Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

INTRODUCTION: In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. METHODS: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. RESULTS: The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: ß = -0.201; p = 0.049). DISCUSSION: Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Synthesis and study of optical properties of a Gd3+-doped NaYF4 phosphor for phototherapy lamp application.

In recent trends, radiation falls under the narrowband ultraviolet-B region (305-315 nm) widely used in phototherapy lamp applications in the treatment of skin diseases. In this paper, we report a Gd3+-doped NaYF4 luminescent material synthesized for the first time using the low-temperature co-precipitation method. It crystallized into a face-centred cubic structure, as confirmed by X-ray diffraction characterization techniques and Rietveld refinement. The photoluminescence property of the as-prepared sample shows a highly intense, sharp emission band obtained at 311 nm, which belongs to the narrowband ultraviolet-B region and corresponds to the transition of the 6P7/2→8S7/2 level of the Gd3+ ions under 272 nm excitation (8S7/2 to 6IJ). The transitions of the Gd3+ ions are detected entirely with different concentrations of Gd3+ ions. Scanning electron microscopy analysis indicated that the average particle was 288 nm. The critical distance for energy transfer was calculated to be equal to 11.5017 Å. Dipole-dipole interaction is responsible for energy transfer, as analyzed by Dexter theory. These excellent optical characteristics, together with their highly efficient and low-cost synthesis approach, indicate that synthesized NaYF4:Gd3+ phosphors have excessive potential for phototherapeutic lamp applications.

Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.

PURPOSE/BACKGROUND: Once-daily extended-release (ER) lorazepam was developed to reduce fluctuations in plasma levels compared with lorazepam immediate-release (IR) for short-term anxiety relief. Here we report a series of phase 1 randomized, open-label, multiperiod crossover studies characterizing ER lorazepam pharmacokinetics and safety in healthy adults. METHODS/PROCEDURES: These phase 1 studies assessed the pharmacokinetics of ER lorazepam administered: (study 1) 3 mg once daily versus IR lorazepam 1 mg 3 times a day (TID; every 8 hours), (study 2) with or without food, and (study 3) intact versus sprinkled onto food. Study 3 further evaluated the proportionality of 1 × 4- versus 4 × 1-mg doses. Safety was also monitored. FINDINGS/RESULTS: There were 43, 27, and 29 subjects who completed studies 1, 2, and 3, respectively. The 90% confidence intervals for Cmax,SS , Cmin , and AUC TAU,SS of once-daily ER lorazepam compared with IR given TID were within 80% to 125% limits establishing steady-state bioequivalence. Maximum mean lorazepam concentrations were achieved at 11 hours compared with 1 hour after dosing for ER versus IR lorazepam, respectively. Pharmacokinetic parameters ( Cmax , AUC last or AUC 0- t , AUC inf or AUC 0-inf ) of ER lorazepam were bioequivalent whether taken with or without food, administered intact or sprinkled onto food, or administered as intact 1 × 4- versus 4 × 1-mg capsules. No serious safety concerns were found. IMPLICATIONS/CONCLUSIONS: Once-daily ER lorazepam provided a pharmacokinetic profile bioequivalent to IR lorazepam given TID and was well tolerated in healthy adults across all phase 1 studies. These data suggest that ER lorazepam could be an alternative for patients currently treated with IR lorazepam.

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; ß*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; ß*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

Nighttime Sleep Quality and Daytime Sleepiness Predicts Suicide Risk in Adults Admitted to an Inpatient Psychiatric Hospital.

As sleep problems have been identified as an important, yet understudied, predictor of suicide risk, the present study analyzed the relationship between daytime sleepiness and nighttime sleep disturbance in a high-risk population of adults admitted to an inpatient psychiatric hospital. Objectives were to (1) examine the time course of subjective daytime sleepiness, nighttime sleep disturbance, and suicide risk throughout inpatient psychiatric treatment, (2) examine pre- to post-treatment changes in sleep disturbance with treatment as usual in an inpatient psychiatric setting, and (3) investigate whether daytime sleepiness and nighttime sleep disturbance predicted suicide risk above and beyond anxiety and depression. Participants were 500 consecutively admitted adults admitted to an intermediate length of stay (4-6 weeks) inpatient psychiatric hospital (47% female; 18-87 years of age). Measures of sleep, suicide risk, depression, and anxiety were completed at admission, weeks 1 through 4, and at discharge. Latent growth curve modeling (LGM) and hierarchal linear modeling (HLM) were conducted. The LGM analysis demonstrated that daytime sleepiness, nighttime sleep disturbance, and suicide risk all improved throughout inpatient treatment. Further, HLM showed that daytime sleepiness predicted suicide risk above and beyond symptoms of anxiety, depression, major sleep medications, and prior suicidal ideation and attempts, while nighttime sleep disturbance predicted suicide risk above and beyond symptoms of anxiety, major sleep medications, and prior suicidal ideation and attempts. Findings indicate the need to reevaluate safety protocols that may impact sleep, particularly that may increase daytime sleepiness, and to develop evidence-based sleep interventions for individuals admitted to inpatient psychiatric hospitals.

