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Multiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer’s Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076–0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145–0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.

To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA isolates were characterized from 246 samples collected from LTCFs, medical tubes of LTCF residents, and hospital environments of two cities, Chiayi and Changhua. Species identification, molecular characterization, and drug resistance analysis were performed. Hospital environments had a higher MRSA detection rate than that of LTCF environments, where moist samples are a hotspot of MRSA habitats, including tube samples from LTCF residents. All MRSA isolates in this study carried the exfoliative toxin eta gene (100%). The majority of MRSA isolates were resistant to erythromycin (76.7%), gentamicin (60%), and ciprofloxacin (55%). The percentage of multidrug-resistant MRSA isolates was approximately 50%. The enterobacterial repetitive intergenic consensus polymerase chain reaction results showed that 18 MRSA isolates belonged to a specific cluster. This implied that genetically similar isolates were spread between hospitals and LTCFs in Changhua city. This study highlights the threat to the health of LTCFs’ residents posed by hospital contact with MRSA.

Objective: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD. Methods: We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I2 statistic. Moderators of effects were explored using metaregression. Results: Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, p < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = −0.1203, p = 0.0004). Conclusions: Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association.

Chun-Hung Chang,1,2 Chieh-Yu Liu,3 Shaw-Ji Chen,4,5 Hsin-Chi Tsai6,7 1Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 2Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 3Biostatistical Consulting Laboratory, Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 4Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung, Taiwan; 5Department of Medicine, Mackay Medical College, New Taipei, Taiwan; 6Department of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan; 7Department of Psychiatry, School of Medicine, Tzu-Chi University, Hualien City, Taiwan Objective: The aim of this study was to examine the effectiveness of light therapy in the treatment of geriatric depression. Methods: A systematic review and meta-analysis were carried out. Data sources for the literature search were PubMed, Cochrane Collaboration’s Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov. Controlled trials of light therapy on older patients with nonseasonal depression and depression rating scales were eligible. Studies were pooled using a random-effect model for comparisons with light therapy. We used effect size (ES), which expresses changes in depression severity, in each selected meta-analysis to calculate the standardized mean difference on the basis of Hedges’ adjusted g; positive values indicated that the depression severity improved after light therapy. All results were presented with 95% CIs. Statistical heterogeneity was explored through visual inspection of funnel plots and the I2 statistic. Moderators of effects were explored using meta-regression. Results: We identified eight trials involving 395 participants that met the inclusion criteria. Light therapy was significantly more effective than comparative treatments, including placebo or dim light, with an ES of 0.422 (95% CI: 0.174–0.709, P=0.001). In addition, six of the eight trials used bright (white) light, resulting in significantly reduced severity of geriatric depression (N=273, ES: 0.460, 95% CI: 0.085–0.836, P=0.016). Furthermore, pale blue light therapy reduced the severity of geriatric depression (N=89, ES: 0.464, 95% CI: 0.046–0.882, P=0.030). Conclusion: Our results highlighted the significant efficacy of light therapy in the treatment of geriatric depression. Additional well-designed, controlled studies are necessary to adopt standard parameters, adequate group sizes, and randomized assignment to evaluate more thoroughly the efficacy of light therapy for treating geriatric depression. Keywords: depression, elderly adults, light therapy

Chun-Hung Chang,1,2 Shaw-Ji Chen,3,4 Chieh-Yu Liu,5 Hsin-Chi Tsai6,7 1Brain Disease Research Center, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan; 2Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 3Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung, Taiwan; 4Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; 5Biostatistical Consulting Lab, Institute of Nursing-Midwifery, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 6Department of Psychiatry, Tzu-Chi General Hospital, Hualien, Taiwan; 7Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan Purpose: The purpose of this study was to investigate the incidence and risk of suicidal drug overdose (SDO) after stroke in older patients. Methods: We enrolled patients aged 60–99years who were diagnosed with new-onset stroke between 2002 and 2013 and age-, sex-, and index-year-matched controls who did not have stroke. Patients with a history of SDO before enrollment were excluded. Both groups were observed until December 31, 2013. The primary end point was the occurrence of newly diagnosed SDO. The cumulative incidence rates of the study and control groups were estimated using the Kaplan–Meier method. Furthermore, we used the Cox proportional hazards model to identify risk factors for SDO. Results: We selected 22,770 individuals. Among them, 11,385 were older patients (aged 60–99years) who had newly diagnosed stroke and 11,385 were controls. Of the 22,770 individuals, 275 (1.21%) had SDO during a mean follow-up period of 5.33±3.30years, comprising 191 (1.68%) from the stroke group and 84 (0.74%) from the control group. Older patients with stroke had a significantly higher risk of SDO than the controls (adjusted hazard ratio: 2.288, 95% confidence interval [CI]: 1.746–2.999, p

This study evaluated the severe hepatic outcome (SHO) in patients with schizophrenia and viral hepatitis who received antipsychotics. Using the nationwide Taiwan National Health Insurance Research Database, patients first diagnosed with schizophrenia between 2002 and 2013 were identified. Patients diagnosed with schizophrenia who had viral hepatitis, including hepatitis B virus (HBV) or hepatitis C virus (HCV), were designated as the viral hepatitis group. A control group without viral hepatitis was matched for age, sex, and index year in a 2:1 ratio. Patients with severe hepatic outcomes before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of a SHO, including liver cancer, liver failure, liver decompensation, or transplantation. Among the 16,365 patients newly diagnosed with schizophrenia between January 2002 and December 2013, we identified 614 patients with viral hepatitis and 1228 matched patients without viral hepatitis. Of these 1842 patients, 41 (2.22%) developed SHOs, including 26 (4.23%) in the viral hepatitis group and 15 (1.22%) in the control group, during the mean follow-up period of 3.71 ± 2.49 years. Cox proportional hazard analysis indicated that the SHO risk increased by 3.58 (95% confidence interval [CI]: 1.859–6.754; P

Acinetobacter baumannii is an important health care-associated bacterium and a common multidrug-resistant pathogen. The use of antibiotics in the husbandry industry has raised concerns about drug-resistant A. baumannii strains, which may affect humans. This study aimed to investigate the seasonal distribution of A. baumannii in aquatic environments near areas of livestock farming. The geographic distribution, antibiotic resistance characteristic, and DNA fingerprinting genotype of A. baumannii were also studied. The results showed that environmental A. baumannii was prevalent during the summer and autumn. The hotspots for A. baumannii were found at the sampling sites of livestock wastewater channels (21.4%, 3/14) and the tributaries adjacent to livestock farms (15.4%, 2/13). The prevalence of A. baumannii at these locations was significantly higher than those adjacent to the Puzi River. Multidrug-resistant strain of A. baumannii was not found in this study, with only one strain (5%, 1/20) being resistant to tetracycline. Of the isolates that were obtained, 10% (2/20) and 20% (4/20) were found to be intermediately resistant to tetracycline and sulphamethoxazole/trimethoprim, respectively. The genotyping patterns and clustering analysis indicated that enterobacterial repetitive intergenic consensus sequence polymerase chain reaction (ERIC-PCR) differentiated A. baumannii strains effectively. There were two major clusters that could then be subtyped into 20 A. baumannii strains with 15 profiles. The A. baumannii strains that were isolated from upstream of the Puzi River and livestock wastewater channels were composed of Cluster I. Cluster II only contained isolates from downstream of the Puzi River area. Furthermore, isolates from adjacent sites were shown to have identical profiles (100%). These results suggest that A. baumannii may have spread through free-flowing water in this study. Therefore, we propose that livestock wastewater is one of the sources that contribute to A. baumannii pollution in water bodies. In summary, continuous monitoring of antibiotic pollution in livestock wastewater is required.

Hsin-Chi Tsai,1,2 Chun-Hung Chang,3,4 Jiann-I Pan,5 Hung-Jen Hsieh,6 Sheng-Tzung Tsai,7 Hsiang-Yi Hung,7 Shin-Yuan Chen1,71Institute of Medical Science, Tzu-Chi University, Hualien City, Taiwan; 2Department of Psychiatry, Tzu-Chi General Hospital, Hualien City, Taiwan; 3Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan; 4China Medical University, Taichung, Taiwan; 5Department of Medical Informatics, Tzu-Chi University, Hualien, Taiwan; 6Nuclear Medicine, Tzu Chi General Hospital, Hualien City, Taiwan; 7Department of Neurosurgery, Tzu-Chi General Hospital, Hualien City, TaiwanObjective: Deep-brain stimulation (DBS) for treating refractory obsessive–compulsive disorder (OCD) has shown positive results in small clinical trials. Ventral capsule/ventral striatum (VC/VS) is one of the promising targets; however, whether or not acute stimulation test can provide substantial information for chronic stimulation is not yet known. We evaluated postoperative test stimulation and examined the relationship of acute simulation-induced smile/laughter and 15-month clinical outcome.Methods: Four adult patients with refractory OCD were implanted with Model 3387 leads bilaterally in an area of VC/VS. Postoperative test stimulation was performed at least 2 weeks after surgery. We performed double-blinded postoperative test stimulation with different contact and voltage. The relationship of stimulation-induced smile/laughter and chronic response was examined.Results: Patients presented smile, laughter, euphoria, increased heart rate, increased blood pressure, smell, chest vibration, dizziness, nausea, heat, or increased sexual drive during acute stimulation. We found that the higher the percentage of smile/laughter (34.3%, 31.3%, 56.3%, and 12.5% for four cases), the greater the reduction in the Yale-Brown Obsessive Compulsive Scale (30.6%, 38.9%, 58.8%, and 7.7% respectively at 15-month DBS).Conclusion: This study showed that acute DBS of the VC/VS might cause mood change, cardiovascular, sensory, or motor effects. These effects were transient or habituated over six months. We suggest stimulation-induced smile/laughter may be a possible predictor for long-term DBS outcome. Larger studies, genetic studies, and imaging studies are needed to evaluate the effects of different parameters and possible predictors in the treatment of OCD.Keywords: deep-brain stimulation, DBS, OCD, VC/VS, nucleus accumbens, NAcc

N -of-1 trials are an effective evidence-based approach in individual patient management. It has been suggested that deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective in the treatment of refractory obsessive–compulsive disorder (OCD). However, it has not been documented in the literature whether a perioperative acute stimulation test can provide substantial information for chronic stimulation. A 21-year-old man with a 6-year history of medication-refractory OCD underwent bilateral DBS on the VC/VS. Two weeks after surgery, an acute stimulation test was performed in an N -of-1 trial. Olfactory hallucinations, laughter, and euphoria were observed during the acute stimulation test. At follow-up after 17 months, the patient's scores improved from 34 at baseline to 14 on the Yale–Brown Obsessive Compulsive Scale, from 34 to 20 (41.2% improvement) on the Hamilton Anxiety Rating scale, and from 41 to 71 (75% improvement) on the Global Assessment of Functioning scale. According to our N -of-1 trial, olfactory hallucinations, in addition to laughter, induced by a perioperative acute stimulation test may be an indicator of good outcome in OCDDBS during chronic stimulation.

