Improvement of bacterial blight resistance of the high yielding, fine-grain, rice variety, Gangavati sona through marker-assisted backcross breeding.

Gangavati sona (GS) is a high-yielding, fine-grain rice variety widely grown in the Tungabhadra command area in Karnataka, India; however, it is susceptible to bacterial blight (BB). Therefore, the present study was conducted to improve the GS variety for BB resistance. Three BB-resistant genes (xa5, xa13, and Xa21) were introgressed into the genetic background of susceptible cultivar GS through marker-assisted backcrossing (MABB) by using Improved samba Mahsuri (ISM), a popular, high-yielding, bacterial blight resistant rice variety as a donor parent. Foreground selection was carried out using gene-specific markers, viz., xa5FM (xa5), xa13prom (xa13), and pTA248 (Xa21), while background selection was carried out using well-distributed 64 polymorphic microsatellite markers. The true heterozygote F1 was used as the male parent for backcrossing with GS to obtain BC1F1. The process was repeated in BC1F1 generation, and a BC2F1 plant (IGS-5-11-5) possessing all three target genes along with maximum recurrent parent genome (RPG) recovery (86.7%) was selfed to obtain BC2F2s. At BC2F2, a single triple gene homozygote plant (IGS-5-11-5-33) with 92.6% RPG recovery was identified and advanced to BC2F5 by a pedigree method. At BC2F5, the seven best entries were selected, possessing all three resistance genes with high resistance levels against bacterial blight, yield level, and grain quality features equivalent to better than GS. The improved versions of GS will immensely benefit the farmers whose fields are endemic to BB.

Health state utilities associated with hyperphagia: Data for use in cost-utility models.

Objective: Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods: Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample. Results: In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were -0.08 (0.10) for mild, -0.28 (0.30) for moderate, and -0.77 (0.58) for severe hyperphagia. Conclusions: These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.

Burden of hyperphagia and obesity in Bardet-Biedl syndrome: a multicountry survey.

BACKGROUND: Signs and symptoms of Bardet-Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their caregivers. Hyperphagia may be a contributing factor to early-onset obesity in BBS; however, there are limited insights into its impacts on patients and caregivers. We quantified disease burden as it relates to the physical and emotional impacts of hyperphagia in BBS. METHODS: The CAREgiver Burden in BBS (CARE-BBS) study was a multicountry, cross-sectional survey of adult caregivers of patients with BBS who have had hyperphagia and obesity. The survey consisted of questionnaires including Symptoms of Hyperphagia, Impacts of Hyperphagia, Impact of Weight on Quality of Life (IWQOL)-Kids Parent Proxy, and Patient-Reported Outcome Measurement Information System (PROMIS) v1.0-Global Health 7. In addition, clinical characteristics, medical history, and weight management questions were included. Outcomes were scored and summarized descriptively in aggregate and by country, age, and obesity severity according to weight class. RESULTS: There were 242 caregivers of patients with BBS who completed the survey. Caregivers observed hyperphagic behaviors throughout the day, with negotiating for food (90%) and waking up and asking or looking for food during the night (88%) being the most frequent. Hyperphagia had at least a moderate negative impact on most patients' mood/emotions (56%), sleep (54%), school (57%), leisure (62%), and familial relationships (51%). Hyperphagia affected concentration at school (78%), and symptoms of BBS contributed to patients missing ≥ 1 day of school a week (82%). Responses from the IWQOL-Kids Parent Proxy suggested obesity most greatly negatively affected physical comfort (mean [standard deviation (SD)], 41.7 [17.2]), body esteem (41.0 [17.8]), and social life (41.7 [18.0]). On the PROMIS questionnaire, mean (SD) global health score for pediatric patients with BBS and overweight or obesity (36.8 [10.6]) was lower than the general population (mean, 50). CONCLUSIONS: Evidence from this study suggests that hyperphagia and obesity may have broad negative impacts on the lives of patients with BBS, including physical health, emotional well-being, school performance, and personal relationships. Therapies that target hyperphagia may alleviate the extensive clinical and nonclinical impacts experienced by patients with BBS and their caregivers.

Caregiver burden in Bardet-Biedl syndrome: findings from the CARE-BBS study.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous obesity syndrome associated with hyperphagia. Given the early onset of BBS symptoms in childhood and multifaceted complications, this study aimed to quantify the caregiver burden associated with BBS. METHODS: A cross-sectional, multi-country survey of caregivers from the United States (US), United Kingdom (UK), Canada, and Germany was designed to quantify the extent of caregiver burden associated with obesity and hyperphagia symptoms (i.e., uncontrollable hunger) among patients with BBS. RESULTS: A total of 242 caregivers across the four countries met the inclusion criteria and completed the survey. The mean (standard deviation [SD]) age of the caregivers was 41.9 (6.7) years, and the mean (SD) age of individuals with BBS in their care was 12.0 (3.7) years. Hyperphagia contributed to a BBS diagnosis in 230 of 242 individuals (95.0%). On average, caregivers used eight different weight management approaches for those in their care and expressed a strong desire for more effective weight management methods. Based on the Impacts of Hyperphagia: Caregiver version, patients' hyperphagia had a moderate-to-severe impact on caregiver mood (56.6%), sleep (46.6%), and relationships (48.0%). Caregivers reported experiencing a high level of personal strain (mean [SD], 17.1 [2.9]) and family impact (mean [SD] score, 26.0 [3.8]) due to BBS, as measured by the Revised Impact on Family Scale. Among caregivers in the workforce, there also was high impairment in total work productivity (mean [SD], 60.9% [21.4%]) due to caring for patients with BBS according to the Work Productivity and Activity Impairment. More than half (53%) of the caregivers reported spending over 5,000 out-of-pocket in local currency for medical expenses for the patient with BBS in their care. CONCLUSIONS: Obesity and hyperphagia have negative impacts on the lives of caregivers of patients with BBS. The burden is demonstrated to be multifaceted, with various components that may interact with and confound each other, including intensive weight management efforts, productivity loses, impaired family dynamics and out-of-pocket medical expenses.

A secured IoT-based intelligent transport system (IoT-ITS) framework based on cognitive science.

As intelligent transport systems (ITS) is the advanced format of Vehicle Ad-hoc Network (VANET), it provides extended support in all the traffic management processes. Afterward, the salient features of the Internet of Things (IoT) are incorporated with ITS. IoT-ITS ensures automated mobility as connected and cooperative. However, the development of IoT-ITS is restricted by the risk factors related to data security and privacy. To overcome such issues, a secured IoT-ITS framework is proposed to use cognitive science. A detailed study is carried out regarding the risks related to the IoT-ITS environment. The main objectives of this security framework are to resolve the security demands of the Intelligent Transport Systems and resolve the associated risk factors without compromise. Cognitive science is utilized to design the security framework that differentiates the legitimate users of the transport system from malicious users. Data analysis is also performed in real-time with the help of cognitive science. Based on the experiment results, better results are attained.

Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome.

INTRODUCTION: Bardet-Biedl syndrome (BBS) is a rare genetic disease associated with hyperphagia, a pathologic insatiable hunger, due to impaired signaling in the melanocortin-4 receptor (MC4R) pathway. The impact of hyperphagia on the lives of patients with BBS and their families has not been fully characterized. METHODS: Patients with BBS or their caregivers who participated in clinical trials of the MC4R agonist setmelanotide (NCT03013543 and NCT03746522) were included in this qualitative study. Telephone interviews were conducted using a semistructured interview guide to explore patient experience and caregiver observations of hyperphagia before and during setmelanotide treatment. RESULTS: Nineteen interviews (8 patients, 11 caregivers) were conducted. The term "hunger" (rather than "hyperphagia") was used in interviews to ensure common terminology. Before setmelanotide treatment, all participants described their (or their child's) hunger as all-consuming, leading to an obsessive focus on food. Nine participants recalled intense, continuous hunger, and most participants (5 patients, 10 caregivers) reported lack of control with eating. Negative impacts on patients' lives included difficulties with concentration, emotional and physical manifestations, and impaired relationships. All participants experienced or observed improvements in hunger and health outcomes during treatment, the most meaningful of which included weight loss and decrease in obsessive focus on food and food-seeking behaviors. All participants reported improvements in either physical and/or emotional well-being and being satisfied with setmelanotide. CONCLUSIONS: Hyperphagia and resulting food-seeking behaviors have notable negative impacts on quality of life in patients with BBS and caregivers. Setmelanotide improved hyperphagia, reduced body weight and obsessive focus on food, and facilitated improvements in physical and emotional well-being for both patients and caregivers. TRIAL REGISTRATION: NCT03013543 and NCT03746522.

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

BACKGROUND: Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet-Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet-Biedl syndrome in a Phase 3 trial following 1 year of setmelanotide treatment (ClinicalTrials.gov identifier: NCT03746522). METHODS: Patients with Bardet-Biedl syndrome and obesity received 52 weeks of treatment with setmelanotide and completed various self-reported health-related quality of life measures. Patients aged < 18 years or their caregiver completed the Pediatric Quality of Life Inventory (PedsQL; meaningful improvement, 4.4-point change); adults aged ≥ 18 years completed the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-Lite; meaningful improvement range, 7.7-12-point change). Descriptive outcomes were reported in patients with data both at active treatment baseline and after 52 weeks of treatment. RESULTS: Twenty patients (< 18 years, n = 9; ≥ 18 years, n = 11) reported health-related quality of life at baseline and 52 weeks. For children and adolescents, PedsQL score mean change from baseline after 52 weeks was + 11.2; all patients with PedsQL impairment at baseline (n = 4) experienced clinically meaningful improvement. In adults, IWQOL-Lite score mean change from baseline was + 12.0. Of adults with IWQOL-Lite impairment at baseline (n = 8), 62.5% experienced clinically meaningful improvement. In adults, IWQOL-Lite score was significantly correlated with changes in percent body weight (P = 0.0037) and body mass index (P = 0.0098). CONCLUSIONS: After 1 year of setmelanotide, patients reported clinically meaningful improvements across multiple health-related quality of life measures. This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden. Trial Registration NCT03746522. Registered November 19, 2018, https://clinicaltrials.gov/ct2/show/NCT03746522 .

Assessment of Nasal Smear Eosinophil Counts in Allergic Rhinitis: How Useful is it?

Objectives: The aim was to find the relationship between nasal smear eosinophil (NSE) counts and allergic rhinitis (AR) along with the impact of treatment on peak nasal inspiratory flow rates and symptom scores in these patients. Material and methods: An observational, comparative study was carried out with 75 patients of AR. Nasal smears were drawn and eosinophil counts were estimated. Nasal symptoms were assessed and compared by visual analogue scale (VAS) and peak nasal inspiratory flow (PNIF) rates before and after treatment. Equal number of healthy individuals formed the control group. Results: There was a strong association between increase in eosinophil count in nasal smears and AR (p = 0.000). A NSE count of 0.2/HPF had a specificity of 98.7%, sensitivity of 53.3%, and positive predictive value of 97.6% in the diagnosis of AR. The mean VAS scores for nasal obstruction improved from 7.35 to 1.01 and the mean peak nasal inspiratory flow from 69.00 L/min to 103.73 L/min (p < 0.0001) after treatment. The mean NSE counts reduced from 4.20/HPF to 0.090/HPF proving a strong correlation between improvement of symptom scores and NSE counts (p = 0.000) in AR. The study also determined that a PNIF value of ≤ 77.50 L/min can be used as a cut off for diagnosing nasal obstruction in these patients. Conclusion: A NSE count of ≥ 0.2 /HPF is to be considered as diagnostic of AR. Nasal congestion is the commonest symptom associated with AR and addition of systemic decongestant is required for management of these patients.

Pleomorphic Adenoma of the Parapharyngeal Space: An Unusually Large Tumour.

Parapharyngeal space (PPS) tumors constitute about 0.5% of all the head and neck tumors.Tumors arising de novo from ectopic salivary tissue in the PPS are very rare. We present a huge primary parapharyngeal pleomorphic adenoma arising from ectopic salivary tissue. Case is being presented for its unusually large size at presentation and its rarity.

A randomized comparative evaluation of C-MAC video-laryngoscope with Miller laryngoscope for neonatal endotracheal intubation.

Background and Aims: An efficient neonatal airway management is peculiarly challenging even in the most experienced hands. Considering the recent interest in assessing the performance of various video-laryngoscopes (VL) in pediatric cohort, the prospective randomized study was contemplated to stage a comparative evaluation of C-MAC with Miller laryngoscope for neonatal endotracheal intubation. Material and Methods: 150 neonates were randomized to undergo intubation with either the C-MAC VL (n = 75) or the Miller laryngoscope (n = 75) performed by an experienced anesthesiologist in a tertiary care perioperative setting. The percentage of glottic opening (POGO), time to best glottic view (TTBGV), time to intubation (TTI), number of attempts, optimal external laryngeal manipulation (OELM) employed, and the complications were assessed and compared between the two groups. Results: C-MAC group demonstrated a significantly higher POGO, compared to the Miller group (88 ± 26.7%;76.8 ± 32.1%, respectively, P = 0.022). TTBGV was significantly lower in the C-MAC (7.7 ± 0.1s) group as opposed to the Miller group (11.3 ± 1.1s). The C-MAC group displayed higher TTI values compared to the Miller group (25.4 ± 1.6s; 19.7 ± 1.2s, respectively, P < 0.01). The first-attempt intubation success rate and the number of attempts were comparable in both the groups. OELM was required in 24% of the patients in the Miller group as opposed to 10.7% in the C-MAC group (P = 0.031). Higher patient percentage in the C-MAC group required the need of stylet for assisting a successful intubation, although the difference between the two groups was not statistically significant. Conclusion: Despite an improved view of the glottis, the TTI was higher for C-MAC compared to direct laryngoscopy with a comparable first-attempt success rate in the two techniques.

Patient Preferences for Attributes of Biologic Treatments in Moderate to Severe Asthma: A Discrete Choice Experiment Study.

Purpose: Multiple biologics are available for moderate to severe asthma. Given the important relationship between patient engagement in healthcare decision-making and health outcomes, patient preference is an increasingly important consideration. This study elicited patients' preferences for attributes of biologic therapies for moderate to severe asthma. Patient and Methods: A discrete choice experiment (DCE) questionnaire was designed to collect data from an existing survey panel of adults with moderate to severe asthma in the United States. Patients were asked to select their preferred hypothetical treatment from profiles with varying attributes related to efficacy, safety, and administration convenience. Conditional logit regression models were used to quantify patient preferences. Results: Of 301 eligible patients who completed the survey, the mean age was 46.7±15.1 years and 71.8% were female. Patients had asthma for 22.5±16.3 years on average, and most (97.3%) had experienced ≥1 asthma attack in the past 12 months. Among treatment attributes examined, patients most valued the absence of a black box warning for the risk of a life-threatening allergic reaction, effectiveness of reducing severe asthma exacerbations, and improvement in lung function (all p < 0.001). Home administration setting for subcutaneous injections (vs doctor's office/clinic) (p = 0.009) and ability of a biologic to treat additional chronic condition(s) (p < 0.05) were also considered important. Dosing frequency and type of injection device were not significant factors. Conclusion: Patients with moderate to severe asthma valued efficacy and safety over convenience attributes when selecting biologic treatments. Awareness of these preferences can facilitate patient-physician shared decision-making when managing moderate to severe asthma in clinical practice.

Fake Information Analysis and Detection on Pandemic in Twitter.

Twitter has become a popular platform to receive daily updates. The more the people rely on it, the more critical it becomes to get genuine information out. False information can easily be shared on Twitter, which influences people's feelings, especially if fake information is linked to COVID-19. Therefore, it is of utmost importance to detect fake information before it becomes uncontrollable. Real-time tweets were used as part of this study. A few features like tweet's text, sentiment etc., were extracted and analyzed. The project returns a set of statistics determining the tweet's veracity. In this study, various classifiers have been used to see which of them works best with the proposed model in classifying the used dataset. The proposed model achieved the best accuracy of 84.54% and the highest F1-score of 0.842 with Random Forest. With careful analysis while feature selection and using few features, the model developed is equivalent in performance to the other models that use a lot of features. This confirms that the model developed is less complex and highly dependable.

Efficacy of antimicrobial photodynamic therapy on the tongue surface in the management of halitosis - A real-time polymerase chain reaction analysis.

AIM: To evaluate the additional effect of a single session of antimicrobial photodynamic therapy (aPDT) on the tongue as an adjunct to scaling and root planing (SRP) on most common volatile sulfur-producing microbes such as Porphyromonas gingivalis (Pg), Treponema denticola (Td) and Fusobacterium nucleatum (Fn) on 3rd, 7th and 14th day postoperatively using RT-PCR analysis. METHOD AND MATERIALS: Twenty-four patients of either sex, presented with moderate to severe malodor, detected by a portable breath checker (Tanita®) were considered for the study and assigned to group A & B. Scaling and root planning was performed in both the groups, followed by photodynamic therapy on the tongue surface in group A. One percent methylene blue photosensitizer was applied on the middle and posterior thirds of the dorsum of the tongue and irradiated in continuous mode at six different points for 90 s at each point. RESULTS: A significant reduction in Halimeter scores throughout the study period was observed. A significant reduction in the tongue coating score on 3rd and 7th day and the total count of Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) on 7th and 14th day was seen in group A (p ≤ 0.05). However, the mean reduction in Treponema denticola (Td) was non-significant in both the groups but a greater fall in the total count was seen in group A compared to group B on all the days (p ≥ 0.05). CONCLUSION: Within the limitations of the study, it was concluded that photodynamic therapy on the tongue along with scaling and root planing was effective in the reduction of malodour and the total count of bacteria responsible for the same. Long-term clinical trials are required to further substantiate the effectiveness of this technique.

Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide.

Context: Rare homozygous or biallelic variants in POMC, PCSK1, and LEPR can disrupt signaling through the melanocortin-4 receptor (MC4R) pathway, resulting in hyperphagia and severe early-onset obesity. In pivotal Phase 3 clinical trials, treatment with the MC4R agonist setmelanotide reduced hunger and weight in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. Objective: To characterize the historical weight trajectory in these patients. Methods: This analysis included data from 2 pivotal single-arm, open-label, Phase 3 trials (NCT02896192, NCT03287960). These were multicenter trials. Patients had obesity due to POMC/PCSK1 or LEPR deficiency. During the trial, patients were treated with setmelanotide. Historical data on measured weight and height were obtained during screening. Results: A total of 17 patients (POMC, n = 8; PCSK1, n = 1; LEPR, n = 8) with historical weight and height data were included in this analysis. Before setmelanotide treatment, patients with obesity due to POMC/PCSK1 or LEPR deficiency were above the 95th percentile for weight throughout childhood, demonstrated continuous weight gain, and did not show long-term weight loss upon interventions (eg, diet, surgery, exercise). Setmelanotide treatment attenuated weight and body mass index trajectories over the observation period of 1 year. Conclusion: In patients with POMC, PCSK1, or LEPR deficiency, traditional interventions for weight loss had limited impact on the trajectory of severe early-onset obesity. However, setmelanotide treatment attenuated weight and body mass index trajectories and led to weight loss associated with health benefits in most individuals.

Real-World Effectiveness of Dupilumab in Atopic Dermatitis Patients: Analysis of an Electronic Medical Records Dataset.

INTRODUCTION: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. METHODS: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). RESULTS: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). CONCLUSIONS: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point.

Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency.

INTRODUCTION: Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL). METHODS: Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: In total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6-12 years old; n = 2) and adolescents (13-17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52. CONCLUSIONS: Patients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.

Understanding the Patient Experience of Hunger and Improved Quality of Life with Setmelanotide Treatment in POMC and LEPR Deficiencies.

INTRODUCTION: In patients with pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency, managing obesity and hyperphagia can be burdensome for patients and caretakers. The impacts on health-related quality of life are under-recognized and are not well characterized. METHODS: We conducted in-depth qualitative interviews in patients with POMC (n = 3) and LEPR (n = 2) deficiencies participating in an ongoing open-label extension of phase 3 clinical trials with the melanocortin receptor 4 agonist setmelanotide to describe the patient experience of hyperphagia and characterize changes following treatment with setmelanotide. RESULTS: Prior to setmelanotide treatment, all five patients described abnormal sensations of hunger with none indicating feeling satiated after meals and also reported that the burden of hyperphagia impacted their families, emotions, and work and/or school functioning. Following setmelanotide treatment, all five patients reported consistent reductions in hunger and weight, decreased eating, and feeling satiated after meals in addition to substantial improvements in each area of functioning they had previously reported. All five patients indicated they were very satisfied with the impact of setmelanotide on their quality of life and would be upset if treatment was discontinued. CONCLUSIONS: In patients with POMC or LEPR deficiency, hyperphagia and the inability to feel satiety negatively impacted quality of life. By reducing hunger and improving satiety, setmelanotide facilitated important changes in the lives of these patients. This qualitative research study suggests that the impact of setmelanotide goes beyond favorable clinical changes (e.g., weight and hunger) to also include quality of life improvements that are highly meaningful to patients.

Depression, Anxiety, Stress, and Insomnia amongst COVID Warriors across Several Hospitals after Second Wave: Have We Acclimatized? A Cross-sectional Survey.

Background: Coronavirus disease-2019 (COVID-19) pandemic has been a cause of significant mental health disturbances in medical health personnel. However, 18 months into the pandemic, healthcare workers (HCWs) have become accustomed to the heightened stress and anxiety that comes with caring for COVID patients. Through this study, we aim to measure depression, anxiety, stress, and insomnia in doctors with the help of validated scales. Materials and methods: This was a cross-sectional study with an online survey design conducted among doctors from major hospitals in New Delhi. The questionnaire included participant demographics, including designation, specialty, marital status, and living arrangements. This was followed by questions from the validated depression, anxiety, stress scale (DASS-21), and insomnia severity index (ISI). Depression, anxiety, stress, and insomnia scores were calculated for each participant, and the data were analyzed statistically. Results: The mean scores of the whole study population showed no depression, moderate anxiety, mild stress, and subthreshold insomnia. Female doctors exhibited more psychological issues (mild depression and stress, moderate anxiety, but only subthreshold insomnia) as compared to males (mild anxiety, but no depression, stress, and insomnia). Junior doctors also had higher depression, anxiety, and stress scores than senior doctors. Similarly, single doctors, those living alone, and those not having kids had higher DASS and insomnia scores. Discussion: HCWs have been under tremendous mental stress during this pandemic which is influenced by multiple factors. Female sex, junior doctors, working on the frontline, not being in a relationship, and living alone may be some of the factors recognized in our study and corroborated by many authors, which may increase the chances of depression, anxiety, and stress in them. HCWs need regular counseling, time off for rejuvenation, and social support to overcome this hurdle. How to cite this article: Kohli S, Diwan S, Kumar A, Kohli S, Aggarwal S, Sood A, et al. Depression, Anxiety, Stress, and Insomnia amongst COVID Warriors across Several Hospitals after Second Wave: Have We Acclimatized? A Cross-sectional Survey. Indian J Crit Care Med 2022;26(7):825-832.

