Impression Scores Research Articles

Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: evidence of clinical benefit.

PurposeTo establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy.MethodsThis retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH.Key FindingsEighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6–18 years). With use of a combination of a behavioral management program and MPH 0.3–1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69–0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH.SignificanceMethylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed.

Clinical subtypes of severe bipolar mixed states

ObjectiveThe aim of the present study was to identify different clinical subtypes in severe, treatment resistant bipolar mixed state (MS). MethodThe sample comprised 202 Bipolar I patients currently in MS referred for an Electro-convulsive Therapy (ECT) trial and evaluated in the first week of hospitalization and one week after the ECT course. Principal component factor analysis (PCA) followed by Varimax rotation was performed on 21 non-overlapping items selected from Hamilton rating-scale for depression (HAMD) and from Young mania rating-scale (YMRS) at baseline evaluation. Cluster subtypes derived from the factor scores were compared in clinical variables and final HAMD, YMRS, Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. ResultsThe principal-component analysis extracted 6 interpretable factors explaining 55.9% of the total variance. Cluster analysis identified four groups, including respectively 63 (31.2%) subjects with Agitated-Irritable Mixed-Depression, 59 (29.2%) with Psychotic Mixed-Mania, 17 (8.5%) with Anxious-Irritable-Psychotic Mixed-Mania, and 63 (31.2%) with Retarded-Psychotic Mixed-Depression. The four clusters were statistically distinct and did not show significant overlap in the main symptomatological presentation. Cluster subtypes reported differences in number of past mood episodes, duration of the current episode, suicide attempts, lifetime comorbidity with panic and eating disorders, baseline and final rating-scale scores and rate of remission after ECT trial. ConclusionsOur study indicates that, at least in severe treatment resistant MS, multiple depressive and manic subtypes can be observed with substantial differences in terms of clinical presentation, course, associated comorbidities and treatment response.

Manual Laparoscopic Skills Development Using a Low-Cost Trainer Box in Tanzania

To explore the feasibility and effectiveness of guided practice using a low-cost laparoscopic trainer on the development of laparoscopic skills by surgeons in a resource-poor setting. This was a prospective trial involving a pretest/posttest single-sample design. Study participants completed a background survey and pretest on the 5 McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) tasks using a simulator developed and validated by researchers from the University of California, San Francisco. On completion of a 3-month guided practice course, participants were again tested on the MISTELS tasks and completed an exit survey. The Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania. Fourteen Tanzanian surgery residents and specialists completed the study. Most of the subjects were surgical residents (64.3%). Only 2 participants (14.2%) had previous laparoscopic training, and baseline laparoscopic surgical experience was limited to intraoperative observation only. Study subjects practiced the MISTELS tasks for an average of 8.67 hours (range: 4.75-15.25) over the 3-month course. On the posttest, participants improved significantly in performance of each of the MISTELS tasks (p < 0.001). Total scores on the tasks increased from 24 ± 44 on the pretest to 384 ± 49 on the posttest (p < 0.001). All study participants were satisfied with the course, found the training personally valuable, and felt that their laparoscopic skills had improved on completion of the training. We have demonstrated the feasibility and effectiveness of training with a low-cost laparoscopic trainer box in Tanzania. Study participants achieved impressive posttest scores on the 5 MISTELS tasks with minimal baseline laparoscopic exposure. We feel that guided training by an expert was key in ensuring correct technique during practice sessions.

