Early Active Motion Versus Sling Immobilization After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

PURPOSE: To compare the effect of early mobilization (EM) with standard rehabilitation (SR) over the initial 24 months following arthroscopic rotator cuff (RC) repair. METHODS: A total of 206 patients with full-thickness RC tears undergoing arthroscopic repair were randomized following preoperative assessment of shoulder range of motion (ROM), pain, strength, and health-related quality of life (HRQOL) to either EM (n = 103; self-weaned from sling and performed pain-free active ROM during the first 6 weeks) or SR (n = 103; wore a sling for 6 weeks with no active ROM). Shoulder ROM, pain, and HRQOL were reassessed at 6 weeks and 3, 6, 12, and 24 months postoperatively by a blinded assessor. At 6, 12, and 24 months, strength was reassessed. At 12 months, ultrasound verified RC integrity. Independent t tests assessed 6-week group differences and 2-way repeated measures analysis of variance assessed changes over time between groups. RESULTS: The groups were similar preoperatively (P > .12). The mean age of participants was 55.9 (minimum, 26; maximum, 79) years, and 131 (64%) were men. A total of 171 (83%) patients were followed to 24 months. At 6 weeks postoperatively, EM participants had significantly better forward flexion and abduction (P < .03) than the SR participants; no other group differences were noted. Over 24 months, there were no group differences in ROM after 6 weeks (P > .08), and pain (P > .06), strength (P = .35), or HRQOL (P > .20) at any time. Fifty-two (25%) subjects (30% EM; 33% SR) had a full-thickness tear present at 12-month postoperative ultrasound testing (P > .8). CONCLUSIONS: EM did not show significant clinical benefits, but there was no compromise of postoperative ROM, pain, strength, or HRQOL. Repair integrity was similar at 12 months postoperatively between groups. Consideration should be given to allow pain-free active ROM within the first 6 weeks following arthroscopic RC repair. LEVEL OF EVIDENCE: Level I, high-quality randomized controlled trial.

Utilizing the physician assistant role: case study in an upper-extremity orthopedic surgical program.

BACKGROUND: Shortages with resources and inefficiencies with orthopedic services in Canada create opportunities for alternative staffing models and ways to use existing resources. Physician assistants (PAs) are a common provider used in specialty orthopedic services in the United States; however, Canada has limited experience with PAs. As part of a larger demonstration project, Alberta Health Services (AHS) implemented 1 PA position in an upper-extremity surgical program in Alberta, Canada, to demonstrate the role in 4 areas: preoperative, operative, postoperative and follow-up care. METHODS: A mixed-methods evaluation was conducted using semi-structured interviews (n = 38), health care provider (n = 28) and patient surveys (n = 47), and 2 years of clinic data on new patients. Data from a double operating room experiment detailed expected versus actual times for 3 phases of surgery (pre, during, post). RESULTS: Preoperatively, the PA prioritizes patient referrals for surgery and redirects patients to alternative care. In the second year with the PA in place, there was an increase in total new patients seen (113%). Postoperatively, the PA attended rounds on 5 surgeons' patients and handled follow-up care activities. Health care providers and patients reported that the PA provided excellent care. Findings from the operating room showed that the preparation time was greater than expected (38.6%), whereas the surgeon time (20.6%) and postsurgery time (37.2%) was less than expected. CONCLUSION: After 24 months the PA has become a valuable member of the health care team and works across the continuum of orthopedic care. The PA delivers quality care and improves system efficiencies.

