Perceived participation and autonomy structural relationships among related factors in patients with stroke and hypertension in China: A ISM model approach.

Aims: To explore the structural relationship between perceived participation and autonomy among older adults with stroke and hypertension in home and community-based services (HCBSs) in the eastern coastal region of China. Design: An explorative cross-sectional study. Methods: From July to September 2021, a total of 714 respondents were reported to have stroke and hypertension, and their information was used in the analysis of this study. A multiple linear regression analysis was used to explore the factors influencing factors older adults' perceived participation and autonomy. Using the ISM model, we analyzed the factors affecting social participation in patients with stroke and hypertension and explained the logical relationships and hierarchy among the factors. Results: The mean score of perceived participation was 58.34 ± 27.57. Age, marital status, health insurance, living status, number of children, chronic diseases, sleep time, frequency of outings, and health utility value were significant factors affecting perceived participation and autonomy with stroke and hypertension patients. Among them, health insurance is the direct factor on the surface, age, number of children, chronic diseases, sleep time, frequency of outings, and health utility value are the intermediate indirect factors, and marital status and living status are the deep-rooted factors. Conclusion: By the study that the hierarchical structure provides a visualization of interrelationships and interdependences among the influencing factors of perceived participation and autonomy. It also may be a significant complement to traditional variable-entered approaches and construct an optimized multidimensional perspective of participation and autonomy. Future research should focus on optimizing the living environment of older adults with stroke and hypertension to explore the model of rehabilitative intervention and help patients successfully reintegrate into their families/societies.

Intelligently Thermoresponsive Ionic Liquid toward Molecular Firefighting and Thermal Energy Management.

Hydrocarbon-based phase change materials (PCMs) are accompanied by an inherent fire risk, which is hindering their further application especially in construction. Molecular-firefighting PCMs can be ideal and promising candidates to simultaneously ensure the highly efficient energy management and fire safety of PCMs. In this work, two novel phosphorus/nitrogen-containing ionic liquids ([DP][MI] and [DP][TEA]), composed of imidazole (MI) or triethylamine (TEA) cations and dicetyl phosphate (DP) anion, were synthesized for fire-proofing thermal energy management. The fire risk assessment confirmed that the extinguishing time of prepared [DP][MI] and [DP][TEA] was greatly shortened to 20 s and 3.5 min from 45 min for controlled sample, respectively. Moreover, the thermal enthalpy of [DP][MI] reached about 99.0 J g-1. In addition, [DP][MI] and [DP][TEA] achieved low supercooling extents of 2.2 and 4.4 °C, separately. Both molecular firefighting and efficient energy management were achieved for [DP][MI] and [DP][TEA]. As applied in wood-plastic composite which is ubiquitous in construction, [DP][TEA] endowed the composite with temperature-regulating capability of about 10 °C in hut test and remarkably suppressed fire hazard of the composite, displaying a potential application value.

Effects of organochlorine exposure on male reproductive disorders in an electronic waste area of South China.

Several studies suggest that organochlorine exposure can affect male reproductive functions, causing poor semen quality, endocrine disruption, or dysregulation of thyroid hormones. This study uses multiple linear regression (MLR) models to analyze the correlation between male reproductive functions and polychlorinated biphenyl (PCBs) congeners or p,p'-DDE levels in serum, semen, and indoor dust samples. Multiple comparisons were all adjusted using the false discovery rate (FDR). The results revealed that the PCB congener levels in seminal plasma were significantly associated with the quality parameters of human semen (i.e., sperm count, morphology, and motility) and thyroid hormones after adjusting for covariates, e.g., associations of the sperm concentration with levels of CB105 (ß = -0.323, 95% CI: -0.561, -0.085, p = 0.009), CB44 (ß = 0.585, 95% CI: 0.290, 0.880, p < 0.001), and CB66 (ß = -0.435, 95% CI: -0.728, -0.143, p = 0.004) in the seminal plasma were observed. Correlations between serum pollutants levels and the semen quality, reproductive hormones, or thyroid hormones were also observed. Moreover, our results demonstrate that the quantification of PCBs in seminal plasma can better describe male reproductive disorders than that in serum or dust. Organochlorine exposure measured in serum or dust, especially in seminal plasma, was associated with semen quality, as well as reproductive and thyroid hormones, thus suggesting that the impacts of persistent pollutants on male reproductive health require further investigation.

MicroRNA-1202 plays a vital role in osteoarthritis via KCNQ1OT1 has-miR-1202-ETS1 regulatory pathway.

BACKGROUND: This study aimed to explore the molecular mechanism of osteoarthritis (OA) and provide information about new genes as potential targets for OA treatment. METHODS: Gene expression profile of GSE105027, including 12 OA serum samples (OA group) and 12 healthy serum samples (ctrl group), was downloaded. The differentially expressed miRNAs (DEMs) as well as miRNA-mRNAs interactions were investigated, followed by function and pathway investigation. Then the protein-protein interaction (PPI) network was performed. Furthermore, the long non-coding RNA (lncRNA)-miRNA-mRNA interactions (competing endogenous RNAs, ceRNAs) were investigated. RESULTS: A total of 17 downregulated miRNAs were revealed between OA and ctrl groups. These DEMs such as has-miR-1202 were mainly enriched in GO functions like histone acetyltransferase binding and KEGG pathways like cellular senescence. The integrated PPI network analysis showed that has-miR-1202, has-miR-33b-3p, has-miR-940, has-miR-4284, and has-miR-4281 were 5 downregulated miRNAs in this network. Furthermore, the lncRNA-miRNA-mRNA interactions such as KCNQ1OT1-has-miR-1202-ETS1 were revealed in the present ceRNA network. CONCLUSION: Key DEMs such as miR-33b-3p, miR-940, and miR-1202 may be involved in OA. miR-1202 may regulate OA development via histone acetyltransferase pathway binding function and cellular senescence pathway. Furthermore, KCNQ1OT1-has-miR-1202-ETS1 might be vital for the process of OA.

Levels and congener profiles of halogenated persistent organic pollutants in human serum and semen at an e-waste area in South China.

Typical halogenated persistent organic pollutants (Hal-POPs), including polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (DDT), are a group of ubiquitous organic pollutants with an endocrine disrupting effect. This study evaluated the accumulation and congener profiles of Hal-POPs in the bodies of men who live/work in areas of South China where electronic wastes are collected and managed, especially in their semen samples. The results show that the detection frequency and serum concentrations of Hal-POP congeners within the high-exposure group (HEG) were higher than those of the low-exposure group (LEG). Furthermore, an identical trend was observed for the seminal plasma concentrations of Hal-POPs. The distribution characteristics, such as their mean, median, and discrete values, of PBDE congeners in serum and semen samples from the same subjects were consistent with each other. However, the distribution characteristics of PCB congeners in serum samples were different from those in semen samples. BDE153 was one of the most abundant congeners found in the serum and semen samples; hence, it can be identified as an indicator PBDE congener. Further research is needed to explore the mechanism of Hal-POPs distribution in human semen and serum samples.

Flame Retardation of Natural Rubber: Strategy and Recent Progress.

Natural rubber (NR) as a kind of commercial polymer or engineering elastomer is widely used in tires, dampers, suspension elements, etc., because of its unique overall performance. For some NR products, their work environment is extremely harsh, facing a serious fire safety challenge. Accordingly, it is important and necessary to endow NR with flame retardancy via different strategies. Until now, different methods have been used to improve the flame retardancy of NR, mainly including intrinsic flame retardation through the incorporation of some flame-retarding units into polymer chains and additive-type flame retardation via adding some halogen or halogen-free flame retardants into NR matrix. For them, the synergistic flame-retarding action is usually applied to simultaneously enhance flame retardancy and mechanical properties, in which some synergistic flame retardants such as organo-montmorillonite (OMMT), carbon materials, halloysite nanotube (HNT), etc., are utilized to achieve the above-mentioned aim. The used flame-retarding units in polymer chains for intrinsic flame retardation mainly include phosphorus-containing small molecules, an unsaturated chemical bonds-containing structure, a cross-linking structure, etc.; flame retardants in additive-type flame retardation contain organic and inorganic flame retardants, such as magnesium hydroxide, aluminum hydroxide, ammonium polyphosphate, and so on. Concerning the flame retardation of NR, great progress has been made in the past work. To achieve the comprehensive understanding for the strategy and recent progress in the flame retardation of NR, we thoroughly analyze and discuss the past and current flame-retardant strategies and the obtained progress in the flame-retarding NR field in this review, and a brief prospect for the flame retardation of NR is also presented.

Metabolic Syndrome, as Defined Based on Parameters Including Visceral Fat Area, Predicts Complications After Surgery for Rectal Cancer.

BACKGROUND/OBJECTIVES: Metabolic syndrome (MetS) has become a major public health problem. However, few studies have examined the impact of MetS on the postoperative complications of colorectal cancer and the conclusions remain controversial. The present study aimed to investigate whether MetS, as defined based on visceral fat area (VFA) instead of BMI or waist circumference, would predict complications after surgery for rectal cancer. SUBJECTS/METHODS: We conducted a retrospective study of patients who underwent surgery for rectal cancer at our department between January 2013 and August 2018. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. A receiver operating characteristic curve analysis was used to determine the gender-specific cut-off values for VFA. RESULTS: A total of 381 patients were included in the study. The optimal cut-off values for VFA were 117.9 cm2 for men and 76.9 cm2 for women, and 153 patients were diagnosed as having MetS. The rate of postoperative complication was significantly higher in the MetS group than that in the non-MetS group (34.6% versus 15.8%, P < 0.001). The multivariate logistic regression analysis demonstrated that MetS (OR 3.712, P < 0.001), NRS 2002 scores ≥ 3 (OR 2.563, P = 0.001), and tumor located at the lower 1/3 (OR 3.290, P = 0.001) were independent risk factors for complications after surgery for rectal cancer. CONCLUSION: Metabolic syndrome, as defined based on parameters including visceral fat area, was an independent risk factor for complications after surgery for rectal cancer.

Determination of folic acid via its quenching effect on the fluorescence of MoS2 quantum dots.

Molybdenum disulfide quantum dots (MoS2 QDs) are used in a fluorometric method for the determination of folic acid (FA) based on fluorescence quenching. The MoS2 QDs synthesized by a hydrothermal method possess bright blue fluorescence (with excitation/emission maxima of 325/415 nm), quantum yield of 3.7%, and excellent storage stability in solution (30 days in the refrigerator). Their fluorescence is quenched by FA, and intensity decreases linearly in the 0.1 to 125 µM FA concentration range. The detection limit is 0.1 µM (at S/N = 3), and the relative standard deviation (for n = 5) is 2.8% for 25 µM concentrations of FA. Studies on the quenching mechanism suggest that the effect is due to static quenching. The FA in commercial FA tablets was successfully determined. Graphical abstract Schematic representation of the hydrothermal method for the preparation of molybdenum disulfide quantum dots (MoS2 QDs) with about 2.7 ± 0.5 nm diameter using Na2MoO4 and L-cysteine as Mo and S sources, and the fluorescence method for the determination of folic acid (FA) based on fluorescence quenching of MoS2 QDs.

Novel Core-Shell Hybrid Nanosphere towards the Mechanical Enhancement and Fire Retardance of Polycarbonate.

It is a huge challenge to achieve highly efficient fire retardance with no mechanical damage to polymers. In our current research, a novel core-shell titanium dioxide@diphenylphosphinic (TiO2@DPP) nanosphere was first synthesized through a hydrothermal reacting process, and applied in simultaneously enhancing the fire retardance and mechanical properties of polycarbonate (PC). The well-designed TiO2@DPP exhibited a significant effect on combustion performance and mechanical reinforcement of PC. At only 0.10 wt % of TiO2@DPP, PC/TiO2@DPP passed the UL-94 V-0 rating, and its oxygen index value rose to 29.3%. Moreover, the peak value of the heat release rate was remarkably decreased by 34.1% in the combustion test, accompanied by the formation of more compacted char layer and the release of more incombustible gas. Equally important another aspect is that the PC containing only 0.10 wt % of TiO2@DPP possessed higher elongation at break and higher tensile strength than pure PC, correspondingly increased by 27.7 and 14.7%. The analysis of the flame-retardant mechanism revealed that the improved fire retardance of PC is primarily ascribed to the barrier action of a cross-linking network containing phosphorus and titanium, the dilution of nonflammable gases such as H2O, and the quenching effect of free radicals which are from the phosphorous group in the gas phase. All these experimental results demonstrate that the core-shell hybrid TiO2@DPP may achieve a simultaneous significant improvement in fire retardance and mechanical properties of PC.

[Successful pregnancy following intracytoplasmic sperm injection?embryo transfer in a patient with premature ovarian insufficiency: a case report].

OBJECTIVE: We report a case of ovarian function fluctuation during long-term follow-up in a patient with premature ovarian insufficiency (POI). The patient finally obtained clinical pregnancy with subsequent uneventful full-term delivery after several intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. This case demonstrates that hormone replacement therapy (HRT) and assisted reproductive therapy should be applied as soon as possible to young patients with POI who have a strong desire for pregnancy in the absence of contraindications. This strategy helps such patients obtain pregnancy and delivery before the exhaustion of ovarian function.

Effects of gene polymorphisms in the endoplasmic reticulum stress pathway on clinical outcomes of chemoradiotherapy in Chinese patients with nasopharyngeal carcinoma.

There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.