Treatment Outcomes with Lisdexamfetamine Dimesylate in Children Who Have Attention-Deficit/Hyperactivity Disorder with Emotional Control Impairments

The purpose of this study was to assess lisdexamfetamine dimesylate (LDX) treatment effects based on baseline emotional control dysfunction in children with attention-deficit/hyperactivity disorder (ADHD) categorized with or without impairments of executive function (EF) emotional control. Post-hoc analyses of a 7 week, open-label LDX study in children with ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision [DSM-IV-TR] defined) and impairments in EF control of emotional response. At baseline, participants were dichotomized by Behavior Rating Inventory of EF (BRIEF) emotional control domain T-scores of ≥65 (with impairment) or <65 (without impairment). ADHD Rating Scale-IV (ADHD-RS-IV), BRIEF Global Executive Composite and emotional control domain, Expression and Emotion Scale for Children (EESC) scores, Pearson correlations for BRIEF versus ADHD-RS-IV and EESC, and Clinical Global Impressions scores were assessed at baseline and end of study (week 7)/early termination (EOS/ET) by baseline category of BRIEF emotional control impairment. Safety assessments included treatment-emergent adverse events (TEAEs). At baseline and EOS/ET, respectively, 53.0% and 20.7% met criteria for emotional control impairment. Participants with and without emotional control impairments had similar ADHD-RS-IV change scores. Mean (SD) change from baseline for those with and without emotional control impairments were -20.8 (12.89) and -14.6 (11.25) for BRIEF global scores and -16.0 (13.19) and -5.0 (9.48) for BRIEF emotional control domain scores. Participants with emotional control impairments had greater mean EESC total score changes. BRIEF emotional control domain and all ADHD-RS-IV scores indicated moderate correlations between change scores (all p<0.0001). Overall, 84.9% of participants had TEAEs (mostly mild-to-moderate in severity); 3.8% discontinued because of TEAEs. The proportion of children with behavioral impairments in EF control of emotional response decreased during LDX treatment. ADHD symptoms improved in both groups. The moderate correlations between EF behaviors and ADHD symptoms suggest there may be utility in evaluating behavioral domains beyond core ADHD symptoms.

Electroconvulsive Therapy for Mood Disorders in Pregnancy

Electroconvulsive therapy (ECT) offers a treatment option for mood disorders during pregnancy. We retrospectively examined 12 pregnant patients who were treated with ECT for their mood disorders. The mean ± SD age of the patients was 28.1 ± 4.8 years. The mean ± SD number of ECTs performed was 9.8 ± 4.5. The mean ± SD Clinical Global Impression score was decreased from 6 to 2.6 ± 0.7 with ECT. No significant adverse events were observed other than early delivery in one patient and pes ekinovarus deformity in a newborn that was most probably not related to ECT causally. Electroconvulsive therapy seems to be an effective and safe treatment option in pregnant patients with mood disorders.

An 8-week, open-label study to evaluate the effect of sertraline on the polysomnogram of depressive patients with insomnia

We want to evaluate the effect of sertraline on polysomnogram (PSG) and clinical variables in depression. An 8-week and open-label trial (n = 31) was applied. The primary outcome was mean baseline-to-visit changes in PSG variables. The secondary outcomes were clinical improvement, side-effects, and the subjective sleepiness. Rapid eye movement (REM) latency was prolonged significantly over the course of the study. The arousal index reached the highest level on the 1st day (13.8 _ 7.2). From the 14th day onward, the sleep latency (SL) and wake after sleep onset (WASO) decreased significantly. The percentage of stage 3 sleep increased in this trial. The Hamilton Rating Scale for Depression (HRSD) and Clinical Global Impression (CGI) scores on the 14th, 28th, and 56th days were significantly lower than baseline. Furthermore, a significant correlation was shown between the decreasing score rate of HRSD on the 56th day and the decreasing score rate of REM latency on the 1st day (r = -0.733, P = 0.003). The effectiveness of sertraline positively correlated with the reduction of REM latency. The final clinical improvement could be predicted by the extent of the prolongation of REM latency on the first night.