CONTEXTE: Le manque de ressources et les inefficacités des services d'orthopédie au Canada créent des possibilités pour de nouveaux modèles de dotation et de mise à contribution des ressources existantes. Aux États-Unis, les adjoints au médecin sont des fournisseurs de soins courants dans les services spécialisés d'orthopédie comparativement au Canada qui en fait une utilisation limitée. Dans le cadre d'un grand projet de démonstration, Alberta Health Services (AHS) a créé un poste d'adjoint au médecin dans un programme de chirurgie des membres supérieurs en Alberta, au Canada, afin de démontrer le rôle de l'adjoint au médecin à 4 étapes des soins : préopératoire, opératoire, postopératoire et suivi. MÉTHODES: Une évaluation avec méthodes mixtes a été effectuée au moyen d'entrevues semi-structurées (n = 38), de sondages auprès de fournisseurs de soins (n = 28) et de patients (n = 47), et de données des nouveaux patients de la clinique sur 2 ans. Les données d'une expérience en salle d'opération double indiquaient le temps prévu et le temps réel de 3 étapes des chirurgies (pré, per et postopératoire). RÉSULTATS: À l'étape préopératoire, l'adjoint au médecin a établi la priorité des patients référés en chirurgie et redirigé les patients vers d'autres soins. Lors de la deuxième année de l'adjoint au médecin, nous avons observé une augmentation du nombre de nouveaux patients accueillis (113 %). À l'étape postopératoire, l'adjoint au médecin a participé aux tournées auprès des patients de 5 chirurgiens et s'est occupé des activités liées aux soins de suivi. Les fournisseurs de soins et les patients ont signalé l'excellence des soins de l'adjoint au médecin. Les résultats de la salle d'opération ont révélé un temps de préparation plus élevé que prévu (38,6 %), alors que le temps de chirurgie (20,6 %) et le temps postchirurgical (37,2 %) étaient inférieurs aux prévisions. CONCLUSION: Après 24 mois, l'adjoint au médecin est devenu un membre valorisé de l'équipe de soins qui travaille à toutes les étapes du continuum des soins orthopédiques. L'adjoint au médecin fournit des soins de qualité et améliore l'efficacité du système.

Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC.

Is Immobilization Necessary for Early Return to Work Following Distal Biceps Repair Using a Cortical Button Technique?: A Randomized Controlled Trial.

BACKGROUND: Improvements in surgical fixation to repair distal biceps tendon ruptures have not fully translated to earlier postoperative mobilization; it is unknown whether earlier mobilization affords earlier functional return to work. This parallel-arm randomized controlled trial compared the impact of early mobilization versus 6 weeks of postoperative immobilization following distal biceps tendon repair. METHODS: One hundred and one male participants with a distal biceps tendon rupture that was amenable to a primary repair with use of a cortical button were randomized to early mobilization (self-weaning from sling and performance of active range of motion as tolerated during first 6 weeks) (n = 49) or 6 weeks of immobilization (splinting for 6 weeks with no active range of motion) (n = 52). Follow-up assessments were performed by a blinded assessor at 2 and 6 weeks and at 3, 6, and 12 months. At 12 months, distal biceps tendon integrity was verified with ultrasound. The primary outcome was return to work. Secondary outcomes were pain, range of motion, strength, shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) score, and tendon integrity. Intention-to-treat analysis was performed. A linear mixed model for repeated measures was used to compare pain, range of motion, strength, and QuickDASH between the groups over time; return to work was assessed with use of independent t tests. RESULTS: The groups were similar preoperatively (p ≥ 0.16). The average age (and standard deviation) was 44.7 ± 8.6 years. Eighty-three participants (82%) were followed to 12 months. There were no differences between the groups in terms of return to work (p ≥ 0.83). Participants in the early mobilization group had significantly more passive forearm supination (p = 0.04), with passive forearm pronation (p = 0.06) and active extension and supination (p = 0.09) trending toward significantly greater range of motion in the early mobilization group relative to the immobilization group. Participants in the early mobilization group had significantly better QuickDASH scores over time than those in the immobilization group (p = 0.02). There were no differences between the groups in terms of pain (p ≥ 0.45), active range of motion (p ≥ 0.09), or strength (p ≥ 0.70). Two participants (2.0%, 1 in each group) had full-thickness tears on ultrasound at 12 months (p = 0.61). Compliance was not significantly different between the groups (p = 0.16). CONCLUSIONS: Early motion after distal biceps tendon repair with cortical button fixation is well tolerated and does not appear to be associated with adverse outcomes. No clinically important group differences were seen. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Curcumin as Add-On to Antipsychotic Treatment in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.

