Comparative Analysis of Hemostatic Efficacy: Local Application of Lancehead Snake Venom Thrombin versus Hemostatic Forceps in Colon Polypectomy.

Background: Colon polypectomy often involves managing bleeding, and the choice of hemostatic methods is critical for patient outcomes. This study addresses the hemostatic effects of lancehead snake venom thrombin compared to hemostatic forceps in the context of colon polypectomy. Objective: To compare and assess the effectiveness and safety of local application of lancehead snake venom thrombin and hemostatic forceps in achieving hemostasis during colon polypectomy. Design: A randomized controlled trial was conducted to investigate and compare the hemostatic outcomes of two different approaches in colon polypectomy. Setting: The study was conducted at the Affiliated Hospital of Hebei University Hospital from January 2022 to June 2022. Participants: A total of 80 patients with colon polyps who met the inclusion criteria were randomly assigned to either the lancehead snake venom thrombin group or the hemostatic forceps group. Interventions: In the hemostatic forceps group, hemostatic forceps were employed to seal the wound post-polyp resection. In the lancehead snake venom thrombin group, aluminium potassium sulfate gel, in conjunction with locally sprayed lancehead snake venom thrombin, was applied to the wound. Primary Outcome Measures: The study assessed (1) intraoperative immediate bleeding and hemostasis; (2) intraoperative hemostasis time; (3) postoperative delayed post-polypectomy bleeding (DPPB); and (4) adverse reactions as primary outcome measures. Results: No significant differences were observed in the incidence rate of intraoperative immediate bleeding and the success rate of intraoperative hemostasis between the two groups. The lancehead snake venom thrombin group exhibited a shorter intraoperative hemostasis time and a lower incidence rate of adverse reactions compared to the hemostatic forceps group. No significant difference was found in the incidence rate of postoperative DPPB between the two groups. Conclusion: Local application of lancehead snake venom thrombin proves to be more effective and safer than hemostatic forceps in promptly managing bleeding during colon polypectomy.

Comprehensive Analysis of Physicochemical Properties and Volatile Compounds in Different Strawberry Wines under Various Pre-Treatments.

Pre-fermentation treatment has an important impact on the color, aroma, taste, and other characteristics of fruit wine. To discover suitable pre-treatment techniques and conditions that yield strawberry wine of excellent quality, the influences of juice fermentation, pulp maceration, thermovinification, and enzymatic hydrolysis pre-treatments on the basic chemical composition, color, antioxidant capacity, and volatile organic compounds in strawberry wines were investigated. The results showed that the color, antioxidant properties, and volatile aroma of strawberry wines fermented with juice were different from those with pulp. Strawberry wines fermented from juice after 50 °C maceration had more desirable qualities, such as less methanol content (72.43 ± 2.14 mg/L) compared with pulp-fermented wines (88.16 ± 7.52 mg/L) and enzymatic maceration wines (136.72 ± 11.5 mg/L); higher total phenolic content (21.78%) and total flavonoid content (13.02%); enhanced DPPH (17.36%) and ABTS (27.55%) free radical scavenging activities; richer essential terpenoids and fatty acid ethyl esters, such as linalool (11.28%), ethyl hexanoate (14.41%), ethyl octanoate (17.12%), ethyl decanoate (32.49%), and ethyl 9-decenoate (60.64%); pleasant floral and fruity notes compared with juice-fermented wines macerated at normal temperatures; and a lighter color. Overall, juice thermovinification at 50 °C is a potential pre-treatment technique to enhance the nutrition and aroma of strawberry wine.

Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps. Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making. Design: The research team performed a randomized controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022. Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation. Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions. Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05). Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

Correlation of Macrophages with Inflammatory Reaction in Ulcerative Colitis and Influence of Curcumin on Macrophage Chemotaxis.