Thermoluminescence studies of zinc borate (ZnB2 O4 ) phosphor doped with rare earths for dosimetric aspects.

A series of ZnB2 O4 phosphors doped with different concentrations of Eu and Dy (0.05 0.1, 0.2, 0.5, 1.0 mol%) and co-doped with Ce (1, 2, 5, 7, 10 mol%) respectively was prepared via the solid-state reaction technique and the thermoluminescence (TL) behaviour of gamma ray-irradiated samples was studied. The synthesized samples were irradiated with γ-rays for the dose range 0.03-1.20 kGy. The TL intensity variations with dose, dopant concentration, and the effect of co-doping were studied. The TL response curves for ZnB2 O4 :Eu3+ and ZnB2 O4 :Dy3+ , ZnB2 O4 :Eu3 ,Ce3+ and ZnB2 O4 :Dy3+ ,Ce3+ phosphor were observed. It was revealed that ZnB2 O4 :Eu3+ showed a linear TL behaviour for the dose 0.03-1.20 kGy and ZnB2 O4 :Dy3+ showed linearity for the gamma dose range 0.03-0.10 kGy. Furthermore, fading for all the samples was observed to be less than 10% for a storage period of 30 days. In addition to this, the trapping parameters, especially activation energies were evaluated using the Ilich method and the initial rise method. The activation energy values obtained from both methods were in complete agreement with each other.

Intensity enhancement of photoluminescence in Tb3+ /Eu3+ co-doped Ca14 Zn6 Al10 O35 phosphor for WLEDs.

This article focuses on the effect of monovalent cation doping on the optical properties of rare earth (RE = Eu3+ , Tb3+ ) co-doped Ca14 Zn6 Al10 O35 which has been synthesized by a low temperature combustion method. Crystalline phase of the Ca14 Zn6 Al10 O35 phosphor was examined and confirmed by X-ray diffraction measurement. Under near-ultraviolet light excitation Eu3+ -doped Ca14 Zn6 Al10 O35 phosphor exhibit characterization of Eu3+ emission bands that are located at a maximum wavelength (λmax ) of approximately 470 nm and other peaks centred at 593 nm and 615 nm, respectively. With Tb3+ -doped Ca14 Zn6 Al10 O35 phosphor showing a green emission band centred at 544 nm under near-ultraviolet range. Furthermore, we studied the energy transfer process in Eu3+ /Tb3+ pair and enhancement in photoluminescence (PL) intensity with doping different charge compensation. Here we obtained the optimum PL emission intensity of the phosphor in broad and intense visible spectral range which may be significant for the fabrication of white light emitting diodes (WLEDs).

Structural, morphological, and photoluminescence properties of RE (RE = Dy3+ , Eu3+ , Sm3+ )-doped CaAlBO4 phosphor synthesized by combustion method.

The CaAlBO4 :RE (RE = Dy3+ , Eu3+ , Sm3+ ) phosphor were prepared via combustion synthesis and studied by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) analysis, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), photoluminescence (PL) spectra and CIE coordinates. The phase formation of the obtained phosphor was analyzed by XRD and the result was confirmed by standard PDF Card No. 1539083. XRD data successfully indicated pure phase of CaAlBO4 phosphor. The crystal structure of CaAlBO4 phosphor is orthorhombic with space group Ccc2 (37). The SEM image of CaAlBO4 phosphor reveals an agglomerated morphology and non-uniform particle size. The EDS image provides evidence of the elements present and the chemical makeup of the materials. Under the 350 nm excitation, the emission spectrum of Dy3+ activated CaAlBO4 phosphor consists of two main groups of characteristic peaks located at 484 and 577 nm which are ascribed to 4 F9/2 → 6 H15/2 and 4 F9/2 → 6 H13/2 transition of Dy3+ respectively. The PL emission spectra of CaAlBO4 :Eu3+ phosphor shows characteristics bands observed around 591 and 613 nm, which corresponds to 5 D0 → 7 F1 and 5 D0 → 7 F2 transition of Eu3+ respectively, upon 395 nm excitation wavelength. The emission spectra of Sm3+ activated CaAlBO4 phosphor shows three characteristic bands observed at 565, 601 and 648 nm which emits yellow, orange and red color. The prominent emission peak at the wavelength 601 nm, which is attributed to 4 G5/2 → 6 H7/2 transition, displays an orange emission. The CIE color coordinates of CaAlBO4 :RE (RE = Dy3+ , Eu3+ , Sm3+ ) phosphor are calculated to be (0.631, 0.368), (0.674, 0.325) and (0.073, 0.185). As per the obtained results, CaAlBO4 :RE (RE = Dy3+ , Eu3+ , Sm3+ ) phosphor may be applicable in eco-friendly lightning technology.