Successful Use of Escitalopram for the Treatment of Visual Hallucinations in Patients With Parkinson Disease.

INTRODUCTION: Patients with Parkinson disease (PD) frequently experience visual hallucinations (VH). Visual hallucinations are most often viewed as an adverse effect of antiparkinsonian treatment. Possible treatments for this disturbance include a reduction of antiparkinsonian medications, adding atypical antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that selective serotonin reuptake inhibitors may be an optional treatment for patients experiencing psychosis or agitation in dementia. Currently, there is no standard recommended treatment for VH in patients with PD. We present here our clinical experience with escitalopram (selective serotonin reuptake inhibitor) for treating this disturbance. METHODS: Thirteen patients with PD (8 men and 5 women; age range 67-83 years) experiencing VH were openly treated with escitalopram 10 or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks of treatment using Clinical Global Impression-Severity and Clinical Global Impression-Improvement. RESULTS: At the end of the 4th week of treatment, of 13 patients, 11 subjects demonstrated improvement, and in only 2 patients were there no changes in their condition. After an additional 4 weeks, 2 of the responders showed very significant improvement, 6 demonstrated much improvement, and 3 patients demonstrated minimal improvement. Only 1 patient showed no change in his condition. One additional patient stopped taking escitalopram after 5 weeks because of an absence of improvement in his state. CONCLUSIONS: Escitalopram was well tolerated as treatment of VH in PD patients. This medication could be a promising optional therapy for this disturbance; however, further randomized controlled and bigger studies are necessary.

Primary Wound Closure After Open Fracture: A Prospective Cohort Study Examining Nonunion and Deep Infection.

OBJECTIVES: Determine the proportion of subjects developing deep infection or nonunion after primary wound closure of open fractures (humerus, radius/ulna, femur, and tibia/fibula). Secondarily, a matched-series analysis compared outcomes with subjects who underwent delayed wound closure. DESIGN: Prospective cohort between 2009 and 2013 of subjects undergoing primary closure. SETTING: Trauma center. PARTICIPANTS: Eighty-three (84 fractures) subjects were enrolled. Eighty-two (99%) subjects (83 fractures) provided follow-up data. Matching (age, sec, fracture location, and grade) was performed using study data of delayed wound closure undertaken at the same center between 2001 and 2009 (n = 68 matched subjects). INTERVENTION: Primary wound closure occurred when the fracture grade was Gustilo grade 3A or lower and the wound deemed clean at initial surgery. Standardized evaluations occurred until the fracture(s) healed; phone interviews and chart reviews were also undertaken at 1 year. MAIN OUTCOME MEASUREMENTS: Deep infection is defined as infection requiring unplanned surgical debridement and/or sustained antibiotic therapy after wound closure; nonunion is defined as unplanned surgical intervention after definitive wound closure or incomplete radiographic healing 1-year after fracture. RESULTS: Three (4%) subjects had deep infections, whereas 10 (12%) subjects developed nonunion in the primary closure cohort. In the matched analyses [n = 68 pairs; (136 subjects)], the primary closure cohort had fewer deep infections [n = 3 (4%) vs. n = 6 (9%)] and nonunions [n = 9 (13%) vs. n = 19 (29%)] than the delayed closure cohort (P < 0.001). CONCLUSIONS: Primary wound closure after an open fracture appears acceptable in appropriately selected patients and may reduce the risk of deep infection and nonunion compared with delayed closure; a definitive randomized trial is needed. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a randomized, double-blind, controlled study.