Objective: Our study aimed to elucidate the correlation of macrophage (mø) with the inflammatory reaction in ulcerative colitis (UC) and the influence of curcumin (Cur) on mø chemotaxis in mice with UC. Methods: A total of 49 patients with UC (research group; RG) admitted between June 2020 and October 2021 and 56 healthy individuals (control group; CG) who visited concurrently were selected as the study participants. The peripheral blood mononuclear cells (PBMCs) were analyzed, and M1-type/M2-type mø and inflammatory factors (IFs) interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-ß) were detected. In addition, 15 BALB/c mice were purchased and divided into the normal group fed normally, the UC model group established with sodium dextran sulfate (DSS) and the Cur group induced by DSS + Cur feeding. Colon tissue mø was collected from mice to measure mø activity via CCK-8 and to quantify levels of IFs and chemokine CCL2 by polymer chain reaction (PCR)c and Western blotting. Results: The RG had a higher percentage of peripheral blood M1-type mø and a lower percentage of M2-type mø and M1/M2 mø ratio than the CG (P < .05). In the RG, IL-1, IL-6 and TNF-α all increased and were inversely correlated with the ratio of M1/M2 mø, while IL-10 and TGF-ß decreased, with a positive connection with the M1/M2 mø ratio. In the UC model mice, mø activity increased, but the apoptosis rate decreased. mø activity was lower in the Cur group than in the model and normal groups; mø apoptosis in the Cur group was higher than in the model group but lower than in the normal group. In addition, proIFs increased and anti-IFs decreased in the model group, and Cur also ameliorated this process. Finally, CCL2 and MCP-1 levels in the model group were also increased, while those in the Cur group were lower compared with the model group. Conclusion: In UC, the M1/M2 mø ratio is severely misadjusted, activation of M1-type mø is enhanced and pro-IFs are released in large quantities. Cur can ameliorate the abnormal activation of mø in mice with UC, inhibit mø chemotaxis and alleviate the inflammatory reaction, which may make it a new option for UC treatment in the future.

Clinical Effects of Biling Weitong Granules in Combination with Quadruple Therapy on Refractory Helicobacter pylori Infection.

Objective: The prevalence of antimicrobial resistance in Helicobacter pylori (HP) infection has increased globally. This study aimed to compare the efficacy of Biling Weitong granules (BLWTG) combined with quadruple therapy in patients with refractory HP infection who had previously failed eradication therapy. Methods: This single-center prospective study enrolled patients with two or more consecutive failed HP treatments. A total of 122 patients with previously failed HP treatment from our hospital were recruited as participants and randomly (1:1) allocated to two eradication groups: patients treated with bismuth-containing quadruple therapy (esomeprazole 40 mg, amoxicillin 1.0 g, bismuth potassium citrate 220 mg, and clarithromycin 500 mg, twice daily [EACB group]) for 14 days. And those treated with BLWTG (5 g three times daily) combined with the EACB group for 14 days (BLWTG+EACB group). The therapeutic effects of the two treatment programs were comprehensively evaluated. Results: The study group had a significantly higher improvement rate in symptoms (dull stomach pain, nausea, gastric distension, loss of appetite, and belching) compared to the control group (P < .05). Eight weeks after drug withdrawal, the eradication rates in the control and study groups were 49.18% and 73.77%, respectively. The levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were significantly lower in both groups after treatment but were significantly lower in the study group than in the control group (P < .05). Conclusions: The combination of BLWTG and standard four-drug therapy had a high eradication rate and low recurrence rate in patients with refractory HP infection. Additionally, this combined therapy could regulate inflammatory reactions and reduce drug-related adverse reactions.