Synthesis and study of luminescence properties of a deep red-emitting phosphor K2 LiAlF6 :Mn4+ for plant cultivation.

Light is the most important component in plant growth and development. This study synthesised a novel Mn4+ -doped K2 LiAlF6 red-emitting phosphor using the coprecipitation method. We observed that on addition of dopant Mn4+ ions to the host K2 LiAlF6 , its phase changed from rhombohedral to cubic due to the change in the lattice position of the atoms. When the atoms are excited at 468 nm, the K2 LiAlF6 :Mn4+ phosphor exhibited a red emission band ranging from 630 to 700 nm, centred at 638 nm, which matched well with the absorption spectra of phytochrome PR. The critical quenching content of Mn4+ ions was ~3 mol%. The critical distance between Mn4+ ions was determined to be 19.724 Å, and non-radiative energy transfer among the nearest-neighbour Mn4+ ions was the mechanism used for the concentration quenching effect. The Commission International de l'Eclairage (CIE) chromaticity coordinates of the K2 LiAlF6 :0.03 Mn4+ sample were (x = 0.7162, y = 0.2837). The luminescence mean decay time was calculated to be 8.29 ms. These results demonstrated the promising prospect of K2 LiAlF6 :Mn4+ as a red-emitting phosphor for application in red light-emitting diodes for plant cultivation.

Optical and thermal properties of rare earth-doped K4 Ca(PO4 )2 phosphor.

The luminescent properties and energy transfer (ET) mechanism in the Ln3+ pair of the RE3+ (RE = Eu3+ , Ce3+ , Dy3+ and Sm3+ ) doped K4 Ca(PO4 )2 phosphor were successfully investigated using a conventional high-temperature solid-state reaction. In the near infrared (NIR) range, Ce3+ -doped K4 Ca(PO4 )2 phosphor exhibited a UV-Vis. emission band, whereas K4 Ca(PO4 )2 :Dy3+ exhibited characteristic emission bands centred at 481 and 576 nm in the near-ultraviolet excitation range. The possibility of ET from Ce3+ to Dy3+ in K4 Ca(PO4 )2 phosphor was confirmed by a significant increase in the photoluminescence intensity of the Dy3+ ion based on the spectral overlap of acceptor and donor ions. X-ray diffraction, Fourier-transform infrared and thermogravimetric analysis/differential thermal analysis TGA/DTA were carried out to study phase purity, presence of functional groups and amount of weight loss under different temperature regimes. Therefore, the RE3+ -doped K4 Ca(PO4 )2 phosphor may be a stable phosphor host for light-emitting diode applications.

Synthesis and novel emission properties of Bi3+ -doped Ca2 BO3 Cl phosphor for plant cultivation.

In the present work, a series of Bi3+ -activated Ca2 BO3 Cl phosphors was synthesized using the conventional high-temperature solid-state reaction method. The crystal structure of the prepared sample was determined to be monoclinic with space group P21/c. Scanning electron microscopy (SEM) analysis demonstrated the surface morphology with aggregated particles and sizes in the nano range. The presence of vibrational features and their luminescence characteristics were studied using Fourier transform infrared spectroscopy and photoluminescence (PL) techniques, respectively. At the 486 nm excitation wavelength, the PL spectrum revealed a sharp emission centred at 732 nm that was attributed to the 3 P1 →1 S0 transition of Bi3+ . The emission spectra exhibited the highest emission intensity at 0.5 mol% Bi3+ ion concentration, beyond this the emission intensity decreased due to the concentration quenching phenomenon attributed to multipolar interaction. The Commission Internationale de l'éclairage coordinates located at (0.7347, 0.2653) confirmed emission in the deep-red region with a colour purity of 99.98%. The obtained outcomes suggested that the reported material may be a promising candidate as a red-emitting phosphor for w-LEDs and plant growth applications.

