Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism

Background

Nephrotic syndrome (NS) is a well-known risk factor for venous thromboembolism (VTE), however preventive measures are not routinely taken. In non-renal populations, statins are associated with lower risk of VTE. Hence, we set up this single-center retrospective cohort study to assess whether statin use influenced VTE risk in NS subjects.

Methods

We analyzed 289 consecutive patients with NS (defined by proteinuria ≥ 3.5 g/day) who were aged > 18 years at the study entry and followed for at least 6 months. Use of statins and concomitant medication were determined.

Results

Of patients with NS (59% men; mean age, 42 years), 48% used statins for at least 1 month during NS. Using univariate and time-dependent Cox regression analyses, hazard ratio for VTE in statin users versus non-users was 0.2 (95%CI, 0.1-0.7) and 0.6 (95% CI, 0.2 -2.0), respectively. Adjustments for potential confounders did not change outcomes. Three VTE events occurred in a total of 812 statin-years, corresponding to an annual incidence of 0.37% (95%CI, 0.12-1.15). In contrast, 17 VTE occurred in a total of 2106 patient-years without statin exposure, annual incidence 0.81% (95%CI, 0.50-1.30).

Conclusions

Although statistically significant, the hazard ratio of 0.2 for VTE risk in statin users versus non-users could have been biased, but the time-dependent hazard ratio of 0.6 was probably not. As the association was in the same direction for both analyses, we conclude that statin use is associated with a lower risk of VTE in patients with NS.     

Comparison and evaluation of a Point-of-care device (CoaguChek XS) to Owren-type prothrombin time assay for monitoring of oral anticoagulant therapy with warfarin

Background

The standardized test used for evaluating the effect of warfarin is the prothrombin time (PT) which is measured and expressed in international normalized ratio (INR). Regular control of treatment intensity is required since inappropriate dosage increases the risk for complications. Portable point-of-care analytical instruments for measurement of capillary whole blood PT have been available for the last decades. The purpose of this study was to compare and evaluate INR values obtained by the point-of-care device CoaguChek XS, to Owren PT in a hospital setting.

Materials and Methods

In 397 warfarin-treated patients, capillary whole blood was analyzed with the CoaguChek XS and the results were compared to analysis of venous plasma samples with the Owren PT assay. To study reproducibility and rule out preanalytical errors, a subgroup of 152 patients had two capillary blood samples analyzed with the CoaguChek XS.

Results

In 397 patients, with a median age(±2SD) of 69.0(50-88) years, there was a positive correlation between results from the CoaguChek XS and the Owren-type PT assay (r = 0.94;p < 0.001) and concordance of 88.2%. The mean INR difference (S.D) was 0.02 (0.22). Comparison of the 152 double samples analyzed with the CoaguChek XS, produced a positive correlation of 0.99; p < 0.001.

Conclusions

The CoaguChek XS presents reproducible, highly comparable results with Owren PT at therapeutic levels of INR. The CoaguChek XS seems to produce better results than the earlier CoaguChek S, probably due to a new method of PT measurement where levels of fibrinogen and haematocrit do not affect the outcome.     

The acute phase reaction explains only a part of initially elevated factor VIII:C levels: a prospective cohort study in patients with venous thrombosis

We determined in a prospective cohort of patients treated with vitamin K antagonists for venous thrombosis, the course of factor VIII (FVIII:C), C-reactive protein (CRP) and fibrinogen levels, to assess the influence of the acute phase reaction on FVIII:C levels. Second, we hypothesized that patients with preceding infectious symptoms might have higher levels of FVIII:C at baseline than patients without those.We included 75 patients. Blood was sampled at baseline, once during treatment (t = 1) and at the end of treatment (t = 2). Mean levels of FVIII:C were 207, 186 and 175 IU/dL (p for trend 0.003) at baseline, t = 1 and t = 2 respectively. Eight-eight percent of patients had an elevated FVIII:C at baseline, 75% at t = 1 and 72% at t = 2 (p for trend 0.045). Mean levels of FVIII:C were not different in patients with or without preceding infectious symptoms (206 versus 205 IU/dL respectively). A baseline CRP level below 62 mg/L could best distinguish between patients who will keep an elevated FVIII:C and those who will drop below 150 IU/dL.We conclude that FVIII:C levels are partially influenced by the acute phase reaction, especially in patients who keep a persistent elevated FVIII:C during treatment.Preceding infectious symptoms did not influence baseline FVIII:C levels.     

缺血性卒中患者因氯吡格雷低反应性改为高维持量及替格瑞洛后血小板抑制率变化

目的探讨用血栓弹力图评价符合双抗治疗的缺血性脑血管病患者,因氯吡格雷低反应性,改为高维持剂量及改服替格瑞洛后血小板抑制率的变化。方法选择符合双抗治疗的缺血性脑血管病患者联合应用抗血小板制剂(阿司匹林肠溶片100 mg/qd+氯吡格雷75 mg/qd)前及后7 d,用血栓弹力图检测患者的花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率,筛选出氯吡格雷低反应性者96例,随机分为3组,常规剂量组(氯吡格雷75 mg/qd,32例)、高维持量组(氯吡格雷150 mg/qd,32例)和替格瑞洛组(替格瑞洛90 mg/bid,32例),3组阿司匹林继续按原剂量服用。分组后3组按新方案治疗7 d,再次复查血栓弹力图。结果分组后高维持量组及替格瑞洛组ADP诱导的血小板抑制率较常规剂量组有显著性差异(P0.05),3组均未发生出血等严重不良事件,替格瑞洛组发生1例轻度呼吸困难。替格瑞洛组高于同一时间点高维持量组ADP途径诱导的血小板抑制率(P0.05)。结论针对常规剂量氯吡格雷的低反应性,替格瑞洛及双倍剂量的氯吡格雷均能有效降低血小板的高反应性,并且替格瑞洛的作用更为明显,且未增加出血等不良事件的发生。     

When knowing what to do is not sufficient to make good decisions: Deficient use of explicit understanding in remitted patients with histories of suicidal acts

Disadvantageous decision-making has been reported in patients who had attempted suicide and may represent a cognitive risk factor for suicide. Making decisions necessitates both implicit/associative and explicit/analytic processes. Here, we explored explicit mechanisms, and hypothesized that suicide attempters fail to use explicit understanding to make favorable choices. The Iowa Gambling Task (IGT) was used to assess decision-making in 151 non-depressed patients with a history of mood disorder and suicidal act, 81 non-depressed patients with a history of mood disorders but no suicidal act, and 144 healthy individuals. After performing the task, we assessed the explicit understanding of the participants of the contingencies in the task, i.e. which options yielded higher gain or loss. Correct explicit understanding was reported less often in suicide attempters and affective controls than in healthy controls (45.7% and 42.0% vs. 66.0%). Moreover, understanding was associated with better performance in healthy and affective controls, but not in suicide attempters, with no between-group difference among those who did not reach understanding. Patients with histories of suicide attempt, therefore, show a disconnection between what they “know” and what they “do”, possibly reflecting underlying impairments in implicit associative processes. These cognitive alterations should be addressed in preventative interventions targeting suicide.     

Quetiapine demonstrates good tolerability and is associated with improvements in extrapyramidal symptoms in patients with schizophrenia switched from other antipsychotics: results of a naturalistic study

Objectives. Compared with conventional agents, atypical antipsychotics such as quetiapine (Seroquel®; AstraZeneca) show improved tolerability and a lower liability to cause extrapyramidal symptoms (EPS). In the routine treatment of schizophrenia, it is usual practice to consider a change of medication when the current treatment is ineffective or poorly tolerated, although few studies are available to guide clinicians. This paper reports the results from the Seroquel Method. Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) trial, a 12-week, open-label, noncomparative study that evaluated clinical benefit and tolerability of switching patients with schizophrenia from their existing antipsychotic to quetiapine. Patients were switched because of intolerance to, or lack of efficacy with, their previous antipsychotic. Quetiapine was titrated to 400 mg/day over 7 days, then dosed flexibly up to 750 mg/day over the remaining weeks (mean modal dose 505 mg/day). Results. In the overall population of 506 evaluable patients, quetiapine was well tolerated, with a low incidence of adverse events and minimal requirement for anticholinergic medication. Significant improvements in EPS, including parkinsonism and akathisia, were observed, irrespective of reason for switching, although greatest improvements were observed in patients switching because of EPS. Conclusions. This study provides further evidence for the utility and tolerability of quetiapine, in patients with schizophrenia who had been switched from a previous antipsychotic, following problems with efficacy or tolerability.     