Impact of polymorphisms in angiogenesis-related genes on clinical outcomes of radiotherapy in patients with nasopharyngeal carcinoma.

The purpose of this paper is to assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The response evaluation criteria in solid tumours were used for assessing efficacies, and the criteria of the Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation. Statistical methods included chi-square test, uni- and multivariate logistic regression analyses. Genotypic carriers of rs1800541 GT were at an elevated risk of developing grade 3+ oral mucositis, and a genetic variant of rs5333 was a predictor for a lower occurring risk of grade 2+ radiation-induced xerostomia. EDN1 rs1800541, rs2071942 and rs5370 variants were associated with a significantly higher risk of severe myelosuppression. SNPs in such angiogenesis-related genes as EDN1 rs1800541, rs2071942 & rs5370 and EDNRA rs5333 may serve as useful biomarkers for predicting the outcomes of NPC patients.

[Pregnancy outcome in a woman with premature ovarian insufficiency complicated by systemic lupus erythematosus during pregnancy: a case report].

OBJECTIVE: We report a case of in vitro fertilization and embryo transfer (IVF?ET) with oocyte donation in a woman with premature ovarian insufficiency (POI) complicated by systemic lupus erythematosus (SLE) during pregnancy. The patient had a diagnosis of POI 4 years earlier and 11 weeks after successful pregnancy by IVF?ET with oocyte donation in 2003, she presented with facial edema, and further examinations confirmed the diagnosis of lupus nephritis. She received treatment with prednisone to control the activity of SLE and aspirin and low?molecular?weight heparin to improve placental blood flow with close monitoring of gravida and fetus throughout pregnancy. The condition of the patient remained unstable during pregnancy, and liver damage and placental circulation disorder occurred in late gestational weeks with suspected intrauterine growth retardation (IUGR) of the fetus. For maternal and fetal safety, the patient received elective caesarean section and delivered a premature boy at 31 weeks of gestation. She subsequently received further medications for SLE and showed good recovery of the immunological parameters and absence of SLE symptoms during the follow?up for 14 years, indicating a clinical cure of SLE. Her son shows normal growth and development. Based on the experience with this case and literature review, we believe that immunological factor is an important cause of POI and thus recommend full immunological examinations in cases of idiopathic POI.

Successful pregnancy following intracytoplasmic sperm injection?embryo transfer in a patient with premature ovarian insufficiency: a case report / 南方医科大学学报

We report a case of ovarian function fluctuation during long-term follow-up in a patient with premature ovarian insufficiency (POI). The patient finally obtained clinical pregnancy with subsequent uneventful full-term delivery after several intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. This case demonstrates that hormone replacement therapy (HRT) and assisted reproductive therapy should be applied as soon as possible to young patients with POI who have a strong desire for pregnancy in the absence of contraindications. This strategy helps such patients obtain pregnancy and delivery before the exhaustion of ovarian function.

Pregnancy outcome in a woman with premature ovarian insufficiency complicated by systemic lupus erythematosus during pregnancy: a case report / 南方医科大学学报

We report a case of in vitro fertilization and embryo transfer (IVF?ET) with oocyte donation in a woman with premature ovarian insufficiency (POI) complicated by systemic lupus erythematosus (SLE) during pregnancy. The patient had a diagnosis of POI 4 years earlier and 11 weeks after successful pregnancy by IVF?ET with oocyte donation in 2003, she presented with facial edema, and further examinations confirmed the diagnosis of lupus nephritis. She received treatment with prednisone to control the activity of SLE and aspirin and low?molecular?weight heparin to improve placental blood flow with close monitoring of gravida and fetus throughout pregnancy. The condition of the patient remained unstable during pregnancy, and liver damage and placental circulation disorder occurred in late gestational weeks with suspected intrauterine growth retardation (IUGR) of the fetus. For maternal and fetal safety, the patient received elective caesarean section and delivered a premature boy at 31 weeks of gestation. She subsequently received further medications for SLE and showed good recovery of the immunological parameters and absence of SLE symptoms during the follow?up for 14 years, indicating a clinical cure of SLE. Her son shows normal growth and development. Based on the experience with this case and literature review, we believe that immunological factor is an important cause of POI and thus recommend full immunological examinations in cases of idiopathic POI.

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis.