Objective: The prevention of infections is crucial in long-term care programs. Investigations of the occurrence and sources of pathogens in long-term care facilities (LTCFs) are still lacking, especially in eastern Taiwan. In this study, we conducted a surveillance of two common pathogens, Acinetobacter baumannii (AB) and methicillin-resistant Staphylococcus aureus (MRSA), in LTCFs in Hualien. Materials and Methods: Pathogenic assays including isolation, identification, and antimicrobial susceptibility tests were conducted for AB and MRSA at LTCFs in Eastern Taiwan. Staphylococcal cassette chromosome mec typing assays were done to understand the relatedness of clonal strains of MRSA. Results: All AB-positive samples in the LTCFs were mainly from water-rich samples and were drug susceptible. Our data indicated that the AB strains from LTCFs were similar to those from Puzi River watersheds in Taiwan, which were not drug resistant to commonly used antibiotics. On the other hand, the drug resistance analysis of MRSA indicated that the genotypes from the LTCFs were similar to those from nearby hospitals. Eight strains of MRSA were isolated from four LTCFs, of which five were identified as hospital-acquired strains according to SSCmed typing assays. Conclusion: These findings suggest that MRSA in LTCFs might propagate from hospitals and could be transmitted between hospitals and LTCFs. Health authorities should be aware of this risk. The long-term follow-up of MRSA is recommended in local medical institutions as well as in LTCFs for correlative analysis.

Rational The therapeutic effect of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD) has been studied, but complications after this treatment have rarely been noted. Patient concerns A 28-year-old man with treatment-resistant OCD received bilateral ventral capsule/ventral striatum stimulation for 12 months. Diagnosis Compulsive skin-picking behavior and infection were noted following 12-month DBS treatment. Intervention We removed the implanted right-side pulse generator. Outcomes The local inflammation and skin-picking behavior gradually improved. The stimulator device was re-implanted 4 months later. Lessons We suggest that patients with the OC spectrum should be evaluated for skin-picking behaviors during presurgical and postsurgical follow-up to reduce the infection and device removal rates.

Shaw-Ji Chen,1,2 Chung-Hung Chang,3 Hsin-Chi Tsai,2,4 Shao-Tsu Chen,2,4 Chaucer CH Lin2,4 1Department of Psychiatry, Mackay Memorial Hospital Taitung Branch, Taitung; 2School of Medicine, Buddhist Tzu Chi University, Hualien; 3Department of Psychiatry, China Medical University Hospital, Taichung; 4Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan Abstract: Depression is a major psychiatric disorder. The standard treatment for depression is antidepressant medication, but the responses to antidepressant treatment are only partial, even poor, among 30%–45% of patients. Refractory depression is defined as depression that does not respond to antidepressant therapy after 4 weeks of use. There is evidence that repetitive transcranial magnetic stimulation (rTMS) may exert effects in treating psychiatric disorder through moderating focal neuronal functions. High-frequency rTMS on the left prefrontal area and low-frequency rTMS on the right prefrontal area were shown to be effective in alleviating depressive symptoms. Given the statistically significant antidepressant effectiveness noted, the clinical application of rTMS as a depression treatment warrants further studies. Application of rTMS as an add-on therapy would be a practical research model. High-frequency (5–20 Hz) rTMS over the left dorsolateral prefrontal cortex was found to have a significant effect on medication-resistant depression. In the present study, we not only measured the acute antidepressant effect of rTMS during treatment and immediately after its completion but also evaluated participants 1 month after completion of the treatment protocol. Study participants were divided into two groups: an active rTMS group (n = 10) and a sham group (n = 10). The active rTMS group was defined as participants who received the rTMS protocol, and the sham group was defined as participants who received a sham rTMS procedure. A significant Hamilton Depression Rating Scale score reduction was observed in both groups after the fifth and tenth treatments. However, those in the active rTMS group maintained their improvement as measured one month after completion of the rTMS protocol. Participants who received active rTMS were more likely to have persistent improvement in depression scores than participants who received sham rTMS. Keywords: major depressive disorder, repetitive transcranial magnetic stimulation, treatment-resistant depression, efficacy, adverse effect

This 28-year-old Chinese man was referred for deep brain stimulation (DBS) evaluation for an 8-year history of refractory obsessive-compulsive disorder. After the patient had signed an informed consent, the authors implanted DBS leads. Hypomania with hypersexuality was noted on stimulation at Contact 2 and became aggravated with a higher voltage (≥ 3 V) during chronic bilateral DBS. After the voltage was decreased to 1 V, the patient's hypomanic symptoms subsided and his libido returned to baseline.