The improvement in respiratory function by inspiratory muscle training is due to structural muscle changes in patients with stroke: a randomized controlled pilot trial

Background: The changes effected by the inspiratory muscle training (IMT) on the structure of inspiratory muscles such as on the diaphragm, in patients with stroke, is unclear.

Objective: To investigate the effect of IMT on inspiratory function, diaphragm thickness, walking endurance, and fatigue in patients with stroke.

Methods: A total of 30 patients with stroke were randomized to either the experimental group or the control group. The experimental group (n = 15) underwent inspiratory muscle training with resistance adjusted to 30% of maximal inspiratory pressure, 90 breaths a day, 5 times a week for 6 weeks. Both groups received regular physical therapy for the same amount of time. The primary outcome measure was the diaphragm thickness ratio. The secondary outcomes were inspiratory function; maximal inspiratory pressure and inspiratory muscle endurance; and gait endurance and fatigue.

Results: There were significant differences between the two groups in the thickness ratio on the affected diaphragm thickness (medium effect size), maximal inspiratory pressure (medium effect size), and inspiratory muscle endurance (large effect size; Bonferroni correction p < 0.005). The gait endurance (medium effect size) and fatigue (small effect size) showed no significant differences in the between group comparison.

Conclusion: Inspiratory muscle training was effective in improving respiratory function and inducing structural changes, especially in the affected diaphragm.     

Drebrin A expression is altered after pilocarpine-induced seizures: time course of changes is consistent for a role in the integrity and stability of dendritic spines of hippocampal granule cells

We used a pathophysiological model of temporal lobe epilepsy induced by pilocarpine in adult rats in order to assess the in vivo role of drebrin A (DA), one of the major regulators of F-actin. This model displays a dynamic reorganization of the glutamatergic network including neo-spinogenesis, morphogenesis, and neo-synaptogenesis associated with an aberrant sprouting of granule cell axons in the dentate gyrus (DG). This reactive plasticity contributes in dentate granule-cell hyperexcitability that could lead to the emergence of recurrent spontaneous seizures. We investigated the hippocampal DA expression changes in pilocarpine animals using immunohistochemical, Western blot, and in situ hybridization analyses. We showed that DA immunoreactivity was decreased in the inner molecular layer (IML) and in the hilus (H) of the DG, at latent stage, when spinogenesis and morphogenesis occur. Western blot analysis confirmed these overall hippocampal decreases of DA protein expression. At chronic stage, when newly formed glutamatergic synapses are being established, the levels of immunolabeling for DA in the H and the IML were similar to control rats. This recovery is likely due to the increase of DA mRNA in perikarya of hilar and granule cells. Interestingly, our data showed that the changes pattern of labeling for Bassoon, a specific marker for presynaptic active zone, in the IML of pilocarpine-treated animals paralleled those found for DA at all time points examined. Furthermore, our double and triple immunofluorescence studies showed that the recovery in DA levels in the IML occurred within the dendritic spines involved in glutamatergic active synapses of presumed granule cells. Altogether, our results indicate that in vivo DA is not critical for spinogenesis and morphogenesis but instead is consistent with an involvement in synaptic structural integrity, stabilization, and function. Thus, DA appears as a novel modulator of reactive synaptic plasticity associated with epilepsy.     

Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation

Despite prolonged survival, patients with multiple sclerosis (MS) experience considerable morbidity, which adversely impacts quality of life. To assess the risk-benefit of a clinical trial of high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation for MS, we sought to determine the natural history of the disease in a comparison group of untreated patients. We identified 285 individuals with 2132 combined observation years (median: 5.6 years; 5th to 95th percentile: 1-21 years), with Expanded Disability Status Scale (EDSS) scores of 3.0-5.5 at baseline observation. Disease-related mortality was zero at five years, 5.4% at 10 years, and 22% at 15 years (40 patients contributing to the data point; 95% confidence interval: 4-32%). Risk for progression to advanced disability, defined as an EDSS score of 8, was very low for the subgroup with a baseline EDSS score of 3-3.5; however, for those with a baseline EDSS score of 4-5.5, 3% had advanced disability after two years, 5% after three years, 6% after four years, 12% after five years, and 40% after 10 years. The estimated probability of disease progression, defined as an increase in EDSS score by > or = 1.0 sustained for at least 180 days, was 5% after one year, 14% after two years, 22% after three years, 38% after five years, 57% after 10 years, and >80% after 20 years of observation. The relevance of these features to the design of the clinical trial is discussed.     

