body weight decreased in subjects receiving placebo (-1.12 kg). CONCLUSIONS: The addition of liraglutide to SU treatment for 24 weeks dose-dependently improved glycaemic control vs. SU monotherapy, without causing major hypoglycaemia or weight gain or loss.

Efficacy and safety of the once-daily human GLP-1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes.

OBJECTIVE: Liraglutide is a once-daily human glucagon-like peptide-1 (GLP-1) analogue developed for the treatment of type 2 diabetes mellitus (T2DM). In Phase 2 and Phase 3 trials, largely conducted in populations of European descent, liraglutide has been shown to lower HbA(1C), weight and systolic blood pressure with a low risk of hypoglycaemia. This Phase 3, 24-week, multi-centre, double-blind, double dummy, randomised parallel-group trial compared the efficacy and safety of liraglutide and glibenclamide monotherapy in Japanese subjects with T2DM, inadequately controlled with diet therapy or oral antidiabetic drug (OAD) monotherapy. RESEARCH DESIGN AND METHODS: A total of 411 Japanese subjects were randomised 2:1 to liraglutide (n = 272) or glibenclamide (n = 139). Liraglutide was administered at a maximum planned dose of 0.9 mg once daily. Glibenclamide was administered once or twice daily at a planned maximum dose of 2.5 mg/day, before or after meals. CLINICAL TRIAL REGISTRATION: NCT00393718. RESULTS: After 24 weeks, glycaemic control with liraglutide was non-inferior/superior to glibenclamide, with HbA(1C) at 24 weeks of 6.99% (SE +/- 0.07) with liraglutide and 7.50% (+/-0.09) with glibenclamide (difference, -0.5%; 95% CI -0.70 to 0.30; p < 0.0001). Mean fasting plasma glucose (FPG) levels at 24 weeks were significantly lower with liraglutide (7.6 mmol/l [SE +/- 0.1]) vs glibenclamide (8.3 mmol/l [+/-0.1]; difference, -0.72 mmol/l; 95% CI -1.0 to -0.4; p < 0.0001). Weight was reduced by -0.92 kg from a baseline of 65.2 kg in liraglutide-treated patients, compared with weight gain of +0.99 kg from a baseline of 64.8 kg with glibenclamide (difference, -1.91 kg; 95% CI -2.34 to -1.48; p < 0.0001). A significantly lower rate of minor hypoglycaemic episodes was achieved with liraglutide compared with glibenclamide (p < 0.0001), and no major hypoglycaemic episodes were reported in either treatment group. The most common gastrointestinal AEs were diarrhoea (liraglutide, 6.3%; glibenclamide, 3.8%) and constipation (liraglutide, 5.6%; glibenclamide, 3.8%). Nausea was infrequent (liraglutide, 4.5%; glibenclamide, 1.5%). CONCLUSIONS: Liraglutide monotherapy, administered once daily for 24 weeks in Japanese subjects with T2DM, was well tolerated. Compared with glibenclamide monotherapy, liraglutide achieved superior glycaemic control and weight outcome, and a significantly lower incidence of hypoglycaemia. Future studies, comprising a greater proportion of true therapy-naïve Japanese patients, will be beneficial in order to establish the true add-on efficacy of liraglutide monotherapy in patients with T2DM.

Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: A double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes.

AIMS: To evaluate dose-response efficacy and safety of once-daily human GLP-1 analog liraglutide in Japanese subjects with type 2 diabetes. METHODS: Patients (226, treated with diet with/without OADs, mean HbA(1c) 8.30%, mean BMI 23.9kg/m(2)) were randomized after OAD discontinuation and washout to receive liraglutide 0.1, 0.3, 0.6 or 0.9mg once daily, or placebo in double-blind, parallel-group design for 14 weeks. RESULTS: Liraglutide dose levels reduced HbA(1c) versus placebo (by 0.79%, 1.22%, 1.64% and 1.85%, respectively; p<0.0001 for linear contrast). Liraglutide 0.9mg/day resulted in 75% of patients achieving HbA(1c) <7.0% and 57% achieving HbA(1c) <6.5%. There were no major or minor hypoglycemic events. Liraglutide also reduced, with significant dose-response (each p<0.0001 for linear contrast) versus placebo: fasting plasma glucose (up to 2.5mmol/L), postprandial (0-3h) glucose excursion (up to 12.8mmol/(Lh)); and increased postprandial insulin secretion (up to 23.0microU/(mLh)) and beta-cell function as evaluated by HOMA-beta (up to around 20.0(microU/mL)/(mg/dL)). Body weight was unchanged; no development of liraglutide antibodies was detected. CONCLUSIONS: Liraglutide was highly effective and well tolerated at doses up to 0.9mg/day in Japanese patients with type 2 diabetes, allowing glycemic control without weight gain or hypoglycemia.

Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder.

BACKGROUND: Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. RESULTS: Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug), before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. CONCLUSION: These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder.