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Treatment-resistant depression (TRD) is commonly defined as non-response to ≥2 antidepressant treatment courses of adequate doses and durations in the current episode in patients with major depressive disorder (MDD). Esketamine (ESK) nasal spray was approved by the Food and Drug Administration in March 2019 for the treatment of TRD in adults in conjunction with an oral antidepressant (AD). This study assessed changes in depressive symptoms following ESK initiation among patients with TRD in a real-world setting.
Methods
The study was a retrospective longitudinal observational cohort study of adults with TRD who initiated esketamine treatment between March 2019 and June 2022. Data were sourced from the PremiOM™ MDD Dataset (OM1, Boston, MA), a continuously updated cohort of over 440,000 patients with MDD in the United States with linked claims and electronic medical record data. Patients were classified as having TRD if they had ≥1 diagnosis of MDD during the 6 months prior to or on the index date (defined as ESK initiation) and a record of ≥2 unique ADs of adequate dose and duration at any time prior to the index date within the same major depressive episode (MDE; defined as no clean period of ≥180 days without ADs and/or MDD diagnoses). The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms. A machine learning model was used to estimate PHQ-9 scores for patients with no documented scores. The latest PHQ-9 score among questionnaires administered in the six months prior to or on the date of first ESK treatment was used as the baseline score. Baseline scores were compared to the latest scores in the 0-3-month and 3-6 month windows after first ESK treatment. A sensitivity analysis excluding the estimated scores was conducted. Marginal models were used to test for differences in post-treatment scores relative to baseline.
Results
The study cohort included 163 patients with a mean age of 49.5 years (standard deviation [SD]=15.4). Most patients were female (58.3%). At baseline, the mean PHQ-9 score was 15.0 (SD=6.7) and 55.8% of patients had either moderately severe or severe depression (PHQ-9 ≥15). Patients experienced statistically significant reductions in PHQ-9 scores of 2.9 points (95% CI: 1.7 to 4.1, p<0.001) in the 0–3-month interval and 4.4 points (95% CI: 3.2 to 5.6, p<0.001) in the 3–6-month interval relative to baseline. The percentage of patients with moderately severe or severe depression (PHQ-9 ≥15) decreased to 34.4% at the 0-3 month interval and 20.9% at the 3-6 month interval. Results were consistent when estimated PHQ-9 scores were excluded.
Conclusions
Among patients with TRD in a real-world setting, PHQ-9 scores significantly decreased in the 6 months following initiation of ESK treatment. Further investigation of longer-term effectiveness of ESK and among key subgroups is warranted.
Funding
Janssen Pharmaceuticals, the manufacturer of esketamine
14CO2 activity in air samples collected at Kakrapar Gujarat Site, India, was measured, and site-specific dilution factor for 14CO2 has been evaluated. 14CO2 activity in air samples was monitored for 72 different sampling events at onsite stack of Nuclear Power Plant (NPP) and at ESL meteorology laboratory (at 1.6 km from NPP stack). 14CO2 activity in air at stack of NPP and at ESL meteorology laboratory was observed to 0.10–0.18 TBq (GWe.year)–1, with mean value 0.12 TBq (GWe.year)–1 and ≤0.04–0.13 Bq m–3, with mean value 0.08 Bq m–3 respectively. The results were correlated with meteorological parameters. Site specific dilution factor for 14CO2 in air was evaluated at 1.6 km and was found to be in the range of 4.6E-05 to 21E-05 s m–3. Inter angle (degree) between plume direction and fixed sampling location and rainfall (mm) are found to be the important influencing parameters for dilution factor of 14CO2 in air.
Patients with major depressive disorder (MDD) with acute suicidal ideation or behavior (MDSI) require immediate intervention. Though oral antidepressants can be effective at reducing depressive symptoms, they can take 4–6 weeks to reach full effect.
Objectives
This study aimed to identify unmet needs in the treatment of patients with MDSI, specifically exploring the potential clinical benefits of rapid reduction of depressive symptoms.
Methods
A Delphi panel consisting of practicing psychiatrists (n=12) from the US, Canada and EU was conducted between December 2020–June 2021. Panelists were screened to ensure they had sufficient experience with managing patients with MDD and MDSI. Panelists completed two survey rounds, and a virtual consensus meeting.
Results
This research confirmed current unmet needs in the treatment of patients with MDSI.
Hopelessness, functional impairment, worsening of MDD symptoms, recurrent hospitalization and higher risk of suicide attempt were considered as key consequences of the slow onset of action of oral antidepressants.
Treatment with rapid acting antidepressant was anticipated by panelists to provide short-term benefit such as rapid reduction of core MDD symptoms which may contribute to shorter hospital stays and improved patient engagement/compliance, allowing for earlier interventions and improved patient outcomes. For long-term benefits, panelists agreed that improved daily functioning and increased trust/confidence in treatment options, constitute key benefits of rapid-acting treatments
Conclusions
There is need for rapid-acting treatments which may help address key unmet needs and provide clinically meaningful benefits driven by the rapid relief of depressive symptoms particularly in patients with MDSI.
Disclosure
SB, ED, KJ, MO’H, QZ, MM, MH, SR, JA and DZ are employees of Janssen and hold stock in Johnson & Johnson Inc. AN is currently employed by Neurocrine Biosciences Inc. RP is an employee of Adelphi Values PROVE hired by Janssen.
Mental health and psychosocial support (MHPSS) staff in humanitarian settings have limited access to clinical supervision and are at high risk of experiencing burnout. We previously piloted an online, peer-supervision program for MHPSS professionals working with displaced Rohingya (Bangladesh) and Syrian (Turkey and Northwest Syria) communities. Pilot evaluations demonstrated that online, peer-supervision is feasible, low-cost, and acceptable to MHPSS practitioners in humanitarian settings.
Objectives
This project will determine the impact of online supervision on i) the wellbeing and burnout levels of local MHPSS practitioners, and ii) practitioner technical skills to improve beneficiary perceived service satisfaction, acceptability, and appropriateness.
Methods
MHPSS practitioners in two contexts (Bangladesh and Turkey/Northwest Syria) will participate in 90-minute group-based online supervision, fortnightly for six months. Sessions will be run on zoom and will be co-facilitated by MHPSS practitioners and in-country research assistants. A quasi-experimental multiple-baseline design will enable a quantitative comparison of practitioner and beneficiary outcomes between control periods (12-months) and the intervention. Outcomes to be assessed include the Kessler-6, Harvard Trauma Questionnaire and Copenhagen Burnout Inventory and Client Satisfaction Questionnaire-8.
Results
A total of 80 MHPSS practitioners will complete 24 monthly online assessments from May 2022. Concurrently, 1920 people receiving MHPSS services will be randomly selected for post-session interviews (24 per practitioner).
Conclusions
This study will determine the impact of an online, peer-supervision program for MHPSS practitioners in humanitarian settings. Results from the baseline assessments, pilot evaluation, and theory of change model will be presented.
The pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a serious global public health issue. Since the start of the outbreak, the importance of hand-hygiene and respiratory protection to prevent the spread of the virus has been the prime focus for infection control. Health regulatory organisations have produced guidelines for the formulation of hand sanitisers to the manufacturing industries. This review summarises the studies on alcohol-based hand sanitisers and their disinfectant activity against SARS-CoV-2 and related viruses. The literature shows that the type and concentration of alcohol, formulation and nature of product, presence of excipients, applied volume, contact time and viral contamination load are critical factors that determine the effectiveness of hand sanitisers.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
Methods
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
Results
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
Conclusions
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Crab Pulsar (PSR B0531+21) is known to emit pulsed emission in all bands of the electromagnetic spectrum. It also emits giant radio pulses (GRPs) frequently, which are roughly a hundred to million times brighter than the normal pulses. We aim to study whether there is a significant X-ray enhancement correlated with the occurrence of GRPs, using simultaneous observations with the ASTROSAT, the Giant Meterwave Radio telescope (1300 MHz) and the Ooty Radio telescope (325 MHz). This required determination of fixed pipeline offsets between different instruments. We find the offset between ASTROSAT and GMRT to be −30.181 ± 0.095 ms and that between ASTROSAT and ORT to be −18.4 ± 0.2 ms. Our preliminary results with 1300 MHz data also show a break in pulse intensity distribution at ~ 33 Jy in the main pulse and ~ 28 Jy in the inter-pulse.
Growth and reproductive potential with respect to season and photosynthetic gas exchange behavior under elevated (short-term) CO2 at varying temperature, relative humidity (RH), and irradiance levels were investigated in ragweed parthenium (also known as carrot grass and congress grass), a noxious weed in India. Lower values of biomass, relative growth rate, net assimilation rate, crop growth rate, leaf area duration, leaf area index, and numbers of flowers and seeds in winter compared with summer stands showed that ragweed parthenium is greatly suppressed by low temperatures during winter. This was due to constrained vegetative growth, seedling emergence, and seed to flower ratio. The species showed maximum photosynthetic response to temperature at 25 to 35 C, and the net photosynthetic rate was reduced considerably at a low temperature (7 C). These temperatures approximately corresponded to the normal temperatures experienced by summer (25–35 C) and winter (7 C) stands of ragweed parthenium. Elevated CO2 enhanced leaf net photosynthetic efficiency, maximum photosynthetic rate, and water use efficiency (WUE) but decreased the light compensation point for net photosynthesis, stomatal conductance, and transpiration rate. The interactive effects of elevated CO2 and temperature resulted in a decrease in light-limited and light-saturated net photosynthetic rates and WUE. The interactive effects also reduced an elevated CO2-induced decrease in light compensation point relative to elevated CO2 alone. Stomatal conductance was insensitive to photosynthetic photon flux but was greatly influenced by RH. Leaves of the species may show increasing rates of net photosynthesis with a rise in CO2 and temperature. However, excessive increase in transpiration with temperature, especially at 47 C (noon temperature during summer in the plains of northern India), appears to be disadvantageous for the leaves when conservation of water is of prime importance.
Plant breeding makes genetic gains over years, so growing newer varieties generally provides greater benefits than growing older ones. However, in low-altitude districts of Nepal, a few rice varieties covered 75% of the rice area and were more than 20 years old (first paper in this series). We test here if this slow rate of adoption of new varieties could be accelerated using a participatory method, Informal Research and Development (IRD), where packets of seeds of new rice varieties are widely distributed to many farmers. From 2008 to 2011, over 117 000 IRD packets were distributed in 18 districts of the Nepal Terai, including over 70 000 of three released varieties from a client-oriented breeding (COB) programme in Nepal. The IRD significantly increased the adoption of the three COB varieties. The benefits obtained by farmers in a single growing season equal the costs of IRD, if for every 75 kits distributed an additional 1 ha is grown. This assumes that the new varieties produce a 10% increase in yield (lower than that evidenced in their release proposals). On an average, fewer than three IRD kits were distributed for each hectare of a new variety grown by farmers in 2011. Furthermore, the effectiveness of IRD could be increased 1.2 to 2.7 fold (depending on the COB variety) if the IRD distribution were to be restricted to the region where the variety was most accepted. The best comparison of IRD with extension by the conventional system was their popularity compared with similar-aged varieties that had been promoted in the two systems. The adoption of three COB varieties was about twicethat of three varieties from the National Rice Research Programme (NRRP) that were closest in release date to the COB varieties. Unlike cost effectiveness assessed by hectares grown per IRD kit distributed, this comparison can only indicate efficacy because, as well as extension method, many factors influenced the adoption rates of the COB and NRRP varieties. The costs of IRD are small, both relative to the cost of breeding new varieties and to the benefits gained; so it is one of the simplest and most cost-effective interventions to increase agricultural productivity.
Farmers who continue to grow old and obsolete varieties do not gain the benefits they could get from growing newer ones. Given the potential large scale of these foregone benefits, relatively few studies have examined the age of varieties that farmers grow. In three surveys, members of over 3300 households were interviewed to find the rice varieties they grew in 2008 and 2011 in 18 districts in the Terai, the low-altitude region of Nepal. This provided the first description of detailed geographical patterns of adoption of rice varieties and their ages that were repeated over time. There were large differences between district and individual varieties that showed specific geographical patterns of adoption. Such detailed knowledge on spatial diversity of varieties is invaluable for planning extension activities and developing breeding programmes, and cheaper ways than household surveys of collecting this information are discussed. Some of the factors considered important in determining this complex pattern of adoption were seed availability, growing environments that differed from east to west and the continued popularity of varieties once they had established markets. Rice diversity was low because a small number of rice varieties occupied large areas. In 2011, nine varieties covered at least 75% of the total rice area in western districts, just four in central districts and eight in eastern districts. Of these, most were released before 1995 resulting in a high average age of the predominant varieties – they always had an average age of over 20 years no matter which region or year was considered. Even though there were some large changes in varietal composition from 2008 to 2011, the average age of the predominant varieties remained almost the same. In a second paper in this series, we examine how these very low varietal replacement rates, that reduce yields and increase risk to farmers, can be accelerated using a participatory research for development approach called Informal Research and Development (IRD) (Joshi et al., 2012).
A regional, multistate investigation into a June–August 2013 cyclosporiasis outbreak was conducted in Nebraska, Iowa, and neighbouring states. Cases were confirmed on the basis of laboratory and clinical findings. Of 227 cases in Iowa (n = 140) and Nebraska (n = 87) residents, 162 (71%) reported dining at chain A/B restaurants – 96% reported house salad consumption. A case-control study identified chain A/B house salad as the most likely vehicle. Traceback was conducted to ascertain production lot codes of bagged salad mix (iceberg and romaine lettuce, red cabbage, and carrots) served as house salad in implicated restaurants. A single production lot code of salad mix supplied by both a common producer and distributor was linked to the majority of confirmed cases in persons reporting regional chain A/B exposure. The salad mix linked to illnesses contained imported romaine lettuce from two separate single-grower fields-of-origin and ⩾1 additional field from another grower.
The thyroid gland is removed en bloc during laryngectomy. There are no objective criteria for deciding the extent of thyroid gland resection in primary hypopharyngeal cancer cases. The present study aimed to determine the incidence of thyroid gland involvement in hypopharyngeal cancer and identify the various predictors of this involvement.
Method:
This paper reports a retrospective analysis of 358 patients with hypopharyngeal cancer, who underwent total laryngectomy with partial or total pharyngectomy at Tata Memorial Hospital, Mumbai between 2004 and 2010.
Results:
The mean age of this population was 61 years. The pyriform sinus was the most common hypopharyngeal subsite involved (in 89 per cent of cases). Most patients underwent hemi-thyroidectomy as part of their surgery. The thyroid gland was involved in only 13 per cent of cases.
Conclusion:
Thyroid gland involvement is not common in hypopharyngeal cancer. Cases that involved the post-cricoid area, subglottic extension, extralaryngeal spread or prior tracheostomy were associated with a higher risk of thyroid gland involvement. Ipsilateral thyroidectomy is sufficient in most patients undergoing surgery (laryngectomy with partial or total pharyngectomy) for hypopharyngeal cancers.
We report observations of a long filament that underwent recurrent partial eruptions on August 4, 6, and 8, 2012. The filament reappeared in the subsequent rotation of the Sun, and disappeared completely on August 31, 2012. We implemented an automated filament detection algorithm developed by us for estimating different attributes of these filaments few hours prior to its disappearance in Hα and studied their evolution. Based on these attributes, we determine the onset time of the disappearance of Hα filaments. We then compared these onset times with that of the associated CMEs observed by LASCO/SOHO coronagraphs. This is also useful to understand temporal relationship of EUV and X-ray flux variation associated with filament disappearances in Hα. Our results show the importance of such studies in understanding the mechanism of CME initiation, particularly the role of eruptive filaments, in this process.
Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.
Experiments demonstrate the ~77× amplification of 0.5 to 3.5-ps pulses of seed light by interaction with Langmuir waves in a low density (1.2 × 1019 cm−3) plasma produced by a 1-ns, 230-J, 1054-nm pump beam with 1.2 × 1014 W/cm2 intensity. The waves are strongly damped (kλD = 0.38, Te = 244 eV) and grow over a ~ 1 mm length, similar to what is experienced by scattered light when it interacts with crossing beams as it exits an ignition target. The amplification reduces when the seed intensity increases above ~1 × 1011 W/cm2, indicating that saturation of the plasma waves on the electron kinetic time scale (<0.5 ps) limits the scatter to ~1% of the available pump energy. The observations are in agreement with 2D PIC simulations in this case.
A review of the outcomes of past attempts at establishing sustainable seed producer groups in Nepal showed that after donor support was withdrawn a lack of marketing skills resulted in the groups no longer producing seed. Learning from this review, when we initiated new attempts at establishing sustainable seed producer groups in Chitwan district, Nepal, we emphasized the strengthening of their marketing and managerial capabilities rather than training in technical issues such as seed quality control. We imparted marketing skills to committee members of farmer groups at an initial training course in Chitwan in 2001. This inspired at least three existing farmer groups in Chitwan, already established for other agricultural activities, to enter into cereal and legume seed production and its marketing. Following their establishment in 2002 we supported them initially by purchasing some of their seed production. This was progressively withdrawn and, after three years, the groups independently marketed all of their substantial seed production. They built up capital reserves mainly from subsidies and by attracting funds from new shareholders with only a small contribution from retained profits that were only about 5% of total turnover. The capital reserves reduced or eliminated the need for loans thus increasing the chances that the enterprises would be sustainable. In contrast, other government-supported groups had practically no cash reserves despite substantial seed sales. By 2010, two of the three groups were still operating and had substantially increased turnover. Shareholders who were also seed producers benefited from being members of the group and from an increased income of 10% by producing seed instead of grain. Our intention in supporting these groups was to promote the scaling out of new rice varieties produced by client-oriented breeding (COB) or identified by participatory varietal selection but most of the seed that was produced was of obsolete varieties. Policies are needed to preferentially promote new varieties by supplying more information about them and increasing the subsidy on their seeds compared with older varieties. Continuing promotion by the organizations that bred them is also desirable but constrained by limited funding for COB.
The effects of green manuring with Sesbania aculeata, or with Leucaena leucocephala leaves and of weed incorporation on the physical properties of a clay loam soil under a rice–wheat rotation were compared at New Delhi, India, in 1986–87. Under puddled conditions, the volumetric moisture content of the saturated topsoils varied from 0·400 cm3/cm3 in the Sesbania-treated plots to 0·425 cm3/cm3 in plots receiving no green manure, but in the unsaturated soils at rice harvest the corresponding values were 0·317 and 0·271 cm3/cm3. The effects of the green manures on the water content of the soils were still evident after a subsequent wheat crop. Other soil physical properties affected by the treatments were the following (data refer to topsoils measured after the rice harvest): settling index (cm/cm), an estimate of structural instability, which ranged from 25·5% (Sesbania-treated plots), to 28·6% (weed incorporation), 29·7% (Leucaena-treated plots) and to 33·5% (NPK-fertilizer only). Soil dispersion increased from 6·0 to 10·0 g/100g through the same treatment sequence. Hydraulic conductivity in the NPK-fertilizer only plots was 31 cm/day, but increased to 4·8 cm/day in the Sesbania-trealed plots. Sesbania was superior to the other green manures for improving soil physical properties after its incorporation.