The effect of morphine added to periarticular multimodal drug injection or spinal anesthesia on pain management and functional recovery after total knee arthroplasty.

BACKGROUND: The efficacy of morphine added to periarticular multimodal drug injection (PMDI) for pain management after total knee arthroplasty (TKA) is controversial. Adding morphine to spinal anesthesia has reportedly improved pain relief for the first 24 h. We examined the effect of morphine added to PMDI or spinal anesthesia on pain management and functional recovery after TKA. METHODS: A total of 97 patients were randomized into three groups: in Group A (34 patients), 10 mg morphine was added to PMDI; Group B (31 patients), 0.1 mg morphine was added to spinal anesthesia; and Group C (32 patients), morphine was added to neither the PMDI nor spinal anesthetic. To evaluate the efficacy of added morphine for pain management, we assessed rest pain, the number of times analgesics were used, and the time period until the first analgesic use. The adverse effects of morphine were assessed by counting the numbers of times vomiting occurred and antiemetics were used. Functional recovery was evaluated by recording the range of motion of the knee and the date of ability to walk. RESULTS: Rest pain was the least in Group B at 6 and 12 h after operation. The number of times analgesics were used was the least in Group B. The time period until the first analgesic use was the longest in Group B. The number of vomiting episodes was the least in Group C. The number of times antiemetics were used was higher in Group A than in Group C. There were no significant differences in the range of motion and date of ability to walk among the three groups. CONCLUSIONS: The efficacy of morphine added to PMDI was limited, and that of morphine added to spinal anesthesia disappeared within 20 h postoperatively. Adding morphine to PMDI or spinal anesthesia did not improve functional recovery and caused some adverse effects.

Retraction: 'Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia'.

The above article from Human Psychopharmacology, first published on 25 January 2012 in Wiley OnlineLibrary (onlinelibrary.wiley.com), and in Volume 90, pp. 90-100, has been retracted by agreement between the authors, the journal Editor in Chief, David Baldwin, and John Wiley & Sons Ltd. The retraction has been agreed following an investigation by the St Marianna University Ethics Committee which determined that the paper was not as originally designed and approved. REFERENCES: Tenjin, T., Miyamoto, S., Miyake, N., Ogino, S., Kitajima, R., Ojima, K., … Yamaguchi, N. (2012). Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia. Hum. Psychopharmacol Clin Exp, 27, 90-100. https://doi.org/10.1002/hup.1276.

Prevalence of and factors associated with lumbar spondylolisthesis in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the prevalence of and elucidate risk factors for lumbar spondylolisthesis in patients with rheumatoid arthritis (RA). METHODS: From 1843 patients registered to the Akita Orthopedic Group on Rheumatoid Arthritis registry, participants comprised 128 patients who had undergone comprehensive radiographic examinations. The presence of lumbar spondylolisthesis (≥5% slip percentage) was assessed from L1 to L5 on lateral plain radiographs. At the time of radiographic evaluation, we also determined the following: RA disease duration; stage and class of Steinbrocker's classification; serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity for RA; history of joint surgery; the presence of cervical spinal instability; and details and doses of medications for RA. RESULTS: Forty-seven (36.7%) patients showed lumbar spondylolisthesis (L4, 48%; L3, 29%; L2, 13%; L5, 10%). Among these, Meyerding Grade was I in 89% and II in 11%. Multivariate analysis showed lumbar spondylolisthesis as significantly and independently associated with higher serum CRP level (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.00-2.25; p = 0.048) and history of joint surgery (OR, 2.87; 95%CI, 1.22-6.72; p = 0.015). CONCLUSIONS: More than one-third of patients with RA in this cohort had lumbar spondylolisthesis, and significant associations with higher serum CRP levels and history of joint surgery were identified.

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group.

OBJECTIVE: To evaluate the clinical and structural efficacy of tocilizumab (TCZ) during its long-term administration in patients with rheumatoid arthritis (RA). METHODS: In total, 693 patients with RA who started TCZ therapy were followed for 3 years. Clinical efficacy was evaluated by DAS28-ESR and Boolean remission rates in 544 patients. Joint damage was assessed by calculating the modified total Sharp score (mTSS) in 50 patients. RESULTS: When the reason for discontinuation was limited to inadequate response or adverse events, the 1-, 2-, and 3-year continuation rates were 84.0%, 76.8%, and 72.2%, respectively. The mean DAS28-ESR was initially 5.1 and decreased to 2.5 at 6 months and to 2.2 at 36 months. The Boolean remission rate was initially 0.9% and increased to 21.7% at 6 months and to 32.2% at 36 months. The structural remission rates (ΔmTSS/year ≤ 0.5) were 68.8%, 78.6%, and 88.9% within the first, second, and third years, respectively. The structural remission rate at 3 years (ΔmTSS ≤ 1.5) was 66.0%, and earlier achievement of swollen joint count (SJC) of 1 or less resulted in better outcomes. CONCLUSIONS: TCZ was highly efficacious, and bone destruction was strongly prevented. SJC was an easy-to-use indicator of joint destruction.