Assessment of dosimetric impact of interfractional 6D setup error in tongue cancer treated with IMRT and VMAT using daily kV-CBCT.

Background: This study aimed to evaluate the dosimetric influence of 6-dimensional (6D) interfractional setup error in tongue cancer treated with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) using daily kilovoltage cone-beam computed tomography (kV-CBCT). Materials and methods: This retrospective study included 20 tongue cancer patients treated with IMRT (10), VMAT (10), and daily kV-CBCT image guidance. Interfraction 6D setup errors along the lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 600 CBCTs. Structures in the planning CT were deformed to the CBCT using deformable registration. For each fraction, a reference CBCT structure set with no rotation error was created. The treatment plan was recalculated on the CBCTs with the rotation error (RError), translation error (TError), and translation plus rotation error (T+RError). For targets and organs at risk (OARs), the dosimetric impacts of RError, TError, and T+RError were evaluated without and with moderate correction of setup errors. Results: The maximum dose variation ΔD (%) for D98% in clinical target volumes (CTV): CTV-60, CTV-54, planning target volumes (PTV): PTV-60, and PTV-54 was -1.2%, -1.9%, -12.0%, and -12.3%, respectively, in the T+RError without setup error correction. The maximum ΔD (%) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54 was -1.0%, -1.7%, -9.2%, and -9.5%, respectively, in the T+RError with moderate setup error correction. The dosimetric impact of interfractional 6D setup errors was statistically significant (p < 0.05) for D98% in CTV-60, CTV-54, PTV-60, and PTV-54. Conclusions: The uncorrected interfractional 6D setup errors could significantly impact the delivered dose to targets and OARs in tongue cancer. That emphasized the importance of daily 6D setup error correction in IMRT and VMAT.

A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine.

BACKGROUND: Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine's specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings. METHODS: Data for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales-specifically, depressed mood, anhedonia, anxiety, and guilt-over time. RESULTS: For participants receiving saline placebo (n = 46), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n = 105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt. CONCLUSIONS: Taken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.

Ketamine for treatment of mood disorders and suicidality: A narrative review of recent progress.

BACKGROUND: Mood disorders are a leading cause of morbidity. Many patients experience treatment-resistant depression (TRD), and suicide rates are rising. Faster-acting and more effective antidepressant medications are needed. Four decades of research has transformed the use of ketamine from an anesthetic to an outpatient treatment for major depressive disorder (MDD). Ketamine is a N-methyl-d-aspartate (NMDA) receptor antagonist and has been shown to rapidly improve mood symptoms and suicidal ideation by targeting the glutamate system directly. METHODS: We used the PubMed database to identify relevant articles published until September 1, 2020. We focused on meta-analyses, randomized controlled trials, and original observational studies. We included relevant studies for depression, MDD, TRD, bipolar disorder, anxiety, posttraumatic stress disorder (PTSD), suicide, ketamine, and esketamine. RESULTS: Both racemic ketamine and esketamine have been shown to rapidly treat depression and suicidality. There is evidence that ketamine can be helpful for anxiety and PTSD; however, more research is needed. Intranasal esketamine has been FDA approved to treat depression. CONCLUSIONS: This narrative review describes the evolution of ketamine to treat mood disorders and suicidality. We provide the evidence supporting recent developments using esketamine as well as unresolved issues in the field, such as dosing and safety.

Pattern of liver function test variations in COVID-19 infection & its clinical significance: A study from a dedicated COVID-19 tertiary care centre from India.