Treatment strategies against acute neuroleptic-induced akathisia (NIA) include anticholinergic (antimuscarinic) agents, dopamine agonists, GABAergic agents, beta-blockers, benzodiazepines, and serotonin antagonists. However, many patients who have acute akathisia fail to respond. In previous studies, mianserin and vitamin B6 were found to be effective in the treatment of acute akathisia. The purpose of this study was to compare the efficacy of B(6), mianserin and placebo in the treatment of acute NIA. Sixty schizophrenia and schizoaffective inpatients who have NIA were randomly divided to receive vitamin B(6) 1,200 mg/d, mianserin 15 mg/d, or placebo for 5 days, in a double-blind design. The Barnes Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Clinical Global Impression were used to assess the severity of NIA and psychotic symptoms. The assessment was made at baseline and daily for the duration of the study. Compared with the placebo group, the vitamin B(6)-treated and mianserin-treated patients showed a significant improvement in the subjective (P < 0.0001), subjective distress (P < 0.0001), and global (P < 0.0001) subscales. The objective subscale did not show significant positive results (P = 0.056), but there was a trend toward symptom amelioration in both groups. A reduction of at least 2 points on the Barnes Akathisia Rating Scale global subscale was noted in the vitamin B(6) group (13/23, 56%) as well as in the mianserin groups (13/20, 65%), and in only one patient in the placebo group (1/17, 6%; P < 0.0005). Our results indicate that high doses of B(6) and a low dose of mianserin may be a useful addition to current treatments of NIA. The efficacy of vitamin B(6) and mianserin suggests that the pathophysiology of acute NIA is heterogeneous with the various subtypes of acute NIA responding differently to the various pharmacological approaches.

Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects.

OBJECTIVES: To determine factors associated with developing nonunion or delayed healing after open fracture. DESIGN: Prospective cohort between 2001 and 2009. SETTING: Three level 1 Canadian trauma centers. PARTICIPANTS: Seven hundred thirty-six (791 fractures) subjects were enrolled. Six hundred eighty-nine (94%) subjects (739 fractures) provided adequate outcome data. INTERVENTION: Subjects were followed until fracture(s) healed; phone interviews and chart reviews were conducted 1 year after fracture. Patient, fracture, and injury information, and time to surgery and antibiotics were recorded during hospitalization. MAIN OUTCOME MEASUREMENTS: Nonunion defined as unplanned surgical intervention after definitive wound closure or incomplete radiographic healing at 1 year and delayed healing defined as 2 consecutive clinical assessments showing no radiographic progression or incomplete radiographic healing between 6 months and 1 year. RESULTS: There were 413 (52%) tibia/fibular, 285 (36%) upper extremity, and 93 (13%) femoral fractures. Nonunion developed in 124 (17%) and delayed healing in 63 (8%) fractures. The median time to surgery was not different for fractures that developed nonunion compared with those who did not (P = 0.36). Deep infection [Odd ratio (OR) 12.75; 95% confidence interval (CI) 6.07-26.8], grade 3A fractures (OR 2.49; 95% CI, 1.30-4.78), and smoking (OR 1.73; 95% CI, 1.09-2.76) were significantly associated with developing a nonunion. Delayed healing was also significantly associated with deep infection (OR 4.34; 95% CI, 1.22-15.48) and grade 3B/C fractures (OR 3.69; 95% CI, 1.44-9.44). Multivariate regression found no association between nonunion and time to surgery (P = 0.15) or antibiotics (P = 0.70). CONCLUSIONS: Deep infection and higher Gustilo grade fractures were associated with nonunion and delayed healing. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Donepezil as Add-on Treatment for Resistant Obsessive-Compulsive Disorder: Retrospective Case Series.