An Intelligent Centrality Measures for Influential Node Detection in COVID-19 Environment.

With an advent of social networks, spamming has posted the most important serious issues among the users. These are termed as influential users who spread the spam messages in the community which has created the social and psychological impact on the users. Hence the identification of such influential nodes has become the most important research challenge. The paper proposes with a method to (1) detect a community using community algorithms with the Laplacian Transition Matrix that is the popular hashtag (2) to find the Influential nodes or users in the Community using Intelligent centrality measure's (3) The implementation of machine learning algorithm to classify the intensity of users.The extensive experimentations has been carried out using the COVID-19 datasets with the different machine learning algorithms. The methodologies SVM and PCA provide the accuracy of 98.6 than the linear regression for using the new centrality measures and the other scores like NMI, RMS, are found for the methods. As a result finding out the Influential nodes will help us find the Spammy and genuine accounts easily.

Treatment Outcomes Associated With Dupilumab Use in Patients With Atopic Dermatitis: 1-Year Results From the RELIEVE-AD Study.

IMPORTANCE: Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making. OBJECTIVE: To evaluate self-reported disease control and quality of life after initiating dupilumab treatment in patients with atopic dermatitis (AD) in the the clinical setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study using an online survey administered prior to (baseline) and at 1, 2, 3, 6, 9, and 12 months after dupilumab initiation included adults with moderate-to-severe AD who initiated treatment with dupilumab through the US patient support program and agreed to participate in the study. Data were collected between January 2018 and January 2020 and the analysis was completed in May 2020. INTERVENTIONS: Clinically driven treatment with dupilumab. MAIN OUTCOMES AND MEASURES: Disease control measured by the Atopic Dermatitis Control Tool (ADCT); concomitant AD therapies; satisfaction with therapy; skin symptoms (skin pain/soreness, hot/burning feeling, sensitivity to touch) assessed using numerical rating scales; flares; health-related quality of life assessed using the Dermatology Life Quality Index; sleep problems assessed using the ADCT item and a stand-alone question; and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 699 patients who initiated dupilumab (431 [61.7%] female, 515 [73.7%] White), 632 and 483 completed the survey at months 1 and 12, respectively. As-observed results showed that most patients achieved adequate disease control (ADCT total score) at month 1 with further improvement at month 12 (385 of 632 patients [60.9%] and 374 of 483 [77.4%] for the 2 time points, respectively, vs 41 of 699 [5.3%] at baseline; both P < .001). Use of other AD therapies was reduced at each follow-up vs baseline, including topical and systemic corticosteroids, which were reduced at month 12 to 40.4% (195 of 483 patients) and 6.2% (30 of 483 patients), respectively, from 68.1% (476 of 699) and 34.9% (244 of 699), respectively, at baseline (both P < .001 vs baseline). Patient satisfaction with AD treatment was higher than baseline (120 of 699 [17.7%]) at each follow-up to 85.1% (411 of 483) at month 12 (P < .001). At each follow-up, patients reported reductions in flares, itch, skin symptoms, and improved sleep, health-related quality of life, and daily activities vs baseline. Results were consistent based on observed data and imputed data using pattern mixture models for missing data. CONCLUSIONS AND RELEVANCE: Consistent with patient-reported outcomes in clinical trials, this cohort study found that dupilumab treatment was associated with rapid and sustained disease control for up to 12 months as demonstrated by statistically significant improvements relative to baseline on all patient-reported outcomes including treatment satisfaction.