A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism

Background

Pharmacogenomic warfarin dosing has been suggested to produce more accurate dosing and an improved patient safety profile; however, very few models have been derived in patients with venous thromboembolism. We sought to develop a new algorithm to predict maintenance dose in a cohort of patients, using clinical variables and genetic polymorphism in CYP2C9, VKORC1, and CYP4F2.

Methods

Patients on a stable maintenance dose of warfarin, with observed dose ranging from 0.6 to 12 mg were recruited from a specialized anticoagulation clinic (Ottawa Hospital Thrombosis Clinic) with genotyping and standardized patient interviews being conducted to collect clinical and genomic variables known to impact warfarin dose. Multivariate linear regression was used to develop the model using a stepwise backwards elimination approach.

Results

From 249 enrolled patients with a mean clinical maintenance dose of 5.58 mg/day, a model with an R² of 58% was developed as: Dose = 1.85-0.048(Age) + 0.041(BMI) + 0.05(Height in cm) - 0.73(Less Exercise) - 1.13(2C9*2 Hetero) - 2.09(2C9*2 Homo) - 1.51(2C9*3 Hetero) -1.43(VKORC1 GA) - 2.86(VKORC1 AA) - 1.33(4F2 CC) -1.24(4F2 CT) - 1.46(Angiotensin II Receptor Antagonist) - 0.84(β-Blockers). Analysis of residual plots revealed that prediction errors were a function of observed maintenance dose with the model tending to predict higher doses than observed in those with low dose requirements and lower doses than observed in those with higher dose requirement.

Conclusion

Our study confirms the importance of the CYP4F2 polymorphism. Our model may prove useful in clinical practice but further validation studies are required before implementation into clinical practice.     

Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: Potential role of protein Z as a powerful determinant of coagulation assays

Background

The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them.

Methods

The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured.

Results

The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0–3.0 was 290.1–494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro.

Conclusions

The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy.     

The influence of oral VPA on the required dose of propofol for sedation during dental treatment in patients with mental retardation: a prospective observer-blinded cohort study

In sedation of dental patients with moderate or severe mental retardation, it is difficult to identify the optimum sedation level and to maintain it appropriately. Moreover, many patients have concomitant epilepsy and are medicated with oral antiepileptic drugs (AEDs), which influence the drug-metabolizing enzymes. In particular, valproate (VPA) has been demonstrated to inhibit propofol metabolism in vitro. Therefore, the objective of the present study was to investigate the clinical influence of oral VPA on the required dose of propofol for sedation, with use of a prospective cohort study design. We studied 45 patients with moderate or severe mental retardation who underwent dental treatment under sedation. Propofol was infused, and sedation was maintained at the same level in all patients using a bispectral index (BIS) monitor. After the completion of treatment for the scheduled patients, patients were divided into those with oral VPA treatment (VPA group: 20 patients) and without any oral antiepileptic treatment (control group: 25 patients). The propofol dose required for sedation and times to the recovery of the eyelash reflex and spontaneous eye opening were evaluated. The median required propofol doses in the VPA and control groups were 4.15 (range 1.97-5.88) and 5.67 (2.92-7.17) mg/kg/h, respectively. We observed a statistically significant difference between the two patient groups with respect to median VPA dose (p < 0.01). However, no statistically significant differences were noted in the time until eyelash reflex recovery or spontaneous eye opening between the two groups. The results suggest that oral VPA reduces the dose of propofol required for sedation during dental treatment in patients with moderate or severe mental retardation.     