Background & objectives: Coronavirus disease 2019 (COVID-19) affects respiratory, gastrointestinal, cardiovascular and other systems disease. Studies describing liver involvement and liver function test (LFT) abnormalities are sparse from our population. This study was undertaken to estimate the LFT abnormalities in patients with COVID-19 in a tertiary care set up in India. Methods: In this retrospective study conducted at a tertiary care centre in Mumbai, India, all consecutive patients with proven COVID-19 by reverse transcriptase-PCR from March 23 to October 31, 2020 were enrolled. Of the 3280 case records profiled, 1474 cases were included in the study. Clinical characteristics, biochemical parameters and outcomes were recorded. Results: Overall 681 (46%) patient had deranged LFTs. Hepatocellular type of injury was most common (93%). Patients with deranged LFTs had more probability of developing severe disease (P<0.001) and mortality (P<0.001). Advanced age (P<0.001), male gender (P<0.001), diabetes mellitus (P<0.001), lower oxygen saturation levels at admission (P<0.001), higher neutrophil-lymphocyte ratio (P<0.001), history of diabetes mellitus and cirrhosiss were associated with deranged LFTs. Acute liver injury was seen in 65 (4.3%) cases on admission and 57 (3.5%) cases during hospital stay. On multivariate analysis for predicting mortality, age >60 yr serum creatinine >2 mg%, PaO2/FiO2 ratio ≤200 and raised AST >50 IU/l (OR: 2.34, CI: 1.59-3.48, P<0.001) were found to be significant. Interpretation & conclusions: In COVID-19, LFT abnormalities were common, and derangement increased as severity progressed. The presence of deranged LFT worsens the clinical outcome and predicts in-hospital mortality.

Box-Behnken design avenue for development and validation of high-performance thin-layer chromatography method for estimation of rutin in Hemidesmus indicus.

The aim of this study was to determine the content of rutin in Hemidesmus indicus and to optimize the high-performance thin-layer chromatography method. The method was validated in compliance with the International Council for Harmonisation guidelines Q2 (R1) for parameters such as linearity, accuracy, precision, robustness, limit of detection, and limit of quantitation. A Box-Behnken design and response surface methodology has been used to investigate the impact of independent variables on the response. Three independent variables, mobile phase composition (% v/v), mobile phase volume (mL), and duration of saturation (min), were studied. Rutin was verified, and its content was determined using a validated high-performance thin-layer chromatography method with good linearity within the range of 200-1000 ng spot-1 with r2 = 0.9998 and correlation coefficient with calibration curve equation y = 0.0297x + 0.0001. The average percentage recovery values varied from 99.03 to 101.15 and 98.88 to 100.12%, respectively, for in-house and marketed mother tincture). The peak area determination at three different concentration levels shows low values of percentage relative standard deviation (<2%) for inter-day (0.04-0.06) and intra-day (0.04-0.05) precision of rutin. The average content of rutin in extract and marketed mother tincture was 229 ± 0.57 and 210 ± 0.57 µg g-1 . The proposed method was simple, precise, and accurate for the determination of rutin with frequent quality control assessment of H. indicus.

Luminescence study of Sm3+ ,Eu3+ -doped Y2 Zr2 O7 host: optical investigation of greenish yellow to red colour tunable pyrochlore phosphor.

Pyrochlore phosphors have shown their worth in modern day lighting in the last few years. Colour tunability of the phosphor is one of the modern techniques used to obtain white light-emitting diodes (WLEDs). In the proposed work, Y2 Zr2 O7 :Sm3+ ,Eu3+ phosphors were investigated for WLED applications as well as display devices. A convectional solid-state diffusion method was used to synthesize the proposed phosphors. X-ray diffraction of the proposed phosphors was performed and compared with the standard Inorganic Crystal Structure Database. The crystal structure of the sample was cubic in nature, obtained from Rietveld refinement. Vibrational and morphological studies on the samples were carried out using Fourier transform infrared spectroscopy and scanning electron microscopy analysis. The photoluminescence study of the colour tunable phosphor showed the characteristic peak of Sm3+ together with the two sharp peaks of Eu3+ ions. Greenish yellow to red colour tunability was observed in the proposed phosphor with enhancement of Eu3+ ions. All these results showed the worth of this sample for WLEDs applications as well as in display devices.

Wet chemical synthesis of BiPO4 :Eu3+ phosphor for w-LED application.

The synthesis of BiPO4 :Eu3+ phosphors has been achieved via a wet chemical process. X-ray diffraction patterns show that the phase of the as-prepared samples matches very well with the standard BiPO4 structure. At 395 nm, the highest excitation intensity was observed. Following 395 nm excitation, two characteristic emission peaks at 592 nm and 616 nm were shown. At 0.5 mol% of Eu3+ ions, concentration quenching occurred. The particle size is within the micrometre range, according to the scanning electron microscope magnification. The chromaticity coordinates for wavelengths 592 nm and 616 nm are (x = 0.586, y = 0.412) and (x = 0.682, y = 0.317), respectively. The findings imply that the prepared phosphor may be used to create white light-emitting diodes.