Transcriptional Analysis on Resistant and Susceptible Kiwifruit Genotypes Activating Different Plant-Immunity Processes against Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa), a bacterial pathogen, is a severe threat to kiwifruit production. To elucidate the species-specific interaction between Psa and kiwifruit, transcriptomic-profiles analyses were conducted, under Psa-infected treatment and mock-inoculated control, on shoots of resistant Maohua (MH) and susceptible Hongyang (HY) kiwifruit varieties. The plant hormone-signal transduction and plant-pathogen interaction were significantly enriched in HY compared with MH. However, the starch and sucrose metabolism, antigen processing and presentation, phagosome, and galactose metabolism were significantly enriched in MH compared with HY. Interestingly, the MAP2 in the pathogen/microbe-associated molecular patterns (PAMPs)-triggered immunity (PTI) was significantly up-regulated in MH. The genes RAR1, SUGT1, and HSP90A in the effector-triggered immunity (ETI), and the NPR1 and TGA genes involved in the salicylic acid signaling pathway as regulatory roles of ETI, were significantly up-regulated in HY. Other important genes, such as the CCRs involved in phenylpropanoid biosynthesis, were highly expressed in MH, but some genes in the Ca2+ internal flow or involved in the reactive oxygen metabolism were obviously expressed in HY. These results suggested that the PTI and cell walls involved in defense mechanisms were significant in MH against Psa infection, while the ETI was notable in HY against Psa infection. This study will help to understand kiwifruit bacterial canker disease and provide important theoretical support in kiwifruit breeding.

Codelivery of satraplatin and aminopyrrolic receptor with Pluronic F127-based polyaniline nanoparticles with NIR induced release for combined chemotherapy.

The acquired drug resistance of the platinum-based drug is a main obstacle in cancer therapy. Herein, an aminopyrrolic receptor 1 was synthesized to sensitize satraplatin for overcoming the drug resistance as well as improving tumor targeted ability. Thus, Pluronic F127-based polyaniline nanoparticles were designed to co-deliver satraplatin and aminopyrrolic receptor 1, which could control the drug release with the Near Infrared laser irradiation (808 nm) due to the polyaniline mediated photothermal conversion. Biological evaluation shows prepared nanoparticles (Pt-ARNPs) exhibited more effective cytotoxicity (IC50 = 2.7µM) against the tested cancer cell lines under laser irradiation, compared with free satraplatin or treatment without Near-infrared radiation. Moreover, Pt-ARNPs showed comparable cytotoxicity against A549 and A549/cis cells, implying that the combination of satraplatin and aminopyrrolic receptor 1 with nano carrier might be a promising strategy to reduce platinum resistance and improve therapeutic effect in cancer therapy.

Effect of Brexpiprazole on Prolactin and Sexual Functioning: An Analysis of Short- and Long-Term Study Data in Major Depressive Disorder.

PURPOSE/BACKGROUND: Evidence supports use of adjunctive atypical antipsychotics in major depressive disorder (MDD). Impaired sexual functioning is common in MDD and may be worsened by antipsychotic adverse effects. We evaluated the effect of brexpiprazole on prolactin and sexual functioning in patients with MDD. METHODS/PROCEDURES: In short-term studies, patients received adjunctive brexpiprazole 1, 2, or 3 mg or placebo. The long-term study was a flexible-dose (0.5-3 mg/d) open-label extension (OLE). Change from baseline and shifts in prolactin status and prolactin-related treatment-emergent adverse events (TEAEs) were assessed. Sexual functioning was assessed by the Massachusetts General Hospital Sexual Functioning Questionnaire. FINDINGS/RESULTS: Median changes in prolactin levels from baseline to week 6 in short-term studies were as follows: brexpiprazole, 5.99 ng/mL (females) and 1.61 ng/mL (males); placebo, -0.15 ng/mL (females) and -0.08 ng/mL (males).Median changes from baseline to week 52 in the OLE were as follows: 0.27 ng/mL (females) and 0.27 ng/mL (males). Prolactin levels in patients with baseline prolactin greater than 1× upper limit of normal values tended to decrease over time.The proportion of brexpiprazole-treated patients with greater than 3× upper limit of normal postbaseline prolactin values in short-term studies for both sexes was low (0%-0.3%) and did not differ from placebo: OLE, 0.5% (females) and 0.8% (males).In short-term studies, the incidence of prolactin-related TEAEs was 3.1% for brexpiprazole and 0.7% for placebo (OLE, 3.1%). There were overall numerical improvements from baseline in sexual functioning for females and males after short- and long-term brexpiprazole treatment, with statistically significant improvements for brexpiprazole versus placebo in females on the items 'interest in sex' (-0.19; 95% confidence interval [CI], -0.33 to -0.05; P = 0.0074), 'sexually aroused' (-0.17; 95% CI, -0.30 to -0.03; P = 0.0154), and 'overall sexual satisfaction' (-0.16; 95% CI, -0.30 to -0.03; P = 0.0184). IMPLICATIONS/CONCLUSIONS: There were small changes in prolactin levels, low proportions of patients with postbaseline elevated prolactin values, low incidences of prolactin-related TEAEs, and modest improvements in sexual functioning with adjunctive brexpiprazole in MDD.

Effect of dehydration techniques on bioactive compounds in hawthorn slices and their correlations with antioxidant properties.

Hawthorn fruits are rich in nutrients and antioxidant compounds. Dehydration is the major processing and preservation method for hawthorn fruits. The rates of moisture loss; polyphenol, flavonoid and triterpenoid acid contents; and antioxidant activities and their relationships were investigated in hawthorn slices that were dried by four dehydration techniques (microwave drying, solar drying, hot air drying and freeze drying) under different operation conditions. The results showed that both the drying method and the processing parameter affected the antioxidants. Microwave drying and hot air drying at high temperatures (≥ 80 °C) resulted in the degradation of the polyphenols, flavonoids and triterpenoid acids in the hawthorn slices. These antioxidant compounds were best preserved by freeze drying and hot air drying at 60 °C. Epicatechin and chlorogenic acid were the major phenolic compounds identified in this research, and these compounds were significantly affected during processing. The antioxidant activities of the hawthorn fruits were significantly related to the total polyphenol, flavonoid and triterpenoid acid contents. Hot air drying at proper temperatures could be suitable for hawthorn slice dehydration processing that conserves the antioxidant properties of the fruit.

Experimental demonstration of optical stealth transmission over wavelength-division multiplexing network.

We propose and experimentally demonstrate an optical stealth transmission system over a 200 GHz-grid wavelength-division multiplexing (WDM) network. The stealth signal is processed by spectral broadening, temporal spreading, and power equalizing. The public signal is suppressed by multiband notch filtering at the stealth channel receiver. The interaction between the public and stealth channels is investigated in terms of public-signal-to-stealth-signal ratio, data rate, notch-filter bandwidth, and public channel number. The stealth signal can transmit over 80 km single-mode fiber with no error. Our experimental results verify the feasibility of optical steganography used over the existing WDM-based optical network.

Microwave photonic filter with multiple independently tunable passbands based on a broadband optical source.

In this paper, a novel microwave photonic filter (MPF) with multiple independently tunable passbands is proposed. A broadband optical source (BOS) is employed and split by a 1:N coupler into several branches. One branch is directed to a phase modulator which is modulated by a radio frequency signal and the other branches are delayed by optical delay lines (ODLs), respectively. All of these branches are combined by another 1:N coupler and sent to a dispersion compensation fiber which is used to introduce group delay dispersion to the optical signal. At a photodetector, each time-delayed broadband lightwave beating with the sidebands produced by the phase modulator forms a passband of the MPF. By tuning the delay of each broadband lightwave, the center frequency of the passband can be independently tuned. An MPF with two independently tunable passbands is experimentally demonstrated. The two passbands can be tuned from DC to 30 GHz with a 3-dB bandwidth of about 250 MHz. The stability and dynamic range of the MPF are also evaluated. By employing more branches delayed by ODLs, more passbands can be generated.

Frequency tunable optoelectronic oscillator based on a directly modulated DFB semiconductor laser under optical injection.

A frequency tunable optoelectronic oscillator based on a directly modulated distributed-feedback (DFB) semiconductor laser under optical injection is proposed and experimentally demonstrated. Through optical injection, the relaxation oscillation frequency of the DFB laser is enhanced and its high modulation efficiency can enable the loop oscillation with a RF threshold gain of less than 20 dB. The DFB laser is a commercial semiconductor laser with a package of 10 GHz, and its packaging limitation can be overcome by optical injection. In our scheme, neither a high-speed external modulator nor an electrical bandpass filter is required, making the system simple and low-cost. Microwave signals with a frequency tuning range from 5.98 to 15.22 GHz are generated by adjusting the injection ratio and frequency detuning between the master and slave lasers. The phase noise of the generated 9.75 GHz microwave signal is measured to be -104.8 dBc/Hz @ 10 kHz frequency offset.

Optical stealth transmission based on super-continuum generation in highly nonlinear fiber over WDM network.

In this Letter, the optical stealth transmission carried by super-continuum spectrum optical pulses generated in highly nonlinear fiber is proposed and experimentally demonstrated. In the proposed transmission scheme, super-continuum signals are reshaped in the spectral domain through a wavelength-selective switch and are temporally spread by a chromatic dispersion device to achieve the same noise-like characteristic as the noise in optical networks, so that in both the time domain and the spectral domain, the stealth signals are hidden in public channel. Our experimental results show that compared with existing schemes where stealth channels are carried by amplified spontaneous emission noise, super-continuum signal can increase the transmission performance and robustness.

Fabry-Pérot cavity based on chirped sampled fiber Bragg gratings.

A novel kind of Fabry-Pérot (FP) structure based on chirped sampled fiber Bragg grating (CSFBG) is proposed and demonstrated. In this structure, the regular chirped FBG (CFBG) that functions as reflecting mirror in the FP cavity is replaced by CSFBG, which is realized by chirping the sampling periods of a sampled FBG having uniform local grating period. The realization of such CSFBG-FPs having diverse properties just needs a single uniform pitch phase mask and sub-micrometer precision moving stage. Compared with the conventional CFBG-FP, it becomes more flexible to design CSFBG-FPs of diverse functions, and the fabrication process gets simpler. As a demonstration, based on the same experimental facilities, FPs with uniform FSR (~73 pm) and chirped FSR (varying from 28 pm to 405 pm) are fabricated respectively, which shows good agreement with simulation results.

Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study.

BACKGROUND: Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. OBJECTIVE: This study aimed to describe a phase 3 remote, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone app-based DTx (CT-152) in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT). METHODS: Participants aged 22-64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to CT-152 or a sham DTx. CT-152 is a smartphone app-based DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of CT-152 are the Emotional Faces Memory Task exercises, brief lessons to learn and apply key therapeutic skills, and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match CT-152 for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period of 4 weeks to assess the durability of the effect. Sites and participants had the option of an in-person or remote screening visit; the remaining trial visits were remote. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale, the Generalized Anxiety Disorder-7, Clinical Global Impression-Severity scale, the Patient Health Questionnaire-9, and the World Health Organization Disability Assessment Schedule 2.0. The durability of the effect was evaluated with the Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scale. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EQ-5D-5L, were summarized using descriptive statistics. RESULTS: This study was initiated in February 2021 and had a primary completion date in October 2022. CONCLUSIONS: This represents the methodological design for the first evaluation of CT-152 as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety end points. Novel considerations included the use of a sham comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of CT-152. TRIAL REGISTRATION: ClinicalTrials.gov NCT04770285; https://clinicaltrials.gov/study/NCT04770285. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/56960.

Apixaban versus enoxaparin for thromboprophylaxis after hip replacement.

BACKGROUND: There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use. METHODS: In this double-blind, double-dummy study, we randomly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours. Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound; enoxaparin therapy was initiated 12 hours before surgery. Prophylaxis was continued for 35 days after surgery, followed by bilateral venographic studies. The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause during the treatment period. Patients were followed for an additional 60 days after the last intended dose of study medication. RESULTS: A total of 1949 patients in the apixaban group (72.0%) and 1917 patients in the enoxaparin group (71.0%) could be evaluated for the primary efficacy analysis. The primary efficacy outcome occurred in 27 patients in the apixaban group (1.4%) and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban, 0.36; 95% confidence interval [CI], 0.22 to 0.54; P<0.001 for both noninferiority and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to 3.5). The composite outcome of major and clinically relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban (4.8%) and 134 of 2659 assigned to enoxaparin (5.0%) (absolute difference in risk, -0.2 percentage points; 95% CI, -1.4 to 1.0). CONCLUSIONS: Among patients undergoing hip replacement, thromboprophylaxis with apixaban, as compared with enoxaparin, was associated with lower rates of venous thromboembolism, without increased bleeding. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00423319.).

Low-cost and wideband frequency tunable optoelectronic oscillator based on a directly modulated distributed feedback semiconductor laser.

A novel scheme to realize a low-cost and wideband frequency tunable optoelectronic oscillator based on a directly modulated distributed feedback (DFB) semiconductor laser is proposed and experimentally demonstrated. In the proposed scheme, neither an external modulator nor an electrical filter is used, and no more than 25 dB of the electrical loop gain is required due to the high modulation efficiency of the relaxation oscillation frequency of the DFB laser. Microwave signals with frequency coarsely tuned from 3.77 to 8.75 GHz are generated by changing the bias current and operation temperature of the DFB laser. The single sideband phase noise of the generated 6.97 GHz microwave signal is measured to be -103.6 dBc/Hz at 10 kHz offset.

Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies.

Objective: Certain atypical antipsychotics, while efficacious as adjunctive treatments in major depressive disorder (MDD), are associated with metabolic adverse effects and weight gain. This analysis determined the effect of adjunctive brexpiprazole on metabolic parameters and body weight in adults with MDD and prediabetes (ie, at risk of developing diabetes) based on pooled data from 3 short-term studies and 1 long-term study.Methods: The short-term studies were 6-week, randomized, double-blind, placebo-controlled studies of adjunctive oral brexpiprazole 1-3 mg/d in outpatients with MDD (DSM-IV-TR criteria) and inadequate response to antidepressant treatment, conducted between June 2011 and May 2016. The long-term study was a 26- to 52-week, open-label extension study conducted between October 2011 and May 2017. Prediabetes was defined based on fasting serum glucose and glycated hemoglobin (HbA1c) levels. Shifts in diabetes status and shifts/changes in fasting metabolic parameters and body weight were determined.Results: Most patients receiving adjunctive brexpiprazole maintained their baseline diabetes status in the short term (568/751; 75.6%) and long term (1,919/2,746; 69.9%). The incidence of categorical shifts in fasting metabolic parameters generally did not differ between treatment groups or between prediabetes and non-diabetes subgroups. Mean changes from baseline in metabolic parameters were small in the short term (all < 5 mg/dL) and long term (all < 6 mg/dL, except < 20 mg/dL for triglycerides). Moderate weight gain was observed in the short term (1.5 kg) and long term (3.4-4.1 kg).Conclusions: Adjunctive brexpiprazole had a limited impact on the metabolic profile of patients with MDD, regardless of diabetes status (prediabetes/non-diabetes).Trial Registration: Data used in this post hoc analysis came from studies with ClinicalTrials.gov identifiers NCT01360645, NCT01360632, NCT02196506, and NCT01360866.

Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial.

Importance: Agitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment. Objective: To confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia. Design, Setting, and Participants: This randomized clinical trial was a 12-week, double-blind, placebo-controlled, fixed-dose, parallel-arm trial that ran from May 2018 to June 2022 at 123 clinical trial sites in Europe and the United States. Participants included patients with agitation in Alzheimer dementia in a care facility or community-based setting. Stable Alzheimer disease medications were permitted. Interventions: In this 2-arm trial, patients were randomized to receive oral brexpiprazole or placebo (2:1 ratio) for 12 weeks. Within the brexpiprazole arm, patients were further randomized to receive fixed doses of 2 mg/d or 3 mg/d in a 1:2 ratio. Main Outcomes and Measures: The primary end point was change in Cohen-Mansfield Agitation Inventory total score (which measures the frequency of 29 agitated behaviors) from baseline to week 12 for brexpiprazole, 2 or 3 mg, vs placebo. Safety was assessed by standard measures, including treatment-emergent adverse events. Results: A total of 345 patients were randomized to receive brexpiprazole (n = 228) or placebo (n = 117); completion rates were 198 (86.8%) for brexpiprazole and 104 (88.9%) for placebo. Mean (SD) age was 74.0 (7.5) years, and 195 of 345 patients were female (56.5%). Patients receiving brexpiprazole, 2 or 3 mg (n = 225), demonstrated statistically significantly greater improvement than those taking placebo (n = 116) in Cohen-Mansfield Agitation Inventory total score from baseline to week 12 (brexpiprazole baseline, 80.6, mean change, -22.6; placebo baseline, 79.2, mean change, -17.3; least-squares mean difference, -5.32; 95% CI, -8.77 to -1.87; P = .003; Cohen d effect size, 0.35). No treatment-emergent adverse events had an incidence of 5% or more with brexpiprazole and greater incidence than placebo. The proportion of patients who discontinued because of adverse events was 12 of 226 (5.3%) for brexpiprazole and 5 of 116 (4.3%) for placebo. Conclusions and Relevance: In this study, patients with Alzheimer dementia who took brexpiprazole, 2 or 3 mg, showed a statistically significant improvement vs placebo in agitation over 12 weeks. Brexpiprazole was generally well tolerated over 12 weeks in this vulnerable patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03548584.

Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data.

BACKGROUND: Patient-reported outcomes can capture domains that are meaningful to patients, such as life engagement in major depressive disorder (MDD), which reflects life fulfillment, well-being, and participation in valued and meaningful activities. This analysis investigated the effects of brexpiprazole adjunct to antidepressant treatment (ADT) on patient life engagement over the short and long term, using the 10-item Inventory of Depressive Symptomatology Self-Report (IDS-SR10) Life Engagement subscale. METHODS: Short-term data were pooled from three 6-week, randomized, double-blind studies of ADT + brexpiprazole 2-3 mg/day versus ADT + placebo in adult outpatients with MDD (DSM-IV-TR criteria) and inadequate response to ADTs. Long-term data were from a 26-52-week, open-label extension study of ADT + brexpiprazole 0.5-3 mg/day. RESULTS: Over 6 weeks, ADT + brexpiprazole (n = 579) showed greater improvement in IDS-SR10 Life Engagement subscale score than ADT + placebo (n = 583), with a least squares mean difference of -1.19 (95% confidence limits: -1.78, -0.59; p = 0.0001; Cohen's d effect size: 0.23). Greater improvement for ADT + brexpiprazole versus ADT + placebo (p < 0.05) was also observed on eight life engagement items, with effect sizes ranging from 0.12 to 0.24. In the long-term study, mean (standard deviation) IDS-SR10 Life Engagement subscale score changed by -2.4 (4.9) points to Week 26 (n = 2047), and -3.7 (5.3) points to Week 52 (n = 768), with mean improvements on all ten items. CONCLUSIONS: Beyond its efficacy on depressive symptoms, adjunctive brexpiprazole may improve patient life engagement, thereby helping patients with MDD to achieve personally meaningful functional outcomes.