Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm, open-label study.

OBJECTIVE: To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting. METHODS: Adults hospitalized with an acute exacerbation of schizophrenia were prospectively treated with open-label flexibly-dosed paliperidone ER 3-12 mg/day for 6 weeks. RESULTS: Overall, 294 patients were treated. The primary endpoint, defined as ≥30% improvement in Positive and Negative Syndrome Scale total scores from baseline to endpoint, was achieved by 66.3% of patients. The percentage of patients rated as at least 'markedly ill' in Clinical Global Impression of Severity scale decreased from baseline (74.1%) to endpoint (20.0%). Patient functioning, assessed by the Personal and Social Performance scale, improved significantly from 50.0 ± 14.3 at baseline to 63.6 ± 14.9 at endpoint (p < 0.0001). Concomitant benzodiazepines were newly initiated in 191 patients (65.0%), and new concomitant medications other than benzodiazepines were started after baseline for 133 patients (45.2%), most frequently paracetamol, zolpidem, and zopiclone. No unexpected adverse events were identified. CONCLUSIONS: These data support findings in more selected patient populations treated with fixed-dose paliperidone ER. Flexibly-dosed paliperidone ER administered in a naturalistic hospital setting to a more representative patient population experiencing an acute episode of schizophrenia, was associated with clinically meaningful treatment response. Strength of conclusions is limited by the open-label design and lack of a comparator group. Furthermore, some of the improvements observed may in part be associated with increased attention provided to patients and concomitant use of psychotropic medications, such as benzodiazepines, during this study.

Metabolic effects of paliperidone extended release versus oral olanzapine in patients with schizophrenia: a prospective, randomized, controlled trial.

Metabolic effects are generally more pronounced with second-generation than first-generation antipsychotics. This study was designed to compare long-term metabolic effects and efficacy of paliperidone extended release (ER) with those of oral olanzapine in patients with schizophrenia. In this 6-month, multicenter, prospective, randomized, controlled, open-label, parallel-group study, adults with schizophrenia were treated with paliperidone ER (6-9 mg/d; n = 239) or oral olanzapine (10-15 mg/d; n = 220). The primary outcome was mean change in the ratio of serum triglyceride level to high-density lipoprotein level (TG/HDL), a marker of insulin resistance. Other outcome measures included the Positive and Negative Syndrome Scale scores, measures of lipid and glucose metabolism, and body weight. Significant improvements in psychotic symptoms were observed with both treatments (P < 0.0001). The TG/HDL ratio was significantly higher at end point versus baseline with olanzapine compared with that of paliperidone ER. Mean end point change in TG/HDL ratio was 0.97 ± 2.72 [corrected] for olanzapine (P < 0.0001, reflecting worsening), with no significant change for paliperidone ER (-0.17 ± 2.51). Newly diagnosed impairment in TG and metabolic syndrome was more common with olanzapine (P < 0.05). Insulin resistance, as measured by the homeostasis model assessment of insulin resistance, worsened significantly with olanzapine (P = 0.0003), but not with paliperidone ER. Glucose sensitivity for insulin worsened significantly with olanzapine (P < 0.03), with no significant changes for paliperidone ER. End point increase in body weight was significantly higher with olanzapine than paliperidone ER (3.8 vs 1.2 kg; P = 0.0013). In summary, both paliperidone ER and olanzapine effectively treated schizophrenia; however, undesirable metabolic effects were significantly greater with olanzapine.

Cardiopulmonary effects of sufentanil long acting on sevoflurane anaesthesia in dogs.

OBJECTIVE: To evaluate the cardiopulmonary effects of sufentanil long acting (SLA) in sevoflurane-anaesthetized dogs. STUDY DESIGN: Randomized prospective study. Animals Forty female dogs (beagles) aged 1-2 years, weighing 11.97 +/- 1.40 kg. MATERIALS AND METHODS: The dogs were divided into five groups of eight. Two control groups were used: group A received intramuscular (IM), SLA (50 microg kg(-1)) alone, while group B received the SLA vehicle followed by sevoflurane anaesthesia for 90 minutes. In the other groups, SLA (50 microg kg(-1) IM) was given immediately before (group C(0)), 15 minutes before (group D(15)) or 30 minutes (group E(30)) before induction [with intravenous (IV) thiopental] of sevoflurane anaesthesia lasting for 90 minutes. Heart rate, arterial blood pressure, respiratory rate (f(r)), arterial oxygen haemoglobin saturation and end-tidal sevoflurane concentration (Fe'SEVO) were measured every 10 minutes during anaesthesia and at 2, 4 and 24 hours after induction (not Fe'SEVO). Acid-base and blood gas analyses were performed. RESULTS: Sufentanil LA reduced heart rate and increased arterial CO(2) tensions during anaesthesia. Respiratory depression was least in group E(30) compared with groups C(0) and D(15). Bradycardia was present for at least 24 hours. Respiratory rate was least in group B although arterial O(2) and CO(2) tension values were acceptable up to 24 hours after anaesthesia. CONCLUSIONS: Pre-anaesthetic medication with SLA moderately aggravated the cardiopulmonary effects of sevoflurane. CLINICAL RELEVANCE: In spite of a moderate depressant effect on cardiorespiratory parameters, SLA may be of use as pre-anaesthetic medication before sevoflurane anaesthesia in dogs. Intermittent positive pressure ventilation may occasionally be necessary.

In vitro studies on the effects of flubendazole against Toxocara canis and Ascaris suum.

Adult Toxocara canis and Ascaris suum were incubated in vitro in media containing 0.1, 1, 10 or 100 micro g/ml flubendazole in order to study drug-derived effects. This incubation was done for 8 h and repeated (in some groups) after 24 h for another 8 h. The onset and intensity of flubendazole-derived effects were dosage-dependent and time-dependent, i.e. the same grade of damage was reached when incubating for a longer period at a low dosage or for a shorter period in medium containing a high amount (10 or 100 micro g/ml) of flubendazole. A repeated incubation in drug-containing medium was superior to a single exposure. Flubendazole is apparently able to penetrate into the worm's interior via the cuticle. This became evident in worms with sealed orifices, which showed identical damage to worms which were not sealed. The type of tissue damage due to flubendazole was identical in both worm species when exposed to any of the drug dosages used. The principal mode of action of flubendazole was based on the complete reduction of microtubuli-polymerisation inside the parasite's cells. This apparently led to the complete destruction of the hypodermis, muscle layer and intestine. Flubendazole also stopped the formation of gametes. Summarising, even low concentrations of flubendazole (0.1 micro g/ml) led to significant and irreversible damage in all worms studied.