Dronabinol for the Treatment of Agitation and Aggressive Behavior in Acutely Hospitalized Severely Demented Patients with Noncognitive Behavioral Symptoms

Behavioral disturbances occur frequently in demented individuals and greatly increase the burden of their care. The efficacy of pharmacotherapeutic treatment options is modest. This study was conducted to explore the efficacy and safety of dronabinol as an adjunctive treatment for agitation and aggressive behavior in severely demented patients. Using a retrospective systematic chart review, we studied 40 inpatients from the McLean Hospital Geriatric Neuropsychiatry Inpatient Unit diagnosed with dementia and treated with dronabinol for behavioral or appetite disturbances. A group of geriatric psychiatrists consulted medical records to rate the patients' behaviors prior to initiation of dronabinol treatment and following up to seven days of treatment, using the Pittsburgh Agitation Scale, Clinical Global Impression, and Global Assessment of Functioning. Data on percentage of food consumed ateach meal, sleep duration, and adverse events werealso collected from medical records. The addition of dronabinol to patients' treatment regimens was associated with significant decreases in all domains of the Pittsburgh Agitation Scale. There were also significant improvements in Clinical Global Impression scores, sleep duration and percentage of meals consumed during the treatment periods. Twenty-six adverse events were recorded during dronabinol treatment, none of which led to medication discontinuation. This report represents the largest studied cohort of dementia patients treated with dronabinol to date and confirms earlier reports that dronabinol can serve as an adjunctive treatment for neuropsychiatric symptoms in dementia. Further research, including prospective controlled trials, is needed to clarify dronabinol's role in treating noncognitive behavioral symptoms of demented individuals.

A Randomized, Multicenter Phase 3 Study Comparing 2% Rebamipide (OPC-12759) with 0.1% Sodium Hyaluronate in the Treatment of Dry Eye

To investigate the efficacy of 2% rebamipide ophthalmic suspension compared with 0.1% sodium hyaluronate ophthalmic solution for the treatment of patients with dry eye. Randomized, multicenter, active-controlled parallel-group study. One hundred eighty-eight patients with dry eye. Following a 2-week screening period, patients were allocated randomly to receive 2% rebamipide or 0.1% sodium hyaluronate, administered as 1 drop in each eye 4 or 6 times daily, respectively, for 4 weeks. There were 2 primary end points: changes in the fluorescein corneal staining (FCS) score to determine noninferiority of 2% rebamipide and changes in the lissamine green conjunctival staining (LGCS) score to determine superiority. Secondary objective end points were Schirmer's test results and tear film breakup time (TBUT). Secondary subjective end points were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and the patients' overall treatment impression score. In the primary analysis, the mean change from baseline in FCS scores verified noninferiority, indicated significant improvement, and, in LGCS scores, verified the superiority of 2% rebamipide to 0.1% sodium hyaluronate. Values for the Schirmer's test and TBUT were comparable between the 2 groups. For 2 dry eye-related ocular symptoms--foreign body sensation and eye pain--2% rebamipide showed significant improvements over 0.1% sodium hyaluronate. Patients had a significantly more favorable impression of 2% rebamipide than of 0.1% sodium hyaluronate; 64.5% rated treatment as improved or markedly improved versus 34.7%, respectively. No serious adverse events were observed. Administration of 2% rebamipide was effective in improving both the objective signs and subjective symptoms of dry eye. Those findings, in addition to the well-tolerated profile of 2% rebamipide, clearly show that it is an effective therapeutic method for dry eye. Proprietary or commercial disclosure may be found after the references.

Preliminary Results of Sacral Transcutaneous Electrical Nerve Stimulation for Fecal Incontinence

Fecal incontinence is a common debilitating condition. The aim of this study is to investigate the feasibility of sacral transcutaneous electrical nerve stimulation as an alternative treatment modality for fecal incontinence. All consecutive patients who presented with fecal incontinence to the senior author's clinic were prospectively recruited between June 2009 and September 2010. The severity of their fecal incontinence was assessed by the Wexner and Vaizey scores and anal physiology. Any improvement following a period of sacral transcutaneous electrical nerve stimulation treatment was determined by repeating the scores. In addition, patient satisfaction with the procedure was assessed by using a patient impression score. Twenty female patients with a median age of 57.5 years (range, 30-86) were evaluated. The median follow-up was 10 months (range, 5-12 months). Two patients did not record a change in their Vaizey score. The overall mean Wexner score was 7.9 ± 4.2 before in comparison with 4.0 ± 3.1 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 2.2-5.7, SE = 0.832). The overall mean Vaizey score was 12.7 ± 5.7 before in comparison with 5.8 ± 5.6 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 4.5-9.4, SE = 1.162). The pretreatment patient impression score was set at a mean of 1 ± 0 in comparison with 2.8 ± 1.1 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 1.2-2.3, SE = 0.25). The preliminary results suggest sacral transcutaneous electrical nerve stimulation is a promising noninvasive alternative to existing modalities in the treatment of idiopathic fecal incontinence.