UNLABELLED: Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with serotonin selective reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued adequate OCD treatment. For patients exhibiting partial or no response to multiple SSRIs, augmentation strategies are usually recommended. Here, we introduce a retrospective consecutive sample of aged patients with resistant OCD treated with donepezil augmentation to regular pharmacotherapy. METHODS: Ten patients (5 males, 5 females; mean [SD] age, 63.8 [7.5] years), suffering from resistant OCD, were openly treated with donepezil 10 mg/d as add-on. Efficacy was assessed at baseline and after 8 weeks of treatment using the Yale-Brown Obsessive Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. RESULTS: The treatment was generally well tolerated without adverse events. In all patients, mean (SD) Yale-Brown Obsessive Compulsive Scale scores diminished from 27.3 (4.3) points at baseline to 16.9 (4.5) points at week 8 (P < 0.0001). Mean (SD) Clinical Global Impression-Severity scores diminished from 5.5 (0.7) points to 3.1 (1.0) points, (P < 0.001). According to Clinical Global Impression-Improvement, 7 patients demonstrated "very much" or "much" improvement and 3 patients did not demonstrate any improvement. CONCLUSIONS: Donepezil was a well-tolerated add-on to regular pharmacotherapy in treatment-resistant OCD patients in this small cases series. Donepezil could be a promising optional therapy for patients suffering from resistant OCD, but further randomized controlled studies are necessary.

Beneficial effect of donepezil in the treatment of elderly patients with tardive movement disorders.

BACKGROUND: Tardive dyskinesia and other delayed-onset abnormal involuntary movement disorders may occur as a result of the use of psychotropic drugs. A distinction is usually made between classic tardive dyskinesia (TD) (orobuccal-lingual-facial) and tardive dystonia, tardive tremor (TT), tardive akathisia, and other related syndromes. In spite of the development of atypical antipsychotics with fewer side effects, tardive movement disorders nevertheless continue to present a significant clinical and therapeutic challenge. Several reports have suggested that donepezil may be helpful in the treatment of TD. METHOD: A preliminary study was conducted of 7 patients (5 women and 2 men) enrolled over a period of 6 months who had been experiencing TT for a period of at least 1 year. The ages of the patients ranged from 64 to 79 years, and all patients were on stable antipsychotic therapy. Donepezil was added to their usual treatment for 8 weeks. The severity of patients' extrapyramidal symptoms was assessed using the tremor subscale of the Simpson-Angus Scale (SAS) and self-rated with a modification of the Clinical Global Impressions scale, the Subjective Clinical Improvement Impression scale. The clinical response was evaluated by comparing the rating scores at baseline prior to donepezil treatment and every 2 weeks thereafter. RESULTS: The addition of donepezil (up to 10 mg/day) was associated with a clinically significant improvement (from 37.5% to 63.6%) on the SAS tremor subscale following 4 weeks of therapy. Only 1 patient discontinued follow-up due to side effects. CONCLUSION: The results suggest that donepezil may be effective in the treatment of TT, and this finding should be evaluated further by a randomized controlled study.

Augmentation with amisulpride for schizophrenic patients nonresponsive to antipsychotic monotherapy.

Despite the effectiveness of antipsychotic medications in treatment of schizophrenia, about 30% of patients who receive an adequate treatment have significant persisting symptoms. The problem of treatment-resistant psychosis is an important and difficult one. The aim of this study was to retrospectively evaluate the efficacy and safety of amisulpride augmentation in treatment-resistant schizophrenic patients. To the best of our knowledge, this is the first report about resistant schizophrenic and schizoaffective patients treated with the combinations of risperidone and amisulpride and ziprasidone and amisulpride. Data were collected from patient records. A total of 15 resistant schizophrenic patients (7 men, 8 women, 54.0 +/- 16.9 years old) were included in the study. Before addition of amisulpride, the patients were treated with monotherapy by atypical neuroleptics (clozapine, olanzapine, risperidone, or ziprasidone). The mean amisulpride dose was 693.3 +/- 279.6 mg/d. The mental state of 12 (80%) patients treated with combination was improved. Three (20%) patients showed no change in their mental state. Only 2 patients treated with a combination of risperidone and amisulpride had mild side effects. The results are preliminary and require confirmation in a randomized controlled trial. The authors suggest that amisulpride may be a promising option as an augmentation strategy in treatment-resistant schizophrenic patients.

Amisulpride as add-on treatment for resistant obsessive-compulsive disorder: retrospective case series.