[Effectiveness of N-acetylcysteine in the treatment of schizophrenia].

Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous antioxidant glutathione and has antioxidant, anti-inflammatory, and neuroprotective properties. NAC is widely available as an over-the-counter nutritional supplement. Increasing lines of evidence suggest that NAC is effective for various mental disorders. In randomized controlled trials, treatment with NAC as an add-on to antipsychotics showed beneficial effects and safety profiles in patients with chronic schizophrenia. The results of a recent preclinical study using a neurodevelopmental model of schizophrenia suggest that NAC may have promising effects in an early stage of schizophrenia and an at-risk mental state. However, there is little clinical evidence for the efficacy and safety of NAC at these stages of schizophrenia. In this review, we summarize the evidence regarding the effectiveness of NAC for the treatment of schizophrenia and its prodromal stage. We also introduce the preliminary results of our research on NAC.

Benefits and limits of anticholinergic use in schizophrenia: focusing on its effect on cognitive function.

All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side-effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripheral side-effects (e.g. dry mouth, urinary disturbances, and constipation) and central adverse effects (e.g. cognitive impairment, worsening of tardive dyskinesia, and delirium). Disturbances in cognitive abilities are cardinal features of schizophrenia from its earliest phases and account for much of the functional disability associated with the illness. It is likely that long-term concomitant administration of anticholinergics exacerbates the underlying cognitive impairment in patients with schizophrenia and subsequently affects patients' quality of life. Thus, current treatment guidelines for schizophrenia generally do not recommend the prophylactic and long-term use of anticholinergics. However, the high use of long-term anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in several countries. To assess the benefits and limits of anticholinergic use in psychosis and schizophrenia, this article will provide a brief review of the pharmacology and clinical profiles of anticholinergic drugs and will focus on their effects on cognitive function in schizophrenia, particularly during the course of the early phase of the illness. In addition, we will address the effects of discontinuation of anticholinergics on cognitive function in patients with schizophrenia and provide a strategy for adjunctive anticholinergic use in patients treated with long-acting injectable antipsychotics.

Long-term efficacy and safety of blonanserin in patients with first-episode schizophrenia: a 1-year open-label trial.

AIMS: The purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. METHODS: Twenty-three antipsychotic-naïve patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial of blonanserin (2-24 mg/day). Clinical evaluations were conducted at baseline and 2, 6, and 12 months after the start of treatment. The main outcome measures were changes in subjective well-being and subjective quality of life, as assessed by the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version and the Schizophrenia Quality of Life Scale-Japanese version, respectively. Secondary outcome measures included the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia-Japanese version, laboratory tests, bodyweight, and extrapyramidal symptoms. RESULTS: Fourteen patients (60.9%) remained on the study at 1 year. In the intention-to-treat analysis, significant improvements were observed in several subscales on the Subjective Well-being under Neuroleptic treatment scale Short form-Japanese version, the Schizophrenia Quality of Life Scale-Japanese version, and the Brief Assessment of Cognition in Schizophrenia-Japanese version, and in all factor scores on the Positive and Negative Syndrome Scale. Improvement in depressive symptoms with blonanserin treatment was positively correlated with improvements in subjective well-being and subjective quality of life, as well as verbal memory. No significant changes were noted for any safety measure during the 1-year study period. CONCLUSIONS: Blonanserin was well tolerated and effective for the treatment of first-episode schizophrenia in terms of subjective wellness, cognition, and a wide range of pathological symptoms. Further large-scale studies are warranted to confirm our findings.

Should central osteophytes within the articular cartilage of the lateral compartment be considered when determining the indication of unicompartmental knee arthroplasty for medial osteoarthritis?

Patients with central osteophytes in the lateral compartment may be poor candidates for unicompartmental knee arthroplasty (UKA) for medial knee arthritis given the thin overlying articular cartilage above the central osteophytes that is inadequate for supporting weight-bearing after UKA. Therefore, attempts should be made to detect central osteophytes to confirm suitability for UKA.

[Blonanserin in the treatment of schizophrenia].

Blonanserin was developed in Japan in 2008 as an antipsychotic drug. It has high affinity for dopamine D2/3 and serotonin 5-HT2A receptors, but shows low affinity for adrenergic alpha1, histamine H1, and muscarinic M1 receptors. Several short-term double-blind trials demonstrated that blonanserin was well tolerated and had equal efficacy to haloperidol and risperidone in terms of positive symptoms and depressive symptoms in patients with chronic schizophrenia. It was also superior to haloperidol in improving negative symptoms. We have recently reported that blonanserin may improve some types of cognitive function associated with the frontal lobe activity in patients with first-episode schizophrenia. Taken together, blonanserin may be a promising candidate for a first-line antipsychotic for patients with first-episode and chronic schizophrenia.