Acute disseminated encephalomyelitis that meets modified McDonald criteria for dissemination in space is associated with a high probability of conversion to multiple sclerosis in Taiwanese patients

Background: Patients with acute disseminated encephalomyelitis (ADEM) may relapse and some may ultimately convert to multiple sclerosis (MS); however, no criteria that can predict MS conversion are available to date. Our aim was to describe the clinical and magnetic resonance imaging (MRI) features of patients with an initial ADEM attack and evaluate which MRI criteria can predict conversion to MS. Methods: We retrospectively reviewed the records of 36 patients diagnosed with ADEM. We determined clinical signs/symptoms, examined the cerebrospinal fluid (CSF), and performed brain MRI scans and compared the findings between patients who did and did not convert to MS. Results: Clinical signs/symptoms, and CSF analysis show no significant difference between the two groups. The rate of conversion to MS from ADEM in Taiwanese patients is low (11%) after a mean follow‐up period of 28.36 months. Modified McDonald criteria were fulfilled in 19/36 patients: 21% (4/19) of those patients developed MS according to Poser criteria subsequently. Of the other patients (17/36) who did not fulfill these criteria, none converted to MS. (log rank test; P = 0.027). Conclusions: It is difficult to predict from initial clinical presentations to address which patients with ADEM will convert to MS. Patients with ADEM whose brain MRI findings met the modified McDonald criteria may have clinically isolated syndrome because they have a significantly higher probability of conversion to MS. In contrast, patients whose brain MRI findings did not meeting these criteria may be considered as having classic ADEM because they have a lower probability of conversion to MS.     

Gabapentin versus vigabatrin as first add-on for patients with partial seizures that failed to respond to monotherapy: a randomized, double-blind, dose titration study. GREAT Study Investigators Group. Gabapentin in Refractory Epilepsy Add-on Treatment

PURPOSE: Our objective was to compare the efficacy and safety of gabapentin and vigabatrin as first-line add-on treatment in patients with partial epilepsy. METHODS: This was a multicenter, double-blind, randomized dose titration study. After baseline assessment and randomization, the dose could be increased if seizures persisted and reduced if side effects occurred. Health-related quality of life was assessed at baseline and at the end of the study. By a protocol amendment post hoc, all randomized patients were offered a standardized perimetry examination at the end of the study. Improvement rate was the proportion of patients with a reduction of seizure frequency of at least 50% during an 8-week period without any adverse events causing withdrawal. RESULTS: One hundred two patients were randomized and analyzed on an intent-to-treat basis. The improvement rate was 48% in the gabapentin group and 56% in the vigabatrin group. The improvement rate, when per protocol criteria were fulfilled, was 57% in the gabapentin group and 59% in the vigabatrin group. The proportion of seizure-free patients was 31% in the gabapentin group and 39% in the vigabatrin group. There was no difference in quality-of-life scores between the groups. Perimetry after termination of the study on 64 patients showed abnormal results in 3 of 32 patients in the vigabatrin group. CONCLUSION: Approximately one third of the patients in both groups became seizure-free. Although no major differences were seen in terms of the improvement rate between the groups, equivalence between the two drugs was not found.     

The effect of long-term treatment with clozapine in schizophrenia: a retrospective study in 96 patients treated with clozapine for up to 13 years

A retrospective study was performed to evaluate the effect of long-term treatment with clozapine in 96 schizophrenic or schizoaffective patients hospitalized at the Psychiatric Research Center in Uppsala during the period 1974-1986. All patients had previously been treated with different neuroleptics but with inadequate response or distressing side effects. The mean duration of the disorder at the start of clozapine treatment was 8 years and 9 months and the mean duration of the treatment 3 years and 11 months. Clozapine treatment was discontinued in 36% of the patients, mainly due to lack of efficacy, poor compliance or temporary withdrawal of the drug from the market in 1975. In two patients the reason was leukopenia or agranulocytosis. In another 10 patients a transient decrement of WBC was seen, which was normalized during ongoing treatment. Four patients died when on clozapine during the follow-up period, but no causal relationship to the treatment could be established. Eighty-five per cent of the patients could be discharged from the hospital. Of the 62 patients who were still on clozapine after 2 years, 18% had full time and 21% half-time employment. A global evaluation of the clinical efficacy revealed a significant improvement in 43% and a moderate improvement in 38% of the patients compared to previous neuroleptic treatments. Common but usually mild side effects were sedation, hypersalivation, weight gain, and obstipation. Four patients had grand mal seizures. No extrapyramidal side effects were observed during clozapine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enzyme-linked immunosorbent assay for human autoantibody to glial fibrillary acidic protein: higher titer of the antibody is detected in serum of patients with Alzheimer''s disease