UNLABELLED: Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with selective serotonin reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued treatment. For partial or nonresponding patients to multiple SSRIs, augmentation strategies are usually recommended. Here we present a consecutive sample of patients with resistant OCD treated with amisulpride augmentation to SSRIs. METHODS: We present 10 patients (5 males, 5 females) experiencing resistant OCD. Subjects were treated openly for 6 weeks with amisulpride 200 mg/d as add-on, excluding 1 patient who was treated with only 100 mg/d due to acute extrapyramidal adverse effect on a larger dose. Efficacy was assessed at baseline and after 6 weeks of treatment using the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. RESULTS: The treatment was generally well tolerated without serious events. In all patients, average Yale-Brown Obsessive-Compulsive Scale scores diminished from 25.3 ± 5.96 points at baseline to 12.2 ± 5.98 at the sixth week (P < 0.0005). Of 10 patients, 7 had significant and partial improvement, and 3 patients did not demonstrate any improvement. CONCLUSIONS: Treatment-resistant OCD patients positively responded and well tolerated amisulpride add-on to their ongoing regular pharmacotherapy. This case series demonstrates that amisulpride could be a promising optional therapy for patients who have resistant OCD. Further randomized controlled studies are necessary.

Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts.

AIM: To evaluate the structure-activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231). MATERIALS & METHODS: Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively. RESULTS & CONCLUSION: Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system.

Vitamin B6 treatment in acute neuroleptic-induced akathisia: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Treatment strategies for acute neuroleptic-induced akathisia (NIA) contain anticholinergic (antimuscarinic) agents, dopamine agonists, gamma-aminobutyric acid (GABA)-ergic agents, beta-blockers, benzodiazepines, and serotonin antagonists. Nevertheless, many patients who suffer from acute akathisia fail to respond to treatment. In earlier studies, vitamin B6 was found to be effective in the treatment of neuroleptic-induced movement disorders. The purpose of this study was to evaluate the efficacy of vitamin B6 in the treatment of acute NIA. This is the first report of B6 as a treatment for NIA. METHOD: This study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design. The Barnes Akathisia Scale (BAS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale (CGI) were used to assess the severity of NIA and psychotic symptoms. The BAS assessment was made at baseline and every day during the study. The BPRS and CGI were completed at baseline and at the end of the study. RESULTS: The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037). CONCLUSION: Our preliminary results indicate that high doses of vitamin B6 may be useful additions to the available treatments for NIA, perhaps due to its combined effects on various neurotransmitter systems.

Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease.

The risk of psychosis among patients with Parkinson's disease (PD) is high, and the management of these patients remains a substantial problem for physicians. Atypical antipsychotics, despite their advantages over conventional antipsychotics, can cause different side effects and deterioration of PD. Several reports have suggested that donepezil can be helpful in the treatment of psychotic conditions in patients with dementia with Lewy bodies and Alzheimer's disease. This report presents the results of preliminary study of six patients (four women, two men; age range, 60-75 years) with PD (range of duration, 3-7 years) and dementia complicated by psychosis. All patients were treated with antiparkinsonian therapy, and donepezil was added to their regular treatment. The severity of the psychotic symptoms was assessed using the Scale for the Assessment of Positive Symptoms, and extrapyramidal symptoms were assessed using the Simpson-Angus Scale. With the addition of donepezil (as much as 10 mg/day) to their constant antiparkinsonian treatment, five patients had clinically significant (more than 53%) improvement on the assessment scale, and one patient had minimal (24%) improvement after 6 weeks of the treatment. None of the patients had side effects or deterioration of parkinsonian symptoms. The results suggest that donepezil may ameliorate psychotic symptoms in patients with PD, but this will need to be tested further in controlled, double-blind trials.

Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer's type.