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the effects of blonanserin, a novel antipsychotic, on cognitive function in first-episode schizophrenia. METHODS: Twenty-four antipsychotic-naïve patients with first-episode schizophrenia participated in the study. Blonanserin was given in an open-label design for 8 weeks. The Brief Assessment of Cognition in Schizophrenia-Japanese language version (BACS-J) was administered as the primary outcome measure at baseline and 8 weeks. Clinical evaluation included the Positive and Negative Syndrome Scale (PANSS), the Schizophrenia Quality of Life Scale-Japanese language version (SQLS-J), and the Clinical Global Impression-Severity of Illness Scale (CGI-S). To exclude the possibility of retest effects on the BACS-J, 10 age-matched patients with chronic schizophrenia treated with blonanserin were tested at baseline and after an 8-week interval. RESULTS: Twenty first-episode patients completed the study. Repeated measures analysis of covariance revealed a significant group-by-time interaction effect on the letter fluency task due to better performance in the first-episode group, but not in the control group. Main effect of time or group-by-time interaction effect on the Tower of London task was not significant; however, the first-episode group, but not the control group, showed substantial improvement with a moderate effect size. All items on the PANSS, SQLS-J, and CGI-S significantly improved after 8 weeks of treatment. CONCLUSIONS: These results suggest that blonanserin improves some types of cognitive function associated with prefrontal cortical function.

A Right Angle Guide for Distal Tuberosity Osteotomy With Medial Open Wedge High Tibial Osteotomy for Varus Knee Osteoarthritis.

Medial open wedge high tibial osteotomy (OWHTO) is usually performed with proximal tuberosity osteotomy or setting the osteotomy line proximal to the tuberosity. However, OWHTO can result in patellofemoral complications due to postoperative patella infera. A new OWHTO technique, biplanar osteotomy with a distal tuberosity osteotomy, was reported in 2004 to prevent postoperative patella infera. To ensure that the 2 osteotomy lines maintain perpendicular, we describe the OWHTO procedure with a distal tuberosity osteotomy technique using a TriS Medial HTO Plate System (Olympus Terumo Biomaterials Corp., Tokyo, Japan) and a right angle guide we developed. In this Technical Note, we describe the procedure and advantages, risks, and limitations, as well as the pearls and pitfalls based on our experience.

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia.

Schizophrenia is a mostly chronic mental disorder, and symptomatic relapse is frequently observed. It is often associated with social and/or occupational decline that can be difficult to reverse. Most patients with the illness need long-term pharmacological treatment, and antipsychotic drugs represent the mainstay of clinical care. Long-acting injectable antipsychotics (LAIs) are an important alternative to oral medication, particularly advantageous in the context of compliance management. Several new-generation antipsychotics (NGAs), including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting formulations, and new evidence has been accumulating. To date, all of the NGA LAIs have demonstrated a statistically and clinically significant decrease of relapse rates over placebo. The results of clinical trials comparing NGA LAIs with oral antipsychotics (OAPs) are not consistent, as being influenced considerably by study design. Superiority of LAIs to OAPs in efficacy is most evident in mirror image and cohort studies. New-generation LAIs are comparable to their oral mother compounds regarding safety and tolerability if one disregards potential injection site complications. There is little evidence of efficacy differences between the available LAIs, but they have different characteristics in terms of pharmacodynamic and pharmacokinetic profiles, injection interval, cost, requirements for oral supplementation, as well as adverse events. Considering these differences is useful for selecting LAIs for the treatment of individual patients. There is increasing evidence suggesting the use of LAIs in special patient groups, such as first-episode or forensic schizophrenia patients. This article reviews data on the use of NGA LAIs in schizophrenia and discusses current issues from clinical and methodological perspectives.

[Critical review of mechanisms of action of second-generation antipsychotic drugs].

The advent of second-generation antipsychotics (SGA) in the wake of clozapine, the prototype for atypical antipsychotics, represents a breakthrough in the pharmacologic treatment of schizophrenia. There is growing evidence that most of the SGA can offer advantages over first-generation antipsychotics within the effective dose range, such as improvement in negative symptoms and cognitive impairment, fewer extrapyramidal side effects, and less hyperprolactinemia. However, the essential pharmacological properties that confer the different therapeutic effects of the SGA have remained elusive, and the search for novel antipsychotics without dopamine D2 receptor antagonism has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current predominant theories of mechanisms of action of SGA, including the serotonin-dopamine hypothesis, the "fast-off-D2 theory," and regional specificity. In addition, it focuses on the roles of N-methyl-D-aspartate receptors, dopamine DI receptors, and alpha-adrenergic receptors in the pharmacology of SGA.