We have developed an enzyme-linked immunosorbent assay (ELISA) to detect anti-glial fibrillary acidic protein (GFAP) autoantibody in human sera. The ELISA was prepared by coating microtest plates with purified GFAP from bovine spinal cord. The autoantibody activities were assayed in the serum from 219 control subjects, 39 Alzheimer's disease patients and 39 cerebrovascular dementia patients. Higher titer of the antibody was observed in the serum of Alzheimer's disease patients. Since the titer showed no significant change with aging or with sex in the control serum, we could determine a certain normal value of the antibody titer. The percentage of abnormal subjects whose antibody levels were over the normal value was 53.8% in Alzheimer's disease (presenile onset) patients, 30.8% in Alzheimer's disease (senile onset) patients, 10.3% in cerebrovascular dementia patients and 5.5% in control subjects. We discuss the relationship between the anti-GFAP autoantibody and the pathogenesis of Alzheimer's disease and suggest that the evaluation of anti-GFAP autoantibody level may be useful in diagnosing Alzheimer's disease.     

Levodopa/DDCI and entacapone is the preferred treatment for Parkinson's disease patients with motor fluctuations in routine practice: a retrospective, observational analysis of a large French cohort

Levodopa is the gold standard drug for the symptomatic control of Parkinson's disease (PD). However, long-term treatment with conventional formulations [levodopa and a dopa decarboxylase inhibitor (DDCI)], is associated with re-emergence of symptoms because of wearing-off and dyskinesia. Treatment with levodopa/DDCI and entacapone extends the half-life of levodopa, avoiding deep troughs in levodopa plasma levels and providing more continuous delivery of levodopa to the brain. In this open-label, retrospective, observational study we investigated the effects of levodopa/DDCI and entacapone therapy in 800 PD patients with motor fluctuations. Levodopa/DDCI and entacapone treatment was assessed as good/very good in improving motor fluctuations (64%) and activities of daily living (ADL; 62%). The therapeutic utility was considered to be good/very good in 70% of cases. Moreover, there was a reduction in levodopa dose in 20% of patients. Neurologists preferred levodopa/DDCI and entacapone compared with increasing levodopa dosage, dose-fractionation or addition of a dopamine agonist (63%, 29% and 23% of patients respectively). Reasons included achieving more continuous dopaminergic stimulation (40%), reducing motor fluctuations (54%) and improving ADL (41%). This analysis reveals the preference of neurologists for levodopa/DDCI and entacapone over conventional levodopa-modification strategies for the effective treatment of PD motor fluctuations in clinical practice.     

Greater sensitivity to novelty in rats is associated with increased motor impulsivity following repeated exposure to a stimulating environment: implications for the etiology of impulse control deficits

Heightened motor impulsivity and increased novelty‐seeking commonly co‐occur in psychiatric disorders, including drug addiction. However, the relationship between these two phenomena remains unclear. One‐time tests of novelty sensitivity commonly used in preclinical experiments, such as the open‐field or novel‐object test, fail to capture the fact that novelty‐seekers repeatedly experience novel, stimulating situations. The present study therefore investigated whether repeated exposure to a novel, stimulating environment (SE) altered impulsive action. Male Long‐Evans rats were trained to perform the five‐choice serial reaction time task (5CSRTT) which measures motor impulsivity in the form of premature responding as well as attention and motivation. Animals were then exposed to a novel SE (1 h/day for 16 days) immediately prior to the 5CSRTT. Significant increases in premature responding were observed in a subgroup of reactive animals termed high responders (HR‐SE). These rats were not more impulsive at baseline, and levels of impulsivity normalised once exposure to the SE was discontinued. No other aspect of 5CSRTT performance was affected by the SE challenge. We also determined that HR‐SE rats were hyperactive in a novel environment. Biochemical analyses revealed changes in gene and protein expression within the dorsal hippocampus of HR‐SE rats, including decreases in mRNA encoding the dopamine D₁ receptor and brain‐derived neurotrophic factor. These results indicate a novel mechanism by which impulsivity and novelty‐reactivity interact that may enhance addiction vulnerability synergistically. Furthermore, studying such context‐induced impulsivity may provide insight into the process by which environmental load precipitates psychiatric symptoms in impulse control disorders.