Warfarin is an oral anticoagulant with significant interpatient variability in dosage. A large number of studies have confirmed that the individual warfarin dose is mainly affected by the cytochrome P450 complex subunit 2C9 and vitamin K epoxide reductase complex subunit 1. However, the association between cytochrome P450 4F2 (CYP4F2) gene polymorphisms and warfarin dosage in the Asian population remains controversial. To investigate the impact of the CYP4F2 polymorphism rs2108622 (p.V433M) on warfarin dose requirement, a systematic review and meta-analysis were conducted. According to the strict inclusion and exclusion criteria set, a comprehensive literature search was performed, and the studies published before August 5, 2015 were searched for in PubMed, EMBASE and the China National Knowledge Infrastructure databases. The references were checked by two independent reviewers. The association between the warfarin maintenance dose and CYP4F2 polymorphism was analyzed. Twenty-two studies were included in the meta-analysis. Compared with the CYP4F2 genotype CC, carriers of the CT and TT genotypes required a 9 [95% confidence interval (CI): 6.0-13.0] and 20% (95% CI, 13.0-27.0) higher warfarin dose, respectively. In the combined analysis, T carriers (CT+TT) required an 11% (95% CI, 8.0-14.0) higher warfarin dose compared to the CC genotype. In addition, there was a 10% (95% CI, 5.0-15.0) higher warfarin dose in TT carriers compared to the CT genotype (all P<0.05). The results of the meta-analysis suggest that the effects of the CYP4F2 polymorphism on individual warfarin dose have a statistically significant difference, and the effect degree is variable in the subgroups. Further studies are expected to explore whether the pharmacogenetics model including the CYP4F2 polymorphism can strengthen the prediction of warfarin dose.

Influence of APOE Gene Polymorphism on Interindividual and Interethnic Warfarin Dosage Requirement: A Systematic Review and Meta-Analysis.

BACKGROUND: Warfarin is the most extensively used coumarin anticoagulant. It has been shown that the anticoagulant effect of warfarin is associated with genetic variation. Apolipoprotein E (ApoE) is a possible candidate to influence the maintenance dose of warfarin. ApoE affects the vitamin K cycle by mediating the uptake of vitamin K into the liver. The vitamin K cycle is the drug target of warfarin. However, the association between genetic variants of the APOE gene and warfarin dose requirement is still controversial. METHODS: Revman 5.3 software was used to analyze the relationship between APOE genotypes and warfarin dose requirements. RESULTS: In our meta-analysis, the E2/E2 genotype was significantly associated with warfarin dose. E2/E2 patients required 12% (P = 0.0002) lower mean daily warfarin dose than E3/E3 carriers. In addition, subgroup analysis showed that Asians with the E4/E4 genotype tended to need lower warfarin maintenance doses, while the African American E4/E4 carriers needed slightly higher doses than E3/E3 carriers; however, these subgroups were very small. CONCLUSION: This is the first meta-analysis of the association between APOE genotypes and warfarin dose. APOE E2/E2 might be one of the factors affecting warfarin dose requirements. The effect of APOE may vary between ethnicities.

Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma.

Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC.

Ketamine safety and tolerability in clinical trials for treatment-resistant depression.

OBJECTIVE: Ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the safety and tolerability of ketamine in this population have not been fully described. Herein we report the largest study to date of the safety, tolerability, and acceptability of ketamine in TRD. METHOD: Data from 205 intravenous (IV) ketamine infusions (0.5 mg/kg over 40 minutes) in 97 participants with DSM-IV-defined major depressive disorder (MDD) were pooled from 3 clinical trials conducted between 2006 and 2012 at 2 academic medical centers. Safety and tolerability measures included attrition, adverse events (AEs), hemodynamic changes, and assessments of psychosis and dissociation. RESULTS: The overall antidepressant response rate, defined as a ≥ 50% improvement in Montgomery-Asberg Depression Rating Scale score, was 67% (65 of 97 participants). Four of 205 infusions (1.95%) were discontinued due to AEs. The overall attrition rate was 3.1% (3 of 97). In the first 4 hours after the infusion, the most common general AEs were drowsiness, dizziness, poor coordination, blurred vision, and feeling strange or unreal. Approximately one third of individuals experienced protocol-defined hemodynamic changes. Ketamine resulted in small but significant increases in psychotomimetic and dissociative symptoms (all P < .05). There were no cases of persistent psychotomimetic effects, adverse medical effects, or increased substance use in a subgroup of patients with available long-term follow-up information. CONCLUSIONS: In this relatively large group of patients with TRD, ketamine was safe and well tolerated. Further research investigating the safety of ketamine in severe and refractory depression is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00419003, NCT00548964, and NCT00768430.

Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.

IMPORTANCE: Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. OBJECTIVE: To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND PARTICIPANTS: Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements. INTERVENTIONS: Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). MAIN OUTCOMES AND MEASURES: The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. RESULTS: Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. CONCLUSIONS AND RELEVANCE: This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00749203.