Factors related to curved femur in elderly Japanese women.

BACKGROUND: Multiple factors are involved in the development of atypical femoral fractures, and excessive curvature of the femur is thought to be one of them. However, the pathogenesis of femoral curvature is unknown. We evaluated the influence of factors related to bone metabolism and posture on the development of femoral curvature. METHODS: A total of 139 women participated in the present study. Curvatures were measured using antero-posterior and lateral radiography of the femur. We evaluated some bone and vitamin D metabolism markers in serum, the bone mineral density (BMD), lumbar spine alignment, and pelvic tilt. RESULTS: We divided the women into two groups, curved and non-curved groups, based on the average plus standard deviation as the cut-off between the groups. When univariate logistic regression analysis was performed to detect factors affecting femoral curvature, the following were identified as indices significantly affecting the curvature: age of the patients, serum concentrations of calcium, intact parathyroid hormone, pentosidine, homocysteine and 25-hydroxyvitamin D (25(OH)D), and BMD of the proximal femur (P < 0.05) both in the lateral and anterior curvatures. When we used multivariate analyses to assess these factors, only 25(OH)D and age (lateral and anterior standardized odds ratio: 0.776 and 0.385, and 2.312 and 4.472, respectively) affected the femoral curvature (P < 0.05). CONCLUSION: Femoral curvature is strongly influenced by age and serum vitamin D.

Comminuted distal humeral fracture treated using the Ilizarov technique in a patient with rheumatoid arthritis and osteoporosis.

The goal of treatment for distal humeral fractures in patients with rheumatoid arthritis (RA) is to obtain sufficient bone union and good elbow function. However, treating comminuted distal humeral fractures in patients with RA and osteoporosis is challenging. We present the case of a 58-year-old woman with RA and osteoporosis who suffered a comminuted distal humeral fracture and was successfully treated with the Ilizarov technique. The Ilizarov technique is minimally invasive compared with conventional open surgery, can obtain good stabilization, and allows earlier rehabilitation, even if the fractured bone is severely osteoporotic. The patient exhibited good elbow function and alignment at the final follow-up examination (18 postoperative months). To the best of our knowledge, the present case is the first in which a comminuted distal humeral fracture in a patient with RA and severe osteoporosis was successfully treated with an Ilizarov external fixator.

Schizophrenia: when clozapine fails.

PURPOSE OF REVIEW: This article reviews the recent evidence for therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) not responding to or only partially responding to clozapine. RECENT FINDINGS: A number of pharmacological and nonpharmacological biological approaches for clozapine-resistant TRS have been evaluated in clinical trials. Among these, the evidence supporting clozapine augmentation by pharmacological approaches is weak and the reported benefits were modest at best. However, the results of a recent randomized trial suggest that electroconvulsive therapy (ECT) may be efficacious for the short-term treatment of patients with clozapine-resistant TRS. SUMMARY: There is currently insufficient evidence for efficacy of pharmacological augmentation strategies to clozapine. ECT may be a promising option, but further research is necessary to confirm its long-term effects. Moreover, further controlled studies are warranted to clarify the potential of other biological and psychosocial approaches to serve as adjuvant treatments in patients with clozapine-resistant TRS.

Amphetamine-induced Fos is reduced in limbic cortical regions but not in the caudate or accumbens in a genetic model of NMDA receptor hypofunction.

A mouse strain has been developed that expresses low levels of the NR1 subunit of the NMDA receptor. These mice are a model of chronic developmental NMDA receptor hypofunction and may therefore have relevance to the hypothesized NMDA receptor hypofunction in schizophrenia. Many schizophrenia patients show exaggerated behavioral and neuronal responses to amphetamine compared to healthy subjects. Studies were designed to determine if the NR1-deficient mice would exhibit enhanced sensitivity to amphetamine. Effects of amphetamine on behavioral activation and Fos induction were compared between the NR1-deficient mice and wild-type controls. The NR1 hypomorphic mice and controls exhibited similar locomotor activation after administration of amphetamine at 2 mg/kg. The mutant mice showed slightly reduced peak locomotor activity and slightly increased stereotypy after 4 mg/kg amphetamine. There were no differences in Fos induction in response to amphetamine in the caudate putamen, nucleus accumbens, medial or central amygdala nuclei, or bed nucleus of the stria terminalis. However, amphetamine-induced Fos was substantially attenuated in the medial frontal (infralimbic) and cingulate cortices, basolateral amygdala, and in the lateral septum of the mutant mice. The results suggest a neuroanatomically selective activation deficit to amphetamine challenge in the NR1-deficient mice.