Changes in conjunctival cytology and tear function tests with radioiodine treatment for hyperthyroidism

Radioiodine (RAI) is used in the treatment of hyperthyroidism and differentiated thyroid cancer. Radioiodine therapy is associated with dry eyes and some side effects are seen especially due to beta rays. In this study, the functional and cytological status of lacrimal glands after RAI therapy was evaluated. Twenty-five patients with a mean age of 55.16 years with planned low-dose RAI therapy were evaluated. Just before and 6 months after the treatment, the lacrimal glands were evaluated with tear break-up time (BUT), Schirmer's test, impression cytology and "Ocular Surface Disease Index (OSDI)" questionnaire. The mean value of Schirmer's test was 16.20 ± 3.61 pre-treatment and 11.28 ± 4.39 post-treatment for the right eye, and 15.76 ± 3.27 and 10.60 ± 4.42 for the left eye, respectively. The mean value of Schirmer's test decreased significantly post-treatment in both eyes (p = 0.0001). The BUT score also decreased significantly post-treatment (p = 0.001). The mean value of OSDI score was 27.5 ± 8.02 pre-treatment and 46.36 ± 10.27 post-treatment. The mean value of OSDI score increased post-treatment (p = 0.0001). The impression scores also increased post-treatment in both eyes (p = 0.0001). Even low-dose (≤30 mci) RAI treatment affects lacrimal gland functions. Low-dose RAI causes a decrease in the value of Schirmer's test and the BUT test, and an increase in the value of OSDI score and impression scores.

Randomized, Sham Controlled Trial of Transcranial Direct Current Stimulation for Painful Diabetic Polyneuropathy

ObjectiveTo investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN).MethodsPatients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure.ResultsAfter the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS.ConclusionFive daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study

Background:The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics.Methods:This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4–65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002–2006 in sequential order.Results:The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as “very satisfied” or “satisfied” by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy.Conclusion:Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.

Estimation of Factor Scores of Impression of Question and Answer Statements by Using Feature Values of Statements

Estimation of Factor Scores of Impression of Question and Answer Statements by Using Feature Values of Statements

The value of the clinical impression in recognizing and treating sepsis patients in the emergency department

Immediate bedside recognition of sepsis in the emergency department (ED) enables early treatment. This study aims to investigate whether the clinical impression score of different health care providers (a) is a good predictor of the severity of sepsis, (b) is mutually agreed, and (c) correlates with the treatment provided in the ED. We performed a prospective observational study in the ED of a tertiary teaching hospital over a 3-month period. The vital signs of all patients of at least 18 years presenting with suspected infection or sepsis were measured on arrival at the ED. In patients with at least one of the 'Systemic Inflammatory Response Syndrome' criteria, the nurse, resident, and attending physician assigned a clinical impression score for the degree of acute illness, ranging from 1 (not ill) to 10 (extremely ill). Additional information collected included demographic and treatment data. We included 123 patients with sepsis and 11 patients with a (suspected) infection with one 'Systemic Inflammatory Response Syndrome' criterion. The clinical impression scores of all health care providers increased significantly between the infection without sepsis, mild sepsis, and severe sepsis groups. The agreement between the health care providers ranged from moderate to good (weighted κ 0.54-0.62). The clinical impression score correlated with time to antibiotics (R=-0.33, P=0.001), amount of volume therapy (R=0.61-0.64, P≤0.001), and amount of oxygen therapy (R=0.58-0.63, P≤0.001). The clinical impression score is associated with the severity of sepsis, is mutually agreed between the different health care providers and is correlated with sepsis treatment provided in the ED.