Traditionally, the neuropsychiatric symptoms of Alzheimer's disease (AD) have been managed with neuroleptics or benzodiazepines, which have serious side effects. Preliminary observations suggest the possible value of cholinesterase inhibitors in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type, dementia with Lewy bodies, and in patients with Parkinson's disease. Twelve inpatients with AD with psychotic symptoms and lack of improvement of their delusions/hallucinations during perphenazine treatment (8 mg/day) for 3 weeks received random open-label donepezil 5 mg daily in addition to an ongoing treatment of 8 mg/day perphenazine or 16 mg/day perphenazine. Assessments conducted at baseline and after weeks 2 and 4 included the Mini-Mental State Examination, the Global Deterioration Scale, the Positive and Negative Symptoms Scale, and the Clinical Global Impressions scale. Frequency of extrapyramidal symptoms was measured according to the Abnormal Involuntary Movement Scale. The donepezil-perphenazine group exhibited substantially greater and clinical improvements in mental state. At the end of the trial (4 weeks), Positive and Negative Symptoms Scale scores revealed significant differences between both groups (p = 0.006). The Clinical Global Impressions scale and the Mini-Mental State Examination scores also showed significant differences between the donepezil-perphenazine group and the perphenazine group (p = 0.028 and p = 0.027 respectively). No significant differences were found in the Global Deterioration Scale scores. Abnormal Involuntary Movement Scale scores showed a significant deterioration in extrapyramidal symptoms in the perphenazine group compared with the donepezil-perphenazine group (p = 0.016). Donepezil augmentation of neuroleptics may be appropriate for those patients for whom neuroleptic monotherapy either does not lead to symptom remission or is associated with intolerable adverse effects. This was an open-label study and there is need for larger studies with double-blind control and a long-term study design to define the efficacy of donepezil for patients with AD and psychotic symptoms.

Time to initial operative treatment following open fracture does not impact development of deep infection: a prospective cohort study of 736 subjects.

OBJECTIVES: To evaluate the association between time to surgery, antibiotic administration, Gustilo grade, fracture location, and development of deep infection in open fractures. DESIGN: Prospective cohort between 2001 and 2009. SETTING: Three Level 1 Canadian trauma centers. PARTICIPANTS: A total of 736 (791 fractures) subjects were enrolled and 686 subjects (93%; 737 fractures) provided adequate follow-up data (1-year interview and/or clinical follow-up >90 days). INTERVENTION: Demographics, injury information, time to surgery, and antibiotics were recorded. Subjects were evaluated using standardized data forms until the fracture(s) healed. Phone interviews were undertaken 1 year after the fracture. MAIN OUTCOME MEASURES: Infection requiring unplanned surgical debridement and/or sustained antibiotic therapy. RESULTS: Tibia/fibula fractures were most common (n = 413, 52%), followed by upper extremity (UE) (n = 285, 36%), and femoral (n = 93, 12%) fractures. Infection developed in 46 fractures (6%). The median time to surgery was 9 hours 4 minutes (interquartile range, 6 hours 39 minutes to 12 hours 33 minutes) and 7 hours 39 minutes (interquartile range, 6 hours 10 minutes to 9 hours 54 minutes) for those without and with infection, respectively (P = 0.04). Gustilo grade 3B/3C fractures accounted for 17 of 46 infections (37%) (P < 0.001). Four UE (1.5%), 7 femoral (8%), and 35 tibia/fibula (9%) fractures developed infections (P = 0.001). Multivariate regression found no association between infection and time to surgery [odds ratio (OR), 0.97; 95% confidence interval (95% CI), 0.90-1.06] or antibiotics (OR, 1.0; 95% CI, 0.90-1.05). Grades 3A (OR, 6.37; 95% CI, 1.37-29.56) and 3B/3C (OR, 12.87; 95% CI, 2.72-60.95) relative to grade 1 injuries and tibia/fibula (OR, 3.91; 95% CI, 1.33-11.53) relative to UE fractures were significantly associated with infection. CONCLUSION: Infection after open fracture was associated with increasing Gustilo grade or tibia/fibula fractures but not time to surgery or antibiotics. LEVEL OF EVIDENCE: Prognostic level I. See instructions for authors for a complete description of levels of evidence.

Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study.

OBJECTIVES: Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. METHODS: Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. CONCLUSIONS: Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.