Electroconvulsive Therapy and Clozapine in Adolescents With Schizophrenia Spectrum Disorders

To evaluate the safety and effectiveness of the combination of electroconvulsive therapy (ECT) and clozapine compared to ECT with other antipsychotics or benzodiazepines in a sample of adolescents diagnosed with schizophrenia spectrum disorders. Data regarding 28 adolescent subjects aged 13 to 18 with diagnoses of schizophrenia spectrum disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and treated with ECT were retrospectively collected. Twelve subjects were also treated with clozapine and 16 with other antipsychotics or benzodiazepines during ECT course and follow-up. Electroconvulsive therapy parameters and adverse effects were assessed using a systematic protocol. Positive and Negative Syndrome Scale and Clinical Global Impression scores before ECT and after acute ECT, and rate of rehospitalization during 1-year follow-up were used to assess effectiveness. Response was defined as a 20% decrease in Positive and Negative Syndrome Scale scores. No differences were observed in the mean charge needed to induce seizure and electroencephalographic duration, but there was a slight difference in the current used. The nonclozapine group showed greater restlessness and agitation, although no differences were found in other adverse effects. The percentage of responders was similar: 66.7% in the clozapine group and 68.8% in the nonclozapine group. However, the rate of rehospitalization was lower in the patients treated with clozapine during 1-year follow-up (7.1%) compared to that of the nonclozapine group (58.3%) (P = 0.009). The main findings of this study were that combining ECT with clozapine, compared to ECT with other antipsychotics or benzodiazepines, was safe and that both treatments were equally effective. Charges needed to induce seizure were similar in both groups. Patients treated with clozapine during 1-year follow-up had a lower rate of rehospitalization.

S15 Is Contrast-Enhanced Computed Tomography (CT) Scoring a Useful tool in Predicting Pleural Malignancy on Thoracoscopy?

BackgroundCT and Thoracoscopy are useful tools in the evaluation of patients with pleural diseases. Previous studies have shown that certain features on CT may help in differentiating malignant and benign...

Prediction of an Essential Gene with Potential Drug Target Property in Streptococcus suis using comparative genomics

Genes that are indispensable for survival are referred to as essential gene. Due to the momentous significance of these genes for cellular activity they can be selected potentially as drug targets. Here in this study, an essential gene for Streptococcus suis was predicted using coherent statistical analysis and powerful genome comparison computational method. At first the whole genome protein scatter plot was generated and subsequently, on the basis of statistical significance, a reference genome was chosen. The parameters set forth for selecting the reference genome was that the genome of the query (Streptococcus suis) and subject must fall in the same genus and yet they must vary to a good degree. Streptococcus pneumoniae was found to be suitable as the reference genome. A whole genome comparison was performed for the reference (Streptococcus pneumoniae) and the query genome (Streptococcus suis) and 14 conserved proteins from them were subjected to a screen for potential essential gene property. Among those 14 only one essential gene was found to be with impressive similarity score between reference and query. The essential gene encodes for a type of `Clp protease`. Clp proteases play major roles in degrading misfolded proteins. Results found here should help formulating a drug against Strptococcus suis which is responsible for mild to severe clinical conditions in human. However, like many other computational studies, the study has to be validated furthermore through in vitro assays for concrete proof.

Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes

Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence.

Rebamipide (OPC-12759) in the Treatment of Dry Eye: A Randomized, Double-Masked, Multicenter, Placebo-Controlled Phase II Study

To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye. A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study. A total of 308 patients with dry eye. After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks. The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score. Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups. Rebamipide was effective in treating both objective signs and subjective symptoms of dry eye and were well tolerated in this 4-week study. Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide in some measures. Proprietary or commercial disclosure may be found after the references.

Sodium Oxybate for Narcolepsy with Cataplexy: Systematic Review and Meta-Analysis

To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients. Systematic review and meta-analysis. Adults with narcolepsy-cataplexy. SXB. Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the efficacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1). Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.